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Bolek H, Kuzu OF, Sertesen Camoz E, Sim S, Sekmek S, Karakas H, Isık S, Günaltılı M, Akkus AF, Tural D, Arslan C, Goksu SS, Sever ON, Karadurmus N, Karacin C, Sendur MAN, Yekedüz E, Urun Y. Evaluating the prognostic role of glucose-to-lymphocyte ratio in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors in first line: a study by the Turkish Oncology Group Kidney Cancer Consortium (TKCC). Clin Transl Oncol 2025; 27:3110-3120. [PMID: 39812937 DOI: 10.1007/s12094-024-03813-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 11/23/2024] [Indexed: 01/16/2025]
Abstract
PURPOSE Identifying prognostic indicators for risk stratification in metastatic renal cell carcinoma (mRCC) is crucial for optimizing treatment strategies and follow-up plans. This study aims to investigate the prognostic role of the glucose-to-lymphocyte ratio (GLR) in patients with mRCC receiving tyrosine kinase inhibitors (TKIs) as first-line therapy. METHODS A retrospective cohort study was conducted using data from the Turkish Oncology Group Kidney Cancer Consortium Database. GLR was calculated by dividing the fasting glucose (mmol/L) by the lymphocyte count (×109/L). We categorized patients into two categories based on their median GLR level. RESULTS The analysis included a total of 598 patients. We found that progression-free survival (PFS) was significantly longer in the GLR-low group, with a median PFS of 15.05 months (95% CI 12.7-17.4) compared to 7.79 months (95% CI 6.6-9.0) in the GLR-high group (p < 0.001). Multivariate analysis identified GLR as an independent risk factor for poor PFS (HR 1.39, 95% CI 1.12-1.72; p = 0.003). Overall survival (OS) was also significantly longer in the GLR-low group, with a median OS of 38.47 months (95% CI, 30.9-46.0) compared to 24.15 months (95% CI 18.0-30.2) in the GLR-high group (p = 0.001). GLR was an independent predictor for OS in multivariate analysis (HR 1.45, 95% CI 1.12-1.86; p = 0.004). CONCLUSION The GLR can be a valuable prognostic marker for glucose metabolism and systemic inflammatory status in this patient population. Our research highlights the potential prognostic value of GLR in patients with mRCC receiving TKIs, indicating its potential as a useful tool for clinical decision-making.
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Affiliation(s)
- Hatice Bolek
- Department of Medical Oncology, Ankara University School of Medicine, 06590, Ankara, Türkiye
- Ankara University Cancer Institute, Ankara, Türkiye
| | - Omer Faruk Kuzu
- Department of Medical Oncology, Gulhane Training and Research Hospital, University of Health Sciences, Ankara, Türkiye
| | - Elif Sertesen Camoz
- Department of Medical Oncology, Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara, Türkiye
| | - Saadet Sim
- Department of Medical Oncology, Ege University School of Medicine, Izmir, Türkiye
| | - Serhat Sekmek
- Department of Medical Oncology, Bilkent City Hospital, Ankara, Türkiye
| | - Hilal Karakas
- Department of Medical Oncology, Bilkent City Hospital, Ankara, Türkiye
| | - Selver Isık
- Department of Medical Oncology, Marmara University School of Medicine, Istanbul, Türkiye
| | - Murat Günaltılı
- Department of Medical Oncology, Cerrahpasa School of Medicine, Istanbul, Türkiye
| | - Aysun Fatma Akkus
- Department of Medical Oncology, Trakya University School of Medicine, Edirne, Türkiye
| | - Deniz Tural
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Türkiye
| | - Cagatay Arslan
- Medical Point Hospital, Izmir University of Economics, Izmir, Türkiye
| | - Sema Sezin Goksu
- Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Türkiye
| | - Ozlem Nuray Sever
- Department of Medical Oncology, Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Türkiye
| | - Nuri Karadurmus
- Department of Medical Oncology, Gulhane Training and Research Hospital, University of Health Sciences, Ankara, Türkiye
| | - Cengiz Karacin
- Department of Medical Oncology, Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences, Ankara, Türkiye
| | | | - Emre Yekedüz
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Yuksel Urun
- Department of Medical Oncology, Ankara University School of Medicine, 06590, Ankara, Türkiye.
- Ankara University Cancer Institute, Ankara, Türkiye.
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Agaoglu AB, Erdogan AP, Sahbazlar M, Ekinci F. Prognostic value of the HALP score in patients with testicular cancer: a retrospective study. Clin Transl Oncol 2025:10.1007/s12094-025-03973-3. [PMID: 40528068 DOI: 10.1007/s12094-025-03973-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2025] [Accepted: 06/04/2025] [Indexed: 06/20/2025]
Abstract
PURPOSE The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a novel immune nutritional index associated with the prognosis of various malignancies. This study aimed to evaluate the clinical relevance of the HALP score in predicting recurrence, metastasis, and survival outcomes in patients with testicular cancer. METHODS This retrospective study included 131 patients with histologically confirmed testicular cancer who were treated between January 2010 and December 2024. HALP scores were calculated using the baseline laboratory parameters. An optimal cutoff value of 304.56 was identified using receiver operating characteristic (ROC) curve analysis (AUC: 0.820; 95% CI 0.708-0.902; p < 0.001). Patients were stratified into high and low HALP groups based on this threshold value. Survival outcomes were evaluated using Kaplan-Meier, and Cox proportional hazards regression analyses. RESULTS The median HALP score was 531.1 (IQR: 348.8-728.5). A low HALP score (≤ 304.56) was significantly associated with poorer 1-year overall survival (54.5% vs. 98.2%, p < 0.001) and a 15.6-fold increased risk of death (HR 15.604, 95% CI 2.718-89.645, p = 0.001) based on Cox regression analysis. In the multivariate analysis, a low HALP score (HR: 7.684, p = 0.016), the presence of comorbidity (HR 13.528, p = 0.002), and tunica albuginea invasion (HR 7.255, p = 0.030) were identified as independent predictors of recurrence or metastasis. In addition, the HALP score was significantly associated with disease stage (p < 0.001), with lower scores more commonly observed in patients with advanced-stage disease. CONCLUSIONS The HALP score was a simple, inexpensive, and effective prognostic biomarker in testicular cancer. A score ≤ 304.56 is independently associated with a higher risk of recurrence, metastasis, and mortality. Incorporating HALP into routine assessments may improve risk stratification and clinical decision-making in this patient population.
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Affiliation(s)
- Ahmet Burak Agaoglu
- Division of Medical Oncology, Faculty of Medicine, Celal Bayar University, Yunusemre, Manisa, Turkey.
| | - Atike Pınar Erdogan
- Division of Medical Oncology, Faculty of Medicine, Celal Bayar University, Yunusemre, Manisa, Turkey
| | - Mustafa Sahbazlar
- Division of Medical Oncology, Faculty of Medicine, Celal Bayar University, Yunusemre, Manisa, Turkey
| | - Ferhat Ekinci
- Division of Medical Oncology, Faculty of Medicine, Celal Bayar University, Yunusemre, Manisa, Turkey
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Cai M, Sun J, Wu J, Liu Y, Huang Y. Prognostic analysis and association of the systemic immune-inflammatory index with immune checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer. Front Oncol 2025; 15:1596223. [PMID: 40575174 PMCID: PMC12197933 DOI: 10.3389/fonc.2025.1596223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2025] [Revised: 05/18/2025] [Accepted: 05/30/2025] [Indexed: 06/29/2025] Open
Abstract
Objective The Systemic Immune-Inflammatory Index (SII) is a comprehensive indicator reflecting immune response and disease burden. However, its significance in immune checkpoint inhibitor-related pneumonitis (CIP) in cases of non-small cell lung cancer (NSCLC) remains poorly explored. This study evaluated the association between SII and the incidence, severity, and prognostic effects of CIP in NSCLC patients. Methods A retrospective analysis involved 215 NSCLC patients receiving immune checkpoint inhibitor (ICI) therapy, of whom 35 developed CIP while 180 did not. Baseline clinical characteristics and dynamic changes in peripheral blood biochemical markers were analyzed. Risk factors associated with the onset and severity of CIP were assessed, along with the diagnostic application of the SII for CIP. Results Multivariate logistic regression identified smoking history (odds ratio [OR]: 3.23; p = 0.01), pre-existing lung disease (OR: 3.36; p < 0.01), squamous cell carcinoma (OR: 2.39; p = 0.03), and combined ICI therapy (OR: 4.77; p < 0.01) as independent risk factors for CIP onset. SII was also identified as independently predictive of severe CIP (OR: 6.35; p = 0.04). Receiver operating characteristic (ROC) curves demonstrated that SII had moderate accuracy for diagnosing CIP (area under the curve [AUC]: 0.63) and high diagnostic accuracy for severe CIP (AUC: 0.81). Multivariate Cox regression also showed that severe CIP was substantially related to reduced overall survival (OS) relative to mild CIP (hazard ratio [HR]: 0.06, 95% confidence interval [CI]: 0.01-0.52; p = 0.01). Conclusion The results suggested the potential of SII as an indicator for diagnosing the presence and severity of CIP. Elevated SII levels were independently associated with the development of severe CIP, which, in turn, emerged as a key prognostic factor influencing overall survival in affected patients.
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Affiliation(s)
| | | | | | | | - Yuanyi Huang
- Department of Radiology, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
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Kim GM, Kim S, Lee MA, Byun MS, Choi D, Yang SH, Woo J, Sung YC, Shin EC, Park SH, Kim TW, Sohn J. GX-I7, a long-acting IL-7, safely and effectively increased peripheral CD8 +/CD4 + T cells and TILs in patients with locally advanced or metastatic solid tumours. Br J Cancer 2025:10.1038/s41416-025-03069-3. [PMID: 40490502 DOI: 10.1038/s41416-025-03069-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 05/07/2025] [Accepted: 05/20/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND GX-I7 (rhIL-7-hyFc, efineptakin alfa) is a hybrid Fc-fused long-acting interleukin-7 (IL-7) with the aim of correcting T-cell deficiency, thereby strengthening the immune response to fight against cancer. This Phase 1b, dose-escalation study was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GX-I7 in patients with locally advanced or metastatic solid tumours. METHODS This study, conducted in patients with advanced solid tumours at three hospitals in Korea, involved intramuscular GX-I7 administration across eight dose levels (60-1700 µg/kg) in 3- and 6-week cohorts. A dose-expansion phase at 720 and 1200 µg/kg further assessed GX-I7's safety and efficacy. RESULTS Anti-tumour responses showed either stable disease (SD) or disease progression (PD). GX-I7 demonstrated dose-dependent increases in the maximum serum concentration (Cmax) and area under the curve up to the last measurable concentration (AUClast). In addition, a dose-dependent increase in circulating CD8+/CD4+ T cells was observed. In five patients who consented for biopsy, a statistically significant increase in tumour-infiltrating lymphocytes (TILs) followed GX-I7 treatment. DISCUSSION Findings suggest GX-I7 is a safe T cell-amplifying agent with peripheral immune activation. Ongoing studies are exploring its ability to enhance immune responses in peripheral immune cells and tumour cells when combined with other anti-cancer agents. CLINICAL TRIAL REGISTRATION NCT03478995.
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Affiliation(s)
- Gun Min Kim
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
| | - Sojeong Kim
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea
- Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Seoul St, Mary's Hospital, The catholic University of Korea, Seoul, Korea
| | | | | | | | | | | | - Eui-Cheol Shin
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea
| | - Su-Hyung Park
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
| | - Tae Won Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
| | - Joohyuk Sohn
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
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García-Castillo MC, Sierra-Mencía Á, Caronna E, Toledo-Alfocea D, Jaimes A, Urtiaga S, Casas-Limón J, Muñoz-Vendrell A, Santos-Lasaosa S, García Martín V, Martín Ávila G, Polanco M, Villar-Martínez MD, Trevino-Peinado C, Rubio-Flores L, Sánchez-Soblechero A, Portocarrero Sánchez L, Luque-Buzo E, Lozano-Ros A, Gago-Veiga AB, Díaz-De-Terán J, Recio García A, Canales Rodríguez J, Gómez García A, González Salaices M, Campoy S, Mínguez-Olaondo A, Maniataki S, González-Quintanilla V, Porta-Etessam J, Cuadrado ML, Guerrero Peral ÁL, Pozo-Rosich P, Rodríguez-Vico J, Huerta-Villanueva M, Pascual J, Goadsby PJ, Gonzalez-Martinez A. Concomitant anti-CGRP and immunomodulatory treatments in patients with migraine: towards integrated management strategies. J Neurol 2025; 272:443. [PMID: 40461909 PMCID: PMC12134006 DOI: 10.1007/s00415-025-13177-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/13/2025] [Accepted: 05/16/2025] [Indexed: 06/29/2025]
Abstract
BACKGROUND Preclinical evidence supports the immunoregulatory role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology. The increasing use of anti-CGRP therapies in patients with migraine and other comorbidities raises the question whether the potential use of anti-CGRP monoclonal antibodies (CGRP-mAbs) therapies in combination with other immunological therapies is effective and safe. METHODS This multicenter study included patients with migraine receiving CGRP-mAbs combined with immunosuppressive and immunomodulatory treatments. Clinical and demographic data, treatment history, laboratory markers and treatment-emergent adverse events (TEAEs) were analyzed. Effectiveness outcomes included the change in monthly migraine days (MMD) and monthly headache days (MHD) at 3, 6, 9 and 12 months, alongside the > 50% response rate. Moreover, autoimmune disease progression was also evaluated. We explored differences between patients with and without autoimmune disease activation. RESULTS Among 89 patients, there were 80 (90%) females with a mean age of 50 years (SD: 11), who had a high prevalence of psychiatric comorbidities (anxiety 44%, depression 49%) and medication overuse (68%). Patients receiving immunological treatments experienced significant reductions in MMD and MHD, with MMD decreasing from 16 (SD: 7) at baseline to 9 (SD: 8) at 6 months, and MHD dropping from 23 (SD: 8) to 17 (SD: 11). A 50% response in MMD was achieved by 46% at 6 months. TEAEs were reported in 28%, most commonly constipation (16%) and dizziness (9%). CONCLUSIONS CGRP-mAbs therapies combined with immunological treatments appear effective and safe in patients with autoimmune diseases. Larger prospective studies are necessary to confirm these findings and optimize management strategies.
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Affiliation(s)
- María Clara García-Castillo
- Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Hospital Universitario de la Princesa, Madrid, Spain
| | - Álvaro Sierra-Mencía
- Headache Unit, Neurology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Edoardo Caronna
- Headache Clinic, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Barcelona, Spain
| | | | - Alex Jaimes
- Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Neurology Department, Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | - Saray Urtiaga
- Neurology Department, Hospital de Torrejón, Madrid, Spain
| | - Javier Casas-Limón
- Headache Unit, Neurology Department, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain
| | - Albert Muñoz-Vendrell
- Headache Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Sonia Santos-Lasaosa
- Neurology Department, Hospital Universitario Lozano Blesa. IIS Aragon, University of Zaragoza, Zaragoza, Spain
| | | | | | - Marcos Polanco
- Neurology Department, Marqués de Valdecilla University Hospital, Santander, Spain
| | | | | | - Laura Rubio-Flores
- Headaches, Craniofacial Pain and Neurological Pain Unit, Vithas Hospitals Group, Vithas Clinical Neuroscience Institute, La Milagrosa, Aravaca & Arturo Soria University Hospitals, Madrid, Spain
| | | | | | - Elisa Luque-Buzo
- Neurology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Alberto Lozano-Ros
- Neurology Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Ana Beatriz Gago-Veiga
- Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Hospital Universitario de la Princesa, Madrid, Spain
- Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid, Madrid, Spain
| | - Javier Díaz-De-Terán
- Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain
- Neurology Department, Hospital Universitario de la Paz, Madrid, Spain
| | - Andrea Recio García
- Headache Unit, Neurology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | - Javiera Canales Rodríguez
- Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Barcelona, Spain
- Hospital San Martín de Quillota, Quillota, Chile
| | - Andrea Gómez García
- Neurology Department, Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | | | - Sergio Campoy
- Headache Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
- Headache Unit, Hospital Universitari de Bellvitge & Hospital de Viladecans - IDIBELL, Universitat de Barcelona, Barcelona, Spain
| | - Ane Mínguez-Olaondo
- Neurology Department, Hospital Universitario Donostia-Osakidetza, Neuroscience Area, Biogipuzkoa Health Institute, Donostia, Spain
- Department of Medicine and Department of Physical Therapy, Faculty of Health Sciences, University of Deusto, Bilbao, San Sebastian, Spain
| | - Stefania Maniataki
- NIHR King's Clinical Research Facility and Wolfson SPaRC King's College London, London, UK
| | | | - Jesús Porta-Etessam
- School of Medicine, Department of Neurology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain
| | - María-Luz Cuadrado
- School of Medicine, Department of Neurology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain
| | - Ángel Luis Guerrero Peral
- Headache Unit, Neurology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
- Departamento de Medicina, Universidad de Valladolid, Valladolid, Spain
| | - Patricia Pozo-Rosich
- Headache Clinic, Neurology Department, Hospital Universitari Vall d'Hebron, Barcelona, Spain
- Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Barcelona, Spain
| | | | - Mariano Huerta-Villanueva
- Headache Unit, Neurology Department, Hospital Universitari de Bellvitge-IDIBELL, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
- Headache Unit, Hospital Universitari de Bellvitge & Hospital de Viladecans - IDIBELL, Universitat de Barcelona, Barcelona, Spain
| | - Julio Pascual
- Neurology Department, Marqués de Valdecilla University Hospital, Santander, Spain
| | - Peter J Goadsby
- NIHR King's Clinical Research Facility and Wolfson SPaRC King's College London, London, UK
- Department of Neurology, King's College Hospital, London, UK
- Department of Neurology, University of California, Los Angeles, CA, USA
| | - Alicia Gonzalez-Martinez
- Facultad de Medicina, Universidad Autónoma de Madrid (UAM), Madrid, Spain.
- Hospital Universitario de la Princesa, Madrid, Spain.
- Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid, Madrid, Spain.
- Neurology and Immunology Department, Hospital Universitario de La Princesa, Calle Diego de León, 62, 28006, Madrid, Spain.
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Li J, Mali R, Gan GN, Lominska C, Guida K, Juloori A, Chen MWR, Li W, Setianegara J, Wang C, Lin Y, Li Q, Chen W, Gao H. Patient-specific modeling of radiation-induced lymphopenia for head and neck cancer. Med Phys 2025; 52:3583-3594. [PMID: 40229136 DOI: 10.1002/mp.17829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 03/20/2025] [Accepted: 03/31/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Radiation-induced lymphopenia (RIL) is a frequent complication in head and neck cancer (HNC) patients undergoing radiotherapy (RT), and its severity is associated with poorer survival outcomes. PURPOSE This work aims to develop a patient-specific modeling method to simulate lymphocyte kinetics during and after RT and evaluate the lymphocyte-sparing effects across different RT treatment regimens. METHODS A cohort of 17 HNC patients receiving unilateral irradiation with protons or photons were included in this study. The dose to circulating lymphocytes was calculated using the HEDOS model, considering lymph nodes on the irradiated side, the esophagus, auto-segmented bilateral carotid arteries and jugular veins, skeletal muscle, fat, skin, compact bone, spongy bone, red marrow, and other skeleton. A patient-specific model was developed to simulate lymphocyte kinetics that account for radiation-induced damage to both circulating lymphocytes and lymph nodes. The weekly absolute lymphocyte counts (ALC) before, during and after RT, were assembled to estimate the patient-specific parameters. Four different RT treatment regimens-conventional fractionation, hypofractionation, stereotactic body radiotherapy (SBRT), and FLASH-were evaluated to compare their lymphocyte-sparing effects. RESULTS Patients treated with protons had 17.1% less grade 3 and 4 RIL compared to photons. The mean dose to circulating lymphocytes was 1.28 ± 0.37 Gy(RBE) for proton therapy and 3.12 ± 0.75 Gy for photon therapy. The patient-specific model captured three distinct patterns of ALC kinetics: plateau phase, normal recovery, and incomplete recovery, with a mean squared error (MSE) of 0.024 ± 0.025 (mean ± SD) between the simulated and observed ALC values. On average, 42.72% of circulating lymphocytes received more than 0.1 Gy(RBE) in proton FLASH, significantly less than the 81.94% in photon FLASH. Hypofractionated RT, SBRT, and FLASH were 6.5%, 20.2%, and 29.9%, respectively, higher than conventional RT in term of ALC levels 3 months post-RT. At 1 year post-RT, most patients achieved at least 70% recovery of baseline ALC for all treatment regimens. CONCLUSION A patient-specific method has been developed for modeling lymphocyte dynamics over the course of RT and the subsequent follow-up period for HNC patients.
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Affiliation(s)
- Jiaxin Li
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
- University of Chinese Academy of Sciences, Beijing, China
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Rahul Mali
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Gregory N Gan
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Christopher Lominska
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Kenny Guida
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Aditya Juloori
- Department of Radiation Oncology, University of Chicago, Chicago, USA
| | - Matthew Wen-Ruey Chen
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Wangyao Li
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Jufri Setianegara
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Chao Wang
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Yuting Lin
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
| | - Qiang Li
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Weiqiang Chen
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Hao Gao
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, USA
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Munhoz J, Newell M, Goruk S, Ghosh S, Patel D, Joy AA, Bigras G, Mazurak V, Courneya KS, Hemmings DG, Field CJ. Docosahexaenoic acid (DHA) supplementation attenuates changes in the concentration, phenotype, and response of immune peripheral blood cells in breast cancer patients undergoing neoadjuvant therapy. Secondary findings from the DHA-WIN trial. Breast Cancer Res 2025; 27:91. [PMID: 40405290 PMCID: PMC12100857 DOI: 10.1186/s13058-025-02048-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2025] [Accepted: 05/16/2025] [Indexed: 05/24/2025] Open
Abstract
BACKGROUND Breast cancer neoadjuvant therapy may negatively impact the immune system. As a secondary outcome of the docosahexaenoic acid (DHA) for women with breast cancer in the neoadjuvant setting (DHA-WIN trial), we sought to assess the effects of an intervention with DHA on parameters of immune function of women undergoing neoadjuvant therapy. METHODS Women with early-stage breast cancer in the neoadjuvant setting were recruited for the DHA-WIN trial and randomly assigned to receive either 4.4 g/day of DHA or a placebo for 18 weeks in conjunction with their neoadjuvant chemotherapy for breast cancer. Venous blood was collected to isolate peripheral blood mononuclear cells. Immune parameters were assessed by measuring white blood cell concentration, flow cytometry, and cytokines concentration after mitogen-stimulated immune response. RESULTS In the placebo group the proportion of T cells (CD3 +), and functionally active monocytes (CD14 + HLA-DR +) was reduced at the last cycle of chemotherapy (15 weeks) but remained constant in the DHA group (P interaction < 0.05). The neutrophil-to-lymphocyte ratio (NLR) was maintained in the DHA group but increased in the placebo at the end of chemotherapy (P-interaction = 0.02). An increase in this ratio was associated with lower chance of achieving pathological complete response (OR = 0.32, 95% CI [0.14,0.16], P = 0.01). After 15 weeks of therapy, the DHA-supplemented group had higher concentrations of stimulated cytokines IL-4, IL-10, and the T helper type 1 cytokine IFN-γ after phytohemagglutinin (PHA) challenge, and higher concentrations of TNF-α and IFN-γ cytokines after lipopolysaccharide exposure (P < 0.05). CONCLUSION Supplementing DHA during breast cancer neoadjuvant chemotherapy improved systemic immune function by attenuating changes in blood cell concentrations, preventing depletion of immune cells, and enhancing ex vivo cytokine secretion after stimulation.
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Affiliation(s)
- Jaqueline Munhoz
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Marnie Newell
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Susan Goruk
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Sunita Ghosh
- Department of Oncology, University of Alberta, Edmonton, T6G 1Z2, Canada
- Department of Public Health Sciences, Henry Ford Hospital, Detroit, USA
| | - Dhruvesh Patel
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Anil Abraham Joy
- Department of Oncology, University of Alberta, Edmonton, T6G 1Z2, Canada
| | - Gilbert Bigras
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - Vera Mazurak
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada
| | - Kerry S Courneya
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, T6G 2H9, Canada
| | - Denise G Hemmings
- Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, T5G 0B6, Canada
| | - Catherine J Field
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
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8
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Tsutsumi C, Ohuchida K, Imamura M, Tan B, Shimada Y, Son K, Kosai T, Katayama N, Mochida Y, Hayashida S, Iwamoto C, Torata N, Horioka K, Shindo K, Mizuuchi Y, Ikenaga N, Nakata K, Oda Y, Nakamura M. Prognostic nutrition index reveals LAG3 in cytotoxic CD8+ T cells and MHC class II in gastric cancer cells. Cancer Immunol Immunother 2025; 74:176. [PMID: 40252096 PMCID: PMC12009253 DOI: 10.1007/s00262-025-04037-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/25/2025] [Indexed: 04/21/2025]
Abstract
BACKGROUND The prognostic nutrition index (PNI) has recently been highlighted as a predictor of immune checkpoint (IC) inhibitor efficacy in gastric cancer (GC). Although LAG3, an IC molecule, has gained considerable attention, its association with PNI remains unexplored. MATERIALS AND METHODS We retrospectively analyzed clinical data from 796 GC patients who underwent radical gastrectomy to identify which previously reported nutritional index had the greatest impact on prognosis. Single-cell RNA sequencing was performed on 38 GC tissues, and multiplex immunofluorescence staining was conducted on 59 GC tissues to evaluate the relationship between nutritional indices and IC molecule expression in cytotoxic CD8-positive T cells. RESULTS A low preoperative PNI was identified as the strongest predictor of poor prognosis among the nutritional indices in GC patients. The expression of not only PDCD1 (encoding PD1) but also LAG3 in cytotoxic CD8-positive T cells was significantly higher in GC with low PNI compared to those with high PNI. Among cytotoxic CD8-positive T cells, the proportion of LAG3-positive cells was greater than that of PDCD1-positive cells, particularly in GC with low PNI, and most LAG3-positive cells did not co-express PDCD1. Additionally, the expression of MHC class II, a ligand for LAG3, was higher in GC cells with high levels of epithelial-mesenchymal transition-related molecules in GC with low PNI compared to those with high PNI. CONCLUSIONS PNI can reflect LAG3 expression in cytotoxic CD8-positive T cells and MHC class II expression in GC cells.
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Affiliation(s)
- Chikanori Tsutsumi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kenoki Ohuchida
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
- Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| | - Masaki Imamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Bryan Tan
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuki Shimada
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kiwa Son
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Takaaki Kosai
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Naoki Katayama
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yuki Mochida
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Sayuri Hayashida
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Chika Iwamoto
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Nobuhiro Torata
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kohei Horioka
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Koji Shindo
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yusuke Mizuuchi
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Naoki Ikenaga
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Kohei Nakata
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
| | - Yoshinao Oda
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masafumi Nakamura
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
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Xie Y, Shi Z, Chen T, Li H, Fan M, Xiang X, Liu F. The Lung Cancer Immune Prognostic Score predicts pathologic complete response and survival in NSCLC patients receiving neoadjuvant immunochemotherapy. Front Immunol 2025; 16:1567565. [PMID: 40308604 PMCID: PMC12040963 DOI: 10.3389/fimmu.2025.1567565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 03/26/2025] [Indexed: 05/02/2025] Open
Abstract
Introduction Neoadjuvant immunochemotherapy (nICT) has significantly improved event-free survival (EFS) and pathologic complete response (pCR) in patients with resectable non-small cell lung cancer (NSCLC). However, the lack of validated biomarkers limits their ability to predict therapeutic efficacy and survival outcomes. This study aimed to develop a novel inflammatory and nutritional index, the Lung Cancer Immune Prognostic Score (LCIPS), to predict pCR and survival prognosis in patients with NSCLC. Methods This retrospective study included 131 patients with clinical stage IB-IIIB NSCLC who underwent neoadjuvant immunochemotherapy between May 2020 and May 2024. Baseline clinical data and hematological parameters were collected. Lasso regression analysis was employed to identify hematological indices associated with pCR, and the LCIPS was constructed based on these factors. Kaplan-Meier survival analysis and log-rank tests were used to assess survival differences. Logistic regression was performed to identify the predictors of pCR, while Cox regression analysis determined independent prognostic factors for disease-free survival (DFS) and overall survival (OS). The predictive performance of the LCIPS was validated using a nomogram. Results Lasso regression identified three core hematological indices: the albumin-to-globulin ratio (A/G), absolute monocyte count (MONO), and absolute lymphocyte count (LYM). The LCIPS formula was as follows: LCIPS=0.900×A/G+0.761×MONO (109/L) -0.065×LYM (109/L). Receiver operating characteristic (ROC) curve analysis showed that the LCIPS had superior predictive efficacy (area under the curve (AUC) = 0.68) compared to other classical markers. Univariate and multivariate logistic regression analyses identified intraoperative lymph node dissection status and A/G and LCIPS as independent predictors of pCR (p < 0.05). Multivariate Cox regression analysis demonstrated that smoking status and LCIPS were independent prognostic factors for DFS and OS. Nomogram validation indicated robust predictive accuracy for LCIPS. Notably, among immune-related adverse events (irAEs), endocrine- and cardiac-related irAEs significantly affected DFS (p < 0.05). Discussion LCIPS is an independent predictor of pCR in patients with NSCLC receiving neoadjuvant immunochemotherapy and is associated with improved DFS and survival outcomes. This novel index offers valuable guidance for personalized treatment strategies.
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Affiliation(s)
| | | | | | | | | | | | - Fang Liu
- Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
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10
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Liana P, Syahbiran HG, Sari NP, Rahadiyanto KY, Nurwany R, Nurhidayat W, Umar TP. Haematology results, inflammatory haematological ratios, and inflammatory indices in cervical cancer: How is the difference between cancer stage? World J Exp Med 2025; 15:96988. [PMID: 40115758 PMCID: PMC11718581 DOI: 10.5493/wjem.v15.i1.96988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 10/22/2024] [Accepted: 11/01/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND Cervical cancer is a prevalent form of cancer affecting women worldwide and it is the second most common cancer among women in Indonesia, accounting for 8.5% of all cancer-related deaths. Cervical cancer progression can be evaluated through laboratory tests to detect anaemia, an increased platelet count, and elevated inflammatory markers, therefore, effective laboratory examination is crucial for early detection and treatment of cervical cancer. AIM To evaluate the association between laboratory findings (haematology, haematology index, and inflammatory index) and the clinical stage of cervical cancer. METHODS This cross-sectional study analyzed adult cervical cancer patients' data from medical records and laboratory results including sociodemographic status, histopathological finding, clinical stage, and complete haematology examination. Numerical data was analyzed by the one-way ANOVA (normal data distribution), while the Kruskal-Wallis test was used for non-parametric data (abnormal distribution), followed by appropriate post-hoc analysis. The categorical data was analyzed by the Chi-square or Fisher Exact tests. The significance level was established at a P value < 0.05. RESULTS This study involved the data of 208 adult cervical cancer patients and found no association between age, marital history, parity history, hormonal contraceptive use and cervical cancer stages. There were significant differences in the clinical laboratory test results based on the clinical stage of cervical cancer, including haemoglobin levels (P < 0.001), leucocytes (P < 0.001), neutrophils (P < 0.001), monocytes (P = 0.002), lymphocytes (P = 0.006), platelets (P < 0.001), neutrophil-lymphocyte ratio/NLR (P < 0.001), lymphocyte-monocyte ratio/LMR (P < 0.001), and platelet-lymphocyte ratio/PLR (P < 0.001). There were also significant differences in the systemic inflammatory index (SII) and systematic inflammatory response index (SIRI) between stage III + IV cervical cancer and stage II (SII P < 0.001; SIRI P = 0.001) and stage I (SII P < 0.001; SIRI P = 0.016), associated with the shifts in previously mentioned complete haematological values with cancer advancement. CONCLUSION The haematological parameters, inflammatory haematological ratios, and inflammatory indices exhibited significant differences between cervical cancer stages, therefore these tests can be utilized to evaluate cervical cancer progression.
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Affiliation(s)
- Phey Liana
- Department of Clinical Pathology, Faculty of Medicine, Universitas Sriwijaya-Dr. Mohammad Hoesin General Hospital, Palembang 30114, Sumatera Selatan, Indonesia
| | - Hanif Gusneri Syahbiran
- Department of Medicine Programme, Faculty of Medicine, Universitas Sriwijaya, Palembang 30114, Sumatera Selatan, Indonesia
| | - Nurmalia Purnama Sari
- Department of Clinical Pathology, Faculty of Medicine, Universitas Sriwijaya-Dr. Mohammad Hoesin General Hospital, Palembang 30114, Sumatera Selatan, Indonesia
| | - Kemas Yakub Rahadiyanto
- Department of Clinical Pathology, Faculty of Medicine, Universitas Sriwijaya, Palembang 30114, Sumatera Selatan, Indonesia
| | - Raissa Nurwany
- Department of Physiology and Medical Physics, Faculty of Medicine, Universitas Sriwijaya, Palembang 30114, Sumatera Selatan, Indonesia
| | - Wahyudi Nurhidayat
- Department of Radiotherapy, Dr. Mohammad Hoesin General Hospital, Palembang 30114, Sumatera Selatan, Indonesia
| | - Tungki Pratama Umar
- Division of Surgery and Interventional Science, Faculty of Medical Sciences, University College London, London WC1E 6BT, United Kingdom
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11
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Ding P, Zhang L, Pei S, Qu Z, Kong X, Wang Z, Wang J, Fang Y. Nomogram construction for overall survival in breast angiosarcoma based on clinicopathological features: a population-based cohort study. Discov Oncol 2025; 16:351. [PMID: 40100579 PMCID: PMC11920551 DOI: 10.1007/s12672-025-02118-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 03/11/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND Breast angiosarcoma (BAS) is a rare, aggressive malignancy with a poor prognosis, often challenging to assess due to its unique biology. This study aimed to develop a nomogram to predict 3- and 5-year overall survival (OS) for BAS patients using key clinicopathological factors. METHODS Data from 450 BAS patients diagnosed between 2000 and 2021 were extracted from SEER database. Key variables, including age, tumor size, tumor grade, and distant metastasis status, were identified through univariate and multivariate Cox regression analyses. These factors were incorporated into a nomogram for OS prediction. The model was validated internally and externally using the concordance index (C-index), calibration curves, and decision curve analysis (DCA) to assess its predictive accuracy and clinical utility. RESULTS The nomogram demonstrated good predictive accuracy, with a C-index of 0.68 in the training set and 0.72 in the test set. ROC analysis indicated strong short-term predictive power, with AUC values of 0.81 and 0.75 for 1-year survival in the training and test sets, respectively, though predictive performance declined over time. DCA showed substantial clinical benefit for 12-month predictions, which diminished over longer time frames. The model effectively distinguished high-risk BAS patients and provided individualized survival estimates, supporting its potential use in clinical decision-making. CONCLUSION This study presents the first BAS nomogram for OS prediction, showing robust short-term accuracy. The long-term utility is limited by heterogeneity and sample size, highlighting the need for external validation to confirm generalizability and clinical applicability.
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Affiliation(s)
- Peikai Ding
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Luxiao Zhang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Shengbin Pei
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zheng Qu
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xiangyi Kong
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhongzhao Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jing Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Yi Fang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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12
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Smeenk MM, van Diessen JN, Boellaard TN, Hartemink KJ, de Vries JF, van der Noort V, Badrising SK, Owers EC, Monkhorst K, van den Heuvel MM, Theelen WS. Tremelimumab plus Durvalumab prior to Chemoradiotherapy in Unresectable, Locally Advanced Non-Small Cell Lung Cancer: The Induction Trial. Clin Cancer Res 2025; 31:1037-1046. [PMID: 39821070 PMCID: PMC11911803 DOI: 10.1158/1078-0432.ccr-24-3476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 12/05/2024] [Accepted: 01/14/2025] [Indexed: 01/19/2025]
Abstract
PURPOSE The phase I induction trial (NCT04287894) assessed the feasibility and safety of induction immunotherapy (IIT) prior to concurrent chemoradiotherapy (cCRT) in patients with locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with unresectable stage II/III NSCLC were eligible for inclusion. Patients received either one cycle of tremelimumab (75 mg) with two cycles of durvalumab (1,500 mg) in cohort I, one cycle of tremelimumab (300 mg) with two cycles of durvalumab in cohort II, or one cycle of tremelimumab (300 mg) with one cycle of durvalumab in cohort III. After IIT, a comprehensive radiological and pathological restaging was performed followed by cCRT. The combined primary endpoint was the feasibility and safety of IIT-cCRT. RESULTS Fifteen of 17 included patients were treated per protocol. IIT-cCRT was completed in 13 of the 15 patients within the predefined feasibility criteria. Grade ≥3 immune-related adverse events occurred in seven of the 15 patients, of which six were treated in the high-dose tremelimumab cohorts, thereby violating the safety criteria in cohorts II and III. The low-dose tremelimumab cohort (I) complied with safety criteria. Eleven patients had multilevel N2 or N3 disease at baseline; eight of these patients were downstaged to either N0/N1 or single-level N2 after IIT. Multiparametric MRI accurately identified nodal downstaging in all seven patients. CONCLUSIONS Induction with high-dose tremelimumab plus durvalumab prior to cCRT in unresectable locally advanced NSCLC was associated with unacceptable toxicity, although IIT resulted in clinically relevant nodal downstaging in eight of the 11 patients with baseline multilevel N2 or N3 disease. Multiparametric MRI showed potential for evaluating treatment response.
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MESH Headings
- Humans
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/therapy
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Carcinoma, Non-Small-Cell Lung/mortality
- Female
- Male
- Middle Aged
- Lung Neoplasms/pathology
- Lung Neoplasms/therapy
- Lung Neoplasms/drug therapy
- Lung Neoplasms/mortality
- Antibodies, Monoclonal/administration & dosage
- Antibodies, Monoclonal/adverse effects
- Antibodies, Monoclonal, Humanized/administration & dosage
- Antibodies, Monoclonal, Humanized/adverse effects
- Aged
- Chemoradiotherapy/methods
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Antineoplastic Combined Chemotherapy Protocols/adverse effects
- Adult
- Neoplasm Staging
- Treatment Outcome
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Affiliation(s)
- Michiel M. Smeenk
- Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Judi N.A. van Diessen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Thierry N. Boellaard
- Department of Radiology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Koen J. Hartemink
- Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands
- Department of Thoracic Oncology, Leiden University Medical Center, Leiden, the Netherlands
| | - Jeltje F. de Vries
- Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Sushil K. Badrising
- Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Emilia C. Owers
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Kim Monkhorst
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
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13
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Xu C, Wu J, Liu B, Meng H, Zhao L, Wang P, Sun J, Wang J, Liu N. Simultaneous integrated dose reduction intensity-modulated radiotherapy improves survival in patients with locally advanced non-small cell lung cancer by reducing cardiac irradiation exposure. Discov Oncol 2025; 16:300. [PMID: 40069527 PMCID: PMC11896949 DOI: 10.1007/s12672-025-02046-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Accepted: 03/04/2025] [Indexed: 03/15/2025] Open
Abstract
The study aimed to evaluate the safety and efficacy of simultaneous integrated dose reduction intensity-modulated radiotherapy (SIR-IMRT) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). In the SIR-IMRT conhort, the prescribed irradiation dose was 60 Gray (Gy) for the planning gross tumor volume (PGTV) and 54 Gy for the planning target volume (PTV), while in the conventional intensity-modulated radiotherapy (C-IMRT) cohort, it was 60 Gy for both PGTV and PTV. The SIR-IMRT group demonstrated better overall survival (OS) than the C-IMRT group, with a median OS of 37.7 versus 31.2 months. The SIR-IMRT group also experienced lower cardiac and esophagusal doses, along with a lower incidence of acute radiation esophagitis and ≥ grade 3 radiation pneumonitis. HeartV20 (the volume of the heart receiving at least 20 Gy) was the only independent risk factor associated with survival. SIR-IMRT significantly reduced cardiac irradiation exposure, improving patient survival and offering a new therapeutic direction for future studies.
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Affiliation(s)
- Chang Xu
- Department of Radiation Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin' s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jiehan Wu
- Department of Radiation Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin' s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Bingxin Liu
- P.C. Rossin College of Engineering and Applied Science, Lehigh University, 27 Memorial Drive West, Bethlehem, PA, 18015, USA
| | - Hanheng Meng
- Department of Radiation Oncology, The Second People's Hospital of Datong Cancer Hospital, Shanxi Datong University Affiliated Cancer Hospital, Datong, Shanxi, China
| | - Lujun Zhao
- Department of Radiation Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin' s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Ping Wang
- Department of Radiation Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin' s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Jifeng Sun
- Department of Radiation Oncology, Konggang Branch of Tianjin Cancer Hospital, Dong Fifth Road, Dongli District, Tianjin, China
| | - Jun Wang
- Department of Radiation Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin' s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Ningbo Liu
- Department of Radiation Oncology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin' s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
- Hetian District People's Hospital, Hetian, 848000, Xinjiang, China.
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14
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Gao Y, Zhang L, Yan M, Sun Z, Zhao H, Zhao L. Development of a prognostic model for patients with extensive-stage small cell lung cancer undergoing immunotherapy and chemotherapy. Front Immunol 2025; 16:1561333. [PMID: 40124379 PMCID: PMC11926142 DOI: 10.3389/fimmu.2025.1561333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 02/25/2025] [Indexed: 03/25/2025] Open
Abstract
Purpose In this study, we aimed to develop a predictive model for patients receiving chemotherapy and immunotherapy for extensive-stage small cell lung cancer. Methods We retrospectively analyzed 112 extensive-stage small cell lung cancer patients treated with first-line immunotherapy and chemotherapy. The relevant clinical data were collected to evaluate the changes during the treatment. The best subset regression, univariate analysis, and LASSO regression with cross-validation were applied for variable selection and model establishment. The nomograms for 1- and 2-year survival probabilities were established, and the calibration curve was utilized to evaluate the correspondence between actual and predicted survival. The model prediction capacity was assessed using decision curve analysis, calibration curves, and receiver operating characteristic curves. Moreover, five-fold cross-validation was conducted for internal validation. According to risk score, the patients were assigned to high- and low-risk groups, and survival curves were generated for each group. Results The LASSO regression model was established based on the variables such as age, ECOG, metastatic sites, NLR, and immunotherapy cycles. This predictive model displayed robust performance, evidenced by the Area Under the Curve of 0.887 and concordance index of 0.759. The nomogram effectively predicted 1- and 2-year survival probabilities and demonstrated a high degree of calibration. The decision curve analysis displayed that the model possessed superior predictive capability. The risk stratification for patients with high- and low-risk categories facilitated more individualized survival assessment. Conclusion The study successfully developed a prognostic model for extensive-stage small cell lung cancer patients undergoing immunotherapy and chemotherapy, demonstrating the good accuracy and predictability.
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Affiliation(s)
- Yunbin Gao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- Department of Oncology, Jining No. 1 People’s Hospital, Jining, Shandong, China
| | - Lixia Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Meng Yan
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Zongwen Sun
- Department of Oncology, Jining No. 1 People’s Hospital, Jining, Shandong, China
| | - Haibo Zhao
- Department of Oncology, Jining No. 1 People’s Hospital, Jining, Shandong, China
| | - Lujun Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
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15
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Osa-Andrews B, van Wijk XMR, Herrera Rivera N, Seifert RP, Harris NS, Marin MJ. An Introduction to the Complete Blood Count for Clinical Chemists: White Blood Cells. J Appl Lab Med 2025; 10:459-475. [PMID: 39873240 DOI: 10.1093/jalm/jfaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 12/26/2024] [Indexed: 01/30/2025]
Abstract
BACKGROUND The most frequently ordered laboratory test worldwide is the complete blood count (CBC). As clinical chemists are increasingly assigned to assist or direct laboratories outside of the traditional clinical chemistry sections, such as the automated hematology section, expertise must be established. This review article is a dedication to that ongoing effort. CONTENT In this primer, the white blood cell (WBC) test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of leukopenia and leukocytosis. SUMMARY The laboratorian's approach to consult cases should be guided by the patient's clinical history and presentation while being able to provide key laboratory-based insights to assist in resolving result discrepancies that may otherwise go unnoticed.
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Affiliation(s)
- Bremansu Osa-Andrews
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Xander M R van Wijk
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States
| | | | - Robert P Seifert
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Neil S Harris
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Maximo J Marin
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
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Pham TN, Coupey J, Thariat J, Valable S. Impact of circulating lymphocyte kinetics following radiotherapy on patient survival: A model-based meta-analysis. Comput Biol Med 2025; 186:109702. [PMID: 39864332 DOI: 10.1016/j.compbiomed.2025.109702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/09/2025] [Accepted: 01/13/2025] [Indexed: 01/28/2025]
Abstract
INTRODUCTION Radiation-induced lymphopenia (RIL) has been shown to adversely affect the prognosis of cancer patients undergoing radiotherapy (RT). This model-based meta-analysis investigated the prognostic significance of lymphocyte counts both early and late after RT and examined the dose‒response relationship between post-RT lymphocyte levels and patient survival. METHODS A literature search of published articles on the effect of RIL on cancer prognosis was conducted using the PubMed and Cochrane databases. A survival model was developed, incorporating absolute lymphocyte count (ALC) thresholds during (1 month after RT initiation, nadir) and 6 months after RT (recovery) as covariates to estimate progression-free survival (PFS) and overall survival (OS). This survival model, with the lymphocyte count cutoff as a covariate, was then used to simulate the benefit of increased PFS and OS in populations without lymphopenia or severe lymphopenia compared to the total population. RESULTS A total of 35 studies met the inclusion criteria for survival analysis. Our survival model revealed an increase in survival in the subgroup without lymphopenia compared to the total population. The subgroup without lymphopenia 1 month after RT initiation showed a 10.28 % and 3.92 % increase in 24-month PFS and OS, respectively. The subgroup without lymphopenia at 6 months showed a 5.82 % and 2.78 % increase in 24-month PFS and OS, respectively. CONCLUSION This study highlights the critical role of lymphocyte nadir and recovery following RT in patient prognosis and strengthens the evidence for a causal relationship between RIL and patient outcomes. Expanding the dataset and including randomized controlled trials would provide a more comprehensive understanding of monitoring or knowledge of ALC profiles following RT.
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Affiliation(s)
- Thao-Nguyen Pham
- Université de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, F-14000, Caen, France; Laboratoire de Physique Corpusculaire UMR6534 IN2P3/ENSICAEN, France - Normandie Université, France; Department of Radiation Oncology, Centre François Baclesse, Caen, Normandy, France
| | - Julie Coupey
- Université de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, F-14000, Caen, France
| | - Juliette Thariat
- Laboratoire de Physique Corpusculaire UMR6534 IN2P3/ENSICAEN, France - Normandie Université, France; Department of Radiation Oncology, Centre François Baclesse, Caen, Normandy, France
| | - Samuel Valable
- Université de Caen Normandie, CNRS, Normandie Université, ISTCT UMR6030, GIP CYCERON, F-14000, Caen, France.
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Xu X, Tian M, Ding CC, Xu H, Wang H, Jin X. Skeletal Muscle Index-Based Cachexia Index as a Predictor of Prognosis in Patients With Cancer: A Meta-Analysis and Systematic Review. Nutr Rev 2025; 83:e852-e865. [PMID: 39001797 DOI: 10.1093/nutrit/nuae094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/15/2024] Open
Abstract
CONTEXT Cachexia is associated with poor survival rates. In the clinical setting, the diagnosis of cancer cachexia is challenging. The cachexia index (CXI), a new index for predicting survival time, is a promising tool for diagnosing cancer cachexia; however, its efficacy in predicting patient survival has not been validated. OBJECTIVE This meta-analysis and systematic review aimed to explore the CXI's prognostic value in patients with cancer. DATA SOURCES The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched for relevant studies to determine the association between CXI findings and prognosis. DATA EXTRACTION The outcomes were overall survival (OS), progression-, disease-, and recurrence-free survival (PFS/DFS/RFS) rates, and the rate of complete response. DATA ANALYSIS The QUality In Prognostic Studies (QUIPS) tool was used to evaluate the quality of the included trials. This meta-analysis comprised 14 studies involving 2777 patients. A low CXI was associated with decreased OS (hazard ratio [HR] 2.34, 95% confidence interval [CI] 2.01-2.72; P < .001), PFS/DFS/RFS (HR 1.93, 95% CI 1.68-2.22; P < .001), and complete response (odds ratio [OR] 0.49, 95% CI 0.36-0.66; P < .001). Patients with a low CXI had a lower body mass index (mean difference [MD] -0.75, 95% CI -1.00 to 0.50; P < .001), skeletal muscle index (standardized MD -0.80, 95% CI -0.98 to -0.61; P < .001), and serum albumin level (MD -0.23, 95% CI -0.26 to -0.20; P < .001); and a higher neutrophil-lymphocyte ratio (MD 1.88, 95% CI 1.29-2.47; P < .001) and more advanced disease stages (OR 0.80, 95% CI 0.71-0.91; P = .001). CONCLUSION A low CXI was found to be associated with poor survival in patients with cancer. While the CXI is a promising marker for predicting cancer cachexia, further studies are required to verify its usefulness.
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Affiliation(s)
- Xintian Xu
- Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China
| | - Mengxing Tian
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China
| | - Chen Chen Ding
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China
| | - Huiting Xu
- Department of Abdominal Oncology 1, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China
| | - Huifen Wang
- Nursing Department, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China
| | - Xin Jin
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, China
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Liu X, Li M, Zhao Y, Jiao X, Yu Y, Li R, Zeng S, Chi J, Ma G, Huo Y, Peng Z, Liu J, Zhou Q, Zou D, Wang L, Li Q, Wang J, Yao S, Chen Y, Ma D, Hu T, Gao Q. The impact of preoperative immunonutritional status on prognosis in ovarian cancer: a multicenter real-world study. J Ovarian Res 2025; 18:30. [PMID: 39962572 PMCID: PMC11831797 DOI: 10.1186/s13048-025-01607-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 01/22/2025] [Indexed: 02/21/2025] Open
Abstract
BACKGROUND To investigate the effect of preoperative immunonutritional status on prognosis in epithelial ovarian cancer patients. METHODS A multicenter real-world study included 922 patients with histologically confirmed epithelial ovarian cancer who received comprehensive staged surgery or debulking surgery at seven tertiary hospitals in China between 2012 and 2023. Prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) were used to assess the immunonutritional status for their superior predictive power to indicate the nutritional status and the inflammatory immunity. Cox regression analyses were employed to identify variables associated with progression-free survival (PFS) and overall survival (OS). RESULTS In the early-stage cohort of 224 epithelial ovarian cancer patients, the optimal cut-off value for PNI was 47.47 for both PFS and OS, while the optimal cut-off value for SII values were 551.37 for PFS and 771.78 for OS. In the late-stage group of 698 patients, the optimal PNI thresholds were 47.76 for PFS and 46.00 for OS, with SII values of 720.96 for PFS and 1686.11 for OS. In multivariate analysis of early-stage patients, high PNI was an independent protective factor for PFS (hazard ratio (HR), 0.39 (95% confidence interval (CI) 0.20-0.76), P = 0.006) and OS (HR, 0.44 (95% CI 0.20-0.97), P = 0.042), respectively. High SII was significantly associated with PFS (HR, 2.43 (95% CI 1.23-4.81), P = 0.011) and marginally unfavorable for OS (HR, 2.05 (95% CI 0.96-4.39), P = 0.064). In advanced population, PNI (HR, 0.77 (95% CI 0.60-0.99), P = 0.043) and SII (HR, 1.34 (95% CI 1.01-1.78), P = 0.041) were independent prognostic factors for OS but had no impact on PFS (P = 0.185, P = 0.188, respectively). CONCLUSION Poor preoperative immunonutritional status has a deleterious effect on the prognosis of patients with ovarian cancer. Intervention in patients suffering from suboptimal preoperative immunonutritional status may facilitate improved survival outcomes.
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Affiliation(s)
- Xingyu Liu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Ming Li
- Department of Gynaecology and Obstetrics, Henan Provincial People's Hospital, Henan, China
| | - Yingjun Zhao
- Department of Gynaecology and Obstetrics, Henan Provincial People's Hospital, Henan, China
| | - Xiaofei Jiao
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Yang Yu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Ruyuan Li
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shaoqing Zeng
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Jianhua Chi
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Guanchen Ma
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Yabing Huo
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Zikun Peng
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Jiahao Liu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Qi Zhou
- Department of Gynecologic Oncology, Chongqing University Cancer Hospital, Chongqing, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
- Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, China
| | - Dongling Zou
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Gynecologic Oncology, Chongqing University Cancer Hospital, Chongqing, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Li Wang
- Department of Cancer Biology Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, Henan, China
| | - Qingshui Li
- Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China
| | - Jing Wang
- Hunan Clinical Research Center in Gynecologic Cancer, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Changsha, Hunan, China
- Department of Gynecologic Cancer, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Shuzhong Yao
- Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Youguo Chen
- Department of Gynecology & Obstetrics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Ding Ma
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China
| | - Ting Hu
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China.
| | - Qinglei Gao
- Department of Gynecological Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- National Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430000, China.
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Wang J, Wang J, Liu H, Chen C. Routine Blood Tests as Predictive Tools for Differentiating Follicular Thyroid Carcinoma From Follicular Adenoma. Int J Gen Med 2025; 18:733-744. [PMID: 39963518 PMCID: PMC11830949 DOI: 10.2147/ijgm.s502626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/04/2025] [Indexed: 02/20/2025] Open
Abstract
Background Thyroid cancer is the most common endocrine malignancy, with an increasing incidence rate, particularly among adolescents. Follicular thyroid carcinoma (FTC), though less common than papillary thyroid carcinoma (PTC), presents greater diagnostic challenges, especially when differentiating from follicular adenoma (FA). Current diagnostic methods lack specificity, underscoring the need for a simple, cost-effective predictive model for FTC.This study aimed to develop a predictive scoring system based on routine blood biomarkers to distinguish between FTC and FA, facilitating early diagnosis and treatment. Methods A retrospective, single-center case-control study was conducted on patients diagnosed with FTC and FA at Renmin Hospital of Wuhan University from 2016 to 2022. Patients' demographic, clinicopathological characteristics, and preoperative blood biomarker data were analyzed. Statistical tests, including chi-square, t-tests, and Mann-Whitney U-tests, were used to compare biomarkers. Significant variables were included in univariate and multivariate logistic regression analyses, leading to the development of a scoring system. The model's performance was assessed using receiver operating characteristic (ROC) curves. Results The study included 23 patients with FA and 26 patients with FTC. Seven blood biomarkers showed significant differences between the groups: ALB, DBIL, TBIL, LYM#, MCHC, RDW-SD, and WBC. Multivariate logistic regression identified ALB and WBC as key predictors, forming a scoring model (Score = 0.54 × ALB - 1.10 × WBC). The model exhibited strong predictive performance (AUC = 0.839), with sensitivity and specificity of 0.808 and 0.826, respectively. Conclusion The study developed a novel predictive model using routine blood biomarkers, offering a non-invasive, cost-effective tool for differentiating between FTC and FA. The model has significant clinical potential, providing a feasible alternative to conventional diagnostic techniques. Further multicenter studies and mechanistic investigations are warranted to validate and refine the model, enhancing its utility in clinical practice.
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Affiliation(s)
- Jiaxi Wang
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Jingwei Wang
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Hanqing Liu
- Department of Thyroid Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
| | - Chuang Chen
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
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Li Y, Yu M, Yang M, Yang J. The association of systemic immune-inflammation index with incident breast cancer and all-cause mortality: evidence from a large population-based study. Front Immunol 2025; 16:1528690. [PMID: 39925802 PMCID: PMC11802490 DOI: 10.3389/fimmu.2025.1528690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 01/08/2025] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND Chronic low-grade inflammation is recognized as a significant factor in various health outcomes, including the development and progression of breast cancer. The Systemic Immune-Inflammation Index (SII), a novel marker derived from routine blood counts, has been suggested as a predictor of all-cause mortality and cardiovascular mortality. However, its predictive value in a nationwide representative population, particularly for breast cancer incidence and mortality, is not well-established. METHODS This study aimed to assess the association of SII and the risk of breast cancer incidence and all-cause mortality in breast cancer patients within the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. SII was calculated from complete blood count parameters. We used multifactor regression models to examine the associations between SII and the outcomes of interest. RESULTS A total of 21,058 female participants were included in the study, of which 557 (2.7%) were identified as having breast cancer. After adjusting for multiple potential confounders, the relationship between SII and the incidence of breast cancer revealed an inverse L-shaped association. The optimal inflection point for SII/100 was determined to be 5.09. Below this threshold, there was a significant increase in the risk of breast cancer (OR=1.05, 95% CI: 1.02-1.09). Within the breast cancer population, SII exhibited a J-shaped relationship with all-cause mortality. The optimal inflection point for SII/100 in this context was 5.22, and above this threshold, there was a marked escalation in all-cause mortality (HR=1.09, 95% CI: 1.04-1.14). CONCLUSION The SII, as a novel inflammatory composite index, is significantly associated with the risk of breast cancer incidence and all-cause mortality in breast cancer patients. These findings highlight the importance of monitoring systemic inflammation and suggest that SII could serve as a valuable prognostic tool.
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Affiliation(s)
- Yu Li
- Breast Surgery, Pingxiang People’s Hospital, Pingxiang, China
- Breast Surgery, Luxi County People’s Hospital, Pingxiang, China
| | - Meng Yu
- Department of Cardiovascular Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Ming Yang
- Department of Cardiovascular Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
| | - Jingqi Yang
- Department of Cardiovascular Medicine, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China
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Zhu B, Cai Y, Zhou L, Zhao L, Chen J, Shan X, Sun X, You Q, Gong X, Zhang W, Zhu HH, Zhang P, Li Y. Injectable supramolecular hydrogel co-loading abemaciclib/NLG919 for neoadjuvant immunotherapy of triple-negative breast cancer. Nat Commun 2025; 16:687. [PMID: 39814714 PMCID: PMC11735626 DOI: 10.1038/s41467-025-55904-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/04/2025] [Indexed: 01/18/2025] Open
Abstract
The efficacy of cancer immunotherapy relies on a sufficient amount of functional immune cells. Triple-negative breast cancer lacks enough immune cell infiltration, and adjuvant therapy is necessary to prime anti-tumor immunity. However, the improvement in efficacy is unsatisfactory with concern about inducing systemic immunotoxicity. Herein, we create an abemaciclib-loaded supramolecular peptide hydrogel formed by peptide-drug amphiphiles for neoadjuvant immunotherapy of triple-negative breast cancer, where the amphiphile is a conjugate of a β-sheet-forming peptide with 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol (NLG919), an inhibitor of indoleamine 2,3-dioxygenase 1. The hydrogel can be injected into the tumor site and retained for at least one week for the sustained release of both abemaciclib and NLG919. The abemaciclib is able to induce immunogenic cell death of cancer cells and increase interleukin-2 secretion by cytotoxic T lymphocytes. Abemaciclib adversely upregulates indoleamine 2,3-dioxygenase 1, whose kynurenine production activity is inhibited by NLG919. The neoadjuvant immunotherapy reduces tumor recurrence and pulmonary metastasis and prolongs the survival of animals. This hydrogel provides a potential platform for neoadjuvant immunotherapy of triple-negative breast cancer with reduced toxicity compared with free abemaciclib.
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Affiliation(s)
- Binyu Zhu
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China
| | - Ying Cai
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China
- Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong, China
| | - Lingli Zhou
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Zhao
- School of Chemical Engineering, Zhengzhou University, Zhengzhou, China
| | - Jiameng Chen
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China
| | - Xiaoting Shan
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China
| | - Xujie Sun
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China
| | - Qian You
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Xiang Gong
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- National Advanced Medical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, China
| | - Wen Zhang
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
- National Advanced Medical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, China
| | - Helen He Zhu
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Pengcheng Zhang
- School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, China.
| | - Yaping Li
- State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
- University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, China.
- Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong, China.
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
- Shandong Laboratory of Yantai Drug Discovery, Bohai rim Advanced Research Institute for Drug Discovery, Shandong, China.
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Bernardo D, Murugan NJ, Voutsadakis IA. Pre-Treatment Peripheral Blood Parameters as Prognostic Biomarkers in Cancer Patients Receiving Immune Checkpoint Inhibitors. Int J Hematol Oncol Stem Cell Res 2025; 19:7-16. [PMID: 40421401 PMCID: PMC12103826 DOI: 10.18502/ijhoscr.v19i1.17819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 07/01/2024] [Indexed: 05/28/2025] Open
Abstract
Background: Immune checkpoint inhibitors have significantly improved outcomes in select cancers; however, not all patients respond to these therapies, and the duration of the response varies among responders. Markers predictive of the response to immunotherapy, such as PD-L1 expression determined by immunohistochemical staining of tumor sections and microsatellite status, have been identified. Some of these are used in companion diagnostics approved for clinical practice. Additional easy-to-use biomarkers may help clinicians to predict the efficacy of these drugs in individual patients. Materials and Methods: A retrospective review of the medical records of patients with metastatic cancer treated with immune checkpoint inhibitors in our cancer center was performed to identify the clinical and hematologic parameters associated with survival outcomes. Results: Among the 163 patients included in the study, most had lung cancer, followed by kidney cancer, melanoma, and bladder cancer. Most patients (61.3%) were male and had good performance status. Nivolumab and pembrolizumab were immune checkpoint inhibitors utilized in 85.9% of cases. Age, sex, and primary cancer type were not associated with survival outcomes. Among the peripheral blood parameters evaluated, lymphocytopenia was the strongest predictor of adverse survival outcomes in univariate analysis and the only clinical or hematologic biomarker that retained significance for overall survival (OS) prediction in multivariate analysis. Conclusion: Among the clinical and hematologic parameters routinely used in the clinic, a lymphocyte count below 1 x 109/ L was predictive of adverse OS in patients with metastatic cancers receiving immune checkpoint inhibitors.
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Affiliation(s)
| | | | - Ioannis A. Voutsadakis
- Algoma District Cancer Program, Sault Area Hospital, Sault Ste. Marie, Ontario, Canada
- Department of Internal Medicine, Division of Clinical Sciences, Northern Ontario School of Medicine, Sudbury, Ontario, Canada
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Zhang C, Yang Z, Li J, Zhao L. Prognostic Significance of Dynamic Lymphocyte Changes in Esophageal Cancer Patients Receiving Fluorouracil-Cisplatin Combined with Radiotherapy: A Systematic Review and Meta-Analysis. Technol Cancer Res Treat 2025; 24:15330338251341431. [PMID: 40388934 PMCID: PMC12089708 DOI: 10.1177/15330338251341431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 04/07/2025] [Accepted: 04/16/2025] [Indexed: 05/21/2025] Open
Abstract
IntroductionChemoradiotherapy (CRT) is important to the esophageal cancer (EC) management. However, the predictive value of lymphocyte-related parameters, such as lymphocyte count (L), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), is not yet fully understood. Moreover, chemotherapy agents like fluorouracil and cisplatin may have an impact on lymphocyte dynamics. This meta-analysis aims to evaluate the prognostic value of these parameters in EC patients undergoing concurrent CRT (eg, radiotherapy combined with fluorouracil and cisplatin), particularly in the context of specific chemotherapy regimens.MethodsElectronic databases were comprehensively searched up to September 2023 for research that assesses the prognostic role of lymphocyte-related indicators in EC patients undergoing CRT. Combined Hazard Ratios (HR) were estimated with a random-effects model, supplemented by meta-regression and subgroup analyses for enhanced insights.ResultsOf the 41 studies selected for qualitative evaluation, 22 were eligible for meta-analysis. These results revealed that increased pre-NLR (HR = 1.87, 95% CI = 1.55-2.26), lower pre-LMR (HR = 1.94, 95% CI = 1.36-2.77), lower dur-L (HR = 1.56, 95% CI = 1.28-1.90), and higher post-NLR (HR = 1.95, 95% CI = 1.08-3.51) predicted poorer overall survival (OS). Lower pre-LMR (HR = 1.73, 95% CI = 1.14-2.65) and lower dur-L (HR = 1.39, 95% CI = 1.14-1.69) were significant predictors of worse progression-free survival (PFS). The predominant chemotherapy regimen analyzed was fluorouracil combined with cisplatin, which significantly influenced lymphocyte counts and ratios during treatment.ConclusionsOur meta-analysis indicates that pre-treatment NLR, pre-treatment LMR, during-treatment L, and post-treatment NLR are valuable prognostic biomarkers for EC undergoing CRT, particularly in those treated with fluorouracil and cisplatin. Further investigations are warranted to explore their prognostic implications and therapeutic potential.
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Affiliation(s)
- Cong Zhang
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Zhi Yang
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Jie Li
- Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Lina Zhao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
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24
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Sun S, Li W, Guo X, Chen J. Prognostic value of the neutrophil-to-lymphocyte ratio and prognostic nutritional index in unresectable hepatocellular carcinoma patients treated with tyrosine kinase inhibitors and immune checkpoint inhibitors. Hum Vaccin Immunother 2024; 20:2394268. [PMID: 39665848 DOI: 10.1080/21645515.2024.2394268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 08/01/2024] [Accepted: 08/16/2024] [Indexed: 12/13/2024] Open
Abstract
This study aimed to investigate the role of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in unresectable hepatocellular carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). The optical cutoff values of the NLR and PNI were determined via time-dependent receiver operating characteristic curve analysis. The associations between overall survival (OS) and various potential risk factors were analyzed. Forty-nine HCC patients were enrolled in this retrospective study. The optimal pretreatment NLR and PNI cutoff values were 2.4 and 41, respectively. The median follow-up was 8 (range 3-36) months. The median OS in the high NLR subgroup was lower than that in the low NLR subgroup (7 vs. 9 months, p < .05). However, the high PNI group had better OS than the low PNI group did (12 vs. 7 months, p < .05). Univariate analysis revealed that tumor distribution (p = .003), PNI < 41 (p = .013), and NLR ≥ 2.4 (p = .010) were associated with unfavorable OS in HCC patients. The multivariate analysis revealed that the PNI (HR = 0.353, 95% CI 0.150-0.831; p = .017) and tumor distribution (HR = 0.336, 95% CI 0.137-0.826; p = .017) were independent indicators of poor prognosis. A pretreatment NLR ≥ 2.4 and PNI < 41 are related to poor survival in unresectable HCC patients receiving TKI and ICI treatment. Moreover, a lower PNI is an independent indicator of poor prognosis when ICIs are combined with TKIs.
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Affiliation(s)
- Shasha Sun
- Department of Oncology, Capital Medical University Beijing Ditan Hospital, Chaoyang District, Beijing, People's Republic of China
| | - Wendong Li
- Department of Oncology, Capital Medical University Beijing Ditan Hospital, Chaoyang District, Beijing, People's Republic of China
| | - Xiaodi Guo
- Department of Oncology, Capital Medical University Beijing Ditan Hospital, Chaoyang District, Beijing, People's Republic of China
| | - Jinglong Chen
- Department of Oncology, Capital Medical University Beijing Ditan Hospital, Chaoyang District, Beijing, People's Republic of China
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Değerli E, Arslan Ç, Selçukbiricik F, Ölmez ÖF, Erdem D, Hamdard J, Yılmaz M, Çolak R, Kapar C, Erman M, Kuş F, Tural D. Association Between Baseline and Changes in Early Neutrophil-to-Lymphocyte Ratio on Survival in Patients with Metastatic Bladder Carcinoma Treated with Immunotherapy. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:2103. [PMID: 39768982 PMCID: PMC11676646 DOI: 10.3390/medicina60122103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 12/13/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025]
Abstract
Background and Objectives: A high baseline neutrophil-to-lymphocyte ratio (NLR) is a poor prognostic factor in various cancers. However, its predictive role in metastatic bladder cancer (mBC) treated with immunotherapy is unclear. In this study, we aimed to investigate the relationship between the baseline and change in NLR and overall survival in mBC patients treated with immunotherapy, with the potential to significantly impact patient care. Materials and Methods: A retrospective analysis was conducted on 56 mBC patients who received second-line immunotherapy after progressing on platinum-based chemotherapy. Patients were classified into high and low NLR groups using a cutoff value of 3.3. A further division was made based on NLR changes after two cycles of immunotherapy: whether NLR increased (≥10%) or decreased (≥10%). The endpoint was to estimate the association between clinicopathological features and survival outcomes. Results: The study included 56 patients, with a median age of 66.6 years and a male-to-female ratio of 2.3:1. A low baseline NLR was associated with better OS than a high baseline NLR (p = 0.005). After two immunotherapy cycles, patients with a decreased NLR (≥10%) had significantly longer OS than those with an increased NLR (≥10%), regardless of the baseline NLR (p = 0.003). The overall median survival was 15 months, with 10 months for the NLR-increased group and not reached for the NLR-decreased group. Conclusions: Our study highlights the potential of baseline NLR and early changes in NLR as valuable prognostic markers for mBC patients receiving immunotherapy. Elevated neutrophils and lymphopenia negatively impact prognosis and treatment effectiveness, and NLR shows promise as a prognostic marker, inspiring further research and potential improvements in patient care.
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Affiliation(s)
- Ezgi Değerli
- Department of Medical Oncology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, 34147 Istanbul, Turkey; (M.Y.); (R.Ç.); (C.K.)
| | - Çağatay Arslan
- Department of Medical Oncology, Medical Park İzmir Hospital, 35230 Izmir, Turkey;
| | - Fatih Selçukbiricik
- Department of Medical Oncology, Faculty of Medicine, Koc University, 34450 Istanbul, Turkey; (F.S.); (D.T.)
| | - Ömer Fatih Ölmez
- Department of Medical Oncology, Medipol University Hospital, 34810 Istanbul, Turkey; (Ö.F.Ö.); (J.H.)
| | - Dilek Erdem
- Department of Medical Oncology, Medical Park Samsun Hospital, 55200 Samsun, Turkey;
| | - Jamshid Hamdard
- Department of Medical Oncology, Medipol University Hospital, 34810 Istanbul, Turkey; (Ö.F.Ö.); (J.H.)
| | - Mesut Yılmaz
- Department of Medical Oncology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, 34147 Istanbul, Turkey; (M.Y.); (R.Ç.); (C.K.)
| | - Rumeysa Çolak
- Department of Medical Oncology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, 34147 Istanbul, Turkey; (M.Y.); (R.Ç.); (C.K.)
| | - Caner Kapar
- Department of Medical Oncology, Bakırköy Dr. Sadi Konuk Training and Research Hospital, 34147 Istanbul, Turkey; (M.Y.); (R.Ç.); (C.K.)
| | - Mustafa Erman
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey; (M.E.); (F.K.)
| | - Fatih Kuş
- Department of Medical Oncology, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey; (M.E.); (F.K.)
| | - Deniz Tural
- Department of Medical Oncology, Faculty of Medicine, Koc University, 34450 Istanbul, Turkey; (F.S.); (D.T.)
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Cheng LY, Su PJ, Kuo MC, Lin CT, Luo HL, Chou CC, Huang SY, Wu CC, Chen CH, Huang CC, Tsai KL, Yu-Li Su H. Combining serum inflammatory markers and clinical factors to predict survival in metastatic urothelial carcinoma patients treated with immune checkpoint inhibitors. Ther Adv Med Oncol 2024; 16:17588359241305091. [PMID: 39687055 PMCID: PMC11648016 DOI: 10.1177/17588359241305091] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
Background Despite the revolutionary impact of immune checkpoint inhibitors (ICIs) on the treatment of metastatic urothelial carcinoma (mUC), the clinical utility of reliable prognostic biomarkers to foresee survival outcomes remains underexplored. Objectives The purpose of this study was to ascertain the prognostic significance of serum inflammatory markers in mUC patients undergoing ICI therapy. Design This is a retrospective, multicenter study. Methods Data were collected from two independent medical centers in Taiwan, encompassing a validation and a training cohort (TC). Patients with histopathologically confirmed urothelial carcinoma who received at least one cycle of ICI monotherapy were included. Serum inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were calculated prior to ICI therapy. Statistical analyses involved the use of receiver operating characteristic (ROC) curves to determine optimal biomarker cutoffs and Cox proportional hazards models to evaluate the independent predictive capability of these markers. Results A total of 192 patients were enrolled. In the univariate analysis, serum markers such as NLR, PLR, SII, and Hb were significantly associated with overall survival (OS) in both the training and validation cohorts (VC). White blood cells, NLR, and SII demonstrated a robust correlation with progression-free survival across both cohorts. Multivariate analysis revealed that Eastern Cooperative Oncology Group performance status ⩾2 (p < 0.001), visceral metastasis (p < 0.001), leukocytosis (p < 0.001), Hb levels ⩾10 mg/dL (p = 0.008), and NLR ⩾5 (p = 0.032) as independent predictors of OS. A prognostic nomogram integrating these independent factors yielded a C-index for a 3-year OS of 0.769 in the TC and 0.657 in the VC. Conclusion Serum inflammatory markers, combined with clinicopathologic factors, provide a practical prognostic tool in mUC treatment with ICIs.
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Affiliation(s)
- Liang-Yun Cheng
- Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Jung Su
- Division of Hematology–Oncology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ming-Chun Kuo
- Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chang-Ting Lin
- Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hao-Lun Luo
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Chi Chou
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Shih-Yu Huang
- Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chia-Che Wu
- Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hsu Chen
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Chieh Huang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kai-Lung Tsai
- Department of Colorectal Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Harvey Yu-Li Su
- Division of Hematology–Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Dapi Road, Niaosong District, Kaohsiung City 833, Taiwan
- Genomic and Proteomic Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
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Koukourakis IM, Georgakopoulos I, Desse D, Tiniakos D, Kouloulias V, Zygogianni A. Lymphopenia is an adverse prognostic factor in rectal adenocarcinoma patients receiving long-course chemoradiotherapy. Radiat Oncol J 2024; 42:263-272. [PMID: 39748527 DOI: 10.3857/roj.2024.00052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 03/08/2024] [Indexed: 01/04/2025] Open
Abstract
PURPOSE Neoadjuvant radiotherapy (RT) or chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal adenocarcinoma. The recent emerging data on preoperative immunotherapy as an effective therapeutic modality for mismatch repair deficient rectal carcinomas suggests that the immune system plays a significant role in tumor eradication. Although RT has been shown to stimulate anti-tumor immunity, it also leads to substantial lymphopenia, hindering the effect of immune response. MATERIALS AND METHODS We retrospectively analyzed 33 rectal adenocarcinoma patients who underwent CRT in our department, aiming to identify the effects of CRT on the peripheral blood lymphocyte counts (LC) and the potential impact of CRT-induced lymphopenia on tumor response and prognosis of patients. RESULTS A statistically significant decrease in the LC of patients was observed after CRT (median values of 2,184/μL and 517/μL before and after treatment, respectively; p < 0.001). While no correlation between ypT-stage, ypN status, and LC was found, poor tumor regression grade was significantly associated with lower LC (p = 0.036). Moreover, lymphopenia was associated with poorer distant metastasis-free survival (p = 0.003). Distant metastases were documented in 0% of patients with post-CRT LC above 518/μL vs. 44.5% of patients with lower LC values. CONCLUSION Although further investigation is demanded, given the limited number of patients analyzed in the study, lymphopenia emerges as a significant adverse event that rectal adenocarcinoma patients face during treatment with neoadjuvant CRT, with subsequent implications on tumor response and prognosis. Protection of the immune system during CRT emerges as an important target for clinical research.
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Affiliation(s)
- Ioannis M Koukourakis
- Radiation Oncology Unit, 1st Department of Radiology, Medical School, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Georgakopoulos
- Radiation Oncology Unit, 1st Department of Radiology, Medical School, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitra Desse
- Radiation Oncology Unit, 1st Department of Radiology, Medical School, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dina Tiniakos
- Department of Pathology, Aretaieion University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Vassilios Kouloulias
- Radiation Oncology Unit, 2nd Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Zygogianni
- Radiation Oncology Unit, 1st Department of Radiology, Medical School, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Cooper R, Ramaswami D, Thomas JS, Nieva JJ, Hsu R. Assessing the predictive role of platelet-lymphocyte ratio in EGFR-mutated non-small cell lung cancer patients treated with tyrosine kinase inhibitors: an analysis across TKI generations. Discov Oncol 2024; 15:689. [PMID: 39570469 PMCID: PMC11582238 DOI: 10.1007/s12672-024-01606-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 11/19/2024] [Indexed: 11/22/2024] Open
Abstract
INTRODUCTION The predictive utility of laboratory markers in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) is an ongoing area of research. The predictability of the platelet-lymphocyte ratio (PLR) on survival outcomes depending on the generation of EGFR TKI is undetermined. METHODS 151 patients treated with EGFR TKIs in Los Angeles were grouped according to generation of TKI. Differences in progression free survival (PFS) by stratification by PLR was determined using Kaplan-Meier analysis. Differences in median change in laboratory markers by generation of TKI was analyzed using Mann-Whitney tests. Cox Hazard Regression was used to perform multivariate analysis. RESULTS Median PFS of those managed with 1st or 2nd generation TKIs was significantly lower in patients with a PLR ≥ 180 (10.5 months) compared to those with PLR < 180 (16.6 months, p = 0.0163). Median PFS was comparable in those treated with osimertinib regardless of PLR. Patients managed with osimertinib had a significant decrease in absolute lymphocyte count (ALC) at 6 weeks and in platelets at 6 weeks and 3 months compared to those managed with 1st or 2nd generation TKIs. DISCUSSION The predictive value of PLR was more apparent in patients treated with 1st or 2nd generation TKIs compared to those treated with osimertinib. Third generation EGFR TKIs may be more efficacious in treating patients with laboratory findings previously shown to predict poor survival. The significant changes in peripheral cell counts suggest variable tumor microenvironment changes dependent on the generation of TKI received.
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Affiliation(s)
- Ryan Cooper
- University of Southern California Keck School of Medicine, Los Angeles, CA, USA
| | | | - Jacob S Thomas
- Department of Internal Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Jorge J Nieva
- Department of Internal Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Robert Hsu
- Department of Internal Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
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Rosichini M, Del Baldo G, De Luca CD, Benini F, Genah S, Vinci M, Cerimele A, Coccetti M, Flamini S, Carsetti R, Cacchione A, Carai A, Mastronuzzi A, Locatelli F, Velardi E. Pediatric brain tumor patients display altered immune activation and reduced lymphopoiesis at the onset of disease. NPJ Precis Oncol 2024; 8:269. [PMID: 39567679 PMCID: PMC11579487 DOI: 10.1038/s41698-024-00755-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 11/04/2024] [Indexed: 11/22/2024] Open
Abstract
Optimal immune function is crucial in preventing cancer development and growth and for the success of anti-cancer therapies. Here, we characterized the peripheral immunological status of 83 steroids-naïve pediatric patients with central nervous system neoplasia at the disease onset. Tumors were classified into low-grade gliomas (LGG), high-grade gliomas (HGG), medulloblastoma, and other tumors. We revealed that glioma patients showed an altered lymphocyte pool. T-cells of HGG patients shifted from naïve to effector memory phenotype. LGG patients exhibited T-cell central memory expansion and higher T-cell activation. Interestingly, HGG patients displayed reduced thymic function. Furthermore, LGG and HGG patients showed reduced activated B-cells and suboptimal B-cell formation. Our data demonstrate that glioma patients have reduced lymphopoiesis at the disease onset, which could contribute to the systemic lymphopenia characterizing these patients. This study offers novel insights into the immunological status of brain tumor patients which may help in designing more effective treatments.
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Affiliation(s)
- Marco Rosichini
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Giada Del Baldo
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Carmen Dolores De Luca
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Francesca Benini
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Shirley Genah
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Maria Vinci
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Alfredo Cerimele
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Marianna Coccetti
- Research Core Laboratory, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Sara Flamini
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Rita Carsetti
- B cell unit Research Area of Immunology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Antonella Cacchione
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Andrea Carai
- Department of Neurosciences, Neurosurgery Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Angela Mastronuzzi
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Franco Locatelli
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- Catholic University of the Sacred Heart, Rome, Italy
| | - Enrico Velardi
- Research Area of Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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Fu YP, Lin H, Ou YC, Wu CH, Fu HC. Bevacizumab as a mitigating factor for the impact of high systemic immune-inflammation index on chemorefractory in advanced epithelial ovarian cancer. BMC Cancer 2024; 24:1377. [PMID: 39529011 PMCID: PMC11552161 DOI: 10.1186/s12885-024-13087-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Predicting chemorefractory disease in advanced epithelial ovarian cancer (EOC) remains challenging. This study aimed to identify clinicopathological factors and hemogram data as predictive markers for chemorefractory EOC and to explore potential therapeutic approaches that may mitigate these unfavorable conditions. METHODS We conducted a retrospective analysis of patients with advanced EOC treated with chemotherapy. Hemogram data and clinicopathological variables were collected. We employed logistic regression to assess factors associated with chemorefractory EOC and used the Kaplan-Meier method for survival analysis. RESULTS Among the 191 patients analyzed, suboptimal surgery, lymphocyte count < 1440/mm3, systemic immune-inflammation index (SII) ≥ 2350, and lack of bevacizumab therapy were independently associated with chemorefractory EOC (OR 19.30, 95% CI 7.01-53.12; OR 9.07, 95% CI 2.76-29.82; OR 12.45, 95% CI 3.87-40.07; OR 6.61, 95% CI 2.01-21.78, respectively). Elevated SII was also identified as a risk factor for poor progression-free (PFS) and overall survival (OS). Specifically, patients with high SII who did not receive bevacizumab had a significantly higher probability of chemorefractory EOC and poorer survival outcomes compared to those who received bevacizumab. CONCLUSIONS Our findings suggest that hemogram parameters and clinicopathological factors such as suboptimal surgery, lymphocyte count, SII, and bevacizumab therapy status are predictive markers for chemorefractory disease in advanced EOC. Elevated SII emerged as a predictor for poorer PFS and OS outcomes, particularly in the absence of bevacizumab therapy.
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Affiliation(s)
- Yan-Ping Fu
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hao Lin
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yu-Che Ou
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Department of Obstetrics and Gynecology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan
| | - Chen-Hsuan Wu
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hung-Chun Fu
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
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Xie W, Ji L, Kang L, Li Q, Luo D, He Q, Mei J. Prevalence of lymphopenia in the American population: Insights from demographic, BMI, and lifestyle factors. PLoS One 2024; 19:e0312540. [PMID: 39495758 PMCID: PMC11534243 DOI: 10.1371/journal.pone.0312540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Accepted: 10/08/2024] [Indexed: 11/06/2024] Open
Abstract
OBJECTIVE To determine the difference in the prevalence of lymphopenia in the American population according to demographic characteristics, body mass index (BMI) and living habits. METHODS A total of 33,365 participants aged over 1 were included in the 2009-2018 National Health and Nutrition Survey (NHANES). All analyses used weighted samples and considered the layering and clustering of the design. RESULTS Using white participants as a reference, the prevalence of lymphopenia in Mexican-American participants was significantly lower than that of white participants (P = 0.018). There was no significant difference in the prevalence of lymphopenia between black participants (P = 0.376) and white participants. The prevalence of lymphopenia was 1.81% (95%CI, 1.53%-2.10%) for white participants, 1.08% (95%CI, 0.78%-1.39%) for black participants, and 0.42% (95%CI, 0.17%-0.68%) for Mexican-American participants. The prevalence of lymphopenia increases with age, reaching a peak of 6.84% among elderly participants aged 75 and above. In terms of the gender difference, the prevalence of lymphopenia in men is significantly higher than that in women (P<0.001). Individuals who smoke (P<0.001), consume alcohol (P = 0.032), engage in regular exercise (P = 0.031), have sleep disorders (P<0.001) and those classified as having an unhealthy weight (P<0.001) had a higher average lymphocyte count. The prevalence of lymphopenia in participants with sleep disorders is significantly higher than those without sleep disorders (P = 0.014). However, no significant differences were observed among the classification variables of smoking, drinking, exercise, and BMI. CONCLUSION In the diagnosis and treatment of lymphopenia, clinicians should consider the influence of factors such as race, gender, age, sleep disorders, and other unhealthy lifestyle habits to improve the accuracy of diagnosis and treatment, thereby reducing the high mortality risk associated with lymphopenia. Consequently, we propose a novel perspective that the diagnosis and treatment of lymphopenia should be tailored to the lymphocyte levels of specific subpopulations, rather than applying a generalized approach.
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Affiliation(s)
- Wenchi Xie
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
| | - Landie Ji
- College of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Landan Kang
- College of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qian Li
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
| | - Dan Luo
- College of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China
| | - Qingquan He
- College of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jie Mei
- Department of Obstetrics and Gynaecology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
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Prades-Sagarra E, Yaromina A, Dubois L. Understanding the impact of radiation-induced lymphopenia: Preclinical and clinical research perspectives. Clin Transl Radiat Oncol 2024; 49:100852. [PMID: 39315059 PMCID: PMC11418132 DOI: 10.1016/j.ctro.2024.100852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/26/2024] [Accepted: 09/01/2024] [Indexed: 09/25/2024] Open
Abstract
Immunotherapy has revolutionized the field of cancer treatment, changing the standard of care to the use of immune checkpoint inhibitors. Radiotherapy can boost anti-tumour immune responses by changing the tumour microenvironment, but it also can cause radiotherapy-induced lymphopenia (RIL), a decrease in circulating lymphocyte counts. RIL has been associated with lower survival in patients undergoing radiotherapy, and new studies have suggested that it can also affect immunotherapy outcome. To study RIL's effects and to explore mitigation treatment strategies, preclinical models closely mimicking the clinical situation are needed. State-of-the-art image-guided small animal irradiators now offer the possibility to target specific organs in small animals to induce RIL, aiding research on its molecular mechanisms and prevention. This review covers the relationship between radiotherapy and RIL, its impact on patient survival, and future directions to generate models to investigate and prevent RIL.
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Affiliation(s)
- E. Prades-Sagarra
- The M-Lab, Department of Precision Medicine, GROW - Research Institute for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - A. Yaromina
- The M-Lab, Department of Precision Medicine, GROW - Research Institute for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands
| | - L.J. Dubois
- The M-Lab, Department of Precision Medicine, GROW - Research Institute for Oncology and Reproduction, Maastricht University, 6229 ER Maastricht, The Netherlands
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Yoneyama M, Zormpas-Petridis K, Robinson R, Sobhani F, Provenzano E, Steel H, Lightowlers S, Towns C, Castillo SP, Anbalagan S, Lund T, Wennerberg E, Melcher A, Coles CE, Roxanis I, Yuan Y, Somaiah N. Longitudinal Assessment of Tumor-Infiltrating Lymphocytes in Primary Breast Cancer Following Neoadjuvant Radiation Therapy. Int J Radiat Oncol Biol Phys 2024; 120:862-874. [PMID: 38677525 DOI: 10.1016/j.ijrobp.2024.04.065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 04/16/2024] [Accepted: 04/21/2024] [Indexed: 04/29/2024]
Abstract
PURPOSE Tumor-infiltrating lymphocytes (TILs) have prognostic significance in several cancers, including breast cancer. Despite interest in combining radiation therapy with immunotherapy, little is known about the effect of radiation therapy itself on the tumor-immune microenvironment, including TILs. Here, we interrogated longitudinal dynamics of TILs and systemic lymphocytes in patient samples taken before, during, and after neoadjuvant radiation therapy (NART) from PRADA and Neo-RT breast clinical trials. METHODS AND MATERIALS We manually scored stromal TILs (sTILs) from longitudinal tumor samples using standardized guidelines as well as deep learning-based scores at cell-level (cTIL) and cell- and tissue-level combination analyses (SuperTIL). In parallel, we interrogated absolute lymphocyte counts from routine blood tests at corresponding time points during treatment. Exploratory analyses studied the relationship between TILs and pathologic complete response (pCR) and long-term outcomes. RESULTS Patients receiving NART experienced a significant and uniform decrease in sTILs that did not recover at the time of surgery (P < .0001). This lymphodepletive effect was also mirrored in peripheral blood. Our SuperTIL deep learning score showed good concordance with manual sTILs and importantly performed comparably to manual scores in predicting pCR from diagnostic biopsies. The analysis suggested an association between baseline sTILs and pCR, as well as sTILs at surgery and relapse, in patients receiving NART. CONCLUSIONS This study provides novel insights into TIL dynamics in the context of NART in breast cancer and demonstrates the potential for artificial intelligence to assist routine pathology. We have identified trends that warrant further interrogation and have a bearing on future radioimmunotherapy trials.
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Affiliation(s)
- Miki Yoneyama
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom
| | - Konstantinos Zormpas-Petridis
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom; Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Ruth Robinson
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Faranak Sobhani
- Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
| | - Elena Provenzano
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Harriet Steel
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom
| | - Sara Lightowlers
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Department of Oncology, University of Cambridge, Cambridge, United Kingdom
| | - Catherine Towns
- Department of Oncology, University of Cambridge, Cambridge, United Kingdom
| | - Simon P Castillo
- Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom
| | - Selvakumar Anbalagan
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom
| | - Tom Lund
- Integrated Pathology Unit, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Erik Wennerberg
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom
| | - Alan Melcher
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom
| | - Charlotte E Coles
- Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; Department of Oncology, University of Cambridge, Cambridge, United Kingdom
| | - Ioannis Roxanis
- The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom
| | - Yinyin Yuan
- Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
| | - Navita Somaiah
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom.
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Yamamoto T, Aoyama Y. Immune reconstitution is the trigger of herpes zoster with lymphopenia and high neutrophil-to-lymphocyte ratio in a retrospective cohort study. Clin Exp Dermatol 2024; 49:1372-1378. [PMID: 38723590 DOI: 10.1093/ced/llae176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 05/01/2024] [Accepted: 05/05/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Herpes zoster (HZ) rarely results in subsequent death, but predictive biomarkers for mortality necessitate further elucidation. OBJECTIVES To investigate immune dynamics prior to an HZ event, risk factors for HZ onset and immune status at initial HZ. METHODS This retrospective study extracted from patient records the absolute neutrophil and lymphocyte counts (ANC and ALC, respectively) at the initial HZ date of appearance and up to 30 days before HZ. A follow-up survey was completed within 180 days of onset of illness. RESULTS Patients with HZ showed a higher neutrophil-to-lymphocyte ratio (NLR) and lower ALC than patients in the control group at the initial date and had a poorer prognosis. In the pre-onset examination, the maximum and minimum ALC values were significantly lower in patients with HZ than in the control group, and the maximum ALC value in patients with HZ was lower than the minimum value in the control group. The lowest ALC was observed 7 days before the onset of HZ. An NLR of 4.53 or more and an ALC of 0.64 × 109 cells L-1 or less were predictive markers of HZ development within 30 days. Patients who died after HZ had a lower minimum ALC than those who survived longer. CONCLUSIONS HZ develops in a state of immune reconstitution in patients with immunocompromised conditions, as part of 'unmasking' the immune reconstitution inflammatory syndrome. Lymphopenia prior to HZ onset is one of the most crucial factors in its pathogenesis and vital prognosis. Limitations of the study were small population size, varying age distribution, retrospective nature, and potential overestimation of pre-onset data.
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Affiliation(s)
- Takenobu Yamamoto
- Department of Dermatology, Kawasaki Medical School, Kurashiki City, Okayama Prefecture, Japan
- Department of Dermatology, Kawasaki Medical School General Medical Center, Kita-ku, Okayama City, Japan
| | - Yumi Aoyama
- Department of Dermatology, Kawasaki Medical School, Kurashiki City, Okayama Prefecture, Japan
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Tobing E, Tansol C, Tania C, Sihombing AT. Prognostic Nutritional Index (PNI) as Independent Predictor of Poor Survival in Prostate Cancer: A Systematic Review and Meta-Analysis. Clin Genitourin Cancer 2024; 22:102142. [PMID: 39079465 DOI: 10.1016/j.clgc.2024.102142] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 06/14/2024] [Accepted: 06/15/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND The concentration of albumin and lymphocyte in the body can serve as indicators of both nutritional status and inflammation. The predictive significance of the prognostic nutritional index (PNI) has been documented in multiple cancer types. Consequently, a meta-analysis was conducted in order to investigate the prognostic impact of PNI on survival outcomes among individuals diagnosed with prostate cancer. METHODS A systematic search was conducted across 4 electronic databases to identify pertinent studies that evaluated the predictive significance of pretreatment PNI in patients with prostate cancer. The outcomes of interest in this study were overall survival (OS) and progression-free survival (PFS). The researchers utilized random-effect models to summarize the time-to-event outcomes, presenting the results as adjusted hazard ratios (aHR) along with their corresponding 95% confidence intervals (CI). RESULTS A total of 2229 prostate cancer patients in 13 studies were included. Pooled analysis from these studies showed that low PNI value was associated with shorter OS [aHR 1.99 (95% CI, 1.45-2.72), P < .0001], and PFS [aHR 1.97 (95% CI, 1.55-2.51), P < .00001]. Sub-group analysis revealed that the ability of PNI to predict poor outcomes was better observed in patients with metastatic castration-resistant prostate cancer (mCRPC) and those who received androgen receptor pathway inhibitors (ARPIs). CONCLUSIONS This study suggests the role of PNI in predicting the survival and progression of prostate cancer. PNI values can be used in the risk stratification of patients with prostate cancer.
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Affiliation(s)
- Edwin Tobing
- Department of Urology, Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Banten, Indonesia
| | - Christiano Tansol
- Department of Urology, Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Banten, Indonesia
| | - Clarissa Tania
- Department of Urology, Faculty of Medicine, Universitas Pelita Harapan, Tangerang, Banten, Indonesia.
| | - Aaron Tigor Sihombing
- Department of Urology, Hasan Sadikin Hospital, Universitas Padjadjaran, West Java, Indonesia
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Petre I, Negru S, Dragomir R, Bordianu A, Petre I, Marc L, Vlad DC. Artificial Intelligence Algorithms in Predictive Factors for Hematologic Toxicities During Concurrent Chemoradiation for Cervical Cancer. Cureus 2024; 16:e70665. [PMID: 39493069 PMCID: PMC11528638 DOI: 10.7759/cureus.70665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/01/2024] [Indexed: 11/05/2024] Open
Abstract
The most recent research conducted for the International Federation of Gynecology and Obstetrics indicates that, depending on the stage of cervical cancer (CC), several therapies can provide similar overall survival and progression-free survival rates. To determine the hematologic toxicities during concurrent chemotherapy for cervical cancer, we evaluated these two therapies (cisplatin or carboplatin). Hematologic markers have been studied using statistical models and descriptive statistics. Artificial intelligence models were built using the treatment data and all the information gathered from each patient after one or more administrations to forecast the CC stage. The information was gathered from stage III cervical cancer patients and provided by Oncohelp Hospital from the West Region of Romania. Many traditional machine learning techniques, such as naïve Bayes (NB), random forest (RF), decision trees (DTs), and a trained transformer called TabPFN, were used in the current study to obtain the tabular data. The algorithms NB, RF, and DTs yielded the greatest classification score of 100% when it came to cervical cancer prediction. On the other hand, TabPFN demonstrated an accuracy of 88%. The effectiveness of the models was evaluated by computing the computational complexity of traditional machine learning methods. Early detection increases the likelihood of a good prognosis during the precancerous and malignant stages. Being aware of any indications and symptoms of cervical cancer can also help to prevent delays in diagnosis. These hematologic toxicities, which have been demonstrated to grow linearly with lowering hematologic markers below their normal expectations, would significantly impair patients' quality of life.
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Affiliation(s)
- Ion Petre
- Department of Biostatistics, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
- Department of Functional Science, Medical Informatics and Biostatistics, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
| | - Serban Negru
- Department of Medical Oncology, Oncohelp Oncology Center, Timisoara, ROU
- Department of Oncology, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
| | - Radu Dragomir
- Department of Obstetrics and Gynecology, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
| | - Anca Bordianu
- Department of Plastic and Reconstructive, Bagdasar-Arseni Emergency Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Izabella Petre
- Department of Obstetrics and Gynecology, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
- Department of Obstetrics and Gynecology, Pius Brinzeu Emergency County Clinical Hospital, Timisoara, ROU
| | - Luciana Marc
- Department of Internal Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
| | - Daliborca Cristina Vlad
- Department of Pharmacology, Victor Babes University of Medicine and Pharmacy, Timisoara, ROU
- Department of Laboratory Medicine, Pius Brinzeu Emergency County Clinical Hospital, Timisoara, ROU
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Salari A, Ghahari M, Bitaraf M, Fard ES, Haddad M, Momeni SA, Inanloo SH, Ghahari P, Mohamoud MM, Mohamadzadeh M, Nowroozi MR, Amini E. Prognostic Value of NLR, PLR, SII, and dNLR in Urothelial Bladder Cancer Following Radical Cystectomy. Clin Genitourin Cancer 2024; 22:102144. [PMID: 39032203 DOI: 10.1016/j.clgc.2024.102144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 06/12/2024] [Accepted: 06/15/2024] [Indexed: 07/22/2024]
Abstract
BACKGROUND Inflammation plays a crucial role in tumor development and progression, with inflammatory markers showing promise in predicting cancer prognosis. However, their significance in muscle-invasive bladder cancer (MIBC), especially in the context of neoadjuvant chemotherapy (NAC), remains poorly understood. This study aims to evaluate the prognostic utility of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR) for overall survival (OS) in bladder cancer (BC) patients undergoing radical cystectomy (RC) in the NAC era. PATIENTS AND METHODS A retrospective review analyzed prospectively-collected data from our institutional BC registry, covering patients with MIBC undergoing RC with curative intent from March 1st, 2016, to December 31st, 2022. Blood samples were collected preoperatively to calculate NLR, PLR, SII, and dNLR. OS was defined from surgery to last follow-up or death. Statistical analyses included ROC curves, Kaplan-Meier Curves, and Cox proportional hazards regression models. RESULTS A total of 187 patients with median duration follow-up of 14.7 month were included in this study and 50.8% experienced death. NAC was administered in 50.3% of cases. The ideal cut-off for dichotomizing NLR, PLR, SII, and dNLR was 1.76, 104.30, 410.66, and 1.30, respectively. In multivariable analysis each of these biomarkers emerged as an independent prognostic factor for predicting OS. The results showed a correlation between higher NLR, PLR, SII, and dNLR levels and a deterioration in OS. CONCLUSION Elevated values of these inflammatory markers indicate poorer survival, highlighting their potential as indicators of disease aggressiveness. Identifying patients with elevated markers can help healthcare providers personalize treatment strategies, improving patient outcomes and survival rates.
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Affiliation(s)
- Abolfazl Salari
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Ghahari
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Bitaraf
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Elahe Samiee Fard
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Haddad
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Ali Momeni
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Hassan Inanloo
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Parichehr Ghahari
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Maryam Mohamadzadeh
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Erfan Amini
- Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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Soyfer V, Lugovoy E, Nikolaevski-Berlin A, Korzets Y, Schlocker A, Gutfeld O, Ospovat I, Amit U, Rabin T, Filomena Natan-Oz Y, Zach L, Merimsky O, Geva R, Peles S, Wolf I. The effect of long-standing lymphopenia after radiation therapy on survival in rectal cancer. Surg Oncol 2024; 56:102119. [PMID: 39146698 DOI: 10.1016/j.suronc.2024.102119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 07/31/2024] [Accepted: 08/05/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Lymphopenia and high neutrophil-to-lymphocyte ratio are known negative prognostic factors in rectal cancer. Until recently, however, lymphopenia was regarded as a minor sequela following radiation therapy (RT). The immune system's influence on rectal cancer treatment outcomes led us to evaluate the impact of lymphopenia at various time points, before, during, and following radiotherapy. We hypothesized that chronic lymphopenia following radiotherapy might negatively influence the survival of patients, and pre-treatment lymphopenia may be predictive of poor outcomes. METHODS This retrospective study involved 110 patients treated for rectal cancer between 2015 and 2019. The oncological outcomes are defined as alive without disease (AWOD), alive with disease (AWD), and death. These outcome probabilities tested against variables of lymphopenia before RT, during RT, and at several post-RT follow-up time points. RESULTS At the end of the study, 69 patients were AWOD (63 %), 13 were AWD (12 %) and 28 had died (25 %). Treatment results were assessed with according level of lymphocytes measured one year following RT: 35 out of 39 patients (89.7 %) with normal values were AWOD. In 65 patients with sustained lymphopenia, 52 % were AWOD, 18.5 % AWD and 29 % died. A similar difference was found at all time-points up to 2 years following RT (p < 0.004). The results of our study shows that pre-existing lymphopenia (prior to RT) is associated with a 3 times greater chance of death compared to patients with normal lymphocyte levels prior to RT. The PFS significantly affected by lymphopenia at all time-points after RT. An NLR of more than 4 was associated with a 3-time higher risk of recurrence than lower NLR scores (p = 0.0054). CONCLUSION Our results support the relevance of lymphopenia and NLR in the prognosis of rectal cancer. We believe this is the first study showing a negative correlation between sustained lymphopenia and OS following RT.
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Affiliation(s)
- Viacheslav Soyfer
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel.
| | - Eli Lugovoy
- Faculty of Medicine, Bar-Ilan University, Israel
| | | | - Yasmin Korzets
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Albert Schlocker
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Orit Gutfeld
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Inna Ospovat
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Uri Amit
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Tatiana Rabin
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | | | - Leor Zach
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Ofer Merimsky
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Ravit Geva
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Sharon Peles
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
| | - Ido Wolf
- Tel Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Israel
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Kobayashi T, Nishimura M, Hosonaga M, Kizawa R, Kawai S, Aoyama Y, Ozaki Y, Fukada I, Hara F, Takano T, Ueno T. Absolute lymphocyte count predicts efficacy of palbociclib in patients with metastatic luminal breast cancer. BMC Cancer 2024; 24:1156. [PMID: 39289642 PMCID: PMC11409475 DOI: 10.1186/s12885-024-12941-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 09/12/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Absolute lymphocyte count (ALC) is a predictive and prognostic factor for various tumor types, including breast cancer. Palbociclib is a CDK4/6 inhibitor widely used for the treatment of metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer. However, predictive biomarkers of the efficacy of palbociclib remain unelucidated. We conducted a retrospective study to examine the predictive value of the baseline ALC in patients treated with palbociclib. METHODS The medical records of patients with ER-positive, HER2-negative breast cancer treated with palbociclib plus hormonal therapy between December 2017 and December 2021 were analyzed retrospectively. The cutoff value of ALC was set at 1800 cells/μL at the initiation of palbociclib treatment. The clinical benefit rate (CBR) was defined as the rate of complete or partial response or stable disease for at least 6 months. Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards regression. RESULTS All of the 202 patients were women, with a median age of 59 years and a performance status (PS) of ≤ 2. The median numbers of lines of chemotherapy and endocrine therapy before palbociclib treatment were 0 (range, 0-9) and 1 (range, 0-7), respectively. Fifty-one patients had liver metastases. Forty-six patients tested negative for progesterone receptor (PgR) expression. The median follow-up time was 9.1 months. The CBR was significantly higher in the ALC-high group than in the ALC-low group (79% vs. 60%; P = 0.018). The median PFS was significantly longer in the ALC-high group than in the ALC-low group (26.8 months vs. 8.4 moths, respectively; P = 0.000013). ALC, age, PS, PgR status, prior chemotherapy, prior endocrine therapy, and liver metastasis were entered into the multivariate analysis. ALC was identified as an independent factor for PFS (P = 0.00085), along with liver metastasis (P = 0.0020), PS (P = 0.026), and prior endocrine therapy (P = 0.019). CONCLUSION ALC can serve as a predictor of palbociclib efficacy in patients with metastatic ER-positive, HER2-negative breast cancer.
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Affiliation(s)
- Takayuki Kobayashi
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan.
| | - Meiko Nishimura
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Mari Hosonaga
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Rika Kizawa
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Saori Kawai
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Yosuke Aoyama
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Yukinori Ozaki
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Ippei Fukada
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Fumikata Hara
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Toshimi Takano
- Department of Breast Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
| | - Takayuki Ueno
- Department of Breast Surgical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-Ku, Tokyo, 135-8550, Japan
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Koc DC, Mănescu IB, Mănescu M, Dobreanu M. A Review of the Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Nonhematologic Malignancies. Diagnostics (Basel) 2024; 14:2057. [PMID: 39335736 PMCID: PMC11431542 DOI: 10.3390/diagnostics14182057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 09/09/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
Biomarkers are crucial in cancer diagnostics, prognosis, and surveillance. Extensive research has been dedicated to identifying biomarkers that are broadly applicable across multiple cancer types and can be easily obtained from routine investigations such as blood cell counts. One such biomarker, the neutrophil-to-lymphocyte ratio (NLR), has been established as a prognostic marker in cancer. However, due to the dynamic nature of cancer diagnosis and treatment, periodic updates are necessary to keep abreast of the vast amount of published data. In this review, we searched the PubMed database and analyzed and synthesized recent literature (2018-February 2024) on the role of NLR in predicting clinical outcomes in nonhematologic malignancies. The search was conducted using the PubMed database. We included a total of 88 studies, encompassing 28,050 human subjects, and categorized the findings into four major groups: gastrointestinal cancer, cancers of the urinary tract and reproductive system, lung cancer, and breast cancer. Our analysis confirms that NLR is a reliable prognostic indicator in cancer, and we discuss the specific characteristics, limitations, and exceptions associated with its use. The review concludes with a concise Q&A section, presenting the most relevant take-home messages in response to five key practical questions on this topic.
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Affiliation(s)
- Defne Cigdem Koc
- Medical Campus Hamburg, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 11-15 Albert-Einstein-Ring, 22761 Hamburg, Germany; (D.C.K.); (I.B.M.)
| | - Ion Bogdan Mănescu
- Medical Campus Hamburg, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 11-15 Albert-Einstein-Ring, 22761 Hamburg, Germany; (D.C.K.); (I.B.M.)
- Department of Laboratory Medicine, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 38 Gheorghe Marinescu, 540142 Targu Mures, Romania
| | - Măriuca Mănescu
- Department of Pediatrics, Emergency County Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu, 540136 Targu Mures, Romania
| | - Minodora Dobreanu
- Department of Laboratory Medicine, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 38 Gheorghe Marinescu, 540142 Targu Mures, Romania
- Clinical Laboratory, Emergency County Clinical Hospital of Targu Mures, 50 Gheorghe Marinescu, 540136 Targu Mures, Romania
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Hong W, Zhang L, Qi Y, Wang Y, Wang W. Impact of Chemotherapy on Circulating Lymphocyte Subsets in Lung Cancer Patients. Cancer Manag Res 2024; 16:1205-1213. [PMID: 39282611 PMCID: PMC11401525 DOI: 10.2147/cmar.s475967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 08/23/2024] [Indexed: 09/19/2024] Open
Abstract
Purpose Lung cancer remains a leading cause of cancer-related death and chemotherapy stands as a fundamental component in therapy. Chemotherapy-induced myelosuppression encompasses a spectrum of hematological declines, including not only neutrophils but also lymphocytes, hemoglobin levels and platelets. This retrospective cohort study investigates alterations in peripheral blood lymphocyte subsets. By uncovering these changes, our goal is to refine patient management strategies, ensuring that the benefits of chemotherapy are maximized while minimizing its detrimental effects. Patients and Methods We retrospectively analyzed 159 lung cancer patients. Patients were categorized as "NT" (n=108, no previous anti-tumor therapy), and "PT" (n=51, prior therapy followed by at least a two-month treatment-free interval). Post-chemotherapy, patients were reassessed and grouped into "EarlyCycle" for those who underwent four or fewer cycles, and "LateCycle" for those who underwent more than four cycles. Results The study focused on analyzing the percentages of lymphocyte subsets, including T cells (CD4+, CD8+), B cells, and natural killer (NK) cells, across these groups. For T cells, the EarlyCycle group exhibited a significant increase compared to NT (0.7783 vs 0.7271; p=0.0017) and PT (0.7783 vs 0.6804; p=1.6e-05). B cells showed a significant decrease from NT to LateCycle (0.1014 vs 0.0817; p=2.2e-05) and from PT to LateCycle (0.1317 vs 0.0817; p=6.2e-10). NK cells significantly decreased in the EarlyCycle group compared to NT (0.1109 vs 0.1462; p=0.00816) and PT (0.1109 vs 0.1513; p=0.00992), with no significant change in the LateCycle group compared to either NT or PT (p>0.05). Conclusion Chemotherapy significantly affects lymphocyte subsets in a treatment-specific manner. The EarlyCycle group experienced a reduction in NK cell and an increase in T cell, suggesting a damage of innate immunity and an early shift towards adaptive immunity. The LateCycle group showed a substantial decrease in B cell, indicating a delayed effect on humoral immunity components.
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Affiliation(s)
- Wei Hong
- Oncology, The Second People's Hospital of Liaocheng, Liaocheng, Shandong, People's Republic of China
| | - Lei Zhang
- Oncology, The Second People's Hospital of Liaocheng, Liaocheng, Shandong, People's Republic of China
| | - Youkun Qi
- Pharmacy, The Second People's Hospital of Liaocheng, Liaocheng, Shandong, People's Republic of China
| | - Yanjun Wang
- Oncology, The Second People's Hospital of Liaocheng, Liaocheng, Shandong, People's Republic of China
| | - Wentao Wang
- Critical Care Medicine, The Second People's Hospital of Liaocheng, Liaocheng, Shandong, People's Republic of China
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Fu J, Xu X, Tian M, Wang H, Jin X. The controlling nutritional status score as a new prognostic predictor in patients with cervical cancer receiving radiotherapy: a propensity score matching analysis. BMC Cancer 2024; 24:1093. [PMID: 39227776 PMCID: PMC11370220 DOI: 10.1186/s12885-024-12872-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 08/28/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND As assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score's prognostic value and survival time in patients with FIGO stage IIB-IIIB cervical cancer treated with radiotherapy. METHODS In this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score's predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS). RESULTS The cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54-5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52-5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis. CONCLUSION The CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.
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Affiliation(s)
- Juan Fu
- Department of Clinical Nutrition, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, China
| | - Xintian Xu
- Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Mengxing Tian
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hongbing Wang
- Department of Gynecology and Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xin Jin
- Department of Clinical Nutrition, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Hu Z, Mohan R, Chu Y, Wang X, van Rossum PS, Chen Y, Grayson ME, Gearhardt AG, Grassberger C, Zhi D, Hobbs BP, Lin SH, Cao W. Clinical Translation of a Deep Learning Model of Radiation-Induced Lymphopenia for Esophageal Cancer. Int J Part Ther 2024; 13:100624. [PMID: 39228692 PMCID: PMC11369390 DOI: 10.1016/j.ijpt.2024.100624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 07/29/2024] [Indexed: 09/05/2024] Open
Abstract
Purpose Radiation-induced lymphopenia is a common immune toxicity that adversely impacts treatment outcomes. We report here our approach to translate a deep-learning (DL) model developed to predict severe lymphopenia risk among esophageal cancer into a strategy for incorporating the immune system as an organ-at-risk (iOAR) to mitigate the risk. Materials and Methods We conducted "virtual clinical trials" utilizing retrospective data for 10 intensity-modulated radiation therapy (IMRT) and 10 passively-scattered proton therapy (PSPT) esophageal cancer patients. For each patient, additional treatment plans of the modality other than the original were created employing standard-of-care (SOC) dose constraints. Predicted values of absolute lymphocyte count (ALC) nadir for all plans were estimated using a previously-developed DL model. The model also yielded the relative magnitudes of contributions of iOARs dosimetric factors to ALC nadir, which were used to compute iOARs dose-volume constraints, which were incorporated into optimization criteria to produce "IMRT-enhanced" and "intensity-modulated proton therapy (IMPT)-enhanced" plans. Results Model-predicted ALC nadir for the original IMRT (IMRT-SOC) and PSPT plans agreed well with actual values. IMPT-SOC showed greater immune sparing vs IMRT and PSPT. The average mean body doses were 13.10 Gy vs 7.62 Gy for IMRT-SOC vs IMPT-SOC for patients treated with IMRT-SOC; and 8.08 Gy vs 6.68 Gy for PSPT vs IMPT-SOC for patients treated with PSPT. For IMRT patients, the average predicted ALC nadir of IMRT-SOC, IMRT-enhanced, IMPT-SOC, and IMPT-enhanced was 281, 327, 351, and 392 cells/µL, respectively. For PSPT patients, the average predicted ALC nadir of PSPT, IMPT-SOC, and IMPT-enhanced was 258, 316, and 350 cells/µL, respectively. Enhanced plans achieved higher predicted ALC nadir, with an average improvement of 40.8 cells/µL (20.6%). Conclusion The proposed DL model-guided strategy to incorporate the immune system as iOAR in IMRT and IMPT optimization has the potential for radiation-induced lymphopenia mitigation. A prospective clinical trial is planned.
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Affiliation(s)
- Zongsheng Hu
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Radhe Mohan
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yan Chu
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Xiaochun Wang
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | | | - Yiqing Chen
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Madison E. Grayson
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Angela G. Gearhardt
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Clemens Grassberger
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Degui Zhi
- The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Brian P. Hobbs
- Department of Population Health, The University of Texas at Austin, Austin, Texas, USA
| | - Steven H. Lin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Wenhua Cao
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Lee DS. Clinical implications of the serum platelet-to-lymphocyte ratio in the modern radiation oncology era: research update and literature review. Radiat Oncol 2024; 19:107. [PMID: 39138484 PMCID: PMC11323450 DOI: 10.1186/s13014-024-02485-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 07/01/2024] [Indexed: 08/15/2024] Open
Abstract
Radiation therapy (RT) continues to be the primary approach for treating cancer, and numerous cancer biomarkers associated with oncological outcomes have been investigated in the context of RT. The serum platelet-to-lymphocyte ratio (PLR) is one of the emerging landmark biomarker in the oncologic field. Mounting evidence indicates that an elevated serum PLR may function as a marker of unfavorable tumor characteristics, adverse treatment outcomes and treatment-related toxicities among individuals undergoing RT. However, the findings of these investigations have revealed a few disparities among researchers, highlighting the need for further meticulously planned studies to draw conclusive results. This article provides a comprehensive literature review and in-depth discussion regarding the clinical implications of the serum PLR in the modern RT era.
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Affiliation(s)
- Dong Soo Lee
- Department of Radiation Oncology, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
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Wei C, Ai H, Mo D, Wang P, Wei L, Liu Z, Li P, Huang T, Liu M. A nomogram based on inflammation and nutritional biomarkers for predicting the survival of breast cancer patients. Front Endocrinol (Lausanne) 2024; 15:1388861. [PMID: 39170737 PMCID: PMC11335604 DOI: 10.3389/fendo.2024.1388861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 07/24/2024] [Indexed: 08/23/2024] Open
Abstract
Background We aim to develop a new prognostic model that incorporates inflammation, nutritional parameters and clinical-pathological features to predict overall survival (OS) and disease free survival (DFS) of breast cancer (BC) patients. Methods The study included clinicopathological and follow-up data from a total of 2857 BC patients between 2013 and 2021. Data were randomly divided into two cohorts: training (n=2001) and validation (n=856) cohorts. A nomogram was established based on the results of a multivariate Cox regression analysis from the training cohorts. The predictive accuracy and discriminative ability of the nomogram were evaluated by the concordance index (C-index) and calibration curve. Furthermore, decision curve analysis (DCA) was performed to assess the clinical value of the nomogram. Results A nomogram was developed for BC, incorporating lymphocyte, platelet count, hemoglobin levels, albumin-to-globulin ratio, prealbumin level and other key variables: subtype and TNM staging. In the prediction of OS and DFS, the concordance index (C-index) of the nomogram is statistically greater than the C-index values obtained using TNM staging alone. Moreover, the time-dependent AUC, exceeding the threshold of 0.7, demonstrated the nomogram's satisfactory discriminative performance over different periods. DCA revealed that the nomogram offered a greater overall net benefit than the TNM staging system. Conclusion The nomogram incorporating inflammation, nutritional and clinicopathological variables exhibited excellent discrimination. This nomogram is a promising instrument for predicting outcomes and defining personalized treatment strategies for patients with BC.
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Affiliation(s)
- Caibiao Wei
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Huaying Ai
- Department of Injection Room, The People’s Hospital of Yingtan, Yingtan, Jiangxi, China
| | - Dan Mo
- Department of Breast, Guangxi Zhuang Autonomous Region Maternal and Child Health Care Hospital, Nanning, China
| | - Peidong Wang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Liling Wei
- Department of Anesthesiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Zhimin Liu
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Peizhang Li
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Taijun Huang
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Miaofeng Liu
- Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
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Deng B, Kong W, Han C, Zhou C, Li J, Song D, Lin Y. Study of long-term effects of pelvic radiotherapy on the function of bone marrow in recurrent cervical cancer patients. Int J Med Sci 2024; 21:2000-2010. [PMID: 39113881 PMCID: PMC11302553 DOI: 10.7150/ijms.95900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Accepted: 06/12/2024] [Indexed: 08/10/2024] Open
Abstract
Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ2=16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy.
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Affiliation(s)
- Boer Deng
- Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, P.R. China
| | - Weimin Kong
- Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, P.R. China
| | - Chao Han
- Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, P.R. China
| | - Chunxiao Zhou
- Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Jing Li
- Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, P.R. China
| | - Dan Song
- Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, P.R. China
| | - Yuxuan Lin
- Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Beijing Maternal and Child Health Care Hospital, Beijing 100006, P.R. China
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Hao T, Jin C, Hu D, Wu C, Zhu Y, Xie J, Huang L, Xu J, Chang W, Liu L, Guo F, Qiu H, Yang Y, Liu S. Dynamic decline of lymphocytes predicts extracorporeal membrane oxygenation-related infections: a retrospective observational study. J Thorac Dis 2024; 16:4429-4439. [PMID: 39144308 PMCID: PMC11320223 DOI: 10.21037/jtd-23-1912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 06/07/2024] [Indexed: 08/16/2024]
Abstract
Background Limited data are available regarding the current microbiological characteristics of extracorporeal membrane oxygenation (ECMO)-related infections in intensive care units (ICUs) in China. This retrospective study aimed to determine the epidemiology, risk factors and impact on the outcome of ECMO-related infections. Methods A retrospective observational study from January 2014 to December 2019 was performed, and adult patients receiving ECMO support for more than 48 hours were included in this study. The primary outcome was the incidence rate of ECMO-related infection. Clinical data were recorded, and risk factors associated with an increased risk of ECMO-related infection were analyzed. Results A total of 174 adult patients who received ECMO and underwent ECMO for 1,670 days were included in this study. Forty-six patients (26.4%) developed ECMO-related infections, corresponding to 27.5 first episodes/1,000 ECMO days. The most common ECMO-related infection observed was ventilator-associated pneumonia (VAP). Infected patients had longer durations of mechanical ventilation {20.2 [interquartile range (IQR), 12.6, 30.7] vs. 9.0 (IQR, 5.8, 14.7) days, P<0.001}, ECMO support [11.6 (IQR, 8.1, 17.3) vs. 7.6 (IQR, 5.6, 9.7) days, P<0.001] and hospital stays (28.2±20.7 vs. 22.0±15.6 days, P<0.001). The factors independently associated with ECMO-related infection were a dynamic decrease in lymphocyte count [adjusted odds ratio (OR) =3.578, 95% confidence interval (CI): 2.175-4.906, P<0.001] and ECMO duration (adjusted OR =1.207, 95% CI: 1.096-1.330, P<0.001). Compared to patients without infection, infected patients had greater hospital mortality (39.1% vs. 78.3%, P<0.001) and 90-day mortality (40.6% vs. 87.0%, P<0.001). ECMO-related infections were associated with worse outcomes (adjusted Kaplan-Meier curve, log rank test P<0.001). Conclusions Patients supported by ECMO had a high risk of developing ECMO-related infection. The most common ECMO-related infection observed was VAP. A dynamic decrease in lymphocyte counts was significantly associated with an increased risk of ECMO-related infection.
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Affiliation(s)
- Tong Hao
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Chenhui Jin
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Dingji Hu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Changde Wu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- The First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yike Zhu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jianfeng Xie
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Lili Huang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Jingyuan Xu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Wei Chang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Ling Liu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Fengmei Guo
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Haibo Qiu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yi Yang
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- The First Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Songqiao Liu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Department of Critical Care Medicine, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
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Shouman S, El-Kholy N, Hussien AE, El-Derby AM, Magdy S, Abou-Shanab AM, Elmehrath AO, Abdelwaly A, Helal M, El-Badri N. SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147. Cell Commun Signal 2024; 22:349. [PMID: 38965547 PMCID: PMC11223399 DOI: 10.1186/s12964-024-01718-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 06/15/2024] [Indexed: 07/06/2024] Open
Abstract
T lymphocytes play a primary role in the adaptive antiviral immunity. Both lymphocytosis and lymphopenia were found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While lymphocytosis indicates an active anti-viral response, lymphopenia is a sign of poor prognosis. T-cells, in essence, rarely express ACE2 receptors, making the cause of cell depletion enigmatic. Moreover, emerging strains posed an immunological challenge, potentially alarming for the next pandemic. Herein, we review how possible indirect and direct key mechanisms could contribute to SARS-CoV-2-associated-lymphopenia. The fundamental mechanism is the inflammatory cytokine storm elicited by viral infection, which alters the host cell metabolism into a more acidic state. This "hyperlactic acidemia" together with the cytokine storm suppresses T-cell proliferation and triggers intrinsic/extrinsic apoptosis. SARS-CoV-2 infection also results in a shift from steady-state hematopoiesis to stress hematopoiesis. Even with low ACE2 expression, the presence of cholesterol-rich lipid rafts on activated T-cells may enhance viral entry and syncytia formation. Finally, direct viral infection of lymphocytes may indicate the participation of other receptors or auxiliary proteins on T-cells, that can work alone or in concert with other mechanisms. Therefore, we address the role of CD147-a novel route-for SARS-CoV-2 and its new variants. CD147 is not only expressed on T-cells, but it also interacts with other co-partners to orchestrate various biological processes. Given these features, CD147 is an appealing candidate for viral pathogenicity. Understanding the molecular and cellular mechanisms behind SARS-CoV-2-associated-lymphopenia will aid in the discovery of potential therapeutic targets to improve the resilience of our immune system against this rapidly evolving virus.
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Affiliation(s)
- Shaimaa Shouman
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12587, Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
| | - Nada El-Kholy
- Department of Drug Discovery, H. Lee Moffit Cancer Center& Research Institute, Tampa, FL, 33612, USA
- Cancer Chemical Biology Ph.D. Program, University of South Florida, Tampa, FL, 33620, USA
| | - Alaa E Hussien
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12587, Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
| | - Azza M El-Derby
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12587, Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
| | - Shireen Magdy
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12587, Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
| | - Ahmed M Abou-Shanab
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12587, Egypt
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
| | | | - Ahmad Abdelwaly
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
- Institute for Computational Molecular Science, Department of Chemistry, Temple University, Philadelphia, PA, 19122, USA
| | - Mohamed Helal
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt
- Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, 41522, Egypt
| | - Nagwa El-Badri
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, 12587, Egypt.
- Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Giza, 12587, Egypt.
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49
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Takemura K, Yuasa T, Lemelin A, Ferrier E, Wells JC, Saad E, Saliby RM, Basappa NS, Wood LA, Jude E, Pal SK, Donskov F, Beuselinck B, Szabados B, Powles T, McKay RR, Gebrael G, Agarwal N, Choueiri TK, Heng DYC. Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium. ESMO Open 2024; 9:103606. [PMID: 38901174 PMCID: PMC11252746 DOI: 10.1016/j.esmoop.2024.103606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 05/18/2024] [Accepted: 05/20/2024] [Indexed: 06/22/2024] Open
Abstract
BACKGROUND Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.
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Affiliation(s)
- K Takemura
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - T Yuasa
- Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - A Lemelin
- Tom Baker Cancer Centre, University of Calgary, Calgary
| | - E Ferrier
- Tom Baker Cancer Centre, University of Calgary, Calgary
| | | | - E Saad
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - R M Saliby
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - N S Basappa
- Cross Cancer Institute, University of Alberta, Edmonton
| | - L A Wood
- Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Canada
| | - E Jude
- Olivia Newton-John Cancer Wellness & Research Centre, Heidelberg, Australia
| | - S K Pal
- City of Hope Comprehensive Cancer Center, Duarte, USA
| | - F Donskov
- Aarhus University Hospital, Aarhus; University Hospital of Southern Denmark, Esbjerg, Denmark
| | - B Beuselinck
- Leuven Cancer Institute, KU Leuven, Leuven, Belgium
| | - B Szabados
- Barts Cancer Institute, Queen Mary University of London, London, UK
| | - T Powles
- Barts Cancer Institute, Queen Mary University of London, London, UK
| | - R R McKay
- Moores Cancer Center, University of California San Diego, La Jolla
| | - G Gebrael
- Huntsman Cancer Institute, University of Utah, Salt Lake City, USA
| | - N Agarwal
- Huntsman Cancer Institute, University of Utah, Salt Lake City, USA
| | - T K Choueiri
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA. https://twitter.com/DrChoueiri
| | - D Y C Heng
- Tom Baker Cancer Centre, University of Calgary, Calgary. https://twitter.com/DrDanielHeng
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50
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Morel D, Robert C, Paragios N, Grégoire V, Deutsch E. Translational Frontiers and Clinical Opportunities of Immunologically Fitted Radiotherapy. Clin Cancer Res 2024; 30:2317-2332. [PMID: 38477824 PMCID: PMC11145173 DOI: 10.1158/1078-0432.ccr-23-3632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 01/09/2024] [Accepted: 02/13/2024] [Indexed: 03/14/2024]
Abstract
Ionizing radiation can have a wide range of impacts on tumor-immune interactions, which are being studied with the greatest interest and at an accelerating pace by the medical community. Despite its undeniable immunostimulatory potential, it clearly appears that radiotherapy as it is prescribed and delivered nowadays often alters the host's immunity toward a suboptimal state. This may impair the full recovery of a sustained and efficient antitumor immunosurveillance posttreatment. An emerging concept is arising from this awareness and consists of reconsidering the way of designing radiation treatment planning, notably by taking into account the individualized risks of deleterious radio-induced immune alteration that can be deciphered from the planned beam trajectory through lymphocyte-rich organs. In this review, we critically appraise key aspects to consider while planning immunologically fitted radiotherapy, including the challenges linked to the identification of new dose constraints to immune-rich structures. We also discuss how pharmacologic immunomodulation could be advantageously used in combination with radiotherapy to compensate for the radio-induced loss, for example, with (i) agonists of interleukin (IL)2, IL4, IL7, IL9, IL15, or IL21, similarly to G-CSF being used for the prophylaxis of severe chemo-induced neutropenia, or with (ii) myeloid-derived suppressive cell blockers.
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Affiliation(s)
- Daphné Morel
- Department of Radiation Oncology, Gustave Roussy, Villejuif, France
- INSERM U1030, Molecular Radiotherapy, Villejuif, France
| | - Charlotte Robert
- Department of Radiation Oncology, Gustave Roussy, Villejuif, France
- INSERM U1030, Molecular Radiotherapy, Villejuif, France
- Paris-Saclay University, School of Medicine, Le Kremlin Bicêtre, France
| | - Nikos Paragios
- Therapanacea, Paris, France
- CentraleSupélec, Gif-sur-Yvette, France
| | - Vincent Grégoire
- Department of Radiation Oncology, Centre Léon Bérard, Lyon, France
| | - Eric Deutsch
- Department of Radiation Oncology, Gustave Roussy, Villejuif, France
- INSERM U1030, Molecular Radiotherapy, Villejuif, France
- Paris-Saclay University, School of Medicine, Le Kremlin Bicêtre, France
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