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Nishioka R, Kawahara D, Imano N, Murakami Y. A nomogram-based survival prediction model for non-small cell lung cancer patients based on clinical risk factors and multiregion radiomics features. Clin Radiol 2025; 84:106826. [PMID: 40088854 DOI: 10.1016/j.crad.2025.106826] [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: 12/15/2023] [Revised: 12/06/2024] [Accepted: 01/02/2025] [Indexed: 03/17/2025]
Abstract
AIM This study focuses on developing a nomogram-based overall survival (OS) prediction model for non-small cell lung cancer (NSCLC) patients by integrating clinical factors with multiregion radiomics features extracted from pretreatment CT images. The proposed nomogram aims to assist clinicians in stratifying patients into high- and low-risk groups for personalised treatment strategies. MATERIALS AND METHODS From 2008 to 2018, 77 NSCLC patients were included. The radiomics feature was extracted from the internal and peripheral tumour region of pretreatment computed tomography (CT) images. The least absolute shrinkage and selection operator (LASSO) and the univariable Cox regression model were used to select the radiomics features. The Rad-score was defined as a linear combination of the selected radiomics features and the Cox proportional hazards regression coefficients. The combined model was constructed based on the clinicopathological factors and the Rad-score. The discrimination capacity of the prediction model was evaluated by Harrell's concordance index (C-index), the calibration curve, and the Kaplan-Meier survival curve. RESULTS We found that nine radiomics features and histology were independent predictors. The combined model showed the best performance (C-index: 0.799 [95% CI: 0.726-0.872]) compared with the clinical model (C-index: 0.692 [95% CI: 0.625-0.759]) and Rad-score (C-index: 0.663 [95% CI: 0.580-0.746]), and could significantly stratify into high-risk and low-risk NSCLC patients. The calibration curve also showed good consistency between the observation and the prediction. CONCLUSIONS The multregion radiomics features have the potential for predicting OS in NSCLC patients. The nomogram-based survival prediction model demonstrates significant potential in guiding clinical decision-making, allowing for precise and personalised treatment for NSCLC patients.
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Affiliation(s)
- R Nishioka
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
| | - D Kawahara
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
| | - N Imano
- Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima 734-8551, Japan
| | - Y Murakami
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan
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Ando K, Kenmotsu H, Nishibori Y, Tamura A, Matsuda S, Morita M, Sekikawa M, Doshita K, Miura K, Kodama H, Yabe M, Morikawa N, Iida Y, Mamesaya N, Kobayashi H, Ko R, Wakuda K, Ono A, Naito T, Murakami H, Takahashi T. Deterioration of performance status before administration of chemotherapy as a prognostic factor in untreated advanced non-small cell lung cancer. Cancer Treat Res Commun 2025; 43:100915. [PMID: 40158267 DOI: 10.1016/j.ctarc.2025.100915] [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: 10/01/2024] [Revised: 03/06/2025] [Accepted: 03/25/2025] [Indexed: 04/02/2025]
Abstract
INTRODUCTION The prognostic impact of changes in performance status (PS) of untreated patients with advanced non-small cell lung cancer (NSCLC) are not clear. This study aimed to evaluate the prognostic impact of acute PS deterioration in patients with untreated advanced NSCLC. METHODS This study is a single center, retrospective, observational study. Patients with Stage IV NSCLC who were referred to our institution between January 2018 and March 2023 were retrospectively reviewed. Patients were divided into three groups: 1) patients with PS 0 or 1 at referral and the start of chemotherapy; 2) patients with PS 2 or worse at initial referral and the start of chemotherapy; and 3) patients with PS 0 or 1 at referral that deteriorated to PS 2 or worse at the start of chemotherapy. The prognoses of Groups 2 and 3 were compared with those of Group 1. RESULTS A total of 373 patients were included: 321 in Group 1, 20 in Group 2, and 32 in Group 3. The median overall survival (OS) of Group 3 was shorter than that of Group 1 (9.3 vs. 27.1 months, hazard ratio [HR] 2.56, p < 0.01). The median OS of Group 2 was also shorter than that of Group 1, although not as significant as in Group 3 (20.2 vs. 27.1 months, HR 1.68, p = 0.06). After adjusting for symptoms, liver and pericardial metastases were associated with PS deterioration in multivariate analysis. CONCLUSION Among patients with untreated advanced NSCLC, acute PS deterioration before chemotherapy administration was associated with poor prognosis.
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Affiliation(s)
- Kenju Ando
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | | | | | - Akiko Tamura
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Suguru Matsuda
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Meiko Morita
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Motoki Sekikawa
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kosei Doshita
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Keita Miura
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Hiroaki Kodama
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Michitoshi Yabe
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Noboru Morikawa
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yuko Iida
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Nobuaki Mamesaya
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Haruki Kobayashi
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ryo Ko
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kazushige Wakuda
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Akira Ono
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Tateaki Naito
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Haruyasu Murakami
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
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Lu Y, Fang D, Guo J, Huang H. Partial transformation from non-small cell lung cancer to small cell lung cancer: a case report and literatures review. Front Oncol 2025; 15:1441182. [PMID: 40134592 PMCID: PMC11933710 DOI: 10.3389/fonc.2025.1441182] [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: 05/30/2024] [Accepted: 02/18/2025] [Indexed: 03/27/2025] Open
Abstract
A fraction of lung adenocarcinoma patients with gene mutations who receive targeted therapy would experience acquired resistance and undergo small cell lung cancer (SCLC) transformation. The mechanisms behind the transformation of tumor pathological types and the treatment strategies are not fully clear. There have been case reports of the transformation from adenocarcinoma to SCLC, but the partial transformation from adenocarcinoma to SCLC has not been reported. We reported a case of a patient with partial transformation from lung adenocarcinoma to SCLC for the first time. The patient was diagnosed as lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 exon mutation and Tumor protein p53 (TP53) mutation. She received Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, the tumor progression occurred and the lung aspiration pathology revealed a transformation from non-small cell lung cancer (NSCLC) to SCLC. The treatment regimen was changed to cisplatin and etoposide (EP) chemotherapy, resulting in a 2-month PFS. It was worth mentioning that adenocarcinoma cells were found in the patient's emerging pericardial effusion, suggesting the co-existence of both adenocarcinoma and SCLC components. This is the first report of partial transformation from NSCLC to SCLC in the context of definitive pathology. It highlights that when no more pathological biopsy is feasible, we should be alert to the partial transformation and adopt the appropriate treatment.
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Affiliation(s)
| | | | | | - Huaqiong Huang
- Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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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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Li Z, Shi P, Qin C, Zhang W, Lin S, Zheng T, Li M, Fan L. Nomogram predicting overall survival of stage IIIB non-small-cell lung cancer patients based on the SEER database. THE CLINICAL RESPIRATORY JOURNAL 2025; 19:e13660. [PMID: 37466041 PMCID: PMC11931320 DOI: 10.1111/crj.13660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 06/22/2023] [Indexed: 07/20/2023]
Abstract
PURPOSE We aimed to evaluate the prognostic value of stage IIIB non-small-cell (NSCLC) lung cancer patients and to construct a nomogram to effectively predict their overall survival (OS). METHODS In total, 4323 patients with stage IIIB NSCLC diagnosed between 1975 and 2018 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple prognostic factors were combined to construct a nomogram for predicting OS of patients with stage IIIB NSCLC. The discrimination and calibration of the nomogram were evaluated by C-indexes and calibration curves. The nomogram was evaluated for predictive ability using receiver operating characteristic (ROC) curves, decision curve analysis curve (DCA), and clinical impact curve (CIC). RESULTS The nomogram was built on data of 4323 patients with stage IIIB NSCLC and consisted of the following prognostic factors: age, race, sex, primary labeled, pathology, T stage, whether to receive surgery, whether to receive radiotherapy, and whether to receive chemotherapy. The C-index in the training and validation sets for the nomogram was 0.672 (95% CI: 0.661-0.683) and 0.675 (95% CI: 0.656-0.694), respectively. According to scores of the nomogram, patients in the complete set, validation set, and training set were classified into two risk groups, low risk and high risk. CONCLUSIONS We developed the first validated nomogram to estimate the OS of patients with stage IIIB NSCLC. The nomogram was based on nine prognostic factors and provided an individualized risk estimate of 3-year and 5-year OS survival in patients with stage IIIB NSCLC.
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Affiliation(s)
- Ziye Li
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Respiratory Medicine, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Pingfan Shi
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Respiratory Medicine, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Chenge Qin
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Respiratory Medicine, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
- Medical School of Nantong UniversityNantong UniversityNantongChina
| | - Wen Zhang
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Respiratory Medicine, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Shumeng Lin
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Respiratory Medicine, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Tiansheng Zheng
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Department of Respiratory Medicine, Shanghai Tenth People's HospitalTongji University School of MedicineShanghaiChina
| | - Ming Li
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
| | - Lihong Fan
- Integrated Chinese and Western Medicine Pulmonary Nodules Center, Shanghai Tenth People's Hospital, School of MedicineTongji UniversityShanghaiChina
- Medical School of Nantong UniversityNantong UniversityNantongChina
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Ikeda S, Ogura T, Miyaoka E, Sekine I, Shukuya T, Takayama K, Inoue A, Okamoto I, Seike M, Takahashi K, Yamamoto N, Yotsukura M, Watanabe SI, Shintani Y. Survival benefit and potential markers of chemotherapy for elderly and poor performance status patients with advanced non-small cell lung cancer: Results from the Japanese Joint Committee of lung cancer registry database. Lung Cancer 2025; 200:108102. [PMID: 39924255 DOI: 10.1016/j.lungcan.2025.108102] [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: 12/12/2024] [Revised: 01/15/2025] [Accepted: 01/18/2025] [Indexed: 02/11/2025]
Abstract
INTRODUCTION Data on chemotherapy for elderly, poor performance status (PS) non-small cell lung cancer (NSCLC) are clinically important but insufficient due to their exclusion from most interventional studies. This study aims to explore actual treatment status and prognosis, as well as factors predicting patients who may benefit from chemotherapy. MATERIALS AND METHODS Advanced NSCLC patients aged ≥75 years with PS 2-3 and no/unknown driver mutations were included. In each of PS2 and PS3 cohorts, we compared the overall survival (OS) of the chemotherapy and Best Supportive Care (BSC) group after adjusting by inverse probability weighting (IPW) method, and analyzed prognostic factors using the COX proportional hazards model. We defined the patients with body weight loss ≥5 % within 6 months as cancer cachexia in this study. RESULTS This study included 282 patients (Chemotherapy;107, BSC;175) in PS2 cohort and 230 patients (Chemotherapy;39, BSC;191) in PS3 cohort. In both PS2 and PS3 cohorts, IPW-adjusted OS was significantly longer in the chemotherapy group than in the BSC group (HR 0.42 [95 % CI 0.32-0.55] and 0.56 [95 % CI 0.41-0.75], p < 0.001 and 0.003, respectively). Multivariate analysis showed that cancer cachexia and stage IV were significantly associated with OS in PS2 cohort. For patients with cancer cachexia in PS3 cohort, chemotherapy did not prolong OS (HR 0.81 [95 % CI 0.45-1.45], p = 0.530). CONCLUSION Chemotherapy might provide a survival benefit even for elderly, poor PS NSCLC patients. In vulnerable PS 3 patients, cancer cachexia may be useful in predicting patients who may benefit from chemotherapy.
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Affiliation(s)
- Satoshi Ikeda
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama 236-0051 Japan.
| | - Takashi Ogura
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama 236-0051 Japan
| | - Etsuo Miyaoka
- Department of Mathematics, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601 Japan
| | - Ikuo Sekine
- Department of Medical Oncology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575 Japan
| | - Takehito Shukuya
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-Ku, Tokyo 113-8431 Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566 Japan
| | - Akira Inoue
- Department of Palliative Medicine, Tohoku University School of Medicine, 2-1 Seiryomachi, Sendai, Miyagi 980-8575, Japan
| | - Isamu Okamoto
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Masahiro Seike
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
| | - Kazuhisa Takahashi
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-Ku, Tokyo 113-8431 Japan
| | - Nobuyuki Yamamoto
- Internal Medicine III, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan
| | - Masaya Yotsukura
- Department of Thoracic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Shun-Ichi Watanabe
- Department of Thoracic Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
| | - Yasushi Shintani
- Department of General Thoracic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
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Xie C, Chen J, Yang S, Ye F, Lin Z, Xu Y, Yang Y, Tong L. Risk Factors for Prognosis of Lung Cancer Patients Receiving Anlotinib Treatment: A Retrospective Cohort Study. THE CLINICAL RESPIRATORY JOURNAL 2025; 19:e70051. [PMID: 39924314 PMCID: PMC11807704 DOI: 10.1111/crj.70051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 10/30/2024] [Accepted: 01/29/2025] [Indexed: 02/11/2025]
Abstract
PURPOSE Anlotinib is widely used in the treatment of lung cancer. However, there remains a lack of predictive biomarkers to effectively gauge the response to anlotinib therapy. We conducted a retrospective study to preliminarily explore potential risk factors that might predict outcomes in lung cancer patients undergoing anlotinib treatment. PATIENTS AND METHODS We retrospectively analyzed lung cancer patients treated with anlotinib at our hospital between 1 June 2018 and 1 June 2021. Data were gathered from electronic medical records. Demographic and clinical characteristics of patients, progression-free survival (PFS), and overall survival (OS) were described. Predictive factors related to treatment efficacy were preliminarily analyzed using Cox regression and Kaplan-Meier survival analyses. RESULTS After adjusting for potential confounders, clinical stage IV (hazard ratio [HR] = 2.52, 95% confidence interval [CI], 1.09-5.82, p = 0.0311), N-terminal fragment brain natriuretic peptides (NT-pro-BNP) > 300 pg/mL (HR = 2.54, 95% CI, 1.17-5.52, p = 0.0183), and neuron-specific enolase (NSE) > 16.3 ng/mL (HR = 1.70, 95% CI, 1.03-2.81, p = 0.0389) were associated with shorter OS, whereas age (HR = 0.96, 95% CI, 0.94-0.99, p = 0.0055) was associated with a longer PFS in fully adjusted model. Kaplan-Meier analyses of cumulative risk factors (clinical stage IV, NT-pro-BNP > 300 pg/mL, and NSE > 16.3 ng/mL) indicated that patients with a greater number of coexisting risk factors had significantly shorter OS (p < 0.0001). CONCLUSION Clinical stage IV, NT-pro-BNP level, and NSE level were identified as independent prognostic factors for lung cancer patients undergoing anlotinib treatment. Patients with multiple high-risk factors may derive limited benefit from anlotinib.
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Affiliation(s)
- Congyi Xie
- Department of Pulmonary MedicineZhongshan Hospital (Xiamen), Fudan UniversityXiamenFujianPeople's Republic of China
- Xiamen Clinical Research Center for Cancer TherapyXiamenFujianPeople's Republic of China
| | - Jinzhan Chen
- Department of Pulmonary MedicineZhongshan Hospital (Xiamen), Fudan UniversityXiamenFujianPeople's Republic of China
| | - Shuwen Yang
- Department of Pulmonary MedicineZhongshan Hospital (Xiamen), Fudan UniversityXiamenFujianPeople's Republic of China
| | - Feiyang Ye
- College of Computer and Data ScienceFuzhou UniversityFuzhouFujianPeople's Republic of China
| | - Zhenyang Lin
- Department of Thoracic SurgeryZhongshan Hospital (Xiamen), Fudan UniversityXiamenFujianPeople's Republic of China
| | - Yijiao Xu
- Department of Pulmonary MedicineZhongshan Hospital (Xiamen), Fudan UniversityXiamenFujianPeople's Republic of China
| | - Yimin Yang
- Department of Vascular SurgeryZhongshan Hospital, Fudan UniversityShanghaiPeople's Republic of China
| | - Lin Tong
- Department of Pulmonary MedicineZhongshan Hospital (Xiamen), Fudan UniversityXiamenFujianPeople's Republic of China
- Department of Pulmonary and Critical Care MedicineZhongshan Hospital, Fudan UniversityShanghaiPeople's Republic of China
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Endo S, Imai H, Mouri A, Tsukamoto K, Masaki K, Hashimoto K, Miura Y, Shiono A, Yamaguchi O, Nakagawa J, Kaira K, Kobayashi K, Kagamu H. Efficacy and safety of first-line nivolumab plus ipilimumab treatment in elderly patients (aged ≥ 75 years) with non-small cell lung cancer. J Cancer Res Clin Oncol 2025; 151:43. [PMID: 39843575 PMCID: PMC11754340 DOI: 10.1007/s00432-025-06089-x] [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: 12/04/2024] [Accepted: 01/09/2025] [Indexed: 01/24/2025]
Abstract
PURPOSE Nivolumab plus ipilimumab (Nivo-Ipi) combination therapy is an effective first-line treatment for advanced non-small cell lung cancer (NSCLC). However, its effectiveness and feasibility in elderly patients (aged ≥ 75 years) remain unclear. This study aimed to investigate the efficacy and safety of first-line Nivo-Ipi therapy in elderly patients with NSCLC. METHODS This retrospective study included 57 patients with NSCLC (52 men and 5 women), aged ≥ 75 years (range: 75-86) who received first-line Nivo-Ipi therapy from December 2020 to November 2022 at four institutes in Japan. Patient characteristics, therapeutic efficacy, and the incidence and severity of adverse events (AE) were assessed. RESULTS The overall response rate was 42.1%, the disease control rate was 73.6%, the median progression-free survival (PFS) was 7.1 months, and the median overall survival (OS) was 14.1 months. Common Grade ≥ 3 AEs included pneumonitis, elevated aspartate transaminase, elevated alanine transaminase, adrenal insufficiency, and colitis. No treatment-related deaths were reported. PFS and OS were longer in patients who experienced treatment-related AEs. Patients with and without AEs had a median PFS of 11.7 and 2.8 months, respectively. Similarly, the median OS of patients with and without AEs was 20.4 and 9.0 months, respectively. CONCLUSION First-line Nivo-Ipi therapy is effective in elderly patients with NSCLC. Although there was an increased incidence of pneumonitis, the treatment was manageable and presented as a viable treatment option. Notably, the occurrence of treatment-related AEs was associated with improved clinical outcomes, suggesting a potential prognostic value of AEs in this population.
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Affiliation(s)
- Satoshi Endo
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
| | - Hisao Imai
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan.
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan.
| | - Atsuto Mouri
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
- Division of Respiratory Medicine, National Hospital Organization Disaster Medical Center, Tachikawa , Tokyo, Japan
| | - Kasumi Tsukamoto
- Division of Respiratory Medicine, National Hospital Organization Disaster Medical Center, Tachikawa , Tokyo, Japan
| | - Kenji Masaki
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
| | - Kosuke Hashimoto
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
| | - Yu Miura
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
| | - Ayako Shiono
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
| | - Ou Yamaguchi
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
| | - Junichi Nakagawa
- Division of Respiratory Medicine, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
| | - Kyoichi Kaira
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
- Division of Respiratory Medicine, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
| | - Kunihiko Kobayashi
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
| | - Hiroshi Kagamu
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka-City, Saitama, 350-1298, Japan
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9
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Gaebe K, Erickson AW, Chen S, Menjak IB, Lok BH, Sahgal A, Chan KK, Das S. Brain metastasis burden and management in patients with small cell lung cancer in Canada: a retrospective, population-based cohort study. EClinicalMedicine 2024; 77:102871. [PMID: 39416386 PMCID: PMC11474380 DOI: 10.1016/j.eclinm.2024.102871] [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: 05/21/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 10/19/2024] Open
Abstract
Background Patients with small cell lung cancer (SCLC) have historically been characterised by poor overall survival (OS) and high risk for brain metastasis (BM), but large-scale real-world evidence on clinical presentation and treatment in this population is lacking. Our aim was to describe the clinical characteristics and outcomes of patients with SCLC and BM in Ontario, Canada. Methods This population-based, retrospective cohort study included all patients in Ontario, Canada, who were diagnosed with SCLC between April 1, 2010, and March 31, 2018. Data were analysed between June 2, 2022, and December 20, 2023. Patients with second cancer diagnosis were excluded. Patients were identified and data retrieved from the Institute for Clinical Evaluative Sciences (ICES) databases. Kaplan-Meier and multivariable Cox regression analyses were performed to compare OS between patient cohorts stratified by disease stage, BM diagnosis, and intracranial treatment modality. Propensity score-matching based on age, disease stage, time to BM, and receipt of chemotherapy was performed to compare OS between intracranial treatment modalities. Findings 8705 patients were included (male: 4433, female: 4272). Median age at diagnosis was 68 years (interquartile range, IQR, 61-75). Median OS of all patients was 7.46 months (95% confidence interval, CI, 7.23-7.69). 32% (n = 2686) of patients developed BM (synchronous, 43.7%; asynchronous, 56.3%) with median OS of 9.76 months (95% CI, 9.36-10.22). 102 (4%), 1654 (62%), and 930 (35%) patients received stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), or no treatment, respectively, for their BM in the first-line setting or after prophylactic cranial irradiation (PCI). In propensity score-matched analyses, OS from time of BM diagnosis was non-inferior between SRS- and WBRT-treated cohorts among patients who did not receive PCI (hazard ratio, HR, 0.68, 95% CI, 0.44-1.06, p = 0.091, n = 86) and in favour of SRS for those who received PCI prior to BM development (HR, 0.47, 95% CI, 0.31-0.72, p = 0.0042, n = 112). Interpretation OS for patients with SCLC remains poor, and many patients present with BM. With careful selection, patients with SCLC and BM may benefit from SRS treatment. Future research should incorporate information on burden of intracranial disease and novel immunotherapies. Funding None.
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Affiliation(s)
- Karolina Gaebe
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Anders W. Erickson
- Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sarah Chen
- Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada
| | - Ines B. Menjak
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Benjamin H. Lok
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Arjun Sahgal
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Kelvin K.W. Chan
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
| | - Sunit Das
- Division of Neurosurgery, Department of Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
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10
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Rousseau G, Dantoing E, Léturgie B, Tillon-Strozyk J, Delberghe N, Grégoire A, Bota S, Corre R, Thiberville L, Guisier F. Brief Report: Carboplatin, Weekly Paclitaxel and Pembrolizumab in Elderly Patients for Advanced Non-Small Cell Lung Cancer With PD-L1 < 50%: Real-World Data. Clin Lung Cancer 2024; 25:e323-e329. [PMID: 38866664 DOI: 10.1016/j.cllc.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 05/14/2024] [Accepted: 05/15/2024] [Indexed: 06/14/2024]
Affiliation(s)
| | | | | | - Julie Tillon-Strozyk
- Department of Pneumology, CHU Rouen, Rouen, France; Department of Pneumology, CH Dieppe, Dieppe, France
| | - Nicolas Delberghe
- Department of Pneumology, CHU Rouen, Rouen, France; Department of Pneumology, CH Evreux, Evreux, France
| | - Antoine Grégoire
- Department of Pneumology, CHU Rouen, Rouen, France; Department of Pneumology, CH Dieppe, Dieppe, France
| | - Suzanna Bota
- Department of Pneumology, CHU Rouen, Rouen, France
| | - Romain Corre
- Department of Pneumology, CH Cornouaille, Quimper, France
| | - Luc Thiberville
- Department of Pneumology and Inserm CIC-CRB 1404, Normandie Univ, UNIROUEN, LITIS Lab QuantIF team EA4108, CHU Rouen, Rouen, France
| | - Florian Guisier
- Department of Pneumology and Inserm CIC-CRB 1404, Normandie Univ, UNIROUEN, LITIS Lab QuantIF team EA4108, CHU Rouen, Rouen, France.
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Tsubokawa N, Mimae T, Mimura T, Kamigaichi A, Fujiwara M, Kawamoto N, Miyata Y, Okada M. Clinical Significance of Preserving Pulmonary Function After Lung Resection in Early-Stage Non-Small-Cell Lung Cancer. Clin Lung Cancer 2024; 25:329-335.e1. [PMID: 38429143 DOI: 10.1016/j.cllc.2024.01.003] [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: 07/18/2023] [Revised: 12/21/2023] [Accepted: 01/18/2024] [Indexed: 03/03/2024]
Abstract
INTRODUCTION To determine the association between changes in pulmonary function before and after surgery, and the subsequent prognosis, of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS A total of 485 patients who underwent lobectomy or segmentectomy for NSCLC with whole tumor size ≤2 cm and clinical stage IA at 2 institutions were retrospectively reviewed. The relationship between the postoperative reduction rate in vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) and overall survival (OS) was investigated. OS determined the cut-off value of the reduction rate, according to the reduction rate of every 10% in pulmonary function. RESULTS Multivariable Cox regression analysis showed that a reduction rate in VC at 12 months postoperatively was an independent prognostic factor for OS (hazard ratio, 1.05; 95% confidence interval [CI], 1.02-1.07; P < .001) but those in FVC and FEV1 were not. OS was classified into good and poor with 20% reduction rate in VC. OS and recurrence-free survival (RFS) in a higher than 20% reduction rate in VC were worse than those in ≤20% reduction rate in VC (5 year-OS; 82.0% vs. 93.4%; P = .0004. Five year-RFS; 80.3% vs. 89.8%; P = .0018, respectively). Multivariable logistic analysis showed that lobectomy was a risk factor for the higher than 20% reduction rate in VC (odds ratio, 1.61; 95% CI, 1.01-2.56; P = .045). CONCLUSIONS Postoperative decrease in VC was significantly associated with the prognosis. Preserving pulmonary function is important for survival of patients with early-stage NSCLC.
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Affiliation(s)
| | - Takahiro Mimae
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Takeshi Mimura
- Department of General Thoracic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan
| | | | - Makoto Fujiwara
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Nobutaka Kawamoto
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Yoshihiro Miyata
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
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12
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Li S, Yu ZS, Liu HZ, Li SJ, Wang MY, Ning FL, Tian LJ. Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study. Cancer Med 2024; 13:e7349. [PMID: 38872402 PMCID: PMC11176590 DOI: 10.1002/cam4.7349] [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: 11/28/2023] [Revised: 05/16/2024] [Accepted: 05/24/2024] [Indexed: 06/15/2024] Open
Abstract
BACKGROUND Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. METHODS In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. RESULTS Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. CONCLUSIONS Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.
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Affiliation(s)
- Shuo Li
- Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
| | - Ze-Shun Yu
- Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
| | - Hong-Zhi Liu
- Department of Orthopedics, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
| | - Shu-Jing Li
- Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
| | - Ming-Yue Wang
- Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
| | - Fang-Ling Ning
- Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
| | - Li-Jun Tian
- Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, People's Republic of China
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Badheeb AM, Obied HY, Al Suleiman M, Qurayshah MA, Awad MA, Abu Bakar A, Alwadai B, Nasher AM, Seada IA, Alyami NH, Aman AA, Ahmed F, Al Qasim A, Badheeb M. Clinical and Therapeutic Characteristics of Hospitalized Patients with Advanced Lung Cancer in Najran, Saudi Arabia: A Retrospective Study. Cureus 2024; 16:e58602. [PMID: 38770472 PMCID: PMC11102885 DOI: 10.7759/cureus.58602] [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: 04/19/2024] [Indexed: 05/22/2024] Open
Abstract
BACKGROUND Lung cancer is one of the top causes of cancer deaths globally, including in Saudi Arabia. Although several prognostic markers have been established, the clinical features and outcomes of lung cancer in Saudi Arabia are not well understood. This study aimed to describe the clinical and therapeutic characteristics of advanced lung cancer in Najran, Saudi Arabia. METHOD A retrospective chart review of 44 patients diagnosed with advanced lung cancer between June 2018 and September 2021 and treated at the Oncology Center of King Khalid Hospital in Najran City, Saudi Arabia. The clinicopathological features, treatment used, response, and survival outcomes were collected and analyzed. RESULT The mean age was 69.3 ± 10.7 years, most of them (n = 35, 79.5%) were male and older than 70 years (n = 24, 54.5%). Adenocarcinoma was the most observed cancer (n = 35, 79.5%), followed by squamous cell carcinoma in six (13.6%). Most cases (n = 42, 95.5%) were in stage IV. Epidermal growth factor receptor (EGFR) mutations were positive in two (4.5%) cases and ALK mutation was positive in two (4.5%) cases. Metastasis to pleura with pleural effusion was the common presentation (n = 41, 93%). Chemotherapy was administered as the first line in 19 cases (43.2%) while 25 cases (56.8%) received chemoimmunotherapy. The commonest chemoimmunotherapy regimen used was carboplatin-pemetrexed-pembrolizumab in 16 (36.4%), followed by carboplatin-paclitaxel-pembrolizumab in 9 (20.5%) cases. The response to initial systemic therapy was as follows disease progression, stable disease, and complete remission in 10 (22.7%), 33 (75.0%), and 1 (2.3%), respectively. Median progression-free survival was 8.7 months (interquartile range (IQR): 5.7-11.4), and the median overall survival was 12.3 months (IQR: 11.1-13.4). Among the total documented 36 (81.8%) dead cases, disease progression was the main cause of death in 25 cases (56.8%). Using chemoimmunotherapy as the first-line therapy was associated with numerical survival improvement compared to using chemotherapy alone (HR: 0.75; 95% CI: 0.39-1.46) however, it was not statistically significant (p = 0.397). CONCLUSION In this study, the majority of lung cancer patients were male and over 70 years old. Adenocarcinoma was the most common histological type. Metastasis to pleura with pleural effusion was the common presentation. The most common treatment used was chemoimmunotherapy with a regimen of carboplatin-pemetrexed-pembrolizumab. Addressing the possible causes of delayed diagnosis of lung cancer is crucial for improved survival outcomes.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Islam A Seada
- Cardiothoracic Surgery, King Khalid Hospital, Najran, SAU
| | - Nasher H Alyami
- Pathology and Hematology, Ministry of Health Holdings, Najran, SAU
| | | | | | | | - Mohamed Badheeb
- Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, USA
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14
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Morgan H, Gysling S, Navani N, Baldwin D, Hubbard R, O'Dowd E. Impact of the SARS-CoV-2 pandemic on lung cancer survival in England: an analysis of the rapid cancer registration dataset. Thorax 2023; 79:83-85. [PMID: 37932123 DOI: 10.1136/thorax-2022-219593] [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: 09/05/2022] [Accepted: 10/12/2023] [Indexed: 11/08/2023]
Abstract
Early changes in lung cancer care can affect survival. Given the decrease in diagnosis during lockdowns, we calculated their impact on survival using National Lung Cancer Audit data. Percentage survival and HRs for death were compared between 2019 and lockdown periods of 2020. Decreased survival was observed from the first national lockdown onwards and within 90 days of diagnosis. HRs were highest for people diagnosed at the end of 2020 at 1.26 (95% CI 1.20 to 1.32) for death within 90 days and 1.51 (95% CI 1.42 to 1.60) for death between 91 and 270 days. Further work is needed on measures to mitigate this impact.
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Affiliation(s)
- Helen Morgan
- Lifespan and Population Health Sciences, University of Nottingham, Nottingham, UK
| | - Savannah Gysling
- Lifespan and Population Health Sciences, University of Nottingham, Nottingham, UK
| | - Neal Navani
- Respiratory Medicine, University College London, London, UK
| | - David Baldwin
- Lifespan and Population Health Sciences, University of Nottingham, Nottingham, UK
- Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Richard Hubbard
- Lifespan and Population Health Sciences, University of Nottingham, Nottingham, UK
| | - Emma O'Dowd
- Lifespan and Population Health Sciences, University of Nottingham, Nottingham, UK
- Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK
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15
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Zhang S, Liu X, Zhou L, Wang K, Shao J, Shi J, Wang X, Mu J, Gao T, Jiang Z, Chen K, Wang C, Wang G. Intelligent prognosis evaluation system for stage I-III resected non-small-cell lung cancer patients on CT images: a multi-center study. EClinicalMedicine 2023; 65:102270. [PMID: 38106558 PMCID: PMC10725055 DOI: 10.1016/j.eclinm.2023.102270] [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: 07/10/2023] [Revised: 09/27/2023] [Accepted: 09/27/2023] [Indexed: 12/19/2023] Open
Abstract
Background Prognosis is crucial for personalized treatment and surveillance suggestion of the resected non-small-cell lung cancer (NSCLC) patients in stage I-III. Although the tumor-node-metastasis (TNM) staging system is a powerful predictor, it is not perfect enough to accurately distinguish all the patients, especially within the same TNM stage. In this study, we developed an intelligent prognosis evaluation system (IPES) using pre-therapy CT images to assist the traditional TNM staging system for more accurate prognosis prediction of resected NSCLC patients. Methods 20,333 CT images of 6371 patients from June 12, 2009 to March 24, 2022 in West China Hospital of Sichuan University, Mianzhu People's Hospital, Peking University People's Hospital, Chengdu Shangjin Nanfu Hospital and Guangan Peoples' Hospital were included in this retrospective study. We developed the IPES based on self-supervised pre-training and multi-task learning, which aimed to predict an overall survival (OS) risk for each patient. We further evaluated the prognostic accuracy of the IPES and its ability to stratify NSCLC patients with the same TNM stage and with the same EGFR genotype. Findings The IPES was able to predict OS risk for stage I-III resected NSCLC patients in the training set (C-index 0.806; 95% CI: 0.744-0.846), internal validation set (0.783; 95% CI: 0.744-0.825) and external validation set (0.817; 95% CI: 0.786-0.849). In addition, IPES performed well in early-stage (stage I) and EGFR genotype prediction. Furthermore, by adopting IPES-based survival score (IPES-score), resected NSCLC patients in the same stage or with the same EGFR genotype could be divided into low- and high-risk subgroups with good and poor prognosis, respectively (p < 0.05 for all). Interpretation The IPES provided a non-invasive way to obtain prognosis-related information from patients. The identification of IPES for resected NSCLC patients with low and high prognostic risk in the same TNM stage or with the same EGFR genotype suggests that IPES have potential to offer more personalized treatment and surveillance suggestion for NSCLC patients. Funding This study was funded by the National Natural Science Foundation of China (grant 62272055, 92259303, 92059203), New Cornerstone Science Foundation through the XPLORER PRIZE, Young Elite Scientists Sponsorship Program by CAST (2021QNRC001), Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities (K.C.), Research Unit of Intelligence Diagnosis and Treatment in Early Non-small Cell Lung Cancer, Chinese Academy of Medical Sciences (2021RU002), BUPT Excellent Ph.D. Students Foundation (CX2022104).
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Affiliation(s)
- Siqi Zhang
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, 100876, China
| | - Xiaohong Liu
- UCL Cancer Institute, University College London, London, WC1E 6DD, UK
| | - Lixin Zhou
- Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Kai Wang
- College of Future Technology, Peking University and Peking-Tsinghua Center for Life Sciences, Beijing, 100871, China
| | - Jun Shao
- State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jianyu Shi
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, 100876, China
| | - Xuan Wang
- Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Jiaxing Mu
- Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Tianrun Gao
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, 100876, China
| | - Zeyu Jiang
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, 100876, China
| | - Kezhong Chen
- Thoracic Oncology Institute and Department of Thoracic Surgery, Peking University People's Hospital, Beijing, 100044, China
| | - Chengdi Wang
- State Key Laboratory of Respiratory Health and Multimorbidity, Department of Pulmonary and Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Guangyu Wang
- State Key Laboratory of Networking and Switching Technology, Beijing University of Posts and Telecommunications, Beijing, 100876, China
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Chang R, Qi S, Wu Y, Yue Y, Zhang X, Qian W. Nomograms integrating CT radiomic and deep learning signatures to predict overall survival and progression-free survival in NSCLC patients treated with chemotherapy. Cancer Imaging 2023; 23:101. [PMID: 37867196 PMCID: PMC10590525 DOI: 10.1186/s40644-023-00620-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 10/16/2023] [Indexed: 10/24/2023] Open
Abstract
OBJECTIVES This study aims to establish nomograms to accurately predict the overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) who received chemotherapy alone as the first-line treatment. MATERIALS AND METHODS In a training cohort of 121 NSCLC patients, radiomic features were extracted, selected from intra- and peri-tumoral regions, and used to build signatures (S1 and S2) using a Cox regression model. Deep learning features were obtained from three convolutional neural networks and utilized to build signatures (S3, S4, and S5) that were stratified into over- and under-expression subgroups for survival risk using X-tile. After univariate and multivariate Cox regression analyses, a nomogram incorporating the tumor, node, and metastasis (TNM) stages, radiomic signature, and deep learning signature was established to predict OS and PFS, respectively. The performance was validated using an independent cohort (61 patients). RESULTS TNM stages, S2 and S3 were identified as the significant prognosis factors for both OS and PFS; S2 (OS: (HR (95%), 2.26 (1.40-3.67); PFS: (HR (95%), 2.23 (1.36-3.65)) demonstrated the best ability in discriminating patients with over- and under-expression. For the OS nomogram, the C-index (95% CI) was 0.74 (0.70-0.79) and 0.72 (0.67-0.78) in the training and validation cohorts, respectively; for the PFS nomogram, the C-index (95% CI) was 0.71 (0.68-0.81) and 0.72 (0.66-0.79). The calibration curves for the 3- and 5-year OS and PFS were in acceptable agreement between the predicted and observed survival. The established nomogram presented a higher overall net benefit than the TNM stage for predicting both OS and PFS. CONCLUSION By integrating the TNM stage, CT radiomic signature, and deep learning signatures, the established nomograms can predict the individual prognosis of NSCLC patients who received chemotherapy. The integrated nomogram has the potential to improve the individualized treatment and precise management of NSCLC patients.
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Affiliation(s)
- Runsheng Chang
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Shouliang Qi
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China.
- Key Laboratory of Intelligent Computing in Medical Image, Ministry of Education, Northeastern University, Shenyang, China.
| | - Yanan Wu
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Yong Yue
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiaoye Zhang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei Qian
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
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17
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Tafenzi HA, Choulli F, Adjade G, Baladi A, Afani L, Fadli ME, Essaadi I, Belbaraka R. Development of a well-defined tool to predict the overall survival in lung cancer patients: an African based cohort. BMC Cancer 2023; 23:1016. [PMID: 37864151 PMCID: PMC10589978 DOI: 10.1186/s12885-023-11355-7] [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: 02/01/2023] [Accepted: 08/31/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Nomogram is a graphic representation containing the expressed factor of the mathematical formula used to define a particular phenomenon. We aim to build and internally validate a nomogram to predict overall survival (OS) in patients diagnosed with lung cancer (LC). METHODS We included 1200 LC patients from a single institution registry diagnosed from 2013 to 2021. The independent prognostic factors of LC patients were identified via cox proportional hazard regression analysis. Based on the results of multivariate cox analysis, we constructed the nomogram to predict the OS of LC patients. RESULTS We finally included a total of 1104 LC patients. Age, medical urgency at diagnosis, performance status, radiotherapy, and surgery were identified as prognostic factors, and integrated to build the nomogram. The model performance in predicting prognosis was measured by receiver operating characteristic curve. Calibration plots of 6-, 12-, and 24- months OS showed optimal agreement between observations and model predictions. CONCLUSION We have developed and validated a unique predictive tool that can offer patients with LC an individual OS prognosis. This useful prognostic model could aid doctors in making decisions and planning therapeutic trials.
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Affiliation(s)
- Hassan Abdelilah Tafenzi
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco.
- Faculty of Medicine and Pharmacy, Biosciences and Health Laboratory, Cadi Ayyad University, Marrakech, Morocco.
| | - Farah Choulli
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco
- Faculty of Medicine and Pharmacy, Biosciences and Health Laboratory, Cadi Ayyad University, Marrakech, Morocco
| | - Ganiou Adjade
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco
| | - Anas Baladi
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco
| | - Leila Afani
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco
| | - Mohammed El Fadli
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco
| | - Ismail Essaadi
- Faculty of Medicine and Pharmacy, Biosciences and Health Laboratory, Cadi Ayyad University, Marrakech, Morocco
- Medical Oncology Department, Avicenna Military Hospital of Marrakech, Marrakech, Morocco
| | - Rhizlane Belbaraka
- Medical Oncology Department, Mohammed VI University Hospital of Marrakech, Marrakech, Morocco
- Faculty of Medicine and Pharmacy, Biosciences and Health Laboratory, Cadi Ayyad University, Marrakech, Morocco
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Denault MH, Feng J, Kuang S, Shokoohi A, Leung B, Liu M, Berthelet E, Laskin J, Sun S, Zhang T, Ho C, Melosky B. Beyond PACIFIC: Real-World Outcomes of Adjuvant Durvalumab According to Treatment Received and PD-L1 Expression. Curr Oncol 2023; 30:7499-7507. [PMID: 37623024 PMCID: PMC10453050 DOI: 10.3390/curroncol30080543] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 07/20/2023] [Accepted: 08/03/2023] [Indexed: 08/26/2023] Open
Abstract
Adjuvant durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). A post hoc exploratory analysis of PACIFIC revealed no OS benefit in the PD-L1 < 1% subgroup. This retrospective analysis assesses the real-world impact of durvalumab on OS according to PD-L1 tumor proportion score (TPS). Patients with stage III, unresectable NSCLC treated by CRT, with available PD-L1 TPS, from 1 March 2018 to 31 December 2020, at BC Cancer, British Columbia, Canada were included. Patients were divided into two groups, CRT + durvalumab and CRT alone. OS and PFS were analyzed in the PD-L1 ≥ 1% and <1% subgroups. A total of 134 patients were included in the CRT + durvalumab group and 117, in the CRT alone group. Median OS was 35.9 months in the CRT + durvalumab group and 27.4 months in the CRT alone group [HR 0.59 (95% CI 0.42-0.83), p = 0.003]. Durvalumab improved OS in the PD-L1 ≥ 1% [HR 0.53 (95% CI 0.34-0.81), p = 0.003, n = 175], but not in the <1% subgroup [HR 0.79 (95% CI 0.44-1.42), p = 0.4, n = 76]. This retrospective study demonstrates a statistically significant improvement in OS associated with durvalumab after CRT in PD-L1 ≥ 1%, but not PD-L1 < 1% NSCLC. Variables not accounted for may have biased the survival analysis. A prospective study would bring more insight.
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Affiliation(s)
- Marie-Hélène Denault
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch Ste-Foy, Québec, QC G1V 4G5, Canada
| | - Jamie Feng
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Shelley Kuang
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Aria Shokoohi
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Bonnie Leung
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Mitchell Liu
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Eric Berthelet
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Janessa Laskin
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Sophie Sun
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Tina Zhang
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Cheryl Ho
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
| | - Barbara Melosky
- BC Cancer, Vancouver Centre, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada
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Gijtenbeek RG, de Jong K, Venmans BJ, van Vollenhoven FH, Ten Brinke A, Van der Wekken AJ, van Geffen WH. Best first-line therapy for people with advanced non-small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status. Cochrane Database Syst Rev 2023; 7:CD013382. [PMID: 37419867 PMCID: PMC10327404 DOI: 10.1002/14651858.cd013382.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/09/2023]
Abstract
BACKGROUND Most people who are newly diagnosed with non-small cell lung cancer (NSCLC) have advanced disease. For these people, survival is determined by various patient- and tumor-related factors, of which the performance status (PS) is the most important prognostic factor. People with PS 0 or 1 are usually treated with systemic therapies, whereas people with PS 3 or 4 most often receive supportive care. However, treatment for people with PS 2 without a targetable mutation remains unclear. Historically, people with a PS 2 cancer are frequently excluded from (important) clinical trials because of poorer outcomes and increased toxicity. We aim to address this knowledge gap, as this group of people represents a significant proportion (20% to 30%) of the total population with newly diagnosed lung cancer. OBJECTIVES To identify the best first-line therapy for advanced lung cancer in people with performance status 2 without a targetable mutation or with an unknown mutation status. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 17 June 2022. SELECTION CRITERIA We included randomized controlled trials (RCTs) that compared different chemotherapy (with or without angiogenesis inhibitor) or immunotherapy regimens, specifically designed for people with PS 2 only or studies including a subgroup of these people. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. overall survival (OS), 2. health-related quality of life (HRQoL), and 3. toxicity/adverse events. Our secondary outcomes were 4. tumor response rate, 5. progression-free survival, and 6. survival rates at six and 12 months' treatment. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS We included 22 trials in this review and identified one ongoing trial. Twenty studies compared chemotherapy with different regimens, of which 11 compared non-platinum therapy (monotherapy or doublet) versus platinum doublet. We found no studies comparing best supportive care with chemotherapy and only two abstracts analyzing chemotherapy versus immunotherapy. We found that platinum doublet therapy showed superior OS compared to non-platinum therapy (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.57 to 0.78; 7 trials, 697 participants; moderate-certainty evidence). There were no differences in six-month survival rates (risk ratio [RR] 1.00, 95% CI 0.72 to 1.41; 6 trials, 632 participants; moderate-certainty evidence), whereas 12-month survival rates were improved for treatment with platinum doublet therapy (RR 0.92, 95% CI 0.87 to 0.97; 11 trials, 1567 participants; moderate-certainty evidence). PFS and tumor response rate were also better for people treated with platinum doublet therapy, with moderate-certainty evidence (PFS: HR 0.57, 95% CI 0.42 to 0.77; 5 trials, 487 participants; tumor response rate: RR 2.25, 95% CI 1.67 to 3.05; 9 trials, 964 participants). When analyzing toxicity rates, we found that platinum doublet therapy increased grade 3 to 5 hematologic toxicities, all with low-certainty evidence (anemia: RR 1.98, 95% CI 1.00 to 3.92; neutropenia: RR 2.75, 95% CI 1.30 to 5.82; thrombocytopenia: RR 3.96, 95% CI 1.73 to 9.06; all 8 trials, 935 participants). Only four trials reported HRQoL data; however, the methodology was different per trial and we were unable to perform a meta-analysis. Although evidence is limited, there were no differences in 12-month survival rates or tumor response rates between carboplatin and cisplatin regimens. With an indirect comparison, carboplatin seemed to have better 12-month survival rates than cisplatin compared to non-platinum therapy. The assessment of the efficacy of immunotherapy in people with PS 2 was limited. There might be a place for single-agent immunotherapy, but the data provided by the included studies did not encourage the use of double-agent immunotherapy. AUTHORS' CONCLUSIONS This review showed that as a first-line treatment for people with PS 2 with advanced NSCLC, platinum doublet therapy seems to be preferred over non-platinum therapy, with a higher response rate, PFS, and OS. Although the risk for grade 3 to 5 hematologic toxicity is higher, these events are often relatively mild and easy to treat. Since trials using checkpoint inhibitors in people with PS 2 are scarce, we identified an important knowledge gap regarding their role in people with advanced NSCLC and PS 2.
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Affiliation(s)
- Rolof Gp Gijtenbeek
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | - Kim de Jong
- Department of Epidemiology, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | - Ben Jw Venmans
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | | | - Anneke Ten Brinke
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
| | - Anthonie J Van der Wekken
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
| | - Wouter H van Geffen
- Department of Pulmonary Diseases, Medical Center Leeuwarden, Leeuwarden, Netherlands
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Ichimata M, Kagawa Y, Namiki K, Toshima A, Nakano Y, Matsuyama F, Fukazawa E, Harada K, Katayama R, Kobayashi T. Prognosis of primary pulmonary adenocarcinoma after surgical resection in small-breed dogs: 52 cases (2005-2021). J Vet Intern Med 2023; 37:1466-1474. [PMID: 37226683 PMCID: PMC10365062 DOI: 10.1111/jvim.16739] [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: 09/13/2022] [Accepted: 05/06/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND Tumor size is an important prognostic factor in lung cancer in dogs, and the canine lung carcinoma stage classification (CLCSC) recently has been proposed to subdivide tumor sizes. It is unclear if the same classification scheme can be used for small-breed dogs. OBJECTIVES To investigate whether the tumor size classification of CLCS is prognostic for survival and progression outcomes in small-breed dogs with surgically resected pulmonary adenocarcinomas (PACs). ANIMALS Fifty-two client-owned small-breed dogs with PAC. METHODS Single-center retrospective cohort study conducted between 2005 and 2021. Medical records of dogs weighing <15 kg with surgically resected lung masses histologically diagnosed as PAC were examined. RESULTS The numbers of dogs with tumor size ≤3 cm, >3 cm to ≤5 cm, >5 cm to ≤7 cm, or >7 cm were 15, 18, 14, and 5, respectively. The median progression-free interval (PFI) and overall survival time (OST) were 754 and 716 days, respectively. In univariable analysis, clinical signs, lymph node metastasis, margin, and histologic grade were associated with PFI, and age, clinical signs, margin, and lymph node metastasis were associated with OST. Tumor size classification of CLCS was associated with PFI in all categories, and tumor size >7 cm was associated with OST. In multivariable analysis, tumor size >5 cm to ≤7 cm and margin were associated with PFI, and age was associated with OST. CONCLUSIONS AND CLINICAL IMPORTANCE The tumor size classification of CLCS would be an important prognostic factor in small-breed dogs with surgically resected PACs.
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Affiliation(s)
- Masanao Ichimata
- Japan Small Animal Cancer Center, Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
| | | | | | - Atsushi Toshima
- Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
| | - Yuko Nakano
- Veterinary Cancer Center, Hayashiya Animal Hospital, UjiKyotoJapan
| | - Fukiko Matsuyama
- Japan Small Animal Cancer Center, Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
| | - Eri Fukazawa
- Japan Small Animal Cancer Center, Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
| | - Kei Harada
- Japan Small Animal Cancer Center, Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
| | - Ryuzo Katayama
- Japan Small Animal Cancer Center, Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
| | - Tetsuya Kobayashi
- Japan Small Animal Cancer Center, Public Interest Incorporated Foundation Japan Small Animal Medical CenterTokorozawaSaitamaJapan
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Tafenzi HA, Choulli F, Baladi A, Essaadi I, Belbaraka R. Lung cancer in middle and southern Morocco. Ecancermedicalscience 2023; 17:1518. [PMID: 37113715 PMCID: PMC10129405 DOI: 10.3332/ecancer.2023.1518] [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: 09/27/2022] [Indexed: 03/14/2023] Open
Abstract
Purpose Determining risk factors associated with a fatal disease such as lung cancer (LC) remains an important key to understanding the factors related to its development and therefore using the correct emergent or accessible treatments. For that, we sought to highlight by describing, and analysing, the risk factors related to LC survival, reflecting the actual situation in Morocco. Patients and methods We included 987 LC patients diagnosed from 2015 to 2021 at the Medical Oncology Department at the Mohammed VI University Hospital of Marrakech. An overview of the LC situation was described, and analysed, to determine the risk factors related to survival. The independent prognostic factors were determined using Cox Proportional Hazards Regression Analysis. To create a distinction between different risks group in the survival curve, stratification was done, respectively, within sex, age, histology type, treatments and radiation therapy. Results We finally included 862 patients with 15 parameters among the 27 extracted, all meeting the inclusion criteria. 89.1% of the patients were male (n = 768) and 10.9% were female (n = 94), of whom 83.5% had a history of tobacco smoking (n = 720). The median survival of both sexes was 716 (5-2,167) days. The average age at diagnosis was 60 years. Five hundred and thirty-four patients presented with advanced stage. Patients above 66 years were the more diagnosed category with adenocarcinoma at T4N2M1c pathological category, and endocrinal comorbidity, in addition to pleurisy syndrome. Moreover, family history was found to be a bad prognostic factor. Interestingly, smoking status was not a bad contributor to survival. Age at diagnosis, histology subtype, performance status, haemoglobin, numbers of cures of the first-line chemotherapy, radiotherapy, anaemia and treatments were identified as risk factors related to survival. Conclusion We established a descriptive and analytical overview of the current LC epidemiology situation in the oncology division of Mohammed VI University Hospital in a non-industrialised state taking into account smoking status.
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Affiliation(s)
- Hassan Abdelilah Tafenzi
- Department of Medical Oncology, Mohammed VI University Hospital of Marrakech, Marrakech 40000, Morocco
- Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech 40000, Morocco
| | - Farah Choulli
- Department of Medical Oncology, Mohammed VI University Hospital of Marrakech, Marrakech 40000, Morocco
- Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech 40000, Morocco
| | - Anass Baladi
- Department of Medical Oncology, Mohammed VI University Hospital of Marrakech, Marrakech 40000, Morocco
| | - Ismail Essaadi
- Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech 40000, Morocco
- Department of Medical Oncology, Avicenna Military Hospital of Marrakech, Marrakech 40000, Morocco
| | - Rhizlane Belbaraka
- Department of Medical Oncology, Mohammed VI University Hospital of Marrakech, Marrakech 40000, Morocco
- Biosciences and Health Laboratory, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech 40000, Morocco
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22
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Zhang C, Huang Y, Fang C, Liang Y, Jiang D, Li J, Ma H, Jiang W, Feng Y. Construction and validation of a prognostic model based on ten signature cell cycle-related genes for early-stage lung squamous cell carcinoma. Cancer Biomark 2023; 36:313-326. [PMID: 36938730 DOI: 10.3233/cbm-220227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
BACKGROUND We performed a bioinformatics analysis to screen for cell cycle-related differentially expressed genes (DEGs) and constructed a model for the prognostic prediction of patients with early-stage lung squamous cell carcinoma (LSCC). METHODS From a gene expression omnibus (GEO) database, the GSE157011 dataset was randomly divided into an internal training group and an internal testing group at a 1:1 ratio, and the GSE30219, GSE37745, GSE42127, and GSE73403 datasets were merged as the external validation group. We performed single-sample gene set enrichment analysis (ssGSEA), univariate Cox analysis, and difference analysis, and identified 372 cell cycle-related genes. Additionally, we combined LASSO/Cox regression analysis to construct a prognostic model. Then, patients were divided into high-risk and low-risk groups according to risk scores. The internal testing group, discovery set, and external verification set were used to assess model reliability. We used a nomogram to predict patient prognoses based on clinical features and risk values. Clinical relevance analysis and the Human Protein Atlas (HPA) database were used to verify signature gene expression. RESULTS Ten cell cycle-related DEGs (EIF2B1, FSD1L, FSTL3, ORC3, HMMR, SETD6, PRELP, PIGW, HSD17B6, and GNG7) were identified and a model based on the internal training group constructed. From this, patients in the low-risk group had a higher survival rate when compared with the high-risk group. Time-dependent receiver operating characteristic (tROC) and Cox regression analyses showed the model was efficient and accurate. Clinical relevance analysis and the HPA database showed that DEGs were significantly dysregulated in LSCC tissue. CONCLUSION Our model predicted the prognosis of early-stage LSCC patients and demonstrated potential applications for clinical decision-making and individualized therapy.
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Affiliation(s)
- Chengpeng Zhang
- Department of Thoracic Surgery, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China.,Department of Thoracic Surgery, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China
| | - Yong Huang
- Department of Thoracic Surgery, Haimen People's Hospital, Nantong, Jiangsu, China.,Department of Thoracic Surgery, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China
| | - Chen Fang
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.,Department of Thoracic Surgery, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China
| | - Yingkuan Liang
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Dong Jiang
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jiaxi Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Haitao Ma
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Wei Jiang
- Department of Thoracic Surgery, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Yu Feng
- Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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23
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Hofmann L, Heinrich M, Baurecht H, Langguth B, Kreuzer PM, Knüttel H, Leitzmann MF, Seliger C. Suicide Mortality Risk among Patients with Lung Cancer-A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:4146. [PMID: 36901154 PMCID: PMC10002176 DOI: 10.3390/ijerph20054146] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 02/18/2023] [Accepted: 02/23/2023] [Indexed: 06/18/2023]
Abstract
The risk for suicide in patients with cancer is higher compared to the general population. However, little is known about patients with lung cancer specifically. We therefore implemented a systematic review and random-effects meta-analysis of retrospective cohort studies on suicide in patients with lung cancer. We searched a high number of common databases up to 02/2021. For the systematic review, a total of 23 studies was included. To exclude bias due to patient sample overlap, the meta-analysis was performed on 12 studies. The pooled standardized mortality ratio (SMR) for suicide was 2.95 (95% Confidence Interval (CI) = 2.42-3.60) for patients with lung cancer as compared to the general population. Subgroups with a pronouncedly higher risk for suicide compared to the general population were found for patients living in the USA (SMR = 4.17, 95% CI = 3.88-4.48), with tumors of late stage (SMR = 4.68, 95% CI = 1.28-17.14), and within one year after diagnosis (SMR = 5.00, 95% CI = 4.11-6.08). An increased risk for suicide was found in patients with lung cancer, with subgroups at particular risk. Patients at increased risk should be monitored more closely for suicidality and should receive specialized psycho-oncological and psychiatric care. Further studies should clarify the role of smoking and depressive symptoms on suicidality among lung cancer patients.
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Affiliation(s)
- Luisa Hofmann
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University, Nußbaumstraße 7, 80336 Munich, Germany
- Department of Psychiatry and Psychotherapy, University of Regensburg, Universitätsstraße 84, 93053 Regensburg, Germany
| | - Michael Heinrich
- Faculty of Medicine, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany
| | - Hansjörg Baurecht
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Berthold Langguth
- Department of Psychiatry and Psychotherapy, University of Regensburg, Universitätsstraße 84, 93053 Regensburg, Germany
| | - Peter M. Kreuzer
- Department of Psychiatry and Psychotherapy, University of Regensburg, Universitätsstraße 84, 93053 Regensburg, Germany
| | - Helge Knüttel
- University Library, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany
| | - Michael F. Leitzmann
- Department of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
| | - Corinna Seliger
- Department of Neurology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
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Zhao Y, Jia S, Zhang K, Zhang L. Serum cytokine levels and other associated factors as possible immunotherapeutic targets and prognostic indicators for lung cancer. Front Oncol 2023; 13:1064616. [PMID: 36874133 PMCID: PMC9977806 DOI: 10.3389/fonc.2023.1064616] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 01/24/2023] [Indexed: 02/18/2023] Open
Abstract
Lung cancer is one of the most prevalent cancer types and the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all cancer incidences. Lung cancer therapy and prognosis largely depend on the disease's degree at the diagnosis time. Cytokines are soluble polypeptides that contribute to cell-to-cell communication, acting paracrine or autocrine on neighboring or distant cells. Cytokines are essential for developing neoplastic growth, but they are also known to operate as biological inducers following cancer therapy. Early indications are that inflammatory cytokines such as IL-6 and IL-8 play a predictive role in lung cancer. Nevertheless, the biological significance of cytokine levels in lung cancer has not yet been investigated. This review aimed to assess the existing literature on serum cytokine levels and additional factors as potential immunotherapeutic targets and lung cancer prognostic indicators. Changes in serum cytokine levels have been identified as immunological biomarkers for lung cancer and predict the effectiveness of targeted immunotherapy.
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Affiliation(s)
- Yinghao Zhao
- Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Shengnan Jia
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun, Jilin, China
| | - Kun Zhang
- Department of Central Lab, The Second Hospital of Jilin University, Changchun, China
| | - Lian Zhang
- Department of Pathology, The Second Hospital of Jilin University, Changchun, China
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25
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Clinical features and lipid metabolism genes as potential biomarkers in advanced lung cancer. BMC Cancer 2023; 23:36. [PMID: 36624406 PMCID: PMC9830782 DOI: 10.1186/s12885-023-10509-x] [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: 05/13/2022] [Accepted: 01/03/2023] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Lung cancer is one of the most lethal tumors with a poor survival rate even in those patients receiving new therapies. Metabolism is considered one of the hallmarks in carcinogenesis and lipid metabolism is emerging as a significant contributor to tumor metabolic reprogramming. We previously described a profile of some lipid metabolism related genes with potential prognostic value in advanced lung cancer. AIM To analyze clinical and pathological characteristics related to a specific metabolic lipid genomic signature from patients with advanced lung cancer and to define differential outcome. METHODS Ninety samples from NSCLC (non-small cell lung cancer) and 61 from SCLC (small cell lung cancer) patients were obtained. We performed a survival analysis based on lipid metabolic genes expression and clinical characteristics. The primary end point of the study was the correlation between gene expression, clinical characteristics and survival. RESULTS Clinical variables associated with overall survival (OS) in NSCLC patients were clinical stage, adenocarcinoma histology, Eastern Cooperative Oncology Group (ECOG), number and site of metastasis, plasma albumin levels and first-line treatment with platinum. As for SCLC patients, clinical variables that impacted OS were ECOG, number of metastasis locations, second-line treatment administration and Diabetes Mellitus (DM). None of them was associated with gene expression, indicating that alterations in lipid metabolism are independent molecular variables providing complementary information of lung cancer patient outcome. CONCLUSIONS Specific clinical features as well as the expression of lipid metabolism-related genes might be potential biomarkers with differential outcomes.
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26
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Chen YH, Lue KH, Chu SC, Chang BS, Lin CB. The combined tumor-nodal glycolytic entropy improves survival stratification in nonsmall cell lung cancer with locoregional disease. Nucl Med Commun 2023; 44:100-107. [PMID: 36437543 DOI: 10.1097/mnm.0000000000001645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To investigate whether combining primary tumor and metastatic nodal glycolytic heterogeneity on 18 F-fluorodeoxyglucose PET ( 18 F-FDG PET) improves prognostic prediction in nonsmall cell lung cancer (NSCLC) with locoregional disease. METHODS We retrospectively analyzed 18 F-FDG PET-derived features from 94 patients who had undergone curative treatments for regional nodal metastatic NSCLC. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models. We used the independent prognosticators to construct models to predict survival. RESULTS Combined entropy (entropy derived from the combination of the primary tumor and metastatic nodes) and age independently predicted OS (both P = 0.008) and PFS ( P = 0.007 and 0.050, respectively). At the same time, the Eastern Cooperative Oncology Group status was another independent risk factor for unfavorable OS ( P = 0.026). Our combined entropy-based models outperformed the traditional staging system (c-index = 0.725 vs. 0.540, P < 0.001 for OS; c-index = 0.638 vs. 0.511, P = 0.003 for PFS) and still showed prognostic value in subgroups according to sex, histopathology, and different initial curative treatment strategies. CONCLUSION Combined primary tumor-nodal glycolytic heterogeneity independently predicted survival outcomes. In combination with clinical risk factors, our models provide better survival predictions and may enable tailored treatment strategies for NSCLC with locoregional disease.
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Affiliation(s)
- Yu-Hung Chen
- Department of Nuclear Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
- School of Medicine, College of Medicine, Tzu Chi University
- Department of Medical Imaging and Radiological Sciences, Tzu Chi University of Science and Technology
| | - Kun-Han Lue
- Department of Medical Imaging and Radiological Sciences, Tzu Chi University of Science and Technology
| | - Sung-Chao Chu
- School of Medicine, College of Medicine, Tzu Chi University
- Departments of Hematology and Oncology
| | | | - Chih-Bin Lin
- Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
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Wang W, Zhou J. A Nomogram to Predict the Overall Survival of Patients With Resected T1-2N0-1M0 Non-Small Cell Lung Cancer and to Identify the Optimal Candidates for Adjuvant Chemotherapy in Stage IB or IIA Non-Small Cell Lung Cancer Patients. Cancer Control 2023; 30:10732748231197973. [PMID: 37703536 PMCID: PMC10501081 DOI: 10.1177/10732748231197973] [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] [Indexed: 09/15/2023] Open
Abstract
BACKGROUND The benefit of adjuvant chemotherapy for IB/IIA non-small cell lung cancer (NSCLC) patients remains uncertain. This study aimed to develop a prognostic model to predict overall survival in resected NSCLC patients with T1-2N0-1M0 stage and identify optimal candidates for postoperative chemotherapy among those with stage IB or IIA disease. METHODS We conducted a retrospective study using the SEER 18 database (2000-2018, November 2020 submission) of patients who underwent radical surgery for T1-2N0-1M0 NSCLC. The patients not receiving adjuvant chemotherapy were randomly divided into training and validation cohorts. A prognostic nomogram was established and evaluated using calibration and receiver operating characteristic curves. Based on the nomogram, stage IB and IIA patients were categorized into two prognostic groups, each further divided into cohorts based on adjuvant chemotherapy status. Kaplan-Meier analysis and log-rank tests were used to compare overall survival between these groups. RESULTS A total of 14 789 patients were enrolled and randomly assigned to the training cohort (n = 10 352) and validation cohort (n = 4437). Ten independent prognostic factors were identified and integrated into the prognostic model. The area under the receiver operating characteristic curve was .706, .699, and .705 in the training cohort, and .700, .698, and .695 in the validation cohort at 1, 3, and 5 years, respectively. Among stage IB and IIA patients, only those in the high-risk group showed a significant benefit from adjuvant chemotherapy, with a 16.4% absolute increase in 5-year overall survival. CONCLUSIONS The nomogram developed in the study may help physicians choose the most appropriate management strategy for each patient.
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Affiliation(s)
- Wei Wang
- Department of Oncology, Huaian Cancer Hospital, Huaian, China
| | - Juying Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Xue T, Peng H, Chen Q, Li M, Duan S, Feng F. A CT-Based Radiomics Nomogram in Predicting the Postoperative Prognosis of Colorectal Cancer: A Two-center Study. Acad Radiol 2022; 29:1647-1660. [PMID: 35346564 DOI: 10.1016/j.acra.2022.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 01/25/2022] [Accepted: 02/06/2022] [Indexed: 01/26/2023]
Abstract
RATIONALE AND OBJECTIVES This retrospective study aimed to develop a practical model to determine overall survival after surgery in patients with colorectal cancer according to radiomics signatures based on computed tomography (CT) images and clinical predictors. MATERIALS AND METHODS A total of 121 colorectal cancer (CRC) patients were selected to construct the model, and 51 patients and 114 patients were selected for internal validation and external testing. The radiomics features were extracted from each patient's CT images. Univariable Cox regression and least absolute shrinkage and selection operator regression were used to select radiomics features. The performance of the nomogram was evaluated by calibration curves and the c-index. Kaplan-Meier analysis was used to compare the overall survival between these subgroups. RESULTS The radiomics features of the CRC patients were significantly correlated with survival time. The c-indexes of the nomogram in the training cohort, internal validation cohort and external test cohort were 0.782, 0.721, and 0.677. Our nomogram integrated the optimal radiomics signature with clinical predictors showed a significant improvement in the prediction of CRC patients' overall survival. The calibration curves showed that the predicted survival time was close to the actual survival time. According to Kaplan-Meier analysis, the 1-, 2-, and 3-year survival rates of the low-risk group were higher than those of the high-risk group. CONCLUSION The nomogram combining the optimal radiomics signature and clinical predictors further improved the predicted accuracy of survival prognosis for CRC patients. These findings might affect treatment strategies and enable a step forward for precise medicine.
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Affiliation(s)
- Ting Xue
- Nantong University, Nantong, Jiangsu, PR China
| | - Hui Peng
- Nantong University, Nantong, Jiangsu, PR China
| | | | - Manman Li
- Nantong University, Nantong, Jiangsu, PR China
| | | | - Feng Feng
- Department of Radiology, Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu 226361, PR China.
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Consistency and prognostic value of preoperative staging and postoperative pathological staging using 18F-FDG PET/MRI in patients with non-small cell lung cancer. Ann Nucl Med 2022; 36:1059-1072. [PMID: 36264439 DOI: 10.1007/s12149-022-01795-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 10/05/2022] [Indexed: 11/01/2022]
Abstract
OBJECTIVE In recent years, positron emission tomography/magnetic resonance imaging (PET/MRI) has been clinically used as a method to diagnose non-small cell lung cancer (NSCLC). This study aimed to evaluate the concordance of staging and prognostic ability of NSCLC patients using thin-slice computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET/MRI. METHODS This retrospective study was performed on consecutive NSCLC patients who underwent both diagnostic CT and 18F-FDG PET/MRI before surgery between November 2015 and May 2019. The cTNM staging yielded from PET/MRI was compared with CT and pathological staging, and concordance was investigated, defining pathological findings as reference. To assess the prognostic value of disease-free survival (DFS) and overall survival (OS), we dichotomized the typical prognostic factors and TNM classification staging (Stage I vs. Stage II or higher). Kaplan-Meier curves derived by the log-rank test were generated, and univariate and multivariate analyses were performed to identify the factors associated with DFS and OS. RESULTS A total of 82 subjects were included; PET/MRI staging was more consistent (59 of 82) with pathological staging than with CT staging. There was a total of 21 cases of CT and 11 cases of PET/MRI that were judged as cStage I, but were actually pStage II or pStage III. CT tended to judge pN1 or pN2 as cN0 compared to PET/MRI. There was a significant difference between NSCLC patients with Stage I and Stage II or higher by PET/MRI staging as well as prognosis prediction of DFS by pathological staging (P < 0.001). In univariate analysis, PET/MRI, CT, and pathological staging (Stage I or lower vs. Stage II or higher) all showed significant differences as prognostic factors of recurrence or metastases. In multivariate analysis, pathological staging was the only independent factor for recurrence (P = 0.009), and preoperative PET/MRI staging was a predictor of patient survival (P = 0.013). CONCLUSIONS In NSCLC, pathologic staging was better at predicting recurrence, and preoperative PET/MRI staging was better at predicting survival. Preoperative staging by PET/MRI was superior to CT in diagnosing hilar and mediastinal lymph-node metastases, which contributed to the high concordance with pathologic staging.
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Salvage chemotherapy in patients with nonsmall cell lung cancer after prior immunotherapy: a retrospective, real-life experience study. Anticancer Drugs 2022; 33:752-757. [PMID: 35946540 DOI: 10.1097/cad.0000000000001330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Patients with advanced nonsmall cell lung cancer (NSCLC) who progress with immune checkpoint inhibitors (ICIs), salvage chemotherapy remains the only viable option for tumors that do not harbor genomic alterations. Data on the efficacy of salvage chemotherapy after immunotherapy (SCAI) are scarce. Our main objective in the current study was to evaluate the efficacy of SCAI. All consecutive patients who were diagnosed as having metastatic NSCLC and received at least one dose of ICIs were retrospectively reviewed. We computed progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) with SCAI. We also analyzed associations between survival and various clinicopathologic factors. We identified 35 patients with advanced NSCLC who received at least one dose of SCAI. The median age was 66 years. Most of patients were male ( n = 26, 74.3%) and former or current smokers ( n = 33, 94.3%). The majority of the patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2 ( n = 22; 62.9%), and there were no patients with driver mutations. SCAI was administered as second-line therapy in 21 (60.0%) patients and third-line in 14 (40.0%) patients. The ORR to SCAI was 20.0% with median PFS and OS were 2.43 (95% CI, 1.69-3.16) months and 4.40 (95% CI, 2.17-6.62) months, respectively. In multivariate analysis, ECOG PS 2 was confirmed as being independently associated with inferior OS. We demonstrated that patients with NSCLC who progressed to ICIs had limited clinical benefit with salvage chemotherapy, particularly for patients who were ECOG PS 2.
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Ulanja MB, Beutler BD, Antwi-Amoabeng D, Governor SB, Rahman GA, Djankpa FT, Alese OB. Prognostic Factors and Survival in Gastrointestinal Extrapulmonary Small Cell Carcinoma: A Retrospective Cohort Study. Ann Surg Oncol 2022; 29:8250-8260. [PMID: 35978206 DOI: 10.1245/s10434-022-12395-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 07/28/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Gastrointestinal extrapulmonary small cell carcinoma (GI EPSCCa) is a rare, aggressive neuroendocrine tumor. Factors affecting survival, including the prognostic significance of primary tumor site, remain under investigation. METHODS Data from the surveillance, epidemiology, and end results (SEER) program were extracted to identify patients diagnosed with GI EPSCCa between 2000 and 2018. Cox proportional hazard models were used to assess prognostic factors based on primary tumor site. RESULTS A total of 1687 patients were included in the survival analysis. The distribution of the primary tumor location was as follows: 31.5% colorectum (CRC), 22.1% esophageal, 20.6% pancreatic, 13.3% hepatobiliary (HB), 10.6% stomach, and 1.8% small intestine (SI). Esophagogastric and SI EPSCCa were more common among Black individuals, whereas CRC, HB, and pancreatic EPSCCa were more common among White patients (p = 0.012). There were no racial differences in OS for GI EPSCCa. HB EPSCCa was associated with inferior OS compared with esophageal tumors (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.00-1.46; p = 0.048), and SI EPSCCa was associated with prolonged survival compared with esophageal EPSCCa (aHR 0.76, 95% CI 0.48-1.20; p = 0.237) but did not reach statistical significance. Surgical intervention and a treatment period after 2006 were associated with superior OS. CONCLUSIONS The prognosis for GI ESPCCa varies based on site. Chemotherapy, radiation, and surgical resection are associated with improved outcomes; however, the prognosis for patients with EPSCCa remains dismal. Prospective studies are needed to guide therapy for this aggressive tumor.
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Affiliation(s)
- Mark B Ulanja
- Christus Ochsner St. Patrick Hospital, Lake Charles, LA, USA.
| | - Bryce D Beutler
- Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | | | - Ganiyu A Rahman
- Department of Surgery, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Francis Tanam Djankpa
- Department of Physiology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Olatunji B Alese
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
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Denault MH, Labbé C, St-Pierre C, Fournier B, Gagné A, Morillon C, Joubert P, Simard S, Martel S. Wait Times and Survival in Lung Cancer Patients across the Province of Quebec, Canada. Curr Oncol 2022; 29:3187-3199. [PMID: 35621649 PMCID: PMC9140092 DOI: 10.3390/curroncol29050259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/23/2022] [Accepted: 04/26/2022] [Indexed: 11/16/2022] Open
Abstract
Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III–IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1–15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I–II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.
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Affiliation(s)
- Marie-Hélène Denault
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
- BC Cancer Agency-Vancouver Center, 600 W 10th Avenue, Vancouver, BC V5Z 4E6, Canada
- Correspondence:
| | - Catherine Labbé
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Carolle St-Pierre
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Brigitte Fournier
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Andréanne Gagné
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Claudia Morillon
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Philippe Joubert
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Serge Simard
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
| | - Simon Martel
- Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Ch. Ste-Foy, Québec, QC G1V 4G5, Canada; (C.L.); (C.S.-P.); (B.F.); (A.G.); (C.M.); (P.J.); (S.S.); (S.M.)
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Jiang M, Zhang X, Chen Y, Chen P, Guo X, Ma L, Gao Q, Mei W, Zhang J, Zheng J. A Review of the Correlation Between Epidermal Growth Factor Receptor Mutation Status and 18F-FDG Metabolic Activity in Non-Small Cell Lung Cancer. Front Oncol 2022; 12:780186. [PMID: 35515138 PMCID: PMC9065410 DOI: 10.3389/fonc.2022.780186] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 03/25/2022] [Indexed: 11/15/2022] Open
Abstract
PET/CT with 18F-2-fluoro-2-deoxyglucose (18F-FDG) has been proposed as a promising modality for diagnosing and monitoring treatment response and evaluating prognosis for patients with non-small cell lung cancer (NSCLC). The status of epidermal growth factor receptor (EGFR) mutation is a critical signal for the treatment strategies of patients with NSCLC. Higher response rates and prolonged progression-free survival could be obtained in patients with NSCLC harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) when compared with traditional cytotoxic chemotherapy. However, patients with EGFR mutation treated with TKIs inevitably develop drug resistance, so predicting the duration of resistance is of great importance for selecting individual treatment strategies. Several semiquantitative metabolic parameters, e.g., maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), measured by PET/CT to reflect 18F-FDG metabolic activity, have been demonstrated to be powerful in predicting the status of EGFR mutation, monitoring treatment response of TKIs, and assessing the outcome of patients with NSCLC. In this review, we summarize the biological and clinical correlations between EGFR mutation status and 18F-FDG metabolic activity in NSCLC. The metabolic activity of 18F-FDG, as an extrinsic manifestation of NSCLC, could reflect the mutation status of intrinsic factor EGFR. Both of them play a critical role in guiding the implementation of treatment modalities and evaluating therapy efficacy and outcome for patients with NSCLC.
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Affiliation(s)
- Maoqing Jiang
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Department of Nuclear Medicine, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Xiaohui Zhang
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Yan Chen
- Department of Physical Examination Center, Ningbo First Hospital, Ningbo, China
| | - Ping Chen
- Department of Nephrology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Xiuyu Guo
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Lijuan Ma
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Qiaoling Gao
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Weiqi Mei
- Department of Nuclear Medicine, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jingfeng Zhang
- Department of Education, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jianjun Zheng
- Department of PET/CT Center, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
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Garinet S, Wang P, Mansuet-Lupo A, Fournel L, Wislez M, Blons H. Updated Prognostic Factors in Localized NSCLC. Cancers (Basel) 2022; 14:cancers14061400. [PMID: 35326552 PMCID: PMC8945995 DOI: 10.3390/cancers14061400] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/06/2022] [Accepted: 03/08/2022] [Indexed: 12/25/2022] Open
Abstract
Lung cancer is the most common cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) represents 80% of lung cancer subtypes. Patients with localized non-small cell lung cancer may be considered for upfront surgical treatment. However, the overall 5-year survival rate is 59%. To improve survival, adjuvant chemotherapy (ACT) was largely explored and showed an overall benefit of survival at 5 years < 7%. The evaluation of recurrence risk and subsequent need for ACT is only based on tumor stage (TNM classification); however, more than 25% of patients with stage IA/B tumors will relapse. Recently, adjuvant targeted therapy has been approved for EGFR-mutated resected NSCLC and trials are evaluating other targeted therapies and immunotherapies in adjuvant settings. Costs, treatment duration, emergence of resistant clones and side effects stress the need for a better selection of patients. The identification and validation of prognostic and theranostic markers to better stratify patients who could benefit from adjuvant therapies are needed. In this review, we report current validated clinical, pathological and molecular prognosis biomarkers that influence outcome in resected NSCLC, and we also describe molecular biomarkers under evaluation that could be available in daily practice to drive ACT in resected NSCLC.
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Affiliation(s)
- Simon Garinet
- Pharmacogenomics and Molecular Oncology Unit, Biochemistry Department, Assistance Publique—Hopitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France;
- Centre de Recherche des Cordeliers, INSERM UMRS-1138, Sorbonne Université, Université de Paris, 75006 Paris, France
| | - Pascal Wang
- Oncology Thoracic Unit, Pulmonology Department, Assistance Publique—Hopitaux de Paris, Hôpital Cochin, 75014 Paris, France; (P.W.); (M.W.)
| | - Audrey Mansuet-Lupo
- Pathology Department, Assistance Publique—Hopitaux de Paris, Hôpital Cochin, 75014 Paris, France;
| | - Ludovic Fournel
- Thoracic Surgery Department, Assistance Publique—Hopitaux de Paris, Hôpital Cochin, 75014 Paris, France;
| | - Marie Wislez
- Oncology Thoracic Unit, Pulmonology Department, Assistance Publique—Hopitaux de Paris, Hôpital Cochin, 75014 Paris, France; (P.W.); (M.W.)
| | - Hélène Blons
- Pharmacogenomics and Molecular Oncology Unit, Biochemistry Department, Assistance Publique—Hopitaux de Paris, Hôpital Européen Georges Pompidou, 75015 Paris, France;
- Centre de Recherche des Cordeliers, INSERM UMRS-1138, Sorbonne Université, Université de Paris, 75006 Paris, France
- Correspondence:
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Julian C, Machado RJM, Girish S, Chanu P, Heinzmann D, Harbron C, Gershon A, Pfeiffer SM, Zou W, Quarmby V, Zhang Q, Chen Y. Real-world data prognostic model of overall survival in patients with advanced NSCLC receiving anti-PD-1/PD-L1 immune checkpoint inhibitors as second-line monotherapy. Cancer Rep (Hoboken) 2022; 5:e1578. [PMID: 35075804 PMCID: PMC9575492 DOI: 10.1002/cnr2.1578] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Revised: 09/21/2021] [Accepted: 10/12/2021] [Indexed: 11/11/2022] Open
Abstract
Background and aim The objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non‐small cell lung cancer (aNSCLC) and to develop a novel prognostic model. Methods A total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second‐line monotherapy were selected from a real‐world deidentified database to build the cohort. Patients could not have received first‐line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti‐programmed cell death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1), and anti‐cytotoxic T‐lymphocyte‐associated protein 4 therapies. Results Patients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real‐world data cohort. The risk‐increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk‐decreasing prognostic factors were PD‐L1 positivity, longer time from advanced diagnosis to start of first‐line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c‐index for the OAK trial validation cohort was 0.65 and 0.67 for the real‐world data cohort. Conclusions Based on baseline demographic and clinical factors from a real‐world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second‐line monotherapy, and it performed well in the real‐world data and clinical trial cohorts.
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Affiliation(s)
| | | | | | | | | | | | - Anda Gershon
- Genentech, Inc, South San Francisco, California, USA
| | | | - Wei Zou
- Genentech, Inc, South San Francisco, California, USA
| | | | - Qing Zhang
- Genentech, Inc, South San Francisco, California, USA
| | - Yachi Chen
- Genentech, Inc, South San Francisco, California, USA
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Dogan I, Khanmammadov N, Ahmed MA, Yıldız A, Saip P, Aydiner A, Vatansever S. Outcomes and Prognostic Factors in Patients with EGFR Mutant Metastatic Non-Small Cell Lung Cancer Who Treated with Erlotinib. CLINICAL CANCER INVESTIGATION JOURNAL 2022. [DOI: 10.51847/rvqewyffbi] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Giuliani ME, Giannopoulos E, Gospodarowicz MK, Broadhurst M, O’Sullivan B, Tittenbrun Z, Johnson S, Brierley J. Examining the Landscape of Prognostic Factors and Clinical Outcomes for Cancer Control. Curr Oncol 2021; 28:5155-5166. [PMID: 34940071 PMCID: PMC8699872 DOI: 10.3390/curroncol28060432] [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: 10/20/2021] [Revised: 11/29/2021] [Accepted: 12/02/2021] [Indexed: 11/23/2022] Open
Abstract
Prognostic factors have important utility in various aspects of cancer surveillance, including research, patient care, and cancer control programmes. Nevertheless, there is heterogeneity in the collection of prognostic factors and outcomes data globally. This study aimed to investigate perspectives on the utility and application of prognostic factors and clinical outcomes in cancer control programmes. A qualitative phenomenology approach using expert interviews was taken to derive a rich description of the current state and future outlook of cancer prognostic factors and clinical outcomes. Individuals with expertise in this work and from various regions and institutions were invited to take part in one-on-one semi-structured interviews. Four areas related to infrastructure and funding challenges were identified by participants, including (1) data collection and access; (2) variability in data reporting, coding, and definitions; (3) limited coordination among databases; and (4) conceptualization and prioritization of meaningful prognostic factors and outcomes. Two areas were identified regarding important future priorities for cancer control: (1) global investment and intention in cancer surveillance and (2) data governance and exchange globally. Participants emphasized the need for better global collection of prognostic factors and clinical outcomes data and support for standardized data collection and data exchange practices by cancer registries.
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Affiliation(s)
- Meredith Elana Giuliani
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (M.K.G.); (B.O.); (J.B.)
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
- Department of Cancer Education, Princess Margaret Cancer Centre, Toronto, ON M5G 2N2, Canada; (E.G.); (M.B.)
- Correspondence: ; Tel.: +1-416-946-2983
| | - Eleni Giannopoulos
- Department of Cancer Education, Princess Margaret Cancer Centre, Toronto, ON M5G 2N2, Canada; (E.G.); (M.B.)
| | - Mary Krystyna Gospodarowicz
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (M.K.G.); (B.O.); (J.B.)
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
- Department of Cancer Education, Princess Margaret Cancer Centre, Toronto, ON M5G 2N2, Canada; (E.G.); (M.B.)
| | - Michaela Broadhurst
- Department of Cancer Education, Princess Margaret Cancer Centre, Toronto, ON M5G 2N2, Canada; (E.G.); (M.B.)
| | - Brian O’Sullivan
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (M.K.G.); (B.O.); (J.B.)
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Zuzanna Tittenbrun
- Knowledge, Advocacy and Policy, Union for International Cancer Control, 1202 Geneva, Switzerland; (Z.T.); (S.J.)
| | - Sonali Johnson
- Knowledge, Advocacy and Policy, Union for International Cancer Control, 1202 Geneva, Switzerland; (Z.T.); (S.J.)
| | - James Brierley
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada; (M.K.G.); (B.O.); (J.B.)
- Department of Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
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Amini M, Nazari M, Shiri I, Hajianfar G, Deevband MR, Abdollahi H, Arabi H, Rahmim A, Zaidi H. Multi-level multi-modality (PET and CT) fusion radiomics: prognostic modeling for non-small cell lung carcinoma. Phys Med Biol 2021; 66. [PMID: 34544053 DOI: 10.1088/1361-6560/ac287d] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 09/20/2021] [Indexed: 12/23/2022]
Abstract
We developed multi-modality radiomic models by integrating information extracted from18F-FDG PET and CT images using feature- and image-level fusions, toward improved prognosis for non-small cell lung carcinoma (NSCLC) patients. Two independent cohorts of NSCLC patients from two institutions (87 and 95 patients) were cycled as training and testing datasets. Fusion approaches were applied at two levels, namely feature- and image-levels. For feature-level fusion, radiomic features were extracted individually from CT and PET images and concatenated. Alternatively, radiomic features extracted separately from CT and PET images were averaged. For image-level fusion, wavelet fusion was utilized and tuned with two parameters, namely CT weight and Wavelet Band Pass Filtering Ratio. Clinical and combined clinical + radiomic models were developed. Gray level discretization was performed at 3 different levels (16, 32 and 64) and 225 radiomics features were extracted. Overall survival (OS) was considered as the endpoint. For feature reduction, correlated (redundant) features were excluded using Spearman's correlation, and best combination of top ten features with highest concordance-indices (via univariate Cox model) were selected in each model for further multivariate Cox model. Moreover, prognostic score's median, obtained from the training cohort, was used intact in the testing cohort as a threshold to classify patients into low- versus high-risk groups, and log-rank test was applied to assess differences between the Kaplan-Meier curves. Overall, while models based on feature-level fusion strategy showed limited superiority over single-modalities, image-level fusion strategy significantly outperformed both single-modality and feature-level fusion strategies. As such, the clinical model (C-index = 0.656) outperformed all models from single-modality and feature-level strategies, but was outperformed by certain models from image-level fusion strategy. Our findings indicated that image-level fusion multi-modality radiomics models outperformed single-modality, feature-level fusion, and clinical models for OS prediction of NSCLC patients.
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Affiliation(s)
- Mehdi Amini
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1205 Geneva, Switzerland.,Department of Biomedical Engineering and Medical Physics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mostafa Nazari
- Department of Biomedical Engineering and Medical Physics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Isaac Shiri
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1205 Geneva, Switzerland
| | - Ghasem Hajianfar
- Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Science, Tehran, Iran
| | - Mohammad Reza Deevband
- Department of Biomedical Engineering and Medical Physics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Abdollahi
- Department of Radiologic Technology, School of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Hossein Arabi
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1205 Geneva, Switzerland
| | - Arman Rahmim
- Departments of Radiology and Physics, University of British Columbia, Vancouver BC, Canada.,Department of Integrative Oncology, BC Cancer Research Institute, Vancouver BC, Canada
| | - Habib Zaidi
- Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1205 Geneva, Switzerland.,Geneva University Neurocenter, Geneva University, CH-1211 Geneva, Switzerland.,Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.,Department of Nuclear Medicine, University of Southern Denmark, Odense, Denmark
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Mojsak D, Kuklińska B, Minarowski Ł, Mróz RM. Current state of knowledge on immunotherapy in ECOG PS 2 patients. A systematic review. Adv Med Sci 2021; 66:381-387. [PMID: 34315013 DOI: 10.1016/j.advms.2021.07.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 05/06/2021] [Accepted: 07/13/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Patients with Eastern Cooperative Oncology Group Performance Status 2 (ECOG PS 2) are not included in most randomized clinical trials and registry studies. Nevertheless, immune checkpoint inhibitors are registered in the USA and Europe regardless of the performance status. Evidence regarding the effectiveness and safety of such treatment in this cohort is sparse. METHODS Using PubMed (to July 2020), the relevant literature on the effect of ECOG PS 2 on the efficacy and safety of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) with ECOG PS 2 was searched. RESULTS A database search conducted using an international repository (PubMed) identified 191 records. Additional 3 records were identified through other sources. After pre-selection, 92 records were excluded, and 102 full-text articles were assessed for eligibility. With further exclusion of articles not meeting the inclusion criteria, 44 studies were entered into the qualitative synthesis. CONCLUSIONS Immunotherapy seems to be justified in PS 2 patients with NSCLC. This method of treatment has been proven to be safe and tolerable. However, outcomes in this population remain suboptimal and the impact of immunotherapy in this cohort is less dramatic. Multiple scales evaluating many factors beyond PS scores have been suggested to help stratify the PS 2 to reinforce the chance of achieving better treatment outcomes. Randomized trials are needed to determine the benefits of immune checkpoint inhibitors (ICIs) for patients with poor ECOG PS.
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Affiliation(s)
- Damian Mojsak
- 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland.
| | - Beata Kuklińska
- 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland
| | - Łukasz Minarowski
- 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland
| | - Robert Marek Mróz
- 2nd Department of Lung Diseases and Tuberculosis, Medical University of Bialystok, Bialystok, Poland
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Heo IR, Kim HC, Lee SJ, Yoo JW, Ju S, Jeong YY, Lee JD, Cho YJ, Jeong JH, Heo M, Jung SW, Kim TH. Impact of coexistent preserved ratio impaired spirometry on the survival of patients with lung cancer: Analysis of data from the Korean Association for Lung Cancer Registry. Thorac Cancer 2021; 12:2478-2486. [PMID: 34337879 PMCID: PMC8447913 DOI: 10.1111/1759-7714.14095] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/15/2021] [Accepted: 07/16/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Preserved ratio impaired spirometry (PRISm) is a common spirometric pattern that is associated with respiratory symptoms and higher mortality rates. However, the relationship between lung cancer and PRISm remains unclear. This study investigated the clinical characteristics of lung cancer patients with PRISm and the potential role of PRISm as a prognostic factor. METHODS We retrospectively reviewed data collected from 2014 to 2015 in the Korean Association for Lung Cancer Registry. We classified all patients into three subgroups according to lung function as follows: normal lung function; PRISm (forced expiratory volume in 1 s [FEV1 ] < 80% predicted and FEV1 /forced vital capacity [FVC] ≥ 0.7); and chronic obstructive pulmonary disease (COPD; FEV1/FVC < 0.7). In non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the overall survival period was compared among the three subgroups. The prognostic factors were investigated using Cox regression analysis. RESULTS Of the 3763 patients, 38.6%, 40.1%, and 21.3% had normal lung function, COPD, and PRISm, respectively. Patients with PRISm had poorer overall survival than those with COPD or normal lung function in NSCLC and SCLC (Mantel-Cox log-rank test, p < 0.05). In the risk-adjusted analysis, overall survival was independently associated with COPD (hazard ratio [HR] 1.209, p = 0.027) and PRISm (HR 1.628, p < 0.001) in NSCLC, but was only associated with PRISm (HR 1.629, p = 0.004) in SCLC. CONCLUSIONS PRISm is a significant pattern of lung function in patients with lung cancer. At the time of lung cancer diagnosis, pre-existing PRISm should be considered a predictive factor of poor prognosis.
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Affiliation(s)
- I Re Heo
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Ho Cheol Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Seung Jun Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Jung-Wan Yoo
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Sunmi Ju
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Yi Yeong Jeong
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Jong Deog Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Yu Ji Cho
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Jong Hwan Jeong
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Manbong Heo
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Republic of Korea
| | - Seung Woo Jung
- Department of Critical Care Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
| | - Tae Hoon Kim
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea
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Yonenaga Y, Naito T, Okayama T, Kitagawa M, Mitsuhashi N, Ishii T, Fuseya H, Inano T, Morikawa A, Sugiyama M, Mori K, Notsu A, Kawabata T, Ono A, Kenmotsu H, Murakami H, Tanuma A, Takahashi T. Impact of Physical Inactivity on the Risk of Disability and Hospitalization in Older Patients with Advanced Lung Cancer. J Multidiscip Healthc 2021; 14:1521-1532. [PMID: 34188479 PMCID: PMC8232865 DOI: 10.2147/jmdh.s311225] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 05/18/2021] [Indexed: 11/25/2022] Open
Abstract
Purpose This prospective observational study aimed to explore the influence of physical inactivity during initial chemotherapy on the risk of disability and hospitalization in later life among older patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods Patients aged 70 or above who were scheduled to receive first-line chemotherapy for newly diagnosed advanced NSCLC were recruited for the study. An electronic pedometer was used to measure daily steps; based on the change rate (cutoff: −12.5%) from pretreatment to 12 ± 4 weeks after enrolment, patients were classified as active or inactive. The Barthel Index estimated activities of daily living. We compared disability-free survival time, mean cumulative functions of hospital stays, and medical costs, between the active and inactive groups. Results Among the 29 patients enrolled, 21 were evaluable. Compared with active patients (n = 11), inactive patients (n = 10) showed shorter disability-free survival (6.4 vs 19.9 months, p < 0.05) and tended to have longer hospital stays (23.7 vs 6.3 days/person) and higher inpatient care cost (¥1.6 vs ¥0.3 million/person [US$16,000 vs US$3000/person]) during the first year. Conclusion Physical inactivity during initial chemotherapy may be a risk factor for developing disability and requiring hospitalization in later life for older patients with advanced NSCLC. Our findings may indicate the need for lifestyle interventions with multidisciplinary teams, which include physicians, nurses, and physiotherapists, for older patients with advanced lung cancer during an active cancer treatment. A large-sample-sized study is needed to validate our findings.
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Affiliation(s)
- Yusuke Yonenaga
- Division of Rehabilitation Medicine, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Tateaki Naito
- Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Taro Okayama
- Division of Rehabilitation Medicine, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Midori Kitagawa
- Division of Rehabilitation Medicine, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Noriko Mitsuhashi
- Division of Rehabilitation Medicine, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Takeshi Ishii
- Division of Rehabilitation Medicine, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Hiroshi Fuseya
- Division of Rehabilitation Medicine, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Toshimi Inano
- Division of Nutrition, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Ayumu Morikawa
- Division of Nursing, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Miwa Sugiyama
- Division of Nursing, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Keita Mori
- Clinical Research Center, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Akifumi Notsu
- Clinical Research Center, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Takanori Kawabata
- Clinical Research Center, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Akira Ono
- Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Hirotsugu Kenmotsu
- Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Haruyasu Murakami
- Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
| | - Akira Tanuma
- Department of Rehabilitation Medicine, Juntendo Shizuoka Hospital, Juntendo University School of Medicine, Izunokuni-shi, Shizuoka, Japan
| | - Toshiaki Takahashi
- Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Shizuoka, Japan
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Foy V, Lindsay CR, Carmel A, Fernandez-Gutierrez F, Krebs MG, Priest L, Carter M, Groen HJM, Hiltermann TJN, de Luca A, Farace F, Besse B, Terstappen L, Rossi E, Morabito A, Perrone F, Renehan A, Faivre-Finn C, Normanno N, Dive C, Blackhall F, Michiels S. EPAC-lung: European pooled analysis of the prognostic value of circulating tumour cells in small cell lung cancer. Transl Lung Cancer Res 2021; 10:1653-1665. [PMID: 34012782 PMCID: PMC8107738 DOI: 10.21037/tlcr-20-1061] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 01/17/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Circulating tumour cell (CTC) number is an independent prognostic factor in patients with small cell lung cancer (SCLC) but there is no consensus on the CTC threshold for prognostic significance. We undertook a pooled analysis of individual patient data to clinically validate CTC enumeration and threshold for prognostication. METHODS Four European cancer centres, experienced in CellSearch CTC enumeration for SCLC provided pseudo anonymised data for patients who had undergone pre-treatment CTC count. Data was collated, and Cox regression models, stratified by centre, explored the relationship between CTC count and survival. The added value of incorporating CTCs into clinico-pathological models was investigated using likelihood ratio tests. RESULTS A total of 367 patient records were evaluated. A one-unit increase in log-transformed CTC counts corresponded to an estimated hazard ratio (HR) of 1.24 (95% CI: 1.19-1.29, P<0.0001) for progression free survival (PFS) and 1.23 (95% CI: 1.18-1.28, P<0.0001) for overall survival (OS). CTC count of ≥15 or ≥50 was significantly associated with an increased risk of progression (CTC ≥15: HR 3.20, 95% CI: 2.50-4.09, P<0.001; CTC ≥50: HR 2.56, 95% CI: 2.01-3.25, P<0.001) and an increased risk of death (CTC ≥15: HR 2.90, 95% CI: 2.28-3.70, P<0.001; CTC ≥50: HR 2.47, 95% CI: 1.95-3.13, P<0.001). There was no significant inter-centre heterogeneity observed. Addition of CTC count to clinico-pathological models as a continuous log-transformed variable, offers further prognostic value (both likelihood ratio P<0.001 for OS and PFS). CONCLUSIONS Higher pre-treatment CTC counts are a negative independent prognostic factor in SCLC when considered as a continuous variable or dichotomised counts of ≥15 or ≥50. Incorporating CTC counts, as a continuous variable, improves clinic-pathological prognostic models.
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Affiliation(s)
- Victoria Foy
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Colin R Lindsay
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
- Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK
- Cancer Research UK Lung Cancer Centre of Excellence, Manchester, UK
| | - Alexandra Carmel
- Service de Biostatistique et d'Épidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
- INSERM U1018 OncoStat, CESP, Université Paris-Sud, Université Paris-Saclay, labeled by Ligue Contre le Cancer, France
| | - Fabiola Fernandez-Gutierrez
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
- Cancer Research UK Lung Cancer Centre of Excellence, Manchester, UK
| | - Matthew G Krebs
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
- Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK
- Cancer Research UK Lung Cancer Centre of Excellence, Manchester, UK
| | - Lynsey Priest
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Mathew Carter
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Harry J M Groen
- Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - T Jeroen N Hiltermann
- Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Antonella de Luca
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italy
| | - Francoise Farace
- INSERM, U981 "Predictive Biomarkers and New Therapeutics in Oncology", F-94805, Villejuif, France
- Gustave Roussy, Université Paris-Saclay. "Rare Circulating Cells" Translational Platform, CNRS UMS3655 - INSERM US23, AMMICA, Villejuif, France
| | - Benjamin Besse
- Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France; Paris-Sud University, Orsay, France
| | - Leon Terstappen
- Department of Medical Cell BioPhysics, University of Twente, Enschede, The Netherlands
| | - Elisabetta Rossi
- Department of Surgery, Oncology and Gastroenterology, Oncology Section, University of Padova, Padova, Italy
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Alessandro Morabito
- Thoracic Medical Oncology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italy
| | - Francesco Perrone
- Clinical Trials Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italy
| | - Andrew Renehan
- Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK
| | - Corinne Faivre-Finn
- Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK
| | - Nicola Normanno
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Napoli, Italy
| | - Caroline Dive
- Cancer Research UK Manchester Institute Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
- Cancer Research UK Lung Cancer Centre of Excellence, Manchester, UK
| | - Fiona Blackhall
- Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
- Division of Molecular and Clinical Cancer Sciences, University of Manchester, Manchester, UK
- Cancer Research UK Lung Cancer Centre of Excellence, Manchester, UK
| | - Stefan Michiels
- Service de Biostatistique et d'Épidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France
- INSERM U1018 OncoStat, CESP, Université Paris-Sud, Université Paris-Saclay, labeled by Ligue Contre le Cancer, France
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Goizueta AA, Estrada-Y-Martin RM, Cherian SV. Lung Cancer in Women: a Review. CURRENT PULMONOLOGY REPORTS 2021. [DOI: 10.1007/s13665-021-00270-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Hueman M, Wang H, Liu Z, Henson D, Nguyen C, Park D, Sheng L, Chen D. Expanding TNM for lung cancer through machine learning. Thorac Cancer 2021; 12:1423-1430. [PMID: 33713568 PMCID: PMC8088955 DOI: 10.1111/1759-7714.13926] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/20/2021] [Accepted: 02/21/2021] [Indexed: 01/05/2023] Open
Abstract
Background Expanding the tumor, lymph node, metastasis (TNM) staging system by accommodating new prognostic and predictive factors for cancer will improve patient stratification and survival prediction. Here, we introduce machine learning for incorporating additional prognostic factors into the conventional TNM for stratifying patients with lung cancer and evaluating survival. Methods Data were extracted from SEER. A total of 77 953 patients were analyzed using factors including primary tumor (T), regional lymph node (N), distant metastasis (M), age, and histology type. Ensemble algorithm for clustering cancer data (EACCD) and C‐index were applied to generate prognostic groups and expand the current staging system. Results With T, N, and M, EACCD stratified patients into 11 groups, resulting in a significantly higher accuracy in survival prediction than the 10 AJCC stages (C‐index = 0.7346 vs. 0.7247, increase in C‐index = 0.0099, 95% CI: 0.0091–0.0106, p‐value = 9.2 × 10−147). There nevertheless remained a strong association between the EACCD grouping and AJCC staging (rank correlation = 0.9289; p‐value = 6.7 × 10−22). A further analysis demonstrated that age and histological tumor could be integrated with the TNM. Data were stratified into 12 prognostic groups with an even higher prediction accuracy (C‐index = 0.7468 vs. 0.7247, increase in C‐index = 0.0221, 95% CI: 0.0212–0.0231, p‐value <5 × 10−324). Conclusions EACCD can be successfully applied to integrate additional factors with T, N, M for lung cancer patients.
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Affiliation(s)
- Matthew Hueman
- Department of Surgical Oncology, John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Huan Wang
- Department of Biostatistics, George Washington University, Washington, District of Columbia, USA
| | - Zhenqiu Liu
- Department of Public Health Sciences, Penn State Cancer Institute, Hershey, Pennsylvania, USA
| | - Donald Henson
- Department of Preventive Medicine & Biostatistics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Cuong Nguyen
- Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Dean Park
- Department of Hematology-Oncology, John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Li Sheng
- Department of Mathematics, Drexel University, Philadelphia, Pennsylvania, USA
| | - Dechang Chen
- Department of Preventive Medicine & Biostatistics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
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Gounant V, Duruisseaux M, Soussi G, Van Hulst S, Bylicki O, Cadranel J, Wislez M, Trédaniel J, Spano JP, Helissey C, Chouaid C, Molinier O, Dhalluin X, Doucet L, Hureaux J, Cazes A, Zalcman G. Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients. Cancers (Basel) 2021; 13:cancers13051040. [PMID: 33801285 PMCID: PMC7958129 DOI: 10.3390/cancers13051040] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 02/23/2021] [Accepted: 02/24/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary Immunotherapies prolong survival of metastatic non-small-cell lung cancer patients. However, their efficacy in patients with very poor general condition is unknown. Best supportive care is the standard of care for these patients because chemotherapy is more toxic and less effective than for patients with good general condition. Most patients die within 1 to 4 months of diagnosis. Consecutive metastatic non-small-cell lung cancer patients with very poor general condition receiving compassionate immunotherapy were accrued by 12 French thoracic oncology departments, over 24 months. Tolerance was acceptable. Overall, 20% of patients were alive at 1 year, and 14% at 2 years. We feel that our study results might suggest that some patients with a very poor general condition (namely those without brain metastases or heavy smokers) could derive long-term benefit from immunotherapy as salvage therapy. We initiated such a prospective phase 2 trial based on these results, which is a cause for hope. Abstract Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.
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Affiliation(s)
- Valérie Gounant
- Department of Thoracic Oncology, Bichat Claude Bernard Hospital, APHP, CIC Inserm 1425, Université de Paris, 75018 Paris, France; (G.S.); (G.Z.)
- Correspondence:
| | - Michael Duruisseaux
- Respiratory Department, Louis Pradel Hospital, Hospices Civils de Lyon, 69002 Lyon, France;
- Université Claude Bernard Lyon 1, 69100 Villeurbanne, France
| | - Ghassen Soussi
- Department of Thoracic Oncology, Bichat Claude Bernard Hospital, APHP, CIC Inserm 1425, Université de Paris, 75018 Paris, France; (G.S.); (G.Z.)
| | - Sylvie Van Hulst
- Department of Pneumology, University Hospital of Nîmes, 30900 Nîmes, France;
| | - Olivier Bylicki
- Respiratory Disease Unit, Hôpital d’Instruction des Armées Sainte-Anne, 83800 Toulon, France;
| | - Jacques Cadranel
- Department of Pneumology and Thoracic Oncology, Tenon Hospital, APHP, GRC Theranoscan and Curamus Sorbonne Université, 75020 Paris, France;
| | - Marie Wislez
- Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Université, INSERM, TeamInflammation, Complement, and Cancer, 75006 Paris, France;
- Oncology Thoracic Unit Pulmonology Department, AP-HP, Hôpital Cochin, 75014 Paris, France
| | - Jean Trédaniel
- Groupe Hospitalier Paris Saint-Joseph, Department of Pneumology, Université de Paris, Sorbonne Paris Cité, Unité INSERM UMR-S 1124, 75014 Paris, France;
| | - Jean-Philippe Spano
- Department of Medical Oncology, Pitié-Salpétrière Hospital, APHP, Sorbonne Université, 75013 Paris, France;
| | - Carole Helissey
- Clinical Research Unit, Hôpital d’Instruction des Armées Bégin, 94160 Saint-Mandé, France;
| | - Christos Chouaid
- Department of Pneumology, Centre Hospitalier Intercommunal de Créteil, University Paris–Est Créteil (UPEC), CEpiA (Clinical Epidemiology and Ageing), EA 7376-IMRB, 94000 Créteil, France;
| | - Olivier Molinier
- Department of Pneumology, Centre Hospitalier Le Mans, 72037 Le Mans, France;
| | - Xavier Dhalluin
- Department of Pneumology and Thoracic Oncology, Calmette Hospital, Centre Hospitalier Universitaire de Lille, 59000 Lille, France;
| | - Ludovic Doucet
- Department of Oncology, Saint Louis Hospital, APHP, 75010 Paris, France;
| | - José Hureaux
- Department of Pneumology, Pόle Hippocrate, University Hospital of Angers, 49100 Angers, France;
| | - Aurélie Cazes
- Department of Pathology, Bichat Claude Bernard Hospital, APHP, Université de Paris, 75018 Paris, France;
| | - Gérard Zalcman
- Department of Thoracic Oncology, Bichat Claude Bernard Hospital, APHP, CIC Inserm 1425, Université de Paris, 75018 Paris, France; (G.S.); (G.Z.)
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Jemielita T, Li XN, Piperdi B, Zhou W, Burke T, Chen C. Overall Survival With Second-Line Pembrolizumab in Patients With Non-Small-Cell Lung Cancer: Randomized Phase III Clinical Trial Versus Propensity-Adjusted Real-World Data. JCO Clin Cancer Inform 2021; 5:56-65. [PMID: 33439727 DOI: 10.1200/cci.20.00099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
PURPOSE To compare and characterize overall survival (OS) differences between clinical trial data from the KEYNOTE-010 trial and real-world data (RWD) from the Flatiron Health database in patients with programmed death ligand 1 (PD-L1)-expressing advanced non-small-cell lung cancer (NSCLC) who received second-line pembrolizumab monotherapy. METHODS Clinical trial data were from the randomized phase II/III KEYNOTE-010 trial that enrolled patients from August 28, 2013, to February 27, 2015. At data cutoff for KEYNOTE-010, the median survival follow-up time for pembrolizumab patients was 11.2 months. RWD were from Flatiron Health advanced NSCLC database and included patients who initiated second-line pembrolizumab from January 26, 2015, to February 28, 2019. At data cutoff for Flatiron, the median survival follow-up time for pembrolizumab-treated patients was 6.1 months. Clinical trial data from KEYNOTE-010 and RWD from Flatiron were analyzed without adjustment, with propensity adjustment, and filtered per the main KEYNOTE-010 eligibility criteria (EC) of histologically/cytologically confirmed PD-L1-positive NSCLC, Eastern Cooperative Oncology Group performance status of 0/1, no prior therapy with docetaxel for NSCLC, and laboratory values indicative of adequate organ function in addition to prior line of therapy requirements. RESULTS Among 243 patients from KEYNOTE-010 and 782 from Flatiron, median age was 63 v 68 years, and 64% v 54% were male, respectively. OS data from KEYNOTE-010 and Flatiron were similar without any adjustment (n = 782; hazard ratio [HR], 0.96; 95% CI, 0.80 to 1.15) and after both filtering and propensity adjustment (n = 221; HR, 0.99; 95% CI, 0.73 to 1.34). CONCLUSION Without any adjustment, as well as after applying similar EC and appropriate statistical methods, RWD demonstrated similar effectiveness for pembrolizumab in second-line NSCLC as observed in randomized clinical trials.
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Affiliation(s)
- Thomas Jemielita
- Biostatistics and Research Decision Sciences (BARDS), Merck & Co, Inc, Kenilworth, NJ
| | - Xiaoyun Nicole Li
- Biostatistics and Research Decision Sciences (BARDS), Merck & Co, Inc, Kenilworth, NJ
| | - Bilal Piperdi
- Oncology Clinical Development, Merck & Co, Inc, Kenilworth, NJ
| | - Wei Zhou
- Center for Observational and Real World Evidence (CORE), Merck & Co, Inc, Kenilworth, NJ
| | - Thomas Burke
- Center for Observational and Real World Evidence (CORE), Merck & Co, Inc, Kenilworth, NJ
| | - Cong Chen
- Biostatistics and Research Decision Sciences (BARDS), Merck & Co, Inc, Kenilworth, NJ
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Yang B, Ji H, Zhong J, Ma L, Zhong J, Dong H, Zhou C, Duan S, Zhu C, Tian J, Zhang L, Wang F, Zhu H, Lu G. Value of 18F-FDG PET/CT-Based Radiomics Nomogram to Predict Survival Outcomes and Guide Personalized Targeted Therapy in Lung Adenocarcinoma With EGFR Mutations. Front Oncol 2020; 10:567160. [PMID: 33262942 PMCID: PMC7686546 DOI: 10.3389/fonc.2020.567160] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 10/05/2020] [Indexed: 12/25/2022] Open
Abstract
Objectives To investigate the development and validation of a radiomics nomogram based on PET/CT for guiding personalized targeted therapy in patients with lung adenocarcinoma mutation(s) in the EGFR gene. Methods A cohort of 109 (77/32 in training/validation cohort) consecutive lung adenocarcinoma patients with an EGFR mutation was enrolled in this study. A total of 1672 radiomic features were extracted from PET and CT images, respectively. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the radiomic features and construct the radiomics nomogram for the estimation of overall survival (OS), which was then assessed with respect to calibration and clinical usefulness. Patients with an EGFR mutation were divided into high- and low- risk groups according to their nomogram score. The treatment strategy for high- and low-risk groups was analyzed using Kaplan–Meier analysis and a log-rank test. Results The C-index of the radiomics nomogram for the prediction of OS in lung adenocarcinoma in patients with an EGFR mutation was 0.840 and 0.803 in the training and validation cohorts, respectively. Distant metastasis [(Hazard ratio, HR),1.80], metabolic tumor volume (MTV, HR, 1.62), and rad score (HR, 17.23) were the independent risk factors for patients with an EGFR mutation. The calibration curve showed that the predicted survival time was remarkably close to the actual time. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful. Targeted therapy for patients with high-risk EGFR mutations attained a greater benefit than other therapies (p < 0.0001), whereas the prognoses of the two therapies were similar in the low-risk group (p = 0.85). Conclusions Development and validation of a radiomics nomogram based on PET/CT radiomic features combined with clinicopathological factors may guide targeted therapy for patients with lung adenocarcinoma with EGFR mutations. This is conducive to the advancement of precision medicine.
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Affiliation(s)
- Bin Yang
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Hengshan Ji
- Department of Nuclear Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jing Zhong
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Lu Ma
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jian Zhong
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Hao Dong
- College of Medical Imaging, Xuzhou Medical University, Xuzhou, China
| | - Changsheng Zhou
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Shaofeng Duan
- Institute of Precision Medicine, GE Healthcare China, Shanghai, China
| | - Chaohui Zhu
- Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Jiahe Tian
- Department of Nuclear Medicine, The Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Longjiang Zhang
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Feng Wang
- Department of Nuclear Medicine, First People's Hospital of Nanjing, Nanjing, China
| | - Hong Zhu
- Department of Nuclear Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Guangming Lu
- Department of Medical Imaging, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
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Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma ≤2 cm in size: A retrospective cohort study. J Formos Med Assoc 2020; 120:874-882. [PMID: 32891489 DOI: 10.1016/j.jfma.2020.08.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 08/10/2020] [Accepted: 08/17/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND/PURPOSE Lung cancer patients can have advanced-stages at diagnosis, even the tumor size is ≤2 cm. We aimed to study the relationship between image characteristics, clinical, and patholoigcal results. METHODS We retrospectively enrolled patients with lung adenocarcinoma at Taichung Veterans General Hospital and Chang Gung Memorial Hospital from 2007 to 2015, who were diagnosed with treatment naïve primary tumor lesions at sizes less than 2 cm, as measured by computed tomography (CT) scans. The patient was analyzed for lymph node (LN) and distant metastasis evaluation, with clinicopathological characteristics, including tumor-disappearance ratio (TDR) (tumor diameter at the mediastinal/lung window) over chest CT scans, pathological diagnosis, disease-free survival (DFS), and overall survival (OS). RESULTS Totally 280 patients were surveyed initially and showed significantly increase of clinical LN involvement and distant metastasis when TDR ≤75% compared with >75% (21.6% vs 0% for LN involvement; 27.1% vs 0% for distant metastasis; both p < 0.001). We included 199 patients having surgical treatment and follow-up for the survival analysis. With a TDR ≤75%, significantly worse DFS (HR, 19.23; 95% CI, 2.60-142.01; p = 0.004) and a trend of worse OS (HR, 4.97; 95% CI, 0.61-40.61; p = 0.134) were noted by Kaplan-Meier method. TDR ≤75% revealed more advanced pathological stage, and more tumors containing micropapillary or solid subtypes when diagnosed adenocarcinoma. CONCLUSION For lung cancer patients with primary tumor ≤2 cm, TDR ≤75% was related to more advanced stages, the presence of micropapillary or solid components of adenocarcinoma subtypes, worse DFS, and a trend of worse OS.
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Gao H, Dang Y, Qi T, Huang S, Zhang X. Mining prognostic factors of extensive-stage small-cell lung cancer patients using nomogram model. Medicine (Baltimore) 2020; 99:e21798. [PMID: 32872080 PMCID: PMC7437828 DOI: 10.1097/md.0000000000021798] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
This study is to establish the nomogram model and provide clinical therapy decision-making for extensive-stage small-cell lung cancer (ES-SCLC) patients with different metastatic sites using the Surveillance, Epidemiology, and End Results (SEER) Program.A total of 10,025 patients of ES-SCLC with metastasis from January 2010 to December 2016 were enrolled from the SEER database. All samples were randomly divided into a derivation cohort and a validation cohort, and the derivation cohort was divided into 6 groups by different metastatic sites: bone, liver, lung, brain, multiple organs, and other organs. Using Cox proportional hazards models to analyze candidate prognostic factors, screening out the independent prognostic factors to establish the nomogram. Compare the different models by Net reclassification improvement and integrated discrimination improvement. Concordance index (C-index) and the calibration curve were used to verify the prediction efficiency of the nomogram in the derivation cohort and validation cohort.In the derivation cohort, the median overall survival was 7 months. The overall survival rates at 6-month, 1-year, and 2-year were 55.07%, 24.61%, and 7.56%, respectively. The median survival time was 10, 8, 7, 9, 7, and 6 months for the 6 groups of different metastatic sites: other, bone, liver, lung, brain, and multiple organs, respectively. Age, sex, race, T, N, distant metastatic site, and chemotherapy were contained in the final nomogram prognostic model. The C-index was 0.6569777 in the derivation cohort and 0.8386301 in the validation cohort.The survival time of ES-SCLC patients with different metastatic sites was significantly different. The nomogram can effectively predict the prognosis of individuals and provide a basis for clinical decision-making.
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Affiliation(s)
- Hongxiang Gao
- Radiotherapy Department, The First Affiliated Hospital of Xi’an Jiaotong University
- Department of Oncology, Chang An Hospital
| | - Yazheng Dang
- Radiotherapy Department, 986 Hospital affiliated to The Fourth Military Medical University, Xi’an, Shaan Xi
| | - Tao Qi
- Radiotherapy Department, 986 Hospital affiliated to The Fourth Military Medical University, Xi’an, Shaan Xi
| | - Shigao Huang
- Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
| | - Xiaozhi Zhang
- Radiotherapy Department, The First Affiliated Hospital of Xi’an Jiaotong University
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Ayala de Miguel P, Enguix-Riego MV, Cacicedo J, Delgado BD, Perez M, Praena-Fernández JM, Quintana Cortés L, Borrega García P, Del Campo ER, Lopez Guerra JL. Prognostic value of the TGFβ1 rs4803455 single nucleotide polymorphism in small cell lung cancer. TUMORI JOURNAL 2020; 107:209-215. [PMID: 32779517 DOI: 10.1177/0300891620946841] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein β1 (HSPB1) and transforming growth factor β1 (TGFβ1) and survival have been investigated. METHODS A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFβ1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFβ1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS Genetic analysis showed the CA genotype of TGFβ1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.
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Affiliation(s)
- Pablo Ayala de Miguel
- Department of Medical Oncology, San Pedro de Alcántara University Hospital, Caceres, Spain
| | - María Valle Enguix-Riego
- Department of Radiation Oncology, University Hospital Virgen del Rocío, Seville, Spain.,Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain
| | - Jon Cacicedo
- Departament of Radiation Oncology, Cruces University Hospital, Barakaldo, Spain
| | - Blas David Delgado
- Department of Radiation Oncology, University Hospital Virgen del Rocío, Seville, Spain
| | - Marco Perez
- Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain
| | | | - Laura Quintana Cortés
- Department of Medical Oncology, San Pedro de Alcántara University Hospital, Caceres, Spain
| | - Pablo Borrega García
- Department of Medical Oncology, San Pedro de Alcántara University Hospital, Caceres, Spain
| | - Eleonor Rivin Del Campo
- Department of Radiation Oncology, Tenon University Hospital, Sorbonne University, Paris, France
| | - Jose Luis Lopez Guerra
- Department of Radiation Oncology, University Hospital Virgen del Rocío, Seville, Spain.,Instituto de Biomedicina de Sevilla (IBIS/HUVR/CSIC/Universidad de Sevilla), Seville, Spain
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