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Zhou Q, Li H, Liang Y, Li R, Wang X, Wang W, Liu M, Duan F, Huang Z. Hepatic arterial infusion chemotherapy combined with lenvatinib and immune checkpoint inhibitor versus lenvatinib for advanced hepatocellular carcinoma: a multicenter study with propensity score and coarsened exact matching. LA RADIOLOGIA MEDICA 2025; 130:662-673. [PMID: 40072804 DOI: 10.1007/s11547-025-01975-3] [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: 08/20/2024] [Accepted: 02/14/2025] [Indexed: 03/14/2025]
Abstract
PURPOSE Hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib (Len) and immune checkpoint inhibitor (ICI) in treating advanced hepatocellular carcinoma (HCC) still needs further confirmation. We aimed to evaluate the efficacy of HAIC combined with Len and ICI (HAIC + Len + ICI) versus Len alone in advanced HCC. METHODS A total of 290 patients in Len group and 349 patients in HAIC + Len + ICI group were analysed. Propensity score matching (PSM), inverse probability treatment weighting (IPTW), and coarsened exact matching (CEM) analyses were used to balance the bias between two groups. Mediation analysis of treatment type in survival was performed for analysis. RESULTS The median progression-free survival (PFS) was 5.9 ± 0.2 months in Len group and 9.2 ± 0.5 months in HAIC + Len + ICI group. The HAIC + Len + ICI group demonstrated significantly better PFS than the Len group across the entire cohort (hazard ratio [HR], 0.50; 95% CI 0.43-0.60; P < 0.001). This advantage in PFS was sustained in the PSM, IPTW, and CEM cohorts. HAIC + Len + ICI group also showed better overall survival (OS) than the Len group (HR, 0.38; 95% CI 0.31-0.46; P < 0.001). The OS was also superior in the PSM, IPTW, and CEM cohorts. The objective response rate (ORR) in HAIC + Len + ICI group was twice as high as that in Len group. Further mediation analysis showed tumor response at 3 and 6 months had different mediation effect on survival. CONCLUSIONS HAIC combined with Len and ICI showed improved better OS and PFS than Len alone. This triple therapy could be considered as a first-line treatment for advanced HCC.
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Affiliation(s)
- Qunfang Zhou
- Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Hui Li
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Dongfeng East Road 651, Guangzhou, 510260, Guangdong Province, China
| | - Ye Liang
- Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Ruixia Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Er Road, Guangzhou, 510080, Guangdong Province, China
| | - Xiaohui Wang
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, 61 Jiefang West Road, Changsha, Hunan Province, China
| | - Wei Wang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Renmin Road No. 2, Jinzhou, 121000, Liaoning Province, China
| | - Mingyu Liu
- Department of Interventional Radiology, The Affiliated Shunde Hospital of Jinan University, Guizhou East Road 50, Foshan, Guangdong Province, China
| | - Feng Duan
- Department of Interventional Radiology, 5th Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
| | - Zhimei Huang
- Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Dongfeng East Road 651, Guangzhou, 510260, Guangdong Province, China.
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McMorrow R, de Bruijn HS, Farina S, van Ardenne RJ, Que I, Mastroberardino PG, Robinson DJ, Mezzanotte L, Löwik CW. Combination of Bremachlorin PDT and Immune Checkpoint Inhibitor Anti-PD-1 Shows Response in Murine Immunological T-cell-High and T-cell-Low PDAC Models. Mol Cancer Ther 2025; 24:605-617. [PMID: 39704624 PMCID: PMC11962392 DOI: 10.1158/1535-7163.mct-23-0733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 04/12/2024] [Accepted: 12/17/2024] [Indexed: 12/21/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging types of cancer with little or no response to immune checkpoint inhibitors (ICI). Photodynamic therapy (PDT) has been shown to ablate tumors and induce an immune response. In our study, we investigated the effect of PDT using the photosensitizer Bremachlorin, in its ability to reduce tumor burden and immunologically sensitize T-cell-high and T-cell-low murine PDAC tumors to the ICIs that blocks PD-1 immune checkpoint. In addition, we monitored the effect on survival and investigated if there was a response in PDT-treated and non-PDT-treated distant tumors. Our results showed that Bremachlorin PDT induces direct tumor killing that increased survival in both "hot" T-cell-high and "cold" T-cell-low PDAC tumors and that it can make T-cell-high tumors more sensitive to ICIs blocking PD-1. We found that T-cell-high tumor-bearing mice had an overall greater response to therapy than did T-cell-low tumor-bearing mice. One mouse with T-cell-high tumors exhibited complete tumor regression in both the treated and nontreated distant tumor 90 days after treatment. These results indicate that combining ICIs with Bremachlorin PDT could be a promising therapeutic intervention for enhancing PDAC's response to therapy.
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Affiliation(s)
- Roisin McMorrow
- Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
- Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Henriette S. de Bruijn
- Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Stefania Farina
- Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Ruben J.L. van Ardenne
- Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Ivo Que
- Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
- Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Pier G. Mastroberardino
- Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
- IFOM-The FIRC Institute of Molecular Oncology, Milan, Italy
- Department of Life, Health, and Environmental Sciences, University of L’Aquila, L’Aquila, Italy
| | - Dominic J. Robinson
- Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Laura Mezzanotte
- Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
- Department of Molecular Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands
| | - Clemens W.G.M. Löwik
- Department of Radiology and Nuclear Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands
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Wang M, Wei D, Cui Z, Zhou Y, Yin C, Zhou Z, D’Journo XB, Wang G. Evaluation of the efficacy and safety of neoadjuvant immunotherapy in locally advanced esophageal squamous cell carcinoma. J Thorac Dis 2025; 17:1711-1722. [PMID: 40223985 PMCID: PMC11986757 DOI: 10.21037/jtd-2025-215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 03/17/2025] [Indexed: 04/15/2025]
Abstract
Background While neoadjuvant therapy combined with surgery remains standard for locally advanced esophageal squamous cell carcinoma (ESCC), survival outcomes remain suboptimal. Refining multimodal neoadjuvant regimens (including chemoradiotherapy, chemotherapy, and emerging immunotherapy) is critical to improving prognosis. This study sought to evaluate the efficacy and safety of neoadjuvant immuno-chemotherapy in the treatment of locally advanced ESCC, and to examine the correlation between tumor regression grade (TRG) and imaging evaluation. Methods In total, 106 patients diagnosed with ESCC-only received a 21-day cycle of intravenous camrelizumab plus nab-paclitaxel and carboplatin. The efficacy was evaluated after two cycles, and the patients subsequently underwent tumor resection. All patients completed the full treatment regime and underwent surgery. Patients' treatment response after neoadjuvant therapy, R0 resection rate, TRG, and pathologic complete response (pCR) rate were measured. The adverse events (AEs) were also documented. Results The R0 resection (resection with microscopically negative margins) was 97.2% (103/106). The pCR (ypT0N0) rate was 39.6% (42/106), and 50% (53/106) of the patients had a complete response (CR) of the primary tumor but had residual disease in the lymph nodes (ypT0N+). The major pathologic response (MPR) rate was 49% (52/106). Preoperative imaging evaluation of the patients showed that 33% (35/106) had a CR, 34% (36/106) had a partial response (PR), 21.7% (23/106) had stable disease (SD), and 11.3% (12/106) had progressive disease (PD). Based on the postoperative TRG classification, 47.1% (50/106) of the patients had grade 0, 11.3% (12/106) had grade 1, 18% (19/106) had grade 2, and 23.6% (25/106) had grade 3. Conclusions This study showed that camrelizumab-based neoadjuvant immuno-chemotherapy was effective in the treatment of locally advanced resectable ESCC. The treatment increased the likelihood of achieving a curative surgical outcome, and the side effects were generally manageable. The treatment warrants further investigation. Moreover, the TRG was found to be significantly associated with imaging assessment; these two approaches can be combined and employed to predict the efficacy of neoadjuvant immuno-chemotherapy.
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Affiliation(s)
- Mingxi Wang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Dandan Wei
- Department of Gastrointestinal Oncology, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, China
| | - Zhen Cui
- Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Yangyang Zhou
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Chuntong Yin
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Zhengguang Zhou
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Xavier Benoit D’Journo
- Department of Thoracic Surgery, North Hospital, Aix-Marseille University, CNRS, INSERM, CRCM, AP-HM, Marseille, France
| | - Guowen Wang
- Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
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Mou YH, Zhang J, Shen H, Yu J, Han L, Li H, Li QF. Multiple pseudoprogressions during ongoing immunotherapy-based treatment of advanced gastric neuroendocrine carcinoma: A case report and review of literature. World J Gastrointest Oncol 2025; 17:102804. [PMID: 40092963 PMCID: PMC11866236 DOI: 10.4251/wjgo.v17.i3.102804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/24/2024] [Accepted: 01/15/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Gastric neuroendocrine carcinomas (NECs) exhibit aggressive features, such as rapid growth, higher rate of metastasis, and a generally unfavorable prognosis compared to gastric adenocarcinoma. As a result, therapeutic options for NECs remain limited, contributing to the poor prognosis of patients. Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs. Nevertheless, the unique clinical response termed pseudoprogression (PsP) has garnered considerable attention in the context of immunotherapy. CASE SUMMARY Presented here is a case of NEC recurrence five and a half months after radical gastric surgery. The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment. The patient ultimately achieved a durable treatment response without altering his treatment regimens, resulting in a substantial therapeutic benefit. CONCLUSION This case report aimed to provide the authors' experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.
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Affiliation(s)
- Yan-Hua Mou
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Juan Zhang
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Hui Shen
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Jing Yu
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Lan Han
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Hui Li
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
| | - Qing-Feng Li
- Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
- Institute of Oncology, Hubei University of Arts and Science, Xiangyang 441021, Hubei Province, China
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Ayeni A, Evbuomwan O, Vangu MDTW. The Role of [ 18F]FDG PET/CT in Monitoring of Therapy Response in Lung Cancer. Semin Nucl Med 2025; 55:175-189. [PMID: 40021362 DOI: 10.1053/j.semnuclmed.2025.02.002] [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: 01/31/2025] [Accepted: 02/06/2025] [Indexed: 03/03/2025]
Abstract
Lung cancer remains a leading cause of cancer deaths worldwide, with an all stage 5-year relative survival rate of less than 30%. Multiple treatment strategies are available and continue to evolve, with therapy primarily tailored to the type and stage of the disease. Accurate monitoring of therapy response is crucial for optimizing treatment outcomes. PET/CT imaging with [18F]FDG has become the standard of care across various phases of lung cancer management due to its ability to assess metabolic activity. This review underscores the pivotal role of [18F]FDG PET/CT in evaluating therapy response in lung cancer, particularly in non-small cell lung cancer (NSCLC). It examines conventional response criteria and their adaptations in the era of immunotherapy, highlighting the value of integrating metabolic imaging with established criteria to improve treatment assessment and guide clinical decisions. The potential of non-[18F]FDG PET tracers targeting diverse biological pathways to provide deeper insights into tumor biology, therapy response and predictive outcomes is also explored. Additionally, the emerging role of radiomics in enhancing treatment efficacy assessment and improving patient management is briefly highlighted. Despite the challenges in the routine clinical application of various metabolic response criteria, [18F]FDG PET/CT remains a crucial tool in monitoring therapy response in lung cancer. Ongoing advancements in therapeutic strategies, radiopharmaceuticals, and imaging techniques continue to drive progress in lung cancer management, promising improved patient outcomes.
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Affiliation(s)
- Akinwale Ayeni
- Division of Nuclear Medicine, Department of Radiation Sciences, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa; Nuclear Medicine, Klerksdorp/Tshepong Hospital Complex, Klerksdorp, North West Province, South Africa; Division of Nuclear Medicine, Department of Radiation Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
| | - Osayande Evbuomwan
- Department of Nuclear Medicine, Faculty of Health Sciences, University of The Free State, Bloemfontein, South Africa
| | - Mboyo-Di-Tamba Willy Vangu
- Division of Nuclear Medicine, Department of Radiation Sciences, Faculty of Health Sciences, University of The Witwatersrand, Johannesburg, South Africa
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Yarza R, Kountouri M, Guedes H, O'Gorman C, Estrada-Lorenzo JM, Coens C, Kroep J, Herrera F, Madariaga A. Progression-free survival as a potential surrogate end point for overall survival in advanced cervical carcinoma. Int J Gynecol Cancer 2025; 35:100012. [PMID: 39971452 DOI: 10.1016/j.ijgc.2024.100012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 11/10/2024] [Indexed: 02/21/2025] Open
Abstract
OBJECTIVE This systematic review and meta-analysis was performed to study the potential of progression-free survival as a surrogate end point for trials evaluating the use of systemic therapy in advanced cervical cancer. METHODS We performed a systematic review selecting phase II and III randomized trials including locally advanced, recurrent, and metastatic cervical cancer, with mature progression-free survival and overall survival data. Our study adhered to the Reporting Items for Systematic Reviews and Meta-Analyses checklist and was registered in International Prospective Register of Systematic Reviews (CRD42023405604). Exclusions comprised trials involving adjuvant treatment as the primary end point. The magnitude of progression-free survival and overall survival was assessed using standardized z-scores. Subgroup analyses were conducted based on treatment type, line of treatment, and prior radiotherapy exposure. Surrogacy was evaluated according to the recommendations by the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. RESULTS A total of 20 studies were included in the final analysis. In the overall population, a moderate correlation between progression-free survival and overall survival was observed (r = 0.75, p < .001). The surrogate threshold effect (STE) indicated a threshold for progression-free survival z-score (z-progression-free survival of 2.53), intersecting with null overall survival outcome (z = 1.96). Subgroup analysis revealed a weak and nonsignificant correlation in chemotherapy trials (r = 0.5, p = .12) with a higher STE (z-progression-free survival = 2.83). Conversely, chemoimmunotherapy combinations exhibited a robust and statistically significant correlation (r = 0.99, p = 0.01) with a lower STE (z-progression-free survival = 2.39). Trials exploring advanced therapy lines demonstrated a higher and more significant correlation (r = 0.98, p = .02) with a lower STE at 2.08, whereas upfront-line therapy trials showed a moderate correlation (r = 0.67, p = 0.01) with an STE magnitude of 2.58. CONCLUSION Progression-free survival exhibits a moderate correlation with a modest STE. For chemoimmunotherapy combinations, there is a strong correlation between overall survival and progression-free survival, with a notably lower STE. This suggests that the relationship between progression-free survival and overall survival may vary significantly based on the treatment strategy.
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Affiliation(s)
- Ramon Yarza
- Drug Development and Phase I Unit, START-CIOCC, University Hospital HM Sanchinarro, Madrid, Spain.
| | - Melpomeni Kountouri
- Radiation Oncology Department, Hôpitaux Universitaires de Genève, Geneva, Switzerland
| | - Helena Guedes
- Medical Oncology Department, Unidade Local de Saúde Gaia e Espinho, Vila Nova de Gaia, Portugal
| | | | | | - Corneel Coens
- Statistical Department, EORTC AISBL/IVZW - European Organisation for Research and Treatment of Cancer, Brussels, Belgium
| | - Judith Kroep
- Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
| | - Fernanda Herrera
- Service of Radiation Oncology, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland; Immuno-Oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland
| | - Ainhoa Madariaga
- Medical Oncology Department, 12 de Octubre University Hospital, Madrid, Spain
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Thunold S, Hernes E, Farooqi S, Öjlert ÅK, Francis RJ, Nowak AK, Szejniuk WM, Nielsen SS, Cedres S, Perdigo MS, Sørensen JB, Meltzer C, Mikalsen LTG, Helland Å, Malinen E, Haakensen VD. Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine. Eur J Nucl Med Mol Imaging 2025; 52:693-707. [PMID: 39133306 PMCID: PMC11732904 DOI: 10.1007/s00259-024-06853-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 07/16/2024] [Indexed: 08/13/2024]
Abstract
PURPOSE The introduction of immunotherapy in pleural mesothelioma (PM) has highlighted the need for effective outcome predictors. This study explores the role of [18F]FDG PET/CT in predicting outcomes in PM treated with immunotherapy. METHODS Patients from the NIPU trial, receiving ipilimumab and nivolumab +/- telomerase vaccine in second-line, were included. [18F]FDG PET/CT was obtained at baseline (n = 100) and at week-5 (n = 76). Metabolic tumour volume (MTV) and peak standardised uptake value (SUVpeak) were evaluated in relation to survival outcomes. Wilcoxon rank-sum test was used to assess differences in MTV, total lesion glycolysis (TLG), maximum standardised uptake value (SUVmax) and SUVpeak between patients exhibiting an objective response, defined as either partial response or complete response according to the modified Response Criteria in Solid Tumours (mRECIST) and immune RECIST (iRECIST), and non-responders, defined as either stable disease or progressive disease as their best overall response. RESULTS Univariate Cox regression revealed significant associations of MTV with OS (HR 1.36, CI: 1.14, 1.62, p < 0.001) and PFS (HR 1.18, CI: 1.03, 1.34, p = 0.02), while multivariate analysis showed a significant association with OS only (HR 1.35, CI: 1.09, 1.68, p = 0.007). While SUVpeak was not significantly associated with OS or PFS in univariate analyses, it was significantly associated with OS in multivariate analysis (HR 0.43, CI: 0.23, 0.80, p = 0.008). Objective responders had significant reductions in TLG, SUVmax and SUVpeak at week-5. CONCLUSION MTV provides prognostic value in PM treated with immunotherapy. High SUVpeak was not associated with inferior outcomes, which could be attributed to the distinct mechanisms of immunotherapy. Early reductions in PET metrics correlated with treatment response. STUDY REGISTRATION The NIPU trial (NCT04300244) is registered at clinicaltrials.gov. https://classic. CLINICALTRIALS gov/ct2/show/NCT04300244?cond=Pleural+Mesothelioma&cntry=NO&draw=2&rank=4.
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Affiliation(s)
- Solfrid Thunold
- Dept of Oncology, Oslo University Hospital, Oslo, Norway.
- Dept of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
| | - Eivor Hernes
- Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Saima Farooqi
- Dept of Oncology, Oslo University Hospital, Oslo, Norway
- Dept of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - Åsa Kristina Öjlert
- Dept of Oncology, Oslo University Hospital, Oslo, Norway
- Dept of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
| | - Roslyn J Francis
- Dept of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, Australia
- Medical School of The University of Western Australia, Perth, Australia
| | - Anna K Nowak
- Medical School of The University of Western Australia, Perth, Australia
- National Centre for Asbestos-Related Diseases, University of Western Australia, Perth, Australia
- Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Weronika Maria Szejniuk
- Clinical Cancer Research Center & Department of Oncology, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Søren Steen Nielsen
- Department of Nuclear Medicine, Aalborg University Hospital, Aalborg, Denmark
| | - Susana Cedres
- Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Marc Simo Perdigo
- Dept of Nuclear Medicine, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Jens Benn Sørensen
- Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Carin Meltzer
- Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Lars Tore Gyland Mikalsen
- Department of Physics and Computational Radiology, Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
- Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, Norway
| | - Åslaug Helland
- Dept of Oncology, Oslo University Hospital, Oslo, Norway
- Dept of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Eirik Malinen
- Dept of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
- Department of Physics, University of Oslo, Oslo, Norway
| | - Vilde Drageset Haakensen
- Dept of Oncology, Oslo University Hospital, Oslo, Norway
- Dept of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
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Wang J, Li Y, Zhang J, Liu T, Lin R, Zhang J, Shan Y. Discovery of an theranostic functional mAb for visualizing the sensitivity and effectiveness of PD-L1 checkpoint therapy. Bioorg Chem 2025; 154:107992. [PMID: 39603072 DOI: 10.1016/j.bioorg.2024.107992] [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: 10/26/2024] [Revised: 11/13/2024] [Accepted: 11/20/2024] [Indexed: 11/29/2024]
Abstract
To address the challenges of inconsistent efficacy, low sensitivity, and subjective screening methods faced by PD-L1-targeted immune checkpoint therapies in the clinic. We propose to construct a therapeutic functional monoclonal antibody with tracking capability using tetrazolium-based bioorthogonal reaction turn-on fluorescence technology, focusing on the molecular biomarker PD-L1 for easy visualisation of therapeutic response. This therapeutic monoclonal antibody enables bioorthogonal reaction turn-on fluorescence to monitoring of tumors with varying degrees of PD-L1 expression, while preserving the activity of the PDL1 monoclonal antibody and improve the immune activation rate and achieve efficient anti-tumor effects. In conclusion, our proposed family of bio-orthogonal reaction-driven fluorescence turn-on methods can be used to identify therapeutic bifunctional monoclonal antibodies to PD-L1, which can be employed alongside the screening of PD-L1 antibodies for therapeutic effects. Abbreviations: CRT, Calreticulin; DCs, Dendritic cells; ELISA, Enzyme-linked immunosorbent assay; IFN-γ, Interferon-γ; IL-2, Interleukin-2; IHC, Immunohistochemistry; WB, Western blot.
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Affiliation(s)
- Jin Wang
- Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yanchen Li
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Junyu Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Tingting Liu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Roujia Lin
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China
| | - Jie Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
| | - Yuanyuan Shan
- Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
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Lauwers Y, De Groof TWM, Vincke C, Van Craenenbroeck J, Jumapili NA, Barthelmess RM, Courtoy G, Waelput W, De Pauw T, Raes G, Devoogdt N, Van Ginderachter JA. Imaging of tumor-associated macrophage dynamics during immunotherapy using a CD163-specific nanobody-based immunotracer. Proc Natl Acad Sci U S A 2024; 121:e2409668121. [PMID: 39693339 DOI: 10.1073/pnas.2409668121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 11/13/2024] [Indexed: 12/20/2024] Open
Abstract
Immunotherapies have emerged as an effective treatment option for immune-related diseases, such as cancer and inflammatory diseases. However, variations in patient responsiveness limit the broad applicability and success of these immunotherapies. Noninvasive whole-body imaging of the immune status of individual patients during immunotherapy could enable the prediction and monitoring of the patient's response, resulting in more personalized treatments. In this study, we developed a nanobody-based immunotracer targeting CD163, a receptor specifically expressed on macrophages. This anti-CD163 immunotracer bound to human and mouse CD163 with high affinity and specificity without competing for ligand binding. Furthermore, the tracer showed no unwanted immune cell activation and was nonimmunogenic. Upon radiolabeling of the anti-CD163 immunotracer, specific imaging of CD163+ macrophages using micro-single-photon emission computerized tomography/computed tomography or micro-positron emission tomography/CT was performed. The anti-CD163 immunotracer was able to stratify immunotherapy responders from nonresponders (NR) by visualizing differences in the intratumoral CD163+ TAM distribution in Lewis lung carcinoma-ovalbumin tumor-bearing mice receiving an anti-programmed cell death protein-1 (PD-1)/CSF1R combination treatment. Immunotherapy-responding mice showed a more homogeneous distribution of the PET signal in the middle of the tumor, while CD163+ TAMs were located at the tumor periphery in NR. As such, visualization of CD163+ TAM distribution in the tumor microenvironment could allow a prediction or follow-up of therapy response. Altogether, this study describes an immunotracer, specific for CD163+ macrophages, that allows same-day imaging and follow-up of these immune cells in the tumor microenvironment, providing a good basis for the prediction and follow-up of immunotherapy responses in cancer patients.
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Affiliation(s)
- Yoline Lauwers
- Molecular Imaging and Therapy Research Group, Vrije Universiteit Brussel, Brussels 1090, Belgium
| | - Timo W M De Groof
- Molecular Imaging and Therapy Research Group, Vrije Universiteit Brussel, Brussels 1090, Belgium
| | - Cécile Vincke
- Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Center for Inflammation Research, Brussels 1050, Belgium
- Laboratory of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium
| | - Jolien Van Craenenbroeck
- Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Center for Inflammation Research, Brussels 1050, Belgium
- Laboratory of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium
| | - Neema Ahishakiye Jumapili
- Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Center for Inflammation Research, Brussels 1050, Belgium
- Laboratory of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium
| | - Romina Mora Barthelmess
- Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Center for Inflammation Research, Brussels 1050, Belgium
- Laboratory of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium
| | - Guillaume Courtoy
- Department of Pathology, Universitair Ziekenhuis Brussel, Brussels B-1090, Belgium
- Laboratory of Experimental Pathology, Supporting Clinical Sciences, Vrije Universiteit Brussel, Brussels B-1090, Belgium
| | - Wim Waelput
- Department of Pathology, Universitair Ziekenhuis Brussel, Brussels B-1090, Belgium
- Laboratory of Experimental Pathology, Supporting Clinical Sciences, Vrije Universiteit Brussel, Brussels B-1090, Belgium
| | - Tessa De Pauw
- Molecular Imaging and Therapy Research Group, Vrije Universiteit Brussel, Brussels 1090, Belgium
| | - Geert Raes
- Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Center for Inflammation Research, Brussels 1050, Belgium
- Laboratory of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium
| | - Nick Devoogdt
- Molecular Imaging and Therapy Research Group, Vrije Universiteit Brussel, Brussels 1090, Belgium
| | - Jo A Van Ginderachter
- Laboratory of Myeloid Cell Immunology, Vlaams Instituut voor Biotechnologie Center for Inflammation Research, Brussels 1050, Belgium
- Laboratory of Cellular and Molecular Immunology, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels 1050, Belgium
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10
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Felfli M, Thinnes A, Jacques S, Liu Y, Iannessi A. Assessing immunotherapy response: going beyond RECIST by integrating early tumor growth kinetics. Front Immunol 2024; 15:1470555. [PMID: 39759519 PMCID: PMC11695367 DOI: 10.3389/fimmu.2024.1470555] [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: 07/25/2024] [Accepted: 11/25/2024] [Indexed: 01/07/2025] Open
Abstract
Objective Assess the contribution of early tumor growth dynamics modeling to predict clinical outcomes in non-small cell lung cancer patients receiving immunotherapy, alongside standard RECIST 1.1 criteria. Methods Our retrospective studies used data from 861 patients with advanced NSCLC enrolled in three randomized Phase III trials evaluating immunotherapy plus chemotherapy were analyzed. Tumor size measurements up to two follow-up time points were used to fit a novel Gompertz model and estimate growth rate (GR) and kinetic parameters representing depth of response (A), speed of response (B), and long-term modulation (M). Correlations between these early tumor growth parameters and clinical outcomes such as progression-free survival (PFS) and time to response (TTR) were assessed. Descriptive and discriminative analyses were performed to delineate tumor growth dynamics across various response profiles based on RECIST 1.1 criteria. Results The novel Gompertz model accurately described early tumor growth kinetics in 861 non-small cell lung cancer patients treated with immunotherapy. Lower growth rate (GR) and model parameter M were associated with longer progression-free survival (PFS) (HR=0.897 and 7.47x10^-7, respectively). Higher GR and parameter A correlated with shorter time to response (HR=0.575 and 0.696, respectively). Responders had significantly lower A (p=1.51e-53) and higher GR (p=0.4e-12) than non-responders. Non-durable stable disease patients had higher GR (p=0.0001) and parameter B (p=0.0002) compared to late responders. Early tumor growth parameters showed potential for predicting long-term outcomes and treatment response patterns.
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Affiliation(s)
- Mehdi Felfli
- Median Technologies, Imaging Lab, Valbonne, France
| | | | | | - Yan Liu
- Median Technologies, Imaging Lab, Valbonne, France
| | - Antoine Iannessi
- Median Technologies, Imaging Lab, Valbonne, France
- Centre Antoine Lacassagne, Radiology Department, Nice, France
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11
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D'Agostino V, Ponti F, Martella C, Miceli M, Sambri A, De Paolis M, Donati DM, Bianchi G, Longhi A, Crombé A, Spinnato P. Dimensional assessment on baseline MRI of soft-tissue sarcomas: longest diameter, sum and product of diameters, and volume-which is the best measurement method to predict patients' outcomes? LA RADIOLOGIA MEDICA 2024; 129:1876-1889. [PMID: 39424744 DOI: 10.1007/s11547-024-01895-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 10/05/2024] [Indexed: 10/21/2024]
Abstract
PURPOSE The longest diameter (LD) is a strong prognostic factor for patients with soft-tissue sarcoma (STS). Other dimensional assessments, such as the sum of diameters (SoD), product of diameters (PoD), and volume (3D-COG - proposed by the Children Oncology Group), can be rapidly performed; however, their prognostic values have never been compared to LD. Our goal was to investigate their performance in improving patients' prognostication for STS of the lower limbs. METHODS All consecutive adults managed with curative intent at our sarcoma reference center for a newly diagnosed STS of the lower limbs between 2000 and 2017, with pre-treatment MRI, were included in this retrospective study. Multivariable Cox regression models were trained to predict metastasis-free survival (MFS) in a Training cohort of 66.7% patients based on LD, PoD, SoD, or 3D-COG (and systematically including age, histologic grade, histotype, radiotherapy, chemotherapy, and surgical margins as covariables). The models were then compared on a validation cohort of 33.3% patients using concordance indices (c-index). The same approach was applied for overall survival (OS) and local relapse-free survival (LFS). Measurement reproducibility among three readers was evaluated with an intraclass correlation coefficient (ICC). RESULTS 382 patients were included in the survival modeling (72/253 [28.5%] metastatic relapses in Training and 36/129 [27.9%] metastatic relapses in Validation). Higher dimensions were associated with lower MFS (multivariable hazard ratio [HR] = 2.44 and P = 0.0018 for LD; HR = 1.88 and P = 0.0009 for PoD, HR = 1.52 and P = 0.0041 for SoD; and HR = 1.08 and P = 0.0195 for 3D-COG). Higher c-indices were obtained with PoD model in Training (c-index = 0.772) and Validation (c-index = 0.688), but they were not significantly higher than those obtained with LD model. None of the measurements was associated with LFS or OS. All measurements demonstrated excellent ICC (> 0.95). CONCLUSION Regarding its simplicity and good performance, LD appeared as the best metric to incorporate in prognostic models and nomograms for MFS.
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Affiliation(s)
- Valerio D'Agostino
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Via GC Pupilli 1, 40136, Bologna, Italy
| | - Federico Ponti
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Via GC Pupilli 1, 40136, Bologna, Italy
| | - Claudia Martella
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Via GC Pupilli 1, 40136, Bologna, Italy
| | - Marco Miceli
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Via GC Pupilli 1, 40136, Bologna, Italy
| | - Andrea Sambri
- Department of Orthopaedic Unit, IRCCS Azienda Ospedaliera Universitaria di Bologna, 40136, Bologna, Italy
| | - Massimiliano De Paolis
- Department of Orthopaedic Unit, IRCCS Azienda Ospedaliera Universitaria di Bologna, 40136, Bologna, Italy
| | - Davide Maria Donati
- Orthopaedic Oncology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136, Bologna, Italy
| | - Giuseppe Bianchi
- Orthopaedic Oncology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136, Bologna, Italy
| | - Alessandra Longhi
- Innovative Therapy Unit, Soft Tissue and Bone Sarcomas, IRCCS Istituto Ortopedico Rizzoli, Osteoncology Bologna, Italy
| | - Amandine Crombé
- Department of Radiology, Pellegrin Hospital, University of Bordeaux, 33076, Bordeaux, France
| | - Paolo Spinnato
- Diagnostic and Interventional Radiology, IRCCS Istituto Ortopedico Rizzoli, Via GC Pupilli 1, 40136, Bologna, Italy.
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12
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Xu Z, Jiang G, Dai J. Tumor therapeutics in the era of "RECIST": past, current insights, and future prospects. Oncol Rev 2024; 18:1435922. [PMID: 39493769 PMCID: PMC11527623 DOI: 10.3389/or.2024.1435922] [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: 05/21/2024] [Accepted: 08/30/2024] [Indexed: 11/05/2024] Open
Abstract
In recent years, advancements in medical treatment and imaging technologies have revolutionized the assessment of tumor response. However, the Response Evaluation Criteria in Solid Tumors (RECIST) has long been established as the gold standard for evaluating tumor treatment. As treatment modalities evolve, the need for continuous refinement and adaptation of RECIST becomes increasingly apparent. This review explores the historical evolution, current applications, limitations, and future directions of RECIST. It discusses the challenges of distinguishing true progression from pseudo-progression in ICIs (immune checkpoint inhibitors), the integration of advanced imaging tools, and the necessity for RECIST criteria tailored to specific therapies like neoadjuvant treatments. The review highlights the ongoing efforts to enhance RECIST's accuracy and reliability in clinical decision-making and the potential for developing new standards to better evaluate treatment efficacy in the rapidly evolving landscape of oncology.
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Affiliation(s)
| | - Gening Jiang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jie Dai
- *Correspondence: Gening Jiang, ; Jie Dai,
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13
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Emens LA, Romero PJ, Anderson AC, Bruno TC, Capitini CM, Collyar D, Gulley JL, Hwu P, Posey AD, Silk AW, Wargo JA. Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision. J Immunother Cancer 2024; 12:e009063. [PMID: 38901879 PMCID: PMC11191773 DOI: 10.1136/jitc-2024-009063] [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] [Accepted: 04/24/2024] [Indexed: 06/22/2024] Open
Abstract
Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor microenvironment. With this rapid clinical and scientific progress, the field of cancer immunotherapy is currently at a critical inflection point, with potential for exponential growth over the next decade. Recognizing this, the Society for Immunotherapy of Cancer convened a diverse group of experts in cancer immunotherapy representing academia, the pharmaceutical and biotechnology industries, patient advocacy, and the regulatory community to identify current opportunities and challenges with the goal of prioritizing areas with the highest potential for clinical impact. The consensus group identified seven high-priority areas of current opportunity for the field: mechanisms of antitumor activity and toxicity; mechanisms of drug resistance; biomarkers and biospecimens; unique aspects of novel therapeutics; host and environmental interactions; premalignant immunity, immune interception, and immunoprevention; and clinical trial design, endpoints, and conduct. Additionally, potential roadblocks to progress were discussed, and several topics were identified as cross-cutting tools for optimization, each with potential to impact multiple scientific priority areas. These cross-cutting tools include preclinical models, data curation and sharing, biopsies and biospecimens, diversification of funding sources, definitions and standards, and patient engagement. Finally, three key guiding principles were identified that will both optimize and maximize progress in the field. These include engaging the patient community; cultivating diversity, equity, inclusion, and accessibility; and leveraging the power of artificial intelligence to accelerate progress. Here, we present the outcomes of these discussions as a strategic vision to galvanize the field for the next decade of exponential progress in cancer immunotherapy.
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Affiliation(s)
| | | | - Ana Carrizosa Anderson
- The Gene Lay Institute of Immunology and Inflammation, Ann Romney Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Tullia C Bruno
- Department of Immunology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Christian M Capitini
- Department of Pediatrics and Carbone Cancer Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Deborah Collyar
- Patient Advocates in Research (PAIR), Danville, California, USA
| | - James L Gulley
- Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | | | - Avery D Posey
- Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Ann W Silk
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
| | - Jennifer A Wargo
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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14
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Ghodsi A, Hicks RJ, Iravani A. PET/Computed Tomography Transformation of Oncology: Immunotherapy Assessment. PET Clin 2024; 19:291-306. [PMID: 38199917 DOI: 10.1016/j.cpet.2023.12.012] [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: 01/12/2024]
Abstract
Immunotherapy approaches have changed the treatment landscape in a variety of malignancies with a high anti-tumor response. Immunotherapy may be associated with novel response and progression patterns that pose a substantial challenge to the conventional criteria for assessing treatment response, including response evaluation criteria in solid tumors (RECIST) 1.1. In addition to the morphologic details provided by computed tomography (CT) and MRI, hybrid molecular imaging emerges as a comprehensive imaging modality with the capacity to interrogate pathophysiological mechanisms like glucose metabolism. This review highlights the current status of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in prognostication, response monitoring, and identifying immune-related adverse events. Furthermore, it investigates the potential role of novel immuno-PET tracers that could complement the utilization of 18F-FDG PET/CT by imaging the specific pathways involved in immunotherapeutic strategies.
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Affiliation(s)
- Alireza Ghodsi
- Department of Radiology, University of Washington, 1144 Eastlake Avenue East, Seattle, WA 98109, USA
| | - Rodney J Hicks
- Department of Medicine, St Vincent's Hospital, The University of Melbourne, Australia; Department of Medicine, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, Australia; The Melbourne Theranostic Innovation Centre, North Melbourne, Australia
| | - Amir Iravani
- Department of Radiology, University of Washington, 1144 Eastlake Avenue East, Seattle, WA 98109, USA.
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15
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Farah C, Mignion L, Jordan BF. Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma. Int J Mol Sci 2024; 25:1725. [PMID: 38339003 PMCID: PMC10855758 DOI: 10.3390/ijms25031725] [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: 12/21/2023] [Revised: 01/26/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
There is currently no consensus to determine which advanced melanoma patients will benefit from targeted therapy, immunotherapy, or a combination of both, highlighting the critical need to identify early-response biomarkers to advanced melanoma therapy. The goal of this review is to provide scientific rationale to highlight the potential role of metabolic imaging to assess response to targeted and/or immune therapy in melanoma cancer. For that purpose, a brief overview of current melanoma treatments is provided. Then, current knowledge with respect to melanoma metabolism is described with an emphasis on major crosstalks between melanoma cell metabolism and signaling pathways involved in BRAF-targeted therapy as well as in immune checkpoint inhibition therapies. Finally, preclinical and clinical studies using metabolic imaging and/or profiling to assess response to melanoma treatment are summarized with a particular focus on PET (Positron Emission Tomography) imaging and 13C-MRS (Magnetic Resonance Spectroscopy) methods.
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Affiliation(s)
- Chantale Farah
- Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium;
| | - Lionel Mignion
- Nuclear and Electron Spin Technologies (NEST) Platform, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium;
| | - Bénédicte F. Jordan
- Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium;
- Nuclear and Electron Spin Technologies (NEST) Platform, Louvain Drug Research Institute (LDRI), Université Catholique de Louvain (UCLouvain), B-1200 Brussels, Belgium;
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16
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Mathew M, Nguyen NT, Bhutia YD, Sivaprakasam S, Ganapathy V. Metabolic Signature of Warburg Effect in Cancer: An Effective and Obligatory Interplay between Nutrient Transporters and Catabolic/Anabolic Pathways to Promote Tumor Growth. Cancers (Basel) 2024; 16:504. [PMID: 38339256 PMCID: PMC10854907 DOI: 10.3390/cancers16030504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Revised: 01/19/2024] [Accepted: 01/22/2024] [Indexed: 02/12/2024] Open
Abstract
Aerobic glycolysis in cancer cells, originally observed by Warburg 100 years ago, which involves the production of lactate as the end product of glucose breakdown even in the presence of adequate oxygen, is the foundation for the current interest in the cancer-cell-specific reprograming of metabolic pathways. The renewed interest in cancer cell metabolism has now gone well beyond the original Warburg effect related to glycolysis to other metabolic pathways that include amino acid metabolism, one-carbon metabolism, the pentose phosphate pathway, nucleotide synthesis, antioxidant machinery, etc. Since glucose and amino acids constitute the primary nutrients that fuel the altered metabolic pathways in cancer cells, the transporters that mediate the transfer of these nutrients and their metabolites not only across the plasma membrane but also across the mitochondrial and lysosomal membranes have become an integral component of the expansion of the Warburg effect. In this review, we focus on the interplay between these transporters and metabolic pathways that facilitates metabolic reprogramming, which has become a hallmark of cancer cells. The beneficial outcome of this recent understanding of the unique metabolic signature surrounding the Warburg effect is the identification of novel drug targets for the development of a new generation of therapeutics to treat cancer.
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Affiliation(s)
| | | | | | | | - Vadivel Ganapathy
- Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; (M.M.); (N.T.N.); (Y.D.B.); (S.S.)
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17
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Roh YH, Park JE, Kang S, Yoon S, Kim SW, Kim HS. Prognostic value of MRI volumetric parameters in non-small cell lung cancer patients after immune checkpoint inhibitor therapy: comparison with response assessment criteria. Cancer Imaging 2023; 23:102. [PMID: 37875970 PMCID: PMC10594817 DOI: 10.1186/s40644-023-00624-0] [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: 07/23/2023] [Accepted: 10/16/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Accurate response parameters are important for patients with brain metastasis (BM) undergoing clinical trials using immunotherapy, considering poorly defined enhancement and variable responses. This study investigated MRI-based surrogate endpoints for patients with BM receiving immunotherapy. METHODS Sixty-three non-small cell lung cancer patients with BM who received immune checkpoint inhibitors and underwent MRI were included. Tumor diameters were measured using a modification of the RECIST 1.1 (mRECIST), RANO-BM, and iRANO adjusted for BM (iRANO-BM). Tumor volumes were segmented on 3D contrast-enhanced T1-weighted imaging. Differences between the sum of the longest diameter (SLD) or total tumor volume at baseline and the corresponding measurement at time of the best overall response were calculated as "changes in SLDs" (for each set of criteria) and "change in volumetry," respectively. Overall response rate (ORR), progressive disease (PD) assignment, and progression-free survival (PFS) were compared among the criteria. The prediction of overall survival (OS) was compared between diameter-based and volumetric change using Cox proportional hazards regression analysis. RESULTS The mRECIST showed higher ORR (30.1% vs. both 17.5%) and PD assignment (34.9% vs. 25.4% [RANO-BM] and 19% [iRANO-BM]). The iRANO-BM had a longer median PFS (13.7 months) than RANO-BM (9.53 months) and mRECIST (7.73 months, P = 0.003). The change in volumetry was a significant predictor of OS (HR = 5.87, 95% CI: 1.46-23.64, P = 0.013). None of the changes in SLDs, as determined by RANO-BM or iRANO-BM, were significant predictors of OS, except for the mRECIST, which exhibited a weak association with OS. CONCLUSION Quantitative volume measurement may be an accurate surrogate endpoint for OS in patients with BM undergoing immunotherapy, especially considering the challenges of multiplicity and the heterogeneity of sub-centimeter size responses.
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Affiliation(s)
- Yun Hwa Roh
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Ji Eun Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
| | - Sora Kang
- Division of Hematology and Oncology, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Shinkyo Yoon
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang-We Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ho Sung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
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18
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Zacherl MJ, Simenhandra A, Lindner M, Bartenstein P, Todica A, Boening G, Fischer M. The assessment of left ventricular volume and function in gated small animal 18F-FDG PET/CT imaging: a comparative study of three commercially available software tools. EJNMMI Res 2023; 13:75. [PMID: 37572238 PMCID: PMC10423195 DOI: 10.1186/s13550-023-01026-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 08/06/2023] [Indexed: 08/14/2023] Open
Abstract
BACKGROUND Several software tools have been developed for gated PET imaging that use distinct algorithms to analyze tracer uptake, myocardial perfusion, and left ventricle volumes and function. Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG PET/CT imaging in mice by three commercially available software tools: PMOD, MIM, and QGS. METHODS AND RESULTS Healthy mice underwent ECG-gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland-Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = -0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment. CONCLUSIONS All three commercially available software tools are feasible in small animal cardiac volume assessment in gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research.
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Affiliation(s)
- Mathias J Zacherl
- Department of Nuclear Medicine, Ludwig-Maximilians-University, 81377, Munich, Germany
| | - Agus Simenhandra
- Department of Cardiology, Medical Clinic and Polyclinic I, University Hospital Munich, Marchioninistraße 15, 81377, Munich, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336802, Munich, Germany
| | - Magdalena Lindner
- Department of Nuclear Medicine, Ludwig-Maximilians-University, 81377, Munich, Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine, Ludwig-Maximilians-University, 81377, Munich, Germany
| | - Andrei Todica
- Department of Nuclear Medicine, Ludwig-Maximilians-University, 81377, Munich, Germany
| | - Guido Boening
- Department of Nuclear Medicine, Ludwig-Maximilians-University, 81377, Munich, Germany
| | - Maximilian Fischer
- Department of Cardiology, Medical Clinic and Polyclinic I, University Hospital Munich, Marchioninistraße 15, 81377, Munich, Germany.
- DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80336802, Munich, Germany.
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19
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Kciuk M, Yahya EB, Mohamed Ibrahim Mohamed M, Rashid S, Iqbal MO, Kontek R, Abdulsamad MA, Allaq AA. Recent Advances in Molecular Mechanisms of Cancer Immunotherapy. Cancers (Basel) 2023; 15:2721. [PMID: 37345057 DOI: 10.3390/cancers15102721] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 06/23/2023] Open
Abstract
Cancer is among the current leading causes of death worldwide, despite the novel advances that have been made toward its treatment, it is still considered a major public health concern. Considering both the serious impact of cancer on public health and the significant side effects and complications of conventional therapeutic options, the current strategies towards targeted cancer therapy must be enhanced to avoid undesired toxicity. Cancer immunotherapy has become preferable among researchers in recent years compared to conventional therapeutic options, such as chemotherapy, surgery, and radiotherapy. The understanding of how to control immune checkpoints, develop therapeutic cancer vaccines, genetically modify immune cells as well as enhance the activation of antitumor immune response led to the development of novel cancer treatments. In this review, we address recent advances in cancer immunotherapy molecular mechanisms. Different immunotherapeutic approaches are critically discussed, focusing on the challenges, potential risks, and prospects involving their use.
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Affiliation(s)
- Mateusz Kciuk
- Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
- Doctoral School of Exact and Natural Sciences, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
| | - Esam Bashir Yahya
- Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, Penang 11800, Malaysia
| | | | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Muhammad Omer Iqbal
- Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
| | - Renata Kontek
- Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha Street 12/16, 90-237 Lodz, Poland
| | - Muhanad A Abdulsamad
- Department of Molecular Biology, Faculty of Science, Sabratha University, Sabratha 00218, Libya
| | - Abdulmutalib A Allaq
- Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Malaysia
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20
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Vaz SC, Graff SL, Ferreira AR, Debiasi M, de Geus-Oei LF. PET/CT in Patients with Breast Cancer Treated with Immunotherapy. Cancers (Basel) 2023; 15:cancers15092620. [PMID: 37174086 PMCID: PMC10177398 DOI: 10.3390/cancers15092620] [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: 03/29/2023] [Revised: 04/27/2023] [Accepted: 05/02/2023] [Indexed: 05/15/2023] Open
Abstract
Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers.
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Affiliation(s)
- Sofia C Vaz
- Nuclear Medicine-Radiopharmacology, Champalimaud Center for the Unkown, Champalimaud Foundation, 1400-038 Lisbon, Portugal
- Department of Radiology, Leiden University Medical Center, P.O. Box 9600-2300 RC Leiden, The Netherlands
| | - Stephanie L Graff
- Division of Hematology/Oncology, Lifespan Cancer Institute, Providence, RI 02903, USA
- Legorreta Cancer Center, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA
| | - Arlindo R Ferreira
- Católica Medical School, Universidade Católica Portuguesa, 2635-631 Lisbon, Portugal
| | - Márcio Debiasi
- Breast Cancer Unit, Champalimaud Center for the Unkown, Champalimaud Foundation, 1400-038 Lisbon, Portugal
| | - Lioe-Fee de Geus-Oei
- Department of Radiology, Leiden University Medical Center, P.O. Box 9600-2300 RC Leiden, The Netherlands
- Biomedical Photonic Imaging Group, University of Twente, P.O. Box 217-7500 AE Enschede, The Netherlands
- Department of radiation Science & Technology, Delft University of Technology, P.O. Postbus 5 2600 AA Delft, The Netherlands
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21
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Berz AM, Boughdad S, Vietti-Violi N, Digklia A, Dromain C, Dunet V, Duran R. Imaging assessment of toxicity related to immune checkpoint inhibitors. Front Immunol 2023; 14:1133207. [PMID: 36911692 PMCID: PMC9995973 DOI: 10.3389/fimmu.2023.1133207] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 02/10/2023] [Indexed: 02/25/2023] Open
Abstract
In recent years, a wide range of cancer immunotherapies have been developed and have become increasingly important in cancer treatment across multiple oncologic diseases. In particular, immune checkpoint inhibitors (ICIs) offer promising options to improve patient outcomes. However, a major limitation of these treatments consists in the development of immune-related adverse events (irAEs) occurring in potentially any organ system and affecting up to 76% of the patients. The most frequent toxicities involve the skin, gastrointestinal tract, and endocrine system. Although mostly manageable, potentially life-threatening events, particularly due to neuro-, cardiac, and pulmonary toxicity, occur in up to 30% and 55% of the patients treated with ICI-monotherapy or -combination therapy, respectively. Imaging, in particular computed tomography (CT), magnetic resonance imaging (MRI), and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT), plays an important role in the detection and characterization of these irAEs. In some patients, irAEs can even be detected on imaging before the onset of clinical symptoms. In this context, it is particularly important to distinguish irAEs from true disease progression and specific immunotherapy related response patterns, such as pseudoprogression. In addition, there are irAEs which might be easily confused with other pathologies such as infection or metastasis. However, many imaging findings, such as in immune-related pneumonitis, are nonspecific. Thus, accurate diagnosis may be delayed underling the importance for adequate imaging features characterization in the appropriate clinical setting in order to provide timely and efficient patient management. 18F-FDG-PET/CT and radiomics have demonstrated to reliably detect these toxicities and potentially have predictive value for identifying patients at risk of developing irAEs. The purpose of this article is to provide a review of the main immunotherapy-related toxicities and discuss their characteristics on imaging.
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Affiliation(s)
- Antonia M Berz
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.,Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt- Universität zu Berlin, Berlin, Germany
| | - Sarah Boughdad
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Naïk Vietti-Violi
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Antonia Digklia
- Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Clarisse Dromain
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Vincent Dunet
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Rafael Duran
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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