Pub Date : 2026-03-05DOI: 10.1001/jamaoncol.2025.6339
Kristina Jenei,Richard Sullivan
{"title":"Implementing Cancer Medicines on the WHO Model Lists of Essential Medicines Into National Systems.","authors":"Kristina Jenei,Richard Sullivan","doi":"10.1001/jamaoncol.2025.6339","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6339","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"198 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1001/jamaoncol.2026.0153
Vivek Subbiah
{"title":"Delivering Precision Oncology at Scale-Infrastructure, Evidence, and the Path Forward.","authors":"Vivek Subbiah","doi":"10.1001/jamaoncol.2026.0153","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.0153","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"61 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1001/jamaoncol.2025.6321
Delphine Maret,Joel B Epstein,Emmanuelle Vigarios
{"title":"Taking Care of Your Mouth During Cancer Treatment.","authors":"Delphine Maret,Joel B Epstein,Emmanuelle Vigarios","doi":"10.1001/jamaoncol.2025.6321","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6321","url":null,"abstract":"","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"17 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147351202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1001/jamaoncol.2026.0127
Frank P Lin,Subotheni Thavaneswaran,John P Grady,Christine E Napier,Maya Kansara,Lucille Sebastian,Damien Kee,Jayesh Desai,Milita Zaheed,Sarah Chinchen,Samantha R Oakes,James Blackburn,Hamish S Scott,Anthony Glover,Stephen B Fox,David Goldstein,Paul Leo,Benhur Amanuel,Antony Mersiades,Michael Millward,Michael P Brown,Michail Charakidis,Adrian M J Pokorny,Paul Craft,David Espinoza,Peter Grimison,Rosemary Harrup,Anthony M Joshua,Ken O'Byrne,Chee Khoon Lee,Mark J Cowley,Mandy L Ballinger,John Simes,David M Thomas,
ImportanceThe clinical utility of matching therapies to genomic biomarkers based on varying levels of evidence remains uncertain, particularly for patients with rare and refractory cancers.ObjectiveTo assess whether a tiered, evidence-based framework for matching genomic biomarkers to therapies is associated with differential overall survival in patients with advanced solid tumors.Design, Setting, and ParticipantsThis multicenter cohort study was conducted within the Molecular Screening and Therapeutic program, a nationwide precision oncology program in Australia. Patients aged 18 years and older with advanced, refractory solid tumors and adequate Eastern Cooperative Oncology Group Performance Status were enrolled from June 2016 to December 2021, with follow-up through July 2022. Data were analyzed from July 2022 to July 2024.ExposuresSystemic therapy following comprehensive genomic profiling. Therapies were classified as matched or unmatched using the TOPOGRAPH (Therapy-Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals) knowledge base, which stratifies biomarker-drug pairs by level of evidence (tiers 1-3A, prospective trial evidence; tiers 3B/4, investigational/repurposed).Main Outcome and MeasuresThe primary outcome was overall survival from date of molecular profiling results. The hypothesis was tested using a time-dependent multivariable Cox proportional hazards model, adjusted for age, Eastern Cooperative Oncology Group Performance Status, cancer type, prior therapy, and prior receipt of matched therapy.ResultsOf 3383 patients (mean [SD] age 57.1 [14.3] years; 1792 [53.0%] female), 1270 (37.5%) had a clinically active (tiers 1-3A) biomarker. Among patients with a tier 1 to 3A biomarker receiving treatment, those receiving matched therapy had a longer median overall survival than those receiving unmatched therapy (21.2 months [95% CI, 17.1-26.8 months] vs 12.8 months [95% CI, 11.7-13.9 months]; adjusted hazard ratio [aHR], 0.60; 95% CI, 0.44-0.82; P = .001). In contrast, among patients receiving therapy matched to investigational evidence (tiers 3B/4), there was not an associated survival benefit compared with unmatched therapy (14.5 months [95% CI, 12.6-18.4 months] vs 12.8 months [95% CI, 12.0-14.7 months]; aHR, 1.04; 95% CI, 0.84-1.29; P = .71). Patients who received therapies repurposed from other cancer types based solely on a biomarker and lacking direct evidence (tier 3B) did not experience longer survival compared with those receiving unmatched therapy (13.6 months [95% CI, 8.0-16.8 months] vs 12.5 months [95% CI, 11.3-13.5 months]; aHR, 1.40; 95% CI, 1.00-1.96; P = .047).Conclusions and RelevanceIn this cohort study of patients with advanced solid tumors, matching therapies to genomic biomarkers was associated with improved survival only when supported by prospective clinical trial evidence. These findings support using an evidence-based framework to prioritize genomically guided therapies.
{"title":"Genomic Therapy Matching in Rare and Refractory Cancers.","authors":"Frank P Lin,Subotheni Thavaneswaran,John P Grady,Christine E Napier,Maya Kansara,Lucille Sebastian,Damien Kee,Jayesh Desai,Milita Zaheed,Sarah Chinchen,Samantha R Oakes,James Blackburn,Hamish S Scott,Anthony Glover,Stephen B Fox,David Goldstein,Paul Leo,Benhur Amanuel,Antony Mersiades,Michael Millward,Michael P Brown,Michail Charakidis,Adrian M J Pokorny,Paul Craft,David Espinoza,Peter Grimison,Rosemary Harrup,Anthony M Joshua,Ken O'Byrne,Chee Khoon Lee,Mark J Cowley,Mandy L Ballinger,John Simes,David M Thomas, ","doi":"10.1001/jamaoncol.2026.0127","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.0127","url":null,"abstract":"ImportanceThe clinical utility of matching therapies to genomic biomarkers based on varying levels of evidence remains uncertain, particularly for patients with rare and refractory cancers.ObjectiveTo assess whether a tiered, evidence-based framework for matching genomic biomarkers to therapies is associated with differential overall survival in patients with advanced solid tumors.Design, Setting, and ParticipantsThis multicenter cohort study was conducted within the Molecular Screening and Therapeutic program, a nationwide precision oncology program in Australia. Patients aged 18 years and older with advanced, refractory solid tumors and adequate Eastern Cooperative Oncology Group Performance Status were enrolled from June 2016 to December 2021, with follow-up through July 2022. Data were analyzed from July 2022 to July 2024.ExposuresSystemic therapy following comprehensive genomic profiling. Therapies were classified as matched or unmatched using the TOPOGRAPH (Therapy-Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals) knowledge base, which stratifies biomarker-drug pairs by level of evidence (tiers 1-3A, prospective trial evidence; tiers 3B/4, investigational/repurposed).Main Outcome and MeasuresThe primary outcome was overall survival from date of molecular profiling results. The hypothesis was tested using a time-dependent multivariable Cox proportional hazards model, adjusted for age, Eastern Cooperative Oncology Group Performance Status, cancer type, prior therapy, and prior receipt of matched therapy.ResultsOf 3383 patients (mean [SD] age 57.1 [14.3] years; 1792 [53.0%] female), 1270 (37.5%) had a clinically active (tiers 1-3A) biomarker. Among patients with a tier 1 to 3A biomarker receiving treatment, those receiving matched therapy had a longer median overall survival than those receiving unmatched therapy (21.2 months [95% CI, 17.1-26.8 months] vs 12.8 months [95% CI, 11.7-13.9 months]; adjusted hazard ratio [aHR], 0.60; 95% CI, 0.44-0.82; P = .001). In contrast, among patients receiving therapy matched to investigational evidence (tiers 3B/4), there was not an associated survival benefit compared with unmatched therapy (14.5 months [95% CI, 12.6-18.4 months] vs 12.8 months [95% CI, 12.0-14.7 months]; aHR, 1.04; 95% CI, 0.84-1.29; P = .71). Patients who received therapies repurposed from other cancer types based solely on a biomarker and lacking direct evidence (tier 3B) did not experience longer survival compared with those receiving unmatched therapy (13.6 months [95% CI, 8.0-16.8 months] vs 12.5 months [95% CI, 11.3-13.5 months]; aHR, 1.40; 95% CI, 1.00-1.96; P = .047).Conclusions and RelevanceIn this cohort study of patients with advanced solid tumors, matching therapies to genomic biomarkers was associated with improved survival only when supported by prospective clinical trial evidence. These findings support using an evidence-based framework to prioritize genomically guided therapies.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"19 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-26DOI: 10.1001/jamaoncol.2025.6324
Omar Abughanimeh
This essay describes a turn of events that compelled a medical oncology fellow to learn to care for young patients with sarcoma and to rediscover why he chose medicine in the first place.
{"title":"Between Ambition and Duty—A Path That I Did Not Choose","authors":"Omar Abughanimeh","doi":"10.1001/jamaoncol.2025.6324","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6324","url":null,"abstract":"This essay describes a turn of events that compelled a medical oncology fellow to learn to care for young patients with sarcoma and to rediscover why he chose medicine in the first place.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"19 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147287123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Importance Nasopharyngeal carcinoma (NPC) is a major health concern in Asia, and treatment options for recurrent or metastatic disease are limited. Immunotherapy plus chemotherapy has shown promise, but long-term data are needed to guide first-line treatment. Objective To evaluate the 3-year efficacy and safety of tislelizumab plus chemotherapy vs placebo plus chemotherapy in participants with recurrent or metastatic NPC and explore potential biomarkers of treatment response. Design, Setting, and Participants The RATIONALE-309 trial was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Asia from April 2019 to December 2023. Treatment-naive adults with histologically or cytologically confirmed recurrent or metastatic NPC were included. Data were analyzed from December 2023 to January 2024. Interventions Participants were randomized 1:1 to receive tislelizumab, 200 mg, intravenously or placebo every 3 weeks, both with gemcitabine and cisplatin for 4 to 6 cycles. Participants in the placebo arm could cross over to tislelizumab monotherapy at disease progression. Main Outcomes and Measures The primary end point was progression-free survival (PFS) assessed by an independent review committee. The primary hypothesis (PFS superiority for tislelizumab vs placebo) was specified in the protocol prior to data collection. Secondary end points included overall survival (OS), PFS after next-line therapy, and safety. Results Of 263 included participants, 206 (78.3%) were male, and the median (range) age was 50 (23-74) years; the median (range) follow-up was 27.5 (0.1-53.0) months. A total of 131 were randomized to the tislelizumab group and 132 to the placebo group. Tislelizumab plus chemotherapy demonstrated improved PFS vs placebo plus chemotherapy (median PFS, 9.6 months [95% CI, 7.6-11.6] vs 7.4 months [95% CI, 5.6-7.6]; hazard ratio [HR], 0.53; 95% CI, 0.39-0.71). The median OS was 45.3 months (95% CI, 33.4 to not estimable) vs 31.8 months (95% CI, 25.0 to not estimable), respectively (HR, 0.73; 95% CI, 0.51-1.05). Rank-preserving structural failure time analysis (HR, 0.56; 95% CI, 0.27-1.19) and 2-stage crossover-adjusted analysis (HR, 0.62; 95% CI, 0.40-0.97) showed greater OS benefit. Treatment-emergent adverse events occurred in 133 of 133 participants (100%) in the tislelizumab arm and 129 of 130 participants (99.2%) in the placebo arm, with comparable grade 3 or higher adverse event rates. Immune-mediated adverse events were more frequent with tislelizumab (71 [53.4%] vs 49 [37.7%]) but mostly of grades 1 or 2. High B-cell gene expression was associated with greater OS benefit (HR, 0.41; 95% CI, 0.23-0.74). Conclusions and Relevance In this secondary analysis of the RATIONALE-309 randomized clinical trial, after 3 years of follow-up, tislelizumab plus chemotherapy provided sustained PFS and meaningful OS improvement vs placebo plus chemotherapy in recurrent or metastatic NPC, with an acceptable safety profile. Greater b
{"title":"First-Line Tislelizumab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Cancer","authors":"Yunpeng Yang, Chia-Jui Yen, Jianji Pan, Hui Wang, Shenhong Qu, Nianyong Chen, Xiaozhong Chen, Yan Sun, Xiaohui He, Chaosu Hu, Lizhu Lin, Yanjie Wu, Shuai Yuan, Chenqi Chen, Xingxing Xu, Xiaopeng Ma, Shiangjiin Leaw, Li Zhang, Wenfeng Fang","doi":"10.1001/jamaoncol.2026.0020","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.0020","url":null,"abstract":"Importance Nasopharyngeal carcinoma (NPC) is a major health concern in Asia, and treatment options for recurrent or metastatic disease are limited. Immunotherapy plus chemotherapy has shown promise, but long-term data are needed to guide first-line treatment. Objective To evaluate the 3-year efficacy and safety of tislelizumab plus chemotherapy vs placebo plus chemotherapy in participants with recurrent or metastatic NPC and explore potential biomarkers of treatment response. Design, Setting, and Participants The RATIONALE-309 trial was a double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Asia from April 2019 to December 2023. Treatment-naive adults with histologically or cytologically confirmed recurrent or metastatic NPC were included. Data were analyzed from December 2023 to January 2024. Interventions Participants were randomized 1:1 to receive tislelizumab, 200 mg, intravenously or placebo every 3 weeks, both with gemcitabine and cisplatin for 4 to 6 cycles. Participants in the placebo arm could cross over to tislelizumab monotherapy at disease progression. Main Outcomes and Measures The primary end point was progression-free survival (PFS) assessed by an independent review committee. The primary hypothesis (PFS superiority for tislelizumab vs placebo) was specified in the protocol prior to data collection. Secondary end points included overall survival (OS), PFS after next-line therapy, and safety. Results Of 263 included participants, 206 (78.3%) were male, and the median (range) age was 50 (23-74) years; the median (range) follow-up was 27.5 (0.1-53.0) months. A total of 131 were randomized to the tislelizumab group and 132 to the placebo group. Tislelizumab plus chemotherapy demonstrated improved PFS vs placebo plus chemotherapy (median PFS, 9.6 months [95% CI, 7.6-11.6] vs 7.4 months [95% CI, 5.6-7.6]; hazard ratio [HR], 0.53; 95% CI, 0.39-0.71). The median OS was 45.3 months (95% CI, 33.4 to not estimable) vs 31.8 months (95% CI, 25.0 to not estimable), respectively (HR, 0.73; 95% CI, 0.51-1.05). Rank-preserving structural failure time analysis (HR, 0.56; 95% CI, 0.27-1.19) and 2-stage crossover-adjusted analysis (HR, 0.62; 95% CI, 0.40-0.97) showed greater OS benefit. Treatment-emergent adverse events occurred in 133 of 133 participants (100%) in the tislelizumab arm and 129 of 130 participants (99.2%) in the placebo arm, with comparable grade 3 or higher adverse event rates. Immune-mediated adverse events were more frequent with tislelizumab (71 [53.4%] vs 49 [37.7%]) but mostly of grades 1 or 2. High B-cell gene expression was associated with greater OS benefit (HR, 0.41; 95% CI, 0.23-0.74). Conclusions and Relevance In this secondary analysis of the RATIONALE-309 randomized clinical trial, after 3 years of follow-up, tislelizumab plus chemotherapy provided sustained PFS and meaningful OS improvement vs placebo plus chemotherapy in recurrent or metastatic NPC, with an acceptable safety profile. Greater b","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"22 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147287120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-26DOI: 10.1001/jamaoncol.2026.0007
Andrea Napolitano, Heikki Joensuu, Sara Rothschild, Denisse Evans, Michael C. Heinrich, Thomas L. Sutton, Skye C. Mayo, Kjetil Boye, Johanna Falkenhorst, Axel Le Cesne, Peter Hohenberger, Piotr Rutkowski, Winan J. van Houdt, Neeltje Steeghs, Hans Gelderblom, Ingrid M. E. Desar, Maria A. Pantaleo, Toshiro Nishida, Peter Reichardt, Jean-Yves Blay, Neeta Somaiah, Elise F. Nassif Haddad, Giovanni Grignani, Giacomo G. Baldi, Sonja E. Steigen, Chiara Braconi, Bengt Nilsson, Arun S. Singh, Elena Fumagalli, Ferdinando C. M. Cananzi, Antoine Italiano, Mariella Spalato Ceruso, Antonella Brunello, Magnús K. Magnússon, Jon G. Jonasson, Gloria Marquina, Nadia Hindi, Claudia Cirilli, Massimo Federico, Valentina Fausti, Andrea Bordoni, Jozef Sufliarsky, Alessandro Mazzocca, Javier Martin-Broto, Alessandro Gronchi, Jonathan C. Trent, Paolo G. Casali, Sebastian Bauer, Robin L. Jones, Bruno Vincenzi
Importance Gastrointestinal stromal tumors (GISTs) harboring <jats:italic toggle="yes">KIT</jats:italic> exon 9 mutations represent a biologically distinct subgroup with reduced sensitivity to standard-dose imatinib in the advanced setting. The benefit of adjuvant imatinib in this population remains uncertain. Objective To evaluate the association between adjuvant imatinib and recurrence-free survival (RFS) and overall survival (OS) in patients with resected GISTs with <jats:italic toggle="yes">KIT</jats:italic> exon 9 mutations. Design, Setting, and Participants This international, multicenter cohort study included patients with localized, molecularly confirmed GISTs with <jats:italic toggle="yes">KIT</jats:italic> exon 9 mutations who underwent curative-intent surgery between January 1990 and July 2022 at 35 referral centers in Europe, the US, and Japan, or were registered in the Life Raft Group database. The analysis took place between January 2025 and November 2025. Exposures Adjuvant imatinib initiated after curative surgery, modeled as a time-dependent covariate to account for immortal time bias. Main Outcomes and Measures The primary end points were RFS (time from surgery to recurrence or death) and OS (time from surgery to death) in the full cohort and in the high-risk subgroup defined by modified National Institutes of Health (mNIH) criteria. Multivariable Cox regression models included established prognostic covariates and cluster-robust standard errors. Overlap weighting (OW) based on propensity scores was used as a causal inference model. Secondary analyses evaluated 400 mg/d vs 800 mg/d dosing in the mNIH high-risk subgroup. Results A total of 367 patients were included, 187 (51.0%) male and 180 (49%) female, with a mean (SD) age of 56 (13) years. Among these, 91 (24.8%) were observed and 276 (75.2%) received adjuvant imatinib (median [IQR] duration, 27.3 [13.5-36.0] months; 116 [42.0%] treated ≥3 years). Consistent with a cytostatic activity, adjuvant imatinib in the full cohort was associated with a reduced early hazard of recurrence or death (HR, 0.19; 95% CI, 0.10-0.36), with attenuation over time (time-interaction hazard ratio [HR], 1.85 per log-year). Treatment was also associated with improved OS (HR, 0.37; 95% CI, 0.17-0.83). Similar results were obtained when limiting the analysis to patients with mNIH high-risk disease. OW models and sensitivity analyses confirmed similar associations with RFS and OS. Among 257 patients with mNIH high-risk disease receiving imatinib, no significant difference was observed between 400 mg/d and 800 mg/d dosing. Conclusion and relevance In this large international cohort study of resected GISTs with <jats:italic toggle="yes">KIT</jats:italic> exon 9 mutations, adjuvant imatinib was independently associated with delayed recurrence and improved survival. These findings support the use of adjuvant imatinib in mNIH high-risk GISTs with <jats:italic toggle="yes">KIT</jats:italic> exon 9 mutations a
{"title":"Adjuvant Imatinib or Observation in Patients With Gastrointestinal Stromal Tumors With KIT Exon 9 Mutations","authors":"Andrea Napolitano, Heikki Joensuu, Sara Rothschild, Denisse Evans, Michael C. Heinrich, Thomas L. Sutton, Skye C. Mayo, Kjetil Boye, Johanna Falkenhorst, Axel Le Cesne, Peter Hohenberger, Piotr Rutkowski, Winan J. van Houdt, Neeltje Steeghs, Hans Gelderblom, Ingrid M. E. Desar, Maria A. Pantaleo, Toshiro Nishida, Peter Reichardt, Jean-Yves Blay, Neeta Somaiah, Elise F. Nassif Haddad, Giovanni Grignani, Giacomo G. Baldi, Sonja E. Steigen, Chiara Braconi, Bengt Nilsson, Arun S. Singh, Elena Fumagalli, Ferdinando C. M. Cananzi, Antoine Italiano, Mariella Spalato Ceruso, Antonella Brunello, Magnús K. Magnússon, Jon G. Jonasson, Gloria Marquina, Nadia Hindi, Claudia Cirilli, Massimo Federico, Valentina Fausti, Andrea Bordoni, Jozef Sufliarsky, Alessandro Mazzocca, Javier Martin-Broto, Alessandro Gronchi, Jonathan C. Trent, Paolo G. Casali, Sebastian Bauer, Robin L. Jones, Bruno Vincenzi","doi":"10.1001/jamaoncol.2026.0007","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.0007","url":null,"abstract":"Importance Gastrointestinal stromal tumors (GISTs) harboring <jats:italic toggle=\"yes\">KIT</jats:italic> exon 9 mutations represent a biologically distinct subgroup with reduced sensitivity to standard-dose imatinib in the advanced setting. The benefit of adjuvant imatinib in this population remains uncertain. Objective To evaluate the association between adjuvant imatinib and recurrence-free survival (RFS) and overall survival (OS) in patients with resected GISTs with <jats:italic toggle=\"yes\">KIT</jats:italic> exon 9 mutations. Design, Setting, and Participants This international, multicenter cohort study included patients with localized, molecularly confirmed GISTs with <jats:italic toggle=\"yes\">KIT</jats:italic> exon 9 mutations who underwent curative-intent surgery between January 1990 and July 2022 at 35 referral centers in Europe, the US, and Japan, or were registered in the Life Raft Group database. The analysis took place between January 2025 and November 2025. Exposures Adjuvant imatinib initiated after curative surgery, modeled as a time-dependent covariate to account for immortal time bias. Main Outcomes and Measures The primary end points were RFS (time from surgery to recurrence or death) and OS (time from surgery to death) in the full cohort and in the high-risk subgroup defined by modified National Institutes of Health (mNIH) criteria. Multivariable Cox regression models included established prognostic covariates and cluster-robust standard errors. Overlap weighting (OW) based on propensity scores was used as a causal inference model. Secondary analyses evaluated 400 mg/d vs 800 mg/d dosing in the mNIH high-risk subgroup. Results A total of 367 patients were included, 187 (51.0%) male and 180 (49%) female, with a mean (SD) age of 56 (13) years. Among these, 91 (24.8%) were observed and 276 (75.2%) received adjuvant imatinib (median [IQR] duration, 27.3 [13.5-36.0] months; 116 [42.0%] treated ≥3 years). Consistent with a cytostatic activity, adjuvant imatinib in the full cohort was associated with a reduced early hazard of recurrence or death (HR, 0.19; 95% CI, 0.10-0.36), with attenuation over time (time-interaction hazard ratio [HR], 1.85 per log-year). Treatment was also associated with improved OS (HR, 0.37; 95% CI, 0.17-0.83). Similar results were obtained when limiting the analysis to patients with mNIH high-risk disease. OW models and sensitivity analyses confirmed similar associations with RFS and OS. Among 257 patients with mNIH high-risk disease receiving imatinib, no significant difference was observed between 400 mg/d and 800 mg/d dosing. Conclusion and relevance In this large international cohort study of resected GISTs with <jats:italic toggle=\"yes\">KIT</jats:italic> exon 9 mutations, adjuvant imatinib was independently associated with delayed recurrence and improved survival. These findings support the use of adjuvant imatinib in mNIH high-risk GISTs with <jats:italic toggle=\"yes\">KIT</jats:italic> exon 9 mutations a","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147287122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-26DOI: 10.1001/jamaoncol.2026.0042
Mazyar Shadman, Michael LeBlanc, Lisa Rimsza, John P. Leonard, Sonali M. Smith, Hongli Li, Jonathan W. Friedberg
Importance Follicular lymphoma (FL) has historically been regarded as incurable, with patients experiencing late relapses after initial chemoimmunotherapy treatment. Objective To provide 15-year follow-up data from the SWOG S0016 trial that evaluated the potential for long-term remission and cure following chemoimmunotherapy with cyclophosphamide, hydroxydaunorubicin/doxorubicin, oncovin, and prednisone/prednisolone (CHOP)–based regimens. Design, Setting, and Participants This multicenter, intergroup study was conducted at academic and community practice locations throughout the US and enrolled patients with untreated, advanced-stage FL. Cure modeling, which involves estimating the proportion of patients cured of the disease, was conducted by incorporating background mortality rates to estimate the proportion of patients cured of FL during the S0016 trial. Patients were enrolled between May 2001 and October 2008 and followed up for a median (IQR) of 15.5 (13.6-16.9) years. The 15-year analysis was conducted in June 2025. Interventions Patients were randomized to receive either rituximab plus CHOP (R-CHOP) or CHOP followed by radioimmunotherapy (CHOP-RIT). Main Outcomes The main outcomes were 15-year progression free survival (PFS) and overall survival (OS). Secondary outcomes included cure modeling. Results A total of 531 eligible patients (242 female patients [46%]; median [IQR] age, 53 [45-61] years) were included in the final analysis (267 [50%] received R-CHOP and 264 [50%] CHOP-RIT). The overall 15-year OS was 70%, with no significant difference between treatment arms, and the 15-year PFS was 40% (95% CI, 36.0%-44.7%). CHOP-RIT demonstrated superior 15-year PFS (47% vs 34%; P = .004) compared with R-CHOP. Cure modeling estimated an overall cure rate of 42%, with the highest cure rates observed in patients with low Follicular Lymphoma International Prognostic Index scores and normal β2 microglobulin levels. The rate of relapse declined substantially over time, from 6.8% during the first 5 years to 0.6% between 15 to 20 years. Conclusions and Relevance The results of this secondary analysis suggest that a subset of patients with advanced-stage FL can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time. This finding represents a paradigm shift in the understanding of and approach to FL, with implications for initial patient discussions and future research strategies. Trial Registration ClinicalTrials.gov Identifier: NCT00006721
滤泡性淋巴瘤（FL）历来被认为是无法治愈的，患者在最初的化学免疫治疗后会出现晚期复发。目的提供SWOG S0016试验的15年随访数据，该试验评估了环磷酰胺、羟柔红霉素/阿霉素、oncovin和泼尼松/泼尼松（CHOP）为基础的化疗免疫治疗后长期缓解和治愈的潜力。这项多中心、组间研究在美国各地的学术和社区实践地点进行，纳入了未经治疗的晚期FL患者。治愈模型包括估计疾病治愈的患者比例，通过合并背景死亡率来估计S0016试验期间FL治愈的患者比例。患者于2001年5月至2008年10月入组，随访时间中位数（IQR）为15.5（13.6-16.9）年。这项为期15年的分析是在2025年6月进行的。干预措施患者随机接受利妥昔单抗加CHOP （R-CHOP）或CHOP后放射免疫治疗（CHOP- rit）。主要结局主要结局为15年无进展生存期（PFS）和总生存期（OS）。次要结局包括治愈模型。结果共纳入531例符合条件的患者，其中女性242例（46%），中位年龄53岁（45-61岁），其中接受R-CHOP的267例（50%），接受CHOP-RIT的264例（50%）。总体15年OS为70%，治疗组间无显著差异，15年PFS为40% （95% CI, 36.0%-44.7%）。与R-CHOP相比，CHOP-RIT显示出更好的15年PFS （47% vs 34%; P = 0.004）。治愈模型估计总治愈率为42%，其中在滤泡性淋巴瘤国际预后指数评分低且β2微球蛋白水平正常的患者中观察到的治愈率最高。随着时间的推移，复发率大幅下降，从前5年的6.8%降至15至20年的0.6%。这一次要分析的结果表明，随着复发率随着时间的推移而下降，一部分晚期FL患者可以通过基于chop的化学免疫治疗获得治愈。这一发现代表了对FL的理解和方法的范式转变，对最初的患者讨论和未来的研究策略具有重要意义。临床试验注册ClinicalTrials.gov标识符：NCT00006721
{"title":"Treatment of Follicular Lymphoma With CHOP and Anti-CD20 Therapy","authors":"Mazyar Shadman, Michael LeBlanc, Lisa Rimsza, John P. Leonard, Sonali M. Smith, Hongli Li, Jonathan W. Friedberg","doi":"10.1001/jamaoncol.2026.0042","DOIUrl":"https://doi.org/10.1001/jamaoncol.2026.0042","url":null,"abstract":"Importance Follicular lymphoma (FL) has historically been regarded as incurable, with patients experiencing late relapses after initial chemoimmunotherapy treatment. Objective To provide 15-year follow-up data from the SWOG S0016 trial that evaluated the potential for long-term remission and cure following chemoimmunotherapy with cyclophosphamide, hydroxydaunorubicin/doxorubicin, oncovin, and prednisone/prednisolone (CHOP)–based regimens. Design, Setting, and Participants This multicenter, intergroup study was conducted at academic and community practice locations throughout the US and enrolled patients with untreated, advanced-stage FL. Cure modeling, which involves estimating the proportion of patients cured of the disease, was conducted by incorporating background mortality rates to estimate the proportion of patients cured of FL during the S0016 trial. Patients were enrolled between May 2001 and October 2008 and followed up for a median (IQR) of 15.5 (13.6-16.9) years. The 15-year analysis was conducted in June 2025. Interventions Patients were randomized to receive either rituximab plus CHOP (R-CHOP) or CHOP followed by radioimmunotherapy (CHOP-RIT). Main Outcomes The main outcomes were 15-year progression free survival (PFS) and overall survival (OS). Secondary outcomes included cure modeling. Results A total of 531 eligible patients (242 female patients [46%]; median [IQR] age, 53 [45-61] years) were included in the final analysis (267 [50%] received R-CHOP and 264 [50%] CHOP-RIT). The overall 15-year OS was 70%, with no significant difference between treatment arms, and the 15-year PFS was 40% (95% CI, 36.0%-44.7%). CHOP-RIT demonstrated superior 15-year PFS (47% vs 34%; <jats:italic>P</jats:italic> = .004) compared with R-CHOP. Cure modeling estimated an overall cure rate of 42%, with the highest cure rates observed in patients with low Follicular Lymphoma International Prognostic Index scores and normal β2 microglobulin levels. The rate of relapse declined substantially over time, from 6.8% during the first 5 years to 0.6% between 15 to 20 years. Conclusions and Relevance The results of this secondary analysis suggest that a subset of patients with advanced-stage FL can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time. This finding represents a paradigm shift in the understanding of and approach to FL, with implications for initial patient discussions and future research strategies. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT00006721\">NCT00006721</jats:ext-link>","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"13 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147287121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-19DOI: 10.1001/jamaoncol.2025.6206
Connie M. Ulrich, Liza-Marie Johnson, Jamie C. Riches, Louis P. Voigt
This Viewpoint examines the challenges and strategies for improving public health literacy related to cancer research and care, including effective communication and ethical engagement among researchers, health care professionals, and patients.
{"title":"Cancer Research and Public Health Literacy—Making Sense","authors":"Connie M. Ulrich, Liza-Marie Johnson, Jamie C. Riches, Louis P. Voigt","doi":"10.1001/jamaoncol.2025.6206","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6206","url":null,"abstract":"This Viewpoint examines the challenges and strategies for improving public health literacy related to cancer research and care, including effective communication and ethical engagement among researchers, health care professionals, and patients.","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"129 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-19DOI: 10.1001/jamaoncol.2025.6504
Jakob Hytting, John Södling, Amanda Hytting, Kenny A. Rodriguez-Wallberg, Elham Hedayati, Panagiotis Mallios, Julianna Lise Holmberg, Robin Keskisärkkä, Martin Singull, Laila Hubbert
This cohort study examines cardiovascular disease risk, incidence, and mortality among adolescents and young adults with cervical high-grade squamous intraepithelial lesions (HSILs).
{"title":"Cardiovascular Events in Women With Prior Cervical High-Grade Squamous Intraepithelial Lesion","authors":"Jakob Hytting, John Södling, Amanda Hytting, Kenny A. Rodriguez-Wallberg, Elham Hedayati, Panagiotis Mallios, Julianna Lise Holmberg, Robin Keskisärkkä, Martin Singull, Laila Hubbert","doi":"10.1001/jamaoncol.2025.6504","DOIUrl":"https://doi.org/10.1001/jamaoncol.2025.6504","url":null,"abstract":"This cohort study examines cardiovascular disease risk, incidence, and mortality among adolescents and young adults with cervical high-grade squamous intraepithelial lesions (HSILs).","PeriodicalId":14850,"journal":{"name":"JAMA Oncology","volume":"120 1","pages":""},"PeriodicalIF":28.4,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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