Milit S Patel,Miranda B Lam,Erin Jay G Feliciano,Edward Christopher Dee
{"title":"Beyond the foundation: building on Medicaid expansion to achieve cancer equity.","authors":"Milit S Patel,Miranda B Lam,Erin Jay G Feliciano,Edward Christopher Dee","doi":"10.1093/jnci/djaf274","DOIUrl":"https://doi.org/10.1093/jnci/djaf274","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDPatients with locally advanced gastric cancer who undergo curative intent gastrectomy experience a decline in health-related quality of life (HRQOL) during adjuvant chemotherapy. The EAGER trial (Electro-Acupuncture in Gastric cancER) sought to evaluate the ability of electro-acupuncture (EA) to preserve HRQOL in these patients.METHODSIn this open-label, multi-center, parallel controlled trial, patients with stage II-III gastric cancer across 11 hospitals in China who were undergoing chemotherapy following gastrectomy were randomly assigned to receive high-frequency EA (HEA), low-frequency EA (LEA), or no EA during the first 3 cycles of chemotherapy. The Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) was reported by patients at baseline and once weekly during the therapy. The primary outcome was the difference among groups in the FACT-Ga Trial Outcome Index (TOI) trajectory during the study duration by the standardized area under the curve (AUC).RESULTSOf 222 patients randomized and analyzed, EA was associated with higher HRQOL measured by TOI-AUC [5678 ± 1229 (HEA), 5558 ± 1226 (LEA), and 4735 ± 1233 (control), P < .001]. No difference was seen based on acupuncture dosing (P = .557). Participants in the EA groups also achieved significantly improved disease-free survival (DFS) [HEA vs. Control, HR = 0.47 (0.24-0.93), P = .026; LEA vs. Control, HR = 0.51 (0.28-0.95), P = .030], fewer grade 3-4 adverse events (20.7% vs. 39.0%, P = .004), and decreased peripheral myeloid-derived suppressor cells (P = .038), compared with the control group.CONCLUSIONSUse of EA resulted in higher HRQOL in gastric cancer patients undergoing adjuvant chemotherapy, irrespective of dosing. EA was also associated with prolonged DFS and lower treatment-associated toxicities, which warrants further confirmative research.TRIAL REGISTRATIONClinicalTrials.gov NCT04360577.
背景：局部晚期胃癌患者接受治疗性胃切除术后，在辅助化疗期间健康相关生活质量（HRQOL）下降。EAGER试验（电针治疗胃癌）旨在评估电针（EA）维持这些患者HRQOL的能力。方法在这项开放标签、多中心、平行对照试验中，来自中国11家医院的II-III期胃癌患者在胃切除术后接受化疗，随机分为前3个化疗周期接受高频EA （HEA）、低频EA （LEA）和不接受EA。患者在基线和治疗期间每周报告一次肿瘤治疗-胃功能评估（FACT-Ga）。主要结局是研究期间各组间FACT-Ga试验结局指数（TOI）轨迹的标准化曲线下面积（AUC）差异。结果在222例随机分析的患者中，EA与TOI-AUC测量的HRQOL升高相关[HEA为5678±1229，LEA为5558±1226，对照为4735±1233，P < 0.001]。针刺剂量组无差异（P = .557）。EA组的参与者也获得了显著改善的无病生存（DFS） [HEA vs. Control, HR = 0.47 (0.24-0.93), P = 0.026；LEA vs.对照组，HR = 0.51 (0.28-0.95), P =。030]， 3-4级不良事件较少(20.7% vs. 39.0%, P =。004)，外周髓源性抑制细胞减少(P =。038)，与对照组相比。结论在胃癌辅助化疗患者中，EA的应用可提高患者的HRQOL。EA还与延长的DFS和较低的治疗相关毒性有关，这需要进一步的确证研究。临床试验注册网站NCT04360577。
{"title":"Electro-acupuncture for quality of life during adjuvant chemotherapy in gastric cancer: a randomized trial.","authors":"Yan-Juan Zhu,Xue-Song Chang,Xiao-Yu Wu,Wei Wang,De-Chang Diao,Yong Li,Hong-Yu Zhang,Jian Xiao,Xiao-Hui Zhai,Jin-Long Yu,Wei Wang,Jing-Xu Zhou,Zhi-Liang Huang,Tao Zhang,Wenwei Ouyang,Yelena Y Janjigian,Samuel L Cytryn,Zhen-Zhen Xiao,Yi-Hong Liu,Rui Zhou,Hao-Chuan Ma,Ya-Dong Chen,Jian-Jun Peng,Jun J Mao,Hai-Bo Zhang","doi":"10.1093/jnci/djaf309","DOIUrl":"https://doi.org/10.1093/jnci/djaf309","url":null,"abstract":"BACKGROUNDPatients with locally advanced gastric cancer who undergo curative intent gastrectomy experience a decline in health-related quality of life (HRQOL) during adjuvant chemotherapy. The EAGER trial (Electro-Acupuncture in Gastric cancER) sought to evaluate the ability of electro-acupuncture (EA) to preserve HRQOL in these patients.METHODSIn this open-label, multi-center, parallel controlled trial, patients with stage II-III gastric cancer across 11 hospitals in China who were undergoing chemotherapy following gastrectomy were randomly assigned to receive high-frequency EA (HEA), low-frequency EA (LEA), or no EA during the first 3 cycles of chemotherapy. The Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) was reported by patients at baseline and once weekly during the therapy. The primary outcome was the difference among groups in the FACT-Ga Trial Outcome Index (TOI) trajectory during the study duration by the standardized area under the curve (AUC).RESULTSOf 222 patients randomized and analyzed, EA was associated with higher HRQOL measured by TOI-AUC [5678 ± 1229 (HEA), 5558 ± 1226 (LEA), and 4735 ± 1233 (control), P < .001]. No difference was seen based on acupuncture dosing (P = .557). Participants in the EA groups also achieved significantly improved disease-free survival (DFS) [HEA vs. Control, HR = 0.47 (0.24-0.93), P = .026; LEA vs. Control, HR = 0.51 (0.28-0.95), P = .030], fewer grade 3-4 adverse events (20.7% vs. 39.0%, P = .004), and decreased peripheral myeloid-derived suppressor cells (P = .038), compared with the control group.CONCLUSIONSUse of EA resulted in higher HRQOL in gastric cancer patients undergoing adjuvant chemotherapy, irrespective of dosing. EA was also associated with prolonged DFS and lower treatment-associated toxicities, which warrants further confirmative research.TRIAL REGISTRATIONClinicalTrials.gov NCT04360577.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ran Zhao,Shalini Kulasingam,Fernando Alarid-Escudero,Adair K Minihan,Madalyn Nones,Inge M C M de Kok,Jan A C Hontelez,Daniel D de Bondt,Priti Bandi,Debbie Saslow,Ahmedin Jemal
BACKGROUNDCervical cancer poses a significant burden in the US. State-level decision-makers need to understand the expected benefits of implementing interventions to reduce this burden. This study aims to estimate the long-term state-level benefits of interventions to reduce the burden of cervical cancer.METHODSWe used a simulation model to estimate the expected reductions in cervical cancer incidence and mortality by achieving 80% (or 90%) vaccination coverage among adolescents aged 13-17 by 2030 and increasing screening uptake by 5% among never screened women aged 21-65 across all 50 US states. We modeled one status quo scenario and three intervention scenarios: increasing vaccination only, increasing screening only, and increasing both vaccination and screening. The benefits of each intervention were presented as the cumulative reduction in cancer incidence and mortality compared to the status quo over a 100-year analytic period.RESULTSCompared to the status quo, the cumulative reduction from the "increase in vaccination coverage only" scenario varied substantially by state, generally being higher in Southern and Western states. The greatest reductions were predicted for Mississippi, with 253.1 cases and 80.0 deaths per 100,000 women. The "increase in both vaccination and screening" scenario reduced cancer incidence from 9.2 (Utah) to 266.0 (Mississippi) per 100,000 women and reduced mortality from 3.3 (Utah) to 85.0 (Mississippi) per 100,000 women.CONCLUSIONOur modeling study suggests that states and regions will differ in the extent to which they will benefit from increasing HPV vaccination coverage and cervical cancer screening uptake.
{"title":"Public-health impact of increasing human papillomavirus vaccination and cervical cancer screening.","authors":"Ran Zhao,Shalini Kulasingam,Fernando Alarid-Escudero,Adair K Minihan,Madalyn Nones,Inge M C M de Kok,Jan A C Hontelez,Daniel D de Bondt,Priti Bandi,Debbie Saslow,Ahmedin Jemal","doi":"10.1093/jnci/djaf311","DOIUrl":"https://doi.org/10.1093/jnci/djaf311","url":null,"abstract":"BACKGROUNDCervical cancer poses a significant burden in the US. State-level decision-makers need to understand the expected benefits of implementing interventions to reduce this burden. This study aims to estimate the long-term state-level benefits of interventions to reduce the burden of cervical cancer.METHODSWe used a simulation model to estimate the expected reductions in cervical cancer incidence and mortality by achieving 80% (or 90%) vaccination coverage among adolescents aged 13-17 by 2030 and increasing screening uptake by 5% among never screened women aged 21-65 across all 50 US states. We modeled one status quo scenario and three intervention scenarios: increasing vaccination only, increasing screening only, and increasing both vaccination and screening. The benefits of each intervention were presented as the cumulative reduction in cancer incidence and mortality compared to the status quo over a 100-year analytic period.RESULTSCompared to the status quo, the cumulative reduction from the \"increase in vaccination coverage only\" scenario varied substantially by state, generally being higher in Southern and Western states. The greatest reductions were predicted for Mississippi, with 253.1 cases and 80.0 deaths per 100,000 women. The \"increase in both vaccination and screening\" scenario reduced cancer incidence from 9.2 (Utah) to 266.0 (Mississippi) per 100,000 women and reduced mortality from 3.3 (Utah) to 85.0 (Mississippi) per 100,000 women.CONCLUSIONOur modeling study suggests that states and regions will differ in the extent to which they will benefit from increasing HPV vaccination coverage and cervical cancer screening uptake.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"134 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BACKGROUNDGastric-type adenocarcinoma (GAC) is the predominant subtype of HPV-independent endocervical adenocarcinoma, characterized by aggressive clinical behavior and poor prognosis. However, its tumor immune microenvironment (TIME) remains largely unexplored.METHODSWe systematically profiled the immune landscape using bulk RNA sequencing and multiplex immunofluorescence staining and comprehensively analyzed the associations between immune features, clinicopathological parameters, and patient outcomes in a multi-institutional cohort of 153 GAC cases.RESULTSGAC tumors exhibited sparse T cell but abundant macrophage infiltration, predominantly with M2-polarized macrophages in advanced stage. Tumors with tertiary lymphoid structure (TLS) demonstrated an immunosuppressive milieu characterized by enrichment of B cells, PD1-CD8+ T cells, and regulatory T cells. While TLS-positive patients were associated with poorer prognosis, two patients showed improved survival with chemoradiotherapy. Moreover, the TLS and FIGO stage-based prognostic model was robust in the risk stratification for tumor recurrence.CONCLUSIONSWe reveal a distinct immunosuppressive TIME and TLS in GAC. TLS might confer an adverse prognosis. Our findings provide valuable clues for individualized therapy for this aggressive cancer in future.
{"title":"An immunosuppressive tertiary lymphoid structure is associated with adverse prognosis in gastric-type endocervical adenocarcinoma.","authors":"Ruiyi Xu,Hong Liu,Tao Zhu,Huarong Tang,Min Wu,Xinyu Yan,Menghan Li,Shuo Yuan,Taotao Yin,Jinglan Chen,Shuyan Wang,Junbin Qian,Junfen Xu,Qing Zhang,Bingjian Lu,Hui Wang","doi":"10.1093/jnci/djaf310","DOIUrl":"https://doi.org/10.1093/jnci/djaf310","url":null,"abstract":"BACKGROUNDGastric-type adenocarcinoma (GAC) is the predominant subtype of HPV-independent endocervical adenocarcinoma, characterized by aggressive clinical behavior and poor prognosis. However, its tumor immune microenvironment (TIME) remains largely unexplored.METHODSWe systematically profiled the immune landscape using bulk RNA sequencing and multiplex immunofluorescence staining and comprehensively analyzed the associations between immune features, clinicopathological parameters, and patient outcomes in a multi-institutional cohort of 153 GAC cases.RESULTSGAC tumors exhibited sparse T cell but abundant macrophage infiltration, predominantly with M2-polarized macrophages in advanced stage. Tumors with tertiary lymphoid structure (TLS) demonstrated an immunosuppressive milieu characterized by enrichment of B cells, PD1-CD8+ T cells, and regulatory T cells. While TLS-positive patients were associated with poorer prognosis, two patients showed improved survival with chemoradiotherapy. Moreover, the TLS and FIGO stage-based prognostic model was robust in the risk stratification for tumor recurrence.CONCLUSIONSWe reveal a distinct immunosuppressive TIME and TLS in GAC. TLS might confer an adverse prognosis. Our findings provide valuable clues for individualized therapy for this aggressive cancer in future.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the link between diabetes and cancer: separating signal from noise.","authors":"Iliana C Lega,Lorraine L Lipscombe","doi":"10.1093/jnci/djaf219","DOIUrl":"https://doi.org/10.1093/jnci/djaf219","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hua-Ren R Cherng,Kai Sun,Soren M Bentzen,Paul D Brown,Terri S Armstrong,Joshua D Palmer,Vinai Gondi,Minesh P Mehta,Mark V Mishra
BACKGROUNDAlthough there are data describing the onset of neurocognitive toxicity following radiation for patients with brain metastases, less is known about the potential for functional cognitive recovery (CR). This study sought to evaluate CR following neurocognitive function failure (NCF) in patients treated with stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and hippocampal avoidance (HA)-WBRT.METHODSA pooled analysis of three (NCCTG N107C/CEC.3, NCCTG N0574, and NRG CC001) clinical trials was performed. Patients with trial-defined NCF and longitudinal cognitive testing were included. The primary endpoint was time to CR, defined as patients no longer exhibiting a one or more standard deviation decline from baseline on any cognitive test.FINDINGS288 patients were included, with a median follow-up of 12.2 months. The cumulative incidence of CR was 38% (95% CI 32.5-43.9%) at 6 months after NCF. Incidence of CR was significantly improved with post-op SRS vs WBRT (HR: 2.68, 95% CI: 1.43-5.03, p = .002) and with SRS vs SRS+WBRT (HR: 2.35, 95% CI: 1.16-4.79, p = .008). On multivariable analysis, SRS was highly prognostic of CR compared to WBRT (HR: 2.42, 95% CI: 1.70-3.45, p < .0001). Meta-analysis demonstrated that conformal RT techniques (SRS or HA-WBRT) conferred a significantly higher rate of CR compared to WBRT (pooled HR 2.12, 95% CI: 1.49-3.02, p < .001). 68% of patients had long-term sustained CR.INTERPRETATIONA sizeable proportion of patients who experience NCF following brain radiation eventually attain full and sustained CR, thereby highlighting that neurocognitive decline may not be permanent. The use of conformal radiation techniques results in greater rates of neurocognitive recovery.
背景：虽然有数据描述了脑转移患者放射后神经认知毒性的发作，但对功能性认知恢复（CR）的潜力知之甚少。本研究旨在评估接受立体定向放射手术（SRS）、全脑放疗（WBRT）和海马回避(HA)-WBRT治疗的患者神经认知功能衰竭（NCF）后的CR。方法对三种NCCTG （N107C/CEC）进行汇总分析。3、NCCTG N0574和NRG CC001)进行临床试验。纳入了试验定义的NCF和纵向认知测试的患者。主要终点是达到CR的时间，定义为患者在任何认知测试中不再表现出一个或多个标准偏差从基线下降。结果纳入288例患者，中位随访时间为12.2个月。NCF后6个月CR的累计发生率为38% （95% CI 32.5-43.9%）。与WBRT相比，术后SRS的CR发生率显著改善(HR: 2.68, 95% CI: 1.43-5.03, p =。002)和SRS vs SRS+WBRT （HR: 2.35, 95% CI: 1.16-4.79, p = 0.008）。在多变量分析中，与WBRT相比，SRS是CR的高度预后因素（HR: 2.42, 95% CI: 1.70-3.45, p < 0.0001）。荟萃分析显示，与WBRT相比，适形放疗技术（SRS或HA-WBRT）的CR率显著更高（合并HR 2.12, 95% CI: 1.49-3.02, p < 0.001）。68%的患者出现长期持续CR。解释相当大比例的脑放疗后经历NCF的患者最终达到完全和持续的CR，因此强调神经认知能力下降可能不是永久性的。适形放射技术的使用可提高神经认知功能的恢复率。
{"title":"Redefining Neurocognitive Outcomes After Radiation for Brain Metastases: A Patient-Level Meta-Analysis of Recovery Following Initial Decline.","authors":"Hua-Ren R Cherng,Kai Sun,Soren M Bentzen,Paul D Brown,Terri S Armstrong,Joshua D Palmer,Vinai Gondi,Minesh P Mehta,Mark V Mishra","doi":"10.1093/jnci/djaf264","DOIUrl":"https://doi.org/10.1093/jnci/djaf264","url":null,"abstract":"BACKGROUNDAlthough there are data describing the onset of neurocognitive toxicity following radiation for patients with brain metastases, less is known about the potential for functional cognitive recovery (CR). This study sought to evaluate CR following neurocognitive function failure (NCF) in patients treated with stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and hippocampal avoidance (HA)-WBRT.METHODSA pooled analysis of three (NCCTG N107C/CEC.3, NCCTG N0574, and NRG CC001) clinical trials was performed. Patients with trial-defined NCF and longitudinal cognitive testing were included. The primary endpoint was time to CR, defined as patients no longer exhibiting a one or more standard deviation decline from baseline on any cognitive test.FINDINGS288 patients were included, with a median follow-up of 12.2 months. The cumulative incidence of CR was 38% (95% CI 32.5-43.9%) at 6 months after NCF. Incidence of CR was significantly improved with post-op SRS vs WBRT (HR: 2.68, 95% CI: 1.43-5.03, p = .002) and with SRS vs SRS+WBRT (HR: 2.35, 95% CI: 1.16-4.79, p = .008). On multivariable analysis, SRS was highly prognostic of CR compared to WBRT (HR: 2.42, 95% CI: 1.70-3.45, p < .0001). Meta-analysis demonstrated that conformal RT techniques (SRS or HA-WBRT) conferred a significantly higher rate of CR compared to WBRT (pooled HR 2.12, 95% CI: 1.49-3.02, p < .001). 68% of patients had long-term sustained CR.INTERPRETATIONA sizeable proportion of patients who experience NCF following brain radiation eventually attain full and sustained CR, thereby highlighting that neurocognitive decline may not be permanent. The use of conformal radiation techniques results in greater rates of neurocognitive recovery.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yago Garitaonaindia,Shawez Khan,Rasmus Friis,Søren Kjær,Troels H Borch,Christina Ruhlmann,Louise M Guldbrandt,Adam A Luczak,Henrik Schmidt,Lars Bastholt,Inge Marie Svane,Marco Donia,Eva Ellebaek
BACKGROUNDEncorafenib is a BRAF inhibitor with a pharmacodynamic profile distinct from that of dabrafenib, including a longer dissociation half-life that may enable more sustained BRAF inhibition. It has been hypothesized that this could translate into superior clinical efficacy. We aimed to determine whether encorafenib plus binimetinib is superior to dabrafenib plus trametinib in terms of clinical activity and outcomes.METHODSPatients were identified through the Danish Metastatic Melanoma Database, a national registry collecting prospective data on systemic treatments. We retrospectively retrieved baseline, treatment, and outcome data for patients with metastatic BRAF-mutant melanoma treated with encorafenib plus binimetinib or dabrafenib plus trametinib from 2017 to 2024. Both unmatched and propensity score-matched analyses were conducted to mitigate potential confounding.RESULTSA total of 751 patients were included (422 dabrafenib plus trametinib, 329 encorafenib plus binimetinib). Baseline characteristics were balanced between groups. In the unmatched cohort, no statistically differences were observed between dabrafenib plus trametinib and encorafenib plus binimetinib in progression-free survival (PFS; median = 7.9 vs 8.0 months; hazard ratio [HR] = 0.99, P = .90), overall survival (median = 15.5 vs 15.4 months; HR = 0.91, P = .30), or melanoma-specific survival (median = 16.2 vs 15.7 months; HR = 0.94, P = .50). Propensity score-matched analyses confirmed these findings (PFS: HR = 1.05, P = .60; overall survival: HR = 0.922, P = .41; melanoma-specific survival: HR = 0.97, P = .74). Post hoc power analysis for detecting a 3-month survival difference was adequate for PFS (97.5%) but limited for overall survival (56.3%) and melanoma-specific survival (52.1%).CONCLUSIONSWe found no evidence that encorafenib plus binimetinib is superior to dabrafenib plus trametinib in metastatic melanoma. These findings suggest that the choice between these combinations should be guided by tolerability profiles and economic considerations rather than efficacy.
背景：encorafenib是一种BRAF抑制剂，其药效学特征与dabrafenib不同，包括更长的解离半衰期，可以实现更持久的BRAF抑制。据推测，这可以转化为优越的临床疗效。我们的目的是确定依科非尼加比尼美替尼在临床活性和结局方面是否优于达非尼加曲美替尼。方法通过丹麦转移性黑色素瘤数据库确定患者，该数据库是一个收集系统性治疗前瞻性数据的国家登记处。我们回顾性检索了2017年至2024年接受恩科非尼+比尼美替尼或达拉法尼+曲美替尼治疗的转移性brf突变黑色素瘤患者的基线、治疗和结局数据。进行了不匹配和倾向评分匹配分析，以减少潜在的混淆。结果共纳入751例患者（达非尼+曲美替尼422例，依科非尼+比尼美替尼329例）。各组间基线特征平衡。在未匹配的队列中，达非尼加曲美替尼和依科非尼加比尼美替尼的无进展生存期（PFS）无统计学差异；中位数= 7.9 vs 8.0个月；风险比[HR] = 0.99, P =。90)，总生存期（中位数= 15.5 vs 15.4个月；HR = 0.91, P = 0.91）。30)，或黑色素瘤特异性生存（中位数= 16.2个月vs 15.7个月；HR = 0.94, P = 0.50）。倾向评分匹配分析证实了这些发现（PFS: HR = 1.05, P = 0.60；总生存率：HR = 0.922, P = 0.41；黑色素瘤特异性生存率：HR = 0.97, P = 0.74）。检测3个月生存差异的事后功率分析对PFS（97.5%）是足够的，但对总生存（56.3%）和黑色素瘤特异性生存（52.1%）是有限的。结论我们没有发现证据表明恩科非尼加比尼美替尼治疗转移性黑色素瘤优于达非尼加曲美替尼。这些发现表明，在这些组合之间的选择应以耐受性和经济考虑为指导，而不是疗效。
{"title":"Dabrafenib plus trametinib vs encorafenib plus binimetinib in BRAF-mutant metastatic melanoma: a real-world propensity score-matched survival analysis.","authors":"Yago Garitaonaindia,Shawez Khan,Rasmus Friis,Søren Kjær,Troels H Borch,Christina Ruhlmann,Louise M Guldbrandt,Adam A Luczak,Henrik Schmidt,Lars Bastholt,Inge Marie Svane,Marco Donia,Eva Ellebaek","doi":"10.1093/jnci/djaf263","DOIUrl":"https://doi.org/10.1093/jnci/djaf263","url":null,"abstract":"BACKGROUNDEncorafenib is a BRAF inhibitor with a pharmacodynamic profile distinct from that of dabrafenib, including a longer dissociation half-life that may enable more sustained BRAF inhibition. It has been hypothesized that this could translate into superior clinical efficacy. We aimed to determine whether encorafenib plus binimetinib is superior to dabrafenib plus trametinib in terms of clinical activity and outcomes.METHODSPatients were identified through the Danish Metastatic Melanoma Database, a national registry collecting prospective data on systemic treatments. We retrospectively retrieved baseline, treatment, and outcome data for patients with metastatic BRAF-mutant melanoma treated with encorafenib plus binimetinib or dabrafenib plus trametinib from 2017 to 2024. Both unmatched and propensity score-matched analyses were conducted to mitigate potential confounding.RESULTSA total of 751 patients were included (422 dabrafenib plus trametinib, 329 encorafenib plus binimetinib). Baseline characteristics were balanced between groups. In the unmatched cohort, no statistically differences were observed between dabrafenib plus trametinib and encorafenib plus binimetinib in progression-free survival (PFS; median = 7.9 vs 8.0 months; hazard ratio [HR] = 0.99, P = .90), overall survival (median = 15.5 vs 15.4 months; HR = 0.91, P = .30), or melanoma-specific survival (median = 16.2 vs 15.7 months; HR = 0.94, P = .50). Propensity score-matched analyses confirmed these findings (PFS: HR = 1.05, P = .60; overall survival: HR = 0.922, P = .41; melanoma-specific survival: HR = 0.97, P = .74). Post hoc power analysis for detecting a 3-month survival difference was adequate for PFS (97.5%) but limited for overall survival (56.3%) and melanoma-specific survival (52.1%).CONCLUSIONSWe found no evidence that encorafenib plus binimetinib is superior to dabrafenib plus trametinib in metastatic melanoma. These findings suggest that the choice between these combinations should be guided by tolerability profiles and economic considerations rather than efficacy.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Discovering plasma proteins associated with breast cancer incidence in postmenopausal women in the Atherosclerosis Risk in Communities study.","authors":"","doi":"10.1093/jnci/djaf284","DOIUrl":"https://doi.org/10.1093/jnci/djaf284","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Qahar K Yasinzai,Pooya Jalali,Sebawe Syaj,Ibrahim Halil Sahin,Ibrahim Nassour,Thomas J George,Anwaar Saeed
BACKGROUNDEarly-onset colorectal cancer (eoCRC) has become a serious public health concern in recent years. This study aims to contribute to the growing body of evidence on the rise in early onset gastrointestinal cancers (eoGIC), anatomical sub-sites of eoCRC, and explore racial and gender disparities in these trends.METHODSWe analyzed data from the NPCR-SEER database (2001-2021) for people aged 20 to 49 with gastrointestinal (GI) cancers. The dataset covers cancer incidence rates for about 98% of United States population. Joinpoint regression was used to calculate average annual percent change (AAPC), and polynomial regression was applied to forecast rates from 2021 to 2031.RESULTSA total of 527,411 cases were analyzed. Colorectal comprised of the highest cases (n = 313,513) followed by pancreatic (n = 50,448). Intrahepatic bile duct had the highest AAPC (+6.24%, 95% CI +5.20 to + 7.45) followed by small intestine (+3.19%, 95% CI: +2.69 to + 3.72), eoCRC (+1.65%, 95% CI: +1.45 to + 1.92), pancreatic (+1.52, 95% CI: +1.37 to + 1.66), and stomach (+1.20, 95% CI: +0.89 to + 1.53). In colorectum, rectum had the highest AAPC (+2.09%). Females (+1.81%) experienced disproportionate rise when compared to males (+0.83%). Projection suggests a demographic shift with female surpassing males in the overall age adjusted rate of eoGIC.CONCLUSIONThe study highlights that eoCRC is not an isolated phenomenon but part of a broader epidemiologic shift across gastrointestinal malignancies. The parallel rise in other sites suggests shared upstream risk factors or exposures and supports investigations into potential environmental, dietary, microbiome, or hormonal risk factors.
{"title":"Trends and Projected Burden of Early-Onset Gastrointestinal Malignancies in the United States: A Population-Based Analysis (2001-2021).","authors":"Abdul Qahar K Yasinzai,Pooya Jalali,Sebawe Syaj,Ibrahim Halil Sahin,Ibrahim Nassour,Thomas J George,Anwaar Saeed","doi":"10.1093/jnci/djaf304","DOIUrl":"https://doi.org/10.1093/jnci/djaf304","url":null,"abstract":"BACKGROUNDEarly-onset colorectal cancer (eoCRC) has become a serious public health concern in recent years. This study aims to contribute to the growing body of evidence on the rise in early onset gastrointestinal cancers (eoGIC), anatomical sub-sites of eoCRC, and explore racial and gender disparities in these trends.METHODSWe analyzed data from the NPCR-SEER database (2001-2021) for people aged 20 to 49 with gastrointestinal (GI) cancers. The dataset covers cancer incidence rates for about 98% of United States population. Joinpoint regression was used to calculate average annual percent change (AAPC), and polynomial regression was applied to forecast rates from 2021 to 2031.RESULTSA total of 527,411 cases were analyzed. Colorectal comprised of the highest cases (n = 313,513) followed by pancreatic (n = 50,448). Intrahepatic bile duct had the highest AAPC (+6.24%, 95% CI +5.20 to + 7.45) followed by small intestine (+3.19%, 95% CI: +2.69 to + 3.72), eoCRC (+1.65%, 95% CI: +1.45 to + 1.92), pancreatic (+1.52, 95% CI: +1.37 to + 1.66), and stomach (+1.20, 95% CI: +0.89 to + 1.53). In colorectum, rectum had the highest AAPC (+2.09%). Females (+1.81%) experienced disproportionate rise when compared to males (+0.83%). Projection suggests a demographic shift with female surpassing males in the overall age adjusted rate of eoGIC.CONCLUSIONThe study highlights that eoCRC is not an isolated phenomenon but part of a broader epidemiologic shift across gastrointestinal malignancies. The parallel rise in other sites suggests shared upstream risk factors or exposures and supports investigations into potential environmental, dietary, microbiome, or hormonal risk factors.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145305505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adela Rodriguez-Hernandez, Miki Horiguchi, Carolyn Horton, Linda M Polfus, Brittany L Bychkovsky, Ryan M Buehler, Suzanne George, Priscilla Merriam, Judy E Garber, Huma Q Rana
Background Germline multi-gene panel testing (MGPT) is not yet integrated into standard care for patients with sarcoma. This study aimed to assess the frequency and distribution of germline pathogenic variants (gPVs) in patients with sarcoma compared to cancer-free controls and identify differences between patients with and without gPVs. Methods This retrospective cohort included 488 sarcoma patients, and 2,440 cancer-free controls matched 1:5 by age, sex, and ethnicity. MGPT was performed between 2016 and 2024 at a single germline testing laboratory. The frequency of gPVs in selected genes was compared using Fisher’s exact test, with odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, within the case-only cohort, clinical characteristics were evaluated to assess associations with the presence of gPVs in any gene. Results Among 488 patients with sarcoma, 67.8% (n = 331) were female, with a median age at sarcoma diagnosis of 47 years (range 0.5-87.5). Cases had a higher frequency of gPVs compared to controls (26.2% vs. 10.5%; OR 3.05, p < .001). We observed a higher frequency of gPVs in TP53, BRCA2, CHEK2, NF1, SDHA, BRIP1, POT1, RB1, and CDH1 among patients with sarcoma compared to controls. Age at sarcoma diagnosis did not differ between groups. Conclusions This study confirms the high detection rate of gPVs in patients with sarcoma and describes several associated genes. These findings indicate that age at sarcoma diagnosis may not reliably predict gPVs. Expanding germline testing for patients with sarcoma would enhance personalized treatment strategies and familial risk assessment.
生殖系多基因面板检测（MGPT）尚未纳入肉瘤患者的标准治疗。本研究旨在评估与无癌对照相比，肉瘤患者中种系致病变异（gPVs）的频率和分布，并确定有和没有gPVs的患者之间的差异。方法该回顾性队列包括488例肉瘤患者和2440例无癌对照，年龄、性别和种族比例为1:5。MGPT于2016年至2024年在单个生殖系检测实验室进行。采用Fisher精确检验比较所选基因中gpv的频率，采用优势比（ORs）和95%置信区间（CIs）。此外，在仅病例队列中，评估临床特征以评估与任何基因中gpv存在的关联。结果488例肉瘤患者中，67.8% （n = 331）为女性，肉瘤诊断时的中位年龄为47岁（范围0.5-87.5）。与对照组相比，病例的gpv发生率更高（26.2% vs. 10.5%; OR 3.05, p < .001）。我们观察到，与对照组相比，肉瘤患者中TP53、BRCA2、CHEK2、NF1、SDHA、BRIP1、POT1、RB1和CDH1中gPVs的频率更高。肉瘤诊断年龄在两组间无差异。结论本研究证实了gpv在肉瘤患者中的高检出率，并描述了几个相关基因。这些发现表明，肉瘤诊断时的年龄可能不能可靠地预测gpv。扩大对肉瘤患者的生殖系检测将增强个性化治疗策略和家族风险评估。
{"title":"Frequency and clinical features of germline pathogenic variants in sarcoma: a case-control study","authors":"Adela Rodriguez-Hernandez, Miki Horiguchi, Carolyn Horton, Linda M Polfus, Brittany L Bychkovsky, Ryan M Buehler, Suzanne George, Priscilla Merriam, Judy E Garber, Huma Q Rana","doi":"10.1093/jnci/djaf294","DOIUrl":"https://doi.org/10.1093/jnci/djaf294","url":null,"abstract":"Background Germline multi-gene panel testing (MGPT) is not yet integrated into standard care for patients with sarcoma. This study aimed to assess the frequency and distribution of germline pathogenic variants (gPVs) in patients with sarcoma compared to cancer-free controls and identify differences between patients with and without gPVs. Methods This retrospective cohort included 488 sarcoma patients, and 2,440 cancer-free controls matched 1:5 by age, sex, and ethnicity. MGPT was performed between 2016 and 2024 at a single germline testing laboratory. The frequency of gPVs in selected genes was compared using Fisher’s exact test, with odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, within the case-only cohort, clinical characteristics were evaluated to assess associations with the presence of gPVs in any gene. Results Among 488 patients with sarcoma, 67.8% (n = 331) were female, with a median age at sarcoma diagnosis of 47 years (range 0.5-87.5). Cases had a higher frequency of gPVs compared to controls (26.2% vs. 10.5%; OR 3.05, p &lt; .001). We observed a higher frequency of gPVs in TP53, BRCA2, CHEK2, NF1, SDHA, BRIP1, POT1, RB1, and CDH1 among patients with sarcoma compared to controls. Age at sarcoma diagnosis did not differ between groups. Conclusions This study confirms the high detection rate of gPVs in patients with sarcoma and describes several associated genes. These findings indicate that age at sarcoma diagnosis may not reliably predict gPVs. Expanding germline testing for patients with sarcoma would enhance personalized treatment strategies and familial risk assessment.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"97 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145295652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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