Journal of the National Cancer Institute最新文献

{"title":"Health-related quality of life in patients with newly diagnosed advanced ovarian cancer receiving maintenance olaparib plus bevacizumab (PAOLA-1/ENGOT-ov25).","authors":"Florence Joly,Amélie Anota,Sylvie Chabaud,Claire Cropet,Frank Priou,Philipp Harter,Sandro Pignata,Isabel Palacio,Edgar Petru,Hiroaki Kobayashi,Ignace Vergote,Gabriella Parma,Johanna Mäenpää,Eric Raymond,Beyhan Ataseven,Carmela Pisano,Nuria Lainez,Irina Tsibulak,Kan Yonemori,Peter Vuylsteke,Maria Teresa Lapresa,Mansoor Raza Mirza,Patrick Bouchaert,Paul Buderath,Domenica Lorusso,Ana Herrero,Lauriane Eberst,Alexander Burges,Giovanni Scambia,Eugenia Ortega,Cécile Guillemet,Eric Pujade-Lauraine,Jean-Emmanuel Kurtz,Isabelle Ray-Coquard","doi":"10.1093/jnci/djag122","DOIUrl":"https://doi.org/10.1093/jnci/djag122","url":null,"abstract":"BACKGROUNDWe analyzed health-related quality of life (HRQoL) and time until definitive HRQoL deterioration (TUDD) for patients with newly diagnosed advanced ovarian cancer receiving olaparib plus bevacizumab or placebo plus bevacizumab in PAOLA-1.METHODSHRQoL and TUDD, prespecified secondary endpoints, were assessed by EORTC Core Quality of Life Questionnaire (QLQ-C30) and Ovarian Cancer module (QLQ-OV28) at baseline and then every 12 weeks for 2 years. HRQoL and TUDD by homologous recombination deficiency (HRD) status and effect of progression on HRQoL were post hoc analyses.RESULTS806 patients were randomized (olaparib plus bevacizumab n = 537; placebo plus bevacizumab n = 269). There were no clinically meaningful between-group differences in adjusted mean global change from baseline in QLQ-C30 or QLQ-OV28 domains overall (between-group difference in QLQ-C30 Global Heath Status (GHS) score [95% CI] 1.65 [-0.27, 3.56]) or in the HRD-positive subgroup (1.23 [-1.25, 3.71]). TUDD estimates of QLQ-C30 GHS scores did not differ between treatment arms in the modified intention-to-treat population (hazard ratio [HR]=0.88; 95% CI = 0.72, 1.07) and favored olaparib plus bevacizumab vs placebo plus bevacizumab in the HRD-positive subgroup (HR = 0.70; 95% CI = 0.52, 0.93). Analyses of patients (103/465 [22.2%]) following disease progression showed clinically meaningful deterioration in QLQ-C30 emotional and social scores.CONCLUSIONAdding maintenance olaparib to bevacizumab showed no clinically meaningful detrimental effect on global HRQoL either overall or in the HRD-positive subgroup. ClinicalTrials.gov ID: NCT02477644.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147739029","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":"Federal housing assistance, cancer care, and overall survival among older adults with prostate cancer.","authors":"Katherine L Chen,Taylor K Craig,Amanda L Blackford,Joan L Warren,Daniel Song,Qinjin Fan,S M Qasim Hussaini,Margaret Katana Ogongo,Xin Hu,Rebecca B Smith,Jordan Kaplan,Robyn N Jordan,Cary P Gross,Daniel Polsky,K Robin Yabroff,Craig Evan Pollack","doi":"10.1093/jnci/djag099","DOIUrl":"https://doi.org/10.1093/jnci/djag099","url":null,"abstract":"BACKGROUNDSurvival disparities in prostate cancer are driven in part by social and economic factors, including housing insecurity. Rent subsidies in the form of federal housing assistance are a well-established strategy for alleviating housing insecurity, but their association with prostate cancer care and survival is unknown.METHODSUsing linked federal housing assistance data, SEER cancer registry data, and Medicare claims, we assessed workup and treatment receipt and two-year survival among individuals aged 66 to 95 who were diagnosed with prostate cancer in 2007 to 2019. We used logistic and Cox regression models to compare outcomes between individuals receiving housing assistance upon prostate cancer diagnosis and a comparison group without housing assistance, using propensity score matching to balance sociodemographic and clinical characteristics.RESULTSThere were 1,839 individuals with housing assistance (and 5,517 without assistance) included in the workup and treatment analyses and 4,451 individuals with housing assistance (and 13,353 without assistance) in the survival models. Receipt of housing assistance was not associated with guideline-concordant workup (62.7% vs 61.2%, OR 1.02 [95% CI 0.97, 1.07], p = 0.48) or active treatment (63.7% vs 62.2%, OR 1.02 [95% CI: 0.99, 1.06], p = 0.22) but was associated with improved overall survival in the 2 years following diagnosis (hazard ratio for mortality: 0.88 [95% CI: 0.81, 0.96]).CONCLUSIONSOlder adults receiving housing assistance at the time of a prostate cancer diagnosis experienced better overall survival than a matched comparison group without housing assistance. Results suggest that expanding access to housing assistance might support greater and more equitable survival in prostate cancer.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"244 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731707","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":"Integrating oncology advanced practice providers and clinical pharmacists into clinical cancer research.","authors":"Christa Braun-Inglis,Jamie Myers,Bridget O'Brien,Lisa Kottschade,Marie Flannery,Alisha T Detroye,Theresa Elko,Amy Leatherwood,Alyssa Mader,Siu Fun Wong,Melyssa Foust,Marie Bakitas,Al B Benson,Jeffrey L Berenberg,Brian Primeaux,Margaret Rosenzweig,Kimberly Demirhan,Tiffany Statler,Wendy Vogel,Virginia Sun","doi":"10.1093/jnci/djag125","DOIUrl":"https://doi.org/10.1093/jnci/djag125","url":null,"abstract":"Oncology Advanced Practice Providers (APPs) including Advanced Practice Registered Nurses, Physician Assistants, and Clinical Pharmacists (CPs), play a vital role in delivering high-quality, patient-centered cancer care across the United States. Despite their widespread presence in oncology practices, APPs remain underutilized in cancer clinical research, representing a missed opportunity to expand trial access and improve patient outcomes. Clinical trials are essential to advancing oncology care, yet participation remains critically low among adult patients. Given Oncology APPs' and CPs' central role in cancer care delivery, their meaningful engagement in oncology clinical trial research is imperative as the standard of oncology care. This position paper, with contributions from five professional societies, presents solutions and resources to barriers limiting APPs' and CPs' involvement in cancer clinical research, including gaps in education, role expectations, limited protected time, restrictive policies, insufficient financial support, and under-recognition of contributions. Integrating APPs and CPs more fully into the clinical research enterprise is essential to improving trial access, patient outcomes, closing equity gaps, and accelerating innovation in oncology care.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731663","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":"Premenopausal and postmenopausal obesity and endometrial cancer risk: circulating biomarkers of inflammation, insulin resistance, and sex hormones as mediators.","authors":"Sabrina E Wang,Vivian Viallon,Carine Biessy,Tracy O'Mara,Maria Kyrgiou,Laura Burney Ellis,Emma J Crosbie,Holly Baker-Rand,James Yarmolinsky,Pekka Keski-Rahkonen,Mattias Johansson,Agnès Fournier,Marianne Canonico,Sabine Naudin,Renée Turzanski Fortner,Charlotte Le Cornet,Matthias Schulze,Marta Crous-Bou,Maria-Jose Sánchez,Amaia Aizpurua,Natalia Cabrera Castro,Marcela Guevara,Giovanna Masala,Rosario Tumino,Maria Teresa Giraudo,Camilla Panico,Ruth C Travis,Marc J Gunter,Sabina Rinaldi,S Ghazaleh Dashti,Laure Dossus","doi":"10.1093/jnci/djag119","DOIUrl":"https://doi.org/10.1093/jnci/djag119","url":null,"abstract":"BACKGROUNDObesity may increase endometrial cancer risk through pathways involving chronic inflammation, insulin resistance, and altered sex hormone levels.METHODSWithin the European Prospective Investigation into Cancer and Nutrition cohort, we investigated these mediating pathways using pre-diagnostic circulating biomarkers measured in 337 matched case-control pairs with postmenopausal measurements and 196 pairs with premenopausal measurements. We estimated the natural indirect effect (NIE) of obesity [body mass index (BMI) ≥30 kg/m2 vs < 25 kg/m2] on endometrial cancer risk: (1) for each biomarker separately, (2) for all biomarkers jointly, and (3) sequentially, accounting for upstream biomarkers based on an assumed causal sequence specified a priori.RESULTSThe adjusted odds ratio (OR) between obesity and endometrial cancer risk was 3.34 [95% confidence interval (CI) 1.97 to 5.65] in the postmenopausal analysis, and 3.24 (1.43 to 7.36) in the premenopausal analysis. Jointly, the ORNIE through all biomarkers was 1.82 [CI 1.21 to 2.74; proportion mediated (P.M.)=50%] in the postmenopausal analysis and 1.79 (0.97 to 3.29; 49%) in the premenopausal analysis. In sequential mediation analysis, estrone [ORNIE =1.20 (CI 1.02 to 1.41); P.M. = 15%] remained a key mediator beyond upstream biomarkers in the postmenopausal analysis and interleukin-6 (IL-6) [1.35 (1.03 to 1.78); 24%] remained a key mediator in the premenopausal analysis.CONCLUSIONSCirculating biomarkers for inflammation, insulin resistance, and sex hormones may mediate the effect of obesity on endometrial cancer risk, with some overlaps in mediating pathways. Sex hormones were the most prominent mediators in postmenopausal obesity, whereas biomarkers for inflammation may play an important role in premenopausal obesity.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731656","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":"Risk of autoimmune and rheumatic diseases in breast cancer patients with silicone breast implants.","authors":"Jonathan Spoor,Marc A M Mureau,Daphne de Jong,Renaud L M Tissier,Marijn Vis,Hinne Rakhorst,Juliëtte Hommes,Mintsje de Boer,Hester S A Oldenburg,Esther M Heuts,Yvonne L J Vissers,Anneriet E Dassen,Daniel J Evers,Linetta B Koppert,Laura H Zaal,Rene R W J van der Hulst,Marie-Jeanne T F D Vrancken Peeters,Eveline M A Bleiker,Flora E van Leeuwen","doi":"10.1093/jnci/djag115","DOIUrl":"https://doi.org/10.1093/jnci/djag115","url":null,"abstract":"BACKGROUNDOver the past decade, various large observational studies have suggested an association between silicone breast implants (SBIs) and autoimmune and rheumatic diseases (ARDs), rekindling long-standing breast implant-safety concerns among breast cancer survivors with breast reconstructions and newly diagnosed breast cancer patients.METHODSWe investigated the association between SBIs and ARDs in a large multicenter cohort of women treated for breast cancer, part of whom received SBIs for reconstructive purposes. Clinical data and events of interest were identified through linkages with prospectively maintained nationwide- and institutional registries. Hazard Ratios (HRs) for ARDs were calculated using Cox proportional hazards regression models adjusted for potential confounders.RESULTSOf 12,262 women in the cohort, 3,082 (25%) had received SBI-based breast reconstructions. Median follow-up time was 12.0 (IQR, 7.0) years. The event rate of ARD-diagnoses was 62.5 per 10,000 person-years. Compared with women without SBI-exposure, women with an implant-based breast reconstruction did not have an increased risk of ARDs (multivariably adjusted HR, 1.06, 95% CI [0.89 to 1.27]). In addition, no statistically significant association was found between SBI-exposure and inflammatory arthritis, systematic rheumatic disease, inflammatory dermatosis, inflammatory bowel disease or any specific condition. Sensitivity analyses in which SBI-exposure was analyzed as a time-dependent variable confirmed the results of the main analysis.CONCLUSIONThe findings of this study indicate that SBI-exposure is not associated with an increased risk of ARDs in women with breast cancer and challenge the results of earlier studies in women with cosmetic implants.REGISTRATIONThis study is registered at ClinicalTrials.gov on June 2nd 2022 (NCT05400954).","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719482","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":"Oncofertility patterns after the overturn of Roe v. Wade.","authors":"Nikita V Baclig,Jordyn Silverstein,Vrushangi Shah,Beth Karlan,Sidharth R Anand,John A Glaspy","doi":"10.1093/jnci/djag111","DOIUrl":"https://doi.org/10.1093/jnci/djag111","url":null,"abstract":"The 2022 U.S. Supreme Court decision Dobbs v. Jackson Women's Health Organization raised concerns about access to fertility care for patients with cancer, yet there is limited evidence of its real-world impact. We conducted a national survey of National Comprehensive Cancer Network (NCCN) Member Institutions to evaluate changes in fertility preservation access and utilization in the 24 months following Dobbs. Of 33 institutions surveyed, 24 (72.7%) responded. Most institutions (83.3%) reported that reproductive care remained a clinical priority, and 62.5% reported increased fertility preservation utilization. Nearly all respondents reported stable or expanded institutional resources and staffing to support oncofertility services. Institutions in less restrictive states appeared to absorb increased demand, however notable non-response from institutions in restrictive policy environments limited our findings. This study suggests relative resilience among academic cancer centers, but highlights the need for further study to ensure equitable access to fertility preservation in the post-Dobbs era.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708466","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":"The impact of survivorship care on burden of disease among Hodgkin lymphoma survivors","authors":"Eline MJ Lammers, Josée M Zijlstra, Michael Schaapveld, Juanita A Haagsma, Cécile PM Janus, Karin M Aarsman, Liane CJ Te Boome, Maaike MG Schippers, Rinske S Boersma, Saskia E Rademakers, Wouter J Plattel, Lara H Böhmer, Marieke Van Den Berg, Adriaantje C Kroeze, Leonie S Strobbe, Wendy Deenik, Heleen S De Lil, Berthe MP Aleman, Flora E Van Leeuwen, Annelies Nijdam","doi":"10.1093/jnci/djag080","DOIUrl":"https://doi.org/10.1093/jnci/djag080","url":null,"abstract":"Background Hodgkin lymphoma (HL) survivors are at increased risk of late adverse events, eg cardiovascular diseases (CVD), breast cancer (bc), hypothyroidism and severe infections. At Dutch BETER clinics, HL survivors are regularly screened for (risk factors for) these adverse events. The impact of survivorship care on burden of disease from adverse outcomes has rarely been evaluated. Methods In a nationwide retrospective cohort study, we compared HL survivors invited for BETER care in 2013 to 2016 (intervention group) with matched survivors who were eligible for such care, but were not invited until 2019 to 2024 (comparison group). Incidence and mortality rates for CVD, bc, hypothyroidism and severe infections were collected from general practitioners and nationwide registries. Disability-adjusted life years (DALYs) attributable to late adverse events were compared using multivariable regression models. Results At study start, survivors in the intervention group (n = 491) and comparison group (n = 373) had a median age of 46 years; median time since HL diagnosis was 15 to 18 years. After 8.5 years (median), there were no significant differences in DALYs attributable to CVD, bc, hypothyroidism and severe infections between the groups. In both groups, approximately one third of survivors acquired DALYs attributable to adverse events. Adherence to recommended screening diagnostics was high, but cardiovascular risk management and vaccination rates were suboptimal. Conclusion After 8.5 years of follow-up, survivorship care for HL survivors was not associated with lower disease burden. Better care coordination, amendment of the cardiovascular risk management guidelines and greater survivor involvement may improve long-term effectiveness of measures to prevent late adverse events.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666516","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":"Vaccine adherence among adult cancer survivors in the United States","authors":"Kimberly Feng, Cancan Zhang, Kenneth J Mukamal","doi":"10.1093/jnci/djag118","DOIUrl":"https://doi.org/10.1093/jnci/djag118","url":null,"abstract":"Adults with cancer are at risk for complications from vaccine-preventable diseases, yet vaccine adherence in this population remains poorly characterized. This cross-sectional study used the National Health Interview Survey 2019 to 2023 to examine trends in influenza, pneumococcal, and shingles vaccines among adults aged ≥50 years with cancer. Of the 6,533 respondents included, only 30.6% (95% confidence interval [CI; 29.3%, 31.9%]) reported receiving all three recommended vaccines. Factors associated with lower vaccination adherence included younger age (odds ratio [OR] comparing ages ≥75 to 50 to 64 years 5.39; 95% CI [4.70, 6.18]), male sex (OR 0.81; 95% CI [0.73, 0.90]), Black (OR 0.59; 95% CI [0.47, 0.73]) or Hispanic race/ethnicity (OR 0.69; 95% CI [0.52, 0.92]), Medicaid insurance (OR 0.79; 95% CI [0.65, 0.96]), and lower educational attainment (OR 0.65; 95% CI [0.58, 0.73]). Preventable disease vaccination remains subpar in the adult cancer population, and further efforts including targeted interventions are necessary to improve preventative health efforts in these patients.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666514","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":"Identification of immune cell type-specific susceptibility genes in multiple cancers using transcriptome-wide association studies.","authors":"Fei Qin,Xing Hua,Xiaoyu Wang,Haoyu Zhang,Jiyeon Choi,Xiaohong R Yang,Tongwu Zhang,Mitchell J Machiela,Samuel Anyaso-Samuel,Maria Teresa Landi,Sonja I Berndt,Mark P Purdue,Demetrius Albanes,Bin Zhu,Kevin M Brown,Jianxin Shi,Kai Yu","doi":"10.1093/jnci/djag108","DOIUrl":"https://doi.org/10.1093/jnci/djag108","url":null,"abstract":"BACKGROUNDTranscriptome-wide association studies (TWAS) integrate gene expression and genome-wide association studies (GWAS) to identify disease susceptibility genes. Because gene expression varies substantially across cell types within tissues, cell type-specific prediction models may enhance the power of TWAS.METHODSWe conducted cell type-specific TWAS leveraging single-cell RNA sequencing data from the OneK1K cohort (14 immune cell types, 1.27 million cells) and GWAS summary statistics for seven cancers (>290,000 cases in total). To improve prediction accuracy, we developed a modeling framework that incorporates shared gene expression effects across cell types.RESULTSAt a false discovery rate of 5% (Bonferroni 5%), we identified 106 (13) previously unreported loci for breast cancer, 51 (4) loci for prostate cancer, 11 (4) loci for lung cancer, 39 (5) loci for melanoma, 9 (1) loci for ovarian cancer, and 2 (1) loci for diffuse large B-cell lymphoma, with most genes exhibiting cell type specificity. Gene set analyses confirmed joint associations of unreported genes with breast and prostate cancer risk in UK Biobank data. Additional lung tissue scRNA-seq data with 113 individuals validated 18 of 32 (56.3%) significant genes for lung cancer. Across cancers, 139 significant genes were shared by at least two cancer types and were primarily enriched in specific immune cell types.CONCLUSIONCell type-specific TWAS improves the identification of novel cancer susceptibility loci and provides insights into the immune landscape of cancer etiology.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663723","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":"Belzutifan Efficacy in Von Hippel-Lindau Disease-Associated Renal Cell Carcinoma Versus Natural History Control Arm.","authors":"W Marston Linehan,Thomas Jemielita,Jerry Cornell,Ke Chen,Mark W Ball,Ramaprasad Srinivasan,Yanfang Liu,Rodolfo F Perini,Cathy Anne Pinto","doi":"10.1093/jnci/djag064","DOIUrl":"https://doi.org/10.1093/jnci/djag064","url":null,"abstract":"BACKGROUNDRandomized controlled trials are the gold standard for demonstrating treatment efficacy. When infeasible, external control arm (ECA) analysis is an effective way to interpret treatment arm results. We developed an ECA for a single-arm trial (LS-004) for a HIF-2α inhibitor (belzutifan) in 61 patients with VHL renal cell carcinoma (RCC) to help interpret results. With a median follow-up of 37.8 months in LS-004, the ORR was 64% (95% CI = 50.6 to 75.8); median time to surgery was not reached.METHODSThe ECA was developed using natural history study data for VHL RCC patients undergoing active surveillance with ≤5 years of follow-up. Key LS-004 eligibility criteria were applied. Propensity score (PS) weighting was used to balance prognostic factors, with balance evaluated using standardized mean difference (SMD). PS adjusted point estimates and 95% CI for ORR and time to surgery (TTS) are presented. For the ECA, ORR was evaluated among patients with ≥3 scans to optimize for confirmed responses.RESULTSThe ECA included 244 patients (167 for ORR analysis). Prognostic factors were balanced with SMD < 0.1 for all covariates. PS adjusted ORR for LS-004 and ECA was 63.9% (95% CI = 51.9 to 76.0) and 1.5% (95% CI = 0.0 to 3.3), respectively. Median TTS was 51.3 (95% CI = 43.8 to not yet reached) months in ECA; not yet reached in LS-004.CONCLUSIONSThe belzutifan treatment effect is large compared with the ECA, supporting belzutifan efficacy in VHL RCC. Although residual confounding is possible, the large effect is unlikely due to chance.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655683","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}