Malay K Sannigrahi, Lovely Raghav, Dominick J Rich, Travis P Schrank, Joseph A Califano, John N Lukens, Lova Sun, Iain M Morgan, Roger B Cohen, Alexander Lin, Xinyi Liu, Eric J Brown, Jianxin You, Lisa Mirabello, Sambit K Mishra, David Shimunov, Robert M Brody, Alexander T Pearson, Phyllis A Gimotty, Ahmed Diab, Jalal B Jalaly, Devraj Basu
{"title":"Tumor-intrinsic and immune-related features associated with treatment failure in human papillomavirus-related oropharyngeal cancer","authors":"Malay K Sannigrahi, Lovely Raghav, Dominick J Rich, Travis P Schrank, Joseph A Califano, John N Lukens, Lova Sun, Iain M Morgan, Roger B Cohen, Alexander Lin, Xinyi Liu, Eric J Brown, Jianxin You, Lisa Mirabello, Sambit K Mishra, David Shimunov, Robert M Brody, Alexander T Pearson, Phyllis A Gimotty, Ahmed Diab, Jalal B Jalaly, Devraj Basu","doi":"10.1093/jnci/djaf053","DOIUrl":"https://doi.org/10.1093/jnci/djaf053","url":null,"abstract":"Background Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors. Methods 50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced. Groups were compared by gene set enrichment analysis, and select differences were validated by immunohistochemistry. Features discriminating groups were scored in each tumor using gene set variation analysis, and scores were evaluated for recurrence prediction ability. Results Cases downregulated pathways linked to anti-tumor immunity (FDR-adjusted p<.05) and contained fewer tumor-infiltrating lymphocytes (p<.001), including cytotoxic T-cells (p=.005). Cases also upregulated pathways related to cell division and other aspects of tumor progression. Upregulated and downregulated pathways were respectively used to define a tumor progression score (TPS) and immune suppression score (ISS) for each tumor. Correlation between TPS and ISS (r=.603, p<.001) was potentially explained by observed upregulation of DNA repair pathways in cases, which might enhance their progression directly and by limiting cytosolic DNA-induced inflammation. Accordingly, cases contained fewer double-strand breaks based on staining for phospho-RPA32 (p=.006) and γ-H2AX (p=.005) and downregulated the cytosolic DNA sensing pathway. A combined score derived from TPS and ISS optimized recurrence prediction and stratified survival in a manner generalizable to three external cohorts. Conclusions We describe a potential link in HPV+ OPSCCs between reduced DNA damage and other tumor-intrinsic and immune-related contributors to recurrence risk, opening opportunities to detect and target this high-risk biology.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599842","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}
Yuhan Huang, Marilyn L Kwan, Susan R Heckbert, Nicholas L Smith, Megan Othus, Cecile A Laurent, Janise M Roh, Eileen Rillamas-Sun, Valerie S Lee, Tatjana Kolevska, Richard K Cheng, Carlos Irribarren, Mai Nguyen-Huynh, Dawn L Hershman, Lawrence H Kushi, Heather Greenlee
{"title":"Endocrine therapy and risk of cardiovascular disease and mortality in postmenopausal breast cancer survivors","authors":"Yuhan Huang, Marilyn L Kwan, Susan R Heckbert, Nicholas L Smith, Megan Othus, Cecile A Laurent, Janise M Roh, Eileen Rillamas-Sun, Valerie S Lee, Tatjana Kolevska, Richard K Cheng, Carlos Irribarren, Mai Nguyen-Huynh, Dawn L Hershman, Lawrence H Kushi, Heather Greenlee","doi":"10.1093/jnci/djaf063","DOIUrl":"https://doi.org/10.1093/jnci/djaf063","url":null,"abstract":"Background There are increasing concerns of cardiovascular safety related to endocrine therapy use in women with breast cancer (BC). We examined risk of cardiovascular disease (CVD) events and mortality associated with endocrine therapy use in postmenopausal women with early-stage BC. Methods Postmenopausal women diagnosed with stage I-III hormone receptor-positive BC from 2005 to 2013 were included (n = 8,495). Women were classified as aromatase inhibitor (AI) users, tamoxifen users, and non-users of endocrine therapy in the 12 months after BC diagnosis. Likelihood ratio tests examined whether the association of endocrine therapy use with CVD and mortality outcomes varied by body mass index (BMI) and history of CVD before BC diagnosis. Results Over a median follow-up of 7.5 years, women who used AIs were less likely to develop major adverse cardiovascular events (MACE) (HR = 0.84, 95% CI: 0.73-0.97) and heart failure (HR = 0.81, 95% CI: 0.66-0.99) compared with non-users of endocrine therapy. No associations between tamoxifen use and CVD outcomes were observed. AI use was associated with lower risk all-cause, CVD-related, and non-CVD-related mortality, compared with non-use of endocrine therapy. Tamoxifen use was associated with lower risk of all-cause mortality and non-CVD-related mortality, compared with non-use of endocrine therapy, and the association was modified by BMI (P for interaction <0.05). Conclusion Our findings suggest endocrine therapy use reduces all-cause mortality risk and may not increase CVD risk in postmenopausal women with early-stage hormone receptor-positive BC.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599811","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}
Mu-Hsing Ho, Lizhen Wang, Justin Wei Ho Wong, Gongkai Xin, Qianyi Zhang, Yen-Kuang Lin, Denise Shuk Ting Cheung, Janette L Vardy, Chia-Chin Lin
{"title":"Comparative effectiveness of various nonpharmacological interventions, including traditional Chinese medicine-based interventions for cancer-related cognitive impairment: a comprehensive network meta-analysis","authors":"Mu-Hsing Ho, Lizhen Wang, Justin Wei Ho Wong, Gongkai Xin, Qianyi Zhang, Yen-Kuang Lin, Denise Shuk Ting Cheung, Janette L Vardy, Chia-Chin Lin","doi":"10.1093/jnci/djaf059","DOIUrl":"https://doi.org/10.1093/jnci/djaf059","url":null,"abstract":"Background Cancer-related cognitive impairment is a common complication of cancer and its treatment. The effectiveness of Traditional Chinese Medicine (TCM)-based interventions in improving subjective and objective cognitive function has not yet been investigated in previous network meta-analyses. This study aimed to evaluate the comparative effectiveness of nonpharmacological interventions including TCM-based interventions, and to rank the best option for improving cognitive function among adults with non-central nervous system cancer. Methods PubMed, Embase, ProQuest, Scopus, and CNKI were searched from their inception until May 2024, for relevant randomized controlled trials. A random-effects model was utilized for conducting network meta-analysis. The primary endpoint evaluated the impact of interventions on subjective or objective cognitive function. Results In total, 84 randomized controlled trials were included and 15 nonpharmacological interventions were identified with no reported significant adverse events. Tai Chi/Qigong demonstrated the highest probability (SMD = 2.10, 95% CI 0.62 to 3.59) of improving subjective cognitive function. Cognitive rehabilitation was ranked the best with the highest probability for improving overall cognitive function (SMD = 1.49, 95% CI 0.41 to 2.58) and executive function as well as language domains. Acupoint stimulation was the top-ranking approach for enhancing visuospatial and motor function domain (SUCRA 84.3%, SMD = 0.94, 95% CI 0.13 to 1.76). Conclusions Tai Chi/Qigong demonstrated the highest effectiveness in addressing subjective cognitive complaints. Cognitive rehabilitation was the most effective intervention across various domains including overall objective cognitive function, executive function, and language. Acupoint simulation was the most effective intervention for improving visuospatial and motor domain functions.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599817","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}
A Jay Holmgren, Nate C Apathy, Jennie Crews, Tait Shanafelt
{"title":"National trends in oncology specialists’ EHR inbox work, 2019–2022","authors":"A Jay Holmgren, Nate C Apathy, Jennie Crews, Tait Shanafelt","doi":"10.1093/jnci/djaf052","DOIUrl":"https://doi.org/10.1093/jnci/djaf052","url":null,"abstract":"Background Electronic health record (EHR) burden is an important driver of the ongoing physician burnout crisis. EHR-based messaging (also known as inbox) in particular, including messages from patients, is associated with burnout and decreased well-being. Little is known regarding EHR messaging burden for oncologists. To address this, we assessed trends in oncologist EHR messaging volume and EHR time from 2019-2022 across oncology sub-specialties. Methods This study used EHR metadata for all US oncology physicians (including medical oncologist/hematologists, radiation oncologists, pediatric oncologists, gynecologic oncologists, and surgical oncologists) providing ambulatory care using an Epic EHR to measure inbox volume and EHR time from July 2019 through April 2022. Descriptive statistics and multi-variable regression were used to evaluate differences over time and across sub-specialties. Results This sample of 15,653 oncology physicians across 43,228,633 ambulatory visits found that message volume for oncologists increased 19.0% from 2019 to 2022, and patient-initiated messages increased 34.0%. EHR time increased 16.2% from 2019 to 2022, while EHR “work outside of work” time increased 12.1%. Medical oncologist/hematologists had the highest inbox volume, patient-message volume, and EHR time of oncology sub-specialists. Conclusion Rising levels of EHR work and message volume among oncology physicians are concerning given the role of EHR burden in physician burnout. Oncologists have seen increased EHR time and message volume, especially patient-initiated messages, following the onset of the COVID pandemic. Health system leaders and policymakers should invest in efforts to reduce EHR and inbox burden for all oncologists, with a focus on those with the greatest burden.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546146","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}
Laura Pala, Federico Merlo, Isabella Sala, Eleonora Pagan, Chiara Oriecuia, Claudia Specchia, Chiara Catania, Emilia Cocorocchio, Daniele Laszlo, Giovanni Ceresoli, Marzia Locatelli, Tommaso De Pas, Alberto Zambelli, Javier Cortes, Giuseppe Giaccone, Kathleen N Moore, Aditya Bardia, Giuseppe Viale, Richard D Gelber, Vincenzo Bagnardi, Fabio Conforti
{"title":"Surrogate endpoints for overall survival in randomized clinical trials testing antibody-drug conjugates","authors":"Laura Pala, Federico Merlo, Isabella Sala, Eleonora Pagan, Chiara Oriecuia, Claudia Specchia, Chiara Catania, Emilia Cocorocchio, Daniele Laszlo, Giovanni Ceresoli, Marzia Locatelli, Tommaso De Pas, Alberto Zambelli, Javier Cortes, Giuseppe Giaccone, Kathleen N Moore, Aditya Bardia, Giuseppe Viale, Richard D Gelber, Vincenzo Bagnardi, Fabio Conforti","doi":"10.1093/jnci/djaf049","DOIUrl":"https://doi.org/10.1093/jnci/djaf049","url":null,"abstract":"Background The surrogacy of overall response-rate (ORR) or progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing antibody-drugs conjugates (ADC) has never been investigated. Methods RCTs testing ADCs in patients with advanced solid tumors and reporting data on OS and PFS and/or ORR were analyzed. The main objective was to assess the trial-level association between the surrogate endpoints (ORR or PFS) and the reference endpoint (OS), overall and in subgroups of trials defined by tumor type, number of previous lines of systemic treatments, and specific ADC features. Results Twenty-five RCTs, for a total of 26 treatment comparisons and 11,729 patients, were included in the analysis. In 21 comparisons the ADC was administered as monotherapy, and in 16 was tested in patients with breast cancer. The association between the hazard ratio for OS and relative risk of ORR was moderate: the R2 from a model adjusted by tumor type was 0.47 (95%CI,0.11-0.83).The association between the hazard ratios for OS and PFS was strong: the R2 from the adjusted model was 0.79 (95%CI,0.66-0.92). Cross-validation analyses showed similar results. Consistent results were obtained across all the subgroups analyzed, with the notable exception of the subgroup of trials testing ADCs for breast cancer, where the association between OS and ORR appeared strong (R2=0.77; 95%CI,0.51-0.90). Conclusions In RCTs evaluating ADCs in advanced solid tumors, PFS serves as a robust surrogate endpoint for OS, offering greater reliability than ORR and adequately supporting accelerated approval of ADCs in future trials.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546208","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}
Yue Liu, Mingyang Song, Edward L Giovannucci, Elizabeth A Platz
{"title":"Pre- and post-diagnostic use of antihypertensive medications and stage I-III colorectal cancer survival: prospective cohort study","authors":"Yue Liu, Mingyang Song, Edward L Giovannucci, Elizabeth A Platz","doi":"10.1093/jnci/djaf046","DOIUrl":"https://doi.org/10.1093/jnci/djaf046","url":null,"abstract":"Antihypertensive medications have been investigated in relation to colorectal cancer (CRC)-specific survival. To address limitations and important unanswered questions in the existing evidence, we investigated associations of pre- and post-diagnostic use of antihypertensive classes—beta-blockers, calcium channel blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, furosemide, and other antihypertensives—with CRC-specific mortality among 2,182 patients with stage I-III CRC in the Nurses’ Health Study and Health Professionals Follow-up Study in a prospective cohort study with long-term follow-up, repeat assessments of antihypertensive use, and rigorous confounding control. Pre- and post-diagnostic use of each antihypertensive class studied was not clearly associated with stage I-III CRC survival compared with either non-users or with patients with high blood pressure who used any other antihypertensives. While we did not detect an association for overall use of specific antihypertensives, future investigations should investigate drug dose and interactions between antihypertensive medications and cancer therapies with CRC survival.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546210","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}
Rishi Robert Sekar, Laura Zebib, Kristian Donald Stensland, Lindsey Allison Herrel
{"title":"Structural inequities in the availability of prostate cancer clinical trial opportunities","authors":"Rishi Robert Sekar, Laura Zebib, Kristian Donald Stensland, Lindsey Allison Herrel","doi":"10.1093/jnci/djaf047","DOIUrl":"https://doi.org/10.1093/jnci/djaf047","url":null,"abstract":"Prostate cancer is marked by vast disparities in clinical outcomes for minoritized and socioeconomically disadvantaged populations. We aimed to evaluate the geographic distribution of prostate cancer clinical trial opportunities relative to prostate cancer mortality and social determinants of health by performing an ecological analysis of linked county-level prostate cancer clinical trial data, epidemiologic data, and the Centers for Disease Control and Prevention Social Vulnerability Index. On analysis of 1,575 counties in the United States with available data, increasing SVI was associated with an increase in prostate cancer mortality (+17.88, 95% CI 14.16–21.61, p < .001), lower odds of having any trial (OR 0.14, 95% CI 0.09–0.23, p < .001), and fewer population-adjusted trials (IRR 0.27, 95% CI 0.19–0.40, P < .001). Identifying communities experiencing adverse social determinants of health for expansion of clinical trial opportunities and mitigation of barriers may be an impactful strategy towards improving equity in clinical trials and cancer care.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546209","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}
Charlotte Ouimet, Bianca Fodor, Joseph C Del Paggio, Jonathan Kimmelman
{"title":"Proportion of patients in phase 2 oncology trials receiving treatments that are ultimately approved","authors":"Charlotte Ouimet, Bianca Fodor, Joseph C Del Paggio, Jonathan Kimmelman","doi":"10.1093/jnci/djaf013","DOIUrl":"https://doi.org/10.1093/jnci/djaf013","url":null,"abstract":"Background Many patients enroll in phase 1 dose expansion cohorts or phase 2 clinical trials (together referred to below as “phase 2”) seeking access to novel treatments. Little is known about the extent to which they benefit by enrolling. Herein, we use a novel metric of benefit—therapeutic proportion—to assess the probability that patients in phase 2 trials receive treatment that eventually advances to FDA (Food and Drug Administration) approval for their condition. Methods We randomly sampled 400 trials identified in a search of Clinicaltrials.gov for cancer phase 2 trials initiated between November 1, 2012 and November 1, 2015. We determined whether the drug/dose/indication tested in each trial advanced to FDA approval within 7.5 years. We determined whether the drug/dose/indication presented substantial clinical benefit using the ESMO-MCBS (European Society for Medical Oncology - Magnitude of Clinical Benefit Scale), or whether it received off-label recommendation in NCCN (National Comprehensive Cancer Network) guidelines. Results Collectively, trials in our sample enrolled 25 002 patient-participants in 608 specific treatment cohorts. A total of 4045 patients received a treatment that advanced to FDA approval (16.2%; 95% CI = 10.3 to 22.7). The therapeutic proportion increased to 19.4% (95% CI = 14.1 to 25.8) when considering NCCN off-label recommendations and decreased to 9.3% (95% CI = 4.7 to 14.6) for FDA-approved regimens considered being of substantial clinical benefit by ESMO-MCBS. Bootstrap test of mean difference showed no statistical difference in proportions based on drug class, trial phase, or sponsorship. Conclusion One in 6 patients in phase 2 clinical trials receives treatments that are eventually approved. This represents a higher therapeutic value than phase 1 trials.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485782","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}
Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi
{"title":"Impact of screening for HPV-positive oropharyngeal cancers: a microsimulation-based modeling study","authors":"Rebecca Landy, Gregory W Haber, Barry I Graubard, Carole Fakhry, Nicole G Campos, Emily A Burger, Li C Cheung, Hormuzd A Katki, Maura L Gillison, Anil K Chaturvedi","doi":"10.1093/jnci/djaf033","DOIUrl":"https://doi.org/10.1093/jnci/djaf033","url":null,"abstract":"Background We estimated the impact of screening on morbidity and mortality of HPV16-positive oropharyngeal cancer among US men aged 45-79 years. Methods We developed an individual-level, state-transition natural history microsimulation model to estimate the impact of screening using oral HPV16 detection, HPV16-E6 antibody detection, and transcervical-ultrasound of neck/oropharynx. We compared clinical detection to counterfactual screen detection for cancer stage, single- vs multiple-modality treatment, and survival. Screening scenarios encompassed four progression speeds across cancer stages (very-slow, slow, fast, and very-fast) and four screening frequencies. Results Among US men aged 45-79 years in 2021 (N = 54,881,311), 163,958 clinically diagnosed HPV-positive oropharyngeal cancers and 32,009 deaths would occur through age 84 in the absence of screening. Assuming very-fast progression, 4%, 20%, 31%, and 60% of these cancers would be detected by one-off, 5-yearly, 3-yearly, and annual screening. Annual screening (very-fast progression) could reduce the number of cancers diagnosed at advanced stages (AJCC 7, Stages III/IV: 90.0% with no screening vs 59.1%) and treated by multiple-modalities (80.6% with no screening vs 50.6%). Cancer mortality would also be reduced by 36.2%, with a gain of 106,000 life-years. Annual screening would have a number needed to screen (NNS) of 561 per screen-detected cancer, 1,118 per additional cancer treated by single-modality, 4,740 per death prevented, and 520 per life-year gained; such high NNS reflect potential inefficiency of population-level screening. Conclusions If proven efficacious in randomized trials and cost-effective, screening for HPV-positive oropharyngeal cancers could provide considerable population-level reductions in advanced stage cancers, treatment-related morbidities, and mortality.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258399","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}
Luca Arecco, Eva Blondeaux, Marco Bruzzone, Grazia Arpino, Carmine De Angelis, Michelino De Laurentiis, Roberta Caputo, Alessandra Fabi, Valeria Sanna, Stefania Gori, Fabio Puglisi, Luca Boni, Simone Nardin, Irene Giannubilo, Marta Perachino, Roberto Borea, Elisa Agostinetto, Evandro de Azambuja, Matteo Lambertini, Lucia Del Mastro
{"title":"Prognostic implications of risk definitions from the monarchE and NATALEE trials","authors":"Luca Arecco, Eva Blondeaux, Marco Bruzzone, Grazia Arpino, Carmine De Angelis, Michelino De Laurentiis, Roberta Caputo, Alessandra Fabi, Valeria Sanna, Stefania Gori, Fabio Puglisi, Luca Boni, Simone Nardin, Irene Giannubilo, Marta Perachino, Roberto Borea, Elisa Agostinetto, Evandro de Azambuja, Matteo Lambertini, Lucia Del Mastro","doi":"10.1093/jnci/djaf031","DOIUrl":"https://doi.org/10.1093/jnci/djaf031","url":null,"abstract":"Background The monarchE and NATALEE trials employed different high-risk inclusion criteria. Main objective is to assess prognostic differences based on their inclusion criteria. Methods Patients with hormone receptor-positive/HER2-negative early breast cancer enrolled in the phase III MIG1, GIM2, and GIM3 trials were categorized as high-risk cohort (HRC) and low-risk cohort (LRC) according to the inclusion criteria of monarchE and NATALEE trials. Subsequently, they were further classified in three different cohorts concordant LRC (low-risk for both trials), discordant risk cohort (high-risk for only one trial), and concordant HRC (high-risk for both trials). Main outcomes were disease-free survival (DFS) and overall survival (OS). Results Among 4,795 patients included, 1,343 (28.0%) and 2,689 (56.1%) were classified as HRC according to the monarchE and NATALEE, respectively.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191925","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}