Journal of the National Cancer Institute最新文献

{"title":"Menopause-related quality of life five years after salpingectomy with delayed oophorectomy versus Salpingo-Oophorectomy.","authors":"Tamar A Gootzen,Rosella Pmg Hermens,Marleen Mhj van Gelder,Elle Heijnen,Majke Hd van Bommel,Mirjam Ja Apperloo,Monique Ma Brood-van Zanten,Sjors Fpj Coppus,Jose Ae Custers,Helena C van Doorn,Katja N Gaarenstroom,Marline G Harmsen,Joanna intHout,Marjan Knippenberg,Luc Rcw van Lonkhuijzen,Marian Je Mourits,Jurgen Mj Piek,Teska N Schuurman,Michiel Simons,Brigitte Fm Slangen,Rachel Tros,M Caroline Vos,Ronald P Zweemer,C Marleen Kets,Joanne A de Hullu,Miranda P Steenbeek","doi":"10.1093/jnci/djag110","DOIUrl":"https://doi.org/10.1093/jnci/djag110","url":null,"abstract":"PURPOSEBRCA1/2 pathogenic variant (PV) carriers have an increased risk of tubo-ovarian cancer. They are recommended to have a risk-reducing salpingo-oophorectomy around age 40, resulting in premature menopause. The alternative risk-reducing salpingectomy (RRS) with delayed oophorectomy (DO) postpones this. We present the five year results of a nationwide preference trial (TUBA study) comparing menopause-related quality of life (QoL) after RRS/DO to salpingo-oophorectomy.METHODSPremenopausal BRCA1/2-PV carriers aged 25 to 40 (BRCA1) or 25 to 45 (BRCA2) chose RRS/DO or salpingo-oophorectomy with or without hormonal replacement therapy (HRT). We compared QoL (Greene Climacteric Scale) between RRS/DO and salpingo-oophorectomy without HRT five years after surgery using linear mixed models. Secondarily, RRS/DO was compared to salpingo-oophorectomy with HRT. Women who underwent oophorectomy in the RRS/DO group were excluded in a sensitivity analysis.RESULTSIn total 410 (71.9%) participants chose RRS/DO and 160 (28.1%) salpingo-oophorectomy. Seventy-three (17.8%) participants underwent oophorectomy within five years after salpingectomy. The adjusted mean difference (aMD) in QoL was 1.8 (95%-confidence interval (CI) -0.6; 4.3) after salpingo-oophorectomy without HRT and 1.4 (95%-CI -0.4; 3.1) after salpingo-oophorectomy with HRT compared to RRS (with and without oophorectomy) at five years follow-up. The sensitivity analysis showed that QoL decreased less after RRS before oophorectomy compared to salpingo-oophorectomy without (aMD 2.4, 95%-CI 0.1; 4.8) and with HRT (aMD 1.9, 95% CI 0.1; 3.7).CONCLUSIONPostponing oophorectomy is key in preventing deterioration of QoL. QoL was similar five years after salpingectomy (with and without oophorectomy) compared to salpingo-oophorectomy (regardless of HRT use). However, QoL was higher when comparing salpingectomy without oophorectomy to salpingo-oophorectomy (regardless of HRT use).","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641553","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":"Consensus radiation therapy organ at risk constraints for NCTN trials in hematologic malignancies","authors":"Austin J Sim, Bradford S Hoppe, Leslie K Ballas, Sarah A Milgrom, Stephanie A Terezakis, Chul S Ha, Nicholas B Figura, Rahul R Parikh, John C Grecula, John P Plastaras, Andrea C Lo, Jeffrey Ryckman, Stella Flampouri, Chelsea C Pinnix, Christopher R Kelsey","doi":"10.1093/jnci/djag112","DOIUrl":"https://doi.org/10.1093/jnci/djag112","url":null,"abstract":"Modern radiation therapy (RT) technologies allow for improved sparing of normal tissues, decreasing the risk of both acute and long-term toxicities. Existing RT dose constraints for prospective trials within the National Clinical Trials Network (NCTN) were formulated in the context of solid malignancies. As patients with hematologic malignancies are often treated with lower RT doses and are usually younger with more favorable prognoses, customized dose constraints are needed. The NRG Oncology Hematologic Malignancies Working Group (NRG HEME) commissioned a review of existing organ at risk (OAR) constraints from published primary literature, the NRG Center for Innovation in Radiation Oncology (CIRO), and national guidelines. Customized constraints were developed by iterative review by NRG HEME. Final recommendations were approved by radiation oncology representatives from all the lymphoma NCTN groups (NRG Oncology, COG, Alliance, ECOG-ACRIN, SWOG, CCTG). For 49 OARs, a strict recommended constraint was determined, of which 20 were not present in CIRO. Of the remaining 29 constraints, 20 were lower, 2 were the same, and 5 used different metrics; 2 were higher than at least one CIRO trial constraint. Acceptable variations were determined and unacceptable variations were added for select critical OARs for plan scoring. While doses to OARs without explicit unacceptable variations should not exceed acceptable variations, violations should not be considered for plan quality assessment on trials. This consensus list of standard OAR constraints should be incorporated for all future NCTN trials in hematologic malignancies. Strict dose constraints will minimize long-term toxicities in this patient population.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"131 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655733","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":"Evaluating the role of medicaid expansion on survival in early onset colorectal cancer.","authors":"Rohin Gawdi,Elizabeth Nilsson Sjolander,Joon Sub Lee,Richard L Whelan","doi":"10.1093/jnci/djag109","DOIUrl":"https://doi.org/10.1093/jnci/djag109","url":null,"abstract":"BACKGROUNDThe Affordable Care Act (ACA) expanded Medicaid eligibility to states on staggered timelines, creating a natural experiment to assess health policy effects on colorectal cancer (CRC) outcomes.METHODSWe conducted a retrospective quasi-experimental cohort study using the SEER database (2006 to 2019). Patients with CRC <65 years were included in primary analyses; a EOCRC cohort aged <50 years was examined. States were classified by Medicaid expansion timing, and each expansion group was propensity score-matched against non-expansion controls. The primary analysis used pooled Bayesian difference-in-differences survival models with censoring at 36 months, with sensitivity analyses at 60 months and uncapped follow-up. Secondary Bayesian logistic models evaluated stage at diagnosis and receipt of surgical resection. Results are reported as hazard ratios (HR) or odds ratios (OR) with 95% credible intervals (CrI) and posterior probabilities of benefit.RESULTSIn pooled analyses among patients younger than 65 years, Medicaid expansion was associated with reduced mortality (36-month HR = 0.86; 95%CrI, 0.81 to 0.92; P(HR < 1)>0.999), with consistent findings across follow-up endpoints. Survival benefit was larger among patients with early-onset CRC (age <50 years). No consistent association was observed among Medicare-eligible patients aged ≥65. Medicaid expansion was not associated with population-level shifts in stage at diagnosis or increased surgical resection.CONCLUSIONMedicaid expansion under the ACA was associated with a high probability of improved CRC survival among non-Medicare-eligible adults, including patients with early-onset disease. Survival gains occurred without corresponding changes in stage or surgical treatment, suggesting benefits mediated through improved access, continuity, and delivery of cancer care.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635842","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":"Cancer prevention in context: interplay of perceived discrimination, neighborhood deprivation, and cancer-related risk and protective factors.","authors":"Carrie A Miller,Anita M Kumar,Jason A Mendoza,Jeremy D Barsell,Obinna R Diala,Trevin E Glasgow,Bassam Dahman,Cathy Bradley,Ken Resnicow,Amy Leader,Katherine J Briant,Jenny N Poynter,Robert A Winn,Bernard F Fuemmeler","doi":"10.1093/jnci/djag101","DOIUrl":"https://doi.org/10.1093/jnci/djag101","url":null,"abstract":"BACKGROUNDSocio-environmental deprivation and discrimination are associated with poorer cancer outcomes, yet their combined impact remains understudied. This study examines the independent and combined impact of these factors on cancer-related outcomes.METHODSSurvey data (2018 to 2020) from 7,977 participants across six NCI-designated cancer centers assessed perceived discrimination (PD), area-level deprivation, lifestyle factors (smoking and obesity), and self-reported breast and colorectal cancer screening behaviors. Multivariate and multilevel logistic regression models estimated associations and the interclass correlation (ICC) quantified variation attributable to area-level factors.RESULTSHigh PD was associated with 2.28 times higher odds of current smoking (95% CI: 1.71-3.05) and 1.33 times higher odds of obesity (95% CI: 1.03-1.72), compared to those with low PD. Living in socially deprived areas increased the odds of smoking by 1.51 (95% CI: 1.20-1.89), relative to socially privileged areas. ICC estimates that 4% of the variation in the association between high PD on smoking, and 2% of the variation between medium PD and obesity, were attributable to area-level factors. Neither PD nor neighborhood disadvantage were significantly associated with being up-to-date on cancer screenings.CONCLUSIONSPD and neighborhood deprivation independently increase risk of smoking and obesity, both cancer risk factors, but were not significantly associated with screening behaviors. Area-level factors explain modest variation in these associations.IMPACTFindings highlight the importance of integrating both social experience (PD) and structural conditions (neighborhood deprivation) in cancer prevention research. For practice and policy, results underscore the need for multilevel strategies and targeted prevention efforts to reduce behavioral cancer risk.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"29 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655912","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":"Use of Low-Value Cancer Care in Practices Acquired by Private Equity Firms.","authors":"Aaron P Mitchell,Miranda B Lam,Caroline Carlin,Kevin Tyan,Maryam Mooghali,Ziad Zakaria,Reshma Ramachandran,Jeah Jung","doi":"10.1093/jnci/djag093","DOIUrl":"https://doi.org/10.1093/jnci/djag093","url":null,"abstract":"Private equity (PE) acquisition of medical practices has been associated with increased prices and use of lucrative treatments. Using Medicare data 2015 to 2021, we compared the prevalence of low-value cancer treatments between PE-owned and non-PE-owned practices. The five low-value treatments were: granulocyte colony stimulating factors (GCSF) for low-risk chemotherapy; denosumab for castration sensitive prostate cancer; nab-paclitaxel for breast or lung cancer; addition of bevacizumab for ovarian cancer; and biologic drugs with biosimilar alternatives. The primary outcome was receipt of a low-value treatment. Comparing patients diagnosed when their oncologist was vs was not practicing at a PE-owned address, adjusted prevalence differences of low-value treatments were: -2.8%-points (-5.5 to -0.2) for GCSF; +3.7%-points (-7.3 to 14.7) for denosumab; -0.7%-points (-3.9 to 1.5) for nab-paclitaxel; -6.5%-points (-12.5 to -0.4) for bevacizumab; and -2.9%-points (-6.0 to 0.2) for biologics. Overall, PE ownership was not associated with increased prevalence of low-value cancer treatments.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577874","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":"Survival and treatment among older patients with brain metastases: a Population-Based study.","authors":"Benjamin Grobman,Nayan Lamba,Paul J Catalano,Shyam K Tanguturi,Rifaquat Rahman,Daphne A Haas-Kogan,Patrick Y Wen,Ayal A Aizer","doi":"10.1093/jnci/djag098","DOIUrl":"https://doi.org/10.1093/jnci/djag098","url":null,"abstract":"BACKGROUNDGeneralizable, large-scale data describing outcomes and treatment approaches for older adults with brain metastases remain limited. In this investigation, we evaluated prognosis and patterns of care in this population over time, with particular attention to the potential impact of social determinants of health.METHODSWe used the SEER-Medicare database to delineate survival, treatment patterns, and disparities among patients aged ≥65 years with brain metastases diagnosed between 2010 to 2020. Survival was assessed with Kaplan-Meier methods and multivariable Cox regression.RESULTSThis study included 67,832 patients (51% female). The median survival from diagnosis of brain metastases was 3.42 months, improving modestly from 2.99 months in 2010 to 3.88 months in 2019. Higher zip-code-level annual income (HR 0.98 per $10,000 increase, 95% CI: 0.97 to 0.98, p < 0.001) and higher rates of high school graduation (HR 0.98 per 10% increase, 95% CI: 0.97 to 0.99, p = 0.001) were associated with lower mortality. Among patients managed with brain-directed radiation, 62% and 38% received non-stereotactic (inclusive of whole brain radiation) and stereotactic approaches, respectively. Use of stereotactic radiation increased from 22% in 2010 to 54% in 2019. Compared to White patients, Black patients (HR 0.79, 95% CI: 0.73 to 0.86, p < 0.001) and Hispanic patients (HR 0.87, 95% CI: 0.79 to 0.95, p = 0.002) were less likely to receive stereotactic radiation.CONCLUSIONSThe prognosis among older patients with brain metastases remains poor. Many patients continue to receive non-stereotactic approaches. Further work to improve the prognosis of older patients with brain metastases and optimize patterns of care is needed.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"408 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577876","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 Subsequent Primary Melanoma in 68,002 five-year survivors of childhood and adolescent cancer in Europe: The PanCareSurFup cohort study.","authors":"Behnoush Shojaie,Jop C Teepen,David L Winter,Mike P Gardner,Melanie Kaiser,Desiree Grabow,Cécile M Ronckers,Julianne Byrne,Roderick Skinner,Daniela Alessi,Hama Baqaeen,Rodrigue S Allodji,Helena Jh Van Der Pal,Momcilo Jankovic,Francesca Bagnasco,Eva Steliarova-Foucher,Ben D Spycher,Grit Sommer,Edit Bárdi,Thorgerdur Gudmundsdottir,Milena M Maule,Gisela Michel,Monica Muraca,Maria W Gunnes,Line Kenborg,Henrik Hjalgrim,Carlotta Sacerdote,Zsuzsanna Jakab,Riccardo Haupt,Thomas Wiebe,Monica Terenziani,Lorna Zadravec Zaletel,Leontien C M Kremer,Claudia E Kuehni,Päivi M Lähteenmäki,Florent De Vathaire,Lars Hjorth,Michael M Hawkins,Raoul C Reulen","doi":"10.1093/jnci/djag094","DOIUrl":"https://doi.org/10.1093/jnci/djag094","url":null,"abstract":"BACKGROUNDSurvivors of childhood cancer are at risk of subsequent primary melanoma (SPM), but the magnitude of the risk after different childhood cancer types and beyond age 50 remains inadequately characterised. We quantified risks in the largest cohort of childhood cancer survivors worldwide.METHODSThe PanCareSurFup cohort includes 68,002 five-year childhood cancer survivors across Europe (diagnosed 1940 to 2008). SPM risks were quantified using standardised incidence ratios (SIRs), absolute excess risks (AERs), cumulative incidence and relative risks (RRs).RESULTSOver 1,239,675 person-years, 197 SPMs were ascertained whereas 84.9 were expected (SIR = 2.3, 95%CI = 2.0 to 2.7). Although the SIR decreased with attained age (Ptrend<0.001), it remained increased at 2.1-fold (95%CI = 1.5 to 3.1) age 50+. By age 65, cumulative incidence was 1.2% (0.8% expected). Of all cancer types, heritable retinoblastoma survivors had the greatest risk (SIR = 16.5, 95% CI = 10.8 to 25.3; AER = 94.4, 95% CI = 59.9 to 148.9), with cumulative incidence of 3.3% at age 50 and 5.5% at age 60. Survivors treated with radiotherapy had a 70% greater risk than those treated without (RR = 1.7, 95% CI = 1.1 to 2.7) increasing to 4-fold age 50 + (RR = 3.9, 95%CI = 1.1 to 13.9). For chemotherapy, no significant association was found (RR‌=0.9, 95%CI = 0.5 to 1.6).CONCLUSIONSChildhood cancer survivors, particularly those with heritable retinoblastoma and those treated with radiotherapy, remain at increased risk of melanoma beyond age 50. Current survivorship guidelines focus principally on treatment history; however, our findings suggest that long-term follow-up guidelines should additionally include childhood cancer type and attained age as risk-stratifying factors, particularly where individual treatment records are unavailable.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147578000","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":"Measuring and defining screening benefit in a new era of cancer early detection.","authors":"Ruth Etzioni,Kemal Gogebakan,Roman Gulati,Lukas Owens,Jane Lange,Larry Kessler,Robert Smith,Deborah Schrag,Hilary A Robbins","doi":"10.1093/jnci/djag100","DOIUrl":"https://doi.org/10.1093/jnci/djag100","url":null,"abstract":"We are at a watershed moment in the history of early cancer detection in which many novel tests are poised to become available for population screening. An ongoing debate concerns how to properly evaluate these tests and specifically whether a shorter-term, incidence-based outcome might substitute for cancer mortality as an endpoint in randomized trials of screening test efficacy. An incidence-based endpoint promises to reduce time and resources, but there is no framework for how studies using this endpoint should report results and how they should be interpreted in terms of clinical utility. We consider whether publication of incidence-based results ahead of any mortality results could result in adoption of new screening tests ahead of reliable mortality results becoming available. We argue that guardrails are needed for this scenario, including standards for conduct and reporting of trials with incidence-based endpoints to assure valid interpretation of clinical utility. For example, information regarding the type and timing of tests used for diagnostic workup in screen and control groups will be needed. Clinicians and policy makers will need to determine acceptable measurements and magnitudes of this modified measure of test efficacy. The roles of incidence-based and mortality-based endpoints in determining practice standards will need to be defined, along with specifications for permissible adjunct evidence, such as modeling studies and real-world data. As screening trials for new multi-cancer tests will soon begin to report incidence-based results, resolution of these questions is a matter of urgency.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"52 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147577875","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":"Declining cervical cancer incidence in young women living in the United States: is it time to stop screening them?","authors":"Philip E Castle","doi":"10.1093/jnci/djag041","DOIUrl":"https://doi.org/10.1093/jnci/djag041","url":null,"abstract":"","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"63 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147536239","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":"Temporal Patterns and Factors Associated with Early Termination in Phase 1 Clinical Trials for Solid Tumors.","authors":"Giovanni Maria Iannantuono,Stefano Sganga,Tommaso Giovagnoli,Luca Mastrantoni,Charalampos S Floudas,Diana Giannarelli,Andrea Spinazzola,Marco Filetti,Francesca Lo Bianco,Antonio Vitale,Roberto Rosenfeld,Pasquale Lombardi,Elena Giudice,Gloria Messina,Anna Ceccarelli,James L Gulley,Alessandra Fabi,Luisa Carbognin,Alessandro Rossi,Martina Mazzuferi,Valeria Altamura,Giuliano Maiolatesi,Alberto Gatto,Emilio Bria,Gennaro Daniele","doi":"10.1093/jnci/djag091","DOIUrl":"https://doi.org/10.1093/jnci/djag091","url":null,"abstract":"BACKGROUNDEarly termination (ET), defined as the discontinuation of a trial before its planned completion, remains poorly characterized in phase 1 cancer trials. We aimed to: (i) identify reasons for ET in phase 1 trials and compare them with those in late-phase studies; (ii) investigate temporal patterns and factors associated with ET in phase 1 trials.METHODSTrials on solid tumors initiated between 2018 and 2023 were identified using the \"Aggregate Analysis of ClinicalTrials.gov\" database. We compared the reasons for ET between phase 1 and phase 2 to 3 trials using the Chi-squared test. We estimated the cumulative probability of ET over time and used a multivariable logistic regression model to investigate determinants of ET.RESULTSWe included 2301 studies: 1740 phase 1 and 561 phase 2 to 3 trials. \"Sponsor/strategic decisions\" was the most common reason for ET in phase 1 trials (51.1%), while \"poor accrual\" predominated in phase 2 to 3 trials (35.5%; p < 0.001). The probability of ET in phase 1 trials increased rapidly between 10 and 30 months after initiation and plateaued after 60 months. Factors associated with a lower probability of ET included academic funding and conduct in Europe, Asia, or Oceania. Conversely, trials conducted globally or enrolling patients with thoracic or gastrointestinal cancers were more likely to discontinue prematurely.CONCLUSIONSPhase 1 trials are primarily discontinued for \"sponsor/strategic decisions\". Funding source, tumor type, and geographic location of recruiting centers are independently associated with ET. The early peak in ET probability marks a critical window for interventions to improve trial sustainability.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"229 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147535689","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}