Journal of the National Cancer Institute最新文献

{"title":"Claims-based frailty, dual eligibility, and potential unmet home-health needs in older breast cancer survivors","authors":"Xuanzi Qin, Jie Chen, Alison Trinkoff, Douglas Yee, Nancy Schoenborn","doi":"10.1093/jnci/djag327","DOIUrl":"https://doi.org/10.1093/jnci/djag327","url":null,"abstract":"Background Older breast cancer survivors often need home-based functional support, yet whether Medicare’s restricted home health (HH) benefit leaves frailty-related need unmet at the population level is not quantified because measurement is lacking. Methods Using linked Surveillance, Epidemiology, and End Results-Medicare-OASIS data, we studied 347 953 survivor-years during 2017-2020 from 134 410 women with invasive breast cancer 2-10 years post-diagnosis. We derived a claims-based predicted deficit-accumulation frailty index (DAFI), calibrated by penalized elastic-net to the observed OASIS Start-of-Care DAFI, the HH-need benchmark. Outcomes were any Medicare HH use and potential unmet need, defined as no HH use among high-need survivor-years (predicted DAFI ≥ 0.25). Logistic models estimated the marginal effects of DAFI on any Medicare HH use by frailty and dual eligibility, and disparities in potential unmet need. Results The claims-based DAFI was closely calibrated to observed OASIS DAFI (area under the curve = 0.715; slope = 1.111). Any HH use rose with frailty (+1.10 percentage points [pp] per +0.01 DAFI; 95% CI = 1.05 to 1.15), most steeply among never-dual survivors (+1.21 pp; 95% CI = 1.16 to 1.26) and less steeply among always-dual survivors (+0.41 pp; 95% CI = 0.30 to 0.53). Among high-need survivor years, 59.6% had no Medicare HH use. Long-term survivors had similar DAFI to 2-5-year survivors (0.216 vs 0.215) and lower HH use, but potential unmet need did not differ. Conclusions A claims-based frailty proxy reveals potential frailty-related needs that Medicare HH does not reach. Expanding Medicare HH to better cover personal care and other home- and community-based services may help address frailty-related needs.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218758","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":"Colonoscopy screening outcomes in Lynch syndrome and differential colorectal cancer paths among MLH1 / MSH2 carriers","authors":"Laurent Briollais, Yun-Hee Choi, Kara Semotiuk, Thomas Ward, Zane Cohen, Melyssa Aronson","doi":"10.1093/jnci/djag392","DOIUrl":"https://doi.org/10.1093/jnci/djag392","url":null,"abstract":"Backgroud Lynch syndrome, caused by pathogenic variants in mismatch repair genes increases the risk of colorectal cancer, which remains elevated even under active colonoscopy surveillance. A deeper understanding of the underlying mechanisms driving CRC development under colonoscopy surveillance in individuals with LS is crucial for evaluating its effectiveness. The goal of this study is to better understand the differential patterns of CRC development focusing more specifically on MLH1 and MSH2 carriers. Methods Patients with Lynch syndrome were identified through the Familial Gastrointestinal Cancer Registry in the Zane Cohen Centre at Mount Sinai hospital, Toronto. This study proposed a general model integrating colonoscopy screening visits, adenoma counts, and CRC occurrence (a joint model) and which accounts for their interdependencies when modelling CRC risk. Results More frequent colonoscopy screenings resulting in an increased number of adenomas detected effectively reduces CRC risk in those with a pathogenic variant in MSH2, potentially due to a risk-reducing effect. MLH1 carriers did not experience the same benefit. After 10-year follow-up, among individuals with adenomas, CRC risk was much higher in MLH1 compared to MSH2 carriers, 7.9% [95% CI = 3.9-15.8%] vs. 4.0% [95% CI = 1.6-9.6%] in males and 4.2% [95% CI = 2.2-8.2%] vs. 1.6% [95% CI = 0.7-3.5%] in females. Conclusions Our study identified differences in MLH1 and MSH2 cancer development which may suggest distinct mechanisms impacting CRC. The inverse relationship between adenoma detection and CRC risk in MSH2 carriers enhances our understanding of the adenoma-carcinoma sequence, while the lack of association in MLH1 carriers suggests alternative carcinogenic pathways requiring further study.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218456","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":"Effects of private health insurance coverage gains on colorectal cancer outcomes: a modeling study","authors":"Rosita van den Puttelaar, Kewei Sylvia Shi, Jingxuan Zhao, V Paul Doria-Rose, Matthias Harlass, Anne I Hahn, Ann G Zauber, K Robin Yabroff, Iris Lansdorp-Vogelaar","doi":"10.1093/jnci/djag395","DOIUrl":"https://doi.org/10.1093/jnci/djag395","url":null,"abstract":"Background Lack of health insurance limits access to health care, leading to potentially preventable inequities in health outcomes. This modelling study estimates the impact of providing insurance to currently uninsured individuals on colorectal cancer (CRC) outcomes in the US. Methods The MISCAN-Colon model was adapted to an uninsured population aged 40-100 during 2025-2055, using age-specific estimates from national data sources for screening, stage distribution, survival and all-cause mortality by insurance status (ages 40-64: privately insured vs. uninsured; ages 65-100: Medicare and private coverage vs. Medicare only). The effects of this uninsured population gaining health insurance coverage in 2025 were compared with the same population remaining uninsured for CRC incidence, mortality, and costs. Both groups were assumed age-eligible for Medicare coverage at 65 years. Results In an uninsured population, the model predicted 170 CRC cases and 73 deaths per 100,000 in 2055. If this population gained private insurance, up to 15 (8.9%) cases and 22 (30.7%) deaths per 100,000 could be averted by 2055. Although insurance gains would decrease treatment costs by $1.37 million per 100,000 (-4.8%) through prevention and earlier diagnoses, total CRC-related costs would increase by $1.29 million per 100,000 (+3.7%) due to increased screening costs ($2.66 million per 100,000, +41.7%). Conclusion If the previously uninsured population gained health insurance, CRC incidence and CRC mortality could be reduced substantially because of improved access to care. Assuming analogous improvements for other cancers, this case study provides an example for the potential benefits of gaining health insurance on mitigating health disparities.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221382","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":"Lifestyle and genetic risk factors for postmenopausal breast cancer in the multiethnic cohort","authors":"Chenya Zhao, Eric S Kawaguchi, Gertraud Maskarinec, David V Conti, Christopher A Haiman, Loïc Le Marchand, Lynne R Wilkens, Anna H Wu, Fei Chen, Eunjung Lee","doi":"10.1093/jnci/djag394","DOIUrl":"https://doi.org/10.1093/jnci/djag394","url":null,"abstract":"Background Adherence to a healthy lifestyle has been consistently associated with reduced breast cancer risk, but whether this benefit varies by genetic susceptibility remains unclear, particularly among racially and ethnically diverse populations. Methods In this prospective cohort analysis, we evaluated the association between a healthy lifestyle index score (HLIS), constructed from diet, alcohol consumption, body mass index, waist circumference, physical activity, and smoking, and risk of invasive breast cancer among postmenopausal women. We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) among 22,725 postmenopausal women in the Multiethnic Cohort (MEC), self-identified as White (22%), African American (13%), Native Hawaiian (8%), Japanese American (38%), and Latino (19%). We also evaluated effect modification by a 313-variant polygenic risk score (PRS) for breast cancer. Results Higher HLIS was associated with a decreased risk of postmenopausal breast cancer. Compared with women in the low HLIS, those in the high HLIS had a 33% lower risk of breast cancer (HR = 0.67; 95% CI: 0.57 to 0.79). Results were similar across the two PRS strata, and we did not observe a multiplicative interaction between HLIS and PRS (low-PRS group: HR = 0.63, 95% CI: 0.48 to 0.82; high-PRS group: HR = 0.70; 95% CI: 0.57 to 0.85; P-interaction=0.48). In race/ethnicity-stratified analyses, the inverse associations were most evident among White and Japanese American women. Conclusion In this multiethnic cohort of postmenopausal women, adherence to a healthy lifestyle was associated with a reduced risk of postmenopausal breast cancer, regardless of inherited genetic susceptibility.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187865","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":"Alignment with lifestyle recommendations and physical health in breast cancer survivors and women without cancer","authors":"Clara Bodelon, Lauren E McCullough, Cassandra York, Marissa M Shams-White, Hormuzd A Katki, Alpa V Patel, Lauren R Teras","doi":"10.1093/jnci/djag388","DOIUrl":"https://doi.org/10.1093/jnci/djag388","url":null,"abstract":"Background Breast cancer (BC) survivors, particularly those treated with chemotherapy, experience declines in physical health compared with age-matched women without cancer. We investigated whether alignment with healthy lifestyle behaviors, including body weight, physical activity, diet, and alcohol, was associated with better physical health among BC survivors. Methods This analysis included 1,610 BC survivors and 16,100 age- and survey date-matched women without cancer from the American Cancer Society (ACS) Cancer Prevention Study-3 prospective cohort. Lifestyle alignment was assessed using the ACS guideline score (0-8), categorized as low (0-4) or high (5-8). Physical health was measured using the Patient-Reported Outcomes Measurement Information System Global Health Scale. Associations between a combined treatment-lifestyle variable and physical health were estimated using linear regression adjusted for matching factors at pre-diagnosis, <3, and ≥3 years post-diagnosis. Results Higher guideline alignment was associated with better physical health (P < 0.001). Compared with women without cancer and low alignment, chemotherapy-treated BC survivors with low alignment had worse physical health (<3 years: β = −2.67, 95% CI = −3.77 to − 1.58; ≥3 years: β = −2.10, 95% CI = −3.70 to − 0.51). In contrast, chemotherapy-treated survivors with high alignment had better physical health (<3 years: β = 1.09, 95% CI = 0.30 to 1.89; ≥3 years: β = 2.56, 95% CI = 1.40 to 3.72). Survivors with higher alignment were predicted to have physical health comparable to the average U.S. population. Conclusion Higher alignment with ACS lifestyle guidelines was associated with better physical health among BC survivors, including chemotherapy-treated survivors. These findings highlight the potential relevance of healthy lifestyle behaviors for supporting physical health among survivors.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152551","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":"Trends in bone health agent use and skeletal events in metastatic castration-resistant prostate cancer","authors":"Kim J M van der Velden, Dianne Bosch, Anneloes M van den Wildenberg, André M Bergman, Maarten J van der Doelen, Reindert J A van Moorselaar, Diederik M Somford, Metin Tascilar, Carin A Uyl–de Groot, Inge M van Oort, Malou C P Kuppen","doi":"10.1093/jnci/djag385","DOIUrl":"https://doi.org/10.1093/jnci/djag385","url":null,"abstract":"Background Bone health agents (BHAs) prevent symptomatic skeletal events (SSEs) in bone-metastatic castration-resistant prostate cancer (mCRPC). We evaluated contemporary BHA utilization and SSE incidence (2016–2021) compared with a historical cohort (2010–2015), during a period of substantial changes in mCRPC treatment. Methods Data from 2,115 CRPC patients with bone metastases (Dutch CAPRI-3 registry) were compared to the CAPRI-2 cohort (N = 1,923). Clinical evolution and SSE outcomes were analysed in 1,792 patients receiving life-prolonging drugs (LPDs), categorized by BHA timing relative to the first LPD: no BHA, early BHA (≤4 weeks), or late BHA (>4 weeks). Results Compared to the historical cohort (2010-2015), patients in the 2016-2021 cohort were older (75 vs. 73 years), frailer (Charlson Comorbidity Index ≥5: 44% vs. 13%), and received LPDs in metastatic castration-sensitive setting more frequently (35% vs. 0%). BHA utilization dropped from 60% to 28%, with only 8% receiving guideline-recommended timing of BHA initiation. However, the overall SSE incidence declined from 0.26 to 0.21 events/patient-year between cohorts. Early BHA initiation was predominantly reserved for high-risk disease; this group experienced the highest SSE density (0.29) and shortest median SSE-free survival (8.7 vs. 14.6 months; p < 0.001) compared with the group without BHA. Conclusions As the mCRPC population becomes older and more pre-treated, guideline-recommended BHA timing remains limited. Although overall skeletal morbidity declined, the high SSE density in high-risk patients underscores the need to identify those patients most likely to benefit from early bone protection.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152552","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 second primary malignancies in older long-term survivors of breast, prostate, colon, and rectal cancer","authors":"Tendai Kwaramba, Sarah Westvold, Jessica B Long, Terry Hyslop, Andrea Silber, Faiza Yasin, Rebecca Forman, Melissa Taylor, Shi-Yi Wang, Michael Leapman, Ira L Leeds, Michael Cecchini, Lisa P Spees, Stephanie B Wheeler, Cary P Gross, Kevin Oeffinger, Michaela A Dinan","doi":"10.1093/jnci/djag383","DOIUrl":"https://doi.org/10.1093/jnci/djag383","url":null,"abstract":"Background Cancer survivors face an increased risk of second primary malignancies (SPMs). Understanding SPM incidence and risk factors is crucial for long-term survivorship care. Methods This was a SEER-Medicare retrospective cohort study of breast, prostate, colon, or rectal cancer survivors diagnosed between 2003-2011 at age 66+ years who survived ≥5 years post-diagnosis. The primary outcome was a ‘late’ SPM, defined as invasive cancer occurring ≥5 years after initial diagnosis. Restricted mean survival time (RMST) regression was used to assess demographic, clinical, and treatment related factors associated with late SPMs. SPMs were categorized as hematologic, screen-detectable (breast, prostate, lung, colon, or rectal), or non-screen detectable solid tumors. Results Of 90,261 long-term survivors, 11.2% (10,116) developed at least one late SPM. The cumulative incidence of late SPMs over 8 years was highest in prostate cancer survivors. Non-screen detectable cancers composed the largest proportion (47.8%) of 10,220 total late SPMs. The most common late SPM site was lung in colon (14.9%), and rectal (16.1%) cancer survivors, urinary bladder in prostate (17.0%), and new-primary breast cancers in breast cancer survivors (36.5%). In RMST regression, significant associations with demographic, index cancer, treatment, and clinical characteristics and late SPMs ranged from 3.6 months shorter to 4.4 months longer time without late SPM during the 8 years assessed. Conclusions Between 10-14% of older long-term cancer survivors developed a late SPM during 5-13 years after index cancer diagnosis. Over 40% of late SPMs were screen-detectable, highlighting the need for surveillance strategies beyond 5 years from index cancer diagnosis.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152553","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":"Clinical and lifetime natural history of oral cancer: implications for screening and surveillance","authors":"Li C Cheung,Guannan Chen,Richard Muwonge,Madeline Reeve,Gigi Thomas,Thara Somanathan,Fangya Mao,Qing Pan,Partha Basu,Rengaswamy Sankaranarayanan,Kunnambath Ramadas,Anil K Chaturvedi","doi":"10.1093/jnci/djag360","DOIUrl":"https://doi.org/10.1093/jnci/djag360","url":null,"abstract":"Abstract Background We estimated the clinical and lifetime natural history of oral cancer to inform empirical screening and surveillance algorithms. Methods We used data from ever-chewers/smokers/alcohol drinkers in the screening arm of the Kerala Oral Cancer Screening Trial (1996-2010), who attended at least one screen (n = 41,225) or two consecutive screens (n = 28,821). The clinical natural history (sensitivity, positive predictive value [PPV] and complement of negative predictive value [cNPV]) was estimated using Kaplan-Meier methods. The multistate natural history across initiation of chewing/smoking/drinking, precancer, early-stage cancer, late-stage cancer, and competing mortality was estimated using semi-Markov models. Results Visual-inspection over 2 consecutive screens (median=3.5 years apart [IQR=2.9-3.9]) had sensitivity=89.2%, PPV=1.55%, and NPV=99.96% for prevalent oral cancers (n = 83). On the first screen, 10.0% were positive with a referable oral lesion/precancer, and 12.9% were positive on either screen. Screen-positivity on both screens provided 32-fold risk-stratification for incident cancers over 11 years of follow-up (PPV=4.13% vs. cNPV in persistent screen-negatives=0.13%). Screen-positives on either screen accounted for 66.1% of incident oral cancers through 11 years of follow-up. In the lifetime/multistate model, an estimated mean=18.2% of ever-smokers/chewers/drinkers would develop oral precancer and mean=6.04% would progress from precancer to early-stage cancer (mean sojourn=19.3 years). The estimated mean sojourn time from early-stage to late-stage oral cancer was 2.7 years. Conclusions Oral cancer screening intervals could be extended to 10 years for repeat negatives on 2 consecutive screens. The high PPV and short sojourn time from early-stage to late-stage cancer indicate the need for intensive surveillance among screen-positives with precancer. Clinicaltrials.gov identifier NCT04494620.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088299","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":"21-Gene recurrence score assay in pN2-3 Early-Stage breast cancer: a national cancer database study","authors":"Carmine Valenza,Yue Zheng,José Pablo Leone,Dario Trapani,Pier Paolo Maria Berton Giachetti,Guilherme Nader-Marta,Laura S Dominici,Sara M Tolaney,Ann H Partridge,Giuseppe Curigliano,Meredith M Regan,Harold J Burstein","doi":"10.1093/jnci/djag374","DOIUrl":"https://doi.org/10.1093/jnci/djag374","url":null,"abstract":"Abstract Background The clinical utility of the 21-gene recurrence score (RS) for guiding adjuvant chemotherapy in patients with pN2-3 early-stage breast cancer (eBC) has not been evaluated in prospective trials. This study aims to assess adjuvant chemotherapy benefit in patients with pN2-3 eBC who underwent RS testing and had a RS ≤ 25. Methods We conducted a retrospective cohort study from the National Cancer Database (NCDB) among patients with hormone receptor-positive/HER2-negative, pN2-3 eBC diagnosed from 2010-2020 who underwent 21-gene RS testing (OncotypeDX) and had RS ≤ 25. Overall survival (OS) was compared between patients who received or did not receive chemotherapy, using propensity score (PS)-weighted Cox regression. Results Among 50,229 eligible patients with pN2-3 eBC, 3,110 (6%) underwent RS testing. Patients who underwent testing had longer OS than those who did not (5-year OS: 86% vs. 79%). Among tested patients, 2,058 (66%) had RS ≤ 25 (median: 15), and 68% of them received chemotherapy. At a median follow-up of 5.3 years, the PS-weighted hazard ratio for OS comparing chemotherapy to no chemotherapy was 0.62 (95% CI: 0.48-0.81; P = 0.0002; E-value: 2.13, 95% CI lower bound: 1.58). Conclusion In this cohort of highly selected patients with hormone receptor-positive/HER2-negative pN2-3 eBC who underwent 21-gene RS testing and had RS ≤ 25, patients who received chemotherapy had a longer OS compared to those who did not receive chemotherapy, despite having similar characteristics. These results should be interpreted with caution, as the presence of confounding by indication and residual confounding in this analysis underscores the need for randomized clinical trials in this population.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092257","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":"Late effects after novel therapies for childhood cancer: Anticipating the future landscape of health outcomes for survivors","authors":"Amy M Berkman,David T Teachey,Matthew J Ehrhardt,Ching-Hon Pui,Hiroto Inaba,Seth E Karol,Sharon M Castellino,Stephanie B Dixon,Jun J Yang,Thomas G Gross,Sara M Federico,Roger J Packer,Alberto S Pappo,Ibrahim Qaddoumi,Ralph Salloum,Stephanie M Smith,Todd Cooper,Tara O Henderson,Douglas S Hawkins,Paul C Nathan,Eric J Chow,Elizabeth Fox,Gregory T Armstrong","doi":"10.1093/jnci/djag371","DOIUrl":"https://doi.org/10.1093/jnci/djag371","url":null,"abstract":"Abstract Five-year survival rates for childhood cancer now exceed 85%, with recent improvements driven by advances in understanding of tumor biology allowing for molecular risk stratification. The introduction of novel therapies, including antibodies, antibody-drug conjugates, immune checkpoint inhibitors, cellular therapy, and targeted small molecule inhibitors into early-phase and pivotal trials has the potential to further improve survival. Although these agents have transformed outcomes for some children with cancer, their long-term toxicity profiles remain poorly defined. Large cohort studies have characterized the late effects of conventional cytotoxic chemotherapies and radiation, informing survivorship guidelines and risk-based surveillance strategies. In contrast, the distinct mechanisms of action of targeted and immune-based therapies introduce new and potentially persistent toxicities affecting cardiovascular, neurologic, endocrine, gastrointestinal, and immune systems. This review synthesizes current evidence on acute toxicities of novel therapies and summarizes available data about persistent long-term toxicities and new onset late effects outcomes, including growth impairment, persistent immune dysfunction, and subsequent malignancies in children treated with these agents. We focus on therapies with U.S. Food and Drug Administration approval for pediatric indications. Current evidence from acute toxicity profiles, limited pediatric long-term follow-up, and emerging data from adult populations highlights the urgent need for systematic evaluation of long-term outcomes in children treated with these therapies. As the use of novel agents continues to expand, extending established survivorship cohorts to include children exposed to novel therapies, while developing complementary approaches to detect previously unrecognized toxicities, will be essential for defining late effects and informing evidence-based surveillance and intervention strategies.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088301","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}