JNCI Journal of the National Cancer Institute最新文献

{"title":"Predictive validity of a 10-item frailty index based on a comprehensive geriatric assessment (FI-CGA-10) in older Japanese adults with cancer.","authors":"Tomohiro F Nishijima, Mototsugu Shimokawa, Kohei Arimizu, Taito Esaki, Masaru Morita, Hyman B Muss","doi":"10.1093/jnci/djag304","DOIUrl":"https://doi.org/10.1093/jnci/djag304","url":null,"abstract":"<p><strong>Background: </strong>The 10-Item Frailty Index Based on a Comprehensive Geriatric Assessment (FI-CGA-10) is a content- and construct-validated measure for quantifying frailty from a CGA. For criterion validation, we assessed its predictive validity for overall survival (OS) in older adults with cancer.</p><p><strong>Methods: </strong>This prospective cohort study included 1,630 patients with cancer who underwent CGA at a geriatric oncology service (median age 80 years). The FI-CGA-10 comprises ten CGA domains; deficits in each domain were scored 0 (no problem), 0.5 (minor problem), or 1.0 (major problem). Domain scores were summed, divided by 10 (range 0-1), and categorized as fit (<0.20), pre-frail (0.20-0.35), or frail (>0.35). Two Cox proportional hazards models estimated hazard ratios (HRs) for OS: a base model (age, sex, cancer type, and stage) and the base model plus FI-CGA-10 as a categorical variable. Model performance was compared using the likelihood-ratio (LR) test and Harrell's c-index.</p><p><strong>Results: </strong>Overall, 22% were fit, 38% pre-frail, and 40% frail; 28% died within one year. Adding FI-CGA-10 to the base model improved prediction (LR χ² = 140.7; P < .001) and increased the c-index from 0.70 to 0.76 (P < .001). Adjusted HRs for pre-frail and frail (vs. fit) were 2.26 (95% CI, 1.61-3.19) and 5.06 (95% CI, 3.64-7.04), respectively. 1-year OS was 87% (fit), 74% (pre-frail), and 55% (frail). Major problems across all ten domains and minor problems in six domains were associated with worse OS in adjusted models.</p><p><strong>Conclusion: </strong>This study provides evidence supporting the predictive validity of the FI-CGA-10 for OS.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Zhang.","authors":"Giulia Maddalena, Scott Kopetz, Kanwal Raghav","doi":"10.1093/jnci/djag299","DOIUrl":"https://doi.org/10.1093/jnci/djag299","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Chen and Huang.","authors":"Hyun Yong Koh, Omid Jafari, Ang Li","doi":"10.1093/jnci/djag301","DOIUrl":"https://doi.org/10.1093/jnci/djag301","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RE: Cancer-associated arterial thromboembolism: real-world burden from a nationwide electronic health record database.","authors":"Shanjiang Chen, Anwu Huang","doi":"10.1093/jnci/djag300","DOIUrl":"https://doi.org/10.1093/jnci/djag300","url":null,"abstract":"","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing the impact of tobacco and alcohol use on cancer-related health outcomes.","authors":"Hang Zhou, Babalola Faseru, Farhad Islami, Nigar Nargis, Maria Elena Martinez, Roy A Jensen, S Gail Eckhardt, Roy S Herbst","doi":"10.1093/jnci/djag138","DOIUrl":"https://doi.org/10.1093/jnci/djag138","url":null,"abstract":"<p><p>Tobacco and alcohol use are significant modifiable risk factors contributing to cancer morbidity and mortality globally. Recognizing the synergistic effects of these substances and their implications for cancer prevention and treatment, a national workshop titled \"Addressing the Impact of Tobacco and Alcohol Use on Cancer-Related Health Outcomes\" was convened in Washington, DC, in March 2025. This workshop brought together leading researchers in behavioral, basic, and clinical sciences, clinicians, public health practitioners, health economists, policymakers, patient advocates, and community stakeholders to review current evidence, identify gaps in practice and policy, and develop actionable recommendations. The goal of the workshop was to examine the evidence linking tobacco and alcohol use to cancer incidence and outcomes and to explore strategies for reducing their use to lower cancer risk and improve health outcomes. This commentary summarizes key themes from five sessions, including epidemiological insights, lessons from tobacco control policy, opportunities for alcohol policy, evidence-based cessation interventions, and strategies to address stigma and gaps in research and practice. The workshop underscored the need for integrated public health strategies, informed by lessons learned from tobacco control, to mitigate the cancer burden attributable to tobacco and alcohol use.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic aging of colorectal mucosa in cancer development.","authors":"Sheetal Hardikar, Biljana Gigic, Jacob K Kresovich, Victoria Damerell, Caroline Himbert, Jennifer Ose, Adetunji T Toriola, David Shibata, Christopher I Li, Jane C Figueiredo, Doratha A Byrd, Erin M Siegel, Christoph Kahlert, Alexander Brobeil, Peter Schirmacher, Cornelia M Ulrich, Timothy M Barrow","doi":"10.1093/jnci/djag297","DOIUrl":"10.1093/jnci/djag297","url":null,"abstract":"<p><strong>Background: </strong>The past decade has seen the development of epigenetic models of aging that accurately estimate chronological age and predict disease incidence and mortality. These estimates are modulated by lifestyle and environmental factors linked to carcinogenesis, but to date this has primarily been studied in blood.</p><p><strong>Methods: </strong>We examined epigenetic aging in normal colonic tissue (n = 96), adjacent mucosa (n = 245) and tumors (n = 208), using models trained on age (Horvath, Hannum, Zhang), mortality (PhenoAge, GrimAge), aging rate (DunedinPACE), cellular mitotic history (EpiTOC, epiTOC2, miAGe), and telomere length (DNAmTL).</p><p><strong>Results: </strong>The Horvath model was the most accurate estimator of chronological age in normal colonic mucosa, with high correlation (r > 0.70) between the Horvath, Hannum, Zhang, PhenoAge and GrimAge models, and between mitotic clocks (r > 0.94). All models showed similar performance in normal tissue and adjacent mucosa, but substantially more variation in estimates in tumors. Significant differences in age acceleration were present between normal and adjacent mucosa by six models (Hannum, Zhang, PhenoAge, EpiTOC, epiTOC2 and miAge), while tumors showed highly significant differences by all models. Age acceleration differed by region of the colon, with varying patterns by model type. Physical activity (PhenoAge), smoking history (GrimAge), and alcohol consumption (Horvath, mitotic clocks) were associated with epigenetic aging in adjacent mucosa, while smoking history, smoking intensity, and alcohol consumption were associated with DNAmTL in tumors.</p><p><strong>Conclusions: </strong>Our study reveals an impact of tissue type, region, and lifestyle factors on epigenetic aging, but also highlights significant heterogeneity between models and the need for careful consideration within study design.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized trial of adjuvant 5-FU-platinum vs paclitaxel-platinum for high-risk penile cancer.","authors":"Vanita Noronha, Nandini Menon, Minit Shah, Vijay Patil, Aditya Dhanawat, Gagan Prakash, Mahendra Pal, Amandeep Arora, Ankit Misra, Supriya Goud, Sucheta More, Akanksha Yadav, Vedang Murthy, Priyamvada Maitre, Santosh Menon, Palak Popat, Nilesh Sable, Archi Agarwal, Venkatesh Rangarajan, Ankush Shetake, Rajendra Badwe, Kumar Prabhash","doi":"10.1093/jnci/djag288","DOIUrl":"https://doi.org/10.1093/jnci/djag288","url":null,"abstract":"<p><strong>Background: </strong>Adjuvant chemotherapy is recommended for high-risk penile squamous cell carcinoma (SCC) metastatic to lymph nodes based on retrospective data, but no randomized trials have been conducted. We compared 5-fluorouracil (5-FU)-platinum with paclitaxel-platinum in this setting.</p><p><strong>Methods: </strong>In this open-label, randomized trial at an Indian tertiary cancer center, men <70 years with resected node-positive penile SCC and ≥1 high-risk feature (perinodal extension, pelvic node involvement, >1 inguinal nodes, or ≥ 4 cm node) were assigned 1:1 to four 3-weekly cycles of 5-FU-platinum or paclitaxel-platinum, followed by cisplatin-based chemoradiotherapy. Primary endpoint was disease-free survival (DFS). Secondary endpoints were overall survival (OS), toxicity, and quality-of-life (QoL).</p><p><strong>Results: </strong>Between 2017 and 2024, 49 patients were randomized (5-FU-platinum: 25, paclitaxel-platinum: 24). At a median follow-up of 69 months, median DFS was 12.4 months (95% CI, 3.38-NR) vs 19.6 months (95% CI, 5.82-NR) (HR, 1.16; 95% CI, 0.55-2.45; P = 0.686) and median OS was 21.3 vs 36.7 months (HR, 1.13; 95% CI, 0.52-2.44; P = 0.754) for 5-FU-platinum and paclitaxel-platinum, respectively. Grade ≥3 toxicities occurred in 77.3% vs 40.9% (P = 0.014), grade ≥3 hematologic toxicities in 54.5% vs 4.5% (P < 0.001), and hospitalization for toxicity in 45.5% vs 9.1% (P = 0.016). Completion of all planned cycles was higher with paclitaxel-platinum (83.3% vs 48%; P = 0.009). QoL and sexual health were similar between the two treatment arms.</p><p><strong>Conclusions: </strong>Adjuvant paclitaxel-platinum was associated with improved tolerability compared with fluorouracil-platinum in high-risk node positive penile cancer and warrants further evaluation in larger multicenter studies. Early termination precluded definitive efficacy comparisons.</p><p><strong>Trial registration: </strong>Clinical Trials Registry of India (CTRI/2016/12/007567).</p><p><strong>Funding: </strong>This work was supported by Indian Cooperative Oncology Network and Tata Memorial Center.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating longitudinal toxicity and adverse event in cetuximab-treated metastatic colorectal cancer: a pooled analysis from 1,302 patients in ARCAD database.","authors":"Jun Yin, Katherine E Francis, Guilherme S Lopes, Jane So, Curt L Olswold, Eric Van Cutsem, Carsten Bokemeyer, Richard Adams, Benoist Chibaudel, Axel Grothey, Takayuki Yoshino, Aimery De Gramont, Qian Shi, Christophe Tournigand, Katrin M Sjoquist, John Zalcberg","doi":"10.1093/jnci/djag287","DOIUrl":"10.1093/jnci/djag287","url":null,"abstract":"<p><strong>Purpose: </strong>Traditional adverse event (AE) reporting in oncology trials focuses on the single worst CTCAE grade, which may underrepresent chronic or recurrent toxicity burden. We applied a longitudinal toxicity framework to compare toxicity profiles of chemotherapy with or without cetuximab in metastatic colorectal cancer.</p><p><strong>Patients and methods: </strong>We pooled two randomized first-line trials in the ARCAD database. AEs examined were diarrhea, rash, hand-foot syndrome (HFS), fatigue, anorexia, and mucositis. Outcomes included grade ≥3 AE, time to first occurrence of maximum grade, early onset (≤6 weeks), and AEL, a normalized measure of cumulative toxicity burden over treatment. Analyses were adjusted for chemotherapy backbone, ECOG performance status, sex, primary tumor location, dose reduction, and treatment duration.</p><p><strong>Results: </strong>Compared with Chemotherapy alone (n = 564), Chemotherapy plus cetuximab (n = 738) was associated with higher grade ≥3 rash (21% vs 0.5%; adjusted odds ratio [OR] 49.89, 95% CI 15.8-157.4), higher rash AEL (0.257 vs 0.069; adjusted mean difference 0.22, 95% CI 0.21-0.23), and more frequent early-onset maximum rash (67% vs 34%; adjusted OR 4.28, 95% CI 2.72-6.74). Rash AEL remained higher with cetuximab within maximum-grade strata. HFS showed higher grade ≥3 risk and overall AEL with cetuximab, but no within-grade AEL difference, indicating higher overall HFS burden reflected grade distribution rather than within-grade chronicity. No consistent differences were observed for other AEs.</p><p><strong>Conclusions: </strong>Incorporating onset timing and AEL distinguished persistent toxicity burden from isolated peak events. This framework may support comparative tolerability assessment when chronic toxicity burden is central to decision-making.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetic variants in the molecular characterization initiative: a report from the children's oncology group.","authors":"Cyrine E Haidar, Wenjian Yang, Rachel D Harris, Andrew Ostrenga, Alberto Pappo, Douglas S Hawkins, Jun J Yang, Philip J Lupo, Melanie Brooke Bernhardt","doi":"10.1093/jnci/djag286","DOIUrl":"10.1093/jnci/djag286","url":null,"abstract":"<p><strong>Background: </strong>The Childhood Cancer Data Initiative Molecular Characterization Initiative (MCI) provides molecular testing to patients with select tumors treated at Children's Oncology Group (COG) sites, advancing our understanding of the genetic basis of pediatric cancers and their treatment. However, the frequency of actionable pharmacogenomic variants in this cohort has not yet been explored.</p><p><strong>Methods: </strong>Germline exome sequencing data were generated by the Institute for Genomic Medicine at Nationwide Children's Hospital. Clinically actionable pharmacogenetic variants for 13 genes were based on guidelines by the Clinical Pharmacogenetics Implementation Consortium. Pharmacogenomic diplotypes were extracted using PharmCAT. The T1K computational method was used to infer HLA alleles. Genetic ancestry was estimated by iAdmix using 1000 genomes as reference. Observed variant allele frequencies were compared to gnomAD and All of Us cohorts.</p><p><strong>Results: </strong>Pharmacogenomic diplotypes were extracted for 3,177 patients. Most patients had a central nervous system (CNS) tumor (69%). Genetic composition of the population was diverse with 51% European, 21% Admixed American, and 9% African. Ninety-three percent (n = 2,940) of patients had at least one actionable pharmacogenomic phenotype necessitating modification to one or more medications. We did not observe a difference across ancestral populations in the frequency of individuals carrying at least one actionable variant (p = 0.07). Variant and allele frequencies were similar to those in the gnomAD and All of Us cohorts (R2>0.99).</p><p><strong>Conclusion: </strong>Overall, the vast majority (93%) of patients diagnosed with pediatric cancer within the MCI had an actionable pharmacogenomic phenotype for 13 pharmacogenes evaluated.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent chemotherapy and external radiation therapy (ConCERT): phase 3 noninferiority randomized clinical trial of cisplatin weekly vs every 3 weeks in locally advanced squamous cell carcinoma of the head and neck.","authors":"Atul Sharma, Manish Kumar Choudhary, Suman Bhasker, Akash Kumar, Alok Thakar, Raja Pramanik, Ahitagni Biswas, Kapil Sikka, Surya V S Deo, Ashok Kumar, Supriya Mallick, Amit Chirom Singh, Pooja Sethi, Amit Sehrawat, Vishnubhatla Sreenivas, Rajeev Kumar, Saphalata Baghmar, Aanchal Kakkar, Vinod Sharma, Babita Kataria, Ranjit Sahoo, Aman Sharma, Prasanth Ganesan, Sudhir Kumar, Amol Patel, Smriti Panda, Sanjay Thulkar, Sandeep Seth, Shikha Halder, Manoj Gupta, Ashish Dutt Upadhyay","doi":"10.1093/jnci/djag276","DOIUrl":"10.1093/jnci/djag276","url":null,"abstract":"<p><strong>Introduction: </strong>Concurrent chemoradiotherapy with cisplatin (100 mg/m² every three weeks) is the standard for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but it is uncertain if weekly cisplatin (40 mg/m²) is non-inferior.</p><p><strong>Method: </strong>This open-label, multicentre, phase III non-inferiority trial randomised patients with non-nasopharyngeal LA-HNSCC in a ratio of 1 1 to receive either the standard cisplatin regimen (100 mg/m² every three weeks) or the experimental weekly regimen (40 mg/m²), both with 70 Gy concurrent radiation. The primary endpoint was 2-year locoregional control (LRC) and non-inferiority margin was kept as 10% (-10%).</p><p><strong>Results: </strong>From April 2018-January 2021, 278 patients were enrolled (137 standard and 141 experimental arm); 272 were eligible for final analysis. Median follow-up was 43.9 months. Two-year LRC rates were 61.3% (experimental arm) and 51.1% (standard arm) with an absolute difference of 10.2% (one-sided 95% CI 0.3), within the non-inferiority margin. Hazard ratio was 0.72 (95% CI: 0.50 to 1.05, P = 0.091). Kaplan-Meier analysis also confirmed non-inferiority (absolute difference 10.8%). Median progression-free survival was 17.9 months (standard) and 20.3 months (experimental) (P = 0.204); median overall survival was 22.2 months (standard) and 24.9 months (experimental) (P = 0.501). Grade 3 or higher adverse events occurred more in the standard arm (60.7% vs 44.7%, P = 0.018), as did hospitalisations (36.8% vs 20.3%, P = 0.004).</p><p><strong>Conclusion: </strong>Weekly low-dose cisplatin-based chemoradiation is non-inferior to 3-weekly high-dose cisplatin and is associated with lower toxicity and fewer hospitalisations, making it a viable treatment option for non-nasopharyngeal LA-HNSCC.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}