JNCI Journal of the National Cancer Institute最新文献

{"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}

{"title":"Reproducibility of overall survival in metastatic colorectal cancer randomized trials using ARCAD-Derived external control arms.","authors":"Morteza Raeisi, Thierry André, Qian Shi, Takayuki Yoshino, Richard Adams, Chiara Cremolini, Jeffrey A Meyerhardt, Jeanne Tie, Romain Cohen, Jean-Baptiste Bachet, Hideaki Bando, Toshihiro Misumi, Carsten Bokemeyer, Leonard B Saltz, Miriam Koopman, Volker Heinemann, Marc Peeters, Eric Van Cutsem, Axel Grothey, Benoist Chibaudel, Aimery de Gramont","doi":"10.1093/jnci/djag291","DOIUrl":"https://doi.org/10.1093/jnci/djag291","url":null,"abstract":"<p><strong>Background: </strong>Synthetic control arms (SCAs) derived from historical trial data can complement randomized controlled trials (RCTs), particularly in oncology where feasibility, ethical, and cost constraints may limit conventional trial designs. However, their validity for overall survival (OS) remains uncertain. We evaluated the feasibility and limitations of constructing SCAs from the ARCAD metastatic colorectal cancer (mCRC) database across multiple treatment lines.</p><p><strong>Methods: </strong>Seven landmark RCTs representing first-, second-, and third-line settings were selected. External control arms were constructed from ARCAD individual patient-level data using propensity score matching based on key clinical and biological variables from a validated ARCAD prognostic score, with adjustment for geographic region and time era when needed. A prespecified two-step benchmarking framework assessed: (1) control-arm OS reproducibility and (2) virtual trial comparisons between matched synthetic controls and original RCT experimental arms. Agreement was evaluated using hazard ratios (HRs) and Z-tests.</p><p><strong>Results: </strong>A total of 28,022 patients met the inclusion criteria. ARCAD-derived SCAs were successfully constructed for all selected RCTs and closely reproduced control-arm OS. After matching, baseline characteristics were well balanced, with minimal differences between included and excluded patients. Virtual trials showed concordant treatment-effect estimates with the original RCTs, with a median absolute HR deviation of 0.05 and no significant differences by Z-tests (P>.05). Survival outcomes were consistently reproduced across treatment lines.</p><p><strong>Conclusion: </strong>ARCAD-derived SCAs reliably reproduced control-arm OS and benchmark treatment-effect estimates from landmark RCTs in mCRC. Despite limitations related to residual confounding and missing data, this framework supports benchmarking, trial design, and exploratory analyses when conventional control arms are impractical.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793415","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":"Anal cancer burden among people with HIV across US states, DC, and major metro areas.","authors":"Ashish A Deshmukh, Haluk Damgacioglu, Kalyani Sonawane, Cameron Haas, Qianlai Luo, Anna Satcher Johnson, Eric A Engels, Meredith S Shiels","doi":"10.1093/jnci/djag285","DOIUrl":"https://doi.org/10.1093/jnci/djag285","url":null,"abstract":"<p><strong>Background: </strong>Anal cancer screening is recommended for people with HIV in the United States (US). Because HIV prevalence varies geographically, the distribution of anal cancer diagnoses occurring among people with HIV may also differ by geography. Characterizing geographic variation can help identify areas needing enhanced screening infrastructure and outreach.</p><p><strong>Methods: </strong>Using data from the HIV/AIDS Cancer Match Study, US cancer registries, and CDC's National HIV Surveillance System, we estimated the proportion of incident anal squamous cell carcinomas (SCC) among people with HIV across the 50 states, the District of Columbia (DC), and major metropolitan statistical areas (MSAs).</p><p><strong>Results: </strong>During 2010-2019, an average of 2,160 anal SCC diagnoses occurred annually among males, 414 (20.1%; Uncertainty Interval [UI]=19.4%-20.6%) among males with HIV. Among females, 58 of an average 4,099 annual anal SCC diagnoses (1.4%; UI = 1.3%-1.5%) occurred among females with HIV. Geographic variation among males was substantial. California had the highest annual number of anal SCC diagnoses among males with HIV (70/239; 29.2% [UI = 26.7%-31.8%]), followed by New York (48/161; 29.8% [UI = 26.3%-33.4%]), Florida (42/182; 23.1% [UI = 20.3%-26.1%]), Texas (36/132; 27.0% [UI = 23.7%-30.4%]), and Georgia (20/80; 25.2% [UI = 20.9%-29.8%]). New York had the highest annual number of diagnoses among females with HIV (10/263; 3.7% [UI = 3.0%-4.5%]). Across MSAs, the highest burden was in New York-Jersey City-White Plains (57 diagnoses [UI = 43-73]), with several MSAs in California, Texas, and Florida also showing a high burden.</p><p><strong>Discussion: </strong>Geographic differences underscore the need for targeted anal cancer screening outreach and implementation.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793353","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":"Benchmarking female breast cancer survival in africa, Central and South america, and asia (SURVCAN-3).","authors":"Mariam Zahwe, Ariana Znaor, Aude Bardot, Shalaka Joshi, Kyu-Won Jung, Reza Malekzadeh, Maria Paula Curado, Gholamreza Roshandel, Maria Cristina Diumenjo, Armando Cortés, Rama Ranganathan, Patumrat Sripan, Daniel Jurado-Fajardo, Andrea Falaschi, Imjai Chitapanarux, Isabelle Soerjomataram","doi":"10.1093/jnci/djag294","DOIUrl":"https://doi.org/10.1093/jnci/djag294","url":null,"abstract":"<p><strong>Background: </strong>In limited-resource settings with high cancer mortality, conditional survival which is the probability of surviving given on survival after a certain period of time since diagnosis, can provide a patient-centred and clinically relevant prognosis indicator. We aimed to benchmark breast cancer prognosis using conditional survival estimates in Africa, Central and South America, and Asia.</p><p><strong>Methods: </strong>We included data for 197,766 females with breast cancer diagnosed in 2008-2012, from 53 population-based cancer registries with at least 3 years of follow-up across 22 countries. We estimated 3-year age-standardised net survival at diagnosis and 1-year post-diagnosis using period approach.</p><p><strong>Results: </strong>In all countries, 3-year survival estimates improved for females with breast cancer who had survived 1 year as compared to the 3-year survival estimates at diagnosis. Countries with poorer initial survival showed the largest increases in conditional survival at 3 years with the highest improvement seen in Zimbabwe (68% vs. 57%), Mauritius (90% vs. 83%), India (80% vs. 74%), and Malaysia (83% vs. 77%, conditional and at diagnosis survival, respectively). Improvement in survival was mainly found among females ≥70 years. Inequalities in survival across countries persisted, whereas 6 out of 10 countries of the Americas and 4 out of 8 Asian countries had conditional survival >90%, this was observed only in 1 out of 4 African countries.</p><p><strong>Conclusion: </strong>Our results highlight the importance of early care on improving breast cancer survival over time and serve as a resource for physicians and patients who are seeking an updated indicator of breast cancer prognosis.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793382","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":"Development and validation of a predictive model of aromatase inhibitor-induced arthralgia among patients with early breast cancer.","authors":"Pietro Lapidari, Maryam Lustberg, Julie Havas, Martina Pagliuca, Chayma Bousrih, Christelle Jouannaud, Marion Fournier, William Jacot, Laurence Vanlemmens, Kaderbhai Courèche, Anne Kieffer, Baptiste Sauterey, Olivier Tredan, Christelle Levy, Anne-Laure Martin, Catherine Gaudin, Gwenn Menvielle, Maria Alice Franzoi, Ines Vaz-Luis, Antonio Di Meglio","doi":"10.1093/jnci/djag280","DOIUrl":"https://doi.org/10.1093/jnci/djag280","url":null,"abstract":"<p><strong>Background: </strong>Aromatase inhibitor-induced arthralgia (AIA) is common in early-stage breast cancer patients on aromatase inhibitors (AI), potentially compromising adherence and outcomes. We developed and validated prediction models for short- and longer-term AIA.</p><p><strong>Methods: </strong>Postmenopausal patients with stage I-III breast cancer on adjuvant AI in CANTO (NCT01993498) were included. Primary outcome was AIA (any grade articular/muscular pain, Common Terminology Criteria for Adverse Events [CTCAE] v4.0) at year 1 (Y-1) and 4 (Y-4) cohort visits. Baseline clinical, behavioral, treatment-related, patient-reported (EORTC QLQ-C30, HADS) variables were modeled using multivariable logistic regression and bootstrap in development and temporal validation cohorts. Baseline inflammatory markers were examined in a sub-cohort.</p><p><strong>Results: </strong>The Y-1 and Y-4 development cohorts included 3,065 and 2,390 patients (mean age 64.0 [SD 7.2] and 63.7 years [6.9]), respectively. AIA occurred in 61.3% (Y-1) and 66.1% (Y-4) patients. Validation cohorts included 1,313 (Y-1) and 1,009 (Y-4) patients with similar characteristics. Across models, higher BMI, greater baseline fatigue, prior articular/muscular disease, chemotherapy exposure, pre-existing pain were associated with subsequent AIA; anastrozole use was associated with AIA at Y-4. AUC was 0.62-0.65 in development cohorts; 0.61-0.67 in validation cohorts. In the biomarker sub-cohort (n = 637), higher baseline IL-8 was associated with lower Y-1 AIA odds (OR 0.74, 95% CI 0.56-0.98).</p><p><strong>Conclusion: </strong>Using baseline clinical and patient-reported data, we generated models identifying patients at increased risk of early and persistent AIA. While performance was modest, risk stratification could help trigger stepped-care pathways to optimize AI adherence and outcomes. IL-8 association requires independent replication.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793355","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":"Leiomyosarcoma survival across anatomical sites identifies high- and low-risk patient groups to inform clinical trial design.","authors":"Ailsa J Oswald, Rashi Krishna, Xiangfei Yan, Patricia Roxburgh, Robert L Hollis","doi":"10.1093/jnci/djag284","DOIUrl":"https://doi.org/10.1093/jnci/djag284","url":null,"abstract":"<p><strong>Background: </strong>Leiomyosarcoma, the commonest subtype of soft tissue sarcoma, affects a wide range of anatomical sites. Few multi-site analyses of leiomyosarcoma have been performed to characterise differences across anatomical sites, and to identify patient or tumour characteristics independently associated with survival. Such information is critical to inform future design of pan-site trials necessary due to the rarity of leiomyosarcoma.</p><p><strong>Methods: </strong>We analysed a study cohort of 11,751 patients with leiomyosarcoma across a range of anatomical sites.</p><p><strong>Results: </strong>The uterus(36.3%), limbs(16.6%), superficial trunk(10.8%) and retroperitoneum (9.2%) were the most common anatomical sites. Median follow-up time was 8.4 years. Uterine tumours accounted for a greater proportion in black patients(P-adj<0.001), while the skin(P-adj<0.001) and limbs(P-adj<0.001) were more common sites in the white population. Marked differences in age, grade and stage at diagnosis were observed across anatomical sites. Multivariable analysis identified site, grade, race, marital status and household income as independently associated with outcome: individuals of black race, widowed patients, and those with the lowest income demonstrated significantly shorter survival. The uterus, urinary tract and trunk were among the highest risk sites, while the limbs, head and neck, and male reproductive tract were associated with more favourable outcomes after adjustment. ATRX mutations were enriched(P-adj<0.0001) within uterine cases compared to other sites in a pooled analysis of publicly available sequencing.</p><p><strong>Conclusion: </strong>Major disparities in outcome are clear across leiomyosarcoma subgroups defined by anatomical site and patient characteristics. Future trials may wish to account for the intrinsic aggressiveness of tumours arising at different anatomical locations.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793372","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}