Journal of the National Cancer Institute最新文献

{"title":"Circulating tumor DNA driving anti-EGFR rechallenge therapy in metastatic colorectal cancer: the RASINTRO prospective multicenter study","authors":"Aziz Zaanan, Elisabeth Sophie Bergen, Ludovic Evesque, Aurelia Meurisse, Pascal Artru, Thierry Lecomte, Olivier Bouché, Céline Lepère, Margherita Ambrosini, Romain Coriat, Astrid Lièvre, Romain Cohen, Valérie Boige, Samy Louafi, Jean-Baptiste Bachet, Sophie Goyer, Julien Taieb, Dewi Vernerey, Hélène Blons, Pierre Laurent-Puig","doi":"10.1093/jnci/djaf229","DOIUrl":"https://doi.org/10.1093/jnci/djaf229","url":null,"abstract":"Background In RAS wild-type (WT) metastatic colorectal cancer (mCRC), preliminary data have suggested that circulating tumor DNA (ctDNA) may select patients for anti-EGFR rechallenge therapy. Methods RASINTRO is a prospective nonrandomized study evaluating anti-EGFR rechallenge strategy in third and later line treatment in RAS/BRAF WT mCRC. Liquid biopsies for ctDNA analysis were collected before the first (C1) and second (C2) cycle of anti-EGFR rechallenge therapy. The primary endpoint was the progression-free survival (PFS) according to RAS/BRAF mutational status on ctDNA at C1. Results Among 74 patients screened between November 2017 to March 2020, 62 were enrolled median age, 66.1 years; median number of previous lines of therapy, 3; panitumumab or cetuximab rechallenge alone (66.2%) or with chemotherapy (33.8%); ctDNA RAS/BRAF status at C1, 42 WT (67.7%) and 20 mutated (32.3%). Median PFS (3.3 vs 1.9 months: HR = 0.43; P < .01) and OS (7.9 vs 4.9 months: HR = 0.46; P = .01) were significantly longer for patients with ctDNA RAS/BRAF WT vs mutated at C1. Among the 32 patients with ctDNA RAS/BRAF WT at C1 and available blood samples at C2, those who have experienced an early decrease of more than 50% in ctDNA concentration (n = 15) had a significantly longer median PFS (4.2 vs 2.8 months; HR = 0.39; P = .01) and OS (10.2 vs 4.2 months; HR = 0.39; P = .02). Conclusion This study showed that anti-EGFR rechallenge therapy in refractory disease is more effective in patients with RAS/BRAF WT on ctDNA, and in those who experienced an early decrease of more 50% in ctDNA concentration. (NCT03259009)","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"66 7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899203","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":"Impact of daily adaptive head and neck radiotherapy on toxicity and quality-of-life: results of the DARTBOARD phase II randomized trial","authors":"David J Sher, Vladimir Avkshtol, Mu-Han Lin, Jing Wang, Liyuan Chen, Chien-Yi Liao, Randall Hughes, Sean Domal, Chul Ahn, Dominic Moon","doi":"10.1093/jnci/djaf232","DOIUrl":"https://doi.org/10.1093/jnci/djaf232","url":null,"abstract":"Background The utility of adaptive radiotherapy (ART) for head and neck squamous cell carcinoma (HNSCC) remains poorly defined. Daily ART (DART) promises both anatomic adaptation and planning target volume (PTV) reduction. In this prospective trial using cone-beam computed tomography-based ART, patients with HNSCC undergoing definitive radiotherapy (RT) or chemoradiotherapy (CRT) were randomized to DART with reduced PTV margins or no ART with standard margins (image-guided RT [IGRT]). Methods Eligibility criteria included a diagnosis of oropharynx, larynx, or hypopharynx HNSCC receiving definitive radiotherapy. All individuals received involved nodal radiotherapy per previous institutional study. The PTV margins were 1 mm (2 mm craniocaudal) versus 5 mm in the DART and IGRT arms, respectively. The primary endpoint was patient-reported xerostomia at one year, assessed with the Xerostomia Questionnaire (XQ). Results Fifty patients were enrolled (26 IGRT, 24 DART) between March 2022 and June 2023. The cohort consisted of 38 oropharynx and 12 larynx/hypopharynx patients. The mean ipsilateral parotid gland, ipsilateral and contralateral submandibular gland doses were significantly lower with DART. There was significantly less acute dermatitis in the DART arm (Grade 0/1/2 0%/69%/31% vs. 17%/75%/8% DART, p = 0.01) but no significant difference in any patient-reported outcome at one year. The adjusted difference in XQ score at one year was 10.0 (95% CI -4.7-24.7, p = 0.58). Conclusion Online DART for HNSCC is oncologically sound and improved acute toxicity profiles, but it did not reduce patient-reported xerostomia, the primary endpoint. Additional evidence is needed to understand the potential benefits and limitations of this paradigm, including its cost-effectiveness. Trial registration Clinicaltrials.gov identifier, NCT04883281","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899191","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":"Antagonistic effect of arsenic exposure and chronic hepatitis viral infection on hepatocellular carcinoma","authors":"Pei-Ju Liao, Chien-Jen Chen, Chen-June Seak, Ming-Kuo Ting, Kuang-Hung Hsu","doi":"10.1093/jnci/djaf233","DOIUrl":"https://doi.org/10.1093/jnci/djaf233","url":null,"abstract":"Background Arsenic from drinking water causes many health hazards including liver diseases, but the long-term effects of arsenic exposure and methylation capability on hepatitis viral infection related liver cancer remain to be elucidated. Methods This 19-year community-based follow-up study included 7,837 participants with urinary arsenic metabolites level from an arseniasis area in northeastern Taiwan. They were recruited in 1991-1994 and followed up to December 2021. A total of 295 liver cancer cases occurred during an average follow-up period of 19.82 years. The data were analyzed using Cox proportional hazards models. Results There was a significantly reverse association between inorganic arsenic level in drinking water and liver cancer showing a hazard ratio (HR) of 0.90 (95% CI = 0.67-1.21), 0.66 (95% CI = 0.48-0.92), and 0.57 (95% CI = 0.41-0.81) for participants with arsenic level in the first, second, and third tertile, respectively, compared to those never exposed. A significantly monotonic decreasing trend was observed between arsenic exposure levels and hepatitis viral infections related liver cancer. Participants with hepatitis viral infection and low inorganic arsenic level in drinking water (≤100.0 ug/L) had at the highest risk of developing liver cancer (HR = 7.04; 95% CI = 4.53-10.94) among study groups. Participants with a higher DMA% had a higher risk of developing hepatitis viral infection related liver cancer (HR = 1.74; 95% CI = 1.19-2.55) than otherwise. Conclusions This long-term follow-up study demonstrates the suppressive role of inorganic arsenic on hepatitis viral related hepatocellular carcinoma. The finding is coherent to previous experimental studies and gives clues for future interventions on hepatitis viral infection related liver cancer.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899190","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":"Mortality after colorectal cancer among survivors of childhood cancer","authors":"Ajay Major, Joanne Chou, Helen Lam, Karen E Kim, Lucie M Turcotte, Wendy Leisenring, Yutaka Yasui, Joseph P Neglia, Michael Curry, Rebecca M Howell, Kevin C Oeffinger, David Hodgson, Paul C Nathan, Greg T Armstrong, Chaya S Moskowitz, Tara O Henderson","doi":"10.1093/jnci/djaf127","DOIUrl":"https://doi.org/10.1093/jnci/djaf127","url":null,"abstract":"Mortality after diagnosis of colorectal subsequent malignant neoplasms (CRC-SMN) among childhood cancer survivors is understudied. Using data from the Childhood Cancer Survivor Study (CCSS) and the Surveillance, Epidemiology, and End Results (SEER) program, we compared all-cause mortality of survivors with CRC-SMN to survivors without CRC-SMN and CRC patients in the general population without a childhood cancer history. Among 25,656 childhood cancer survivors, 96 developed CRC-SMN, with 50% diagnosed before age 40 and 19% before age 30. Of those diagnosed before age 40, 35% had no prior abdominal/pelvic-directed radiation therapy. The cumulative incidence of CRC-SMN in CCSS survivors was 0.7% (95%CI: 0.5%-0.9%) by age 45 and 1.1% (95%CI: 0.8%-1.4%) by age 50. There were 31 deaths after CRC-SMN. Adjusted all-cause mortality was threefold higher (HR 3.34, 95%CI: 2.25-4.59) than for survivors without CRC and significantly higher for survivors diagnosed under age 30 compared to SEER CRC patients (HR 2.51, 95%CI: 1.29-4.89).","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899187","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":"Outcomes of subsequent treatment regimens after trastuzumab deruxtecan in patients with metastatic breast cancer.","authors":"Paolo Tarantino,Do Lee,Julia Foldi,Pamela R Soulos,Cary P Gross,Tess O'Meara,Thomas Grinda,Stefania Morganti,Adrienne G Waks,Eric P Winer,Nancy U Lin,Ian E Krop,Sara M Tolaney,Sarah Sammons,Maryam Lustberg","doi":"10.1093/jnci/djaf220","DOIUrl":"https://doi.org/10.1093/jnci/djaf220","url":null,"abstract":"BACKGROUNDMost patients with metastatic breast cancer (MBC) are eligible for treatment with trastuzumab deruxtecan (T-DXd). No data are available to guide treatment after exposure to T-DXd.METHODSWe utilized a nationwide electronic health record-derived, deidentified database to review data of patients with MBC who initiated T-DXd between 12/2019 and 9/2023 and who received an additional line of treatment after T-DXd. Tumors were categorized as HER2-positive if ever positive before T-DXd, HER2-negative if never HER2-positive before T-DXd. We compared real-world progression-free survival (rwPFS) and overall survival for post-T-DXd treatments using the Kaplan-Meier method and the log-rank test.RESULTSWe identified 793 patients receiving a post-T-DXd treatment. Post-T-DXd treatment outcomes differed significantly by MBC subtype: median rwPFS was 4.6 months for HER2-positive, 3.4 months for hormone receptor- (HR)-positive/HER2-negative and 2.8 months for triple-negative MBC (p < .001). Outcomes with post-T-DXd treatments also varied significantly according to treatment regimen (p < .001). Among patients with HER2-positive MBC, median rwPFS ranged from 6.7 months with endocrine treatment regimens to 2.3 months with sacituzumab govitecan (SG). Among patients with HR-positive/HER2-negative MBC, rwPFS ranged from 5.9 months with eribulin to 2.5 months with SG. Among patients with triple-negative MBC, poor outcomes (rwPFS ≤3 months) were observed with most treatment regimens, including SG (3 months), eribulin (2 months) and multiagent chemotherapy (2.5 months).CONCLUSIONSOutcomes of post-T-DXd treatments differ significantly by MBC subtype and type of regimen administered. The use of SG immediately after T-DXd was associated with relatively short rwPFS across subtypes, highlighting some degree of cross-resistance with T-DXd.TRIAL REGISTRATIONN/A.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850826","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":"Active surveillance for low-risk prostate cancer: long-term utilization and outcomes among black men.","authors":"Zhiyu Qian,Stephan Korn,Hanna Zurl,Daniel Stelzl,Filippo Dagnino,Mansoo Cho,Danesha Daniels,Stuart Lipsitz,Hari S Iyer,Alexander P Cole,Quoc-Dien Trinh","doi":"10.1093/jnci/djaf224","DOIUrl":"https://doi.org/10.1093/jnci/djaf224","url":null,"abstract":"Concerns persist that low-risk prostate cancer in non-Hispanic Black (NHB) men may be more aggressive, with clinicians uncertain if active-surveillance (AS) should be used in this population. Using the SEER Prostate Cancer Specialized Database (2010-2020), we analyzed 106,486 men with low-risk prostate cancer, of whom 16.6% were NHB. AS or watchful waiting (AS/WW) was less frequently used in NHB men compared to non-Hispanic White (NHW) men (32.9% vs 37.5%), NHB men showed consistently lower utilization of AS/WW over the years (aOR = 0.91, 95%CI: 0.86, 0.95), with absolute differences ranging from 3.4% to 8.5%. In multivariable competing risks analysis, 10-year PCSM did not significantly differ by race (SHR = 1.03, 95% CI: 0.66-1.60). These findings suggest AS/WW is a safe option for NHB men and its use may be underutilized in this group despite comparable long-term cancer-specific outcomes.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850828","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":"Thyroid hormones and epithelial ovarian cancer risk and survival: results from the EPIC study.","authors":"Azam Majidi,Sabina Rinaldi,Carine Biessy,Beatrice Vozar,Therese Truong,Renée Turzanski Fortner,Charlotte Le Cornet,Matthias B Schulze,Camilla Panico,Rosario Tumino,Giovanna Masala,Fulvio Ricceri,Claudia Vener,Maria-José Sánchez,Raúl Zamora-Ros,Marta Crous-Bou,Sandra M Colorado-Yohar,Marcela Guevara,Pernilla Israelsson,Ruth Travis,Elio Riboli,Agnès Fournier,Laure Dossus","doi":"10.1093/jnci/djaf222","DOIUrl":"https://doi.org/10.1093/jnci/djaf222","url":null,"abstract":"BACKGROUNDThyroid-stimulating hormone (TSH) and thyroid hormones (free triiodothyronine[fT3] and free thyroxine[fT4]) may influence cancer outcomes, but evidence for ovarian cancer is limited.METHODSWe conducted a nested case-control study comparing 578 epithelial ovarian cancer (EOC) cases to matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). To examine associations between circulating TSH, fT3, and fT4 levels and EOC risk, we estimated risk ratios (RRs) and 95% confidence intervals (CIs) per standard deviation (SD) using conditional logistic regression. Among cases, we evaluated all-cause and EOC-specific survival by pre-diagnostic hormone levels. Hazard ratios (HRs) and 95% CIs were calculated using multivariable Cox regression. We also estimated covariate-adjusted restricted mean survival time (RMST) and survival probabilities at 5 and 10 years.RESULTSThyroid hormones were not associated with EOC risk (RR[95%CI] per SD increase: TSH = 0.99[0.87-1.12]), fT3 = 1.12[0.70-1.79], and fT4 = 1.08[0.56-2.07]) levels. However, higher TSH levels were associated with better survival (HR[95%CI] per SD: all-cause death = 0.90[0.82-0.99], EOC-specific = 0.88[0.79-0.97]), while higher fT4 levels were associated with worse survival (all-cause = 1.10[1.00-1.22], EOC-specific = 1.17[1.05-1.30]), but no association for fT3. RMST and survival probabilities showed similar patterns: for TSH , 10-year RMST and survival increased from 5.3 years and 42.2% in Q1 to 6.4 years and 50.7% in (Quartile[Q]4). Conversely, for fT4, 10-year RMST declined from 5.6 years (Q1) to 5.1 years Q4, and survival from 46.3% to 37.8%.CONCLUSIONTSH and Thyroid hormones might not affect ovarian cancer risk. However, high fT4 and low TSH concentrations may be associated with poorer survival. Further evaluation is suggested in other populations.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850830","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":"Financial difficulty among patients with cancer participating in clinical trials and its association with patient survival and quality of life.","authors":"Bishal Gyawali,Nan Chen,Dongsheng Tu,Joseph Pater","doi":"10.1093/jnci/djaf221","DOIUrl":"https://doi.org/10.1093/jnci/djaf221","url":null,"abstract":"BACKGROUNDThe incidence and worsening of financial difficulty (FD) among patients with cancer participating in clinical trials, and their relationship with mortality, quality of life (QOL), and toxicity outcomes have been understudied. The objective of this study was to understand the incidence of FD among Canadian patients participating in systemic therapy trials at baseline and after trial participation, and to assess the relationship of FD with clinical outcomes.METHODSThis is a retrospective cohort study among participants of 14 systemic therapy trials conducted by the Canadian Cancer Trials Group for adult patients with advanced cancer. Incidence of FT at baseline and after trial participation were measured using EORTC QLQ-C30 questionnaire. Association of FD with trial characteristics, as well as with patient outcomes (mortality, QOL and toxicity) were studied.RESULTSOverall, 2766 patients from 14 trials were included, of which 37% had FD at baseline and 25% experienced worsening of FD after trial enrollment compared to their baseline status. Baseline FD, but not the worsening of FD, was associated with worse mortality outcomes. Worsening of FD was however associated with poor global QOL outcomes and increased odds of clinical toxicities.CONCLUSIONSEven in the setting of a public health system of Canada, one third patients experience FD, with a quarter of them experiencing worsening of FD with trial participation, and both were related to worse patient outcomes. Targeted policy level interventions are needed to understand and address the cause for FD in patients with cancer.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851244","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":"Stereotactic MRI Guided Adaptive Radiotherapy: a pooled analysis of a master prospective trial","authors":"Jonathan E Leeman, Kee-Young Shin, Alexander Droznin, Paul Catalano, Daniel N Cagney, Lisa Singer, Rasheedat Damilola Oniyangi, Kris Zhai, Grant Benham, Sejal Chirmade, Jennifer Campbell, Sara Boyle, Abbie Saranteas, Christopher L Williams, Elizabeth Huynh, Zhaohui Han, Atchar Sudhyadhom, Yue-Houng Hu, Dianne Ferguson, Kamal Singhrao, Shu-Hui Hsu, Jeremy Bredfeldt, Neil E Martin, Joseph D Mancias, Harvey J Mamon, Ritchell Van Dams, Veena Venkatachalam, Shyam K Tanguturi, Mai Anh Huynh, Kelly J Fitzgerald, Hesham Elhalawani, Danielle S Bitterman, Jonathan D Schoenfeld, Paul Nguyen, Daphne A Haas-Kogan, Raymond Mak","doi":"10.1093/jnci/djaf208","DOIUrl":"https://doi.org/10.1093/jnci/djaf208","url":null,"abstract":"Background Master clinical trial protocol structures offer administrative, procedural and statistical advantages but have not been applied in assessing new radiotherapy devices. Herein, we report on a pooled analysis from a first-of-kind master trial evaluating stereotactic MRI-guided adaptive radiotherapy (SMART). Methods Subjects were enrolled on a prospective master protocol evaluating SMART for multiple oncologic indications. CTCAE v5 toxicities, patient reported outcome measures (PROMs), and treatment efficiency metrics were assessed across the entire cohort and in anatomic subsets. Results 193 subjects were enrolled into 20 sub-protocols for different SMART indications. Data were analyzed from the first 161 subjects. The median time from subprotocol amendment submission to activation was 70.5 days (range 63-93). All completed phase I sub-protocols (n = 9) met the primary endpoints of safety and feasibility. The risk of grade 3+ toxicity was 1.9% (95%CI 0.4-5.3%), 7.1% (95%CI 0.9-23.5%), 1.8% (95%CI 0.05-9.6%) and 0% (95%CI 0.0-4.7%) in the overall cohort and thoracic, abdominal and pelvic subsets, respectively. PROMs (PROMIS-10) during and after SMART were unchanged from baseline in all subsets. SMART delivery efficiency improved over the study period (first vs final 3 months: 78.5 vs 48.2 minutes, p &amp;lt; .001). Adaptive planning performed for 771 fractions resulted in clinically significant plan improvements in 93.0% of fractions (52.7% for organ-at-risk sparing, 20.5% for target coverage and 19.8% for both). Conclusions SMART is feasible and safe for multiple thoracic, abdominal and pelvic radiotherapy indications. The master protocol platform offers an adaptable approach for assessment of new oncologic treatment technologies applicable to multiple indications. Clinical Trial NCT04115254","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"143 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825330","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":"Predicting ovarian function loss after chemotherapy and anti-HER2 therapy in young breast cancer patients.","authors":"Matteo Lambertini,Deirdre Allegranza,Ruediger P Laubender,Nadia Harbeck,Sandra M Swain,Charles E Geyer,Dennis J Slamon,Gabriella Bobba,Chiara Lambertini,Sanne de Haas,Eleonora Restuccia,Ines Vaz-Luis,David A Cameron,Ian E Krop,Eric P Winer,Richard A Anderson","doi":"10.1093/jnci/djaf198","DOIUrl":"https://doi.org/10.1093/jnci/djaf198","url":null,"abstract":"BACKGROUNDThe ability to predict ovarian function loss after anticancer treatment is important for appropriate oncofertility counselling and to aid in therapy decision-making for young women with early breast cancer (eBC).METHODSThis biomarker analysis of the BETH (NCT00625898) and KAITLIN (NCT01966471) randomized trials investigated anti-Müllerian hormone (AMH) use, alone and combined with follicle stimulating hormone (FSH) and estradiol (E2), for predicting ovarian function loss following currently adopted chemotherapy and anti-HER2 therapy in premenopausal women with HER2-positive eBC.Serum samples were centrally tested measuring AMH, FSH and E2 using Roche Elecsys assays.RESULTSAmong 194 included patients (BETH: n = 62; KAITLIN: n = 132), AMH values declined from baseline median 8.44 pmol/L to undetectable levels (<0.07 pmol/L) at end of therapy, with partial recovery at 36 months (median 0.14 pmol/L).AMH measured at baseline was predictive of ovarian loss (AUC = 0.784). Addition of age to AMH slightly improved AUC to 0.800. AMH measured at the end of therapy had AUC 0.741, which increased to 0.785 with addition of age. The combination of AMH at baseline and end of therapy increased prediction to 0.808 and with addition of age to 0.820. Addition of baseline FSH and E2 did not improve prediction in any analysis.CONCLUSIONSThese results support the use of pretreatment measurement of AMH in predicting ovarian function loss in premenopausal women with HER2-positive eBC receiving chemotherapy and anti-HER2 therapy. Measurement of AMH at end of treatment was comparable to pretreatment and added slightly to the value of pretreatment sampling.","PeriodicalId":501635,"journal":{"name":"Journal of the National Cancer Institute","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825705","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}