JNCI Cancer Spectrum最新文献

{"title":"TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.","authors":"Daiki Higuchi, Maiko Yamaguchi, Erisa Fujii, Mayumi Kobayashi Kato, Kengo Hiranuma, Yuka Asami, Hanako Ono, Takafumi Koyama, Masaaki Komatsu, Ryuji Hamamoto, Yasuhisa Terao, Koji Matsumoto, Akihiko Sekizawa, Mitsuya Ishikawa, Takashi Kohno, Hiroshi Yoshida, Hideki Makinoshima, Kouya Shiraishi, Tomoyasu Kato","doi":"10.1093/jncics/pkaf082","DOIUrl":"10.1093/jncics/pkaf082","url":null,"abstract":"<p><strong>Background: </strong>Human papillomavirus infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix, a rare aggressive subtype without human papillomavirus infection.</p><p><strong>Methods: </strong>To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma in 3 independent cohorts of patients with gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma. The first cohort comprised 8 gastric-type adenocarcinoma of the cervix and 22 patients with usual-type endocervical adenocarcinoma treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing. The other 2 cohorts comprised 52 patients with gastric-type adenocarcinoma of the cervix and 109 patients with usual-type endocervical adenocarcinoma and 39 patients with gastric-type adenocarcinoma of the cervix and 232 patients with usual-type endocervical adenocarcinoma, whose mutational data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (Japanese patients) and Genomics Evidence Neoplasia Information Exchange (US patients) public databases, respectively. Metabolomic analysis was performed in 8 patients, including 5 with gastric-type adenocarcinoma of the cervix.</p><p><strong>Results: </strong>TP53 mutations were more prevalent in gastric-type adenocarcinoma of the cervix than in usual-type endocervical adenocarcinoma in all 3 cohorts. Transcriptome analysis consistently revealed frequent suppression of TP53-related pathways in gastric-type adenocarcinoma of the cervix. Metabolites preferentially detected in gastric-type adenocarcinoma of the cervix tissues suggest TP53 alterations are implicated in intratumoral metabolic properties.</p><p><strong>Conclusion: </strong>The development of gastric-type adenocarcinoma of the cervix is likely driven by TP53 mutations, which play a large role in shaping intracellular signaling and metabolic profiles within tumor cells.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"REaCT-5G: a randomized trial of bone pain with 5-day filgrastim vs pegfilgrastim for neutropenia in breast cancer.","authors":"Terry L Ng, Peter Greenstreet, Carol Stober, Stuart Nicholls, Jennifer Shamess, Natalie Mills, Mohammed Ibrahim, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Parvaneh Fallah, Nasser Alqahtani, Daniel Davoudpour, Kelly Daigle, Fiona MacDonald, Lisa Vandermeer, Monica Taljaard, Mark Clemons","doi":"10.1093/jncics/pkaf081","DOIUrl":"10.1093/jncics/pkaf081","url":null,"abstract":"<p><strong>Background: </strong>Granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, are associated with bone pain, potentially impacting treatment adherence. This study hypothesized that a 5-day regimen of filgrastim would result in less bone pain than single-dose pegfilgrastim in patients receiving chemotherapy for early breast cancer.</p><p><strong>Methods: </strong>In this multicenter, open-label, randomized controlled trial, patients requiring prophylactic G-CSF during chemotherapy were randomly assigned 1:1 to receive either 5-day filgrastim or pegfilgrastim. The primary outcome was patient-reported bone pain, assessed as area under the curve of daily pain scores (0 = no pain to 10 = worst pain) over the first 5 days following G-CSF in cycle 1. Secondary outcomes included bone pain in cycles 2-4, febrile neutropenia, hospitalizations, chemotherapy delays, dose reductions, early discontinuations, chemotherapy-related deaths, health-related quality of life, and health-care resource utilization.</p><p><strong>Results: </strong>From June 2021 to March 2023, a total of 233 patients were randomly assigned, with 219 analyzed (110 filgrastim and 109 pegfilgrastim) after excluding those who withdrew before receiving treatment. Adjusting for stratification factors and prespecified baseline covariates using repeated measures linear regression, the mean area under the curve (0-40) for cycle 1 bone pain was 10.2 (11.2) for 5-day filgrastim and 10.2 (9.81) for pegfilgrastim, with an adjusted mean difference of 0.70 (95% confidence interval = 1.62 to 3.02; P = .556). Although no clinically significant differences were observed in most secondary outcomes, the 5-day filgrastim group exhibited a numerically higher incidence of febrile neutropenia (6.4% vs 0.9%, P = .065) and hospitalization (10.0% vs 3.7%, P = .106).</p><p><strong>Conclusion: </strong>There was no significant difference in bone pain between 5-day filgrastim and pegfilgrastim.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12471350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy between real-world and randomized studies of palbociclib+endocrine therapy in HR-positive/HER2-negative metastatic breast cancer: systematic review and meta-analysis.","authors":"Francesco Schettini, Sabrina Nucera, Giuseppe Di Grazia, Fabiola Giudici, Carla Strina, Manuela Milani, Richard Tancredi, Benedetta Conte, Carmen Criscitiello, Mario Giuliano, Matteo Lambertini, Rodrigo Sánchez-Bayona, Tomás Pascual, Grazia Arpino, Lucia Del Mastro, Paolo Vigneri, Massimo Cristofanilli, Hope S Rugo, Alessandra Gennari, Giuseppe Curigliano, Daniele Generali","doi":"10.1093/jncics/pkaf083","DOIUrl":"10.1093/jncics/pkaf083","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard-of-care for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC). Palbociclib, the first approved CDK4/6i, significantly improved progression-free survival (PFS) in randomized controlled trials (RCTs). However, real-world (RW) outcomes may differ due to broader patient populations. This meta-analysis evaluates the applicability of pivotal RCT findings to RW settings.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of RW studies on HR+/HER2- MBC treated with palbociclib+aromatase inhibitors (AI) or fulvestrant, reporting median PFS (mPFS) and/or overall survival (mOS). Pooled mPFS/OS was estimated using the median of medians (MM) and weighted MM (WM). RW estimates were deemed comparable to RCTs if MMPFS/OS or WMPFS/OS fell within RCTs' 95% confidence intervals (CIs). Similar criteria applied to pooled hazard ratios (HRs) of PFS/OS for palbociclib+AI vs AI in visceral/nonvisceral subgroups.</p><p><strong>Results: </strong>Twelve RW studies were analyzed. First-line palbociclib+AI MMPFS (22.5 months, 95% CI = 19.5 to 31.8) aligned with PALOMA-1/2 pooled mPFS (23.9, 95% CI = 20.2 to 27.6). First-line palbociclib+fulvestrant MMPFS (13.5, 95% CI = 11.6 to 28.5) exceeded PALOMA-3 (11.2, 95% CI = 9.5 to 12.9). Second-line palbociclib+fulvestrant MMPFS (11.5 months, 95% CI = 6.3 to 15.3) was consistent with PALOMA-3. RW first-line mOS (51.2 months, 95% CI = 49.1 to 53.3) surpassed PALOMA-1/2 pooled mOS (45.7, 95% CI = 37.5 to 53.8). WMOS (49.1 months, 95% CI = 49.1 to 53.3) was slightly lower than RCTs (53.7, 95% CI = 37.5 to 53.8). Palbociclib+AI outperformed AI in RW visceral disease, aligning with RCTs, and showed heterogeneous but favorable benefit in nonvisceral disease.</p><p><strong>Conclusions: </strong>RW data confirm palbociclib+endocrine therapy effectiveness, reinforcing its applicability to broader patient populations.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pretransplant screening and lower incidence of breast and prostate cancers among organ transplant recipients in the United States.","authors":"Shyfuddin Ahmed, Michael J Silverberg, Eric A Engels","doi":"10.1093/jncics/pkaf080","DOIUrl":"10.1093/jncics/pkaf080","url":null,"abstract":"<p><p>Solid organ transplant recipients (SOTRs) in the United States have lower risks for breast and prostate cancers than the general population. To explore whether pretransplant screening explains this observation, we conducted a case-control study of US adults aged 65 years or older using the SEER-Medicare database (2000-2019). We included 252 279 breast cancer cases, 3 855 275 female controls, 316 981 prostate cancer cases, and 2 361 846 male controls. We used Medicare claims to identify solid organ transplant procedures and screening with mammography or prostate-specific antigen testing before case/control selection. SOTRs exhibited reduced risks for breast cancer (adjusted odds ratio = 0.60, 95% CI = 0.45 to 0.80) and prostate cancer (0.84, 95% CI = 0.71 to 1.00). These inverse associations were significant among screened individuals, although a borderline association for breast cancer was suggested in unscreened women. Pretransplant cancer screening probably largely explains the reduced risks of breast and prostate cancer among US SOTRs, but there may also be other protective factors.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Political determinants of US states' screening-amenable cancer stage at diagnosis and premature cancer mortality.","authors":"Nancy Krieger, Soroush Moallef, Tori L Cowger, Jarvis T Chen, Ruchita Balasubramanian, Alecia J McGregor, Loni Philip Tabb, William P Hanage, Mary T Bassett","doi":"10.1093/jncics/pkaf073","DOIUrl":"10.1093/jncics/pkaf073","url":null,"abstract":"<p><strong>Background: </strong>Political determinants of cancer risk are largely unexplored, conceptually and empirically.</p><p><strong>Methods: </strong>Observational analysis of associations present in 2017-2021 between 5 state-level political metrics and 4 age-standardized cancer outcomes (regional and distant stage at diagnosis for breast, cervical, and colorectal cancer among screening-age adults and premature cancer mortality), overall and in standardized linear regression models adjusting for state-level poverty and medical uninsurance.</p><p><strong>Results: </strong>In fully adjusted models (adjusted for state-level poverty and state-level medical uninsurance variables: % working age adults [age 35-64] without medical insurance; number of years of state Medicaid expansion), each 1 SD shift toward a more liberal political ideology (measured by voting record) among elected officials in the US House of Representatives was associated with decreased risk of diagnosis with regional and distant breast and colorectal cancer (respectively: -0.76, 95% confidence interval [CI] = -1.26 to -0.25; -0.75; 95% CI = -1.5 to 0). Risk of premature cancer mortality likewise was lower, in the fully adjusted models, with each 1 SD shift toward more liberal scores for the state electoral college vote (-2.01, 95% CI = -3.68 to -0.33), the state liberalism policy index (-2.51, 95% CI = -4.48 to -0.54), and political ideology of elected officials in the US Senate (-1.93, 95% CI = -3.71 to -0.14).</p><p><strong>Conclusion: </strong>Our state-level analyses suggest that political metrics are associated with preventable cancer outcomes. Efforts to reduce population burdens of cancer and inequities in these burdens could benefit from analyses of sociopolitical drivers of cancer risk across the cancer continuum.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":"9 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006193","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":"Predictors of LexisNexis residential history availability and registry data concordance for childhood cancer research.","authors":"Natalie R Binczewski, Libby M Morimoto, Joseph L Wiemels, Xiaomei Ma, Catherine Metayer, Verónica M Vieira","doi":"10.1093/jncics/pkaf075","DOIUrl":"10.1093/jncics/pkaf075","url":null,"abstract":"<p><strong>Background: </strong>Use of a commercial database to obtain residential history information in environmental epidemiologic studies of cancer can lead to information bias if data availability varies by individual sociodemographic factors or case status. Residential data that are not missing at random and data that are discordant with cancer registry or birth record address data can impact subsequent exposure assessments. In our study of childhood cancers, we aimed to determine if the availability of residential history information differs by case status or other potential confounders and if there was agreement with cancer registry and birth records address data.</p><p><strong>Methods: </strong>We worked with LexisNexis to retrieve residential histories for mothers of 3573 childhood cancer cases and 7160 controls born 2000-2015 in Los Angeles and Orange Counties in Southern California. We used linear regression to determine independent predictors of having residential history returned by LexisNexis. We assessed concordance between maternal address at birth and child's address at diagnosis available from registry data and the LexisNexis residential history by comparing street addresses and geocoded coordinates.</p><p><strong>Results: </strong>Maternal characteristics (birthplace, race and ethnicity, education, insurance provider) and child's case status were associated with the mother having any address returned by LexisNexis. When comparing geocoded coordinates of cases, less than 10% of LexisNexis addresses during the diagnosis year matched cancer registry addresses. Birth record addresses matched LexisNexis-provided addresses for 47% of mothers.</p><p><strong>Conclusion(s): </strong>This study elucidates potential implications of using commercial databases such as LexisNexis to reconstruct residential histories and derive exposure measures in cancer case-control studies.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerating precision exercise medicine in cancer patients using pooled individual patient data: POLARIS experience.","authors":"Laurien M Buffart, Marlou-Floor Kenkhuis, Robert U Newton, Anne M May, Daniel A Galvão, Kerry S Courneya","doi":"10.1093/jncics/pkaf078","DOIUrl":"10.1093/jncics/pkaf078","url":null,"abstract":"<p><p>Numerous exercise oncology trials have been completed, greatly informing exercise recommendations for patients with cancer. Exercise medicine can be administered in various types, doses, and schedules at various time points. Advancing precision exercise medicine requires understanding of how the effects of different exercise interventions vary by characteristics of individual patients. The Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study provides an international infrastructure and shared database to perform pooled analyses of individual patient data (IPD) from multiple randomized controlled trials. This commentary aims to highlight the value of pooled IPD analyses, summarize key findings from published pooled IPD analyses on the effects of physical exercise on various outcomes, and provide guidance to advance precision exercise medicine for patients with cancer. POLARIS currently includes IPD from 52 exercise trials. Findings to date indicate that exercise interventions in patients with cancer have beneficial effects on physical fitness, fatigue, health-related quality of life, self-reported cognition (posttreatment), sleep disturbances, and symptoms of anxiety and depression. Additionally, it was determined that the exercise effects varied by characteristics of the patients, including the initial value of the outcome, age, marital status, and education level, and by characteristics of the intervention, including exercise supervision and specificity. Future research opportunities to advance precision exercise medicine for patients with cancer include pooling of trial data from understudied populations, data on clinical outcomes, and biomarkers, as well as applying machine learning models for identifying combinations of covariables that modify intervention effects and predictions of individual treatment effects.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12401491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-diagnostic circulating bile acid concentrations and liver cancer risk: a nested case-control analysis of 12 cohorts.","authors":"Cody Z Watling, Jessica L Petrick, Barry I Graubard, Xuehong Zhang, Matthew J Barnett, Julie E Buring, Yu Chen, A Heather Eliassen, J Michael Gaziano, Jonathan N Hofmann, Wen-Yi Huang, Jae H Kang, Jill Koshiol, Erikka Loftfield, I-Min Lee, Steven C Moore, Lorelei A Mucci, Marian L Neuhouser, Christina C Newton, Julie R Palmer, Mark P Purdue, Lynn Rosenberg, Howard D Sesso, Martha Shrubsole, Lesley Tinker, Matthew Triplette, Caroline Y Um, Kala Visvanathan, Eleanor L Watts, Jean Wactawski-Wende, Walter Willett, Fen Wu, Wei Zheng, Peter T Campbell, Dinesh Barupal, Katherine A McGlynn","doi":"10.1093/jncics/pkaf086","DOIUrl":"10.1093/jncics/pkaf086","url":null,"abstract":"<p><strong>Background: </strong>Bile acids are produced in the liver and are important for lipid digestion. Higher-circulating bile acid levels, however, have been linked to metabolic disorders, inflammation, and gut microbiota dysbiosis, which have been implicated in liver carcinogenesis. To date, few epidemiological studies have explored the association between circulating bile acids and liver cancer risk.</p><p><strong>Methods: </strong>We conducted a nested case-control study among 12 prospective cohort studies located in the United States. Fifteen prediagnostic circulating bile acids were measured from blood samples among 872 individuals who developed liver cancer and 872 matched control participants. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted conditional logistic regression analysis of circulating bile acid levels and liver cancer risk.</p><p><strong>Results: </strong>Primary conjugated bile acid concentrations were positively associated with higher risk of liver cancer (OR per doubling in concentrations [log2] and 95% CI of glycocholic acid: 1.32, 1.24 to 1.40; glycochenodeoxycholic acid: 1.33, 1.24 to 1.43; taurocholic acid: 1.28, 1.22 to 1.35; and taurchenodeoxycholic acid: 1.32, 1.24 to 1.39). Secondary conjugated bile acids were also positively associated with liver cancer risk (doubling of concentrations OR ranged from 1.11 to 1.22). Unconjugated bile acid concentrations were generally not associated with liver cancer risk, except lithocholic acid (OR per doubling: 1.27, 1.16 to 1.39). When analyses were separated into the 2 main subtypes of liver cancer, hepatocellular carcinoma (HCC; 438 cases/438 controls) and intrahepatic cholangiocarcinoma (ICC; 111 cases/111 controls), significant heterogeneity was observed for primary conjugated bile acid concentrations (all P < .001) that showed positive significant associations with HCC but not ICC.</p><p><strong>Conclusions: </strong>These results suggest that bile acids may be important markers of HCC risk and contribute to hepatocarcinogenesis; however, further research using serial measurements is needed.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12510164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of progression-free survival surrogacy by sex in randomized trials testing immunotherapy in non-small cell lung cancer.","authors":"Eleonora Pagan, Isabella Sala, Laura Pala, Fabrizio Natali, Federico Merlo, Chiara Oriecuia, Claudia Specchia, Tommaso De Pas, Chiara Catania, Emilia Cocorocchio, Daniele Laszlo, Giovanni Ceresoli, Marzia Locatelli, Priscilla Cascetta, Flaminia Facella, Benedetta Tinterri, Martina Pino, Jacopo Canzian, Giuseppe Giaccone, Vincenzo Bagnardi, Fabio Conforti","doi":"10.1093/jncics/pkaf085","DOIUrl":"10.1093/jncics/pkaf085","url":null,"abstract":"<p><strong>Background: </strong>The surrogacy of progression-free survival (PFS) for overall survival (OS) at the trial-level in randomized clinical trials (RCTs) testing immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancers (NSCLC) is influenced by several clinical-pathological factors. However, potential heterogeneity of PFS surrogacy according to patients' sex has never been investigated.</p><p><strong>Methods: </strong>RCTs testing ICIs as monotherapy or combined with chemotherapy in patients with advanced NSCLC reporting hazard ratios (HRs) for PFS and OS according to patients' sex were included. The main objective was to assess sex-based heterogeneity in the trial-level association between PFS (surrogate endpoint) and OS (reference endpoint), overall and in subgroups defined by treatment type (ICIs as monotherapy vs ICIs plus chemotherapy). We used the coefficient of determination (R2) to quantify surrogacy.</p><p><strong>Results: </strong>Twenty RCTs, for a total of 7528 male and 3008 female patients, were included. Overall, the association between OS-HR and PFS-HR was moderate: the R2 from a model adjusted by the type of treatment administered in the experimental arm was 0.69 (95% confidence interval [CI] = 0.34 to 0.88). Sex-disaggregated analysis showed heterogeneity in PFS surrogacy: the association was strong in male patients (adjusted R2 = 0.77; 95% CI = 0.56 to 0.89), but poor in female (adjusted R2 = 0.31, 95% CI = 0.03 to 0.63). Consistent results were obtained in subgroups analyses by treatment type, and in cross-validation analysis.</p><p><strong>Conclusions: </strong>In RCTs testing ICIs alone or combined with chemotherapy in patients with advanced NSCLC, PFS is a robust surrogate endpoint for OS in male patients but not in female.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unplanned hospitalization among advanced prostate cancer patients by diabetes status: a population-based study.","authors":"Amy L Shaver, Krupa Gandhi, Scott W Keith, Nikita Nikita, Christopher C Yang, Felix J Kim, Hushan Yang, William Kevin Kelly, Stephen J Freedland, Grace Lu-Yao","doi":"10.1093/jncics/pkaf070","DOIUrl":"10.1093/jncics/pkaf070","url":null,"abstract":"<p><strong>Background: </strong>Older adults with advanced prostate cancer and type 2 diabetes mellitus are underrepresented in trials of androgen receptor pathway inhibitors. This study examined changes in unplanned hospitalization rates in patients receiving androgen receptor pathway inhibitors by type 2 diabetes mellitus status and assessed if unplanned hospitalization varies according to androgen receptor pathway inhibitors.</p><p><strong>Methods: </strong>This population-based study of advanced prostate cancer patients aged older than 66 years used Surveillance, Epidemiology, and End Results-Medicare data. Prepost androgen receptor pathway inhibitor initiation changes and androgen receptor pathway inhibitor differences in unplanned hospitalization rates were estimated by adjusted incidence rate ratio with considerations for interactions between period, androgen receptor pathway inhibitor, and type 2 diabetes mellitus status. Linear contrasts were used to estimate and test conditional incidence rate ratios. Tests were 2-sided, and a P value less than .05 was considered statistically significant.</p><p><strong>Results: </strong>The study included 12 240 patients: 3160 (25.8%) with type 2 diabetes mellitus, 7191 (58.8%) received abiraterone acetate with prednisone, and 5049 (41.2%) received enzalutamide. Unplanned hospitalization rates increased after androgen receptor pathway inhibitor initiation by 65% among patients with type 2 diabetes mellitus complications (adjusted incidence rate ratio = 1.65, 95% confidence interval [CI] = 1.37 to 1.98) and 109% in nondiabetics (adjusted incidence rate ratio = 2.09, 95% CI = 1.94 to 2.26). Among patients with type 2 diabetes mellitus without complications, the increase in unplanned hospitalization rates depended on the androgen receptor pathway inhibitor initiated: 103% after abiraterone acetate with prednisone (adjusted incidence rate ratio = 2.03, 95% CI = 1.70 to 2.43) and 47% after enzalutamide (adjusted incidence rate ratio = 1.47, 95% CI = 1.21 to 1.80) and a 38% greater increase in unplanned hospitalization rates after abiraterone acetate with prednisone than enzalutamide (ratio of abiraterone acetate with prednisone adjusted incidence rate ratio divided by enzalutamide adjusted incidence rate ratio = 1.38, 95% CI = 1.06 to 1.80).</p><p><strong>Conclusions: </strong>All patients had higher unplanned hospitalization rates after androgen receptor pathway inhibitor. Our findings highlight the importance of using real-world data to better understand the interplay between preexisting health conditions and treatment outcomes, a critical step toward precision medicine.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}