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Background: Parity and breastfeeding are associated with systemic changes in maternal inflammation and reduced risk of ovarian cancer, but little is known about their impact on the ovarian tumor immune microenvironment., Methods: We evaluated the associations of self-reported parity and history of breastfeeding with tumor-infiltrating T cells among 1,706 ovarian carcinoma cases with tumor tissue collected across four studies. The abundance of tumor-infiltrating T cells was measured by multiplex immunofluorescence in tumor tissue microarrays. Odds ratios (OR) and 95% confidence intervals (CIs) for the positivity of tumor immune cells were calculated using beta-binomial models and stratified by histotype., Results: Compared to ovarian tumors in nulliparous women, there was no association between parity and ovarian tumor T cell abundance among all histotypes combined, but suggestion of increased cytotoxic T cells and T cell exhaustion among parous women with clear cell tumors. When restricted to parous women, history of breastfeeding was associated with increased odds for all T cell types (i.e., total, cytotoxic, helper, regulatory, and exhausted T cells), with ORs ranging from 1.11-1.42. For every 6 months of breastfeeding, we observed increased odds of activated helper T cell infiltration (CD3+CD4+CD69+, OR:1.13, 95% CI: 0.99-1.29), with a similar association for high-grade serous tumors, but lower odds in clear cell tumors (OR:0.43, 95% CI:0.21-0.87)., Conclusions: History of breastfeeding may alter the ovarian tumor immune microenvironment by modulating the abundance of tumor-infiltrating T cells., Impact: While replication is required, history of breastfeeding may play a role in activation of the ovarian tumor immune response.

Background: There is uncertainty around clinical applicability of tumor mutational burden (TMB) across cancer types, in part because of inconsistency between TMB measurements from different platforms. The KEYNOTE 158 trial supported United States Food and Drug Administration (FDA) approval of the Foundation Medicine test (FoundationOneCDx) at TMB≥10 mut/Mb as a companion diagnostic (CDx) for single-agent pembrolizumab in second+line. Using a large real-world dataset with validated survival endpoint data, we evaluated clinical validity of TMB measurement by the test in over 8000 patients across 24 cancer types who received single-agent immune checkpoint inhibitor (ICI)., Methods: Patients with advanced-stage cancers from 24 cancer types treated with single-agent anti-PD(L)1 therapy in standard-of-care settings were included. Deidentified data from electronic health records from approximately 280 cancer treatment facilities were captured into a clinico-genomic database. This study used the TMB algorithm from the FDA-approved test supporting solid tumor CDx and composite mortality variable validated against the national death index: real-world overall survival (rwOS). Following a prespecified analysis plan, rwOS by TMB level was assessed using Cox PH models adjusted for Eastern Cooperative Oncology Group performance status, prior treatment, microsatellite instability, sex, age, opioid rx pretherapy, and socioeconomic assessment., Results: 8440 patients met inclusion criteria. Adjusting for aforementioned factors, increasing TMB was significantly associated with rwOS across tumor types; HRs (95% CIs) relative to TMB<5: TMB 5 to <10: 0.95 (0.89 to 1.02), TMB 10 to <20: 0.79 (0.73 to 0.85), TMB≥20: 0.52 (0.47 to 0.58). For individual cancer types with prespecified statistical power, adjusted rwOS comparing TMB≥10 vs TMB<10 significantly favored TMB≥10 in 9 of 10 cancer types. In microsatellite stable subcohorts (except colorectal cancer), TMB≥10 remained associated with enriched ICI benefit. Exploratory assessments of patients receiving ICI+chemotherapy (n=4369) observed more favorable rwOS only in TMB≥20., Conclusions: Across >8000 patients treated with single-agent ICI, and within individual cancer types with sufficient power, elevated TMB based on the FDA-approved CDx was associated with more favorable rwOS compared with similar patients with lower TMB levels. This biomarker deserves further clinical investigation to potentially guide the use of immunotherapy in expanded clinical contexts., Competing Interests: Competing interests: Financial disclosures: GL, JQ, RSPH, JSR, DF, GRO and RG are employees of Foundation Medicine, a wholly owned subsidiary of Roche and have equity interest in Roche. Roche produces atezolizumab, an ICI. JSR also reports activity as a consultant and equity ownership in Tango Therapeutics and Celsius Therapeutics. JS, LB, CC-P and MP are employees of Flatiron Health, which is an independent member of the Roche Group, and stock ownership in Roche. JS also reports equity ownership in Flatiron Health. DG reports institutional research grants from Amgen, AstraZeneca, Genentech, Merck; and consultant/advisory board activity for Adagene (institutional), AstraZeneca (institutional), Roche-Genentech (institutional), Guardant Health (institutional), IO Biotech (institutional), Oncocyte (institutional), OncoHost (institutional), Merck (consultant). NA reports no conflicts since April 15, 2021. NA reports lifetime disclosures of consultancy to Astellas, Astra Zeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; and institutional research funding (lifetime) from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon.SG is a Consultant/Advisor for Bristol Myers Squibb, Bayer, Pfizer, EMD Sorono, Merck, Seattle Genetics, Gilead Sciences, Foundation Medicine, Guardant, Loxo Oncology. She is/has served on the Speakers Bureau for Gilead Sciences, Bristol Myers Squibb, Seattle Genetics and Janssen. She has stock options in Moderna, Buo Tech and Nektar Therapeutics. Her Institution has received research funding from Merck, Novartis, EMD Sorono, Gilead Sciences, Bristol Myers Squibb, Seattle Genetics, Moderna, Exelixis, Pfizer. SJK has served in a consultant/advisory role for Bristol Myers Squibb, Merck, Eli Lilly, Astellas, Daiichi-Sankyo, Pieris, Natera, Novartis, AstraZeneca, Mersana, Sanofi-Aventis, Servier, and Coherus. SJK reports stock/equity in Turning Point Therapeutics (ended 6/2022) and Nuvalent (ended 11/2022). MCA reports advisory board participation and honoraria from MSD Australia; honoraria from Pierre Fabre Australia and research funds to institution from MSD Australia and BMS Australia. AM is on speakers bureau with AstraZeneca and Exelixis. He has received honorarium from Taiho Oncology and Eisai and research funding from Pfizer. VS reports advisory board participation for Relay therapeutics, Roche, Pfizer, Bayer, Labcorp, Illumina, Jazz Pharmaceuticals, Aadi Biosciences. RE reports research funding (institutional) from Clovis Oncology, GSK, Merck, AstaZeneca; consulting fees (including participation on Data Safety Monitoring Board or Advisory Board) from Astra Zeneca, Clovis, Eisai, GSK, Immunogen, Mersana, Myriad, Novocure, Onconova, Elevar Therapeutics, Daichi Sankyo; payment for presentations/writing/educational events from Astra Zeneca, GSK, Immunogen, Merck, Medscape, CURIO, Great Debates and Updates; role as GOG P Associate Clinical Trial Advisor; role as Scientific and Medical Advisor to Clearity Foundation. DPC reports activity as a consultant for AstraZeneca, Nexus, Abbvie, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, EMD Serono, GSK, Incyte, Inivata, Inovio, Kyowa Hakko Kirin, Loxo, Merck, Novartis, Pfizer, Takeda, Flame, G1 Therapeutics, GenePlus, Genentech/Roche, Gloria Biosciences, Lilly, Oncocyte, OncoHost, Amgen, Curio Science, Johnson & Johnson, Sanofi, Novartis, Novocure, Janssen, Gritstone, Iovance. JWR reports consulting/advisory board activity for Blueprint, Beigene, Daiichi Sankyo, EMD Serano, Janssen, Regeneron, Sanofi, Biodesix, Bayer, Turning Point, Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Roche/Genentech, Boehringer Ingelheim, Merck, SeaGen; and research funding (to institution) from Merck, Novartis, AstraZeneca, Spectrum, Revolution Medicines, Arrivent, IO Biotech, Vitrac. SS reports research funding from Astra Zeneca, Seagen, Eli Lilly, and Sermonix; and consulting for Eli Lilly, Astra Zeneca, Foundation Medicine, Gilead, Seagen, Pfizer, Novartis, Stemline, and Daiichi Sankyo., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Prognosis following a diagnosis of invasive epithelial ovarian cancer is poor. Some studies have suggested modifiable behaviors, like diet, are associated with survival but the evidence is inconsistent., Objective: To pool data from studies conducted around the world to evaluate the relation between dietary indices, foods, and nutrients from food sources and survival after a diagnosis of ovarian cancer., Methods: This analysis from the Multidisciplinary Ovarian Cancer Outcomes Group within the Ovarian Cancer Association Consortium included 13 studies with 7,700 individuals with ovarian cancer, who completed food-frequency questionnaires regarding their pre-diagnosis diet. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for associations with overall survival were estimated using Cox proportional hazards models., Results: Overall, there was no association between any of the seven dietary indices (representing pre-diagnosis diet) evaluated and survival; however, associations differed by tumor stage. While there were no consistent associations among those with advanced disease, among those with earlier stage (local/regional) disease, higher scores on the alternate Healthy Eating Index (aHR Quartile 4 versus 1 = 0.66, 95% CI=0.50, 0.87), Healthy Eating Index-2015 (aHR 0.75; 95% CI=0.59, 0.97) and alternate Mediterranean diet (aHR 0.76; 95% CI=0.60, 0.98) were associated with better survival. Better survival was also observed for individuals with early-stage disease who reported higher intakes of dietary components that contribute to the healthy diet indices (aHR for Q4 versus Q1: vegetables 0.71; 95% CI=0.56, 0.91), tomatoes (aHR 0.72; 95% CI=0.57, 0.91) and nuts and seeds (aHR 0.71; 95% CI=0.55, 0.92). In contrast, there were suggestions of worse survival with higher scores on two of the three inflammatory indices and higher intake of trans-fatty acids., Conclusions: Adherence to a more heathy, less inflammatory diet may confer a survival benefit for individuals with early-stage ovarian cancer., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Penelope M Webb reports a relationship with AstraZeneca Australia that includes: funding grants. Membership of an Advisory Board for Pfizer to enhance minoritized and underrepresented populations in clinical trials, unrelated to this study (EVB). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Objectives: Our study aims to 1) propose an approach to standardize individual-level and neighborhood-level socioeconomic status (SES) measures from administrative records across three decades, 2) determine the degree of agreement between individual-level and neighborhood-level SES measures, and 3) compare the associations of individual-level and neighborhood-level SES measures and childhood health., Study Design: Retrospective observational study., Methods: Our cohort included children born in Utah during 1978-2008. Parental SES indicators including education, occupation, and area household income corresponding to maternal addresses were collected from birth certificates. Spearman rank correlation tests were used to determine the correlation between SES measures. Cox regression models and causal mediation analyses were used to assess the association between three childhood health outcomes-mortality, failure-to-thrive, and asthma- and three SES measures: highest education level and occupational status score of parent(s) and area household income., Results: 819,108 children were included in the final analysis. We observed moderate agreement (r ranges 0.43-0.49) between individual-level SES measures (education and occupation) and weak agreement (r ranges 0.19-0.25) between these measures and neighborhood-level SES measures. Parental education had the strongest association with childhood health. The associations of parental occupation and area household income with childhood health, and their mediating effects on parental education, varied by the severity of health outcomes., Conclusions: We introduced an approach to standardize SES measures from administrative records for longitudinal analyses. We confirmed that individual-level and neighborhood-level SES measures are distinct indicators of social standing and validated the importance of the choice of SES measures when analyzing childhood health., (Copyright © 2025 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Body mass index (BMI) may misclassify obesity-related cancer (ORC) risk, as metabolic dysfunction can occur across BMI levels. We hypothesized that metabolic dysfunction at any BMI increases ORC risk compared with normal BMI without metabolic dysfunction. Postmenopausal women (n = 20,593) in the Women's Health Initiative with baseline metabolic dysfunction biomarkers [blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), and high-sensitive C-reactive protein (hs-CRP)] were included. Metabolic phenotype (metabolically healthy normal weight, metabolically unhealthy normal weight, metabolically healthy overweight/obese, and metabolically unhealthy overweight/obese) was classified using four definitions of metabolic dysfunction: (i) Wildman criteria, (ii) National Cholesterol Education Program Adult Treatment Panel III, (iii) HOMA-IR, and (iv) hs-CRP. Multivariable Cox proportional hazards regression, with death as a competing risk, was used to assess the association between metabolic phenotype and ORC risk. After a median (IQR) follow-up duration of 21 (IQR, 15-22) years, 2,367 women developed an ORC. The risk of any ORC was elevated among metabolically unhealthy normal weight (HR = 1.12, 95% CI, 0.90-1.39), metabolically healthy overweight/obese (HR = 1.15, 95% CI, 1.00-1.32), and metabolically unhealthy overweight/obese (HR = 1.35, 95% CI, 1.18-1.54) individuals compared with metabolically healthy normal weight individuals using Wildman criteria. The results were similar using Adult Treatment Panel III criteria, hs-CRP alone, or HOMA-IR alone to define metabolic phenotype. Individuals with overweight or obesity with or without metabolic dysfunction were at higher risk of ORCs compared with metabolically healthy normal weight individuals. The magnitude of risk was greater among those with metabolic dysfunction, although the CIs of each category overlapped. Prevention Relevance: Recognizing metabolic dysfunction as a significant risk factor for ORCs underscores the importance of preventive measures targeting metabolic health improvement across all BMI categories., (©2024 American Association for Cancer Research.)

Background Diagnostic imaging and biopsy are used to evaluate abnormal screening mammography. Differences in on-site availability and receipt of these diagnostic services may contribute to disparities in breast cancer outcomes across sociodemographic groups. Purpose To identify multilevel factors associated with on-site availability and receipt of diagnostic imaging and biopsy after screening mammography. Materials and Methods This retrospective study included female patients (age range, 40-89 years) who underwent screening mammography at 136 facilities in the United States from January 2010 to December 2020. The primary exposure variables were race and ethnicity and neighborhood-level educational attainment, household income, and rurality. The adjustment variables were age, breast density, breast biopsy history, personal and family history of breast cancer, time from prior mammographic examination to screening mammography, screening modality, facility academic affiliation, and screening examination year. The relative risk (RR) of factors for on-site availability at screening facilities and undergoing standard-of-care imaging (ie, mammography and/or US) and advanced diagnostic imaging (ie, digital breast tomosynthesis, MRI) and biopsy, and undergoing any same-day diagnostic service and biopsy were estimated using modified Poisson regression. Results In total, 1 123 177 female patients (median age, 59 years; IQR, 51-67 years) underwent 3 519 502 screening mammographic examinations: 10.3% Asian patients (362 440 of 3 519 502), 12.7% Black patients (447 777 of 3 519 502), 6.5% Hispanic patients (227 177 of 3 519 502), 68.3% White patients (2 403 159 of 3 519 502), and 2.2% all other races and ethnicities (78 949 of 3 519 502). In most fully adjusted models, race or ethnicity and neighborhood-level socioeconomic status were not associated with on-site diagnostic service availability. However, compared with White patients, patients belonging to racial and ethnic minority groups were less likely to undergo same-day diagnostic services after abnormal screening mammography (Asian patients: RR, 0.74 [95% CI: 0.64, 0.85]; Black patients: RR, 0.56 [95% CI: 0.49, 0.63]; Hispanic patients: RR, 0.61 [95% CI: 0.52, 0.71]). Black patients were less likely to undergo same-day biopsies after an abnormal diagnostic workup (RR, 0.46; 95% CI: 0.33, 0.65). Conclusion Although no evidence existed that on-site diagnostic service availability varied by race and ethnicity in most models, patients in racial and ethnic minority groups were less likely to be provided same-day diagnostic services and Black patients were less likely to undergo same-day biopsy. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Mullen in this issue.

Background: There are no established predictors of post-operative atrial fibrillation (POAF) in non-cardiac thoracic surgery. Pre-operative left atrial imaging has been shown to identify patients with POAF undergoing cardiac surgery. The purpose of this study was to determine whether pre-operative left atrial strain (LAS) predicts POAF in patients undergoing lung resection., Methods: One hundred forty-nine patients who underwent cancer lung resection were retrospectively analyzed. Pre-operative imaging involved conventional transthoracic echocardiography with comprehensive speckle-tracking strain. The additional advanced LAS analysis involved three components of atrial function: reservoir, conduit, and booster., Results: POAF occurred in 17 (11.4%) patients. We found no differences in demographics and peri-operative variables. Patients with POAF were more likely to have atrial fibrillation history (6.8% vs. 29.4%, p = 0.003). Preoperative imaging analysis revealed an increased LA volume index in patients with POAF (25.9 ± 8.8 vs. 32.3 ± 11.9 mL/m 2 , p = 0.046). All three components of LAS were reduced in the POAF group. The most prominent reduction was reservoir-compliance strain (35.5% ± 4.6% vs. 24.2% ± 6.6%, p < 0.001), then conduit strain (-18.3% ± 8.7% vs. -12.6% ± 4.7%, p < 0.001), and booster strain (-18.3% ± 8.7% vs. -12.6% ± 4.7%, p < 0.001). On univariable analysis, LAS reservoir strain was associated with POAF status (OR: 0.86 [95% CI: 0.78-0.92]), with a c-index of 0.81. Optimized multivariable model considering left atrial volume index, reservoir LAS, and atrial fibrillation history improved c-statistic to 0.880., Conclusion: Reduced LAS metrics are more specific and sensitive than conventional demographics and standard echocardiography in predicting POAF. Preoperative LA imaging might aid with identifying patients undergoing lung resection who are high-risk and benefit from prophylactic therapy., (© 2025 Wiley Periodicals LLC.)

Background: Bolivian Andean Aymara highlanders, living at 4,000 m for 14,000 years, have evolved genetic adaptations to hypoxia. These include EGLN1 encoding prolyl hydroxylase 2 (PHD2), a regulator of transferrin transcription. Transferrin level increases in hypoxia and iron deficiency. Contrasting reports indicate that elevated transferrin is associated with experimentally induced thrombosis in mice undergoing short-stay at high altitude, but with decreased thrombosis in a congenital disorder of hypoxia-sensing., Methods: A retrospective study was conducted in people living at high altitude (3,650 - 4,150 m). We analyzed serum transferrin concentration and thrombosis history in Aymara patients with high-altitude erythrocytosis (n = 149, median age 55 years, female gender 30%, iron deficiency 23%) or high-altitude anemia (n = 137, median age 43 years, female gender 86%, iron deficiency 57%)., Results: The median transferrin concentration was 339 mg/dL in erythrocytosis patients versus 310 mg/dL in anemia patients (P = 0.037); it was 367 mg/dL in iron deficient versus 312 mg/dL in iron replete patients (P < 0.001). Thrombosis history was present in 13% of erythrocytosis and 8% of anemia patients (P = 0.25) and was present in 16% of iron deficient and 7% of iron replete patients (P = 0.017). After adjustment for erythrocytosis and iron deficiency in multivariate regression analysis, the mean (95% confidence interval) transferrin concentration was 277 (237 - 316) mg/dL in 30 patients with thrombosis history versus 324 (306 - 341) mg/dL in 256 patients without thrombosis history (P = 0.018). Similar trends occurred for the subgroups of arterial thrombosis history (P = 0.044) and venous thrombosis history (P = 0.22)., Conclusions: In individuals with extreme environmental hypoxia, we found no evidence that increased transferrin is associated with increased thrombosis history. Rather, we observed a trend to decreased thrombosis history with increased transferrin levels., Competing Interests: None to declare., (Copyright 2025, Amaru et al.)

The objective of this study was to explore whether the time of day (AM vs. PM) resistance exercise is performed influences glucose and insulin concentrations, body composition, and muscular strength in adults with prediabetes. A secondary data analysis was conducted using data from the "Resist Diabetes" study, a phase II exercise intervention. Participants (age: 59.9 ± 5.4 yr; BMI: 33 ± 3.7 kg/m 2 ) with prediabetes and overweight or obesity were categorized into AM ( n = 73) or PM ( n = 80) exercisers based on when they completed all of their supervised exercise sessions during a 12-wk, 2×/wk resistance exercise intervention. Blood glucose and insulin derived from oral glucose tolerance tests, body composition, and muscular strength were assessed pre- and post resistance exercise training. Inverse propensity score weighting approach was used to estimate the efficacy of AM versus PM exercise on the change of clinical responses. Paired samples t test was used to compare pre-/post-outcomes within AM and PM groups. No differences between AM and PM exercisers were detected in the change in glucose or insulin area under the curve (AUC), body composition, or muscular strength. When exploring within-group changes, PM exercisers reduced glucose AUC (change: -800.6 mg/dL·120 min; P = 0.01), whereas no significant change was detected for AM exercisers (change: -426.9 mg/dL·120 min; P = 0.26). Only AM exercisers increased fat-free mass (change: 0.6 kg; P = 0.001). The time of day resistance exercise is performed may have some impact on glucose concentrations and body composition response. Future randomized clinical trials are needed to understand how exercise timing influences cardiometabolic outcomes in at-risk adults. NEW & NOTEWORTHY In this secondary analysis, there was no difference between AM and PM exercisers in blood glucose, insulin, body composition, or muscular strength following 12 wk of supervised exercise. However, examining within-group changes, glucose area under the curve (AUC) was significantly reduced in PM exercisers, but not in AM exercisers.

Objective: In the TITAN trial of patients with metastatic castration-sensitive prostate cancer (mCSPC), deep and rapid prostate-specific antigen (PSA) decline with apalutamide plus androgen deprivation therapy (ADT) was associated with longer overall survival (OS), radiographic progression-free survival (rPFS), time to PSA progression (TTPP), and time to castration resistance (TTCR) compared with no decline (all p < 0.0001). This post hoc analysis evaluated PSA kinetics in the Asian subpopulation., Methods: Data were analyzed for patients enrolled in China, Japan, and Korea and treated with apalutamide (n = 111) or placebo (n = 110) plus ADT. Examined were depth of PSA response, rates of PSA decline, and associations between a deep PSA response and clinical outcomes in apalutamide-treated patients., Results: Confirmed PSA response rates were higher with apalutamide than placebo: 73.9% versus 33.6% for PSA ≤0.2 ng/mL, 90.1% versus 58.2% for PSA reduction ≥50% [PSA50], and 74.8% versus 25.5% for PSA reduction ≥90% [PSA90]. Median (Q1; Q3) time to PSA ≤0.2 ng/mL, PSA50 and PSA90 response in the apalutamide group was 1.9 (1.0; 3.7), 1.0 (1.0; 1.0), and 1.8 (1.0; 1.9) months, respectively. PSA responses with apalutamide or placebo were consistent irrespective of high- or low-volume disease. Achievement of confirmed PSA ≤0.2 ng/mL or PSA90 response with apalutamide at landmark 3 months was associated with significantly (nominal p-values) longer OS (hazard ratio: 0.23; p = 0.0009), TTPP (0.16; p = 0.0001), TTCR (0.20; p < 0.0001), and time to progression on first subsequent therapy or death (0.19; p < 0.0001) compared with no decline., Conclusion: PSA kinetics have applications for early prognostic evaluation in Asian patients with mCSPC., (© 2024 The Japanese Urological Association.)

Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: Cancer survivorship care planning is a recognized yet underutilized aspect of care delivery, and the opportunity for telehealth in cancer survivorship is examined., Methods: We conducted a mixed-methods study in Vermont and New Hampshire to characterize perceptions of rural cancer providers and survivors regarding survivorship transitions in care, consisting of (a) key informant interviews with primary care and oncology clinicians, (b) a broader survey of clinicians, and (c) surveys and focus group discussions with cancer survivors. In these interactions, we also explored the use of a shared telehealth survivorship care planning appointment between oncology clinicians, primary care clinicians, and survivors., Results: Results from surveys and interviews clustered around several themes, namely (1) infrequent care transitioning back to primary care, (2) lack of mental health services, (3) lack of side effect education, (4) low perceived utility of survivorship care plans, (5) clinicians exclusively communicate using the EMR and finding it imperfect, and (6) clinicians and survivors reported conflicting perceptions regarding survivors' access to telehealth options., Conclusions: Our results suggest that telehealth has the potential to augment the delivery of survivorship care planning; however, key technical and logistical concerns need to be addressed, particularly enhanced coordination across clinician scheduling and ensuring payment parity for various telehealth implementation strategies., Implications for Cancer Survivors: Cancer survivorship care planning is a recognized yet underutilized aspect of care delivery. There is an opportunity for the application of telehealth for supportive care in survivorship care planning, which should be a focus of further research., Competing Interests: Declarations. Ethics approval: Study procedures and materials were reviewed and approved by the Dartmouth-Hitchcock Health Institutional Review Board (IRB). Consent to participate: The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research, supporting data is not available. Conflict of interest: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HR rectum  = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes., (© 2025 UICC.)

Background: Research on social determinants of genetic testing uptake is limited, particularly among unaffected patients with inherited cancer susceptibility., Methods: We conducted a secondary analysis of the Broadening the Reach, Impact, and Delivery of Genetic Services (BRIDGE) trial at University of Utah Health and NYU Langone Health, involving 2,760 unaffected patients meeting genetic testing criteria for inherited cancer susceptibility and who were initially randomized to either an automated chatbot or an enhanced standard of care (SOC) genetic services delivery model. We used encounters from the electronic health record (EHR) to measure the uptake of genetic counseling and testing, including dichotomous measures of (1) whether participants initiated pre-test cancer genetic services, (2) completed pre-test cancer genetic services, (3) had genetic testing ordered, and (4) completed genetic testing. We merged zip codes from the EHR to construct census tract-weighted social measures of the Social Vulnerability Index. Multilevel models estimated associations between social vulnerability and genetic services utilization. We tested whether intervention condition (i.e., chatbot vs. SOC) moderated the association of social vulnerability with genetic service utilization. Covariates included study arm, study site, age, sex, race/ethnicity, language preference, rural residence, having a recorded primary care provider, and number of algorithm criteria met., Results: Patients living in areas of medium socioeconomic status (SES) vulnerability had lower odds of initiating pre-test genetic services (adjusted OR [aOR] = 0.81, 95% CI: 0.67, 0.98) compared to patients living in low SES vulnerability areas. Patients in medium household vulnerability areas had a lower likelihood of completing pre-test genetic services (aOR = 0.80, 95% CI: 0.66-0.97) and having genetic testing ordered (aOR = 0.79, 95% CI: 0.63-0.99) relative to patients in low household vulnerability areas. We did not find that social vulnerability associations varied by intervention condition., Conclusions: These results underscore the importance of investigating social and structural mechanisms as potential pathways to increasing genetic testing uptake among patients with increased inherited risk of cancer. Census information is publicly available but seldom used to assess social determinants of genetic testing uptake among unaffected populations. Existing and future cohort studies can incorporate census data to derive analytic insights for clinical scientists., Trial Registration: BRIDGE was registered as NCT03985852 on June 6, 2019 at clinicaltrials.gov., Competing Interests: Declarations. Ethics approval and consent to participate: The UHealth and NYULH Institutional Review Boards (IRBs) approved the BRIDGE trial study protocol as a single IRB protocol (IRB 00115509). Eligible individuals received a study invitation letter with a link to an IRB-approved consent cover letter and a questionnaire. Individuals reviewed the consent cover letter first and then indicated their consent to participate in the trial by completing the questionnaire. The trial has an approved waiver of documentation of consent so a signature is not required. This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC., Patients and Methods: Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment). Escalating dose levels of SLM (2500, 3000 and 4000 μg) were administered orally twice daily for 14 days, then once daily concurrently with axitinib 5 mg twice daily using a 3+3 design in Phase I. Patients were treated at the 4000 μg dose level in the expansion cohort to obtain preliminary estimates of efficacy., Results: No dose limiting toxicities occurred at the 4000 μg SLM dose level. Among the 27 patients treated with 4000 μg of SLM, the overall response rate was 55.6%, median duration of response was 18.4 months, median progression-free survival was 14.8 months, and median overall survival was 19.6 months. Preliminary results have shown that plasma selenium concentrations, inhibition of TGF-β1 and stabilization of tumor vasculature by SLM are time dependent., Conclusions: SLM (4000 μg) in sequential combination with axitinib is well tolerated with encouraging efficacy.

Background: Non-Hodgkin lymphoma (NHL) is the seventh most common cancer among Asian, Native Hawaiian and Pacific Islanders (ANHPIs), yet the risk of death in specific ANHPI subgroups in the US is unknown., Methods: We used Surveillance, Epidemiology, and End Results data to investigate relative survival and the risk of death among NHL patients in ANHPI subgroups. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CI), comparing ANHPI subgroups to non-Hispanic White (NHW) NHL patients for all-cause death and NHL-specific death. Prognostic factors were further estimated within each ANHPI subgroup., Results: We identified 4,513 East Asian, 4,034 Southeast Asian, 1,052 South Asian, 674 Native Hawaiian and Pacific Islander (NHPI), and 116,922 NHW patients with NHL. Compared to NHW patients, East Asian, Southeast Asian, and NHPI patients had a lower 5-year relative survival. The risk of 5-year all-cause death was 1.10-fold higher for East Asian patients (95% CI 1.04, 1.15), 1.34-fold higher for Southeast Asian patients (95% CI 1.27, 1.41), and 1.62-fold higher for NHPI patients (95% CI 1.43, 1.83) compared to NHW patients. Potential prognostic factors among ANHPI NHL patients included older age at cancer diagnosis, non-married status, advanced cancer stage, and a diagnosis of DLBCL or T-cell lymphoma., Conclusion: Our study revealed significant disparities in survival among ANHPI patients with NHL, particularly among East Asian, Southeast Asian, and NHPI patients. Addressing these disparities calls for the implementation of preventive strategies and interventions tailored specifically to ANHPI subgroups. Further studies are imperative to explore adverse health outcomes within these ANHPI subgroups., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The University of Utah IRB has designated that analysis of SEER data does not require IRB review., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: Interstitial lung disease (ILD) is a well described and potentially fatal complication of trastuzumab-deruxtecan (T-DXd). It is currently unknown if specific monitoring is beneficial in the early detection of ILD in these patients. We describe the efficacy and feasibility of a novel ILD monitoring protocol in breast cancer patients treated with T-DXd at our institution., Methods: An ILD monitoring protocol developed at our institution included baseline and ongoing monitoring with pulmonary function testing (PFTs) and high-resolution chest computed tomography (HRCT) at pre-specified intervals. Patients with metastatic HER2+ or HER2-low breast cancer treated at Huntsman Cancer Institute who received ≥ 1 cycle of T-DXd between 2020 and 2023 were included (n = 68). Patient outcomes and provider adherence to the protocol were retrospectively evaluated. Providers were classified as "no adherence" if they did not elect to participate in any elements of the recommended protocol or as "some adherence" if they had at least some monitoring per protocol., Results: 10 cases of ILD were identified with an incidence of 12% (3/25) in the no adherence group and 16% (7/43) in the some adherence group. ILD cases in the no adherence group included one grade 2 and two grade 5 cases. The some adherence group included three grade 1 and four grade 2 cases., Conclusion: An ILD monitoring protocol consisting of baseline PFTs and ongoing monitoring with PFTs and HRCT is a feasible approach as evidenced by a majority provider adherence rate. This type of protocol may be effective in preventing severe cases of ILD and identifying grade 1 events that may permit treatment re-challenge., Competing Interests: Declarations. Competing interests: KK received honoraria from the Binaytara Foundation for speaking at conferences, worked as a consultant on an advisory board for Immunogen, and is currently a member of Immunogen’s 2024 Speaker’s Bureau. All other authors have no relevant financial or non-financial interests to disclose. Ethical approval: Ethics approval was not needed. Consent to participate: An informed consent waiver was granted for this study., (© 2025. The Author(s).)

Background: Reovirus (RV) is an oncolytic virus with natural tropism for cancer cells. We previously showed that RV administration in multiple myeloma (MM) patients was safe, but disease control associated with viral replication in the cancer cells was not observed. The combination with proteasome inhibitors (PIs) has shown to enhance RV therapeutic activity, but the mechanisms of action have not been fully elucidated., Methods: Electron microscopy, q-RT-PCR, single-cell mass cytometry (CyTOF), flow cytometry, plaque assays, immunohistochemistry, and Western blot analysis were used to assess RV infection of both myeloma and immune cells. Immune fluorescence, flow cytometry, and luciferase reporter assays were used to assess NF-κB pathway activation upon RV treatments. Immune profiling changes, both ex vivo and in MM patients, were analyzed by flow cytometry and CyTOF analysis. T-cell receptor (TCR) sequencing was also conducted both in immune competent MM mice and in patients enrolled in a phase 1b trial per a standard 3 + 3 dose escalation schedule., Results: Here we show ex vivo and in vivo that proteasome inhibitors (PIs) potentiate reovirus replication in circulating classical monocytes, increasing viral delivery to myeloma cells. We found that the anti-viral signals in monocytes primarily rely on NF-κB activation and that this effect is impaired by the addition of PIs. Conversely, the addition of PIs to RV therapy supports immune activation and killing of MM, independently of direct PI sensitivity. To validate the importance of PIs in enhancing oncolytic viral therapy independently of their killing activity on cancer cells, we then conducted a phase 1b trial of the reovirus Pelareorep together with the PI carfilzomib in 13 heavily pretreated PI-resistant MM patients. Objective responses, which were associated with active reovirus replication in MM cells, T cell activation, and monocytic expansion, were noted in 70% of patients., Conclusions: Although characterized as immunosuppressive drugs, PIs improved RV delivery to MM cells but also enhanced anti-MM efficacy through immune-mediated killing of myeloma cells, independently of their PI sensitivity. These results highlight a more generalizable use of PIs as therapeutic companions to support oncolytic-based therapies in cancers., Trial Registration: clinicaltrials.gov, NCT02101944., Competing Interests: Declarations. Ethics approval and consent to participate: The Ohio State University Cancer Institutional Review Board (Columbus, OH) approved this study, and informed consent was obtained from all enrolled patients ( www.clinicaltrials.gov , NCT 02101944). All animal experiments were approved by the City of Hope Institutional Animal Care and Use Committee. Consent for publication: Not applicable. Competing interests: GJN received research funding from Oncolytics Biotech Inc. MC is employed by Oncolytics Biotech Inc. CCH received research funding from BMS, Oncolytics Biotech, Sanofi, and Nektar; he received personal funds from GlaxoSmithKline, Oncopeptides, BMS, Janssen, Sanofi, and Celgene for advisory board participation, and patent-related funds from Recursion Pharmaceuticals. DWS received personal funds for consultation and advisory board participation from Sanofi, Janssen, SkylineDx, GlaxoSmithKline, Legend Biotech and Amgen., (© 2024. The Author(s).)

Introduction: The relations between coffee and tea consumption and head and neck cancer (HNC) incidence are unclear. With increasing global HNC burden, this study aims to examine the association between coffee, tea, and HNC., Methods: A pooled analysis of 9548 HNC cases and 15,783 controls from 14 individual-level case-control studies was conducted from the International Head and Neck Cancer Epidemiology consortium. Random-effects logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for HNC and its subsites, adjusting for sociodemographic and lifestyle factors., Results: Compared to non-coffee drinkers, drinking >4 cups of caffeinated coffee daily was inversely associated with HNC (OR, 0.83; 95% CI, 0.69-1.00), oral cavity (OR, 0.70; 95% CI, 0.55-0.89), and oropharyngeal cancers (OR, 0.78; 95% CI, 0.61-0.99). Drinking 3-4 cups of caffeinated coffee was inversely associated with hypopharyngeal cancer (OR, 0.59; 95% CI, 0.39-0.91). Drinking decaffeinated coffee and drinking between >0 to <1 cup daily were inversely associated with oral cavity cancer (OR, 0.75; 95% CI, 0.64-0.87 and OR, 0.66; 95% CI, 0.54-0.81). Drinking tea was inversely associated with hypopharyngeal cancer (OR, 0.71; 95% CI, 0.59-0.87). Daily tea consumption of >0 to ≤1 cup was inversely associated with HNC (OR, 0.91; 95% CI, 0.84-0.98) and hypopharyngeal cancer (OR, 0.73; 95% CI, 0.59-0.91), but drinking >1 cup was associated with laryngeal cancer (OR, 1.38; 95% CI, 1.09-1.74)., Conclusion: These findings support reduced HNC risk among coffee and tea drinkers. Future studies are needed to address geographical differences in types of coffee and tea to improve our understanding of the association of coffee and tea and global HNC risk., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Horse antithymocyte globulin carries a black box warning for life-threatening anaphylactic reactions, and prescribing information recommends test doses to identify patients at highest risk of this adverse effect. The predictive value of such test doses is not well validated, and practicality of use is unclear., Methods: This was a planned secondary analysis of a multicenter, retrospective cohort study in adults with severe aplastic anemia being managed with horse antithymocyte globulin as part of their treatment regimen. Qualitative and quantitative descriptions of test doses and infusion reactions are summarized, alongside key institutional administration practices., Results: Of 49 patients who received intradermal test doses, two experienced positive reactions and went onto receive their full horse antithymocyte globulin course through prolonged infusion time or desensitization. Infusion reaction rate in patients with negative test doses was 61%, corresponding to a negative predictive value of 39%. Premedication, infusion time, and infusion reaction management were similar across institutions., Conclusion: Horse antithymocyte globulin has a high risk of infusion reactions that must be monitored and managed closely. However, test doses do not consistently predict who will experience an infusion reaction, and their practicality may be limited with current administration practices., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Exercise can attenuate the deleterious combined effects of cancer treatment and aging among older adults with cancer, yet exercise participation is low. Telehealth exercise may improve exercise engagement by decreasing time and transportation barriers; however, the utility of telehealth exercise among older adults with cancer is not well established., Objective: We aimed to evaluate the preliminary effectiveness of a one-on-one, supervised telehealth exercise program on physical function, muscular endurance, balance, and flexibility among older adults with cancer., Methods: In this retrospective study, we analyzed electronic health record data collected from the Personal Optimism With Exercise Recovery clinical exercise program delivered via telehealth among older adults with cancer (≥65 y) who completed a virtual initial program telehealth assessment between March 2020 and December 2021. The virtual initial assessment included the following measures: 30-second chair stand test, 30-second maximum push-up test, 2-minute standing march, single leg stance, plank, chair sit and reach, shoulder range of motion, and the clock test. All baseline measures were repeated after 12-weeks of telehealth exercise. Change scores were calculated for all assessments and compared to minimal clinically important difference (MCID) values for assessments with published MCIDs. Paired samples t tests (2-tailed) were conducted to determine change in assessment outcomes., Results: Older adults with cancer who chose to participate in the telehealth exercise program (N=68) were 71.8 (SD 5.3) years of age on average (range 65-92 y). The 3 most common cancer types in this sample were breast (n=13), prostate (n=13), and multiple myeloma (n=8). All cancer stages were represented in this sample with stage II (n=16, 23.5%) and III (n=18, 26.5%) being the most common. A follow-up telehealth assessment was completed by 29.4% (n=20) of older adults with cancer. Among those who completed a follow-up telehealth assessment, there were significant increases in the 30-second chair stand (n=19; mean change +2.00 repetitions, 95% CI 0.12 to 3.88) and 30-second maximum push-up scores (n=20; mean change +2.85 repetitions, 95% CI 1.60 to 4.11). There were no significant differences for the 2-minute standing march, plank, single leg stance, sit and reach, shoulder mobility, or clock test (P>.05). Nine (47.3%) older adults with cancer had a change in 30-second chair stand scores greater than the MCID of 2 repetitions., Conclusions: Our findings suggest a one-on-one, supervised telehealth exercise program may positively influence measures of physical function, muscular endurance, balance, and flexibility among older adults with cancer, but more adequately powered trials are needed to confirm these findings., (© Emily R Dunston, Sonal Oza, Yang Bai, Maria Newton, Leslie Podlog, Kish Larson, Darren Walker, Rebecca W Zingg, Pamela A Hansen, Adriana M Coletta. Originally published in JMIR Cancer (https://cancer.jmir.org).)

Background: The COVID-19 pandemic involved business closures (e.g., gyms), social distancing policies, and prolonged stressful situations that may have impacted engagement in health behaviors. Our study assessed changes in cancer-related health behaviors during the pandemic, specifically physical activity, fruit/vegetable intake, smoking/tobacco use, and alcohol consumption., Methods: Eight cancer centers administered mailed/web-based/telephone surveys between June 2020 and March 2021. Surveys assessed demographics, perceptions on social distancing, and self-reported changes of behaviors (less/same/more) associated with cancer prevention or risk, e.g., physical activity, fruit/vegetable intake, tobacco/smoking use, and alcohol consumption. Descriptive analyses and logistic regression models assessed association of variables with behavior change., Results: Most of the 21,911 respondents reported adhering to at least 4(of 5) social distancing measures (72%) and indicated social distancing was very/somewhat important to prevent the spread of COVID-19 (91%). 35% of respondents reported less physical activity, 11% reported less fruit/vegetable intake, 27% reported more smoking/tobacco use (among those who used tobacco/smoking products in past 30 days), and 23% reported more alcohol consumption (among those who reported at least 1 drink in past 30 days) than before the pandemic. Urban residence, younger age, female gender, and worse general health were associated with less physical activity, less fruit/vegetable intake, more smoking/tobacco use, and more alcohol intake. Higher educational attainment was associated with less physical activity and fruit/vegetable intake and more alcohol consumption. Reporting social distancing as important and adhering to more COVID-19 safety practices were associated with less physical activity and more alcohol consumption., Conclusion: Our findings suggest that certain demographics and those who adhered to social distancing measures were more likely to self-report unfavorable changes in health behaviors during the pandemic. Future studies should examine if the behaviors returned to baseline following relief from pandemic restrictions, and if these behavior changes are associated with increased cancer incidence and mortality., Competing Interests: Declarations. Ethics approval and consent to participate: Written informed consent was obtained from all participants via an informed consent document included in survey packets. The informed consent document explained the purpose of the survey, how the data will be stored and analyzed, that their de-identified data may be analyzed for publication, and any benefits and risks associated with survey participation. Research was performed in accordance with the Declaration of Helsinki. Institutional Review Board (IRB) approval for this study was received from each individual site. The following sites were approved after full IRB review: Colorado Multiple IRB (Study ID PAM020-2), and Vanderbilt IRB (IRB #190235). To note, Colorado’s survey was conducted as an extension of an existing survey; thus, the approval for Colorado’s added COVID survey is shown as an amendment. The following sites received expedited review or were ruled exempt from full IRB review: University of Iowa (#IRB00000099), University of Virginia IRB for Health Sciences Research (IRB-HSR #22747), Wayne State University IRB (IRB #20-05-2219-B3), University of Alabama at Birmingham IRB (IRB #00000196/#00000726), Oregon Health & Science University IRB (IRB #300002135), and Ohio State University Cancer IRB (Study #2020C0081). Data use agreements were obtained from each site to transmit de-identified data to the coordinating center at the University of Alabama at Birmingham (UAB). Consent for publication: Written consent was received via an informed consent document included in survey packets. The informed consent document explained the purpose of the survey, how the data will be stored and analyzed, that their de-identified data may be analyzed for publication, and any benefits and risks associated with survey participation. Competing interests: Deanna Kepka is the Principal Investigator of two Merck Investigator Studies Program (MISP) Awards to Huntsman Cancer Institute at the University of Utah. Electra Paskett is the MPI on grants to the institution from Merck Foundation, Pfizer, Genentech, and Guardant Health and is an advisor for Glaxo Smith Kline. Jamie Studts provides consultation to Genentech and the J&J Lung Cancer Initiative. Monica Baskin is an advisor to Janssen Global Services, LLC; none are related to this work. The rest of the authors (BBG, AC, MEC, JS, EAB, HT, IS, LCH, EAC, CJGA, KC, HA, JJP, FWKH, SB, VP, YK, BF, CB, HK, MD, JC, VC, BFD, KLD, DLF, MIE, SKM, and WFC) declare they have no competing interest(s)., (© 2024. The Author(s).)

Background: Young adult (YA) LGBTQ+ cancer survivors face inequities and unmet needs that impact their well-being. However, the impact of age and cancer among LGBTQ+ individuals have not been adequately assessed. Methods: The North Carolina LGBTQ+ Health Needs Assessment survey, conducted at local Pride events, aimed to collect data to describe the well-being of LGBTQ+ people in NC. Chi-squared tests and multivariable logistic regression models controlling for demographic factors were used to assess age and cancer-related differences in discrimination, violence, mental health, and substance use outcomes among LGBTQ+ individuals. Results: A total of N = 3170 LGBTQ+ individuals took part in the survey, n = 89 of which were YA (aged 18-39) cancer survivors and n = 111 of which were middle to older adult (M/OA, age 40+) cancer survivors. In bivariate analyses, YA LGBTQ+ cancer survivors reported significantly more LGBTQ+ violence (43.8%), sexual assault (61.4%), experiencing homelessness (33.7%), post-traumatic stress disorder (32.6%), cocaine use (16.9%), opioid use (15.7%), and having ever accidental overdose (43.8%) in comparison with YAs without a cancer history as well as M/OA with and without a cancer history. In multivariable models, YA LGBTQ+ survivors remained at elevated odds of all outcomes in comparison with M/OA survivors without a cancer history. Outcomes varied by intersecting identities among YA survivors. Conclusions: The overlap of anti-LGBTQ+ stigma and discrimination, being young, and having been diagnosed with cancer positions YA LGBTQ+ cancer survivors to experience a higher burden of serious and life-threatening outcomes.

Wilms tumors are commonly associated with predisposition syndromes. Many of these syndromes are associated with specific phenotypic features and are discussed in the related article from the AACR Pediatric Cancer Working Group. Guidelines for surveillance in this population were published in 2017, but since then several studies have identified new genes with recurrent pathogenic variants associated with increased risk for Wilms tumor development. In general, variants in these genes are less likely to be associated with other phenotypic features. Recently, members of the AACR Pediatric Cancer Working Group met to update surveillance guidelines for patients with a predisposition to Wilms tumors with a review of recently published evidence and risk estimates. Risk estimates for Wilms tumor for the more recently described genes are discussed here along with suggested surveillance guidelines for these populations. Several other emerging clinical scenarios associated with Wilms tumor predisposition are also discussed, including patients with family histories of Wilms tumor and no identified causative gene, patients with bilateral tumors, and patients with somatic mosaicism for chromosome 11p15.5 alterations. This perspective serves to update pediatric oncologists, geneticists, radiologists, counselors, and other health care professionals on emerging evidence and harmonize updated surveillance recommendations in the North American and Australian context for patients with emerging forms of Wilms tumor predisposition., (©2024 American Association for Cancer Research.)