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Analyzing hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) expression and survival in patients with hepatocellular carcinoma (HCC) using cBioPortal.
e16236 Background: The ketogenic diet (KD) has been shown to up-regulate the rate-limiting enzyme of ketogenesis (Lan, 2022), hydroxymethylglutaryl-CoA synthase 2 (HMGCS2), which may play role in hepatocellular carcinoma (HCC) suppression when over-expressed (Cui, 2022). The open-source nature of cancer genomics websites like cBioPortal enables resource-constrained investigators the ability to engage with translational hypothesis generating research and is used here to explore the relationship between HMGCS2 expression and retrospective clinical data to guide future research. Methods: After selecting the PanCancer Atlas Liver Hepatocellular Carcinoma study for its patient-level data on both overall survival and tumor gene expression, the integrated cBioPortal query function was used to stratify the expression of HMGCS2 by over-expression (EXP > 1), under-expression (EXP < -1), or unaltered expression. The integrated survival analysis was used to generate Kaplan-Meier curves with hazard ratios derived from the long-rank test. Median overall survival (OS) and hazard ratios (HR) are reported with 95% confidence intervals. Results: 366 patients’ samples with HCC were analyzed with 73 (20%) of samples having alterations in HMGCS2 expression. 39 samples (11%) had HMGCS2 over-expression (EXP > 1), 34 (9%) were under-expressed (EXP < -1), and 292 samples had no expression alterations. Compared to the unaltered expression group with a median OS of 53.39 months (45.11-83.24), patients with HMGCS2 over-expression had a median OS of 70.06 (51.29 - NA) months for a HR of 0.592 (0.352 - 0.997). Patients with decreased expression of HMGCS2 had a median OS of 37.31 (13.48 - NA) with a HR of 1.367 (0.698 - 2.676) compared to patients with unaltered expression. Conclusions: This retrospective analysis of HMGCS2 expression in patients with HCC provides further support for the pre-clinical / translational research performed thus far with increased HMGCS2 expression associated with improved overall survival. Metabolic interventions targeting HMGCS2 expression such as the KD may warrant further investigation. Lan, Y., Jin, C., Kumar, P., Yu, X., Lenahan, C., & Sheng, J. (2022). Ketogenic Diets and Hepatocellular Carcinoma. Frontiers in Oncology , 12 , 879205. https://doi.org/10.3389/FONC.2022.879205 Cui, X., Yun, X., Sun, M., Li, R., Lyu, X., Lao, Y., Qin, X., & Yu, W. (2022). HMGCL-induced β-hydroxybutyrate production attenuates hepatocellular carcinoma via DPP4-mediated ferroptosis susceptibility. Hepatology International , 17 (2), 377. https://doi.org/10.1007/S12072-022-10459-9.
Evaluating the impact of multi-level interventions on immunohistochemistry uptake in breast cancer patients in Nigeria: A retrospective cross-sectional study.
e13639 Background: Breast cancer (BCA) is the most common malignancy globally, with highest mortality in Sub-Saharan Africa (SSA). Immunohistochemistry (IHC) is crucial for prognostic and predictive molecular subtyping. Despite the introduction of IHC infrastructure in Nigeria 25 years ago and multi-level interventions, IHC uptake remains low. Methods: This retrospective cross-sectional study assessed IHC uptake among 1,746 newly diagnosed BCA patients at a large tertiary public hospital in Nigeria (2019-2023). IHC rate was calculated as the proportion of patients with recorded molecular receptor subtype data. Treatment plan and mortality outcome were also documented. Results: Only 35.1% (613/1746) of patients obtained IHC workup prior to treatment. Among patients with IHC results, 63.0% were Triple Negative Breast Cancer (TNBC), 26.8% Hormone Receptor Positive, 4.89% Her2 Positive, and 2.44% Triple Positive. Compared to previous reports (21.6%), there's a 14% absolute increase in IHC uptake over a decade. Conclusions: Despite multi-level interventions, IHC uptake remains suboptimal, contributing to high BCA mortality in SSA compared to high income countries. Culturally adapted, patient-facing interventions are needed to improve IHC uptake and mortality outcomes.
Advancing equity in precision oncology: Impact of in-house NGS for NSCLC in a safety-net hospital.
e20704 Background: Next-generation sequencing (NGS) is essential for NSCLC management, yet access remains inequitable. We evaluated in-house NGS at New England’s largest safety-net hospital, where 65% of patients identify as racial or ethnic minorities, to assess its impact on uptake, turnaround time, test failure, and time to treatment. Methods: We conducted a retrospective study of adults with stage II–IV NSCLC treated at Boston Medical Center from 01/2019–01/2024 (n = 277). In-house NGS was implemented on 10/01/2022. Patients were classified as receiving in-house NGS, send-out NGS (external laboratories such as Foundation or Guardant), limited molecular testing (e.g., FISH, PCR), or no testing. Outcomes included NGS uptake, turnaround time, time to treatment, and testing failure. Interrupted time series evaluated changes in uptake, and multivariable regression identified factors associated with NGS receipt. Results: The cohort was 59.2% non-White, 10.8% Hispanic, 26.0% non–English-speaking, and 61% insured by Medicaid or Medicare; 44% lived in the most socioeconomically deprived neighborhoods per Area Deprivation Index. Overall, 147 patients (53.1%) received tissue-based NGS. NGS use was increasing before in-house implementation, with no discrete change in uptake attributable to implementation. Importantly, NGS receipt was comparable across race, ethnicity, insurance status, and primary language groups. Among patients receiving tissue-NGS, in-house testing shortened turnaround time (17 vs 22 days, p = 0.0005) and time to treatment (30 vs 42 days, p = 0.015) compared with send-out testing. Testing failure was lower with in-house NGS (15.3% vs 25.3%), though not statistically significant. First-line targeted therapy was more common after solid-tumor NGS (21.8%) than after limited or no testing (5.7%). Conclusions: In a diverse safety-net population, in-house NGS significantly reduced turnaround time and expedited treatment initiation, with higher use of targeted therapy. Although differences in testing failure rates did not reach statistical significance, likely due to limited power, failures were less frequent with in-house NGS, potentially reflecting closer integration with in-house pathology. Together, these findings support in-house NGS as an effective strategy to improve access to timely molecular testing in resource-limited settings. These findings support in-house NGS as a practical strategy to enhance access to timely precision oncology in resource-limited settings.
Comparative safety of immune checkpoint inhibitor–chemotherapy regimens across multiple tumor types: A systematic review and network meta-analysis.
e14571 Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become standard first-line treatment for multiple solid tumors, yet their safety profiles vary across therapeutic agents and tumor types. This systematic review and network meta-analysis (NMA) compared the safety of ICI plus chemotherapy regimens across multiple tumor types, particularly focusing on immune-related adverse events (irAEs). Methods: We systematically searched PubMed, Embase, and Web of Science for eligible phase III randomized controlled trials (RCTs) published between January 1, 2015, and November 30, 2025, that evaluated first-line ICI plus chemotherapy regimens in advanced solid tumors. The primary outcome was the grade ≥3 irAEs; additional outcomes included the all-grade irAEs. An NMA was performed estimating odds ratios (ORs) with 95% credibility intervals (CrI) and ranking regimens using Bayesian ranking probabilities. This study was registered with PROSPERO (CRD420251239812). Results: A total of 58 phase III RCTs were included, comprising 36664 patients and regimens combining chemotherapy with 20 distinct ICIs across multiple tumor types including lung, gastric/gastroesophageal junction, esophageal, breast, urothelial, nasopharyngeal, biliary tract, and head and neck squamous cell cancers. For grade ≥3 irAEs, cumulative ranking probabilities showed that top three safest ICI regimens were adebrelimab (47.0%), avelumab (22.0%) and finotonlimab (21.1%), with pooled OR versus chemotherapy alone of 1.62 (95% CrI 0.28–9.83), 2.78 (95% CrI 0.45–16.08) and 3.38 (95% CrI 0.42-37.26), respectively. Regarding all-grade irAEs, cumulative ranking probabilities identified avelumab as most likely to rank first (47.3%), followed by retifanlimab (42.3%) and adebrelimab (31.0%), with pooled OR versus chemotherapy alone of 1.54 (95% CrI 0.61–4.04), 1.61 (95% CrI 0.62–4.33) and 1.86 (95% CrI 0.69–4.96), respectively, showing better safety profile than other regimens. Conclusions: This study identifies clinically meaningful differences in safety profiles among ICI plus chemotherapy regimens across multiple solid tumors.
Impact of electronic patient-reported outcome measure (ePROM)–triggered, collaborative care (CC)–based symptom intervention on depression and anxiety in young adults (YAs) with cancer.
12007 Background: YAs with cancer, defined as those diagnosed prior to the age of 40, may experience greater symptom burden compared to those diagnosed at older ages. We evaluated the impact of an ePROM-triggered, CC-based, supportive care intervention on symptom burden in YAs with cancer. Methods: The Enhanced, Electronic Health Record-facilitated Cancer Symptom Control (E2C2) trial was a cluster-randomized, pragmatic trial (NCT03892967) that enrolled oncology patients seen at Mayo Clinic Rochester and within the Mayo Clinic Health System (sites in Minnesota and Wisconsin) between March 2019 and January 2023. Patients routinely reported the severity of six SPPADE symptoms (Sleep deficit, Pain, Physical function impairment, Anxiety, Depression, and Energy deficit/fatigue) on 11-point numerical rating scales. Symptom severity was classified as none to mild (0-3), moderate (4-6), or severe (7-10). Those with moderate or severe symptoms were offered symptom management education, while those with severe symptoms were also offered the option to work virtually with a symptom care manager. In this post hoc analysis, we examined the effects of the intervention on change in symptom scores among YAs and time to improvement to a mild/moderate level in those with at least one severe symptom. Results: Among 40,659 patients who responded to at least one survey, 2,598 were YAs and 38,061 were adults ≥ 40 years. Among YAs, 10.7%, 24.3%, and 65.1% were 18-24 years, 25-31 years, and 32-39 years, respectively. A greater proportion of YA patients were female (61.5% vs 57.0%), of a non-white race (12.4% vs 5.3%), living in an urban setting (65.7% vs 55.1%), single (36.4% vs 9.6%), on non-government insurance (78.1% vs 36.6%), employed (72.6% vs 37.4%), and had a Bachelor’s degree or greater (37.8% vs 28.3%, p < 0.001 for all). Fewer YA patients had metastatic disease compared to older patients (24.2% vs 35.2%, p < 0.001). Compared to a pre-intervention baseline, the mean change in symptom score for YA patients following the intervention demonstrated improvements in anxiety (-0.195) and depression (-0.168, p < 0.0001 for both), while physical function impairment worsened over the intervention period (0.101, p = 0.014). Compared to adults ≥ 40 years, YAs experienced greater intervention effects for management of depression ( p < 0.001), fatigue ( p = 0.01), pain ( p < 0.0001), and physical function impairment ( p < 0.0001). Among YAs with a severe symptom during the intervention period, median time to improvement to a mild/moderate level was longer for anxiety compared to those ≥ 40 years (3.5 vs 2.7 months, p = 0.009). Conclusions: Routine ePROM surveillance, coupled with CC-based symptom management, led to improvements in anxiety and depression among YAs with cancer, although, time to improvement was longer for anxiety compared to adults ≥ 40 years.
Impact of bevacizumab on the efficacy of antibody–drug conjugates as later-line treatment of basal-like immune-suppressed triple-negative breast cancer.
1020 Background: Basal-like immune-suppressed (BLIS) triple-negative breast cancer (TNBC) is associated with a poor prognosis; however, prior analyses from the FUTURE and FUTURE-SUPER clinical trials indicated clinical responsiveness to anti-angiogenic therapy. We conducted this study to evaluate the safety and efficacy of combining bevacizumab with antibody–drug conjugates (ADCs) in patients with the BLIS subtype. Methods: The FUTURE 2.0 study (NCT05749588) is an ongoing, open-label, multi-arm phase II platform trial evaluating novel molecularly targeted agents in patients with histologically confirmed TNBC who progressed after ≥1 line of systemic therapy for recurrent or metastatic disease. This report presents results from the BLIS arms: arm C (HER2-low) and arm D (HER2-zero). In arm C, patients received either SHR-A1811 (anti-HER2 ADC, 4.8 mg/kg IV q3w) alone (C1) or with bevacizumab (15 mg/kg IV q3w) (C2). In arm D, patients received either SHR-A1921 (Trop2-targeted ADC, 3.0 mg/kg IV q3w) alone (D1) or with bevacizumab (7.5 mg/kg IV q3w) (D2). The primary endpoint was confirmed objective response rate (ORR). Safety was assessed in all treated patients with available safety data. Results: From April 2022 to October 2025, 100 women were enrolled: 60 assigned to bevacizumab-combination arms (C2 and D2) and 40 to ADC monotherapy arms (C1 and D1). All 100 patients completed at least one post-baseline assessment. Confirmed ORR was 40.0% (8/20; 95% CI: 21.9–61.3%) in C1, 86.7% (26/30; 95% CI: 70.3–94.7%) in C2, 40.0% (8/20; 95% CI: 21.9–61.3%) in D1, and 83.3% (25/30; 95% CI: 66.4–92.7%) in D2. All four arms met the protocol-specified ORR success criterion with high posterior probability. Median PFS was 9.2 months in the combination group versus 4.6 months in the monotherapy group (HR = 0.47; 95% CI: 0.30–0.74), indicating a clinically meaningful improvement. Grade ≥3 treatment-related adverse events occurred in 27.5% (11/40) of monotherapy patients and 33.3% (20/60) of combination patients. No treatment-related deaths occurred. Conclusions: This study provides preliminary evidence of synergy between bevacizumab and ADCs, supporting a promising new strategy—especially for basal-like, immune-suppressed TNBC. Phase III trials are ongoing to confirm the efficacy and safety of this combination. Clinical trial information: NCT05749588 . The efficacy table. ADC monotherapy ADC combined with bevacizumab A1811 N=20 A1921 N=20 Total N=40 A1811+ Bev N=30 A1921+ Bev N=30 Total N=60 ORR, n (%, 95% CI) 8 (40.0) 21.9 – 61.3 8 (40.0) 21.9 – 61.3 16 (40.0) 26.4 – 55.4 26 (86.7) 70.3 – 94.7 25 (83.3) 66.4 – 92.7 51 (85.0) 73.9 – 91.0 mPFS (mo, 95% CI) 4.9 4.1 – 5.7 4.4 3.7 – 5.1 4.6 3.9 – 5.3 9.1 7.2 – 11.1 9.3 8.2 – 10.5 9.2 7.3 – 11.0 HR in PFS, 95% CI 0.470.30 – 0.74 ( P =0.001)
AQUARIUS: A longitudinal multi-center molecular biomarker discovery registry for patients with hematologic malignancies.
TPS7105 Background: Despite therapeutic innovations over the past decade in hematologic malignancies, there remains a significant unmet need in understanding disease progression, identifying progression and resistance biomarkers, and accurately predicting responses to various treatments. Identifying new therapeutic targets by moving deeper into the molecular and genetic architecture of the tumor is key to overcoming resistance and tailoring interventions to the unique biological profile of each individual. For example, follicular lymphoma (FL) demonstrates heterogeneous clinical behavior ranging from not requiring therapy (active observation), with not as yet well-defined high risk features for early progression, to patients who relapse early after initial therapy (POD24) and the ongoing risk of transformation to aggressive histology. Registry studies, in particular, provide insights into tumor heterogeneity, progression patterns, and clinical behaviors, which are essential for designing effective clinical trials and developing targeted therapies. The Tempus AQUARIUS hematologic biomarker discovery registry (NCT07154823) is a non-interventional, multi-center registry study aiming to create a robust dataset of molecular and clinical data from patients with hematologic malignancies to facilitate clinician-led research using whole genome sequencing (WGS) to generate hypotheses for predictive biomarkers, identify potential resistance mechanisms, and guide therapy selection. Methods: AQUARIUS is designed as a master protocol with multiple real world (rw) cohorts continuously added as future research questions emerge. The first cohort is on patients with FL, followed by additional cohorts in 2026. The FL cohort will encompass the following populations: newly diagnosed active observation (n: 100), newly diagnosed high risk (n: 150), relapsed/refractory high risk POD24 (n: 125), and transformed FL (n: 125), aiming to enroll 500 patients in total. Lymph node tissue or bone marrow aspirate and blood samples are collected during routine standard of care visits, with blood samples collected at all follow-up timepoints. Clinical data is collected—including demographics, medical history, treatment, and outcomes—at all timepoints, along with standard of care images. The emerging DNA WGS assay (Tempus xH) and existing RNA whole transcriptome sequencing assay (Tempus xR) will be performed at screening and progression/primary refractory disease to capture specific molecular alterations and potential genomic variants. Multimodal molecular profiling data will be generated prospectively. The following endpoints will be assessed: rw Overall Survival (OS), rw Progression Free Survival (PFS), rw Time to Next Treatment (TTNT), rw Time to Discontinuation (TTD), and changes in biomarkers over time. The study is open and actively enrolling. Clinical trial information: NCT07154823 .
A digital health intervention to enhance well-being among adolescent and young adult survivors of cancer: Results from the EMPOWER full factorial trial.
12006 Background: Adolescent and young adult (AYA) survivors of cancer are at significant risk of adverse psychological outcomes, yet scalable, efficacious interventions to address their needs are limited. We evaluated a self-guided digital health intervention with affective, behavioral, and cognitive skills, “Enhancing Management of Psychological Outcomes With Emotion Regulation” (EMPOWER), for improving psychological outcomes. Methods: We recruited AYAs ( n = 352; 74% female, median age 33 years) from three comprehensive cancer centers between Dec 2021 and Sept 2024. AYAs were diagnosed at and currently aged 15 to 39 years, within 5 years post-curative treatment, and had internet access. In a full factorial design, AYAs were randomly assigned to 5 weekly components, either EMPOWER intervention or attention control (2 5 = 32 arms): 1. positive events, capitalizing & gratitude (vs. cognitive skills); 2. mindfulness (vs. financial literacy); 3. positive reappraisal (vs. nutrition); 4. personal strengths & goal-setting (vs. weight management); 5. acts of kindness (vs. sun protection). Didactic lessons and skills practices were delivered via a website designed specifically for the study. AYAs completed PROMIS measures for positive affect (primary outcome), and depression and anxiety (secondary outcomes) at pre-intervention, post-intervention, and two and four months post-intervention. Using the intent-to-treat principle and a mixed model with linear contrasts, we estimated average within-person changes over time by component (intervention/control) for AYAs and compared changes by component. Results: From pre to post-intervention, positive affect increased (p<0.05) among those in 3 of the 5 EMPOWER and 4 of the 5 control components (mean change = 1.4 to 1.9) and anxiety decreased (p<0.05) for those in 4 of 5 EMPOWER and 4 of 5 control components (mean change = -1.2 to -2.0). Further, anxiety was significantly lower (p<0.05) for all EMPOWER and control components at two and four-months post intervention (mean change = -1.3 to -2.4). There was little change in depression for any group. We found no treatment effects for any outcome whereby AYAs who received intervention content had significantly greater improvements than those receiving attention control content. Instead, some EMPOWER (positive events, capitalizing, & gratitude; acts of kindness) and control components (nutrition) were associated with clinically meaningful changes in outcomes, based on PROMIS metrics. Conclusions: Our findings suggest a range of affective, behavioral, and cognitive strategies drawn from both positive psychology and health education domains are similarly effective in enhancing positive affect and mitigating post-treatment anxiety and highlight the potential benefit of low-touch, self-guided digital health strategies for AYA survivors of cancer. Clinical trial information: NCT04317417 .
Genome-wide association and Mendelian randomization analyses of body mass index and breast cancer risk in women of African ancestry.
10598 Background: The relationship between adiposity and breast cancer risk is complex and incompletely understood, particularly among women of African ancestry. We investigated the association between genetically predicted and excess body mass index (BMI) and breast cancer risk in the African Ancestry Breast Cancer Genetic Consortium (AABCG) using complementary genetic and epidemiologic approaches. Methods: We conducted a genome-wide association study (GWAS) of BMI in AABCG. Independent BMI-associated variants were then used as instrumental variables in one-sample Mendelian randomization (MR) analyses, using two-stage residual inclusion with logistic regression to estimate the causal effect of BMI on breast cancer risk. To explore the joint influence of genetic and non-genetic contributions to BMI, we constructed a BMI polygenic risk score and defined the BMI polygenic-measured gap (BMI-PGM) as the difference between the percentile of observed BMI and the percentile of genetically predicted BMI. BMI-PGM was categorized into three groups based on quartile distribution: discordantly low (≤25 th percentile), concordant (25 th -75 th percentile), and discordantly high (≥75 th percentile). The association between BMI-PGM and breast cancer risk was evaluated. Results: We identified thirteen loci that were associated with BMI at the genome-wide significance level. Of these, seven loci had not been reported in prior GWAS of BMI. In the MR analyses (n = 31,522), genetically predicted BMI was inversely associated with overall breast cancer risk: odds ratio (OR) = 0.92 per 5 kg/m 2 increase, 95% confidence interval (CI) 0.86-0.99, p = 0.028. In stratified analyses, there was a stronger inverse relationship observed for estrogen receptor (ER) negative compared with ER positive breast cancer. Inverse associations with similar effect sizes were observed in analyses stratified by menopausal status. Compared with women whose observed BMI was discordantly low relative to their genetically predicted BMI, those with concordant BMI had a modestly increased risk of breast cancer (OR = 1.08, 95% CI 1.02-1.14, p = 0.0074), while women with discordantly high BMI had a 12% higher risk of breast cancer (OR = 1.12, 95% CI 1.05-1.19, p = 0.00049). Conclusions: Genetically predicted higher BMI was associated with lower breast cancer risk, whereas BMI in excess of genetic predisposition was associated with increased risk. These opposing associations highlight a distinction between genetically mediated body size versus excess weight that likely reflects adverse metabolic processes. Together, these results underscore the roles of both genetic susceptibility and modifiable influences on adiposity in breast cancer etiology and highlight the importance of maintaining a healthy weight to reduce breast cancer risk, despite variability in genetic predisposition to adiposity across the population.
Chemotherapy or targeted therapy?: Real-world comparative outcomes in advanced and recurrent head and neck cancer in resource-limited settings.
e18013 Background: Head and neck cancer (HNC) poses a significant global health burden, with 1.43 million new cases and 0.51 million deaths reported in 2020, over 90% of which are squamous cell carcinomas. Early-stage disease is typically managed with surgery, radiation, chemotherapy, or combinations thereof. For unresectable or advanced HNC, treatment options are expanding to include immunotherapy-based regimens; however, access to these therapies is often limited in resource-constrained settings due to financial burden. In this context, affordable and effective alternatives remain essential. Our study evaluates the safety and efficacy of Cisplatin plus 5-fluorouracil versus the EGFR inhibitor gefitinib in advanced HNC in a resource-limited setting. Methods: After institutional review board approval, 180 patients (>18 years) with advanced HNC were enrolled between May and December 2022. Patients with stage I/II disease, pregnancy, lactation, medical unfitness for chemotherapy, or allergies to study drugs were excluded. Participants were randomized to receive either CF (n=96) every 3 weeks for 6 cycles or gefitinib 250 mg BID daily for 3 months. Tumor response was assessed by CT scans at baseline and every 8 weeks. Toxicities were recorded each cycle. Comparisons were made using chi-square or Fisher’s exact tests; p<0.05 was significant. Results: A total of 180 patients were included, with 53.3% receiving CF and 46.7% receiving Gefitinib. Overall response rates were similar between groups, with 50% achieving complete or partial responses. Complete responses occurred in 7.3% of CF patients versus 4.8% with Gefitinib, and partial responses in 42.7% versus 48.8%, respectively. Progressive disease was seen in 51.5% of CF patients versus 48.5% with Gefitinib, while stable disease was reported in 64.6% versus 42.6%. There was no statistically significant difference in overall response. Treatment discontinuation was higher in the CF group (34.4% vs. 22.6%), and adverse events including vomiting, renal insufficiency, fever, bone marrow suppression, hearing loss, and skin rashes were more frequent with CF. Conclusions: Our study showed that both palliative care approaches effectively halted disease progression in the majority of patients with advanced HNC. Adverse effects from chemotherapy remain a significant concern, affecting both treatment adherence and quality of life. Gefitinib monotherapy demonstrated a favorable safety profile with fewer adverse events and represents a practical therapeutic option due to its oral administration. Further multi-center, long-term studies are needed to fully establish its efficacy in patients who have difficult access to immunotherapy.
Disparities in cancer screening across disease sites for transgender and gender-diverse patients.
10530 Background: Over 2 million Americans identify as transgender, nonbinary, or gender-diverse (TGD) and limited data exist on cancer screening in this population. This study examines uptake rates of recommended breast, cervical, colorectal, and prostate cancer screening in TGD persons and reports factors predictive of screening uptake. Methods: A cross-sectional single-institution cohort study was conducted at a tertiary referral center with a specialized LGBTQIA+ Inclusion Health Clinic (IHC). Adult patients self-identifying as TGD with a healthcare encounter from January 2023-May 2025 were identified in our Clinical Research Data Warehouse. Demographic, clinical, and screening data for breast, cervical, colorectal, and prostate cancers were collected. The American Cancer Society, National Comprehensive Cancer Network, and UCSF transgender breast cancer screening guidelines were used as standards for screening indications. Multivariable logistic regression was conducted to evaluate factors predictive of guideline-concordant screening uptake. Results: We identified 2,478 TGD patients (821 transgender men (TGM), 789 transgender women (TGW), and 868 gender-diverse (GD) patients). Median age was 28 years (range 18-86) and 62% were treated at the IHC. Most patients were White (78.3%) and non-Hispanic (91.1%). Sixty-four percent of patients used private health insurance, 26.2% used government insurance, and 9.2% were uninsured. Average duration of gender-affirming hormone therapy was 4.0 years (IQR 2.0, 6.0), and 31% of patients had received gender-affirming surgery. Fifty-two percent of patients had some family cancer history at any disease site. Rates of guideline-concordant cancer screening uptake are presented in Table 1. On multivariate analyses, GD gender identity (OR 2.55, 95% CI 1.68-3.88, p<0.001), age (OR 1.05, 95% CI 1.02-1.08, p<0.001), and treatment at the IHC (OR 2.24, 95% CI 1.50-3.40, p<0.001) were predictors of cervical cancer screening uptake. No significant predictors were identified of screening uptake for other disease sites. Conclusions: Gender-specific medical care is valuable for promoting guideline-concordant cancer screening uptake. Even in a specialized care center, we found poor rates of recommended cancer screening uptake in TGD patients, demonstrating opportunities to improve uptake of gender-specific cancer screening. Rates of guideline-concordant cancer screening uptake by disease site and gender identity. Disease Site Overall (n=2,478) TGW (n=789) TGM (n=821) GD (n=868) p -value Breast 49.2% 40.8% 38.5% 60.0% 0.12 Cervical 41.3% NA 31.5% 51.2% <0.001 Colorectal 43.4% 41.7% 31.0% 51.4% 0.3 Prostate 20.7% 19.6% NA 26.3% 0.7
Clinical and demographic determinants of overall survival in early-onset head and neck cancers: A multicenter database study.
e18118 Background: The incidence of early-onset (EO) head and neck cancers (HNC), defined as diagnosis before age 50 years, is increasing. EO-HNC exhibits a heterogeneous clinical course, and factors influencing overall survival (OS) remain incompletely characterized. We sought to identify clinical and demographic variables associated with OS in patients with EO-HNC. Methods: We conducted a multicenter retrospective cohort study using the TriNetX Research Network, a federated database of de-identified electronic health records. Adults diagnosed with EO-HNC were identified. The association between clinical and demographic covariates and OS was evaluated using Cox proportional hazards regression. Covariates included age at diagnosis, sex, race, primary tumor site, nicotine dependence, alcohol use disorder, obesity, type 2 diabetes mellitus, hypertension, and chronic obstructive pulmonary disease (COPD). Results: A total of 39,358 patients with EO-HNC were identified, of whom 56.9% were male. Factors significantly associated with increased mortality included male sex (HR 1.72; 95% CI, 1.59–1.85; P<0.0001), increasing age at diagnosis (HR 1.03; 95% CI, 1.02–1.03; P<0.0001), primary tumor site at the base of tongue (HR 2.81; 95% CI, 2.00–3.94; P<0.0001) or oropharynx (HR 2.05; 95% CI, 1.38–3.04; P<0.0001), White race (HR 1.09; 95% CI, 1.00–1.19; P=0.04), Black or African American race (HR 1.44; 95% CI, 1.27–1.62; P<0.0001), nicotine dependence (HR 1.29; 95% CI, 1.14–1.45; P<0.0001), alcohol use disorder (HR 1.61; 95% CI, 1.32–1.96; P<0.0001), COPD (HR 1.58; 95% CI, 1.22–2.05; P=0.001), and hypertension (HR 1.21; 95% CI, 1.08–1.36; P=0.001). Primary tumor site at the tonsil was associated with improved survival (HR 0.55; 95% CI, 0.32–0.94; P=0.029). Primary site at the palate or larynx, obesity, type 2 diabetes mellitus, and HPV status were not significantly associated with OS. Conclusions: In this large multicenter cohort of patients with EO-HNC, survival was adversely affected by male sex, increasing age at diagnosis, race, select primary tumor sites, tobacco and alcohol use, and cardiopulmonary comorbidities. Tonsillar primary tumors were associated with improved outcomes likely secondary to impressive response rates to chemoradiation in this often HPV positive cohort. These findings underscore the prognostic heterogeneity of EO-HNC and may aid in risk stratification and patient counseling.
Clinical predictors and disparities in second primary malignancy risk and survival after index head and neck cancer: A SEER population analysis.
e18090 Background: Survivors of head and neck squamous cell carcinoma (HNSCC) carry a substantial lifelong risk of developing second primary malignancies (SPMs) driven by carcinogenic exposures, field cancerization, treatment effects, and underlying behavioral or environmental factors. Previous studies suggest sociodemographic disparities in cancer outcomes; however, population-level analyses evaluating disparities in SPM survival among HNSCC survivors remain limited. Methods: We conducted a retrospective cohort study of adults (≥18 years) diagnosed with first-primary HNSCC from 2000–2015 to allow for follow-up through at least 2020 using SEER. Exclusions included autopsy-only diagnoses, synchronous tumors, and third-or-greater primaries. Key variables included sociodemographic indicators, primary cancer characteristics, and survival outcomes. Kaplan–Meier survival curves assessed racial/ethnic differences in overall survival (OS), cancer-specific survival (CSS), SPM-specific survival, and other-cause mortality. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) for SPM-specific death. Results: Among 28,608 HNSCC survivors, SPMs exhibited substantial variation in SPM histology, with squamous cell neoplasms (39.7%), adenocarcinomas (29.8%), epithelial neoplasms (8.0%), and melanomas (4.2%) representing major categories. Patients developing SPMs were older, with a median age shifting toward 65–84 years. Treatment patterns differed between primary and secondary cancers as SPM patients were less likely to receive chemotherapy (24.8% vs. 37.1%) or radiation (27.9% vs. 66.8%). The Black race was independently associated with higher SPM-specific mortality (aHR 1.41; 95% CI 1.35–1.48; p < 0.001). Non-White/Other race also conferred elevated risk (aHR 1.28; 95% CI 1.13–1.46). Patients residing in low-income counties (<$50,000 median household income) had 37% higher adjusted mortality risk from SPMs compared to the highest-income regions (p < 0.001). Non-metropolitan residence remained an independent predictor of mortality (aHR 1.07; p = 0.004). Increasing age at SPM diagnosis strongly predicted worse outcomes, with a stepwise rise in mortality from ages 45–54 through 85+ (aHRs 1.33–3.61; all p < 0.001). Conclusions: SPMs affected nearly 30% of HNSCC survivors, underscoring SPMs as a major late driver of mortality. Black survivors, residents of low-income counties, and non-metropolitan populations experienced significantly worse SPM-specific survival independent of tumor and treatment factors. The parallel excess in both cancer-specific and non-cancer mortality among Black survivors highlights the contribution of structural and health-system inequities beyond tumor biology alone. These support a shift towards risk-adapted survivorship care and targeted early detection strategies.
Real-world comparison of Dara-VRD, VRD, and Dara-RD in transplant-ineligible older adults with newly diagnosed multiple myeloma.
e19561 Background: Older adults with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible represent a clinically heterogeneous population frequently underrepresented in clinical trials. Treatment selection in this group must balance efficacy with tolerability, comorbidity burden, and geriatric vulnerability. While daratumumab (Dara) based regimens have improved outcomes in NDMM, real-world comparative data in older adults aged 70 years or older remain limited. Methods: We conducted a retrospective cohort study using the TriNetX research network. Patients aged 70 years or older with NDMM between 2017-2024 who received frontline bortezomib, lenalidomide, and dexamethasone (VRD); Dara-RD; or Dara-VRD, and did not undergo autologous stem cell transplant were included. Propensity score matching was performed to balance age, sex, comorbidities, and high-risk cytogenetics if available. The primary endpoint was overall survival (OS). Secondary endpoints were treatment-related adverse events with relevance to older adults, including anemia, thrombocytopenia, sepsis, and peripheral neuropathy. Survival was estimated using Kaplan–Meier methods and compared using Cox proportional hazards models. Results: A total of 1543 patients were identified (Dara-VRD: n = 227 ; Dara-RD: n = 400 ; VRD: n = 916 ). Median age at diagnosis was 75, 77, and 76 years respectively. Median OS was not reached for either the Dara-VRD or Dara-RD cohorts, with no significant difference in all cause mortality. Rates of sepsis, and peripheral neuropathy were similar between these regimens. A higher incidence of anemia and thrombocytopenia was observed in the Dara-VRD cohort (Table 1). Compared with VRD, patients treated with Dara-RD demonstrated a significantly lower all cause mortality and better OS (74% vs. 51%; log- rank p = 0.01). VRD was associated with higher rates of anemia, thrombocytopenia, and peripheral neuropathy compared with Dara-RD. On multivariable Cox analysis, Dara-RD was associated with a significantly lower risk of death compared with VRD (HR 0.66, 95% CI 0.49–0.88; p = 0.005). Conclusions: In this real-world analysis of transplant-ineligible adults aged 70 years or older with NDMM, Dara-RD was associated with improved survival and a more favorable toxicity profile compared with VRD. While Dara-VRD demonstrated comparable survival to Dara-RD, it was associated with a higher rates of cytopenias. Long-term follow-up is needed to further evaluate survival differences between Dara-VRD and Dara-RD and to identify subsets of older patients likely to derive the greatest benefit from quadruplet therapy. Outcome Dara-VRD Dara-RD P Dara-RD VRD P All-cause mortality 13% 16% 0.28 17% 29% 0.0002 Anemia (any grade) 55% 35% 0.001 37% 45% 0.02 Thrombocytopenia (any grade) 26% 16% 0.03 12% 22% 0.001 Sepsis 9% 10% 0.53 11% 12% 0.58 Peripheral neuropathy 11.5% 6% 0.09 5% 12% 0.002
Representation of classical and rare head and neck cancers in basket clinical trials: A pooled analysis.
e18137 Background: Basket clinical trials (BCTs) aim to expand access to novel therapies across tumor types, including rare cancers. Head and neck cancers (HNC) comprise biologically heterogeneous entities with marked differences in incidence, etiology, and therapeutic sensitivity. How these factors influence specific representation of classical squamous cell carcinoma (HNSCC) and rare HN histotypes in BCTs remains poorly characterized. Methods: We conducted a systematic review of BCTs published between April 2018 and December 2024. BCTs were classified by biomarker (BM) selection: none, single, or multiple. Cancer-specific crude incidence rates (IR per 100,000 persons; 2022) were derived from the Global Cancer Observatory and harmonized across the EU and US (both sexes, age >20 years). Associations between IR and BCT enrollment were assessed using semi-log and log-log linear models. HNC representation was evaluated for HNSCC, nasopharyngeal carcinoma (NPC), salivary gland carcinoma (SGC). Adenoid cystic carcinoma (AdCC) was analyzed descriptively using literature-derived IR. Observed-to-expected (O/E) enrollment ratios (ER) were calculated comparing observed BCT accrual with expected numbers based on subtype-specific incidence-weighted counts. Drug class (immunotherapy [IO], targeted therapy [TT], antibody–drug conjugates [ADC]) and geographic distribution were annotated. Results: Among 137 screened publications, 26 BCTs enrolling 2,488 patients across 372 centers (57% US, 29.3% EU), met the inclusion criteria: 8 no-BM, 12 single-BM and 6 multi-BM. Across 25 cancer types, IR was associated with enrollment in both semi-log (β ≈ 69.7, 95%CI 26.8–112.5, p=0.003, R² ≈ 0.34) and log–log models (β ≈ 0.39, 95%CI 0.08–0.69, p=0.015, R² ≈ 0.24), indicating a robust but not-proportional relationship. Overall, 134 HNC patients (5.3%) were included: 68 HNSCC, 34 NPC, 19 SGC, 13 AdCC. HNSCC patients were included in 11 BCTs (6 TT-, 3 IO-, 2 ADC-based, O/E ER 0.6), 69% requiring a single BM. Most NPC patients (88%) were enrolled in 2 no-BM IO trials (O/E ER 8.8), while 89.5% of SGC accrual occurred in TT- or ADC-based single-BM trials (O/E ER 2.2). AdCC patients were enrolled in 6 no-BM, 3 single-BM, 4 multi-BM trials, showing the highest O/E ER (25.9). Neither NPC nor SGC appeared in multi-BM trials. When contextualized by IR in comparison with other cancers, HNSCC was under-represented in the semi-log but well-represented in the log-log analyses. Conclusions: Representation of HNC in contemporary BCT is highly heterogeneous. Patients with rare entities such as NPC and SGC achieve proportional enrollment, and AdCC is well represented, whereas patients with HNSCC experience limited absolute accrual. These findings suggest that other factors - e.g. tumor biology, therapeutic mechanism, clinical referral to specialized facilities - rather than incidence alone, influence the access of HNC patients to BCTs.
Effects of RPL37 on the proliferation, migration, and invasion of non–small cell lung cancer cells.
e20513 Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Despite advances in targeted therapy and immunotherapy, overall prognosis remains poor, underscoring the need to better understand the molecular drivers of tumor progression. Ribosomal proteins, including ribosomal protein L37 (RPL37), have been implicated in extra-ribosomal oncogenic functions in several cancers, but their role in NSCLC is unclear. This study aimed to investigate the function and mechanism of RPL37 in NSCLC pathogenesis. Methods: Bioinformatics analysis of TCGA data assessed RPL37 expression in NSCLC. RPL37 was modulated in A549, H1299, and PC9 cell lines via siRNA/plasmid transfection and lentiviral knockdown. Functional assays included colony formation, wound healing, and Transwell migration/invasion. EMT markers (E-cadherin, ZO-1, N-cadherin, Vimentin, Snail) and Wnt/β-catenin pathway components (cyclin D1, β-catenin, MMP9, c-myc) were analyzed by Western blot. Subcutaneous xenograft models in nude mice evaluated tumor growth in vivo. Transcriptome sequencing identified potential downstream pathways. Results: We found that RPL37 is upregulated in NSCLC tissues compared to adjacent normal tissues. Using loss-of-function and gain-of-function approaches in A549, PC9, and H1299 cell lines, we demonstrated that RPL37 promotes NSCLC cell proliferation, migration, and invasion in vitro, and facilitates epithelial-mesenchymal transition (EMT). In vivo, RPL37 knockdown significantly inhibited tumor growth in a subcutaneous xenograft model. Mechanistically, transcriptome sequencing and western blotting revealed that RPL37 regulates key components of the Wnt/β-catenin pathway, including cyclin D1, β-catenin, MMP9, and c-myc. Conclusions: Collectively, our findings indicate that RPL37 functions as an oncoprotein in NSCLC by enhancing malignant phenotypes through activation of the Wnt/β-catenin signaling pathway. RPL37 may thus represent a potential therapeutic target for NSCLC intervention.
Tucatinib + subcutaneous (SC) trastuzumab (Tuc + Trast SC) in patients (pts) with solid tumors with <i>ERBB2</i> alterations (alts): Results from the targeted agent and profiling utilization registry (TAPUR) study.
3104 Background: TAPUR is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alts. Combined results of four cohorts of pts with solid tumors with ERBB2 alts treated with Tuc + Trast SC are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was done in CLIA-certified, CAP-accredited labs. Dosing was 300 mg of Tuc given orally twice daily, 600 mg of Trast and 10,000 units of hyaluronidase SC every 3 weeks (wks), until disease progression. Primary endpoint was disease control (DC) per investigator definition as complete (CR) or partial (PR) response or stable disease (SD) of at least 16 wks duration (SD16+) per RECIST v.1.1. The hypothesized null DC rate of 15% was rejected if the lower limit of a 1-sided 90% CI was >15%. Inferences were based on a beta-binomial model, which accounts for tumor type variance. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response (OR), duration of response, duration of SD (DOSD), and safety. Results: 78 pts (histology-pooled [n=40], lung [n=16], biliary tract [n=11], uterus [n=11]) with 21 tumor types with ERBB2 alts ( ERBB2 amplification [amp], n=38; mutation [mut], n=32; mut and amp, n=6; overexpression [OE], n=2) were enrolled. All cohorts were combined for analysis. 3 pts were not evaluable. Table shows demographics and outcomes. 1 CR (urothelial carcinoma [UC], ERBB2 mut), 6 PR (uterus [2], esophagus [1], lung, neuroendocrine [1], ovary [1], UC [1]; ERBB2 amp [5], mut [1]) and 18 SD16+ (10 tumor types; ERBB2 amp [7], mut [10], OE [1]) were observed for a DC rate of 33% (1-sided 90% CI, 27 to 100) and an OR rate of 9% (95% CI, 4 to 18). The null hypothesis was rejected. Duration of CR in 1 pt was 87 wks. Median (med) duration of PR was 12 wks (range, 6-72). Med DOSD in pts with SD16+ was 28 wks (range, 12-57). 20 pts (26%) had ≥1 grade 3 tx-related AE or SAE. All were consistent with tx label except back pain, cardiac troponin increase, chronic kidney disease, heart failure, hypomagnesemia, hypophosphatemia, pericardial and pleural effusion, peripheral motor and sensory neuropathy, sinus tachycardia, systemic inflammatory response syndrome and UTI. Conclusions: Tuc + Trast SC demonstrated antitumor activity in pts with advanced solid tumors with ERBB2 alts, warranting additional study. Clinical trial information: NCT02693535 . Demographics (N=78) and efficacy outcomes (n=75). Med age, years (range) 67 (39, 88) ECOG PS, No. (%) 0 29 (37) 1 44 (56) 2 5 (6) Prior systemic regimens, No. (%) 0-2 43 (55) ≥3 35 (45) DC (OR plus SD16+) rate, % (1-sided 90% CI), p-value 33 (27, 100) OR rate, % (95% CI) 9 (4, 18) Med PFS, wks (95% CI) 10 (8, 16) Med OS, wks (95% CI) 44 (30, 55)
Emergence of single-week adjuvant breast radiation therapy for early-stage breast cancer in the United States.
e12500 Background: Over the past two decades, adjuvant radiation therapy (RT) following lumpectomy for early-stage breast cancer has shifted toward shorter treatment courses (hypofractionation). Originally delivered over 5-6 weeks, RT has since been shown through Level 1 evidence to be equally effective when shortened to 3-4 weeks, with prior studies (PMID 32693964) revealing significantly higher treatment completion rates associated with shorter RT regimens (99% vs 80%). The 2020 FAST-Forward trial further demonstrated through Level 1 evidence that ultrahypofractionated RT (UHRT), a 1-week regimen, was equivalent to 3-week adjuvant RT. This study evaluates national trends in the adoption of UHRT before and after the COVID-19 pandemic. Methods: From 2018-2019 (pre-COVID) and 2021-2022 (post-COVID), early-stage breast cancer patients having received lumpectomy and adjuvant RT were assessed using the National Cancer Database (NCDB). UHRT was defined as 5.2 Gy per fraction with a total dose of 26 Gy. As the COVID-19 pandemic occurred between these intervals, adoption of 1-week RT (5.2 Gy per fraction x 5 fractions) and RT completion rates both before and after the pandemic were assessed. The Chi-square test was used to compare UHRT adoption and completion rates before and after the pandemic. Significance was defined as a two-sided p-value less than 0.05. Results: Over the two intervals, pre- and post-COVID, a total of 27,835 patients with early-stage breast cancer received adjuvant RT following lumpectomy: 13,154 pre-pandemic and 14,321 post-pandemic. In the two years prior to the COVID-19 pandemic (2018-2019), 133 patients (0.98%) underwent UHRT. In the post-COVID period (2021-2022), 2,044 patients (14.27%) underwent UHRT (p<0.0001). Prior to the pandemic, completion rates were 83.12% for patients undergoing standard fractionated RT (SFRT), 97.21% for patients undergoing hypofractionated RT (HFRT), and 100.00% for patients undergoing UHRT. After the pandemic, the completion rates were the following: SFRT: 80.48%; HFRT: 97.48%; and UHRT: 99.46%. Compared with UHRT, completion rates were significantly lower for SFRT in all periods (p<0.0001) and were comparable but slightly lower for HFRT pre-pandemic (p=0.0509), with a significant difference emerging post-pandemic (p<0.0001). Conclusions: This first nationwide analysis of the adoption of UHRT following lumpectomy for early-stage breast cancer demonstrates a 14-fold increase in the utilization of 1-week RT from 2018 to 2022. Despite this growth, UHRT remains underutilized compared to standard and hypofractionated regimens. Importantly, completion rates for UHRT were near perfect, exceeding those for SFRT and HFRT. These findings highlight a growing but still limited rate of adoption of 1-week RT in the United States, indicating fertile ground for increased adoption in breast cancer care nationwide.
Ultra-sensitive circulating tumor DNA (ctDNA) detection as predictor of survival outcomes in endometrial cancer patients undergoing frontline treatment.
5611 Background: For endometrial cancer (EC), clinicopathologic and molecular characterization add to the risk stratification complexity, but remain limited to predict risk of recurrence. Precise biomarkers are needed to guide treatment. This study seeks to investigate the value of circulating tumor DNA (ctDNA) in EC patients. Methods: In an ongoing, single-institution prospective study of EC patients undergoing primary surgical management, serial plasma samples were collected at multiple timepoints: pre-(pre-op)/post-operatively (post-op), post-definitive treatment (dTx), and surveillance. If patients did not have adjuvant therapy, the post-op time point was considered the dTx timepoint. ctDNA analysis was performed on banked samples at the non-surveillance timepoints using NeXT Personal, a personalized whole genome sequencing-based tumor-informed assay tracking up to 1800 mutations, (Personalis, Fremont, CA). Primary endpoint was ctDNA detection rate. Secondary endpoints included correlation with survival outcomes (recurrence free survival [RFS] and overall survival [OS]). Multivariable analysis was performed for RFS adjusting for dTX ctDNA detection, stage, and TP53 mutation status. Given the limited number of deaths, multivariable analysis was not performed for OS. Results: 99 patients and 254 samples were included for ctDNA analysis. Median age at surgery was 65.1 (range 42-85) years. After a median follow-up of 24.1 (range 3.4 – 67) months, there were 25 recurrences and 10 deaths. Majority had stage I (68.7%), grade 3 (73.7%) tumors, non-endometrioid histologic tumor components (63.7%), and received adjuvant therapy (79.8%; therapy declined in 4 [4%] patients). Adjuvant radiation and chemotherapy was given in 67 (67.7%) and 53 (53.5%) patients, respectively. ctDNA was detected in 83.3% (75/90) of pre-op, 19.5% (17/87) of post-op, and 14.1% (9/64) of dTx samples. Although pre-op ctDNA was not associated with survival, post-op ctDNA detection was associated with worse RFS (HR 6.3, 95% CI 2.6-15.5; p<0.001) and OS (HR 24.6, 95% CI 3-205; p=0.003). Post-op detection in the ultrasensitive range (<100 PPM) were also significantly prognostic of worse RFS (HR: 5.1, 95% CI 1.3-19.5, P=0.02). Similarly, dTx detection was associated with worse RFS (HR 27.7, 95% CI 8.9-86.6; p<0.001) and OS (HR 7.5, 95% CI 1.7-33.7; p=0.01). On multivariable analysis, dTx detection was independently associated with worse RFS (HR 27.7, 95% CI: 8.9-86.6; p<0.001). Conclusions: In a predominantly early-stage, high-risk cohort of EC patients, post-op and dTx ctDNA detection is associated with inferior survival. ctDNA detection in the ultrasensitive range may hold promise to identify EC patients at risk for recurrence which may not be identified in conventional assays. These results support ctDNA as a promising biomarker for clinical decision-making in EC.
Prostate cancer prevalence in Ohio: Rural–urban differences, environmental toxicity, and correlation with breast cancer incidence.
e22626 Background: Prostate cancer is one of the most common cancers among men worldwide and in the United States. Socioeconomic conditions and environmental exposures play an important role in shaping risk, and inequalities in these factors are linked to differences in survival outcomes. To better characterize this geographic variation in prostate cancer burden in Ohio, we evaluated geographic hotspots of prostate cancer incidence, assessed rural–urban differences, and association between high incidence regions and environmental toxic exposures to aid in the development of targeted public health interventions and prioritization of high-need regions in Ohio. Methods: This retrospective, population-based study analyzed de-identified data from 2018–2025 obtained from the Ohio Cancer Incidence Surveillance System. Following Ohio Department of Health IRB approval and execution of a Data Use Agreement, analyses were conducted at the University of Toledo. County-level toxic release data were obtained from the EPA Toxic Release Inventory. Prostate cancer incidence was analyzed at the ZIP code level using two-way analysis of variance (ANOVA) to assess associations with rural–urban classification (0–4 scale) and environmental toxin release quartiles, with interaction terms evaluating effect modification. Pearson correlation coefficients assessed linear associations between ZIP code–level prostate and breast cancer incidence. Post hoc comparisons were performed using Tukey’s honestly significant difference test, with statistical significance defined as p < 0.05. Results: Two-way ANOVA test demonstrated a marginally significant elevation in prostate cancer rates in ZIP codes located in rural counties.(p = 0.077) . No significant difference was found for environmental toxicity releases ( p = 0.169). No significant interaction effect between geography and toxicity was observed (p = 0.828). However, Pearson’s correlational analysis revealed a strong, and significant positive correlation between regional prostate cancer rates and breast cancer rates (r = 0.848, p < 0.0001). Conclusions: A marginal association was observed between prostate cancer incidence and rurality but no significant association with EPA-tracked toxic chemical releases. Prostate cancer incidence was strongly correlated with breast cancer incidence across regions, suggesting shared geographic or healthcare-related factors. Further investigation into regional screening practices, stage at diagnosis, and healthcare access is warranted to better understand prostate cancer disparities in Ohio. Factor Categories Anova Statistic (F) P value Urban-Rural Classification 0–4 0.00021613 2.13 0.0770 Toxicity level Quartiles (1=lowest 4=highest) 0.00012872 1.69 0.1687 Urban–rural × toxicity interaction Interaction term 0.00014759 0.58 0.8280