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The gap: Recognizing the inequities in oncology research and clinical practice guidelines—An analysis of clinical guidelines in multiple myeloma.

e23213 Background: Despite significant efforts to address inequities in oncology research, and American Society of Clinical Oncology’s (ASCO) Clinical Practice Guidelines for Hematologic Malignancies in Multiple Myeloma (MM) being updated as of 2026, a critical gap remains. These guidelines aim to promote uniformity of care for all patients with MM, yet there is still an imperative need for additional, disease-specific guidelines in hematologic malignancies, as well as for clinical research that more accurately reflects the diversity of patient epidemiology. Representative studies must be done to reflect the racial prevalence of MM, as more than twice the incidence is found in Black individuals than White Individuals (Kanapuru et al., 2022). The DRIVE ranking score assesses representation in clinical trials based on disease epidemiology (Birhiray & Birhiray, 2023). A DRIVE Score of 3 or higher is the benchmark for clinical excellence and relevance based on racial representation. An analysis of the new ASCO guidelines using the DRIVE score evaluates the generalizability and transportability of the referenced clinical trials. Methods: Following the publication of “Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline the authors analyzed the clinical trials that were used (Mikhael et al., 2026). 70 studies were utilized, with 47 studies involving adult human participants in the United States. These studies were reviewed using the National Cancer Institute (NCI) clinical trial results section and related articles. Results: Twenty-three studies were excluded due to all testing locations being outside of the U.S. The remaining 47 studies received the following DRIVE scores: 10 received a 0x, 6 received a 0, 4 received a 0*, 18 received a 1, 0 received a 2, 7 received a 3, and no studies scored a 4 or 5. Two additional studies are still in progress and were not scored. Conclusions: ASCO, as a leader in oncology research and clinical practice, must ensure transparency and accessibility for patients, clinicians, and scientists while promoting reliable and inclusive data. This analysis reveals a significant gap in utilizing population-representative studies, and a lack of representative guidelines for MM and perhaps other malignancies. The guidelines should utilize trials that are representative of patient populations, or use a subanalysis of the data to make generalizable recommendations for all patient groups. Accurate representation must be utilized in all clinical trials in order to reflect the patient population. By prioritizing diversity in clinical research, ASCO can strengthen the evidentiary foundation of its guidelines while reducing disparities and improving outcomes for patients and clinicians. These guidelines cannot truly uniformize care while being based on unrepresentative data.

Sentinel lymph node positivity in microinvasive breast cancer: A systematic review and meta-analysis.

e12620 Background: Breast cancer is a leading cause of cancer-related mortality. Advances in screening and imaging have increased detection of early-stage disease, including lesions along the spectrum of ductal carcinoma in situ (DCIS) and invasive breast cancer. Microinvasive breast cancer (T1mi), defined as ≤1 mm of stromal invasion, represents a small subset of cases and demonstrates favorable outcomes that more closely resemble DCIS than larger invasive tumors. Sentinel lymph node biopsy (SLNB) is standard for invasive breast cancer but not recommended for DCIS, rendering its role in T1mi controversial. We evaluated SLNB positivity in T1mi using published clinical outcomes. Methods: A meta-analysis of seven published studies identified through a systematic PubMed search was performed. Studies reporting the number of T1mi patients, SLNB procedures, and SLNB-positive cases were included. When available, data on macrometastasis, micrometastasis, and isolated tumor cells (ITCs) were extracted. A single-arm random-effects meta-analysis was conducted. The primary outcome was pooled SLN positivity. Results: Seven studies including 11,243 patients with T1mi were analyzed. Overall, 500 patients (4.4%) were SLN positive, with reported rates ranging from 2.9% to 21.5%. The pooled SLN positivity rate was 9% (95% CI, 6–13%). Four studies reporting ITCs (n = 110 SLN-positive cases) demonstrated substantial heterogeneity, with ITCs comprising 9%–56% of nodal metastases; the pooled ITC proportion was 39% (95% CI, 24–55%). Five studies reporting micrometastatic and macrometastatic disease (n = 186 SLN-positive cases) showed pooled proportions of 40% (95% CI, 29–51%) and 29% (95% CI, 14–47%), respectively. Conclusions: SLN positivity in T1mi is uncommon but not negligible. When nodal metastases are present, they are most often low-volume, although macrometastatic disease occurs in a subset of patients. These findings highlight heterogeneity in axillary involvement and support individualized SLNB decision-making in T1mi breast cancer. Sentinel lymph node outcomes in microinvasive breast cancer (T1mi). Outcome No. of Studies No. of Patients Range (%) Pooled Estimate (95% CI) Any SLN positivity 7 11,243 2.9-21.5 9% (6-13) Isolated tumor cells (≤0.2 mm)* 4 110† 9-56 39% (24-55) Micrometastasis (0.2–2 mm)* 5 186† 17-55 40% (29-51) Macrometastasis (>2 mm)* 5 186† 16-51 29% (14-47) *Proportions calculated among SLN-positive patients† SLN-positive cases with available stratification data.

Toripalimab plus chemotherapy and radiotherapy for treatment-naïve advanced esophageal squamous cell carcinoma: Long-term survival and recurrence patterns.

4064 Background: Concurrent chemoradiotherapy plus PD-1 blockade is standard for locally advanced esophageal squamous cell carcinoma (ESCC), but its role in advanced disease remains undefined. We investigated the safety and efficacy of Toripalimab combined with chemotherapy and radiotherapy (RCIT) as first-line treatment for advanced ESCC, analyzing long-term survival, recurrence patterns, and immune biomarkers. Methods: This single-arm, phase II trial enrolled treatment-naïve patients with stage IV ESCC (N3 nodal or oligometastases; 5 lesions in 3 organs). Treatment comprised induction chemoimmunotherapy (2 cycles) followed by concurrent radiotherapy (Cycles 3-4) and maintenance immunotherapy. Patients received Paclitaxel (135-175 mg/m2) and Carboplatin (AUC 4-6) plus Toripalimab (240 mg) on day 1 (Q3W). Intensity-modulated radiotherapy (50-50.4 Gy/25-28f) targeted primary/regional lesions, while SBRT (30-40 Gy/3-5f) targeted oligometastases. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), recurrence patterns, health-related quality of life (HRQOL), and biomarker analysis via multiplex immunofluorescence (mIF). Results: Thirty-three patients were enrolled. At a median follow-up of 33.4 months, the 2-year PFS and OS rates were 30.3% (95% CI: 18.1-50.8) and 48.5% (95% CI: 34.1-68.9), respectively. In the efficacy-evaluable population completing radiotherapy (n = 26), outcomes were significantly superior to those who did not, with a median OS of 27.4 months and a 2-year OS of 61.5% (HR = 0.26, p = 0.004). Recurrence occurred in 26 (78.8%) patients, comprising locoregional only (27.3%), distant only (18.2%), and combined failure (33.3%). Notably, among patients completing RT, in-field recurrence (57.7%) remained a predominant failure pattern despite multimodal therapy. HRQOL analysis demonstrated significant post-induction improvement in pain and social functioning scores, whereas radiotherapy transiently worsened dysphagia at 3 months post-RT (p = 0.041). Translational analysis revealed that high baseline tumor infiltration of CD8+ T cells, PD-L1+ dendritic cells, and PD-L1+ macrophages, alongside elevated serum IL-4, IL-17, and IFN-γ\gamma, were significantly associated with long-term survival (OS ≥24 months; p < 0.05). Conclusions: First-line RCIT yields promising long-term survival in advanced oligometastatic ESCC, particularly in patients completing the full radiotherapeutic course, achieving a 2-year OS of 61.5%. However, high rates of in-field recurrence suggest a need for further optimization of local control strategies. Baseline immune infiltrates and cytokine profiles offer potential predictive value for patient stratification. Randomized trials are warranted to validate these findings. Clinical trial information: ChiCTR2100046715.

Barriers to fertility preservation counseling in young cancer patients: A retrospective chart review.

e13732 Background: The possibility of infertility is a major concern for young cancer patients facing chemotherapy. While guidelines state that all patients diagnosed with cancer during their reproductive years should be referred to a fertility specialist, prior data confirm that many patients report never being granted that opportunity. Cancer treatment regimens have advanced significantly over the past few decades, leading to improved survival rates. As a result, fertility preservation counseling (FPC) has become an essential component of comprehensive treatment planning. By examining demographic factors and patient characteristics, this retrospective chart review aims to evaluate the factors that may influence a patient's likelihood of being referred for fertility preservation. Methods: Data were sourced from the electronic medical record at a single academic medical center and included patients diagnosed between May 1, 2018, and May 31, 2025. Eligible patients were between the ages of 18 and 40 at the time of diagnosis. Exclusion criteria included past medical history of genetic disorders that predispose to infertility, and/or a history of hysterectomy, tubal ligation, or vasectomy. Variables that were collected and analyzed included age, sex, cancer type, cancer stage, race/ethnicity, marital status, zip code, and chemotherapy risk level. Zip codes were utilized as a proxy for median household income. Documentation of FPC or fertility referral was extracted as a variable, which was utilized as the primary outcome. A multivariable logistic regression model was implemented using RStudio to evaluate how these factors were associated with FPC. Results: Among 308 patients, 214 (69.48%) had a documented fertility referral or counseling in their medical record, while 94 (30.52%) patients did not. Based on a multivariable logistic regression model, lower household income was associated with reduced odds of fertility referral (OR=0.779). Although higher income levels were associated with increased fertility referral rates (64.2% in $50k–99k vs 72.6% in $100k–149k vs 92.3% in ≥$150k), these differences did not reach statistical significance (p = 0.144). In contrast, age, race, marital status, cancer type, and stage showed little association with fertility referral. Conclusions: Although no variables were statistically significant, observed differences regarding household income still suggest potential disparities in fertility referral practices. Additionally, there should be further exploratory analysis to understand why a third of young cancer patients remained without FPC amidst gonadotoxic chemotherapy. Future work will examine provider-level factors, including physician gender, to assess whether referral practices differ between male and female clinicians and may influence access to fertility preservation services.

Cerebrospinal fluid proteomics to identify biomarkers for the diagnosis and prediction of leptomeningeal metastasis from non–small cell lung cancer.

e15009 Background: Leptomeningeal metastasis (LM), a terminal complication of non-small-cell lung cancer (NSCLC), lacks validated diagnostic criteria. This study developed machine-learning classifiers that integrate cerebrospinal fluid (CSF) proteomic, clinical-epidemiologic and biochemical variables to enable accurate and minimally invasive diagnosis and prognostication of LM. Methods: CSF samples were collected from NSCLC patients undergoing lumbar puncture at the Second Affiliated Hospital of Nanchang University between September 2023 and December 2025 , followed by quantitative proteomic profiling. Integrative machine-learning models were trained using the proteomic and corresponding clinical datasets to identify optimal diagnostic biomarkers for LM. Parallel reaction monitoring (PRM) validation was subsequently performed in patients from the prospective cohort. Differential CSF proteome profiling and prognostic model construction were conducted in EGFR-mutant NSCLC patients with LM versus Non-LM controls. Results: 1350 proteins differed between LM (n = 61) and Non-LM (n = 34) in the retrospective cohort. Machine model selecting a minimal 4-protein panel (C7, FZD9, IL1RAP, SERPINA3) that distinguished LM from Non-LM with AUC 0.934, sensitivity 86.5%, specificity 95.0%. Parallel reaction monitoring (PRM) confirmed quantitative differences. In EGFR-mutant LM, down-regulation of FKRP, ERBB4, and MACF1 together with up-regulation of ASS1 predicted longer overall survival. Conclusions: CSF proteome-clinical machine-learning models provide a robust, minimally-invasive 4-protein diagnostic signature for NSCLC-LM and a separate survival classifier for EGFR-mutant disease, supporting early detection and risk-stratified management.

Induction chemotherapy response–guided selection for hypoxia-directed major radiation de-escalation in T3–T4 HPV-positive oropharyngeal cancer.

6103 Background: De-escalation trials in human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) often exclude patients with very locally advanced disease. We previously demonstrated in several Phase II study that for patients with T1-T2 HPV+OPC, de-escalation to 30Gy of definitive chemoradiation based on lack of hypoxia on 18 F-FMISO (fluoromisonidazole) PET (30-ROC Study) is associated with excellent outcomes (JNCI 2021; JCO 2024). Here, we hypothesized that induction chemotherapy (ICT) response could be used to select appropriate locally advanced (T3-T4) HPV+OPC for de-escalation while simultaneously improving tumor hypoxia. Methods: We conducted a pilot study in HPV+ OPC patients with AJCC v7 T3-T4 and/or large volume N2b-N2c-N3 disease (who were ineligible for 30-ROC Study (NCT03323563)). ICT – carboplatin (AUC2), paclitaxel (90 mg/m2), and cetuximab (250 mg/m2 after 400 mg/m2 loading dose) weekly for 6 weeks. To be eligible for de-escalation (30-ROC), after ICT, patients needed to be down-staged (<=T2 and <=N3 disease). 18 F-FMISO PET scan done prior to ICT, after ICT, and, if eligible for ROC study, about 2 weeks after start of radiation therapy. If an 18 F-FMISO PET scan showed no hypoxia prior to the start of chemoradiation, no further scans were necessary and patients received 30Gy of radiation therapy with 2 cycles of chemotherapy concurrently. Primary outcome is 2-year local control rate in 20 evaluable patients. Results: 20 patients were accrued 3/2023-12/2023. Median age - 70 years old (46-88); Male – 95%; ECOG PS 0 – 80%. Tumor stage – T3 (70%); T4a (30%); N2b (70%); N2c (30%). All 20 patients had pretreatment hypoxia by 18 F-FMISO. All 20 patients had sufficient downstaging to be treated by 30-ROC Study and converted to no hypoxia by 18 F-FMISO. The estimated progression free survival and local control rate at 2 years is 90% (95% CI 76.9%-100%). There were no distant failures. The median follow up is 23 months (range 12-29 months). All patients were alive and without evidence of disease at last follow up. Conclusions: Preliminary results suggest that ICT can allow more advanced tumors (T3/T4), that are typically excluded from de-escalation studies, to be de-escalated and may eliminate tumor hypoxia in a large proportion of cases. This small pilot study shows similar results seen in the larger ROC studies published to date, but a larger study is needed to confirm these results and is currently ongoing. Clinical trial information: NCT05491512 .

Targeting the Warburg effect: Mitochondrial metabolic modulation with intermittent fasting during neoadjuvant chemoradiation in rectal cancer compared with standard neoadjuvant chemoradiation and total neoadjuvant therapy.

3612 Background: Cancer cells demonstrate metabolic inflexibility characterized by glycolytic dependence and dysfunctional mitochondrial oxidative phosphorylation [Warburg Effect]. Fasting and glucose restriction induce a metabolic shift toward mitochondrial fatty acid oxidation and ketone utilization in normal cells, while cancer cells are unable to adapt, resulting in increased oxidative stress and radio-sensitization. We evaluated whether inducing a fasting-mimicking metabolic state during neoadjuvant chemoradiation improves pathological complete response (pCR) rates in rectal cancer compared with total neoadjuvant therapy (TNT) and standard neoadjuvant chemoradiation (nCRT). Methods: 90 patients with locally advanced rectal adenocarcinoma were analyzed (30 per group). All patients had cT3N+ disease. Radiotherapy was delivered using IMRT/IGRT or adaptive techniques, receiving long-course radiotherapy (50.4 Gy in 28 fractions) with concurrent capecitabine. Group 1 received nCRT under a fasting-mimicking metabolic state using a structured low-carbohydrate diet [Non-Calorie Restricted] with ≥14 hours of daily fasting, titrated using continuous glucose monitoring [CGM] to achieve 16–17 hours per day with blood glucose levels <90 mg/dL. Group 2 received TNT consisting of nCRT followed by CAPEOX. Group 3 received standard nCRT without dietary intervention. The primary endpoint was pCR (ypT0N0) at surgery. pCR rates were compared between groups using the chi-square test or Fisher’s exact test, as appropriate, with a two-sided p value <0.05 considered statistically significant. Results: Baseline characteristics were balanced across groups; all patients had cT3N+ disease. Median age was 55 years, with all adenocarcinoma histology. pCR rates were 93.3% (28/30) in the fasting-state nCRT group, 73.3% (22/30) in the TNT group, and 33.3% (10/30) in the standard nCRT group. Fasting-state nCRT was associated with significantly higher pCR rates compared with standard nCRT (χ²=25.2, df=2; p<0.001). TNT was also superior to standard nCRT (p=0.004). The difference between fasting-state nCRT and TNT showed a strong numerical trend but did not reach statistical significance (p=0.08). Conclusions: Fasting-state metabolic modulation during neoadjuvant chemoradiation was associated with a striking increase in pCR rates. Mitochondrial stress induced by glucose restriction may enhance tumor radio-sensitivity through increased reactive oxygen species and impaired metabolic compensation. Precision-guided fasting represents a promising, low-cost therapeutic strategy warranting prospective larger cohort validation. Clinical trial information: CTRI/2024/10/075843. Comparison pCR p-value Fasting-state nCRT 93.3% (28/30) < 0.001 TNT 73.3% (22/30) 0.004 Standard nCRT 33.3% (10/30) 0.08

Impact of sociodemographic factors on molecular testing patterns in localized and metastatic malignancies.

e13510 Background: Next-generation sequencing (NGS) identifies actionable mutations that guide precision therapy in both localized and metastatic cancer. This study evaluated sociodemographic factors associated with NGS timing and outcomes across malignancies. Methods: Patients undergoing tissue NGS at a single institution through Caris Life Sciences were identified and grouped as having localized or metastatic at the time of testing. Associations between sociodemographic variables and time from diagnosis to NGS and overall survival (OS) were evaluated using log-linear regression, Cox proportional hazards models, and Kaplan-Meier analysis (p < 0.05 significant). Results: Among 913 patients, 43.8% were female, 33.4% non-white, 17.1% Hispanic, 8.8% non-English speaking, 7.7% veterans, and 29.9% reported disabilities. Median age at diagnosis was 60.5 years. The most common primary malignancies were skin (15.6%), colorectal (15.4%), pancreas (7.2%), and prostate (7.1%). Insurance included Medicare (47.6%), private/commercial (37.7%), and Medicaid/Medi-Cal (13.3%). 354 (39.3%) patients had localized disease and 547 (60.7%) had metastatic disease at time of NGS. Median time from diagnosis to NGS was 4.1 months for localized and 4.2 months for metastatic disease. In adjusted analysis among patients with localized disease at time of NGS, patients with Medicare underwent NGS later than patients with Medicaid (p = 0.007). Among patients with metastatic disease at time of NGS, older age was associated with shorter time to NGS (p = 0.001), and female sex was associated with longer time to NGS (p = 0.03). Median follow-up was 43.2 months. Among patients with metastatic disease, 127 (24.7%) underwent NGS testing within 6 months of death. Disability was associated with lower odds of testing within 6 months of death (OR = 0.59, p = 0.02), while race, insurance, and other SES factors were not significantly associated with this outcome. Among patients with localized disease, 52 (15%) underwent testing within 6 months of death. Overall, 416 (75.0%) of patients with metastatic disease harbored alterations with FDA-approved targeted therapies available compared to 244 (70.1%) in localized disease. In multivariable Cox models stratified by primary tumor, worse OS was associated with increasing age (localized HR = 1.04/year, p < 0.001; metastatic HR = 1.01/year, p = 0.02) and Medicaid (localized HR = 6.66, p < 0.001; metastatic HR = 1.58, p = 0.03). Conclusions: Sociodemographic factors influenced NGS timing and survival. Medicaid was associated with worse OS across both localized and metastatic disease, while Medicare was associated with delayed NGS in localized disease. Age and sex also affected time to NGS in metastatic patients. These disparities highlight the need for interventions to ensure equitable access to precision oncology.

Epidemiological trends in colorectal cancer incidence, prevalence, and mortality burden in the United States, 1990–2023: Retrospective analysis and advanced machine learning forecasting to 2050.

e15588 Background: Colorectal cancer remains one of the leading causes of cancer incidence and mortality in the United States, though widespread screening, lifestyle interventions, and therapeutic advances have contributed to declining age-standardized burden over recent decades. This study analyzed age-standardized rates (ASRs) of DALYs, deaths, incidence, and prevalence from 1990 to 2023, and projected future burden to 2050 with ARIMA time-series forecasting. Methods: Age-standardized rates per 100,000 population were extracted from the Global Burden of Disease 2023 database for the United States, stratified by sex (Both, Female, Male). Historical trends (1990–2023) were quantified using estimated annual percentage change (EAPC) derived from linear regression on log-transformed ASRs. Future projections (2024–2050) employed ARIMA models fitted to historical time series, generating point forecasts and 95% prediction intervals (PI). Results: From 1990 to 2023, age-standardized DALYs (Both sexes) declined substantially from 474.99 (95% UI: 441.94–506.86) to 318.71 (95% UI: 294.23–340.32), with an EAPC of -1.36% (95% CI: -1.44 to -1.28); declines were similar in females (EAPC -1.38%, 95% CI: -1.47 to -1.29) and slightly steeper in males (EAPC -1.44%, 95% CI: -1.52 to -1.36). Age-standardized death rates fell from 20.81 to 12.64 (EAPC -1.68%, 95% CI: -1.75 to -1.60), with stronger reductions in males (EAPC -1.81%) than females (EAPC -1.67%). Incidence decreased from 51.04 to 37.61 (EAPC -1.19%, 95% CI: -1.31 to -1.06), and prevalence from 292.54 to 239.01 (EAPC -0.87%, 95% CI: -1.00 to -0.75), reflecting successful screening and earlier detection. ARIMA forecasts indicate continued marked declines in age-standardized DALYs (Both: from 313.97 in 2024 to ~190.84 by 2050), deaths (to ~5.95), and incidence (to ~26.69), while prevalence stabilizes or slowly decreases. Conclusions: Age-standardized burden of colorectal cancer in the US decreased significantly from 1990–2023 across DALYs, mortality, incidence, and prevalence, with consistent progress in both sexes. Projections to 2050 anticipate further substantial reductions in key metrics, highlighting the effectiveness of public health interventions, though absolute case numbers may remain elevated due to demographic changes, reinforcing the importance of prevention and early detection strategies. Measure Sex EAPC Lower 95%CI Upper 95%CI DALYs Both -1.36 -1.44 -1.28 DALYs Female -1.38 -1.47 -1.29 DALYs Male -1.44 -1.52 -1.36 Deaths Both -1.68 -1.75 -1.6 Deaths Female -1.67 -1.75 -1.59 Deaths Male -1.81 -1.88 -1.74 Incidence Both -1.19 -1.31 -1.06 Incidence Female -1.18 -1.31 -1.06 Incidence Male -1.29 -1.41 -1.17 Prevalence Both -0.87 -1 -0.75 Prevalence Female -0.92 -1.04 -0.79 Prevalence Male -0.92 -1.04 -0.79

Inpatient mortality and length of stay associated with splanchnic vein thrombosis in gastrointestinal cancers: A National Inpatient Sample analysis.

e16335 Background: Splanchnic vein thrombosis (SVT) is a rare but serious complication in gastrointestinal (GI) cancer patients. This study investigated its features and outcomes in U.S. hospitalizations. Methods: Hospitalizations (≥18 years old) with a GI malignancy (ICD-10-CM C15–C26) and portal vein thrombosis (PVT) (I81), hepatic vein thrombosis (HVT) (I82.0), or mesenteric/splenic vein thrombosis (MSVT) (I82.890 + K55) in any of the 40 diagnosis fields were found in 2022 National Inpatient Sample. Exclusions: non-GI cancers (C00-C14, C27-C96), thrombophilia (D68.5, D68.6, D45, D47.1, D59.5), or cirrhosis (K74, K70.3). Demographics and outcomes (in-hospital mortality, length of stay [LOS], and total hospital charges [TOTCHG]) were compared between SVT and non-SVT groups using unweighted descriptive statistics (medians, IQRs), χ², and Mann-Whitney U tests. Multivariable regression of mortality, LOS, and TOTCHG were adjusted for age, sex, race, income quartile, insurance type, hospital region and bed size, and comorbidity burden (elixsum). Stata 17.0 was used. Results: Among 51,940 GI cancer hospitalizations (mean age 68.37 ± 12.79 years; 44.46% female), 833 (1.60%) had SVT. SVT group was younger (66.60 ± 11.76 vs. 68.40 ± 12.80 years; p < 0.001). Sex distribution was similar (58.34% vs. 55.50% male; p = 0.101). Common cancers in SVT: liver (n=427; 51.26%), pancreas (n=310; 37.21%), and colorectal (n=42; 5.04%). SVT prevalence was highest in liver (7.10%), pancreatic (3.14%), gallbladder (2.65%), and biliary (2.13%) cancers. PVT was the predominant subtype (n=788; 94.60%), followed by HVT (n=21; 2.52%), MSVT (n=4; 0.48%), and multiple SVT sites (n=20; 2.40%). SVT subtype distribution was: PVT (n=788; 94.60%), HVT (n=21; 2.52%), MSVT (n=4; 0.48%), and multiple sites (n=20; 2.40%). SVT had longer median LOS (5 [3–10] vs. 4 [3–8] days; z = -6.666, p < 0.001), similar median charges ($65,053 [I33,560–130,026] vs. $66,433 [35,897–121,038]; z = -0.76, p = 0.447), and higher mortality (9.48% vs. 4.41%; χ² = 49.042, p < 0.001). In adjusted analyses, SVT had higher mortality (aOR = 2.23, 95% CI 1.74–2.85, p < 0.001), longer LOS by 1.50 days (95% CI 0.99–2.02, p < 0.001), and 14.63% higher TOTCHG (coefficient 0.136, 95% CI 0.051–0.222, p = 0.002). Conclusions: SVT affects ~1.6% of GI cancer hospitalizations, is most prevalent in liver cancer, and associated with longer stays and higher mortality, underscoring the need for proactive monitoring. Multivariable regression analyses of SVT on clinical outcomes (unweighted sample). Outcome SVT Effect 95% CI P-value Interpretation In-hospital mortality OR 2.23 1.74–2.85 <0.001 SVT doubles odds of in-hospital death Length of stay (days) +1.50 0.99–2.02 <0.001 SVT associated with ~1.5 extra hospital days Total hospital charges ($) +0.136 (log scale) 0.051–0.222 0.002 SVT increases hospital costs by ~14.63%

Body mass index and mortality in immune checkpoint inhibitor–treated cancers: A real-world propensity-matched analysis.

11069 Background: Immune checkpoint inhibitors (ICIs) are a cornerstone of treatment for multiple solid tumors, including lung cancer and melanoma. Emerging evidence suggests that body mass index (BMI) may influence outcomes with immunotherapy, though findings remain inconsistent and largely derived from clinical trial populations. We evaluated the association between BMI and mortality among patients with cancers treated with ICIs using real-world data. Methods: We conducted a retrospective observational study using data from TriNetX, a global real-world research platform based on de-identified electronic health records. Adult patients with lung cancer or melanoma who received immune checkpoint inhibitor therapy, including durvalumab, pembrolizumab, nivolumab, ipilimumab, or atezolizumab, were identified. Patients were stratified by documented baseline body mass index into two groups: BMI 19–24.9 (Normal) and BMI 30–49.9 (Obese). To address baseline differences, 1:1 propensity score matching (PSM) was performed using demographics and major comorbidities. The primary endpoint was all-cause mortality; secondary endpoints included inpatient hospitalization frequency. Results: Before matching, the cohorts consisted of 7,951 patients (BMI 30–49.9) and 4,651 patients (BMI 19–24.9). After PSM, 4,152 patients were included in each cohort. Baseline characteristics, including age (mean 67 years), sex (59% male), and comorbidities (hypertension, diabetes, CKD), were well-balanced (p > 0.05).All-cause mortality was significantly higher in the BMI 19–24.9 group compared to the BMI 30–49.9 group (49.2% vs 43.4%), with a risk ratio of 0.88 (95% CI,0.84–0.92; p < 0.001). Overall survival was significantly longer in the obese cohort, with a median survival of 1,043 days compared to 579 days in the normal BMI cohort. High BMI was associated with a 27.5% reduction in the hazard of death (HR 0.725, 95% CI 0.68–0.77; p < 0.001). Conversely, the high BMI cohort had a higher risk of inpatient encounters (57.6% vs 55.3%; p = 0.032) and a higher mean number of hospitalizations (5.4 vs 4.6; p < 0.001). Conclusions: In this large real-world study, higher BMI was associated with significantly lower mortality and nearly double the median survival time in patients treated with ICIs. While higher BMI was also associated with increased hospitalization frequency, the overall survival benefit remains robust. These findings support the "obesity paradox" in immunotherapy and suggest that nutritional status is a critical determinant of long-term ICI efficacy and healthcare utilization.

Framing and availability of information regarding alternative cancer therapies by top U.S. cancer centers.

e13713 Background: Patients with a cancer diagnosis increasingly encounter online claims promoting alternative treatment therapies, including repurposed pharmacologic agents, when researching potential treatment options. Recent studies have shown as many as 1 in 4 adult cancer patients may receive advice regarding alternative means to cure their cancer, and up to 70% of adult cancer patients are exposed to misinformation regarding treatment online. The extent to which leading cancer centers address these claims and alternative therapies on patient-facing websites is not well characterized. Methods: We performed a cross-sectional review of publicly available, patient-facing webpages of the top twenty U.S. cancer centers as ranked by U.S. News & World Report. Each institution’s website was systematically interrogated using a standardized manual web search strategy. This included (1) direct navigation from the homepage through patient education, treatment, integrative medicine, and supportive care sections, and (2) site-specific keyword searches using the terms “ivermectin”, “fenbendazole”, “methylene blue”, “alternative cancer therapy”, “integrative medicine”, and “complementary therapy”. Only content intended for patients or caregivers was included; provider-facing, academic, or internal materials were excluded. Descriptive statistics were reported using binomial proportions with 95% confidence intervals (95% CI). When alternative therapies were discussed, sentiment was categorized as positive, neutral, or negative by two independent investigators. Results: None of the twenty cancer center websites which were examined discussed ivermectin, fenbendazole, or methylene blue. Nine out of twenty cancer centers (45%; 95% CI 23.0%-68.5%) provided patient-facing content addressing alternative cancer therapies more generally. Of the nine centers which discussed alternative cancer therapies, five framed them negatively (55.6%; 95% CI 21.2%-86.3%), while four centers were neutral in their discussion (44.4%, 95% CI 13.7%-78.8%). None of the cancer centers which discussed alternative therapies presented them in a positive or promotional manner. Conclusions: Among top U.S. cancer centers, patient-facing online information regarding alternative cancer therapies is limited. When addressed, alternative therapies are most likely to be framed critically, emphasizing caution rather than therapeutic benefit. These findings highlight an imbalance between the prevalence of alternative therapy claims encountered by patients online and institutional messaging from leading oncology centers, potentially impacting patients’ treatment decisions.

UGT1A1 status and clinical outcomes in pancreatic cancer patients receiving liposomal irinotecan.

e16429 Background: Pancreatic cancer (PCa) is one of the most lethal malignancies with limited effective treatment options. Liposomal irinotecan (nal-IRI) in combination with 5-fluorouracil/leucovorin ± oxaliplatin is utilized across multiple PCa disease stages. Nal-IRI is metabolized to its active form SN-38, which is inactivated by the UGT1A1 enzyme. UGT1A1 gene polymorphisms decrease enzyme activity, potentially increasing toxicity. While UGT1A1 polymorphisms are known to impact conventional irinotecan toxicity, and the NAPOLI-1 trial protocol included reduced starting doses of nal-IRI for UGT1A1*28 homozygotes, subsequent studies of liposomal irinotecan show conflicting results. Real-world data examining UGT1A1 status and outcomes in diverse US populations is limited. This study evaluates the relationship between UGT1A1 metabolizer status and clinical outcomes in patients (pts) treated with nal-IRI-based regimens. Methods: This retrospective study analyzed 86 pts with PCa who received nal-IRI at Ochsner Health between September 2020 and January 2025. UGT1A1 genotypes were classified as normal (NMT), intermediate (IMT), or poor metabolizers (PMT). Outcomes included grade 3/4 toxicities, dose reductions, and overall and progression free survival. Chi-square tests compared proportions of toxicities and dose reductions across groups. Kaplan-Meier curves with log-rank tests and Cox regression models analyzed survival. Results: Of 86 pts reviewed (mean age 69 years, 51% female, 67% White, 31% Black), 85 had metastatic disease and 57 (66%) had a documented UGT1A1 status. 24 (42%) were NMT, 23 (40%) were IMT and 10 (18%) were PMT. The median nal-IRI starting dose for pts with NMT and IMT was 70 mg/m2. 90% of PMT patients received reduced starting doses, with a median initial dose of 50mg/m2. Subsequent dose reductions occurred in 33% NMT, 22% IMT, and 30% PMT (p = 0.67). Grade 3/4 toxicities were observed in 37.5% NMT and 42% IMT/PMT, with diarrhea (28%) and neutropenia (9%) being most common. Mortality rates at data cutoff were 79% NMT, 87% IMT, and 90% PMT (p = 0.71). There were no significant overall survival differences between metabolizer groups (PMT vs NMT: HR 1.32, 95% CI 0.56-2.90; IMT vs NMT: HR 1.77, 95% CI 0.92-3.42). Conclusions: Consistent with existing guideline recommendations, most pts in our analysis were treated with nal-IRI at a reduced starting dose of 50 mg/m2. Otherwise, UGT1A1 metabolizer status was not significantly associated with severe toxicities, dose reductions, or survival in pts receiving nal-IRI. Whether these findings suggest that the liposomal formulation may attenuate the genotype-associated toxicity seen with conventional irinotecan or reflect lower starting doses, they cannot be determined from this study's limited, retrospective data. Larger prospective studies are needed to determine whether UGT1A1 testing should guide nal-IRI dosing in practice.

Patterns of care and long-term survival in metastasizing ameloblastoma: An NCDB study.

e18153 Background: Metastasizing ameloblastoma (MA) is diagnosed when a benign but aggressive ameloblastoma spreads to distant sites without malignant transformation, with metastases typically found in the lungs and lymph nodes. MA most commonly affects 40–50-year-old men, and although rare and histologically benign, conservative treatment—such as curettage or enucleation—often results in recurrent disease and associated health risks. Given the rarity of MA, population-level data remain limited, and evaluating demographic patterns using the National Cancer Database (NCDB) may improve understanding of its epidemiology. Methods: A retrospective cohort analysis was performed using patients with histologically confirmed MA (ICD-O-3 Code 9310) in the 2004–2020 NCDB. Demographic, clinical, and socioeconomic variables (sex, race, Hispanic origin, facility type and location, insurance status, income, year of diagnosis, primary tumor site, analytic stage group, and Charlson-Deyo score) were summarized with descriptive statistics. Trends in incidence were evaluated using regression analysis. Results: A total of 308 patients with MA were identified from 2004–2020, with a stable incidence over time (R²=0.03). Patients were predominantly male (61.7%), non-Hispanic (86.0%), and White (54.5%), with a notably high representation of Black patients (34.7%). Nearly half received care at academic centers (48.1%), and most lived in metropolitan areas (87.0%). Private insurance was the most common payer (51.9%). The mandible (C411) was the most frequent primary site (73.7%), and 47.7% presented with stage I disease. Most patients had a Charlson-Deyo score of 0 (87.3%). Surgery was the primary treatment (90.3%), with complete resection achieved in 67.5% of cases. Radiation was used in 9.1%, and chemotherapy in a small minority; hormone and immunotherapies were not utilized. Palliative care was uncommon (1.6%). The mean age at diagnosis was 48.1 years, and tumors measured 44.5 mm on average. Early mortality was low (1.1% at both 30 and 90 days), consistent with the tumor’s benign histopathology. Likewise, mean overall survival was 14.2 years, with two-, five-, and ten-year survival rates of 95.2%, 89.3%, and 80.7%, respectively. Conclusions: This study provides the first population-level analysis of MA using the NCDB, addressing a major gap in understanding this rare entity. Consistent with prior case reports, MA primarily affected middle-aged men and most often originated in the mandible. We also describe socioeconomic patterns, showing that patients frequently resided in metropolitan areas and received care at academic centers. Surgical resection remained the predominant treatment, with excellent long-term survival reflecting the tumor’s indolent biology. Further investigation is warranted to better define demographic and healthcare access factors influencing presentation and management in this rare disease.

Updated results from a pilot trial of neoadjuvant durvalumb in combination with tremelimuab for cisplatin-ineligible high-risk urothelial carcinoma.

e16584 Background: We previously reported that neoadjuvant immune checkpoint therapy (ICT) with durvalumab (D) plus tremelimumab (T) was safe and effective in cisplatin-ineligible patients (pts) with high-risk muscle-invasive urothelial carcinoma (MIUC). Here, we present outcomes from a second cohort treated with higher-dose T plus D, updated outcomes from the first cohort, and an analysis of tertiary lymphoid structures (TLS). Methods: Cohort 2 (n = 13) pts with cisplatin-ineligible MIUC and high-risk features (lymphovascular invasion, bulky tumor, variant histology, high grade upper tract disease, and/or hydronephrosis) received D 1500mg + T 300mg, followed by D 1500mg 4 weeks later. Cohort 1 (n = 28) pts were treated with D 1500mg + T 75mg every 4 weeks for 2 cycles. Cystectomy was planned 4-6 weeks after therapy. Primary endpoint was safety; overall survival (OS) and relapse free survival (RFS) were secondary endpoints. All pts were included for OS analysis and only pts who completed cystectomy were included for RFS analysis using Kaplan Meier method. Exploratory analysis assessed TLS association with response (downstage to pT< / = 1N0) using Chi-square test. TLS association with OS/RFS were evaluated using Cox proportional hazard regression. TLS were defined as lymphocyte aggregates co-expressing CD20 and CD3 with germinal-center-like morphology. Results: In cohort 2, 9/13 pts underwent cystectomy; two declined surgery and two were unable to proceed due to treatment-related toxicities. Three pts experienced grade 3+ immune related adverse events (irAEs): colitis (n = 1), hepatitis (n = 1), and myositis/myocarditis (n = 1) myositis/myocarditis (n = 1), prompting early termination of this cohort. Among pts completing cystectomy, pathologic complete response rate was 44% (4/9) and 1-year RFS 67% (SE = 16%). 1- year OS was 62% (SE=14%) and the two pts unable to proceed to surgery due to irAEs died before receiving additional treatment while the two pts who declined surgery continue to have no evidence of disease. Updated 5-year OS for cohort 1 was 82% (SE = 7%) and RFS was 74% (SE = 9%). In combined cohorts, 69% (11/16) TLS high pts were responders vs 29% (6/21) TLS low pts (OR 0.18, 95% CI 0.04, 0.75). Median RFS for TLS high not reached (95% CI NR,NR) compared to 59 months (95%CI 8.4-NR) for TLS low (HR 0.24, 95%CI 0.05-1.1, p = 0.047); median OS for TLS high not reached (95%CI NR, NR) compared to 63 months (95%CI 14, NR) in TLS low (HR 0.32, 95% CI 0.09-1.2, p = 0.068). Conclusions: Neoadjuvant ICT remains promising for cisplatin-ineligible MIUC; however, higher T dose increased serious irAEs, underscoring the need for optimized dosing. Baseline TLS density may represent a predictive biomarker and warrants further validation with larger cohorts. Clinical trial information: NCT02812420 .

Temporal trends in pregnancy-associated cancer mortality in the United States: A national analysis 2018-2023.

11029 Background: Cancer during pregnancy is rare but increasing due to rising rates of early-onset cancers and more parents delaying childbearing to older ages. Cancer treatment during pregnancy is complex, as capacity to deliver timely, multimodality anti-cancer treatment may be limited by risk of fetal compromise. As pregnancy-associated cancer is an increasingly recognized contributor to maternal mortality, this study sought to evaluate national temporal trends. Methods: Using CDC WONDER Multiple Cause of Death files (2018–2023), pregnancy-associated deaths involving malignant neoplasms (ICD-10 C00–C97) were identified. Age-adjusted mortality rates (AAMR) per 100,000 live births and annual percent changes (APCs) were calculated, excluding unknown race, ethnicity, or age. AAMR was evaluated by state, including comparison of 1) states with trigger laws banning abortion in 2022 vs states that did not have such laws and 2) states that expanded Medicaid by 2018 vs states that did not. Mortality data for locations with <10 deaths is censored. Results: From 2018–2023, there were 723 pregnancy-associated deaths in people with cancer. Most (72%) were in White patients and occurred in the late postpartum period (59%) (42-365 days after birth). Only 19% of patients had documented metastatic cancer. Overall AAMR was 3.40 (95%CI 3.16–3.65); it was highest among Black patients (4.54), exceeding White (3.24), Hispanic (3.08), and AIAN/AAPI (2.64) mortality. Breast (n=162, AAMR 0.76 95%CI 0.65-0.88) had the greatest cancer-specific mortality burden, followed by hematological malignancies (n=101, AAMR 0.48, 95% CI 0.38-0.57) and colorectal cancer (n=71, AAMR 0.12, 95%CI 0.088-0.15). AAMR for those with metastatic disease was 0.64 and increased over time (APC +7.54%; 95%CI 1.52–14.55; p=0.009). Late maternal deaths also rose (APC +4.75%; 95%CI 0.99–8.87; p=0.006). Otherwise, overall (APC −0.37%, 95%CI -0.37-4.30, p=0.83) and race/ethnicity specific pregnancy-associated cancer mortality have not significantly changed over time. Among 25 states with ≥10 deaths, state-level mortality ranged from 1.37 in California to 6.95 in Virginia. Limited state comparative analysis found that AAMR for pregnancy-associated cancer was higher in states with trigger laws (4.43) compared to non-trigger states (3.22); it was also higher in non-Expansion states (4.00) compared to states that expanded Medicaid (3.31). Conclusions: Despite known improvements in cancer mortality, pregnancy-associated cancer mortality remains stagnant, with notable mortality rises in pregnant patients with metastatic disease and late postpartum deaths. The large variability in state-level mortality may reflect state policies that affect access to prenatal or oncological care. More research and advocacy work to optimize care for pregnancy patients with cancer is essential to improve outcomes for this vulnerable population.

REINFORCE: A phase III randomized trial of treatment intensification with docetaxel in metastatic hormone-sensitive prostate cancer patients without deep PSA response after initial apalutamide therapy.

TPS5147 Background: Androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitors (ARPIs) is the standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). However, a substantial proportion of patients fail to achieve a deep prostate-specific antigen (PSA) response, which is consistently associated with worse outcomes. Deep PSA response has emerged as a robust early prognostic marker across multiple phase III trials. Patients lacking this favorable PSA decline represent a poor-risk subgroup with limited treatment personalization. Docetaxel improves survival in high-volume mHSPC and may benefit biologically aggressive disease identified by suboptimal early PSA response. REINFORCE evaluates a PSA-guided strategy of treatment intensification with docetaxel in patients without deep PSA response after apalutamide. Methods: REINFORCE is an international, multicenter, open-label, phase III randomized trial. Eligible patients are men ≥18 years with histologically confirmed mHSPC, ECOG performance status ≤1, PSA > 5 ng/ml at diagnosis of metastatic disease, ≤12 weeks of ADT before apalutamide, adequate organ function, who have received apalutamide plus ADT for 24–30 weeks, have not progressed, and have failed to achieve a deep PSA response. Deep PSA response is defined as PSA ≤ 0.2 ng/ml or PSA response ≥ 90% in combination with a PSA ≤4 ng/ml. Approximately 320 patients from 85 sites located in 6 countries will be randomized 1:1 to treatment intensification with docetaxel (75 mg/m² every 3 weeks for 6 cycles) plus continued apalutamide and ADT, or continuation of apalutamide plus ADT alone. Randomization is stratified by metastasis timing (synchronous vs metachronous), presence of visceral metastases, and PSA at study entry (≤4 vs > 4 ng/mL). The primary endpoint is event-free survival (EFS), defined as time from randomization to PSA progression, radiographic progression of soft tissue, visceral or bone lesions, according to PCWG3, or death from any cause. Secondary endpoints include time to castration resistance, radiographic and PSA progression-free survival, overall survival, safety, PSA response rates, and patient-reported outcomes. Preliminary evidence suggests that apalutamide is associated with a ≲ 10% decrease in docetaxel AUC; a dedicated pharmacokinetic sub-study will assess docetaxel drug-drug interaction and bioequivalence when co-administered with apalutamide. An independent data monitoring committee will oversee patient safety, including an early safety review after the first 18 patients included, review a pre-planned interim efficacy analysis, and evaluate pharmacokinetic data, providing recommendations to the sponsor regarding study continuation. Clinical trial information: 2025-524408-30-00.

Consumer wearables and medical care utilization in gastrointestinal cancers: A Fitbit data analysis in NIH All of Us Research Program.

11100 Background: Patients with gastrointestinal (GI) cancers may experience delayed or forgone care due to cost, travel, or health system barriers. Wearable devices are widely used and capture physical activity that may reflect health status, mobility, and social factors. Whether wearable activity data can help identify patients at risk for delayed care is not well understood. We examined associations between activity levels and delayed or forgone care among adults with GI cancers in the NIH All of Us Research Program. Methods: Adults with GI cancers who contributed wearable activity data and healthcare utilization surveys were included; ≥30 valid Fitbit days were required. Mean daily step counts were calculated and categorized into cohort-specific quartiles: Q1 (≤3,621 steps/day), Q2 (3,621–5,591), Q3 (5,591–8,272), and Q4 ( > 8,272). Delayed or forgone care was determined from survey items asking whether participants postponed or avoided medical care due to financial or access barriers. Analyses were performed in the overall GI cohort (n = 407) and stratified by cancer site (colorectal, pancreatic, upper GI, hepatobiliary, and other). Logistic regression evaluated associations between activity and delayed care using categorical quartiles, continuous log-transformed steps, and age-adjusted models. Results: The analytic cohort included 407 participants with GI cancers. After age adjustment, higher daily step counts—analyzed continuously and across ordered quartiles—were associated with lower odds of delayed or forgone care. Age itself was independently associated with fewer delays (OR per 10 years 0.62, p = 0.001–0.002). In categorical models using Q3 as the reference, participants in Q1 had higher odds of delayed care (OR 3.57, 95% CI 1.06–12.10, p = 0.041), while Q2 and Q4 did not differ significantly from Q3, supporting a non-linear association. Site-stratified analyses showed similar non-linear patterns; for example, pancreatic cancer (n = 60) had delayed care prevalences of Q1 11.1%, Q2 0%, Q3 5.0%, Q4 9.1%, and upper GI cancers (n = 59) had Q1 9.1%, Q2 0%, Q3 6.3%, Q4 13.3%. In colorectal cancer (n = 210), Q3 had the lowest delayed care vs Q1 (OR 0.25, 95% CI 0.05–1.32), although other quartile estimates were less precise due to small event counts. Conclusions: Among patients with GI cancers who contributed wearable and survey data, delayed or forgone care showed a non-linear association with activity, with the lowest odds in the moderate–high activity range. Participants in Q1 had higher odds of delayed care compared with Q3 after age adjustment. Wearable activity data may help identify patients who face barriers to timely care, although this cross-sectional study cannot show cause and effect. Longitudinal studies are needed to determine whether passive wearable data can support care navigation and healthcare utilization in oncology.

Antimicrobials from nano sulfur: Innovations, applications, and future perspectives

Quantifying the Triboelectric Series of Liquid Phase Materials

ABSTRACT Contact electrification has been extensively investigated and harnessed, yet quantifying the triboelectrification capacity of liquid phase materials remains elusive due to their non‐fixed shape and complex flow dynamics. Here, we report a novel gas‐regulated flow strategy to stabilize liquid columns, effectively decoupling fluid kinetics from electrification processes. By optimizing material selection, electrode configurations, and flow regimes, we established a standardized triboelectric series encompassing 50 diverse liquids, including organic solvents and ionic solutions. Our results reveal that liquid‐phase triboelectrification is synergistically governed by molecular functional groups, ionic species, and concentrations. Specifically, hydroxyl groups and dilute ion concentrations promote charge transfer, whereas alkyl groups and excessive ions exert a suppressive effect. This study elucidates that liquid‐solid electrification arises from a sophisticated interplay of electron transfer, molecular polarization, ion adsorption/screening, which collectively dictate charge redistribution. By providing a quantitative triboelectric matrix, this work facilitates the design of high‐efficiency energy harvesters and safer industrial liquid‐handling systems, advancing the fundamental understanding of liquid‐interface physics.