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Patient priorities for a digital health platform to support Lynch syndrome surveillance and research engagement: A needs assessment survey.
e22556 Background: Lynch syndrome requires lifelong, multi-organ surveillance and ongoing family communication to enable cascade testing. Despite established surveillance guidelines, patients with Lynch syndrome often lack integrated, patient-centered tools to coordinate screening, prepare for clinical encounters, and engage in research. Precision Insight is a patient-led digital health community in development to support hereditary cancer families in these tasks. We surveyed Living with Lynch workshop alumni to prioritize platform features. Methods: A voluntary, de-identified online survey was emailed to 60 prior Living with Lynch Workshop participants. Respondents selected their top three tasks the platform should make easier and rated proposed features on a 1–5 scale. Survey items were informed by prior Living with Lynch workshops and patient advisory input. Descriptive statistics are reported. Results: Twenty-nine participants responded (48%). Most identified as a person with Lynch syndrome (25/29, 86%); 17/29 (59%) were cancer survivors and 8/29 (28%) previvors. Top priority tasks were screening planner + reminders (24/29, 83%), research/registry explainers and interest sign-up (20/29, 69%), moderated peer forums (17/29, 59%), private family coordination hub (15/29, 52%), and clinic-visit preparation tools (14/29, 48%). Highest-rated features were screening planner reminders (mean 4.52/5; 26/29 rated 4–5) and clinic-visit prep tools (mean 4.24/5; 23/29 rated 4–5), followed by micro-learning (mean 4.00/5; 22/29 rated 4–5) and peer forums (mean 4.07/5; 20/29 rated 4–5). Beta participation interest was high (mean 8.45/10; 22/29 [76%] rated ≥8). Conclusions: Workshop alumni prioritized tools supporting surveillance tracking, visit preparation, peer support, and research engagement. These findings inform Precision Insight’s initial build and demonstrate feasibility for patient-partnered beta testing; broader validation in more diverse Lynch syndrome populations is warranted. Participant priorities and perceived value of key Precision Insight capabilities (n=29). Platform capability Selected as a top-3 task, n/N (%) Rated 4–5/5, n/N (%) Mean value rating (1–5) Screening planner + reminders 24/29 (83%) 26/29 (90%) 4.52 Research/registry explainers & interest sign-up 20/29 (69%) — — Moderated peer forums 17/29 (59%) 20/29 (69%) 4.07 Clinic-visit preparation tools 14/29 (48%) 23/29 (79%) 4.24 Micro-learning (short videos) 2/29 (7%) 22/29 (76%) 4.00 Private family coordination hub 15/29 (52%) — — Participants selected up to three ‘top priority tasks.’ Feature value was rated on a 1–5 Likert scale (5 = very valuable); ‘Rated 4–5/5’ represents respondents selecting 4 or 5. Dashes indicate that a corresponding feature value rating was not collected for that specific task category in the survey.
A multi-center phase II study of chemotherapy (SOX) plus tislelizumab as first-line therapy for gastric cancer with liver metastasis.
e16047 Background: Grim prognosis and medical scarcities of gastric cancer (GC) with liver metastasis (LM) presents the significant challenge. Chemotherapy plus programmed cell death inhibitors provided promising opportunities to solve such problems and the dedicated trail is warranted. Methods: In this prospective, single-arm phase 2 trail, untreated synchronous GC-LM are eligible and receive SOX plus Tisleizumab (200mg, Q3W) for 8 cycles, maintenance therapy is S-1 within 1 year plus Tisleizumab within 2 years, or until disease progression. The primary endpoint was objective response rate (ORR), secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). This exploratory study hypothesized chemotherapy plus tislelizumab would increase ORR from 25% to 56%, with one-sided α of 0.05, statistical power of 0.8, considering 10% dropout, 33 patients are required. Results: 34 patients were enrolled and 4 patients were excluded from efficacy analysis (3 withdrawal of consent, 1 loss to follow-up). Median follow-up was 24.00m (14.18-33.82, 95%CI). ORR is 73.33% (22/30) and DCR is 86.67% (26/30). Median PFS and OS is 21.00m (14.13-27.87) and 24.00m (14.18-33.82). Mean maximal tumor volume regression of GC is 36.17% and the time to reach maximal tumor regression is 3.5m, correspondingly, 46.67% and 3.87m are observed in LM. 33.33% (10/30) patients received conversion surgery (CS) and TRG0 ratio is 16.67% (5/30). CS has significantly better median OS (P = 0.004) and median PFS/DFS (P = 0.005). Conclusions: Chemotherapy (SOX) plus Tisleizumab as first line treatment of GC-LM demonstrated clinically meaningful benefits in both treatment response and prolonged survival. Particularly, increased CS rate provided additional survival benefits. Clinical trial information: NCT05325528 . N MedianOS (95% CI) P-value MedianPFS (95% CI) P-value All patients 30 Age ≥65 18 28.00 (NR-NR) 0.129 21 (NR-NR) 0.273 ＜65 12 20.00 (NR-NR) 16.00 (NR-NR) Sex Female 3 28.00 (10.17-45.83) 0.526 17.00 (NR-NR) 0.525 Male 27 24.00 (NR-NR) 21.00 (1.37-40.63) N stage N1-2 18 24.00 (NR-NR) 0.710 17.00 (NR-34.31) 0.736 N3a&b 12 28.00 (NR-NR) 21.00 (NR-NR) Gastric tumor diameter<5cm 14 32.48 (NR-NR) 0.068 NR 0.012 diameter≥5cm 16 12.00 (NR-25.28) 4 (NR-18.00) Liver metastasis Unilobar 13 NR (NR-NR) 0.045 NR 0.112 Multilobar 17 20.00 (4.65-35.35) 16.00 (.446-31.55) Tumor number <5 15 20.00 (4.461-35.54) 0.082 NR 0.188 Tumor number ≥5 15 NR (NR-NR) 17.00 (.83-33.17) Maximal tumor diameter<5cm 17 NR (NR-NR) 0.006 27.00 (NR-NR) 0.014 Maximal tumordiameter≥5cm 13 20.00 (3.10-36.89) 16 (NR-34.79) PD-L Negative 13 12.00 (3.39-26.26) 0.407 18.28 (0.00-36.15) 0.654 ≥1 17 28.00 (12.89-43.11) 23.00 (NR-NR) Conversion surgery Yes 10 NR 0.004 NR 0.005 No 20 20.00 (1.19-41.81) 16.00 (0.00-38.99) Recist PR+CR 22 28.00 (NR-NR) 0.001 NR (NR-NR) 0.000 SD+PD 8 5.00 (2.44-7.56) 1.13 (NR)
Assessment of racial and ethnic reporting in clinical trials cited by the NCCN bladder cancer treatment guidelines.
e23125 Background: Clinical trials cited in national treatment guidelines are standard references of care. However, the extent to which these trials report racial and ethnic participant demographics remains unclear. We evaluated racial and ethnic reporting and representation in interventional clinical trials cited within the NCCN Bladder Cancer Guidelines. Methods: All references cited in the NCCN Bladder Cancer Guidelines (Version 3.2025) were reviewed. Only randomized controlled trials were included. Race and ethnicity reporting was assessed based on baseline demographic data reported in each study. Trials were categorized by publication year and further subclassified to predefined time blocks (1980–1999, 2000–2004, 2005–2009, 2010–2014, 2015–2019, and 2020–2024). Trials were also classified as U.S.-based versus non-U.S.-based. Temporal trends and subgroup comparisons were evaluated using Fisher exact testing, as provided by the biostatistical analysis. Results: Among 346 NCCN-cited references, 133 (38.4%) were randomized controlled trials. Overall, 33 trials (24.8%) reported race or ethnicity. Among trials with available publication-year stratification (n = 81), race reporting increased significantly over time, from 0% in trials published before 2000 to 65% in trials published between 2020 and 2024 (p = 0.0012). Trials published after 2015 were significantly more likely to report race compared with earlier periods (p < 0.01). U.S.-based trials demonstrated higher rates of race reporting than non-U.S.-based trials, although this difference was not consistently statistically significant across all comparisons. Among trials reporting race, participants were predominantly White (72.9%), with lower representation of Asian (13.6%), Black (2.6%), Hispanic (0.2%), American Indian/Alaska Native (0.2%), Native Hawaiian/Pacific Islander (0.1%), and multiracial participants (6.4%). Conclusions: Less than half of the trials cited in the NCCN Bladder Cancer Guidelines report racial or ethnic participant data, although reporting has improved significantly in recent decades. When reported, trial populations remain predominantly White, with limited representation of historically underrepresented racial and ethnic groups. There is a need for standardized reporting of race and ethnicity in bladder cancer clinical trials to ensure that guidelines apply to all patient populations.
Lung cancer and stroke mortality trends in middle-aged and older US adults, 1999-2023: A CDC WONDER analysis.
e20774 Background: Lung cancer is the leading cause of cancer mortality in the U.S., while stroke ranks fourth overall. Shared risk factors, including tobacco use and cancer-associated hypercoagulability, link these conditions. This study evaluates long-term mortality trends and disparities among U.S. adults aged ≥45 years. Methods: We analyzed U.S. mortality data using CDC WONDER (1999-2023) for lung cancer (ICD-10: C34) and stroke (ICD-10: I60–I69) deaths. Age-adjusted mortality rates (AAMRs, per 100,000 population) were calculated using the 2000 U.S. standard population and stratified by age, sex, race/ethnicity, U.S. census region, states, urbanization, and place of death. Joinpoint regression identified trend inflection points, quantified using annual percent change (APC) and average annual percent change (AAPC). Statistical significance was defined as P < .05. Results: From 1999–2023, 95,328 stroke- and lung cancer–related deaths occurred among ≥45 adults, rising 29% despite an overall decline in AAMR (AAPC -0.93). AAMR first declined from 1999–2015 but increased from 2015–2023 across most subgroups. During 2015–2023, males had higher AAMRs (3.20-3.67), but females had a greater rise (APC 3.13). By race/ethnicity, non-Hispanic Blacks had a notable rise (3.36-4.42), and adults aged ≥65 years had the largest increase (5.86-7.10). AAMRs rose more in metropolitan areas (2.58-2.82) than non-metropolitan areas (APC 1.83), with regionally the greatest increase in the Midwest (2.82-3.54) and the smallest in the West (2.41-2.69). Most deaths occurred in inpatient medical facilities (n = 37,792). From 1999–2020, Alaska had the highest AAMR (4.76) and Utah the lowest (1.19); from 2021–2023, Mississippi was highest (5.75) and Utah remained lowest (1.35). Conclusions: Despite long-term declines, lung cancer-related stroke mortality has risen since 2015, disproportionately affecting older adults, males, non-Hispanic Blacks, and residents of the Midwest, Mississippi, and Alaska. This reversal underscores the need for targeted interventions and may reflect increased stroke risk in longer-surviving lung cancer patients, persistent healthcare disparities, and COVID-19-related care disruptions. Annual percent change of for stroke- and lung cancer- related age-adjusted mortality rates among middle aged and older us adults from 1999-2023; stratified by sex, race/ethnicity, age, urbanization and census regions. Variable APC -1999-2015 APC -2015-2023 Overall -2.83* 2.98* Male -3.71* 2.46* Female -1.90* 3.13* NH Black or African American -3.04* a 4.05* b NH White -2.54* 3.02* ≥65 -3.01* 2.85* Metropolitan areas -2.90* c 2.16* d Midwest -2.53* a 3.75* b West -3.37* e 1.62* f Abbreviations: AAMR, age adjusted mortality rate; APC, annual percent change; NH, Non-Hispanic; *Denotes p < 0.05. a: 1999-2016; b: 2016-2023; c : 1999-2015; d: 2015-2020 e: 1999-2014 f - 2014-2023.
Patient-reported barriers to treatment access and home delivery in rare cancers across five European countries.
1551 Background: Patients with rare diseases, including rare cancers, frequently experience barriers to timely treatment access. Sciensus, an end-to-end pan-European service partner, and Rare Patient Voice, a patient-led advocacy organisation, conducted a multicounty, European survey to characterise treatment logistics, delivery models and patient burden, with a focus on implications for oncology populations. Methods: A cross-sectional survey was conducted in December 2025 among adult patients with rare diseases, including cancer diagnosis, and caregivers across Italy, the United Kingdom, France, Spain, and Germany. Quantitative and qualitative data were collected on treatment access, medication collection or home delivery, financial and emotional burden, reliability of services, and participation in Early Access Programs (EAPs). Descriptive analyses were performed. Results: Among 860 respondents, approximately 120 (14% of total; 28% of validated rare disease responses) reported a cancer diagnosis spanning ~34 cancer types. While most respondents reported infrequent treatment delays, a notable minority experienced frequent disruptions. Over half reported no access to, or lack of awareness of, home delivery services. However, more than 40% indicated that home delivery would significantly or fundamentally improve quality of life. Ratings of homecare reliability varied widely, ranging from very poor to excellent, indicating substantial inconsistency across delivery models and regions. Conclusions: Patients with rare cancers in Europe experience fragmentation and heterogeneity across treatment access pathways. Limited awareness, variable availability, and inconsistent reliability of homebased delivery services likely contribute to ongoing burden. Additional longitudinal study of burden should be conducted to confirm the findings of the experiences in this study. Expanding, standardising and systematising patient-centred delivery models represents a key opportunity to improve continuity of care and quality of life for oncology patients with complex needs.
Impact of Medicaid expansion on survival across five cancer types.
e23036 Background: Prior population-based registry studies found Medicaid expansion is associated with improved cancer survival, but registries often lack comorbidity and treatment-setting detail. The National Cancer Database (NCDB) includes these factors, enabling assessment of expansion-associated survival effects in hospital-based data. We used a difference-in-differences (DiD) approach to evaluate expansion-associated changes in Medicaid-at-diagnosis and 5-year overall survival (OS) across five cancers spanning a range of baseline survival. Methods: We included 1,400,501 adults from NCDB aged 18–64 at time of diagnosis with breast, cervical, colon, non-small cell lung (NSCLC), or pancreatic cancer from 2005-16. States were dichotomized as Medicaid expansion in 2014 (AR, AZ, CO, DE, HI, IA, IL, KY, MA, MD, ND, NM, NV, NY, OH, OR, RI, VT, WV) vs non-expansion (AL, FL, GA, ID, KS, ME, MO, MS, NC, NE, OK, SC, SD, TN, TX, UT, VA, WI, WY). Seven late expansion states were omitted. Using DiD, we quantified (1) changes in proportion covered by Medicaid and (2) estimated 5- year OS using multivariable Cox models adjusted for comorbidity, treatment-setting factors and robust standard errors clustered by facility.Primary analyses did not include area-level income/education quartiles and urbanicity; sensitivity analyses added these covariates. Pre- expansion trends for Medicaid-at-diagnosis and 5-year OS were similar across cancers, except pancreatic cancer. Results: Medicaid-at-diagnosis increased more in expansion states across cancers (DiD +3.9 to +10.8 percentage points). In DiD Cox models of 5-year OS, expansion was significantly associated with lower mortality for colon cancer (HR 0.68–0.69) and NSCLC (HR 0.75) across primary and sensitivity analyses; cervical (primary HR 0.84, 95% CI 0.64–1.10) and pancreatic cancer (primary HR 0.83, 0.66–1.04) were not significant in either analysis (Table). Breast cancer was borderline in sensitivity (HR 0.68, 0.46–1.00) but significant in the primary analysis (HR 0.67, 0.47–0.96). Conclusions: In a multi-cancer, quasi-experimental DiD analysis of the NCDB, Medicaid expansion was associated with a higher proportion of patients with 5 cancer types on Medicaid and improved 5- year OS for patients with colon cancer and NSCLC, with breast cancer showing significant association only in primary analyses; cervical and pancreatic cancer showed no significant differences. These findings add to evidence that Medicaid expansion can improve cancer survival, with benefits that vary by cancer type. DiD estimates for 5-year OS (Cox models). Cancer N Primary aHR (95% CI) Sensitivity Analysis aHR (95% CI) Breast 816,418 0.67 (0.47-0.96) 0.68 (0.46-1.00) Cervical 40,684 0.84 (0.64-1.10) 0.80 (0.59-1.08) Colon 176,529 0.68 (0.52-0.88) 0.69 (0.53-0.91) NSCLC 292,401 0.75 (0.59-0.96) 0.75 (0.58-0.97) Pancreas 74,469 0.83 (0.66-1.04) 0.82 (0.64-1.05)
Clinical characterization and association with autoimmunity in immune checkpoint inhibitor (ICI)–mediated thyroid dysfunction in a real-world sample.
e24159 Background: ICI mediated thyroid dysfunction (TD) usually presents as transient hyperthyroidism followed by hypothyroidism or as isolated hypothyroidism. Antibodies (Abs) associated with autoimmune TD (Hashimoto’s and Grave’s disease) include antibodies against thyroid peroxidase (TPO), thyroglobulin (TgAb), and thyroid stimulating immunoglobulin (TSI). Current guidelines do not have recommendations for monitoring these Abs during ICI therapy. We studied a racially diverse, real-world sample of patients (pts) treated with ICI who developed TD to better characterize the role of auto-Abs in these toxicities. Methods: This is a retrospective study utilizing a real-world clinical dataset of 1927 pts treated with ICI within the MedStar-Georgetown health system. A cohort of pts with immune mediated TD were extracted from the GU Immunotherapy registry and included in this analysis. Results: 173 pts experienced ICI-related TD: 84 (48.6%) female, 37 (21.4%) African American, 121 (70.0%) White, average age 63.7 (22-94). 59 (34.1%) experienced a hyperthyroid (hyperTD) phase followed by hypothyroidism (hypoTD), 15 (8.7%) experienced a hyperTD that resolved without permanent hypoTD, and 99 (57.2%) experienced hypoTD without an associated hyperTD. Frequency of testing and presence of anti-thyroid Abs were TPO (20/27, 74.1%), TSI (5/14, 35.7%), and TgAb (6/13, 46.2%). Overall, TPO Ab positivity was found to be higher than TgAb in this study (74.1% vs 46.2, p=0.0829). The average time from initiation of ICI to development of hyperTD was 54.9 days (9-242), and average time from onset of hyperTD to development of hypoTD was 57.1 days (4-287). Higher response rates were seen in pts who tested positive for TPO (13/20, 65% vs 2/7, 29%, p=0.095). Out of 1213 pts with available autoimmune history, 102/1213 (8.4%) had a history of hypoTD, 13/173 (7.5%) with TD had a known history. Pts with a TD history had a numerically higher rate of TD however not statistically significant (13.7% vs 10.2%, p=0.2618). Those experiencing thyroid toxicity were more likely to respond to immunotherapy (68.5% vs 39.2%, p=0.001). Conclusions: Presence of thyroid autoAbs in cases of ICI-TD suggests an autoimmune etiology. The high rates of Abs suggests that pre-existing subclinical autoimmunity becomes unleashed after the administration of ICI. Given the known correlation between ICI-related endocrine toxicity and ICI response, future studies of thyroid Ab presence could be used to identify populations with higher rates of both ICI TD toxicity and treatment response. TPO TSI TgAb Lung 63 8/11 (72.7%) 3/5 (60%) 2/2 (100%) Melanoma 52 7/8 (87.5%) 1/4 (25%) 3/5 (60%) Total 173 20/27 (74.1%)0-6683 5/14 (35.7%)0-99 6/13 (46.2%)0-555
Impact of GLP-1 receptor agonists in hormone receptor–positive breast cancer patients receiving CDK4/6 inhibitors.
1100 Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and obesity due to their efficacy in weight reduction and glycemic control. Beyond their metabolic benefits, GLP-1 RAs delay gastric emptying, which may affect the absorption of oral medications like cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i). Additionally, CDK4/6i and GLP-1 RAs share overlapping gastrointestinal (GI) toxicities such as diarrhea and nausea, which could impact medication tolerability and clinical outcomes. This investigation aimed to characterize the safety of concomitant GLP-1 RA and CDK4/6i use in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: We performed a single-center, retrospective chart review evaluating adult patients prescribed a CDK4/6i for HR+ breast cancer at Winship Cancer Institute between October 2022 and May 2025. Patients receiving concomitant GLP-1 RA and CDK4/6i (Group 1) were matched 1:1 to patients receiving a CDK4/6i without GLP1-RA (Group 2). Matching criteria included prescribed CDK4/6i, treatment indication (adjuvant or metastatic), age (≥65 years, 45-64 years, and <45 years), and race. The primary outcome was safety, assessed by adverse drug reactions, dose reductions, and discontinuations. Results: 82 patients were reviewed, median age 54 years old. Half (41 patients, 50%) were prescribed abemaciclib, 21 (25.61%) palbociclib, and 20 (24.39%) ribociclib. 41 patients receiving concomitant GLP-1 RA and CDK4/6i (Group 1) were matched to 41 patients receiving a CDK4/6i without GLP1-RA (Group 2). Of those in Group 1, 20 were prescribed a GLP-1 RA for diabetes and 18 for obesity. Median BMI was 32.76 kg/m2 (range, 28.44-36.28 kg/m2) in Group 1 compared to 26.32 kg/m2 (range, 23.74-28.05 kg/m2) in Group 2. Semaglutide and tirzepatide were the most prescribed GLP-1 RAs. 38 patients (51.35%) in Group 2 experienced an ADR associated with CDK4/6i compared to 36 patients (48.65%) in Group 1 (p-value, 0.457). Median time to first documented ADR was 14 days (range, 8-21 days) in Group 2 compared to 18 days (range, 11-36 days) in Group 1 (p-value, 0.086). 24 patients (55.81%) in Group 1 experienced a GI ADR compared to 19 patients (44.19%) in Group 2 (p-value, 0.269). Conclusions: Patients receiving CDK4/6i without GLP-1 RA experienced earlier onset and a numerically higher incidence of ADRs compared with those receiving concomitant GLP-1 RA and CDK4/6i therapy, though differences did not reach statistical significance. Ongoing analyses of treatment adherence and progression-free survival will be reported out at a later date. Larger, multi-center studies are warranted to further characterize safety and potential pharmacologic interactions between GLP-1 RAs and CDK4/6i.
A harmonized workflow to enable efficient tumor-normal matched whole genome sequencing from HMW gDNA and FFPE samples.
e15116 Background: Whole genome sequencing (WGS) in clinical oncology offers a comprehensive approach to tumor genomic profiling, enabling detection of actionable mutations, structural variants, copy number alterations, and other genomic signatures that may be missed by targeted panels. As sequencing costs continue to decline and computational capacity expands, WGS is becoming increasingly accessible and represents a scalable alternative to targeted assays and whole exome sequencing. Importantly, tumor-normal matched WGS allows for accurate discrimination between somatic and germline variants, substantially reducing variant misclassification commonly observed with tumor-only analyses and thereby increasing confidence in biomarker identification and therapeutic decision-making. Methods: To support clinical implementation, we established a harmonized WGS workflow capable of processing both high molecular weight (HMW) genomic DNA (gDNA) and DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tumor samples using a single standardized protocol. We evaluated the Watchmaker DNA Library Prep Kit with Fragmentation as a unified library preparation solution to generate consistent WGS libraries across diverse clinical sample types while minimizing turnaround time in a clinical testing environment. Performance was assessed using commercial FFPE samples and a combination of Genome in a Bottle HMW gDNA and FFPE reference materials. All sequencing data were analyzed using the Illumina DRAGEN WGS pipeline. Results: After optimizing DNA input, DNA fragmentation and PCR cycles, the Watchmaker DNA Library Prep Kit produced high-quality WGS libraries across all sample types, characterized by low duplication rates (≤10%) and uniform genome-wide coverage. Robust variant calling performance was observed, demonstrating strong concordance with reference datasets as well as high reproducibility across technical replicates, regardless of sample type. Conclusions: In summary, the Watchmaker DNA Library Prep Kit with Fragmentation enables efficient, high-quality WGS library generation through a harmonized workflow applicable to both HMW gDNA and FFPE samples. This approach supports accurate somatic variant detection with reduced turnaround time, providing a scalable and practical solution for implementing WGS in clinical oncology settings, like variant selection for tumor-informed MRD applications.
A phase 1/2, first-in-human, open-label, dose-escalation and -expansion study of TAK-188, a novel antibody-drug conjugate (ADC) targeting CCR8 <sup>+</sup> regulatory T cells, in adult patients with locally advanced or metastatic solid tumors.
TPS3155 Background: Regulatory T cells (Tregs) are key contributors to an immunosuppressive tumor microenvironment (TME). Their abundance in solid tumors is often linked to poor patient prognosis, decreased overall survival, and resistance to immunotherapy. Tumor-infiltrating Tregs express high levels of chemokine receptor CCR8, making CCR8 an attractive target for immunotherapy. TAK-188 is a first-in-class anti-CCR8 ADC that aims to enhance patients’ own antitumor activity by selectively eliminating CCR8-positive Tregs within the TME. It uses a novel amanitin payload capable of killing both actively dividing and non-dividing cells and is linked to the antibody via a cleavable linker. The nonclinical toxicology profile demonstrated monitorable and partially-to-completely reversible toxicities at doses exceeding projected clinically efficacious exposures. Preclinical evaluation of TAK-188 showed robust and deep depletion of CCR8 + cells in vitro and in vivo , and demonstrated anti-tumor activity as a single agent in non-clinical models (Casson et al. AACR 2026). Methods: This phase 1/2 study (NCT07205718) is enrolling adult patients with locally advanced or metastatic solid tumors known to express high levels of CCR8 on Tregs in the TME (gastroesophageal adenocarcinoma [GC] and esophageal squamous cell carcinoma [ESCC], pancreatic ductal adenocarcinoma, non-squamous and squamous non-small cell lung cancer [NSCLC], head & neck SCC [SCCHN], or colorectal cancer), and whose disease has progressed on, or are intolerant to, all standard therapies. Eligible patients must have Eastern Cooperative Oncology Group performance status ≤1 and radiographically measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. In phase 1, TAK-188 is intravenously administered weekly at escalating dose levels following a Bayesian Optimal Interval design, to determine the recommended phase 2 dose (RP2D) and dosing schedules for the cohort-expansion phase. The primary objective is to determine the safety and tolerability of TAK-188 in phase 1 and to assess the preliminary efficacy in phase 2 in NSCLC, SCCHN and GC. Secondary objectives include characterization of the RP2D and pharmacokinetic parameters for TAK-188, changes in T cell populations (abundance and ratio of Tregs and effector T cells) within the tumor post-treatment, and preliminary efficacy in select cancer types. Exploratory objectives include the impact of TAK-188 on CCR8 + Tregs, molecular response determined by circulating tumor DNA (ctDNA) analysis, and changes in cytokines and chemokines in peripheral blood. The study plans to enroll up to 223 patients in the USA (47 patients across 15 sites for dose-escalation; 62–176 patients across ~35 sites in cohort-expansion). Clinical trial information: NCT07205718 .
Expression levels of clock genes <i>PER2</i> and <i>PER3</i> in nasopharyngeal carcinoma and their correlation with survival prognosis and other factors.
e18055 Background: Nasopharyngeal carcinoma is a malignant tumor of the head and neck that originates from the mucosal epithelium of the nasopharynx. It has distinct geographical and racial distribution characteristics, with a particularly high incidence in Southeast Asia and southern China. The main reasons for treatment failure in nasopharyngeal carcinoma include distant metastasis and local recurrence. Therefore, there is an urgent need in clinical practice to explore new and effective prognostic markers to assess the survival and prognosis of nasopharyngeal carcinoma patients. This study investigates the expression levels of clock genes PER2 and PER3 in nasopharyngeal carcinoma tissues and their relationship with the survival prognosis of nasopharyngeal carcinoma patients, aiming to discover novel molecular markers for the prognosis of nasopharyngeal carcinoma. Methods: survival prognosis of nasopharyngeal carcinoma patients through bioinformatics analysis. Additionally, 64 tissue specimens of chronic nasopharyngeal inflammation and 64 tissue specimens of locally advanced nasopharyngeal carcinoma were included. All patients received standard concurrent radiotherapy or induction chemotherapy followed by concurrent radiotherapy. The mRNA levels and protein expression levels of PER2 and PER3 genes in the two groups of tissues were detected using qRT-PCR (Quantitative Real-time PCR) and immunohistochemical techniques. Statistical analysis was conducted using ROC curves, Kaplan-Meier survival analysis, and Cox proportional hazards model analysis. Results: The bioinformatics analysis revealed that the expressions of PER2 and PER3 genes were higher in chronic inflammatory tissues of the nasopharynx than in nasopharyngeal cancer tissues. Moreover, the 5-year overall survival rate (OS) of patients with high expression of PER2 and PER3 was better than that of the low-expression group (P < 0.05). The results of qRT-PCR and immunohistochemistry showed that the mRNA and protein expressions of PER2 and PER3 genes in nasopharyngeal cancer tissues were lower than those in inflammatory tissues (P < 0.05). The survival analysis indicated that the patients with high expression of PER2 and PER3 genes in nasopharyngeal cancer had better 1-, 3-, and 5-year OS and distant metastasis-free survival rate (DMFS) than those with low expression. The protein level expression of PER2 and PER3 genes was an independent prognostic factor for nasopharyngeal cancer patients (P < 0.05). Conclusions: The PER2 and PER3 genes are expressed at a low level in nasopharyngeal carcinoma tissues, and patients in the low-expression group have a poorer prognosis compared to those in the high-expression group. The PER2 and PER3 genes are expected to become potential molecular markers for evaluating the prognosis of nasopharyngeal carcinoma.
Phase II study of bipolar androgen therapy combined with sipuleucel-T for patients with metastatic castration resistant prostate cancer (mCRPC).
e17081 Background: Bipolar androgen therapy (BAT) is an investigational therapy comprising monthly supraphysiologic testosterone injections and continuous androgen deprivation therapy (ADT). BAT demonstrated clinical activity in patients with metastatic castration resistant prostate cancer (mCPRC) progressing on abiraterone acetate (Denmeade S et al JCO 2021). Preclinical studies showed that dihydrotestosterone increases the cytotoxicity of macrophages against prostate cancer cell lines in a concentration-dependent manner (Lee GT et al Endocrinology 2019). Sipuleucel-T, an autologous cellular immunotherapy manufactured from peripheral blood mononuclear cells cultured with PA2024, Prostatic Acid Phosphatase linked to GM-CSF, improved overall survival (OS) in patients with mCRPC. Interferon-gamma (IFN-g) enzyme-linked immunosorbent spot (ELISPOT) response to PA2024 was an immune response parameter that had the strongest correlation with OS benefit (Sheikh N et al. CII. 2012). The ELISPOT response was, however, detected only in 50% of patients treated with sipuleucel-T. We hypothesized that treatment with BAT prior to sipuleucel-T could enhance ELISPOT response rate. Methods: Patients with progressive mCRPC and with clinical indication for sipuleucel-T were enrolled. The key eligibilities included PSA < 20ng/mL, no opioid use for cancer-related pain, no hepatic metastasis, no prior chemotherapy for mCRPC, and no active autoimmune disease. Patients continued with ongoing ADT and received testosterone cypionate 400mg intramuscularly every 4 weeks until they are no longer deriving clinical benefit. Sipuleucel-T started after two 4-weekly testosterone injections and administered every 2 weeks for 3 cycles. Research blood was collected before each testosterone injection and each sipuleucel-T infusion. The primary endpoint was ELISPOT response, defined as > 10 IFN-g response spots to the PA2024 antigen. Results: Compared to the historical control of 50%, PA2024 ELISPOT response rate, eleven of 11 (100%) evaluable patients achieved positive ELISPOT responses ( > 10 spots) to PA2024 antigen. The mean number of spots was 232 (95% Confidence Interval (CI) 147, 317). 100% of patients achieved T cell proliferation response to PA2024 antigen ( > 12 Stimulation Index (SI)). Mean SI (95% CI) was 23 (17,30). One of two RECIST-evaluable patients achieved confirmed PR. Two of 11 evaluable patients had PSA50 responses. No grade 3 or higher adverse events or serious adverse events were observed. Conclusions: BAT followed by sipuleucel-T is safe and effective in potentiating immune response to Sipuleucel-T. Encouraging clinical activity has been observed. The study is currently enrolling to the second stage of the Simon’s design. Clinical trial information: NCT06100705 .
Longitudinal ecological momentary assessment compliance among patients with cancer pain.
e23017 Background: Ecological momentary assessments (EMA) allow for frequent assessments and reduce retrospective reporting biases by prompting participants to answer surveys during moments of their everyday life. The validity of EMAs relies on participants completing the surveys (i.e., compliance) for the duration of the protocol, which varies across studies. EMA compliance has been correlated with sample- and participant-level characteristics across limited timeframes; however, no study has investigated EMA compliance, and associated patient characteristics, across a 12-month multi-site study in an oncology population. Methods: Ambulatory outpatients with cancer-related pain enrolled in an ongoing observational, multi-site study assessing the role of cannabis in pain management were asked to complete EMAs (see: NCT06037681). These included seven consecutive days of EMAs each month for 12 months. One survey was administered every morning and three random surveys throughout the day (i.e., a total of 336 surveys per participant). Participant compliance was defined as the percentage of surveys completed (out of 336). Compliance data were analyzed over the study period and descriptive data are presented. Results: A total of 166 participants across Western New York and Eastern Pennsylvania who completed their 12-month visit to date, irrespective of if they completed or missed monthly sessions across the study period, were included in analyses. Of these, 66 (40%) participants reported using cannabis and 100 participants (60%) did not. Approximately 69% of the sample identified as White, and 31% as Black or African American, 66% identified as female, and the mean age was 57 years old. The most frequently reported cancer type was Breast (n = 52), followed by Gastrointestinal (n = 28). Overall, our sample demonstrated a high aggregate, 12-month, mean compliance of 77% across the 12-month study period. Associations with participant characteristics are shown in the table. The average compliance for months 1 to 6 was the same as months 7 to 12 (~77%). Conclusions: Oncology outpatients in our sample demonstrated a sustained high compliance across our 12-month study period, indicating a promising method to assess how participants manage their pain symptoms throughout the day. Investigating trends in long-term EMA compliance can inform future research protocols to improve the collection of real-time data to study daily behaviors and associated outcomes in the oncology population. Associations between quarterly compliance and participant characteristics. Months 1-3 Months 4-6 Month 7-9 Months 10-12 Age a -0.08 0.03 -0.05 0.01 Gender Male Female 77%79% 77%77% 74%79% 76%80% Race White African American/Black 81%71% 80%72% 81%69% 82%73% a Pearson correlations.
Donafenib plus transarterial chemoembolization (TACE) with or without anti–PD-1 antibodies for unresectable hepatocellular carcinoma second-line or later therapies: A retrospective multicenter study.
e16208 Background: Currently , there is still unsatisfactory effect of treatment regimen for patients with hepatocellular carcinoma (HCC) who have progressed after frontline combination therapy with immune checkpoint inhibitors. The Phase III clinical trial ZGDH3 has demonstrated donafenib improves overall survival (OS) in HCC patients. This study evaluated the efficacy and safety of donafenib combined with transarterial chemoembolization (TACE) ± programmed death-1 (PD-1) inhibitor for HCC second-line or later treatment. Methods: We retrospectively analyzed patients with HCC who received Donafenib combination therapy as second-line or above treatment at the first affiliated hospital Sun Yat-sen university, Shanghai oriental hepatobiliary hospital, Peking University Cancer Hospital, Sun Yat-sen memorial hospital and Henan cancer hospital between Jun 13, 2021 and Jun 21, 2025.The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: All of 41 patients were received donafenib combined with transarterial chemoembolization (TACE)±programmed death-1(PD-1) inhibitor. Second-line treatment accounted for 78.0%, and 22.0% used it as post-line treatment. 82.9% of the patients received the triple therapy with TACE, donafenib, and PD-1 inhibitor. Patients were classified as BCLC stage A (2.4%), B (22.0%) and C(75.6%). ORR were 34.1% per RECIST 1.1 and 61% per mRECIST, disease control rate (DCR)was 87%. In patients who had only received systemic therapy previously, ORR was 38.9% (RECIST 1.1), while in those who had previously undergone interventional therapy combined with systemic therapy, ORR was 30.4% (RECIST 1.1). The mPFS was 7.5 months and 12-month OS rate was 76.7%. 65.9% of patients had at least one treatment-emergent adverse events(TEAEs) and 7 patients (17.1%) had grade 3 and above TEAEs. During the treatment course, 56.4% of patients maintained stable liver function as assessed by the ALBI score, while 12.8% showed improvement. Conclusions: Donafenib combined TACE with or without PD-1 inhibitor has shown good efficacy and safety in the second-line or later therapies for HCC patients. ORR of the patients receiving different frontline treatment. ORR RECIST 1.1 n(%) mRECIST n(%) Overall (n=41) 14 (34.1) 25 (61.0) Frontline Therapy Interventional therapy with systemic therapy (n=23) 7 (30.4) 12 (52.1) With immunotherapy (n=19) 5 (26.3) 10 (52.6) Without immunotherapy (n=4) 2 (50.0) 2 (50.0) Systemic therapy alone (n=18) 7 (38.9) 13 (72.2) With immunotherapy (n=12) 4 (33.3) 8 (66.7) Without immunotherapy (n=6) 3 (50.0) 5 (83.3)
Development of novel anti-cancer drug by “locking inhibition” of amino acid transporter LAT1.
e15105 Background: Large Amino Acid Transporter 1 (LAT1) is critical for transporting essential amino acids, enabling the growth and proliferation of cancer cells. LAT1 is overexpressed via oncogene Myc-pathway in aggressive tumors, making it a promising therapeutic target. LAT1 inhibition disrupts mTORC1 pathway and the metabolic programs, vital for cancer progression. To address the limitations of currently developed reversible inhibitors, we developed APL1101, a first-in-class LAT1 inhibitor that achieves an effectively irreversible, noncovalent “locking” mechanism to durably block amino acid transport. Methods: Preclinical efficacy studies of APL1101 involved in vitro and in vivo models, including LAT1-overexpressing xenograft tumors such as non-small cell lung cancer and triple-negative breast cancer. Toxicity, and pharmacokinetics (PK) were evaluated in rodents and canines to assess safety, drug distribution, and LAT1 occupancy. Combination studies were also performed to explore synergy with existing therapies. Results: APL1101 demonstrated potent and selective LAT1 inhibition in vitro (Ki < 20 nM), significantly reducing tumor cell proliferation. In vivo, it achieved more than 70% tumor growth suppression in xenograft models without causing systemic toxicity or weight loss. PK studies revealed sufficient Cmax and a long half-life, supporting sustained efficacy. Toxicology studies in rodents and canines confirmed a favorable safety profile, with no off-target effects and high tolerability. Notably, preclinical data suggest that combining APL1101 with immune checkpoint inhibitors or standard chemotherapy agents can synergistically enhance anti-tumor efficacy. Clinical Development: Preparations for a Phase 1/2a clinical trial are underway, with Phase 1 scheduled to begin in Q4 2026. The trial will evaluate safety, tolerability, and efficacy in patients with advanced solid tumors. Phase 2a will focus on LAT1-overexpressing cancers using biomarker-driven stratification. APL1101’s mechanism of action, targeting mTORC1 pathway and metabolic programs, underscores its broader potential across multiple solid and hematologic malignancies. Conclusions: APL1101’s innovative irreversible LAT1 inhibition mechanism demonstrates robust preclinical efficacy and safety, supporting its potential as a transformative therapy for aggressive cancers. Its versatility as a monotherapy or in combination regimens with chemotherapeutics and immunotherapies offers significant promise for broader cancer treatment. The upcoming clinical trials will provide critical insights into its full therapeutic potential.
Association of neutrophil percentage-to-albumin ratio with progression-free survival and overall survival in cancer patients treated with PD-1/PD-L1 inhibitors.
2574 Background: The Neutrophil Percentage-to-Albumin Ratio (NPAR) reflects systemic inflammation and nutritional status. Its prognostic and predictive value in cancer patients treated with PD-1/PD-L1 inhibitors remains unclear. We investigated the association of the baseline of NPAR with PFS and OS in cancer patients who received PD-1/PD-L1 inhibitors. Methods: A retrospective cohort of 532 patients treated with PD-1/PD-L1 inhibitors at the Second Xiangya Hospital of Central South University between 2018 and 2024 was enrolled. Participants were divided into tertiles based on the baseline of NPAR. PFS and OS were assessed using Kaplan–Meier method and log-rank tests. Univariable and multivariable Cox proportional hazards models were employed to examine the association between NPAR and survival outcomes, with sequential adjustment for clinically relevant confounders. Results: The median PFS and OS of total patients was 21.3 months (IQR, 10.5–32.7) and 24.7 months (IQR, 16.9–41.5), respectively. Individuals with elevated NPAR experienced significantly worse PFS and OS than those with low NPAR and medium NPAR (PFS: p < 0.05; OS: p < 0.0001). Subgroup analyses showed the consistent results in the lung cancer patients (PFS: p < 0.05; OS: p < 0.01). In univariate COX regression analyses, each one-unit increment in NPAR corresponded to hazard ratios (HRs) of 1.032 (95% CI, 1.004–1.062; p < 0.05) for PFS and 1.069 (95% CI, 1.035–1.104; p < 0.001) for OS. Multivariate Cox regression analysis identified that a high NPAR level remained independently associated with inferior survival outcomes after adjusting for confounders. Compared with the low NPAR group, the high NPAR group showed worse PFS (HR, 1.38; 95% CI, 1.03-1.84; p < 0.05) and OS (HR, 1.95; 95% CI, 1.36-2.79; p < 0.001) in the fully adjusted model (Model 4). Conclusions: Elevated NPAR can independently predict worse PFS and OS in cancer patients receiving PD-1/PD-L1 inhibitors and represents a simple, low-cost biomarker for clinical risk stratification. Association between NPAR and PFS/OS of cancer patients. Model 1HR (95%CI) p-value Model 2HR (95%CI) p-value Model 3HR (95%CI) p-value Model 4HR (95%CI) p-value NPAR PFS OS PFS OS PFS OS PFS OS PFS OS PFS OS PFS OS PFS OS Low group ref ref ref ref ref ref ref ref High group 1.40(1.06-1.85) 2.05(1.45-2.90) 0.018 <0.001 1.42(1.07-1.89) 1.98 (1.40-2.82) 0.015 <0.001 1.40 (1.05-1.87) 1.99 (1.40-2.83) 0.023 <0.001 1.38 (1.03-1.84) 1.95 (1.36-2.79) 0.032 <0.001 Model 1: unadjusted. Model 2: adjusted for sex, diabetes, hyperlipidemia, cardiovascular disease, cerebrovascular disease, pulmonary tuberculosis and viral hepatitis type B. Model 3: adjusted for model 2 + single ICIs, chemotherapy, radiotherapy. Model 4: adjusted for model 3 + NSAIDS, PPI, β-blocker, hormone, whiteboard-raising drugs, anticoagulant and antithrombotic drugs.
Trends in mortality from unspecified malignant neoplasm of the liver among U.S. adults aged ≥45 years, 1999–2023.
e16196 Background: Unspecified malignant neoplasm of the liver (ICD-10: C22.9) represents a diagnostic category encompassing liver cancers that lack detailed histologic or anatomic classification. Although this category may reflect limitations in diagnostic testing, reporting, or documentation, it has substantial implications for the accuracy of cancer surveillance and mortality trend interpretation. Over the past two decades, advances in diagnostic imaging, pathology, and coding practices have improved cancer classification, yet a considerable proportion of liver cancer deaths continue to be recorded as “unspecified.” Such cases may obscure the true epidemiologic patterns of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), complicating national and regional assessments of disease burden. Moreover, mortality patterns related to unspecified malignancies may reveal underlying inequities. Thus, this study evaluates long-term trends in mortality attributed to unspecified malignant neoplasm of the liver among U.S. adults aged ≥45 years from 1999 through 2023, stratified by sex, age, race and ethnicity, geographic region, and level of urbanization. Methods: We analyzed CDC WONDER underlying cause-of-death data, identifying deaths coded as C22.9. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, and Joinpoint regression was used to estimate average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: A total of 198,299 deaths were recorded from 1999–2023. The overall AAMR decreased slightly but in a statistically insignificant manner from 5.4 to 5.2 (AAPC:-0.02%, 95% CI: -0.49 to 0.45). Males had lower decrease in mortality than females (AAPC: -0.082% vs. -0.21%, P-value: 0.75 vs. 0.68). Non-Hispanic (NH) Asian or Pacific Islander individuals showed the largest decrease (AAPC: -2.57%), while NH Black (AAPC: -0.85%) and Hispanic populations (AAPC: -0.51%) maintained elevated AAMRs. Regionally, the South had the highest mortality burden (n = 88,703; AAPC: 0.32%, P-value: 0.46). Adults aged 65–85+ had the greatest mortality increase (AAPC: 0.34%), while those aged 45–64 showed declines (AAPC: -0.9%, P-value: < 0.01). Non-metropolitan areas had greater mortality increase than metropolitan areas (AAPC: 0.58% vs. 0.51%). Conclusions: Despite marked progress in liver cancer diagnostics and classification, mortality associated with unspecified malignant neoplasm of the liver has remained largely stable in the United States over the past quarter century. However, addressing these disparities through enhanced diagnostic precision, standardized reporting, and targeted public health interventions could improve understanding of true liver cancer epidemiology and guide equitable resource allocation for prevention, detection, and treatment across demographic and geographic subgroups.
Cost-effectiveness analysis of aspirin and structured exercise as adjuvant therapy in localized colorectal cancer.
3650 Background: The ALASCCA trial demonstrated that 160 mg of aspirin daily for 3 years reduced the risk of localized colorectal cancer recurrence in patients with PIK3CA exons 9/20 (group A) or PIK3R1/PTEN/other PIK3CA alterations (group B). The CHALLENGE trial demonstrated that increasing recreational aerobic activity above baseline through a 3-year structured exercise program reduces the risk of colon cancer recurrence. These interventions have not been adopted into Canadian clinical practice (CCP), and we evaluated the cost-effectiveness of strategies to implement them as adjuvant therapy for localized, operable colorectal cancer from the Canadian public healthcare perspective. Methods: We developed a decision model to project clinical and economic consequences of six strategies: (1) “CCP,” defined as no exercise or aspirin interventions; (2) “Aspirin for group A PI3K alterations,” defined as testing for group A PI3K alterations and treating positive patients with aspirin; (3) “Aspirin for group A/B PI3K alterations,” defined as testing for group A/B PI3K alterations and treating positive patients with aspirin; (4) “Aspirin for all,” defined as treating all patients with aspirin regardless of PI3K status; (5) “Structured exercise alone,” defined as initiating all patients on a structured exercise program with no aspirin intervention; and (6) “Aspirin for group A/B PI3K alterations and structured exercise,” defined as testing for group A/B PI3K alterations, treating positive patients with aspirin, and initiating all patients on a structured exercise program. The model was parameterized using survival data from the ALASCCA and CHALLENGE trials, and cost and utility data from Alberta, Canada, and Canadian sources. Costs are presented in 2025 Canadian dollars. Future costs and benefits were discounted at 1.5%. Results: Compared with the CCP, all interventional strategies were associated with greater QALY gains and lower per-person costs, resulting in overall cost savings (Table). The “aspirin for group A/B PI3K alterations and structured exercise” strategy emerged as the dominant intervention, yielding the highest QALYs gained and greatest cost savings per person. Implementing this strategy into CCP would avert disease recurrence in 940 patients per year, generate 2,625 total QALYs annually, and produce total budget savings of $399 million per year. Conclusions: The integration of PI3K group A/B–guided aspirin therapy with structured exercise as adjuvant treatment for localized colorectal cancer should be adopted into CCP, given its considerable societal benefit. Strategy Inc. QALY gained/pers. Cost saving/pers. CP Ref Ref Aspirin for group A PI3K alterations 0.05 9,400 Aspirin for group A/B PI3K alterations 0.12 20,200 Aspirin for all 0.07 14,700 Structured exercise alone 0.13 23,700 Aspirin for group A/B PI3K alterations and structured exercise 0.22 33,700
RECON: A trainee-led, needs-informed professional development and global connectivity model for young oncologists in low- and middle-income countries.
9039 Background: Oncology trainees and early-career oncologists (ECOs) in low- and middle-income countries (LMIC) face persistent gaps in structured mentorship, research exposure, and non-clinical professional skills, limiting academic development and global engagement. In response, the Residents & Early Career Oncologists Network (RECON) was established in 2024 under the Society of Medical Oncology Pakistan as a national, trainee-led, needs-informed initiative delivering scalable, low-cost, collaborative educational interventions aligned with learner priorities. Methods: RECON implemented a needs-informed, multi-component professional development framework for oncology trainees and ECOs (≤5 years post-training) across Pakistan. Core components included: (1) structured mentorship; (2) digital education via the Second Opinion Podcast addressing non-clinical competencies; (3) conference-linked outreach workshops on abstract preparation and peer networking; and (4) monthly international virtual oncology case rounds with young oncologists from Türkiye. Engagement was prospectively tracked, and post-session surveys assessed acceptability and self-reported learning outcomes using 5-point Likert scales (1–5). Results: RECON enrolled 104 members (79 trainees, 25 ECOs) and engaged 32 national and international faculty mentors. Baseline survey data (n = 104) demonstrated substantial unmet needs across multiple professional domains, with high interest in professional development (83%), research collaboration (80%), mentorship opportunities (61%), and general networking (60%). Digital education initiatives achieved over 10,000 cumulative podcast views, and three national outreach workshops engaged 155 participants. Post-session surveys from the case rounds series (n = 37) demonstrated high acceptability, with 92% rating sessions as very good or excellent. Participants reported greater confidence in international oncology case discussions (84% rating 4–5) and improved ability to critically appraise alternative management approaches (81% rating 4–5). International perspectives were rated as highly relevant to clinical practice. Conclusions: This early evaluation demonstrates the feasibility and acceptability of a national, trainee-led, needs-informed initiative in an LMIC setting. RECON’s low-cost, digitally enabled model was associated with high engagement and perceived educational value, particularly in fostering global connectivity and professional confidence among oncology trainees and ECOs. Future evaluation will explore longitudinal outcomes and support iterative refinement, with consideration of adaptation across similar resource-limited contexts.
Evaluating large language models for ADHD education: A comparative study of ChatGPT 5, DeepSeek V3, and Grok 4
Background Children with attention-deficit/hyperactivity disorder (ADHD) often face barriers to participating in organized sports, particularly when physical education (PE) is delivered by outsourced coaches with limited training in disability inclusion. Meanwhile, large language models (LLMs) such as ChatGPT, DeepSeek, and Grok are increasingly used to generate educational content, yet their readability, stability, and accuracy for non-specialist educators remain unclear. Methods This study systematically compared three advanced LLMs, ChatGPT 5, DeepSeek V3, and Grok 4, using identical prompts related to ADHD definitions, symptoms, and medication–exercise interactions. Thirty responses per model were collected. The primary endpoints were content accuracy, readability, and response stability. Readability was evaluated using the Flesch–Kincaid Reading Ease score (FKRE), the Flesch–Kincaid Grade Level (FKGL), and the Simple Measure of Gobbledygook (SMOG), alongside measures of lexical complexity. Results All models aligned with DSM-5 in describing ADHD but differed in emphasis and stability. DeepSeek V3 produced the broadest and most variable outputs, Grok 4 showed the greatest consistency and clinical structure, and ChatGPT 5 generated concise and strengths-based explanations. However, all models exhibited high reading levels (FKGL > 12, FKRE < 40, SMOG > 12), exceeding recommended public-health readability standards for general audiences, which are typically around Grade 6–8. Conclusion While LLMs demonstrate strong potential for generating ADHD-related educational materials, their current readability and stability limitations restrict accessibility for non-specialist educators. Future work should focus on optimizing prompt design and language calibration to enhance usability in inclusive education contexts.