Browse Articles

Impact of rurality on screening and prevention strategies for patients with hereditary breast and ovarian cancer syndrome.

e22662 Background: Patients with hereditary breast and ovarian cancer syndrome (HBOC) with a germline pathogenic variant in BRCA1/2 are at a high lifetime risk of breast and ovarian cancer. Existing cancer surveillance and prevention strategies improve survival or detect cancer at an earlier stage in this population. Despite this, barriers to uptake exist. Rurality is a known barrier to healthcare access but its impact on adherence to guideline-based cancer surveillance and prevention among women with HBOC remains poorly understood. Methods: We enumerated a cohort of patients with pathogenic BRCA1 / 2 variants residing in Vermont or northern New York who were seen by the Cancer Genetics Program at the University of Vermont Cancer Center. Cancer surveillance and prevention methods analyzed included adherence to guideline-based mammography, breast MRI and bilateral salpingo-oophorectomy (BSO). Rates of risk-reducing mastectomy (RRM) were also determined. Compliance with breast cancer surveillance imaging among patients who had not undergone RRM was defined as annual screening breast MRI for patients >25 years old and mammogram for patients >30 years old with a 3-month grace period. Adherence to BSO was determined based on gene-specific age recommendations from the NCCN guidelines . We classified rurality status by converting residential ZIP codes into Rural-Urban Commuting Area (RUCA) codes, with RUCA>7 comprising the most rural patients. We compared adherence proportions for the screening/prevention strategies adjusted for participation in longitudinal follow-up via stratified analysis. Results: We enrolled 285 natal females with HBOC, of whom 120 (43%) had previously undergone RRM. Annual mammogram and screening breast MRI were recommended for 98 (34%) and 110 (39%) of enrolled patients, respectively. Mean age was 49.7 years (SD 15.1), and 90 (32%) patients resided in a small town/rural setting. For eligible patients, adherence was 54% for mammography 43% for breast MRI. Uptake of chemoprevention was 2.5%. Compared with metropolitan/micropolitan patients, small town/rural patients were less likely to adhere to screening mammography (RR adj = 0.63, 95% CI: 0.41, 0.97) and somewhat less likely to adhere to screening breast MRI (RR adj 0.73, 95% CI 0.45, 1.2). Rates of RRM and BSO were similar by rurality. Conclusions: In a cohort of BRCA1/2 carriers, adherence to screening mammogram and breast MRI was lower for rural patients compared with non-rural patients. Adherence rates to screening mammogram and breast MRI overall were suboptimal but comparable to previously reported rates in HBOC patients. Uptake of chemoprevention was lower than expected. Rates of BSO and RRM were similar to previously published results. Research resources should be invested to identify and ameliorate other barriers to uptake of cancer prevention and surveillance strategies in the HBOC population.

Mapping the treatment journey following antibody-drug conjugate (ADC) initiation: Sequencing patterns and real world overall survival (rwOS) in non-breast solid tumors in a US community setting.

e23362 Background: With the clinical application of ADCs in solid tumors, there is a need to understand treatment sequencing of ADCs and outcomes in the real-world (rw) setting. This retrospective observational study evaluates the characteristics, treatment patterns, and OS in patients (pts) with non-breast solid tumors who received ADC treatment in a rw setting. Methods: This study included pts (≥18 y) who initiated a 1st ADC (index ADC) for bladder, ovarian, NSCLC, gastric, or cervical cancers from Jan 2020 to Aug 2024 based on deidentified pt-level data in a US community setting from the iKnowMed EHR database (cut off: Feb 28, 2025). Primary index date was defined as initiation of index ADC treatment. For cohorts with ≥30 pts, rwOS was assessed based on tumor type and the setting in which the index ADC was received. Results: Among 1592 pts included in this study, 1045 had bladder cancer, 243 had ovarian cancer, 119 had NSCLC, 93 had gastric cancer, and 92 had cervical cancer. Across tumor types, median age ranged 51–73 y. At initial diagnosis, 52.3%, 37.9%, 75.6%, 67.7%, and 45.7%, respectively, had stage IV disease. Median follow-up was 7.6, 8.0, 8.1, 5.1, and 6.7 mo, respectively. Index ADC distribution by tumor type and treatment setting is shown in Table. Among pts with bladder cancer who received a 2nd ADC after index ADC (n=139 [13.3%]), 20 received enfortumab vedotin (EV) + pembrolizumab (pembro) as the index ADC, of whom 17 (85.0%) received sacituzumab govitecan (SG) as the 2nd ADC; 109 pts received EV monotherapy or EV + other (non-pembro) as the index ADC, of whom 106 (97.2%) received SG as the 2nd ADC. Among pts who received ADC in metastatic settings, median rwOS for metastatic regimen 1 (R1) and metastatic regimen 2 or beyond (R2+) was 17.4 and 12.6 mo for bladder cancer, 19.4 and 16.3 mo for ovarian cancer, 16.7 and 14.4 mo for NSCLC, and 10.8 and 7.8 for gastric cancer, respectively; median rwOS for R2+ was 12.1 mo for cervical cancer. Conclusions: Across 5 solid tumor types, rw ADC sequencing patterns varied. Median rwOS remains low, although it was longer in pts who received ADC as R1 vs later lines (R2+). These rw data provide a necessary bridge from clinical trial results to clinical practice by informing optimal sequencing and timing of ADCs. Distribution of index ADC treatments received by setting and tumor type. ADC Treatment Bladder (n = 1045) NSCLC (n = 119) Gastric (n = 93) Ovarian (n = 243) Cervical (n = 92) EV + pembro EV mono or EV + other (non-pembro) T-DXd SG T-DM1 T-DXd T-DXd Mirvetuximab soravtansine T-DXd Tisotumab vedotin T-DXd Neoadjuvant or adjuvant n 81 25 - 2 1 - 6 18 1 6 - % 75.0 23.1 - 1.9 100 - 100 94.7 5.3 100 - R1 n 355 163 1 12 18 65 39 48 3 23 1 % 66.8 30.7 0.2 2.3 21.7 78.3 100.0 94.1 5.9 95.8 4.2 R2+ n 53 335 - 18 8 27 48 161 12 58 4 % 13.1 82.5 - 4.4 22.9 77.1 100.0 93.1 6.9 93.5 6.5 T-DM1, trastuzumab emtansine; T-DXd, trastuzumab deruxtecan.

High-performance nanostructured uncooled MWIR PbSe photodetectors enabled by low-damage O+ ion implantation

Uncooled mid-wave infrared (MWIR) photodetectors are an important development direction for next-generation infrared technology. However, due to the narrow bandgap and thermal noise, MWIR photo-detection is difficult to achieve with conventional photoconductive (PC) and photovoltaic (PV) photodetectors. This paper proposes a low-damage design based on O+ ion implantation in PbSe, achieving enhanced MWIR photoconductive response. The surface morphology of the nanostructures was observed. The optical bandgap of the thin films became smaller, making them more suitable for mid-infrared radiation detection. Increasing the implantation dose reduced the Urbach energy from 136.9 to 53.37 meV, indicating a reduction in band tail disorder and shallow defect states. An optimal dose (1 × 1018 cm−2) achieved a peak responsivity of 2.1 A/W at a wavelength of 4 μm, with a detectivity of 2.3 × 109 Jones at 4 μm, 300 K under bias voltage of 15 V, and chopping frequency of 400 Hz. The photoresponse is attributed to the formation of a built-in carrier separation region and the generation of deep-level traps, thereby enhancing carrier separation and prolonging minority carrier lifetime. Additionally, extremely high carrier mobility (4480–8320 cm2 V−1 s−1) was achieved, which improves the collection efficiency of photogenerated carriers. This work demonstrates a defect engineering strategy through O+ implantation, achieving excellent carrier mobility and responsivity for the high-performance uncooled MWIR photodetector.

Marine cuttlebone-derived chitosan nanoparticles as natural antioxidants for oxidative stress management

Interim results from a prospective phase II study of stratified treatment of localized cervical esophageal squamous cell carcinoma by induction immunochemotherapy (SCENIC trial).

4086 Background: Definitive concurrent chemoradiotherapy (dCRT) is the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). However, when dCRT fails, salvage esophagectomy is technically challenging. Moreover, optimizing patient selection for dCRT remains an unresolved concern. We propose a stratified screening strategy by incorporating induction immunochemotherapy, aiming to identify suitable candidates for organ-sparing dCRT and timely surgical treatment. Methods: This prospective interventional phase II study (SCENIC, ChiCTR2200057732) enrolled patients with clinical stage T 2-4 N any M0 (AJCC TNM 8th) resectable CESCC. Eligible participants received induction therapy (IT) of intravenous PD-1 inhibitor tislelizumab (200mg, day 1) plus nab-paclitaxel (100 mg/m 2 , day 1,8,15) and carboplatin (area under curve of 5 mg/mL/min, day 1), administered over two 3-week cycles. Four weeks after IT, treatment response was evaluated via endoscopy and PET-CT. Patients were then divided into 3 groups: remarkable response (RR); limited partial response (LPR); and poor response (POR). RR patients received dCRT, while LPR and POR patients underwent radical surgery. Tislelizumab was maintained after dCRT in RR patients, and postoperative adjuvant therapy was dependent on the patient’s condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint is 2-year event-free survival (EFS). Results: From Jul 2022 to Sep 2024, 42 patients were enrolled, with 40 completing two-cycle IT and response evaluation. Post-IT responses were RR in 62.5% (25/40), LPR in 25.0% (10/40), and POR in 12.5% (5/40). All RR patients received subsequent dCRT. In 11 non-RR patients,7 underwent total phryngo-laryngo-esophagectomy(TPLE), 4 received dCRT. Overall, 40 patients (96.0%) had any-grade treatment-related adverse events with leukocytopenia being most prevalent. 5 patients (12.5%) had adverse events of grade 3 or worse. With a median follow-up of 22.3 months (range, 4.5-40.9 months), 2-years EFS rate and overall survival (OS) rate in ITT population was 60.9% and 76.6%. 2-years EFS rate and OS rate in RR group and non-RR group is 78.8% vs 28.0%(p = 0.0011) and 84.8% vs 70.1%(p = 0.0703), respectively. Conclusions: The 2-year survival of RR patients with dCRT followed by IT appears promising compared to historical data. This stratified strategy of induction immunochemotherapy is effective in identifying candidates suitable for dCRT in patients with resectable CESCC. Clinical trial information: ChiCTR2200057732.

Clinical outcomes and safety profile of dendritic cell–based vaccination in melanoma: Meta-analysis of reconstructed time to event data.

e14597 Background: Dendritic cell (DC) vaccination has been investigated as adjuvant immunotherapy for melanoma; however, results from randomized trials remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of DC vaccines on survival outcomes and safety in patients with completely resected advanced melanoma. Methods: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials comparing adding DC-based vaccines vs standard treatment in patients with completely resected stage III/IV melanoma.The hazards ratios (HRs) with 95% confidence intervals (CIs) were pooled for recurrence- free survival (RFS) and overall survival (OS) using a random-effects on R software version 4.3.1. When HRs were not directly reported, Kaplan–Meier curves were digitized to reconstruct individual time-to-event data, allowing pooled Kaplan–Meier estimation and log-rank testing. Results: Four trials (three phase II and one phase III), comprising 397 patients, met the eligibility criteria. DC vaccination was not associated with a statistically significant OS benefit compared with control (HR 0.70; 95% CI 0.30–1.63; p = 0.13; I² = 46.7%). Similarly, no significant difference was identified for RFS (HR 0.99; 95% CI 0.70–1.42; p = 0.21; I² = 31.3%). Pooled Kaplan–Meier curves reconstructed from published plots showed substantial overlap between groups for both RFS (log-rank 2p = 0.7) and OS (log-rank 2p = 0.8), with diminishing precision at later timepoints as the numbers at risk declined (at 60 months: RFS 1 vs 1; OS 1 vs 3 for vaccine vs control). Reconstruction fidelity was acceptable across studies (RMSE ~0.003–0.030; Kolmogorov–Smirnov p-values generally > 0.05). Severe toxicity was similar between arms (grade ≥3 adverse events: (OR 0.81; 95% CI 0.44 –1.47; p = 0.67; I² = 0%), and injection-site reactions did not differ significantly (OR 1.21; 95% CI 0.67–2.17; p = 0.45; I² = 0%). Conclusions: In patients with completely resected stage III/IV melanoma, current randomized evidence is insufficient to establish a survival benefit with DC vaccination, while severe toxicity rates appear similar to control. Larger, adequately powered randomized trials are required to define the clinical role and optimal strategies for DC-based vaccination.

Reducing stress and improving quality of life for adult breast cancer patients.

e23428 Background: Ellie Fund provides essential non-medical support services to ease daily life stressors for individuals undergoing breast cancer treatment, enabling greater focus on recovery, family, and healing. In 2019, Ellie Fund launched an Outcomes Measurement Program to empirically assess the impact of these services on patients’ physical, emotional, and financial well-being, and overall quality of life (QOL). This study expands upon research previously presented at SABCS by incorporating a larger dataset and deeper demographic analysis (e.g., race, income), examining how these factors correlate with stress reduction following receipt of Ellie Fund services. Long term, this work aims to explore links between supportive services and improved breast cancer outcomes. Methods: Participants selected two services (e.g., groceries, meals, transportation, childcare, integrative therapies). Services were delivered monthly for 3 months for non-metastatic (Stages 0–3) and 6 months for metastatic (Stage 4) patients. Voluntary pre- and post-service surveys included the Perceived Stress Scale (PSS-14) and 12 additional QOL questions using a 4-point Likert scale. Analysis included patients enrolled from 2019–2025 who completed both surveys. McNemar tests assessed changes in perceived stress (primary outcome) and differences by disease type (secondary outcome). Cochran–Mantel–Haenszel tests examined associations between stress reduction and race, controlling for income. Results: A total of 1,047 patients completed at least one survey; analyses included matched pre/post responses. Significant reductions were observed in the proportion of patients reporting high perceived stress after services (p < 0.05), with improvements across emotional, physical, financial, and daily life stress domains. Significant QOL gains were reported in six areas: maintaining household order, managing treatment side effects, physical self-care, food access, focus on family, and medication access. Both metastatic and non-metastatic patients experienced significant stress reduction (p < 0.05), with a greater decrease among non-metastatic patients (67% vs. 60%). Among non-White patients, higher income was associated with 3.4 times greater odds of stress reduction compared with lower income (statistically significant), while this association was not significant among White patients. Conclusions: Ellie Fund services are associated with meaningful reductions in stress and improvements in QOL among breast cancer patients. Findings suggest that patients below certain income thresholds may require more intensive or sustained interventions. These results reinforce the value of integrating non-medical supportive care into cancer treatment and highlight its potential role in improving treatment access, stability, and equity. Further research is needed to clarify mechanisms driving QOL improvements and long-term outcomes.

Neighborhood social vulnerability and chemotherapy response in breast cancer patients.

e23083 Background: Sociodemographic disparities are a well-known influence on oncologic outcomes, however their relationship to treatment response remains incompletely characterized. Evaluating neighborhood-level social vulnerability as it relates to standard cytotoxic chemotherapy response offers an opportunity to better understand and address disparities in cancer care. We sought to assess the impact of Social Vulnerability Index (SVI) on response to standard of care cytotoxic chemotherapy in breast cancer patients. Methods: We conducted a retrospective cohort study of 180 breast cancer patients treated with cytotoxic chemotherapy at a safety-net academic center. Patients with stage I–IV disease who received chemotherapy in the neoadjuvant or adjuvant setting with curative intent were included. Neighborhood-level social vulnerability was assigned using the Center for Disease Control SVI, based on zip code of residence at diagnosis. Outcomes were analyzed within 5 years of diagnosis and categorized as alive without documented disease progression, disease progression or recurrence on surveillance imaging, or death. Ordinal logistic regression was used to evaluate the association between SVI and chemotherapy response, adjusting for clinical stage and age at diagnosis. Results: Among the 180 patients, 25% resided in low-SVI zip codes, 28% in low-medium, 31% in medium-high, and 17% in high-SVI zip codes. At 5 years, 61% of patients were alive without documented progression, 22% experienced disease progression, and 17% died. Increasing SVI was directionally associated with worse 5-year outcomes, with higher odds of progression or death per one-category increase in SVI (OR 1.36, 95% CI 0.45–4.08; p = 0.589), consistent with higher observed rates of progression or death in higher SVI categories. The direction of association was consistent across alternative SVI categorizations. Conclusions: In our cohort, higher neighborhood-level social vulnerability trended toward worse 5-year outcomes following cytotoxic chemotherapy among breast cancer patients. Findings were limited by sample size and were not statistically significant, but the consistent directional association supports further study. These results suggest that social vulnerability may meaningfully influence long-term chemotherapy response, highlighting the need for larger studies to inform targeted interventions aimed at mitigating disparities in cancer care.

Comparative effectiveness of doublet versus triplet therapy in high-volume metastatic hormone-sensitive prostate cancer: A real-world evidence study.

e17084 Background: Although the combination of androgen deprivation therapy (ADT) with an androgen receptor pathway inhibitor (ARPI) is the established standard of care for patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), the added benefit of intensifying therapy with docetaxel to create a triplet regimen remains undefined. In the absence of direct comparative randomized trial data, real-world evidence (RWE) is crucial to inform this treatment intensification decision. Methods: Our multicenter retrospective study included patients with high-volume mHSPC (by CHAARTED criteria) who initiated doublet (ADT + ARPI) or triplet (docetaxel + ADT + ARPI) therapy between 2022 and 2024. To mitigate confounding, patients were matched using cardinality matching at a 2:1 ratio. The primary endpoint was 2-year progression-free survival (PFS). Secondary end-points was overall survival (OS). PFS was defined as the time from treatment initiation to clinical/radiological progression, commencement of subsequent systemic therapy, or death from any cause. Results: Of 183 patients 122 received triplet (ADT+docetaxel+abiraterone or ADT+docetaxel+enzalutamide), 61 doublet therapy (ADT+enzalutamide or apalutamide). The triplet regimen demonstrated superior outcomes: 2-year PFS was 75.9% vs. 48.9% (HR 0.50, 95% CI 0.31–0.80) and 2-year OS was 82.9% vs. 66.8% (HR 0.47, 95% CI 0.28–0.79). The benefit of docetaxel addition was pronounced in patients aged < 65 years (PFS: HR 0.28, 95% CI 0.12-0.68; OS: HR 0.17, 95% CI 0.06-0.54), patients with liver metastases (PFS: HR 0.16, 95% CI 0.04-0.68; OS: HR 0.12, 95% 0.02-0.61), Gleason score ≥8 (PFS: HR 0.49, 95% 0.29-0.82; OS: HR 0.45, 95% CI 0.25-0.84) and detectable baseline erythroblasts in blood sample (PFS: HR 0.29, 95% CI 0.11-0.76; OS: HR 0.24, 95% CI 0.07-0.77). No significant survival difference between triplet and doublet therapy was found in patients > 65 years or with metachronous high-volume disease. Conclusions: Real-world data confirms the superiority of triplet therapy for the majority of patients with synchronous high-volume mHSPC. Treatment intensification can be effectively guided by routine clinical characteristics.

National trends in non-Hodgkin lymphoma incidence in the CAR-T era: A population-based analysis using SEER Explorer data.

e19062 Background: Non-Hodgkin lymphoma (NHL) is a common hematologic malignancy in the United States. Chimeric antigen receptor T-cell (CAR-T) therapies were first approved in 2017, representing a major therapeutic milestone. However, population-level incidence trends of NHL in the CAR-T era remain incompletely characterized. We evaluated national NHL incidence trends before and after the introduction of CAR-T therapies using SEER Explorer data. Methods: Using SEER Explorer, we analyzed age-adjusted NHL incidence rates (per 100,000 population) from 2010 to 2021. Era-based comparisons were pre-specified based on FDA approval timelines: pre–CAR-T era (2010–2016) and post–CAR-T era (2018–2021), with 2017 excluded as a transition year. Mean annual incidence rates were calculated for each era. Secondary analyses examined incidence patterns stratified by age group and sex. Results: The mean age-adjusted incidence rate of NHL declined from 19.71 per 100,000 in the pre–CAR-T era to 18.95 per 100,000 in the post–CAR-T era, representing a 3.9% reduction. Across both eras, incidence remained highest among adults aged ≥65 years, who accounted for the majority of NHL cases nationally. Although modest declines were observed in the post–CAR-T era among age groups <65 years, age-related disparities persisted. Males consistently demonstrated higher NHL incidence than females throughout the study period, with parallel temporal trends and modest post–CAR-T declines by sex. Conclusions: In this population-based analysis using age-adjusted SEER data, NHL incidence demonstrated a modest decline in the post–CAR-T era compared with the pre–CAR-T period. After accounting for COVID-19–related reporting disruptions, long-term incidence trends remained stable. Persistently higher incidence among older adults and males highlights ongoing demographic disparities and underscores the need for continued epidemiologic surveillance in the CAR-T era. Population-level incidence patterns of NHL in the pre- and post–CAR-T eras. Outcome Pre–CAR-T (2010–2016) Post–CAR-T (2018–2021) Key Finding Mean age-adjusted incidence (per 100,000) 19.71 18.95 3.9% overall decline Incidence trend (APC/AAPC) — — Modest negative trend Age ≥65 years Highest incidence Highest incidence Majority of cases Age <65 years Lower incidence Modest Declined Consistent pattern Age pattern ↑ with age ↑ with age Persistent disparity Sex pattern Male > female Male > female Stable male predominance Abbreviations: NHL, non-Hodgkin lymphoma; CAR-T, chimeric antigen receptor T-cell; APC, annual Percent Change; AAPC, average Annual Percent Change. Incidence rates are per 100,000 population and age-adjusted to the 2000 US standard population. 2017 was excluded as a transition year.

Predictors of progression, survival, and psychosocial burden in early-stage breast cancer: A real-world cohort study.

e12761 Background: While early-stage breast cancer is associated with high survival rates, recurrence risk and long-term psychosocial morbidity vary widely. Treatment-related factors, such as surgical timing, and procedure type, may influence both oncologic and quality-of-life outcomes. We conducted a real-world analysis to evaluate predictors of progression, survival, and treatment-related morbidity in early-stage breast cancer. Methods: We queried the TriNetX, a US Nationwide de-identified database, to identify female patients above 18 years old with Stage I or II breast cancer. Propensity score matching was performed across cohorts defined by demographics and comorbidities. Outcomes included all-cause mortality, disease progression, lymphedema, chronic pain, depression and anxiety. Odds ratios (OR) and 95% confidence intervals (CI) were calculated over a follow up period from 1 year post-operation to death or loss of follow up. Results: Overall, Stage I patients had significantly lower all-cause mortality (OR 0.30, 95% CI 0.24-0.36) and disease progression (OR 0.39, CI 0.31-0.49) compared to Stage II, along with lower risk of lymphedema, anxiety, and depression. Age was a significant modifier of psychosocial outcomes. Among Stage I patients, those under 50 years had lower rates of chronic pain (OR 0.45, CI 0.29-0.71) and depression (OR 0.62, CI 0.42-0.93) compared to older patients, without differences in mortality or progression. A similar trend was observed in Stage II patients, where younger age was associated with reduced anxiety (OR 0.61, CI 0.39-0.95). Delay in surgery beyond 30 days was not associated with higher mortality or disease progression in either stage. However, patients with delayed surgery in Stage I experienced significantly higher anxiety (OR 1.18, CI 1.03-1.36). Surgical type also influenced outcomes. In Stage I, mastectomy was associated with lower mortality (OR 0.25, CI 0.13-0.48) compared to lumpectomy but resulted in significantly higher rates of lymphedema (OR 2.58, CI 1.23-5.44), depression (OR 1.82, CI 1.20-2.75), and anxiety (OR 1.97, CI 1.38-2.81). A similar pattern was observed in Stage II, where mastectomy was also associated with higher rates of depression (OR 1.88, CI 1.03–3.44) and anxiety (OR 1.73, CI 1.01-2.95), along with a numerically lower, but not statistically significant mortality compared to lumpectomy. Conclusions: Mastectomy may offer survival benefit in Stage I, but is associated with increased psychological and physical complications. While Stage II disease is linked to worse cancer outcomes, decisions about surgical approach play a significant role in shaping long-term survivorship quality. These findings emphasize the need for individualized treatment strategies that weigh both clinical efficacy and long-term quality of life.

Exercise therapy in survivors of gastroesophageal cancer: A phase I, randomized dose-finding study of an individually tailored, remotely supervised exercise intervention.

TPS12169 Background: Advances in perioperative systemic therapy and surgery have extended survival for patients with locoregional gastroesophageal cancer (GEC). However, intensive multimodality treatment often causes substantial physical function decline, leading to loss of independence and poor quality of life. No evidence-based interventions are currently approved to prevent or reverse this decline. Although exercise can improve fatigue, quality of life, and functional outcomes in other malignancies, it remains poorly studied in survivors of GEC. In patients with colon cancer, exercise after treatment is feasible, improves quality of life, and alleviates anxiety and depression. More recently, the CHALLENGE randomized trial demonstrated that a structured, in-person, supervised exercise intervention after chemotherapy for early-stage colon cancer can improve physical function, decrease cancer recurrence, and increase survival versus health education alone. However, the in-person exercise intervention was limited by low adherence and lack of exercise dose optimization, with only one target dose tested. These findings may not generalize to survivors of GEC, where treatment is more intensive and surgery more morbid. In this patient population, we hypothesize that aerobic exercise up to 225 minutes per week will be feasible, but higher doses will lead to lower levels of relative exercise dose intensity (REDI), defined as the ratio of completed to prescribed exercise dose over the course of the intervention. Methods: This phase I, randomized dose-finding study will enroll 24 adults (age ≥18 years) with stage I-III GEC who completed perioperative systemic therapy within 12 months and are sedentary ( < 30 minutes/week of moderate-to-vigorous physical activity). Participants will be randomized 1:1:1 to one of three individually tailored, remotely supervised aerobic programs led by an exercise physiologist. Each 16-week program will target either 75 minutes (25 minutes, 3x/week), 140 minutes (35 minutes, 4x/week), or 225 minutes (45 minutes, 5x/week) of moderate-intensity exercise. Demographic and disease/treatment data will be collected at enrollment. Assessments at baseline and post-intervention include measures of cardiorespiratory fitness (submaximal exercise test), other measures of physical, cognitive, and psychological function, and quality of life. Heart rate, body weight/composition, and step count will be measured throughout using remote monitoring devices. The primary outcome is feasibility, as measured by the REDI. An exercise dose will be considered feasible if > 60% of the participants (≥5/8 per arm) achieve a REDI of > 75%. Secondary outcomes include changes in cardiorespiratory fitness and other functional and quality of life measures. This study has been IRB approved and is ongoing (NCI202600630). Clinical trial information: NCI202600630 .

A phase 1 study of BGB-A3055 (anti-CCR8) with or without tislelizumab (anti–PD-1) in patients with solid tumors.

2523 Background: BGB-A3055 is a humanized monoclonal antibody targeting C-C motif chemokine receptor 8 (CCR8), a receptor highly expressed on intratumoral regulatory T cells (Tregs). CCR8 overexpression correlates with poor prognosis in certain tumor types. Preclinical studies have shown potent antitumor activity of BGB-A3055 . Here, we present results from a phase 1a dose-escalation trial of BGB-A3055 alone (Part A [A]) or combined with tislelizumab (TIS; Part B [B]) in patients (pts) with advanced or metastatic solid tumors (NCT05935098). Methods: Eligible pts had histologically confirmed advanced or metastatic solid tumors with high prevalence of CCR8 expression. In A, pts received BGB-A3055 (six dose levels) intravenously (IV) every 3 weeks (Q3W). In B, pts received BGB-A3055 (six dose levels) and TIS 200 mg IV Q3W . Primary endpoint was safety; secondary endpoints included preliminary antitumor activity (RECIST v1.1). Results: As of Nov 19, 2025, 98 pts were treated with BGB-A3055 ± TIS (A: n=42; B: n=56). Median (range) study follow-up was 3.94 (0.9-19.0) months in A and 4.67 (0.5-16.8) months in B. Treatment-emergent adverse events (TEAEs) are provided in the Table. The most common BGB-A3055-related TEAEs were neutrophil count decreased (23.8%) in A and pyrexia (23.2%) in B. The most common serious TEAE was immune-mediated enterocolitis (A: 4.8%; B: 7.1%). The most common immune-mediated adverse events (imAEs) were rash, rash maculo-papular, and hypothyroidism in A (7.1% each) and rash maculo-papular in B (17.9%). Dose-limiting toxicities occurred in 1 pt in A (immune-mediated hepatitis) and 3 pts in B (colitis, nephrotic syndrome, and rash maculo-papular in a single pt each). No treatment-related TEAEs leading to death were reported. Maximum tolerated dose was not reached. Unconfirmed objective response rate was 7.5% (95% confidence interval [CI]: 1.6-20.4; 3 partial responses [PRs]) in A and 18.2% (95% CI: 9.1-30.9; 1 complete response and 9 PRs) in B. Disease control rate was 35.0% (95% CI: 20.6-51.7) in A and 56.4% (95% CI: 42.3-69.7) in B. Among the 13 responders, 6 received prior immunotherapies. Robust Treg reduction was observed in peripheral blood and tumor tissue post-treatment, indicating potent on-target pharmacodynamic activity of BGB-A3055. Conclusions: BGB-A3055 ± TIS demonstrated a safety profile consistent with selective CCR8 on-target effects in pts with advanced solid tumors and had preliminary antitumor activity. Clinical trial information: NCT05935098 . Part ABGB-A3055 monotherapy(n=42) Part BBGB-A3055 + TIS(n=56) Any TEAE, n (%) 41 (97.6) 55 (98.2) Grade ≥3 26 (61.9) 47 (83.9) Serious 17 (40.5) 37 (66.1) Leading to death 1 (2.4) 3 (5.4) Leading to treatment discontinuation 9 (21.4) 23 (41.1) Any BGB-A3055-related TEAE, n (%) 35 (83.3) 53 (94.6) Grade ≥3 18 (42.9) 31 (55.4) Serious 5 (11.9) 20 (35.7) Any imAE, n (%) 15 (35.7) 33 (58.9)

Impact of concomitant antibiotic exposure on overall survival in patients with esophagogastric cancer treated with immune checkpoint inhibitors: A real-world cohort study.

11160 Background: Gut microbiota composition plays a critical role in mediating response to immune checkpoint inhibitors (ICIs). Antibiotic exposure has been associated with impaired ICI efficacy across tumor types; however, data specific to esophagogastric cancers remain limited. We evaluated the association between peritreatment antibiotic exposure and overall survival (OS) among patients with advanced esophagogastric cancer receiving ICIs in routine clinical practice. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adult patients with advanced or metastatic esophageal or gastric adenocarcinoma who received nivolumab- or pembrolizumab-based therapy between 2016 and 2024 were identified. Patients were categorized as antibiotic-exposed (receipt of systemic antibiotics within 60 days before or after ICI initiation) and non-exposed (no documented antibiotic exposure during the same period). Cohorts were 1:1 propensity score matched for age, sex, cancer subtype, Charlson comorbidity index, infection-related diagnoses, baseline corticosteroid use, and hospitalization within 30 days prior to ICI initiation. The primary endpoint was OS. Kaplan–Meier and Cox proportional hazards models were used for analysis. Sensitivity analyses evaluated the timing and duration of antibiotic exposure. Results: After matching, 3,024 patients were included (1,512 per cohort). Baseline characteristics were well balanced (mean age 63.7 years; 34% female; median Charlson comorbidity index 5). At a median follow-up of 19.8 months, antibiotic exposure was associated with significantly worse overall survival compared with non-exposure. Median OS was 10.6 months in antibiotic-exposed patients versus 14.3 months in non-exposed patients (log-rank p < 0.001). Antibiotic exposure was independently associated with inferior OS (HR 1.34, 95% CI 1.22–1.47). The negative association was most pronounced among patients with broad-spectrum antibiotic exposure (HR 1.41) and among those with antibiotic exposure within 30 days prior to ICI initiation (HR 1.38). Findings remained robust in sensitivity analyses excluding patients with documented sepsis or prolonged hospitalization. Conclusions: In this large real-world cohort of patients with esophagogastric cancer treated with ICIs, peritreatment antibiotic exposure was associated with significantly worse overall survival. These findings further support the role of the gut microbiome in modulating immunotherapy response and underscore the importance of judicious antibiotic use during ICI therapy.

Clinical significance of neutrophil-to-lymphocyte ratio dynamics during cabozantinib therapy in unresectable hepatocellular carcinoma.

e16240 Background: Neutrophil-to-lymphocyte ratio (NLR) dynamics have been reported as prognostic biomarkers in hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitor (ICI)–based regimens and other molecular targeted agents. However, the clinical relevance of NLR dynamics during cabozantinib therapy remains unclear, particularly in patients previously exposed to ICIs. Methods: We retrospectively analyzed 62 patients with unresectable HCC treated with cabozantinib. Baseline NLR was calculated prior to treatment initiation. Early on-treatment NLR dynamics were assessed at 4 weeks using the log-transformed NLR ratio (week 4/baseline). Associations between baseline NLR, NLR dynamics, and progression-free survival (PFS) and overall survival (OS) were evaluated. Results: The median age was 75 years, 77% were male, and 77% had Child–Pugh class A liver function. BCLC stage C disease accounted for 61% of patients. Cabozantinib was administered as second- or third-line therapy in 61% of patients and as fourth-line or later therapy in 39%. Prior ICI-based regimens had been used in 87% of patients. With a median follow-up of 9.7 months, median PFS and OS were 3.8 months (95% CI, 3.0–4.9) and 15.8 months (95% CI, 9.2–19.1), respectively. Baseline NLR was not significantly associated with PFS or OS. At 4 weeks, the median log-transformed NLR ratio was −0.13 (IQR, −0.41 to 0.16). However, early NLR dynamics did not stratify PFS or OS. These findings were consistent across treatment lines. Conclusions: These results suggest that the prognostic relevance of NLR dynamics during cabozantinib therapy may differ from that observed with other systemic treatments for HCC. From a clinical perspective, baseline or early on-treatment NLR may be less informative for patient stratification during cabozantinib therapy.

Penpulimab plus oral anlotinib and capecitabine as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC): A multicenter, single-arm, phase 2 clinical trial.

6036 Background: Patients (pts) with NPC progressing after intensive radical treatment often have limited treatment tolerance and poor prognosis. Incorporation of oral agents into triple therapy combining chemotherapy, immunotherapy, and targeted therapy may improve efficacy while reducing toxicity. Methods: This multicenter, single-arm, phase 2 trial evaluated first-line penpulimab (a PD-1 blockade) plus oral anlotinib (a tyrosine kinase inhibitor) and capecitabine in pts with R/M NPC previously treated with radical chemo/radiotherapy for non-metastatic disease. Pts from 4 academic hospitals in China received 4–6 cycles of penpulimab 200 mg IV d1, anlotinib 10 mg PO qd d1–14, and capecitabine 650 mg/m 2 PO bid d1–21 q3w, followed by penpulimab-capecitabine maintenance until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and quality-of-life (QoL; assessed by the EORTC and FACT surveys). This trial was to be considered positive if the median PFS significantly reached an expected value of 11 mo than a historical threshold of 7 mo, with a 1-sided α of 2.5% and 80% power. This trial was registered with ClinicalTrials.gov (NCT05807880) and is now ongoing. Results: Between Sept. 2023 and July 2025, 59 eligible pts (median [IQR] age, 50 [40–58] yrs; 33.9% women) were included, of which 23 (38.9%) and 41 (69.5%) pts had recurrent and metastatic diseases, respectively. Overall, 74.6% (44/59) of pts completed at least the required 4 cycles of the triple therapy. After a median follow-up of 10 mo (data cutoff: Nov. 14, 2025), the median PFS was 13.5 mo (95% CI, 13.1–not reached [NR]) and the 12-mo PFS was 64.4% (95% CI, 50.3–78.5%). The median OS was NR, and the 12-mo OS was 87.8% (95% CI, 78.4–97.2%). The ORR was 71.4% in 56 pts with available assessments, including complete and partial responses in 5 (8.9%) and 35 (62.5%) pts, respectively. Pts with baseline EBV DNA ≤ 4000 copies/mL had higher median PFS (NR vs 6.0 mo) and 12-mo PFS rate (71.3% vs 41.7%) than those with EBV DNA > 4000 copies/mL ( p = 0.024). Twelve (20.3%) pts had grade 3–4 acute treatment-related adverse events (trAEs), with the most frequent trAE of palmar–plantar erythrodysesthesia (5.1%). Fifty-seven (96.6%) pts had all-grade trAEs, mainly including palmar–plantar erythrodysesthesia (39.0%), hypothyroidism (37.3%), stomatitis (33.9%), sore throat (32.2%), anemia (27.1%), and leukopenia (23.7%). Two treatment-related deaths were observed. Twenty-nine of 37 QoL domains (78.4%) remained stable or showed clinically meaningful improvement. Conclusions: First-line therapy of penpulimab plus oral anlotinib and capecitabine provides promising antitumor efficacy, low toxicity, and favorable QoL for pts with R/M NPC. Clinical trial information: NCT05807880 .

Molecular and demographic landscape of advanced cutaneous melanoma: A 10-year experience of a national reference laboratory in Colombia (2014–2023).

e21523 Background: Cutaneous melanoma (CM) exhibits significant biological heterogeneity. While BRAF V600 mutations are reported in 40-50% of cases globally, their frequency varies by ethnicity. In Latin America, subtypes like acral lentiginous and mucosal melanoma are more prevalent, presenting distinct mutational profiles. We characterized the BRAF status and demographics of a large cohort processed at a National Reference Laboratory to address the regional data gap in precision oncology. Methods: A retrospective observational study was conducted on 604 patients with advanced CM (Stages III-IV) whose samples were centralized and processed at a single reference unit (UDHO) in Cali, Colombia. BRAF mutations in Exon 15 (codons 600-601) and Exon 11 (codons 466-469) were detected using qPCR with IVD/CE certified kits. DNA was extracted from FFPE tissue with a minimum neoplastic content of 10%, analyzed via automated software (Oncology Life Science Research) to ensure standardization. Results: The cohort (n = 604) showed a nearly balanced sex distribution (51.5% male, 48.5% female). Patient age ranged from 12 to 90 years, with 76.8% of the population being older than 50 years at diagnosis. BRAF mutations were identified in 26.7% of valid cases, while 67.5% were wild-type. Among mutated cases, V600K was specifically identified in 14.3%. Notably, a marked health equity gap was observed: 94.4% of molecular tests were sponsored by the pharmaceutical industry, with only 5.6% covered by national health entities. The invalid result rate was low (5.8%), reflecting high pre-analytical quality. Conclusions: The population analyzed at this National Reference Laboratory presents a distinct molecular signature with a significantly lower BRAF mutation rate (26.7%) than global averages. This 10-year experience underscores the importance of centralized high-quality testing to identify regional genetic particularities. Our findings highlight a major health equity challenge, as diagnostic access remains heavily dependent on industry sponsorship, and emphasize the need for tailored therapeutic strategies in the Colombian population.

Ultrasensitive tumor-informed ctDNA MRD detection to identify metastatic relapse and as predictor of recurrence-free survival following resection of early-stage NSCLC.

3060 Background: After curative-intent resection of non-small cell lung cancer (NSCLC), patients remain at risk for metastatic relapse and development of second primary malignancies. Circulating tumor DNA (ctDNA) molecular residual disease (MRD) detection has prognostic value, but sensitivity in early-stage disease has been limited. We evaluated an ultrasensitive tumor-informed whole-genome sequencing (WGS) assay that leverages phased variants (PVs) for longitudinal MRD detection in a cohort from the ctDNA Lung DETECT study (NCT05254782). Methods: Patients with clinical stage I NSCLC treated with upfront surgery were enrolled at Princess Margaret Cancer Centre/University Health Network. Resected tumor tissue underwent WGS to generate personalized tumor-informed assays tracking up to 5000 somatic variants, including prioritized PVs prioritized (CLARITY, Foresight Diagnostics). Plasma samples (pre-operative, 3-6 weeks post-operative landmark, 6 months, 12 months, and at recurrence) were analyzed retrospectively with labs blinded to outcomes. Endpoints were MRD detection, recurrence free survival (RFS), MRD clearance patterns. Results: Of 128 clinical stage I patients with banked samples, 121 (95%) had sufficient tumor for WGS. Pathologic stage distribution AJCC 8th Ed. was stage 0/I/II/III/IV (n=1/86/22/1). Among 121 patients, 16 (13%) experienced distant recurrence and 15 (12%) developed second primary malignancies: lung, breast, ovarian, prostate and sarcoma. MRD detection at pre-operative (HR 5.6, p=0.002) and post-operative landmark (HR 4.2, p=0.002) was significantly associated with RFS. MRD+ at 12 months post-resection demonstrated stronger prognostic value, as 97% (91/94) MRD-negative patients remained recurrence free compared to 15% (2/13) MRD+ patients (HR 48.3, p<0.0001). We assessed MRD clearance between post-op landmark and later samples in patients who received adjuvant therapy. In total, 34 received adjuvant therapy; of these, 10 were MRD+ post-operatively with at least 1 subsequent sample. MRD clearance during or after adjuvant therapy was significantly associated with improved RFS (p=0.019). Patients with MRD clearance at any time after adjuvant therapy had 0% recurrence (0/4), while 83% (5/6) patients who failed to clear MRD despite adjuvant therapy had recurrence. In recurrence, MRD was detected in 94% (15/16) prior to or at recurrence. Only 1 MRD-negative patient recurred, >2 years after the last assessed sample. Conclusions: Ultrasensitive tumor-informed ctDNA MRD detection identifies patients at high risk for metastatic relapse following NSCLC resection, including pathologic Stage I, and may provide substantial lead time over conventional imaging. Clearance of post-surgical MRD with adjuvant therapy may inform post-resection surveillance and future studies of adjuvant therapy. Clinical trial information: NCT05254782 .

Real-world evaluation of germline pathogenic variants (PVs) in cancer-predisposition genes among unselected South Asian women with breast or ovarian cancer.

10513 Background: Prior reports of high frequency of BRCA1 and BRCA2 ( BRCA1/2 ) PVs among South Asian women from Bangladesh, India, Nepal, and Pakistan with breast or ovarian cancer require validation in large prospective unselected cohorts. Methods: Individual-level anonymized patient data from two prospective cohorts were pooled to evaluate the prevalence of germline PVs among South Asian women: the South Asian Regional Alliance for Hereditary Cancers (SARAH Consortium) in Bangladesh, Nepal, and Pakistan, and the previously reported Nurse-led Genetic Counseling and Awareness (NuGenA) expansion cohort in India. Both studies enrolled consecutive cases of histologically confirmed newly diagnosed breast or epithelial ovarian cancer irrespective of age at diagnosis or family history. In both studies, participants completed questionnaires on personal and family history (first-, second- or third-degree) and provided blood for germline genetic testing after written consent. PVs in cancer predisposition genes including ATM, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, MLH1, MSH2, MSH6, PALB2, RAD51C, RAD51D, and TP53 were identified as part of the studies utilizing a multigene panel and the results were returned to ordering clinicians. The data cutoff date for this analysis was November 30, 2025. Results: The analysis included 1,711 South Asian women with breast (n=1,210) or ovarian (n=501) cancer. A family history of breast or ovarian cancer was noted in 177 (10.3%). Among breast cancers, 94% were invasive, 84% were ductal, 35% were triple-negative and over two-thirds presented with nodal involvement. Germline PVs across 13 predisposition genes were observed in 17.7% of breast and 35.9% of ovarian cancers. Notably, BRCA1/2 PVs accounted for most of these PV (13.6% of breast and 28.3% of ovarian cancer cases) with PVs in all genes except BRCA1/2 under 1%. The frequency of BRCA1/2 PVs was 24.4% in triple-negative breast cancer and 8.0% in ER+/HER2-. BRCA1/2 PV carriers were diagnosed with breast cancer at a younger age than non-carriers (Median age: 42 vs 46 years, P<0.001), with no age difference observed in ovarian cancer (50 vs. 51 years, P=0.79). Notably, among the 306 BRCA1/2 PV carriers identified, 229 (74.2%) did not report a family history of breast or ovarian cancer. Conclusions: We confirm a high prevalence of BRCA1/2 PVs among unselected South Asian women with either breast or ovarian cancer. The observations of younger age at cancer diagnosis, and low rates of family history support the need for population-specific germline genetic testing and risk management strategies in South Asia.

Triplet combination of anlotinib plus nab-paclitaxel and gemcitabine (AG) as a first-line strategy for advanced primary cardiac angiosarcoma: A high-volume center experience.

11562 Background: Primary cardiac angiosarcoma (PCAS) is an exceedingly rare and lethal mesenchymal malignancy characterized by aggressive growth and high metastatic potential. Despite the use of taxane-based regimens, the prognosis remains dismal, with a historical median overall survival (mOS) of approximately 11 months. Given the highly vascular nature of PCAS, we hypothesized that integrating a multi-target anti-angiogenic TKI (anlotinib) with cytotoxic chemotherapy could synergistically improve outcomes. This study evaluated the efficacy and safety of anlotinib plus nab-paclitaxel and gemcitabine (AG) in advanced PCAS. Methods: We retrospectively analyzed patients with metastatic or unresectable PCAS treated at Zhongshan Hospital, Fudan University. The triplet regimen consisted of anlotinib (8-12 mg QD, days 1-14, q3w), nab-paclitaxel (200 mg), and gemcitabine (1000 mg/m²) on days 1 and 8 every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety (CTCAE v5.0). Survival outcomes were estimated using the Kaplan-Meier method and compared via log-rank tests. Results: A total of 24 patients were included, with a median age of 44 years. Most tumors (91.7%) originated in the right atrium, and 70.8% of patients received this regimen as first-line therapy. Efficacy: At a median follow-up of 31.4 months, the ORR was 62.5% and the DCR was 95.8%. Survival: The median PFS was 9.5 months (95% CI, 8.4-20.7). Notably, the median OS reached 24.9 months (95% CI, 15.2-NR), significantly exceeding historical benchmarks. Prognostic Indicators: Subgroup analysis identified liver metastasis (45.8%) as a significant negative prognostic factor for PFS (p = 0.018). Additionally, a numerical trend toward shorter survival was observed in patients with baseline D-dimer > 5 mg/dL (Median OS: 5.5 vs. 10.5 months; p = 0.428). Safety: Treatment-related adverse events (TRAEs) of any grade occurred in 95.8% of patients. Grade≥3 TRAEs (41.7%) were primarily hematological (neutropenia, thrombocytopenia) and were manageable via dose modification. No severe treatment-related cardiotoxicity was observed. Conclusions: The triplet combination of anlotinib and AG demonstrates unprecedented survival benefits and a manageable safety profile in advanced PCAS. With a mOS exceeding twice the historical data, this regimen represents a potent new treatment strategy. Liver involvement serves as a critical prognostic indicator for risk stratification, while the clinical significance of baseline D-dimer levels as a surrogate marker for tumor burden warrants further investigation in larger cohorts.