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Long term outcomes of implantable central venous access devices (chemoports) in patients with malignancies: A prospective observational study.

e23349 Background: Central venous access devices (CVADs) play a critical role in the delivery of long-term intravenous therapy in oncology. Despite advances in device design and maintenance, chemoport related complications particularly infections remain clinically relevant, with limited prospective data from India and other low and middle income countries. This study evaluated the indications, complications, and outcomes associated with chemoport use in patients with malignancies. Methods: This prospective observational study was conducted over 18 months at the Department of Medical Oncology, Apollo Hospital International Ltd, India. Fifty consecutive patients with histologically confirmed malignancies undergoing chemoport insertion were enrolled. All devices were placed under ultrasound guidance, followed by routine post-procedure chest radiography. Patients were assessed for indications of chemoport insertion, underlaying malignancy and prospectively monitored for catheter care, complications, and outcomes. Complications were categorised as infectious, mechanical, procedure-related, thrombotic or other. Results: Fifty patients were included, with a mean age of 51.7 ± 18.7 years (range, 4–80); 74% were female. Breast cancer was the most common diagnosis (36%), followed by colorectal (18%), gynecologic (10%), sarcoma (6%), and hepatobiliary malignancies (6%). Infusional chemotherapy was administered in 98% of patients. The mean duration of catheter use was 8.4 months (range, 15 days–18 months). The right internal jugular vein was the most frequently used access site (84%). Across 983 catheter-days, six complications were observed, corresponding to a rate of 6.1 per 1,000 catheter-days. Mechanical complications occurred in two patients (4%). Infectious complications were documented in four patients (8%), including catheter-associated bloodstream infection (n=3) and port-site infection (n=1). Isolated organisms included Escherichia coli and Staphylococcus species. Infections resolved with conservative management in three patients; catheter removal was required in one patient. No immediate post-procedure complications were noted. Conclusions: Chemoport use demonstrated a favourable safety profile with a low complication rate in patients with malignancies. Infection was the most frequent complication, underscoring the importance of meticulous aseptic technique and vigilant catheter surveillance to minimize adverse events.

INCA033890-303: A randomized, double-blind, phase 3 study of FOLFOX and bevacizumab with or without INCA33890 in the first-line treatment of metastatic microsatellite-stable colorectal cancer.

TPS3683 Background: Immune checkpoint inhibitors have demonstrated limited efficacy in the treatment of microsatellite stable colorectal cancer (MSS CRC), especially when the liver is involved. Transforming growth factor β (TGFβ) signaling within the tumor microenvironment suppresses T-cell proliferation and effector function, contributing to an immune-excluded phenotype. Although clinical targeting of the TGFβ pathway has been previously attempted, these approaches have been hampered by limited efficacy and significant toxicity. INCA33890 is a first-in-class bispecific antibody targeting both TGFβ receptor 2 (TGFβR2) and programmed cell death protein 1 (PD-1). This molecule is designed to inhibit TGFβR2 and PD-1 signaling specifically in PD-1–positive cells, sparing PD-1–negative cells from TGFβ inhibition. In the phase 1 INCA 33890-101 study (NCT05836324), INCA33890 demonstrated a manageable safety profile and durable single-agent activity in patients with refractory MSS CRC, including in patients with active liver metastases. The monotherapy objective response rate (ORR) was 15.2% overall (n = 105), including 12.0% in patients with liver metastases (n = 75) and 23.3% (n = 30) in patients without liver metastases. Methods: The multicenter, global, phase 3 INCA033890-303 study (NCT07284849) activated in December 2025 and is planned to open at 225 sites across 23 countries. The primary objective of this study is to evaluate the efficacy of INCA33890 versus intravenous placebo, each in combination with FOLFOX and bevacizumab, as first-line treatment for patients with previously untreated, histologically confirmed, unresectable metastatic MSS CRC. Prior neoadjuvant or adjuvant therapy is allowed provided there was no recurrence within 12 months of treatment completion. Key exclusion criteria include microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) status, BRAF V600E mutation, untreated or progressing brain metastases, and active autoimmune disease requiring systemic immunosuppression. Approximately 700 patients will be randomized 1:1 to receive intravenous INCA33890 or placebo, each in combination with FOLFOX and bevacizumab. Randomization will be stratified by tumor sidedness, the presence of liver metastases, and programmed death-ligand 1 (PD-L1) score. The primary endpoint is progression-free survival as assessed by investigators. The key secondary endpoint is overall survival. Additional secondary endpoints are ORR, safety and tolerability, duration of response, and patient-reported outcomes. Trial enrollment is ongoing. Clinical trial information: NCT07284849 .

Efficacy and safety of antibody-drug conjugates in advanced colorectal cancer: A systematic review and single-arm meta-analysis of early-phase clinical trials.

e15616 Background: Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. Despite standard-of-care systemic therapy for metastatic CRC (mCRC), most patients experience disease progression with limited subsequent treatment options. Antibody-drug conjugates (ADCs) deliver cytotoxic payloads directly to tumor cells via tumor-specific monoclonal antibodies and represent a promising therapeutic class. While multiple ADCs are approved for other solid tumors, disease-specific ADC options for CRC remain an unmet need. This meta-analysis evaluates the efficacy and safety of ADCs in advanced CRC. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through December 2025 for clinical trials evaluating ADCs in advanced/metastatic CRC. Primary outcomes included median progression-free survival (mPFS) and median overall survival (mOS). Safety outcomes included any grade and grade ≥3 treatment-related adverse events (TRAEs). Pooled estimates were calculated using random-effects models with 95% confidence intervals (CIs). Statistical analyses were performed using R software. Results: Four early-phase clinical trials comprising 289 patients were included. ADCs evaluated included indusatumab vedotin, labetuzumab govitecan, trastuzumab deruxtecan, and precemtabart tocentecan. Median treatment duration ranged from 6 to 24 weeks across studies. Pooled analysis demonstrated a mPFS of 4.39 months (95% CI: 2.67-6.12; I² = 93.9%, p < 0.0001). Among 168 patients with available OS data, mOS was 10.1 months (95% CI: 3.7-16.4; I² = 96.5%, p < 0.0001). Safety analysis of 203 patients revealed any-grade TRAEs in 99.8% (95% CI: 98.1-100) and grade ≥3 TRAEs in 55.2% (95% CI: 41.6-68.5; I² = 74%, p = 0.009). Conclusions: ADCs demonstrate modest antitumor activity in heavily pretreated advanced CRC with manageable but notable toxicity. The mPFS of 4.39 months and mOS of 10.1 months suggest potential clinical benefit in this population with limited therapeutic options. However, the high incidence of any-grade TRAEs (99.8%) and grade ≥3 TRAEs (55.2%) warrants careful patient selection and monitoring. Significant heterogeneity indicates efficacy varies by ADC platform. Patient selection strategies and randomized controlled trials are warranted to definitively establish the role of ADCs in CRC.

Maternal and neonatal complications associated with breast cancer systemic treatments: A VigiBase disproportionality analysis study.

626 Background: Pregnancy-associated breast cancer (PrBC) presents unique diagnostic and therapeutic challenges, with rising incidence due to delayed childbearing. Understanding maternal-fetal safety of systemic anticancer therapies during pregnancy is critical for informed treatment planning. Methods: We performed a case/non-case disproportionality analysis using VigiBase, the WHO global pharmacovigilance database up to January 2024, to evaluate maternal and fetal/neonatal outcomes associated with breast cancer (BC) systemic treatments. We included reports involving pregnancy, antineoplastic treatment during pregnancy, and cancer. The exposure group consisted of reports mentioning a BC treatment at any time during pregnancy. The primary outcome was the reporting odds ratio (ROR) of maternal-fetal complications in the BC treatment group involving at least one of the four main BC treatments: doxorubicin, epirubicin, docetaxel, paclitaxel, compared to other anticancer treatments. Secondary analyses assessed outcomes with all BC treatments and trimester-specific risks of the four main treatments. Results: Of 3,310 pregnancy-related reports, 1,789 involved BC treatments. Median maternal age was 27.4 years (standard deviation SD 13.8) in the BC treatment group versus 29.3 years (SD 11.7) in the other anticancer treatment group. Adverse pregnancy or neonatal outcomes were reported in 998 (55.8%) BC treatment reports versus 470 (30.9%) in other anticancer treatments. Anthracyclines were associated with neonatal immunodeficiency (ROR=11.0, 95%CI 3.2–40), hematologic disorders (ROR=1.7, 95%CI 1.1–2.5), infections (ROR=2.3, 95%CI 1.4–3.8), and pregnancy complications including IUGR (ROR=2.1, 95%CI 1.7–2.7) and hypertension/pre-eclampsia (ROR=1.9, 95%CI 1.2–2.9). Epirubicin was linked to craniofacial (ROR=7.6, 95%CI 2.5–23.5) and genitourinary malformations (ROR=6.3, 95%CI 2.1–18.9). Taxanes were associated with IUGR (paclitaxel ROR=2.8; docetaxel ROR=2.8), with paclitaxel linked to sensory defects (ROR=5.2, 95%CI 2.2–12.3) and hyperbilirubinemia (ROR=4.1, 95%CI 2.0–8.4), and docetaxel to neonatal neurologic disorders (ROR=3.6, 95%CI 1.4–9.3). First-trimester exposure (n=26) markedly increased risks of congenital malformations, i.e. face (ROR=13, 95%CI 2-79) and musculoskeletal malformation (ROR=8, 95%CI 1.1-60). Conclusions: BC treatments during pregnancy are associated with increased specific maternal and neonatal risks, with distinct drug- and trimester-specific variations. These findings highlight the need for individualized treatment planning and targeted fetal surveillance.

Impact of radiation interruption and associated factors on overall survival in head and neck cancer at Tikur Anbessa Specialized Hospital, Ethiopia.

e18058 Background: Unplanned interruption in radical radiotherapy for head and neck squamous cell carcinoma is associated with poorer outcome. In Ethiopia, however, the effect of interruption and contributing factors on overall survival have not been well-studied. Methods: We retrospectively analyzed the records of 126 patients enrolled for radical radiotherapy using a linear accelerator in our tertiary hospital from May 2021 to February 2024. We summarized all of the relevant information such as patient characteristics, treatment received, treatment outcomes, overall treatment time, as well as more information of treatment interruption were collected. Overall survival was estimated using the Kaplan-Meier method and verified by log-rank test. Variables with a log-rank value < 0.05 were considered significant associations. Results: Most patients were in the age group of 37-61 years with males comprising 64.3% of cases. The Nasopharynx was the most common subsite involved (50%) followed by the oral cavity (20.63%) and the larynx (15.08 %). The average radiotherapy dose prescribed was 68.71Gy (SD±3.262), while the average dose received was 62.36Gy (SD±14.604). Concurrent chemoradiation was given to 43% of patients. The mean radiotherapy treatment time (RTT), including interruptions, was 49 days, while the average interruption duration was 8 days. Treatment interruption occurred in 82.5 %, of which radiotherapy machine-related issues contributed to 44.5% followed by holiday at 34.86%. Approximately 50% of patients experienced multiple interruptions during treatment. The proportion of patients with treatment interruption time ≤ 5 days was 58 (49.6 %). At the time of this retrospective review, 77 patients (61.11%) were alive, with a median follow-up of 13 months, while 38(30.6%) patients died. The 1-year overall survival rate of all patient’s cohort was 65% (95%CI 57.2,75.3). Univariate and multivariate analysis showed radiation break and duration of interruption exceeding 5 days were a significant prognostic factors for overall survival. The presence of radiation break was a 2.65 times increased risk chance of poor survival compared to those without interruption (HR=2.654, 1.313-6.725, P=0.025). In addition, longer than 5 days length of interruption was an independent predictor of poor survival compared to interruption less than 5 days (HR=2.036, 1.009-4.1017, P=0.031). Conclusions: The presence of radiation break and the length of interruption exceeding 5 days are independent predictors of poor overall survival in head and neck squamous cell cancer patients undergoing radical radiotherapy. We should minimize the interruption of radiotherapy whenever possible to improve patients' outcomes.

Multi-modal quality improvement's impact on colorectal cancer screening among people experiencing homelessness at a safety-net clinic.

e23290 Background: Preventive cancer screening rates are low among people experiencing homelessness (PEH), contributing to high cancer-related mortality. Fecal immunohistochemical tests (FITs) paired with quality improvement (QI) offer a scalable approach to promote colorectal cancer (CRC) screening in PEH, but evidence is limited. This Lean QI project aimed to improve CRC screening rates among PEH at Venice Family Clinic (VFC), a federally qualified health center in Los Angeles. Methods: Building on prior root cause analysis at The People Concern Annenberg Access Center (OPCC), a PEH-serving site within VFC, five interventions were sequentially employed over each of five months (Apr-Aug 2025): 1) shifting staff roles for FIT handling; 2) permanent $10 grocery card incentive for FIT return; 3) clinic posters promoting screening; 4) provider training to discuss bathroom access; 5) visual-based CRC and FIT education. Measures were obtained monthly including CRC screening rate (outcome), FIT order rate, and FIT completion rate within 2 months (process), with balance measures pending. Pre- (Dec 2024-Mar 2025) and post-intervention (Apr-Nov 2025) comparisons were made against a concurrent control clinic within VFC using a difference-in-differences (DiD) design. Logistic regression estimated pre–post changes and DiD odds ratios. Parallel trends were assessed with pre-intervention slope comparisons. Event study analyses were conducted when appropriate. Results: Baseline characteristics and CRC screening disparities at VFC were previously reported. OPCC saw 36.5 ± 9.6 screening-eligible PEH per month across the study period compared to 236.3 ± 29.8 PEH at the control clinic. CRC screening rates for PEH at OPCC increased from 26.3% pre- to 42.5% post-intervention (OR 2.07, 95% CI 1.35-3.17; p<0.001) but declined at the control clinic (32.6% to 29.2%; OR 0.85, 95% CI 0.72-1.01; p=0.062). DiD analysis showed significant intervention effect (OR 2.43, 95% CI 1.54-3.84; p<0.001) with a null placebo test (OR 1.08; p=0.688). Event study analysis indicated the largest post-intervention gain began in month three. FIT order rates for eligible PEH rose at OPCC from 27.1% to 70.3% (OR 6.35, 95% CI 3.71-10.87; p<0.001) and modestly at the control clinic (23.4% to 36.5%; OR 1.88, 95% CI 1.52-2.33; p<0.001). FIT completion rates increased at OPCC from 15.6% to 35.8% (OR 3.02, 95% CI 1.08-8.40; p<0.05) but declined at the control clinic (40.7% to 12.9%; OR 0.22, 95% CI 0.14-0.33; p<0.001). Pre-intervention trends for FIT process measures were non-parallel, limiting causality. Conclusions: A multi-modal QI intervention was associated with significant improvement across all CRC screening measures for PEH at a safety-net setting, with shifted staff roles and FIT incentives seeming to most benefit total screening rates. Future work aims to target linkage to colonoscopy and oncology care.

Comorbidity-related medical expenditures and health outcomes in cancer patients.

1641 Background: Comorbidities are common among adults with cancer and necessitate effective medical management. However, research is scarce on how cancer affects healthcare utilization and expenditures for comorbid conditions. This study used a U.S. database to compare medical expenditures and health outcomes between adults with comorbidities who have cancer and those without. Methods: This longitudinal analysis utilized the data from the 2008-2014 Medical Expenditure Panel Survey (Household Component). Participants with one or more of 19 chronic health conditions (ICD-9 coded) relevant to primary care were classified based on self-reported cancer history. Outcomes from the second year of each panel (2009-2015) included comorbidity-specific healthcare utilization, medical expenditures, functional status, HRQoL, and health utility. Cost differences conditional on positive expenditures were analyzed using generalized linear models (gamma regression and log-link), while differences in healthcare utilization were examined using negative binomial regression. All models were adjusted for demographic, socioeconomic, and lifestyle covariates. Results: A weighted total of 24,057,137 adults with at least one comorbidity (mean age 58.3±15.8 years; 59% female) were included, of whom 10% (n=2,393,300) reported a history of cancer. Compared with non-cancer patients, cancer patients received more comorbidity-specific home health visits (IRR 2.01, 95% CI 1.13-3.57) but had lower total comorbidity-specific expenditures (OR 0.81, 95% CI 0.71-0.92). Cancer patients also incurred lower comorbidity-specific hospitalization costs and out-of-pocket costs for emergency department (ED) visits (p<0.05). Specifically, they had reduced total expenditures for arthritis (OR 0.60, 95% CI 0.39-0.93) and stomach problems (OR 0.42, 95% CI 0.22-0.81) and reduced out-of-pocket costs for thyroid problems (OR 0.55, 95% CI 0.36-0.86) and osteoporosis (OR 0.41, 95% CI 0.18-0.92). Among multimorbid patients (≥2 conditions; 55.4%), cancer patients incurred lower out-of-pocket costs for ED visits (OR 0.42, 95% CI 0.26-0.68). For health outcomes, cancer patients reported more functional limitations than non-cancer patients in instrumental activities of daily living (10.8% vs 8.5%), role functioning (26.2% vs 20.5%), and cognitive function (13.6% vs 11.2%), all p<0.05. Moreover, multimorbid patients with cancer had lower HRQoL and health utilities (p<0.05). Similar trends were observed for cancer patients with depression, hypertension, chronic lung disease, osteoporosis, and thyroid problems. Conclusions: Cancer patients with comorbidities had greater functional limitations but lower medical expenditures for comorbidity care than non-cancer patients, suggesting inequities in primary care. Healthcare resources should be prioritized for cancer patients with comorbidities and poor functional status.

Alternative therapeutic targets in patients treated with immune checkpoint inhibitors for advanced urothelial cancer: Real-world data of German comprehensive cancer centers (ATTICI biomarker study).

e16583 Background: Erdafitinib is the first targeted therapy for inoperable or metastatic urothelial carcinoma (mUC). Its use requires FGFR2/3 alterations in tumor tissue and failure of immune checkpoint inhibitor (ICI) therapy. Though, timely molecular testing in non-clinical trial settings can be challenging. This study explores the molecular background of mUC patients (pts) treated with ICI in a real-world setting, focusing on FGFR alterations and other targetable molecular changes. Methods: Following IRB approval, clinical data on mUC pts treated with ICI (01/13-09/24) and with available FFPE tumor samples from 9 German academic centers were documented. Data included demographics, clinical characteristics, treatment, and survival. FFPE samples prior to therapy underwent INVIEW Oncoprofiling NGS analysis, filtering for oncogenic variants. Interpretation used dbNSFP, OncoKB, ClinVar, and variant effect predictors. Further, IHC for potential therapeutic markers (Her2, EGFR, FGFR3, Nectin4, Trop2, MTAP, AR and ER status, FRalpha, Claudin18.2) was performed. Results: 182/251(72.5%) pts had clinical data, sufficient tissue samples for NGS, and consent available for analysis (median age 68 (IQR 60-77) years, 66.5% male. ECOG PS 0, 1, 2+ and missing in 30, 22, 13, and 35%). 82.4% of pts had UICC stage IV disease at start of ICI treatment (1st line 37%, 2 nd line 49%). mFU was 22.2 months. PFS and OS was 4.4 (95%CI 2.9-5.9) and 16.8 (95%CI 13.2-20.3) months, respectively. 22% responded (radiographic complete or partial response) to ICI monotherapy, while 45% progressed. On average, 9 oncogenic variants were found per patient. Potentially, targetable FGFR variants were present in 12/182 (6,6%), ERBB2 variants in 12/182(6.6%), TP53 mutations in 84/182 (46.2%), and SPEN mutations in 64/182 (35.2%). Other variants included NBN, APC, and KMT2C. By IHC, overexpression of Her2, EGFR, FGFR3 and Trop2 was noted in 53/139 (38.1%), 18/142 (12.4%), 67/140 (47.9%), and 80/140 (57.1%), respectively. CPS was ³10 in 10/142 (7.0%). Nectin4 was positive (H-Score > 100) in 31,7%, MTAP loss was noted in 88/142 (62.0%). AR and ER positivity and FRalpha were rare, and Claudin18.2 was not expressed. Comparing ICI-responders and non-responders, FGFR (15/45 [33%] vs. 47/78 [60%]) and HER2 (19/45 [33%] vs. 36/78 [46%] overexpression was more frequent in non-responders; other molecular parameters assessed did not differ between these groups. Conclusions: Frequency of FGFR alterations was low, though further targetable gene alterations as well as overexpression of alternative ADC target Her2, especially in ICI non-responders was detected. Frequent loss of MTAP expression points towards PRMT5 inhibitor therapy in some mUC pts. Our data favours early, comprehensive and consistent testing of pts with a mUC at the start of ICI therapy.

Optimization of tumor-infiltrating lymphocyte (TIL) manufacturing in non-small cell lung cancer (NSCLC) using an IL-7/IL-15/IL-2 expansion protocol.

2559 Background: Adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) is a promising strategy in non-small cell lung cancer (NSCLC), although ex vivo expansion remains challenging due to variability in yield and product quality. Optimizing cytokine support during TIL expansion may improve manufacturing robustness while preserving a clinically relevant immunophenotype. Methods: Tumor tissue specimens were obtained from immediately resected NSCLC lesions and processed for TIL outgrowth and rapid expansion over 28 days using either standard IL-2 or an experimental IL-7/IL-15/IL-2 protocol. Manufacturing endpoints included expansion yield, viability and CD3⁺ proportion. Multiparametric flow cytometry assessed memory differentiation subsets and exhaustion-associated markers at baseline, pre-REP and post-REP. Clinical-pathological variables included disease stage, PD-L1 expression and prior systemic treatment. Results: 11 NSCLC TIL expansions were analyzed (experimental: n=7; IL-2: n=4). Median age was 73.1 years (range 48.5–92.3) and ECOG was 0–1 in 91% of patients; 64% had early-stage disease and 27% had advanced-stage (III–IV). PD-L1 was <1% in 73%, 9% showed PD-L1 1–49%, and none ≥50%. The cohort included pretreated patients, including prior anti–PD-1 exposure. Compared with IL-2, IL-7/IL-15/IL-2 resulted in a modest reduction in expansion yield (15–28%) and a lower CD4+/CD8+ ratio (6.62 vs 19.86), but showed improved manufacturing robustness, with all expansions meeting predefined quality criteria, whereas standard IL-2 expansions showed more variable product quality. Immunophenotypic profiling showed a more stable memory-oriented differentiation pattern with IL-7/IL-15/IL-2, including reduced naïve and TEMRA subsets and increased CD4+ TCM cells; CD8+ TCM remained predominant in both protocols. A polarisation towards the effector memory phenotype (CCR7⁻CD45RA⁻) was observed in the experimental protocol. CD28 remained highly expressed in both protocols, while CD134 tended to decrease with IL-7/IL-15. During pre-REP, PD-1 and TIM-3 were reduced in several subpopulations under the experimental protocol, suggesting a transiently less exhausted phenotype. After REP, these differences disappeared, with comparable levels between protocols. During REP, Th1 and Tfh increased in both protocols, while Th2 and Th17 remained low. Conclusions: Supplementation with IL-7 and IL-15 during NSCLC-derived TIL expansion improves consistency of product quality and supports a favorable memory-oriented and functional phenotype without increasing exhaustion markers at the end of manufacturing. This approach may enable more reliable generation of clinically applicable TIL products in heterogeneous and pretreated NSCLC populations, facilitating broader implementation of TIL-based therapies.

NRG-HN006: Randomized phase II/III trial of sentinel lymph node biopsy versus elective neck dissection for early-stage oral cavity cancer.

TPS6138 Background: Patients with early-stage oral cavity cancer (OCC; T1-2N0M0; AJCC 8th edition) have a 20-30% risk of occult nodal metastases despite clinical and radiographic evaluations. Standard-of-care treatment for most patients includes elective neck dissection (END), which requires surgical removal of the regional cervical lymph nodes, even though 70-80% of these necks are disease-free. Sentinel lymph node biopsy (SLN Bx), a less invasive procedure, could assess the first echelon lymph nodes as an alternative to END, potentially reducing morbidity and costs. A pivotal clinical trial comparing SLN Bx to END (NCT#04333537) is underway to inform efforts to establish optimal disease management for early-stage OCC. Methods: To assess the efficacy of SLN Bx in this population, we activated an international, multi-institutional, prospective phase II/III trial in July 2020, randomizing patients to two surgical arms: SLN Bx and END. A node-negative 18 F-FDG PET/CT imaging biomarker study with centralized read was required before randomization. OCC patients with a positive PET/CT remained in a registry to compare imaging findings with final neck pathology. Given the current evidence on morbidity for SLN Bx versus END, the phase II was designed to determine whether the change in patient-reported neck and shoulder function and related quality of life (QOL) from baseline to 6 months after surgery, using the Neck Dissection Impairment Index (NDII), showed a signal of superiority of SLN Bx compared to END (minimum important difference ³ 7.5; one-sided a = 0.10; 90% power). As of December 2024, 261 patients had been randomized and 203 were analyzed for the “Go/No-Go” decision to move forward into phase III. The phase III portion is a non-inferiority (NI) trial with disease-free survival (DFS) as the primary endpoint (NI margin hazard ratio 1.34 based on a 5% absolute difference in 2-year DFS; one-sided a = 0.05; 80% power, and two interim looks). The change in NDII from baseline to 6 months after surgery is a hierarchical co-primary endpoint for phase III. Phase III opened in October 2025 upon receiving a “Go” signal from phase II. Target accrual for phase III is 686 node-negative PET/CT patients, including those randomized in phase II (425 additional patients). In addition to sites requiring radiotherapy and imaging credentialing, quality assurance will include central pathology review of all negative SLN Bx cases and surgeon credentialing through an education course with SLN Bx and END case review by the surgical co-chairs. A surgical quality assurance working group will review all trial SLN Bx and END procedures. As of 01/12/26, 351 patients have been screened, and 273 of the planned 686 have been randomized. Clinical trial information: NCT#04333537 .

A rationally designed local delivery platform (OncoPLEX) for sustained docetaxel release to overcome therapeutic barriers in post-resection solid tumors and glioblastoma.

e15099 Background: Post-surgical recurrence is a leading cause of treatment failure in solid tumors, particularly glioblastoma (GBM), where the blood-brain barrier (BBB) and infiltrative disease limit the efficacy of systemic chemotherapy. We developed OncoPLEX, a localized, controlled-release formulation of docetaxel (TDX), designed to deliver sustained, high local concentration of bioactive drug to the surgical margin while minimizing systemic exposure and toxicity. Methods: Efficacy was evaluated in multiple models, including post-partial resection of subcutaneous colorectal carcinoma model (CT-26) and non-resected orthotopic intracranial 9L gliosarcoma. Outcomes included tumor regrowth, overall survival (OS), systemic toxicity, and 16-week intracranial safety. Plasma pharmacokinetics (PK) were measured and compared with intravenous (IV) DTX administration. Results: OncoPLEX demonstrated enhanced potency with a 50.3% lower IC50 in the CT-26 cells relative to free DTX. In CT-26 post-resection model, OncoPLEX achieved near-complete growth inhibition and significantly extended survival (p < 0.05). In non-resected orthotopic gliosarcoma, a single intracranial dose of OncoPLEX (50 mg) produced an OST of 35 days, nearly doubling median OS of the untreated (18 days) and systemic temozolomide (23 days) groups. PK analysis confirmed a 13-fold lower Cmax compared with IV administration (67 vs. 881 ng/mL) while maintaining comparable total exposure (AUC). No permanent neurotoxicity or systemic decline was observed over 16 weeks. Antitumor activity demonstrated distal radial diffusion from the site of administration into the tumor mass. Conclusions: Localized, controlled, and prolonged DTX delivery via OncoPLEX enables superior outcomes by bypassing the BBB, overcoming chemoresistance, and potentially providing extended tissue penetration depth. Unlike systemic nanoparticle-based delivery systems, this platform provides a sustained, high-concentration local therapeutic effect with improved safety. OncoPLEX represents a highly translatable strategy for improving outcomes in high-risk solid tumors and aggressive CNS malignancies.

An AI-based pathology classifier to predict benefit from enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC) from ENZAMET (ANZUP 1304).

108 Background: The ENZAMET trial established that adding enzalutamide (ENZ) to androgen deprivation therapy (ADT) improves overall survival (OS) in mHSPC. However, heterogeneity in treatment response and toxicity complicate clinical decision-making. We evaluated a previously developed Artificial Intelligence Pathology Image Classifier (APIC) to determine whether it could identify ENZAMET participants (pts) more likely to benefit from adding ENZ rather than NSAA to ADT. Methods: This AI biomarker study analyzed digitized H&E tumor specimens from ENZAMET (ANZUP 1304, NCT02446405), a phase 3 trial randomizing pts with mHSPC to ADT plus ENZ or a non-steroidal antiandrogen (NSAA), with early docetaxel (EDx) permitted. APIC, a model quantifying nuclear morphology and tumor-immune architecture validated in CHAARTED (Medina et al, Clin Can Res 2025), was applied without modification. The primary multivariable analysis evaluated the treatment-APIC interaction for OS using Cox models adjusted for disease volume (CHAARTED criteria), EDx, and age. Sensitivity analyses excluded pts receiving EDx. APIC associations with 18 circulating immune markers were explored. All tests were two-sided with p<0.05 considered significant. Results: Among 393 evaluable pts (median follow-up 70 months), 248 (63%) were APIC-negative and 145 (37%) APIC-positive. APIC significantly modified ENZ benefit (interaction p=0.010). APIC-negative was associated with improved OS with ENZ versus NSAA (HR 0.42, p<0.001; 5-year OS 82% vs 59%), while APIC-positive showed no benefit (HR 0.98, p=0.92; 5-year OS 57% vs 57%). APIC-treatment interaction was significant (p=0.02) in the multivariable model adjusted for clinical covariates. In low-volume disease, ENZ improved OS in APIC-negative (HR 0.19, p=0.0001) but not APIC-positive (HR 1.12, p=0.8; interaction p=0.002). Excluding EDx use (n=227), APIC-negative was associated with ENZ benefit (HR 0.29, p<0.001; 5-year OS 88% vs 60%, interaction p=0.043), while no significant benefit was observed for APIC-positive (HR 0.75, p=0.39; 5-year OS 61% vs 54%) (Table). Analysis of circulating immune markers identified elevated plasma myeloid progenitor inhibitory factor 1 (MPIF1) in APIC-positive pts (1.32-fold, 95% CI 1.11–1.58, p=0.002). Conclusions: APIC status was associated with benefit of ENZ for pts with mHSPC. APIC might help guide treatment selection for pts with mHSPC considered for androgen receptor pathway inhibitors and/or docetaxel. Clinical trial information: NCT02446405 . APIC Status HR (95% CI) P Value Interaction P Biomarker cohort (n=393) Negative 0.42 (0.27–0.64) <0.001 0.01 Positive 0.98 (0.61–1.56) 0.9 Low-Volume Disease Subgroup (n=209) Negative 0.19 (0.08–0.44) 0.0001 0.002 Positive 1.12 (0.55–2.29) 0.8 No docetaxel cohort (n=227) Negative 0.29 (0.15–0.56) <0.001 0.04 Positive 0.75 (0.40–1.44) 0.4

A phase I/II clinical study of DOC1021 (dubodencel) dendritic cell immunotherapy for refractory melanoma.

TPS9602 Background: DOC1021 is an autologous dendritic cell (DC)-based immunotherapy. Loading of DC in tandem with both patient autologous tumor protein and amplified mRNA induces p38MAPK and mTORC1 signaling cascades that initiate cDC1-like skewing of monocyte-derived DC, generating downstream development of highly cytolytic memory effectors. This approach targets the multitude of antigens in a patient’s own tumor, does not require myeloablative chemotherapy and has demonstrated a favorable safety profile in Phase I glioblastoma (NCT04552886) and pancreatic cancer trials (NCT04157127). Pre-clinical studies in a variety of animal models, including melanoma (subcutaneous B16F0-OVA tumors), have also shown improved tumor responses and evidence of antigen-specific immunity. While immune checkpoint inhibitors (ICI) have improved clinical outcomes in melanoma, many patients ultimately develop resistance, resulting in refractory disease. We hypothesize that DOC1021 may overcome ICI resistance in refractory melanoma through the generation of durable T cell responses with novel specificities, promoting long-term anti-tumor T cell surveillance and improved survival. Methods: This is a prospective, multi-center, open-label Phase I/II study in patients with refractory cutaneous melanoma, unresectable or metastatic, with progression following ≥1 prior systemic therapies including anti-PD-1. The study consists of two components: an initial Phase I study to confirm safety/tolerability of DOC1021 in refractory melanoma, and subsequently, a single-arm Phase II cohort to assess efficacy. Up to 12 patients will be enrolled in Phase I, and up to 35 evaluable patients will be enrolled in Phase II using a Simon’s optimal two-stage design. DOC1021 will be prepared from mobilized peripheral blood mononuclear cells (PBMC), loaded with autologous tumor lysate and amplified tumor mRNA. All patients will receive 2 courses of DOC1021 (12 x 10 6 cells per administration) 2 weeks apart via perinodal injections near active disease sites, plus peg-interferon (pIFN) adjuvant on the day of each DOC1021 administration and 1 week after for 4 total doses. An optional DOC1021 booster course may also be given approximately 6 months after the first DOC1021 administration. The primary endpoint of the Phase I study is dose-limiting toxicities of DOC1021, while the primary endpoint of the Phase II study is the overall response rate per RECIST 1.1 criteria. This study will also evaluate survival, tumor responses, changes in circulating tumor DNA, as well as further investigate DOC1021’s mechanism of action through biomarker-rich analyses of serial tumor biopsies and blood sampling. The first patient to enroll in the Phase I safety study is planned for early 2026. Clinical trial information: NCT07288112 .

The use of complementary and alternative medicine in the Middle East for managing neutropenia in cancer patients: A systematic review and meta-analysis of randomized controlled trials.

e23411 Background: Neutropenia, a common life-threatening complication of systemic cancer therapies, heightens infection risk, delays treatment, and impairs quality of life. In the Middle East, complementary and alternative medicine (CAM) is widely used alongside conventional oncology care, yet robust clinical evidence for its role in neutropenia management remains scarce. Methods: A PRISMA 2020-compliant systematic review and meta-analysis of randomized controlled trials (RCTs) was performed. Comprehensive literature searches were conducted in Scopus, CENTRAL, MEDLINE, and Embase. Eligible studies included cancer patients undergoing systemic therapy, complementary and alternative medicine (CAM) interventions relevant to the WHO Eastern Mediterranean Region, and neutropenia-related outcomes. Results: A total of 10,263 records were identified across databases and trial registers, including Scopus (n = 4,394), CENTRAL (n = 2,497), MEDLINE (n = 1,805), and Embase (n = 1,567). After removal of 2,711 duplicates (2,698 via Covidence and 13 manually), 7,552 records were screened, of which 7,304 were excluded. The 230 full-text articles were assessed for eligibility, and 7 randomized controlled trials (RCTs) met the inclusion criteria for present meta-analysis. Complementary and alternative medicine (CAM) interventions significantly improved absolute neutrophil count (SMD = 0.64, 95% CI 0.32-0.96; p < 0.001) and reduced the risk of neutropenia-related complications (OR = 0.53, 95% CI 0.34-0.83; p = 0.005). CAM use was also associated with fewer infections and reduced treatment interruptions. No serious adverse events or clinically relevant herb-drug interactions were reported, and the overall risk of bias across included studies was low to moderate. Conclusions: CAM therapies commonly used in the Middle East appear to be safe and potentially effective adjuncts for managing neutropenia in cancer patients. Larger, high-quality RCTs are warranted to confirm these findings and guide clinical integration. Characteristics of randomized clinical studies and type of complementary and alternative medicine (CAM) intervention. Sr. No. Author (Year) Country Cancer Type CAM Intervention Comparator Sample Size Outcomes 1 Tröger et al., 2009 Serbia Breast Mistletoe extract Standard care 61 Neutropenia, QoL 2 Tröger et al., 2014 Serbia Breast Helixor A Standard care 65 ANC, QoL 3 Pelzer & Tröger, 2018 Multi-center Breast Mistletoe extracts Standard care 95 Febrile neutropenia 4 Shahriari et al., 2021 Iran Leukemia Chamomile Control 70 ANC, WBC 5 Bar-Sela et al., 2007 Israel Breast Wheat grass juice Standard care 60 Myelotoxicity 6 Araújo et al., 2012 Brazil Mixed Uncaria tomentosa Placebo 40 Immune recovery 7 Pilot RCT Iran Mixed Herbal CAM Standard care 45 Neutropenia duratio

Cardiovascular comorbidity burden and in-hospital outcomes in patients with lung cancer: A retrospective analysis.

e20111 Background: Patients with lung cancer have the highest prevalence of pre-existing cardiovascular disease and face the greatest risk of cardiovascular events following diagnosis. In addition, lung cancer therapies may exacerbate underlying cardiac comorbidities. Therefore, we wanted to evaluate the prevalence of cardiovascular disease among patients hospitalized with lung cancer and assess its impact on in-hospital mortality. Methods: We conducted a retrospective analysis of the National Inpatient Sample (NIS) from 2016–2020. Adult hospitalizations with a primary diagnosis of lung cancer were identified using ICD-10-CM codes, and cardiac comorbidities were captured from secondary diagnosis fields. Categorical variables were compared using the chi-square test, and continuous variables using the Student’s t-test. Multivariable regression models were used to adjust for potential confounders and to estimate adjusted odds ratios (aORs). A two-sided p value < 0.05 was considered statistically significant. Results: A total of 200,6760 patients were hospitalized with a primary diagnosis of lung cancer. The prevalence of cardiac risk factors was higher among older adults. The mean age of patients admitted with lung cancer was 69 years. Of these patients, 48% were female and 52% were male. Among the total cohort, 17% had congestive heart failure (CHF), 25% had coronary artery disease (CAD), 12% had atrial fibrillation, 2% had ventricular arrhythmias, and 0.08% had endocarditis. Overall, in-hospital mortality was higher among patients with these cardiac risk factors.On multivariable regression analysis, the presence of cardiac comorbidities remained significantly associated with increased odds of mortality. CAD was associated with increased mortality (aOR 1.9, p = 0.001), as were CHF (aOR 1.3, p < 0.001) and atrial fibrillation (aOR 1.15, p < 0.001). Ventricular arrhythmias and endocarditis showed the strongest associations, each with an aOR of 2.3 (p < 0.001). Conclusions: In this analysis, cardiovascular co-morbidities were highly prevalent among patients with lung cancer. The presence of baseline cardiovascular co-morbidities can worsen outcomes. Early recognition these risk factorsmay reduce adverse events, improve clinical outcomes, and enhance overall quality of life for patients with lung cancer. In-hospital mortality among patients hospitalized with lung cancer stratified by cardiac comorbidities. Cardiac Risk factors Mortality in lung cancer patients Percentage Adjusted Odds ratio P-value Congestive heart failure 38169/334569 11% 1.3 <0.001 Coronary Artery Disease 40164/491324 8.1% 1.9 0.001 Atrial Fibrillation 23829/237054 10% 1.15 <0.001 Ventricular Arrhythmia 8289/44294 18% 2.3 <0.001 Endocarditis 304/1664 18% 2.3 <0.01

The clinical significance of <i>TET2</i> -driven clonal hematopoiesis ( <i>TET2</i> -CH) in ICI-treated melanoma patients.

9549 Background: Clonal hematopoiesis (CH) arises from age-related somatic mutations in hematopoietic stem cells and has been linked to altered immune function and clinical outcomes in solid tumors. While recent studies in colorectal and lung cancers suggest TET2 -mutant CH may enhance immunotherapy responses, the impact of CH genotype on melanoma outcomes remains unclear and potentially context-dependent. Methods: We performed a retrospective cohort study of 361 patients with unresectable stage III/IV melanoma who underwent whole blood sequencing prior to anti-PD-1-based immunotherapy (2014-2024). CH was defined as somatic mutations in CH driver genes with variant allele fraction (VAF) &gt; 2%. Progression-free survival (PFS) and overall survival (OS) were measured from ICI initiation; patients without events were censored at last follow-up. Kaplan-Meier curves and multivariable Cox models adjusted for age, sex, BRAF V600E status, stage, and prior therapy estimated hazard ratios (HRs) compared to patients without CH. Chi-squared analysis assessed CH prevalence among melanoma patients compared to a healthy control cohort (n = 12,346) matched for age and sex. Results: CH prevalence was significantly elevated in melanoma patients compared to age and sex-matched healthy controls (27.7% vs. 21.4% χ² = 7.94, p = 0.004). Among 361 patients, 32 (8.9%) harbored TET2 -driven CH, 48 (13.3%) had DNMT3A -CH, and 20 (5.5%) had other CH mutations. TET2 -CH was associated with significantly worse OS compared to patients without CH (HR = 1.79, p = 0.014) and a trend toward inferior PFS (HR = 1.42, p = 0.119). In contrast, neither DNMT3A -CH (N = 48) nor other CH genotypes demonstrated significant associations with clinical outcomes ( DNMT3A -CH: OS HR = 1.38, p = 0.11; PFS HR = 1.21, p = 0.32), establishing genotype-specific effects. Conclusions: In this cohort of patients with unresectable Stage III/IV melanoma receiving ICI therapy, TET2 -CH was associated with inferior survival outcomes, while no significant survival differences were found among patients with DNMT3A -CH or other CH genotypes. Incorporating CH genotyping into pre-treatment risk stratification may identify high-risk melanoma patients who could benefit from alternative or intensified therapeutic strategies. Mechanistic studies are warranted to elucidate the biological basis for these genotype-specific effects and explore therapeutic interventions targeting CH-driven immune dysfunction. Multivariable PFS and OS hazard ratios by clonal hematopoiesis genotype in ICI-treated melanoma patients. CH Group Number (N) PFS HR (95% CI) PFS p-value OS HR (95% CI) OS p-value No CH 261 1.00 (reference) - 1.00 (reference) - CH 100 1.21 (0.92-1.60) 0.178 1.48 (1.10-1.99) 0.010 TET2- CH 32 1.42 (0.91-2.19) 0.119 1.79 (1.12-2.84) 0.014 Non- TET2 CH 68 1.13 (0.82-1.56) 0.445 1.36 (0.97-1.92) 0.079 DNMT3A -CH 48 1.21 (0.83-1.74) 0.319 1.38 (0.93-2.03) 0.108

Format matters: Digital vs print delivery of a job retention intervention during breast cancer therapy.

11060 Background: Talking to Employers and Medical Staff about Work (TEAMWork) is an English/Spanish intervention, delivered as a booklet or mobile app, which was developed to improve work outcomes among women undergoing (neo)adjuvant breast cancer therapy. TEAMWork provides education on work accommodations based on vocational rehabilitation principles, employer negotiation strategies, symptom self-management tools, and guidance on communicating with clinicians to enhance support (e.g., obtain work documentation). Here we present data on predictors of intervention use during systemic therapy from an ongoing randomized controlled trial comparing the TEAMWork app to the booklet. Methods: Eligible participants were women aged 18-65 years with stage I-III breast cancer who spoke English and/or Spanish, were employed pre-diagnosis, and undergoing or planning to undergo systemic (neo)adjuvant chemotherapy. Patients were recruited between October 2021 – March 2025 from multiple New York City sites. Data on socio-demographics, work characteristics, and intervention use were collected through patient surveys at baseline and after completion of chemotherapy. Multivariable logistic regression was used to assess predictors of intervention use during systemic therapy. Results: Of 372 participants (89% English; 11% Spanish), 54% identified as White, 17% Black, and 20% Hispanic/Latina. The mean age was 48 years. 70% were college-educated. All were employed at diagnosis, but only 77% were actively working (e.g., not on leave) at baseline. Participants worked in various occupations: managerial/professional (50%), sales/technical/administrative support (24%), service providers (21%), arts/media/athletics (5%), and operators/fabricators/laborers (1%). All participants received chemotherapy, with 53% starting therapy before the baseline survey. Slightly over half of participants (53%) reported using TEAMWork during systemic therapy; 120/187 (64%) in the mobile app arm and 76/185 (41%) in the booklet arm. In multivariable analysis, assignment to the mobile app arm was positively associated with intervention use during treatment (OR 2.54, 95% CI 1.61-4.05, p&lt;.001). However, age, race, ethnicity, language, US-born (yes/no), educational attainment, occupational category, and chemotherapy initiation prior to randomization were not independently associated with intervention use. Conclusions: After adjusting for sociodemographic, occupational, and treatment-related characteristics, participants randomized to the mobile app arm had more than double the odds of using TEAMWork compared to those in the booklet arm. These findings underscore the importance of delivery format in the design of supportive interventions. Although mobile app development can be time- and resource-intensive, this approach may offer meaningful advantages in promoting patient engagement during therapy.

Phase I/II, first-in-human study of yttrium-90 carbon microspheres in patients with unresectable hepatocellular carcinoma: Safety and early efficacy profiles.

4169 Background: Yttrium-90 microsphere selective internal radiation therapy (Y-90 SIRT) plays a significant role in the treatment of unresectable hepatocellular carcinoma. The phase I clinical study evaluated the safety and efficacy of Y-90 Carbon Microspheres Injection in patients with unresectable hepatocellular carcinoma. Methods: This multicenter, single-arm, prospective study was conducted across eight centers in China. It enrolled all eligible patients with uHCC who underwent radioembolization between 2023 and 2024. Eligibility criteria included unresectable hepatocellular carcinoma, Child-Pugh A cirrhosis, and an Eastern Cooperative Oncology Group performance status of 0-1. The primary endpoints included the incidence of adverse events and serious adverse events post-infusion, and the objective response rate in the treated area at first assessment according to mRECIST criteria. Among the 40 enrolled patients, 40.0% had an ECOG status of 0. According to China Liver Cancer Staging (CNLC), there were 12 cases (30.0%) in stage Ia, 9 cases (22.5%) in stage Ib, 6 cases (15.0%) in stage IIa, 4 cases (10.0%) in stage IIb, and 9 cases (22.5%) in stage IIIa of liver cancer. The median tumor size was 55.36 mm (range: 11.2–141.2). Results: All subjects received radioembolization as primary treatment, with a median tumor target absorbed dose of 450 Gy (range: 196.5 Gy-2000 Gy). According to the SPECT/CT results after treatment with NRT6003 injection, the median tumor absorbed dose was 429.93 Gy (range: 197.1 Gy-2827.7 Gy). As of February 21, 2025, the median follow-up of 9.5 months, a total of 221 treatment-related adverse events were reported, including 16 events of grade ≥3 and 2 serious adverse events (Upper abdominal pain, gastrointestinal bleeding). The best overall objective response rates were 92.5% (37/40) for whole-body and 97.5% (39/40) for local responses. The confirmed objective response rates were 82.5% (33/40) for whole-body and 85% (34/40) for local assessments. Six patients were re evaluated for surgical treatment due to tumor shrinkage. Conclusions: In this multicenter Y-90 SIRT study, treatment with Y-90 Carbon Microspheres demonstrated a favorable safety and efficacy were observed in the treatment of unresectable HCC, providing a highly promising treatment option. Clinical trial information: NCT06310590 .

Ring-augmented versus conventional one-anastomosis gastric bypass: Perioperative and short-term results in the randomized controlled RiMini trial

Purpose Recurrent weight gain remains a challenge in metabolic bariatric surgery (MBS). Recent publications focused on ring-augmented Roux-en-Y gastric bypass (RYGB) and ring-augmented sleeve gastrectomy (SG), but few studies have addressed the potential of ring-augmentation for one-anastomosis gastric bypass (OAGB). Objectives The RiMini trial is a single-center randomized controlled trial that investigates the difference in long-term weight reduction, associated medical comorbidities, quality of life, and procedure-related adverse events of ring-augmented OAGB compared to conventional OAGB in adult patients eligible for primary OAGB. This analysis reports the trial’s short-term outcomes, including the peri-operative safety of the procedure, short-term adverse events, and weight outcomes at one year postoperatively. Methods Between July 2022 and December 2023, a total of 214 patients (107 per group) underwent either ring-augmented or conventional OAGB after randomization. Peri- and postoperative adverse events, and total and excess weight loss percentages (%TWL and %EWL) were assessed by intention-to-treat and per-protocol analysis. Results At baseline, there were no differences between groups regarding age, gender, and body mass index (BMI). Mean operation time was 51 minutes (±13) in both groups (p = 0.84). One patient in each group experienced a perioperative complication (p = 1.00; 0.9%). There was no significant difference in postoperative minor (Clavien Dindo (CD) 1–2) (p = 0.68) or major (CD3–5) (p = 0.77) complications. In the first year, two Minimizer rings were electively removed at patients’ request, without observed complications related to the ring. At one year, mean BMI was comparable in both groups (28 kg/m 2 ). There was no statistically significant difference between ring-augmented and conventional OAGB in %TWL (33% vs 31%; p = 0.30), and %EWL (86% vs 84%; p = 0.45). Conclusions The 1-year analyses of the RiMini trial showed that ring-augmented OAGB is comparable in safety to conventional OAGB. At 1 year, there was no statistically significant difference in weight loss between the groups.

Green synthesis and photocatalytic detoxification of fabric dyes using MoS2/TiO2/PVP nanocomposites