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Safety and efficacy of nivolumab combined with brentuximab vedotin in patients with relapsed and refractory classic Hodgkin lymphoma: Systematic review and meta-analysis.

e19040 Background: Relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) remains a therapeutic challenge despite high frontline cure rates due to its resistance to chemotherapy. Checkpoint inhibitors targeting PD-1 as Nivolumab, and antibody–drug conjugate therapy as Brentuximab Vedotin, have each demonstrated substantial activity in R/R cHL. Their combination has been evaluated across multiple clinical trials and real-world studies; however, the pooled efficacy and safety of this regimen have not been systematically quantified. This study aims to evaluate the safety and efficacy of Nivolumab as PD-1 inhibitors combined with Brentuximab Vedotin in treating relapsed or refractory cHL (rrHL). Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted in Jan 2026. Eligible studies were 8, including 7 prospective clinical trials and one retrospective cohort study. evaluating Nivolumab plus Brentuximab Vedotin in patients with R/R cHL. Primary outcomes were overall response rate (ORR) and complete response (CR). Secondary outcomes included progression-free survival (PFS), overall survival (OS), and adverse events (AEs). A random-effects model was used to pool effect estimates. Statistical heterogeneity was assessed using the I² statistic. Risk of bias was evaluated using Cochrane risk of bias 2 (ROB 2) and ROBINS-I. Results: A total of 8 studies including 315 patients with relapsed or refractory Hodgkin lymphoma were included in the meta-analysis. The pooled overall response rate (ORR) was 83.4% (95% CI, 78.2–87.6), with moderate heterogeneity (I² = 47%, tau² = 0). The pooled complete response (CR) rate was 62.5% (95% CI, 56.4–68.2). Grade ≥3 adverse events occurred in 37.5% of patients, most commonly [nausea and sensory peripheral neuropathy]. Conclusions: This meta-analysis suggested that the combination of Nivolumab and Brentuximab vedotin improves the outcomes of response and survival rates with tolerable AEs in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). These findings support the regimen as an effective chemotherapy-free option.

Clinical actionability and molecular landscapes of fusion-driven sarcomas: A multi-modal integration analysis of comprehensive genomic profiling, targeted RNA-sequencing, and PD-L1 expression.

e23525 Background: Sarcomas are a heterogeneous group of mesenchymal malignancies frequently driven by pathognomonic chromosomal translocations. A complete molecular and immunological landscape of sarcoma patients requires DNA, RNA, and Immuno-Oncology biomarker testing. This study integrates fusion prevalence with other molecular and immunotherapy biomarker characterization in community-based sarcoma patients. Methods: Data was obtained from patients with a broad range of sarcomas tested in our clinical laboratory with a pan-cancer Comprehensive Genomic Profiling (CGP) assay, which tests DNA mutations and CNVs on 517 genes and fusions on 55 genes by RNA-seq (n=517) or with a targeted RNA-seq Sarcoma Fusion panel interrogating 97 genes (n=1,443). For SNV/CNV and TMB associations, only data from the CGP tested patients were analyzed. PD-L1 expression was determined by a CLIA grade IHC with disease-specific clones. An IRB-approved protocol was followed. Results: We found that 5.6% (29/517) of patients tested with the CGP assay expressed a fusion, whereas 28.1% (406/1443) tested positive in a sarcoma fusion-enriched RNA-seq clinical assay. Of the 295 unique fusions detected, 266 were observed in patients tested with the sarcoma panel, of which 189 were covered only by this panel. We found that 144 fusions were pathogenic/likely pathogenic, 79 had diagnostic value, 25 were prognostic, and 36 could guide therapy selection. The most frequent fusions were EWSR1::FLI1 (34), COL1A1::PDGFB (26), NAB2::STAT6 (25), CIC::DUX4 (23), JAZF1::SUZ12 (22), CEP170::RAD51B (21), FUS::DDIT3 (20), SS18::SSX1 (18), FUS::CREB3L2 (15), and EWSR1::NR4A3 (11). In the CGP fusion-positive subgroup, TP53 was the most frequently altered gene, followed by KIT, TERT, CHEK2, and KMT2A. Concurrent PDL1 IHC was ordered for 168/1960 of the patients. While 69% of fusion-positive patients expressed PD-L1, 84% of fusion-negative patients were PD-L1 positive. TMB was low in 83% (429/516) of the CGP tested sarcomas. However, while TMB was High (10.2-12.5 Mut/Mb) in 10% (3/29) of the fusion-positive patients, a wider TMB High range (10.2-482 Mut/Mb) was observed in 17% (84/487) of fusion-negative patients. Conclusions: CGP testing integrated with sarcoma-specific RNA-seq identifies actionable fusions in nearly one-third of community patients tested, offering a significantly higher diagnostic yield for fusions than CGP alone. Fusion-positive sarcomas exhibit a unique PD-L1 protein expression profile—frequently PD-L1 positive despite low TMB—suggesting a distinct immunobiological class that may bypass traditional TMB-based immunotherapy stratification. Utilizing multi-modal DNA/RNA and PD-L1 protein testing is critical for maximizing diagnostic, prognostic, and therapeutic precision in sarcoma clinical care.

A phase II clinical study of PD-1 inhibitor tislelizumab combined with chemotherapy for unresectable recurrent locally advanced nasopharyngeal carcinoma (RETICULA-NPC trial).

e18061 Background: For unresectable locally rNPC patients, re-irradiation with intensity-modulated radiotherapy remains the standard approach, despite its survival and safety limitations. We designed a prospective clinical trial to explore the efficacy and safety of tislelizumab combined with chemotherapy for unresectable recurrent locally advanced NPC patients. Methods: This was a prospective, single-arm, open-label phase II clinical trial. The key inclusion criteria were patients aged 14 to 75 years with histologically confirmed locally recurrent rII-IVA (rT3-4N0-2M0) nasopharyngeal carcinoma occurring more than 12 months after completion of definitive primary treatment. Eligible participants were with medically unresectable tumor or had residual disease after surgery. Participants were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were excluded if they had received any prior radiotherapy, systemic therapy. All patients initially received 4 cycles of combination therapy comprising tislelizumab (200 mg, d1, Q3W) plus investigator-determined chemotherapy regimens. Radiological tumor assessments were performed every 6 weeks by RECIST v1.1. Patients demonstrating objective response (complete or partial response) or stable disease continued treatment with tislelizumab monotherapy maintenance (200 mg every 3 weeks or 400 mg every 6 weeks). In cases of documented disease progression, patients were transitioned to salvage re-irradiation with intensity-modulated radiation therapy. Results: Between the March 2021 and March 2024, a total of 20 eligible patients were enrolled in this study. By the time of December 30, 2025, the median follow-up duration was 39.0 months (range: 15.2-51.8 months). The median progression-free survival was not reached (95% CI: [9.4, NR]). The 1-year PFS rate was 77.3% (95% CI: [49.6%-91.0%]), and the 2-year PFS rate was 70.3% (95% CI: [41.9%-86.7%]). All adverse events were graded according to the CTCAE v5.0. The treatment demonstrated a favorable safety profile overall. 18 (90%) experienced at least one treatment-emergent adverse event (TEAE), with the majority being grade 1-2 events that were clinically manageable. Conclusions: Our study establishes tislelizumab combined with chemotherapy as a feasible and effective treatment strategy for unresectable recurrent locally advanced NPC. The sequential approach demonstrates promising efficacy with manageable toxicity, offering a potential paradigm shift in the management of this challenging patient population. These results support the continued investigation of immunotherapy-based strategies in recurrent NPC and highlight the importance of innovative treatment sequencing in optimizing outcomes.

Enhanced thermal stability and shape stabilization of n-octadecane via nano-confinement in a nickel-based metal-organic framework for thermal energy storage

Molecular Modification Strategy for Efficient NiO _x ‐based Tin‐Lead Perovskites Solar Cells and All‐perovskite Tandems

ABSTRACT For low‐bandgap tin‐lead (LBG Sn–Pb) devices, conventional organic hole transport materials (HTMs) fail to balance efficiency and stability, drawing attention to inorganic nickel oxide (NiO x ) as a promising alternative. However, the inferior compatibility between NiO x and Sn–Pb perovskite severely hinders the development of NiO x ‐based Sn–Pb perovskite solar cells (PSCs) due to mismatched energy levels and oxidizing active species. Here, we propose a versatile strategy by introducing ammonium 2‐hydroxyethanesulphonate (AHES) on NiO x films to fabricate efficient and stable NiO x ‐based Sn–Pb PSCs. The ─SO 3 − in AHES could react with NiO x to regulate film morphology and optimize energy level alignment. Meanwhile, the presence of ─OH in AHES acting as Lewis base provides lone pair electrons to form hydrogen bond to modulate the crystallization process and improve film uniformity, resulting in enhanced lattice strength. As a result, our NiO x ‐based Sn–Pb device yields an efficiency of 22.98% (versus 20.02% for control) and retains 80% of the initial efficiency after continuous 1‐sun illumination after 212 h (versus 90 h for control), which is among the best NiO x ‐based Sn–Pb PSCs. Finally, the champion four‐terminal (4T) all‐perovskite tandem solar cell achieves a remarkable efficiency of 30.38%.

Prediction of response to neoadjuvant dose-dense chemotherapy in luminal breast cancer using a genomic risk probability model.

e12627 Background: Response to neoadjuvant chemotherapy (NACT) in hormone receptor-positive, HER2-negative (ER+/HER2-) breast cancer (BC) is heterogeneous. Genomic assays predict chemotherapy benefit but are not widely available. We evaluated a clinicopathologic model estimating the probability of high genomic risk as a predictor of response to dose-dense NACT (AC q2w followed by Docetaxel q3w). Methods: We retrospectively analyzed 280 patients with stage II-III ER+/HER2- BC treated with NACT (median age 45 years; 70,3% premenopausal) in a single center. Most patients had locally advanced disease (86,8%), nodal involvement (93,9%), and luminal B subtype (95,4%). Pathologic response was assessed using Residual Cancer Burden (RCB). The probability of high genomic risk (corresponding to Recurrence Score ≥26) was calculated using the model developed by S. Yamamoto et al. according to the following formula: p = 1 / {1 + exp [−(4.611 + 1.2342×HER2 − 0.0813×ER − 0.0489×PR + 0.0857×Ki-67)]}, where HER2=0-2; ER, PR, Ki-67=% positive nuclei. A cutoff of ≥50% was predefined as in the original study since the accuracy, sensitivity, specificity, positive predictive and negative predictive values are 90,5%, 72,2%, 94,8%, 76,4% and 93,5%, respectively. Univariable and multivariable logistic regression analyses were performed to identify predictors of favorable response (RCB 0-1). RCB 0-1 as an end point was chosen due comparable long-term results in ER+/HER2- BC as per meta-analysis. Results: RCB 0 was achieved in 12,9% of patients and RCB 0-1 in 24,3%. Mean probability of high genomic risk was 40,3%, with 36,8% classified as high probability (≥50%). Germline testing was performed in 83,2% of patients; mutations (BRCA1/2, ATM, PALB2, CHEK2) were identified by NGS in 18,0% of all tested cases (BRCA2 being the most common - 9%) and were slightly more frequent in patients with high vs low genomic risk probability (22,2% vs 15,2%). In univariable analysis, factors associated with RCB 0-1 included age ≤50 years (OR 2,09, 95% CI 1,07-4,07), initially operable disease (OR 2,44, 95% CI 1,19-5,04), T1–3 stage (OR 1,80, 95% CI 1,03-3,13), presence of germline mutations (OR 2,82, 95% CI 1,41-5,67), and high genomic risk probability ≥50% (OR 2,64, 95% CI 1,51-4,62; all p <0,05). In multivariable analysis, high genomic risk probability ≥50% remained an independent predictor of RCB 0-1 (OR 2,80, 95% CI 1,48-5,30; p =0,001), together with germline mutation status (OR 2,32, 95% CI 1,11-4,85; p =0,025), while age, T stage and operability were not significant. Survival analysis is ongoing. Conclusions: A clinicopathologic model estimating the probability of high genomic risk independently predicts response to NACT in luminal breast cancer and may support selection of ER+/HER2- patients most likely to benefit from NACT when genomic testing is unavailable.

Exploring neural correlates of chemotherapy-induced peripheral neurotoxicity (CIPN) and the impact of exercise: A URCC NCORP nationwide phase II randomized controlled trial (RCT).

11023 Background: More than half of patients with cancer receiving neurotoxic chemotherapy (e.g., taxane, platinum, vinca alkaloid) develop CIPN, a dose-limiting, sometimes-debilitating condition characterized by numbness, tingling, and pain in the hands and feet. There are limited treatment options for CIPN partly due to limited understanding of CIPN pathophysiology. Methods: We conducted a phase II RCT examining the effect of exercise on CIPN via URCC NCORP Research Base. Patients who received neurotoxic chemotherapy within the past 9 months and report CIPN symptoms (rated ≥4 out of 10 at its worst in the past 2 weeks) were randomized 1:1 to usual care (UC) or virtually delivered Exercise for Cancer Patients (vEXCAP). vEXCAP is a 6-week personalized walking and resistance band exercise intervention. As part of our secondary aims, we investigated (1) whether CIPN symptoms are exacerbated by impairments in the brain’s descending pain modulation circuitry—quantified by functional connectivity between the dorsolateral prefrontal cortex (DLPFC) and 23 sensory-related brain regions—and (2) whether exercise can improve both CIPN and brain functional connectivity. We recruited 35 patients from 7 community oncology practices spanning 6 US states. Sensory CIPN severity was assessed using the patient-reported EORTC QLQ-CIPN20 sensory subscale and functional brain connectivity was measured via magnetic resonance imaging (MRI) at pre- and post-intervention. Results: An ANCOVA showed that exercise, compared to UC, reduced sensory CIPN severity (-7.66±3.05 (MCID is 4), effect size (ES) = -0.43, p = 0.158) (N = 35, 57 ± 10 yrs, 89% female, 60% breast cancer). At pre-intervention, correlation analysis revealed sensory CIPN severity was negatively correlated with functional connectivity between the left DLPFC and several brain areas, including the left anterior insula (r = -0.53, p = 0.001), left thalamus (r = -0.44, p = 0.009), and left precuneus (r = -0.32, p = 0.057). Participants who showed a decrease in sensory CIPN severity at post intervention had an increase in functional connectivity between the left DLPFC and left precuneus (r = -0.25, p = 0.152), and this increase in connectivity was greater in vEXCAP group (effect size (ES) = 0.2, p = 0.460). Conclusions: The association of sensory CIPN severity with lower brain connectivity with the left DLPFC may reflect impairment of descending pain inhibition pathways in the brain. vEXCAP may improve brain connectivity with the precuneus while lowering CIPN symptom severity. We believe that this line of research will ultimately inform better CIPN biomarkers and treatments. Funded by NCI UG1CA189956, UG1CA189861, UG1CA189805, UG1CA189961, K07CA221931, and R21CA256154. Clinical trial information: NCT04888988 .

Insights from an artificial intelligence (AI)–powered cancer navigation platform: Digital support and treatment decision confidence.

e13674 Background: Patients with cancer are often overwhelmed with the complexity of their diagnosis, treatment options, and communicating effectively with their care teams. While digital health tools have proliferated, few provide personalized, disease-specific guidance that adapts to individual patient journeys. We developed Manta Cares (ASCO 2025 abst e13713), now with an AI-powered cancer navigation platform featuring Hope AI: a conversational AI companion that empowers patients with knowledge and preparation for clinical conversations. Methods: We analyzed patient interactions from the Manta Cares platform (11/25 – 1/26), including breast cancer, lung cancer, and other malignancies. Key platform features included: personalized cancer maps explaining treatment options; symptom tracker for logging physical and emotional symptoms with severity ratings; appointment notebook for organizing questions for clinical visits; and AI-guided treatment information with curated questions for care teams. We examined feature utilization, patterns in patient-initiated conversations with HopeAI, and qualitative indicators of patient engagement and confidence. Results: Patient interactions clustered around three primary themes: understanding treatment options (42%), navigating appointments and care coordination (31%), and managing treatment impact on daily life (27%). Symptom discussions appeared in approximately half of patient conversations, primarily focused on fatigue, pain, and anxiety. Patients demonstrated increased engagement with appointment preparation features, with users documenting specific questions tailored to their disease subtype and treatment phase. The platform supported patients from diagnosis to survivorship, with active treatment as the most common stage. Patients frequently expressed gratitude for 24/7 support, which helped them feel less alone and more prepared for clinical encounters. The AI companion helped patients discuss prognosis, treatment trade-offs, and quality-of-life issues they found hard to address with their care teams. Conclusions: An AI-powered cancer navigation platform can address critical gaps in patient education and empowerment regardless of tumor type. Manta Cares enhances traditional cancer care through personalized guidance, symptom tracking, and appointment preparation, empowering patients to navigate their experience with greater confidence. Integration of AI-powered navigation tools can complement clinical care and improve patient engagement and treatment decision-making.

Patient preference for subcutaneous vs. intravenous immune therapy (PSI-Immune).

TPS1678 Background: Immune checkpoint blockade (ICB) has improved outcomes for patients (pts) with advanced solid tumors. Conventional intravenous (IV) route of administration (RoA) requires repeated, time-intensive infusions involving cannulation, monitoring, pharmacy preparation, and chair time, increasing treatment burden and constraining infusion center capacity, staffing, and scalability as ICB use expands. Subcutaneous (SC) formulations of pembrolizumab and nivolumab—two widely used PD-1 inhibitors—have recently been approved across multiple indications. PD-1 ICB SC formulations contain the same active drug as IV formulations and have demonstrated comparable PK exposure, efficacy and safety profiles (CheckMate 8KX; 3475A-D77). Beyond pt convenience, SC RoA may enable more scalable delivery by reducing infusion chair utilization, nursing time, and workflow bottlenecks, supporting access across high-volume cancer networks. Real-world pt preference and perceived health-system impact of SC versus IV PD-1 ICB remain incompletely characterized. We therefore designed a distributed, real-world clinical trial to evaluate patient preference and health-system implications of PD-1 ICB RoA across a large integrated cancer network (>70 sites across 4 states). Methods: PSI-Immune is a randomized, phase II, open-label, crossover study evaluating pt preference for SC versus IV RoA of PD-1 ICB in pts with locally advanced (LA) or advanced/metastatic (A/M) solid tumors pending initiation PD-1–based therapy, either as monotherapy or in combination. The primary endpoint is pt preference for ICB RoA, assessed using a validated pt preference questionnaire (PPQ). Key secondary endpoints include pt-reported treatment satisfaction (TASQ), HCP-reported time and resource utilization, pt-reported health-related quality of life (HRQoL), and time to next therapy (TTNT). A subcohort permits enrollment of pts who are already on IV PD-1 ICB. Eligible pts must have an FDA-approved indication for SC pembrolizumab or nivolumab singly or in combination with other FDA-approved agents and a planned duration of PD-1–based therapy exceeding six months. Patients are randomized 1:1 to receive either SC therapy for three cycles followed by IV therapy for three cycles, or the reverse sequence (crossover phase). Subsequently, pts select their preferred route of administration (continuation phase). Treatment regimen is identical across cohorts and differs only by ICB RoA. Randomization is stratified by disease setting (LA vs A/M) and ICB regimen (monotherapy vs combination). The planned sample size is 280 patients. Assuming equal allocation and up to 10% attrition, the exact 95% confidence interval for the proportion of patients preferring SC administration will exclude 50% if the observed preference rate is at least 60%. This study is open and enrolling across the entire UPMC Hillman Cancer Center Network (NCT07223424). Clinical trial information: NCT07223424 .

Reducing cost and complexity in tumor-informed MRD by combining patient probe panels using Enspyre.

e14533 Background: Tumor-informed minimal residual disease (MRD) assays track patient-specific variants, achieving higher sensitivity than tumor-naïve approaches, but requiring custom probe panels for each patient. For high-throughput laboratories, buying, storing, and handling tens or hundreds of thousands of custom panels brings significant cost and complexity, while little or no negative control data are generated for each panel, limiting assay specificity. Combining multiple probe panels reduces cost, as one large panel is cheaper than multiple small, and alleviates operational complexity. It also provides negative control data, since most probes in a given panel should be negative for each single patient. However, in standard MRD assays this approach dramatically increases the sequencing required due to capture of DNA from regions not of interest for a specific patient. Enspyre enriches variant-containing molecules prior to sequencing, meaning that probes targeting variants absent in a sample are inactive and do not result in significant unwanted DNA. This presents an opportunity to combine probe panels without increasing sequencing requirements, bringing significant benefits in performance, cost, and complexity. Methods: Five cell lines were used to assess the effect of combining panels, with a sixth used to mimic background cfDNA. Panels of 2,000 probes were designed to target variants present in each of the five cell lines but not the sixth, and were tested individually and in combination against a serial dilution of each cell line. Limit of detection was estimated for each panel using probit regression-based analysis, and compared to the limit of detection obtained using the combined pool on each cell line. The impact of pooling probe panels on sequencing depth requirements was assessed through downsampling of sequence reads in silico . Results: Consistent ‘ultra sensitive’ ctDNA detection at or below 10ppm was achieved across individual probe panels and using the combined 10,000 probe panel for all targeted cell lines. Sequencing depth requirements were not significantly increased through pooling, with ultra sensitivity achieved using as few as 10M read pairs (vs 100-500M read pairs using standard hybridization-capture sequencing). Conclusions: This work confirms that Enspyre’s variant enrichment enables combinatorial use of multiple probe panels without associated increases in sequencing depth requirements. In real-world settings this could have significant impact, enabling reductions in cost of custom probes and the logistical complexity of storing and tracking vast numbers of bespoke panels. Further, pooling of five 2,000 probe panels into a single pool results in up to 8,000 ‘known negative’ probes for each patient tested, providing substantial negative control data for each individual probe without incurring any additional burden, solving a significant challenge in the field.

Use of multiplexed functional profiling to reveal antiproliferative activity of PARP inhibitors missed by cytotoxicity-only assays in primary ovarian cancer tissues.

e15123 Background: PARP inhibitors (PARPi) are primarily used as maintenance therapy in ovarian cancer, where clinical benefit often reflects disease stabilization rather than tumor regression. Most ex-vivo drug response assays rely on cytotoxicity alone, potentially overlooking biologically relevant antiproliferative effects. We sought to characterize cytotoxic and antiproliferative responses of PARP inhibitors in primary ovarian cancer tissues and to assess functional concordance between olaparib, niraparib, and rucaparib. Methods: Primary ovarian cancer specimens were processed in a CLIA-certified laboratory to generate patient-derived microtumors preserving their native tumor architecture. Ex-vivo responses to olaparib, niraparib, and rucaparib were assessed using multiplexed cytotoxicity and anti-proliferation assays. Pearson correlation coefficients with 95% confidence intervals were calculated to evaluate associations between cytotoxicity and antiproliferation, as well as the concordance of those PARP inhibitors within this class. Results: Across 18 tumors, cytotoxic and antiproliferative effects were weakly correlated or uncorrelated for individual PARP inhibitors and for the drug class overall (overall r = −0.04, p = 0.78). Multiple specimens demonstrated marked suppression of proliferation ( > 50%) with minimal cytotoxicity ( < 20%). Correlations of PARP inhibitors were only moderate for both cytotoxic and antiproliferative responses (PARP to PARP r ranging 0.35–0.75), indicating incomplete functional overlap within the class. Thus, while median antiproliferative effects were comparable across PARP inhibitors there was substantial functional drug response variability between the tumors. Conclusions: PARP inhibitor activity in primary ovarian cancer tissues is not adequately characterized by cytotoxicity alone. Instead, multiplexed functional profiling that includes biologically relevant antiproliferative effects may be necessary to better capture maintenance-associated disease stabilization with PARP inhibitors. Furthermore, the only moderate concordance of antiproliferative activity across individual PARP inhibitors suggests that the presumed class effect may be less uniform than generally assumed, warranting further investigation, ideally in conjunction with multiplexed antiproliferative functional profiling, to demonstrate its clinical relevance.

Enhancing colonoscopy outcomes: A systematic review and meta-analysis of randomized controlled trials evaluating artificial intelligence–assisted adenoma and polyp detection.

e15519 Background: Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Colonoscopy is the cornerstone of CRC screening; however, adenoma detection is operator dependent and susceptible to human error. Artificial intelligence (AI)–assisted colonoscopy has emerged as a real-time adjunct to enhance lesion recognition and procedural quality. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of AI-assisted colonoscopy on adenoma detection rate (ADR) and polyp detection rate (PDR). Methods: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Google Scholar, and the Cochrane Library were searched from inception through August 2025 for RCTs comparing AI-assisted colonoscopy with standard colonoscopy. ADR was defined as the proportion of patients with ≥1 histologically confirmed adenoma per colonoscopy, and PDR as the proportion with ≥1 detected polyp. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a DerSimonian–Laird random-effects model. Statistical heterogeneity was assessed using the I² statistic, and statistical significance was defined as p < 0.05. Results: Twenty-six RCTs comprising 14,056 patients were included (AI-assisted: n = 7,026; standard colonoscopy: n = 7,030). AI-assisted colonoscopy was associated with significantly higher detection rates compared with standard colonoscopy, with pooled ORs of 1.37 (95% CI 1.25–1.51; p < 0.001) for ADR and 1.36 (95% CI 1.19–1.56; p < 0.001) for PDR. Moderate heterogeneity was observed for ADR (I² = 60%) and substantial heterogeneity for PDR (I² = 75%), likely reflecting variability in AI platforms, baseline detection rates, and operator experience. Sensitivity analyses confirmed the robustness of the findings. Funnel plot assessment did not suggest significant publication bias. Risk of bias assessment demonstrated low risk for random sequence generation and outcome assessment blinding, with performance bias primarily related to the inability to blind endoscopists to AI assistance. Conclusions: AI-assisted colonoscopy significantly improves adenoma and polyp detection compared with standard colonoscopy, supporting its role as a tool to enhance screening quality and procedural performance. These improvements may reduce missed lesions and potentially lower interval CRC risk. Further large-scale implementation and real-world effectiveness studies are warranted to optimize integration across diverse practice settings.

Adjuvant chemotherapy versus chemoradiotherapy in high-risk extrahepatic cholangiocarcinoma and gallbladder carcinoma: A National Database analysis.

e16298 Background: High-risk extrahepatic biliary tract cancers (BTC), including extrahepatic cholangiocarcinoma (EHCC) and gallbladder carcinoma (GBCA), have aggressive clinical behavior and high recurrence rates despite adjuvant chemotherapy. The benefit of adding adjuvant radiotherapy to chemotherapy following surgical resection remains uncertain. Methods: The National Cancer Database was queried for adults diagnosed between 2004 and 2023 with resected EHCC (perihilar, cystic duct, distal bile duct) or GBCA adenocarcinoma. High-risk disease was defined as pathologic T2-T4 tumors, or node positive disease, or positive surgical margins, to reflect the patient population in SWOG S0809 trial. Patients were categorized by adjuvant treatment received: chemotherapy alone or chemoradiotherapy. Baseline characteristics were compared using Wilcoxon rank-sum and Fisher’s exact tests. Overall survival (OS) was estimated using Kaplan–Meier methods and compared with the log-rank test. Multivariable Cox proportional hazards models adjusted for age and Charlson–Deyo Comorbidity Index (CDCC). Results: A total of 4724 patients were included; 1265 (27%) received adjuvant chemoradiotherapy and 3459 (73%) received chemotherapy alone. The cohort was predominantly White (78%). The chemotherapy-alone group had a higher proportion of R0 resections (71% vs 60%). On univariate analysis, patients receiving chemotherapy alone demonstrated longer median OS compared with those receiving chemoradiotherapy (36.7 vs 31.2 months; log-rank P < 0.01). In disease-specific subgroup analyses, among patients with EHCC, chemotherapy alone was associated with significantly longer median OS compared with chemoradiotherapy (38.0 vs 29.9 months; log-rank P < 0.001) (Table). On multivariable analysis, chemoradiotherapy remained associated with worse OS in the EHCC subgroup (hazard ratio 1.20; 95% confidence interval (CI), 1.06–1.37; p = 0.005). No OS difference was observed among patients with GBCA. Across both subgroups, higher pathologic T and N stages, and R1 resection were consistently associated with worse OS. Conclusions: In this national cohort of high-risk biliary tract malignancies, adjuvant chemoradiotherapy did not confer an overall survival benefit over chemotherapy alone. Chemoradiotherapy was associated with worse survival in patients with extrahepatic cholangiocarcinoma. Pathologic T and N stages, and margin status emerged as the strongest predictors of survival. BTC (GBCA+EHCC) GBCA subgroup EHCC subgroup Treatment group Median OS (months)(95% CI) Log-rank P Median OS (months)(95% CI) Log-rank P Median OS (months)(95% CI) Log-rank P Adjuvant Chemotherapy 36.67(34.43- 39.03) <0.0001 35.48(32.20- 39.23) 0.071 37.95(35.55- 41.03) <0.01 Adjuvant Chemoradiotherapy 31.18(28.19- 33.02) 32.07(28.09- 36.63) 29.90(26.28- 32.79)

National trends and racial disparities in diffuse large B-cell lymphoma mortality in the United States, 1999–2023.

e19092 Background: Advances in immunochemotherapy and cellular treatment have improved outcomes for diffuse large B-cell lymphoma (DLBCL), but the population-level effect and equity of benefit are unclear. Understanding mortality trends and inequality is critical to developing targeted medicines. Methods: We used ICD-10 codes to assess DLBCL mortality from the CDC WONDER Multiple Causes of Death data (1999-2023). The age-adjusted mortality rates (AAMR) per 100,000 were calculated using the 2000 US standard population. Trends were assessed using Joinpoint regression to calculate annual percent change (APC) and average annual percent change (AAPC). Mortality was broken out by gender, race/ethnicity, age group, US Census area, and urban-rural categorization. Results: From 1999 to 2023, the national AAMR for DLBCL decreased from 3.8 to 2.5 per 100,000 (AAPC -2.1%) (p < 0.001). Non-Hispanic White patients saw the greatest decline (AAPC -2.5%), followed by non-Hispanic Black patients (AAPC -1.2%), resulting in increasing racial inequalities (rate ratio Black:White 1.35 in 2023 vs. 1.18 in 1999). Urban areas had much larger mortality decreases than rural areas (AAPC −2.3% versus −1.1%). Regional disparities were clear, with rates typically higher in the Southeast and Midwest. Inflection points were identified in 2006 and 2012, coinciding with widespread use of rituximab-based therapy and better availability of second-line medications. Conclusions: Although DLBCL mortality has decreased throughout the US over the last two decades, progress has been patchy, with significant racial and regional differences. Clinical Takeaway: Targeted interventions addressing access to therapy and early detection in high-risk populations are needed to close persistent DLBCL outcome gaps.

Circulating tumor DNA for characterizing intratumor heterogeneity and outcomes in metastatic colorectal cancer.

3585 Background: Intratumor heterogeneity (ITH) drives CRC resistance, yet tissue-based assessments remain limited. ctDNA captures heterogeneity, though variable tumor fractions confound measurements. We assessed raw vs fraction-adjusted ITH in ctDNA for overall survival (OS) in metastatic CRC (mCRC). Methods: We analyzed two real-world mCRC cohorts from MD Anderson: a 73-gene panel (1,137 patients, 2014-2023; limit of detection (LoD) 0.1%) and a 701-gene panel (150 patients, 2024-2025; LoD 0.5%). Quality filters included ≥ 3 detected variants, MaxVAF > 0.01, and bioinformatic filtering of putative germline variants. ITH was quantified via raw Mutant-Allele Tumor Heterogeneity (rMATH; VAF distribution width) and the Shannon entropy-based, MaxVAF-normalized (VAF/Max_VAF) blood ITH (bITH; multiplies bin entropy by clonality weights). OS was assessed using Cox models by continuous variables and optimal cut-points determined by maximally selected log-rank statistics. A stress test subset (top 50% MaxVAF) was analyzed to decouple findings from analytical noise inherent at low tumor fractions. Results: In the 73-gene cohort (median age 53.2; 91% MSS, 14% BRAF mutated, 64% RAS mutated), MaxVAF was the strongest predictor of worse OS in both univariable (HR 1.32, p < 0.001) and multivariable (MV) models (HR 1.31, p < 0.001). Paradoxically, high rMATH was associated with improved OS (MV HR 0.89, p = 0.014). This protective signal of high heterogeneity was more pronounced in the dichotomized model (MV HR 0.71, p < 0.001) and persisted in the subset of high-burden patients (top 50% MaxVAF) (MV HR 0.69, p < 0.001) and the MSS subset (MV HR 0.68, p = 0.003). In the 701-gene panel cohort, MaxVAF remained the dominant independent predictor (MV HR 2.37, p < 0.001). bITH was not independently prognostic (MV HR 0.98, NS). Conclusions: MaxVAF serves as the primary ctDNA-derived driver of clinical outcomes in mCRC, confirming that ctDNA-inferred ITH metrics are heavily confounded by total tumor shedding. The unexpected association between high rMATH and improved OS suggests that increased clonal diversity, at a fixed tumor burden, may indicate a less evolutionarily pruned or consolidated tumor compared to those that have undergone a selective clonal sweep. These results highlight that while ctDNA can characterize clonal architecture, the clinical interpretation of heterogeneity must be contextualized within the tumor’s total systemic volume and evolutionary state. Cohort Variable (High vs Low) Multivariable HR (95% CI)* p-value 73-gene panel MaxVAF 1.31 (1.20–1.43) <0.001 Raw MATH 0.89 (0.81–0.98) 0.014 bITH 0.98 (0.90–1.08) 0.716 701-gene panel MaxVAF 2.37 (1.52–3.71) <0.001 Raw MATH 0.85 (0.50–1.44) 0.536 bITH 1.23 (0.82–1.87) 0.320 *HR per 1 SD increase. Raw MATH was adjusted for MaxVAF, while bITH was tested without redundant MaxVAF adjustment. All models adjusted for age, sex, MSI, BRAF, and RAS status.

Patterns of unscheduled oncologic consultations at a tertiary center in North Africa: Are we treating emergencies or filling gaps?

e13622 Background: Improvements in cancer treatment have improved survival, transforming many malignancies into chronic diseases. This evolution has led to an increasing number of acute situations requiring rapid and specialized oncological management owing to the complexity of the disease. Understanding the context of unscheduled oncology consultations is essential to ensure effective patient management and optimizing patient flow within oncology services, particularly in low- and middle-income settings. ObjectivesThis study aimed to identify the reasons why patients seek unscheduled medical oncology consultations and to evaluate the clinical appropriateness of these visits. Methods: This descriptive prospective study was about 202 patients who attended unplanned consultations at the Department of Medical Oncology with an analysis of demographic, clinical characteristics, referral mode, consultation reason, deployed resources and outcomes. Results: Breast (55%) and digestive (15%) cancers are the most common. 87% patients were receiving active anticancer therapy at the time of consultation and 54% had metastatic disease. 91% patients were self-referred. Consultations were primarily for administrative issues (38%), only 18% patients presented for true emergencies, mainly due to pain (8%). 14% of patients benefit from diagnostic and therapeutic procedures. 14% had attended similar consultations within the previous three months. Disease progression was confirmed in 14% of cases, and mortality rate is 2% in the overall cohort, rising to 8% among patients presenting with true oncological emergencies. Conclusions: Most unscheduled oncological consultations were non-urgent, illustrating the need for patient education and structured care pathways, while true oncological emergencies constituted only a small proportion, indicating where clinical attention and resources should be prioritized.

The applicability of the 21-gene assay to inform chemotherapy benefit in lymph node–positive hormone receptor–positive male breast cancer.

e12509 Background: There are no studies focusing on the applicability of the 21-gene Oncotype Dx Recurrence Assay (RS) assay in predicting the benefit from chemotherapy in hormone receptor positive (HR+) Her2 negative (Her2-) lymph node positive(LN+) male breast cancers (BC). The aims of our study were to determine if chemotherapy administration based on RS in men with HR+Her2-LN+ BC impacted overall survival (OS). Methods: We conducted a retrospective cohort study on adult men and women with HR+ Her2-, 1-3 axillary LN + BC, with a valid oncotype DX RS assay, diagnosed between the years 2004-2020, using the National Cancer Database. RS risk categories were defined as low risk: 0-13, intermediate risk:14-25, and high risk: ≥26. Results: Higher RS (both as a continuous and categorical variable) was significantly associated with worse OS in males (p=0.003 continuous, p=0.006 categorical), females ≤50 years old (p<0.001 both continuous and categorical), and females >50 years old (p<0.001 both continuous and categorical). In the stratified unadjusted and adjusted models (adjusted for race, lympho-vascular invasion, comorbidities, tumor grade, and year of diagnosis), there was no association between receipt of chemotherapy and OS in males for all RS groups. Conversely, chemotherapy improved the survival for women ≤50 years old who belonged to the intermediate and high RS risk groups (p=0.01 and p<0.001 respectively) and also improved OS for females >50 in all RS risk groups (p<0.001 for each of the three risk groups). Conclusions: RS is associated with OS in men and women with HR+ Her2- LN+ BC. However, RS is not an indicator of the benefit of chemotherapy on OS in men, in contrast to women, with HR+ Her2- LN+ BC.

Assessment of ctDNA tumor fraction and confidence in driver-negative liquid biopsy findings.

e15126 Background: Circulating tumor DNA (ctDNA) analysis enables non-invasive detection of tumor-specific genomic alterations, supporting the clinical utility of liquid biopsy in cancer diagnosis, prognosis, and treatment selection. However, negative results can be difficult to interpret when circulating tumor DNA (ctDNA) levels (viz. Tumor fraction) are low. ctDNA tumor fraction is a key determinant of assay sensitivity and may distinguish true negative findings from cases with insufficient tumor shedding. ctDNA tumor fraction varies by cancer type, disease stage, and tumor burden, and low tumor fraction can limit mutation detection. Understanding the impact of ctDNA tumor fraction is critical for interpreting liquid biopsy results, optimizing assay performance, and guiding clinical decision-making. This study evaluates ctDNA tumor fraction as a clinically actionable metric to guide treatment decisions and advise reflex tissue testing upon negative liquid biopsy results using the OncoIndx next-generation sequencing (NGS) assay. Methods: A retrospective concordance analysis was performed on paired tissue biopsy (TBx) and liquid biopsy (LBx) samples from 279 patients with diverse solid tumors tested using the OncoIndx next-generation sequencing assay. Positive percent agreement between tissue and liquid biopsy for detection of oncogenic driver alterations was calculated. Patients were stratified by ctDNA tumor fraction ( > 20% vs < 20%) to evaluate positive and negative concordance between TBx and LBx findings. Results: From the analysis, we found that 176 patients were ctDNA-negative and 103 were ctDNA-positive. From the ctDNA positive cohort, 99 patients showed concordance with tumor fraction ( > 20%) with a positive predictive agreement of 96.1% while 4 patients were found to have tumor fraction < 20%. From the ctDNA negative cohort of 176 patients, 161 patients were found to have ctDNA tumor fraction above 20% ( > 20%) and only 15 patients were found with tumor fraction < 20%. This clearly indicates that 91.5% (n = 161) of patients in the ctDNA negative cohort with high tumor fraction fall under the category of true NMD which was also found to be negative in paired tissue biopsy sample. Whereas, the 8.5% (n = 15) of patients in ctDNA negative cohort who might require reflex testing since their tumor fraction was below the 20% cut-off. Conclusions: ctDNA tumor fraction is a critical interpretive biomarker that can guide reflex tissue testing after negative liquid biopsy results. Incorporation of tumor fraction thresholds into clinical reporting with OncoIndx may reduce unnecessary invasive procedures while minimizing the risk of missed actionable mutations, thereby improving confidence in precision oncology decision-making.

Comparative outcomes of hypofractionated versus conventional radiotherapy following mastectomy for breast cancer: A systematic review and meta-analysis.

e12544 Background: Previous meta-analyses have compared hypofractionated versus conventional postmastectomy radiotherapy, but there have been new observational studies highlighting the need for an updated analysis. Our meta-analysis compares hypofractionated and conventional fractionated postmastectomy radiotherapy in breast cancer patients, with a focus on reconstruction-related complications. Methods: An updated systematic search of PubMed, Embase, Scopus, Web of Science and the Cochrane Library was performed from the last search date of the most recent eligible meta-analysis(i.e January 10, 2025) to January 20, 2026. Randomized controlled trials and retrospective cohort studies comparing hypofractionated and conventional fractionated radiotherapy after mastectomy were included. Outcomes of interest included overall complications, infection, capsular contracture, reconstruction failure, fat necrosis, hematoma, wound dehiscence and reoperation. Pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Risk of bias was assessed using RoB 2 for randomized trials and ROBINS-I V2 for non-randomized studies. Results: The updated search identified 03 additional studies, expanding the evidence base to 14 studies including 4047 patients. HFRT was associated with complication rates comparable to CFRT, including major complications (OR = 0.81, 95% CI 0.53-1.23, p = 0.32), infections (OR = 0.93, 95% CI 0.55-1.56, p = 0.78) and capsular contracture (OR = 0.60, 95% CI 0.33-1.07, p = 0.08). No significant differences were observed for reconstruction failure, wound dehiscence, fat necrosis, reoperation or hematoma. Effect estimates were consistent with prior meta-analyses, with improved precision for several endpoints. Conclusions: This updated meta-analysis incorporating recent randomized and observational evidence supports the safety of HFRT comparable to CFRT, with respect to reconstruction-related complications, reinforcing its role as an alternative to conventional fractionation in appropriately selected patients.

Real-world resource use and cost in patients treated with originator or biosimilar rituximab in a large U.S. insurance claims database.

11159 Background: Rituximab-pvvr, Rituximab-arrx, and Rituximab-abbs are monoclonal antibodies approved by the FDA as biosimilars to originator rituximab. All are approved for treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Biosimilars are intended to deliver equal clinical outcomes to originators at a lower cost, but there remains limited ‘real-world’ investigation of these outcomes. This study describes and compares resource use and cost for patients receiving originator or biosimilar rituximab in the Carelon Research Healthcare Integrated Research Database (HIRD). Methods: We conducted a retrospective cohort study of adults with newly diagnosed NHL and CLL identified by ICD-10 codes between 1/1/2018 and 7/31/2024 in the Carelon Research HIRD and treated with rituximab. Included patients had ≥1 claim for originator or biosimilar rituximab after NHL or CLL diagnosis. Baseline demographics were assessed at rituximab initiation ( index date ). Inpatient, outpatient, and emergency department (ED) resource use and medication cost were assessed over one year following rituximab initiation. Costs were inflation-adjusted to 2024 USD. Originator and biosimilar rituximab groups were compared using t-test or ANOVA to assess mean differences in resource use and cost. Results: A total of 11,525 patients met inclusion criteria with mean age of 64.4 years, 57.2% male, and 76.9% reporting white non-Hispanic race/ethnicity. Most of the cohort (89.8%) were diagnosed with NHL. There were no significant differences in mean follow-up duration (p=0.960), rituximab infusions (p=0.987), treatment duration (p=0.106), inpatient hospitalizations (p=0.241), or ED visits between groups (p=0.702) ( see table ). Mean overall medication costs were significantly lower in all biosimilar groups vs. originator (p<0.001). Conclusions: In this large real-world cohort of NHL and CLL patients, resource use was similar in patients treated with originator and biosimilar rituximab, but medications costs were significantly lower in the biosimilar groups. Our findings demonstrate how biosimilar therapies in cancer can deliver similar clinical outcomes to originators, while generating meaningful cost savings for the U.S. healthcare system. Mean 1-Year Outcomes Originator Rituximab (n=7,123) Biosimilar Rituximab-pvvr (n=1,846) Other Rituximab Biosimilars (n=2,556) Follow-Up Duration, Months (SD) 10.8 (2.7) 10.8 (2.7) 10.8 (2.7) Count of Rituximab Infusions (SD) 5.7 (2.5) 5.7 (2.6) 5.7 (2.5) Rituximab Treatment Duration, Months (SD) 4.2 (3.3) 4.1 (3.3) 4.1 (3.3) Count of All-Cause Inpatient Stays (SD) 1.6 (3.1) 1.6 (3.2) 1.5 (2.9) Count of All-Cause ED Visits 0.6 (1.4) 0.6 (1.3) 0.6 (1.2) Medication & Related Costs (SD)* $123,499 ($145,374) $77,728 ($96,377) $90,868 ($122,510) *Includes all medications paid under medical benefit, including rituximab.