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Association of incidence and severity of neurotoxicity with six FDA-approved chimeric receptor T-cell therapies: A meta-analysis of 61 studies including 8,376 patients.

e23351 Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a significant and serious side effect of chimeric antigen receptor-T (CAR-T)-cell therapies, with incidence varying widely across different CAR-T products. The true overall risk and product-specific rates of ICANS have not been fully quantified. We conducted a meta-analysis to determine the pooled incidence of ICANS, including severe ICANS (grade ≥3), across six FDA-approved CAR-T cell therapies. Methods: We conducted a systematic review of the published literature for clinical trials and observational studies reporting ICANS rates with six FDA-approved CAR-T products [axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), lisocabtagene maraleucel (liso-cel), brexucabtagene autoleucel (brexu-cel), idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel)]. The primary endpoint was incidence of any grade ICANS; secondary endpoint was incidence of severe ICANS (grade ≥3). Pooled incidence proportions of any grade ICANS and grade ≥3 ICANS were estimated using a random-effects model. Between-study heterogeneity was assessed (I² statistic, Cochran Q). Results: We analyzed 61 studies encompassing 8,376 patients treated with CAR-T. Overall, the pooled incidence of any grade ICANS was 28.3% (95% confidence interval [CI] 23.6–33.6), and severe ICANS (grade ≥3) occurred in 9.4% (95% CI 7.5–11.8). Between-study heterogeneity was high (I² = 95%, p < 0.001), reflecting broad variability across products and settings. ICANS rates differed markedly by product. Any grade ICANS incidence ranged from 9.3% with cilta-cel (targeting BCMA for myeloma patients) to 60.9% with brexu-cel (targeting CD19 for lymphoma patients), with intermediate incidences for ide-cel (19.0%), tisa-cel (15.8%), liso-cel (26.5%), and axi-cel (53.3%). Similarly, grade ≥3 ICANS ranged from 3.5% with cilta-cel to 28.9% with brexu-cel, with ide-cel 3.9%, tisa-cel 4.1%, liso-cel 8.9%, and axi-cel 18.3%. Differences across products were statistically significant ( p < 0.001). Conclusions: Approximately 28% of CAR-T recipients develop ICANS, but risk varies substantially by each CAR-T product. CD28-costimulatory CD19 CAR-T therapies (axi-cel, brexu-cel) carry the highest neurotoxicity risk, whereas 4-1BB-based CD19 and BCMA-targeted CAR-T products have much lower rates. The overall risk for severe ICANS is roughly 1 in 10 patients. These findings underscore the significance of product-specific risk stratification for not only patient counseling, and strategies for monitoring and early intervention, but also providing benchmarks for developing safer next-generation CAR-T therapies.

Phase angle is independently associated with muscle strength across multiple handgrip strength metrics in young adults: A cross-sectional study

Objective Phase angle derived from bioelectrical impedance analysis has been proposed as a marker of muscle quality associated with muscle function; however, the extent to which its association with muscle strength is influenced by health status, dietary patterns, physical activity, and demographic factors remains incompletely characterized. This study examined the association between phase angle and muscle strength assessed using multiple handgrip strength (HGS) metrics, accounting for relevant clinical and lifestyle factors. Methods This cross-sectional study included 1,125 adults with complete data on phase angle, skeletal muscle mass, and HGS. Phase angle was measured using bioelectrical impedance analysis. Muscle strength was assessed as absolute HGS and HGS normalized to height² (HGS/h²). Low muscle strength was defined using sex- and age-specific international normative values below the 10 th percentile for both HGS and HGS/height². Results Phase angle was consistently associated with muscle strength across both continuous and dichotomous analyses. In multivariable linear regression models, phase angle was positively associated with HGS (β std  = 0.26; P < 0.001) or HGS/ h² (β std  = 0.38; P < 0.001). In logistic regression models, higher phase angle was associated with lower odds of low muscle strength (in fully adjusted Model 2 HGS: OR, 0.37; 95% CI, 0.29–0.48; HGS/h²: OR, 0.31; 95% CI, 0.24–0.41; both P < 0.001). These associations were independent of sex, age, body fat percentage, physical activity level, and comorbidity categories. Conclusions and relevance Phase angle was consistently associated with muscle strength across continuous and dichotomous outcomes after adjustment for adiposity, physical activity, and comorbidities. These findings suggest that phase angle may have potential utility as a supportive population-level marker in similar young adult populations; however, it should not be used as a substitute for direct muscle strength assessment at the individual level.

Time-dependent gate breakdown of Schottky p-GaN gate HEMTs down to 15 K

This work reveals the role of electron mean free path (λL) in time-dependent gate breakdown (TDGB) of Schottky p-GaN gate through cryogenic temperature measurements down to 15 K. Contrary to the monotonic temperature dependence commonly observed at high temperatures, the temperature dependence of mean time-to-failure and predicted gate lifetime exhibits a distinct transition below 200 K. Specifically, the TDGB lifetime decreases from 300 to 200 K but remains almost unchanged from 200 to 15 K. The dual-mode temperature dependence is attributed to the change of electron energy. The electron energy increases from 300 to 200 K as λL increases, but saturates from 200 to 15 K as λL becomes longer than the depletion width (WD) of the Schottky junction.

Advancements in nanotechnology for enhancing the efficiency of advanced oxidation processes: A review

A self-supervised depth-aware method for pose optimization in hybrid bronchoscopic navigation

Supporting activities of cognate redox partners for sterol-metabolizing P450 enzymes in Mycobacterium neoaurum

Association of baseline clinical factors and treatment-related variables with survival in phase I solid tumor trials.

11039 Background: Phase I trials in solid oncology increasingly use biomarker-based enrollment and evaluate diverse therapeutic mechanisms. However, outcomes among patients with advanced solid tumors remain heterogeneous, and the relative contribution of baseline patient factors versus treatment-related variables to survival is incompletely defined. Methods: We conducted a retrospective analysis of patients with advanced solid tumors treated on Phase I clinical trials in UCLA’s Drug Development Program between Jan 2013 and Sept 2025. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using the Kaplan–Meier method. Multivariable Cox proportional hazards models identified factors independently associated with OS, adjusting for clinical variables, treatment characteristics (including combination vs monotherapy, mechanism of action [MOA] of study therapy, and participation in biomarker-selected trials vs unselected patients), and baseline laboratory values. Results: 726 patients were included across 106 trials. ORR was 13.3%, and DCR was 61.7%. Median PFS was 2.9 months (95% CI 2.66–3.39), and median OS was 10.4 months (95% CI 9.15–12.34). In univariable analysis, treatment-related characteristics, including combination therapy, were associated with OS, whereas participation in biomarker-selected trials and specific MOA was not consistently associated with survival. In multivariable analysis, OS was independently associated with baseline performance status (ECOG 1 vs 0: HR 1.35, 95% CI 1.12-1.63, p = 0.0015), combination therapy (HR 0.81, 95% CI 0.68-0.98, p = 0.0283) and female sex (HR 0.79, 95% CI 0.65-0.96, p = 0.0164). Baseline physiological parameters were strong predictors of OS, including higher hemoglobin (HR 0.90 per 1g/dL increase, 95% CI 0.85-0.96, p = 0.0018), higher albumin (HR 0.48 per 1g/dL increase, 95% CI 0.38-0.61, p < 0.0001), and higher lymphocyte count (HR 0.75 per 1.0K/µL increase, p = 0.0005). Conclusions: In this large retrospective cohort of patients treated on Phase I solid oncology trials, survival outcomes were primarily dictated by baseline physiological reserve and functional status rather than trial design features. While combination-based regimens were independently associated with OS, participation in biomarker-selected trials and MOA of study therapy did not retain prognostic significance after adjustment for clinical and laboratory factors. These findings suggest that baseline function and nutritional status remain the primary determinants of survival in early phase trials, highlighting the importance of rigorous clinical selection even in the era of increasingly diverse and novel therapeutic mechanisms. Ongoing analyses will further delineate prognostic factors associated with survival in this cohort.

Intracellular pharmacology and trafficking to support sequential activation of SynchroLINK T2X antibody-drug conjugates in cancer.

e15045 Background: Clinical performance of antibody–drug conjugates (ADCs) is often constrained by rapid payload release, Cmax-driven toxicity, and limited therapeutic index. SynchroLINK T2X ADCs are designed to enable sequential intracellular activation, potentially supporting sustained intracellular exposure while reducing non-specific toxicity. We evaluated the intracellular pharmacology of T2X ADCs to assess whether this activation paradigm produces exposure–response characteristics relevant to clinical translation. Methods: T2X ADCs were evaluated in cancer cell models expressing relevant surface targets using time-dependent cytotoxicity assays designed to model transient and sustained exposure conditions. Washout experiments were performed to assess persistence of intracellular pharmacologic activity following limited extracellular exposure. Confocal imaging and colocalization analyses were used to characterize subcellular distribution following internalization. Pharmacologic perturbation of intracellular transport and lysosomal function was employed to probe dependencies relevant to sequential activation. Results: T2X ADCs exhibited time-dependent cytotoxicity profiles distinct from conventional ADC comparators, with preserved potency following transient exposure and washout. Intracellular tracking demonstrated efficient internalization and predominant localization within perinuclear, membrane-associated compartments consistent with regulated intracellular processing rather than rapid diffusional payload release. Disruption of intracellular trafficking pathways attenuated cytotoxic activity, indicating dependence on controlled intracellular transport for functional activation. These findings support sustained intracellular pharmacologic activity despite limited extracellular exposure. Conclusions: Intracellular pharmacology and trafficking studies support a sequential activation mechanism for SynchroLINK T2X ADCs in cancer that decouples cytotoxic activity from short-duration extracellular exposure. This controlled intracellular behavior provides a translational rationale for improved therapeutic index and supports further clinical development of precision activation strategies for ADC-based cancer therapies.

Stereotactic body radiotherapy versus non-SBRT radiotherapy for medically inoperable stage I non–small cell lung cancer in elderly patients: A systematic review and meta-analysis.

e20038 Background: Elderly patients with medically inoperable stage I non–small cell lung cancer (NSCLC) are commonly treated with radiation therapy. While stereotactic body radiotherapy (SBRT) is widely used, its benefits compared with conventional and hypofractionated radiotherapy in this population remain debated. We performed a systematic review and meta-analysis to clarify differences in survival, disease control, and toxicity. Methods: Eight comparative studies were included. Outcomes assessed were overall survival (OS), progression-free survival (PFS), local control, patterns of failure, mortality, and severe toxicity. Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CI) were calculated. Results: SBRT was associated with significantly improved overall survival (OS) compared with non-SBRT radiotherapy (HR 0.74, 95% CI 0.68–0.80; p<0.00001; I²=20%). No significant OS difference was observed when SBRT was compared specifically with conventional radiotherapy (HR 1.06, 95% CI 0.79–1.42). Time-specific analyses demonstrated no OS difference at 1 year; however, SBRT improved 2-year OS (RR 1.24, 95% CI 1.02–3.41), primarily when compared with conventional radiotherapy. Progression-free survival at 2 years was similar between groups. SBRT significantly improved local tumor control at 1–3 years, with the greatest benefit at 2 years (RR 1.23, 95% CI 1.09–1.38), and reduced local failure at 2 years (RR 0.33, 95% CI 0.24–0.46) and 3 years (RR 0.47, 95% CI 0.34–0.66). SBRT significantly reduced lung cancer–specific mortality compared with conventional radiotherapy (RR 0.47, 95% CI 0.24–0.93), but not when compared with hypofractionated radiotherapy. Severe overall and pulmonary toxicities were low and comparable between SBRT and non-SBRT treatments. Conclusions: In elderly patients with medically inoperable stage I NSCLC, SBRT offers meaningful improvements in survival and local tumor control compared with conventional radiotherapy, without added toxicity. Outcomes are similar between SBRT and hypofractionated radiotherapy, highlighting the importance of modern dose-delivery strategies in this population.

Enhanced detection of clinically actionable non-V600 <i>BRAF</i> alterations by DNA+RNA amplicon-based sequencing in a real-world solid tumor cohort.

e15086 Background: Although BRAF V600 mutations are established therapeutic targets, growing evidence suggests that non-V600 BRAF alterations—particularly class II mutations—may also be actionable through combined RAF/MEK inhibition. DNA+RNA amplicon-based sequencing has been increasingly adopted in solid tumors; however, its performance in detecting uncommon but clinically relevant driver alterations remains uncertain. This study characterized BRAF alterations in a large real-world solid tumor cohort and compared the performance of DNA capture–based sequencing with DNA+RNA amplicon-based sequencing in detecting clinically meaningful BRAF variants. Methods: Next-generation sequencing (NGS) data from 33,118 solid tumors were analyzed using DNA capture–based or DNA+RNA amplicon-based sequencing, with BRAF alterations classified into functional classes I–III for cross-platform comparison. Results: Overall, BRAF alterations were detected in 8.55% (1,414/33,118) of tumors. Detection rates were comparable between DNA capture–based sequencing (4.39%, 700/15,957) and DNA+RNA amplicon-based sequencing (4.16%, 714/17,161; P = 0.322), demonstrating non-inferior overall performance. Across the cohort, class I BRAF mutations accounted for the majority of alterations (47.03%). Notably, despite similar overall detection rates, DNA+RNA amplicon-based sequencing identified a significantly higher proportion of clinically relevant non-V600 BRAF alterations. In the amplicon group, previously reported class II (20.02% vs 13.43%) and class III (21.99% vs 10.00%) variants were more frequently detected（ P &lt; 0.001）, particularly in exon 11 and exon 14, which are increasingly recognized as candidates for dual-target therapies, including RAF/MEK inhibition strategies. In contrast, DNA capture–based sequencing detected a higher proportion of rare or unclassified variants with unclear clinical significance. Consistently, variants of unknown clinical significance were significantly more frequent in the capture-based group than in the amplicon-based group (27.9% vs 0.42%, P &lt; 0.001). These findings indicate that while capture-based sequencing offers broader variant detection, amplicon-based sequencing enriches for clinically actionable alterations. Conclusions: In a large real-world solid tumor cohort, DNA+RNA amplicon-based sequencing demonstrated non-inferior overall BRAF detection compared with DNA capture–based sequencing and superior sensitivity for clinically relevant non-V600 BRAF alterations. Enhanced detection of class II BRAF mutations by DNA+RNA sequencing may expand access to targeted and combination therapies, supporting its clinical utility in precision oncology.

Atezolizumab for Alveolar Soft Part Sarcoma: A Clinical Trial Update

We previously reported initial results of the pivotal phase II trial of atezolizumab for patients with alveolar soft part sarcoma (ASPS; ClinicalTrials.gov identifier: NCT03141684 ). Here, we report on three additional years of observation. Fifty-three patients with ASPS received atezolizumab. Median duration of response increased to 37.0 months. Objective response rate (ORR) and median progression-free survival (mPFS) remained essentially as previously reported (35.8% [95% CI, 23.1 to 50.2] and 20.8 months [IQR, 7.6-not reached], respectively). ASPSCR1::TFE3 fusion type was determined for 47/53 patients; ORR and mPFS were higher among the 41 patients expressing type 1 (43.9% [95% CI, 28.5 to 60.2] and 28.3 months [IQR, 9.2-not reached], respectively) than the six patients expressing type 2 (0% [95% CI, 0 to 45.9] and 7.5 months [IQR, 3.9-not reached], respectively, PFS HR, 3.2 [95% CI, 1.01 to 10.2]). Eleven patients chose a per-protocol drug holiday (range, 3.5-26.4 months) after ≥2 years of treatment; two experienced disease progression during the holiday. Nine eligible patients elected to receive bevacizumab plus atezolizumab after progressing on monotherapy; ORR was 0% and mPFS was 18.5 months (IQR, 7.9-21.1) in this small cohort. Long-term results support using atezolizumab to treat ASPS, even for several years; a drug holiday with careful monitoring may be an option for some patients.

CDC analysis of pancreatic cancer and diabetes-associated pancreatic cancer mortality among older adults (1999-2020).

e16447 Background: Pancreatic cancer is a major cause of cancer related mortality in the United States. New-onset diabetes occurring one to three years before diagnosis may serve as an early clinical marker of pancreatic cancer, while long-standing diabetes is an established risk factor for disease development. Despite these known associations, mortality trends in individuals with diabetes associated pancreatic cancer remain poorly characterized. Understanding long-term mortality trends in this population is essential to inform public health strategies and guide clinical practice. Methods: Mortality data were obtained from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2020, including individuals aged ≥55 years identified using ICD-10 codes. Age-adjusted mortality rates (AAMRs) per 100,000 population and annual percentage change (APC) were calculated and stratified by sex, race/ethnicity, and geographic region. Statistical significance was defined as p &lt;0.05. Results: From 1999 to 2020, a total of 775,072 deaths were attributed to pancreatic cancer (PC), with age-adjusted mortality rates (AAMRs) increasing from 46.9 to 50.0 per 100,000 population. Among these, 57,777 deaths were attributed to diabetes-associated pancreatic cancer (DM-PC), with AAMRs rising from 3.1 to 4.5. DM-PC AAMRs peaked between 2018 and 2020, demonstrating a significant increase (APC: 9.03; 95% CI: 5.86–11.00; p &lt;0.01). Men exhibited higher AAMRs than women for both PC and DM-PC. PC-related AAMRs were highest among non-Hispanic African American and non-Hispanic white populations, whereas DM-PC AAMRs were highest among African American and Hispanic populations. Regionally, PC AAMRs were highest in the Northeast, while DM-PC AAMRs were highest in the West. Urban areas demonstrated higher AAMRs for PC, whereas rural areas consistently exhibited higher AAMRs for DM-PC. Conclusions: DM-PC mortality increased significantly over the past two decades, disproportionately affecting men, African Americans, Hispanics, and population from the West. These findings highlight the importance of early clinical recognition of DM-PC to reduce avoidable deaths and guide future resource allocation.

Tumor miRNA expression as a potential biomarker of immune-related toxicity in patients with melanoma or urothelial carcinoma treated with immune checkpoint inhibitors.

e14588 Background: Immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes in several solid tumors, including melanoma and urothelial carcinoma. However, their clinical benefit is often limited by the development of immune-related adverse events (irAEs), which can compromise treatment continuation and patient quality of life. Identifying molecular biomarkers capable of predicting immune-related toxicity remains an unmet clinical need in oncology. MicroRNAs (miRNAs), small non-coding RNAs involved in immune regulation and tumor biology, have emerged as promising biomarkers, due to their potential role in predicting ICI- related toxicity. Methods: We investigated the association between tumor tissue miRNA expression and the development of irAEs in patients with melanoma (n = 69) or urothelial carcinoma (n = 108) treated with ICI agents. MiRNAs were extracted from formalin-fixed paraffin-embedded tumor biopsies, and their expression were analyzed by quantitative PCR. Nineteen miRNAs were selected based on evidence from publicly available studies addressing implication in immune response and signaling pathways potentially associated with the development of irAEs after ICI treatment. Results: In this study, miRNA expression levels were not associated with sociodemographic characteristics or type of ICI in either cohort. In the melanoma cohort, 55.1% of patients developed irAEs. Lower tumor expression of miR-125b-5p (p = 0.05), miR-182-5p (p = 0.031), miR-192-5p (p = 0.031), and miR-199a-5p (0.035) were significantly associated with the occurrence of global irAEs. Similarly, reduced expression of these miRNAs was observed in patients who developed fatigue/asthenia, the most common irAE, occurring in 36.8% of melanoma patients with irAEs. Furthermore, distinct miRNAs expression patterns were associated with specific irAE, including arthritis, hepatitis, and thyroiditis. In the urothelial carcinoma cohort, no miRNAs were associated with global irAEs. However, lower tumor expression of miR-34c-5p was significantly associated with ICI-induced pneumonitis (p = 0.037) and miR-493-5p expression with ICI-induced asthenia (p = 0.027). Conclusions: Tumor miRNAs expression were associated with global irAEs in patients with melanoma treated with ICIs, whereas such associations were not observed for overall toxicity in urothelial carcinoma. Exploratory associations were found between specific miRNAs expression and individual irAEs in both cohort of patients suggesting the potential role of miRNAs as biomarkers of irAEs. Further studies will be required to validate these preliminary results. Key words: Immune checkpoint inhibitors (ICIs), Immune-related adverse events (irAEs), Melanoma, Urothelial carcinoma, tumor miRNAs expression.

RAPID: A pilot feasibility study of rapid dinutuximab infusion in patients with relapsed/refractory (RR) high-risk neuroblastoma (HRNBL).

10013 Background: Dinutuximab is a key component of therapy for HRNBL and is widely used in the RR setting. Standard administration requires inpatient infusions of ~10 hours daily. Emerging pediatric and adult data support shorter infusion durations. Evaluating rapid infusion of dinutuximab (RID) with chemotherapy may reduce pain, facilitate outpatient delivery, and decrease healthcare burden. Methods: This prospective, single-institution pilot study enrolled patients from 11/2022-12/2025 following IRB approval. Eligible patients included those ≥1 year old with RR-NBL, adequate organ function, and prior dinutuximab exposure. Patients received chemoimmunotherapy consisting of dinutuximab 17.5 mg/m²/day for 4 days (over 2-4 hours) combined with irinotecan/temozolomide (ITD) or cyclophosphamide/topotecan (CTD) for up to 6 cycles. Outpatient administration was permitted after cycle 1 if tolerated. The primary feasibility endpoint was successful dinutuximab administration over ≤5 hours with ≤1 patient experiencing unacceptable toxicity (UT) during cycle 1 in a 10-patient cohort. Secondary and exploratory endpoints included infusion duration, serial pain scores assessed during and post-infusion, opioid use in morphine milligram equivalents (MME), toxicity, feasibility of outpatient administration, pharmacokinetics (PK) and human anti-chimeric antibody (HACA). Changes in MME were compared using a one-sample t-test. Results: Eleven patients (median age 14 years, range: 3-24) received ITD (n=6) or CTD (n=5). All patients met the primary feasibility endpoint. Median infusion time was 2 hours (range 2-4) across all cycles. One patient (3 years old), enrolled in the early post-transplant period developed UT (grade 3 ventricular dysfunction). The protocol was amended to exclude patients within 6 months of transplant, require dinutuximab tolerance within 2 months, and extend cycle 1 infusion to 4 hours for patients &lt;12 years of age; this patient was replaced per protocol. Across cycles 1-6, mean pain score was 0.4 (SD 0.46), and mean opioid usage was 0.04mg/kg MME (SD 0.07), reflecting a 78% reduction of opioid use in cycle 1 RID compared to the pre-enrollment standard-infusion cycle (p&lt;0.001). Outpatient RID was administered in seven patients without hospital admission; 1 patient was admitted for chemotherapy-related toxicity, 3 patients remained inpatient (social reasons). RID showed expected PK levels; HACA was noted in 1 patient. Most common grade 3 toxicities (27%): increased ALT and hypokalemia; 1 patient (with UT) had grade 4 toxicity (dyspnea, hypocalcemia). Conclusions: RID was feasible and well tolerated, including in the outpatient setting. Pain control was achieved with standard premedication and significantly reduced opioid requirements compared with standard infusion. These data support planned multi-institutional evaluation of RID. Clinical trial information: NCT05421897 .

Non-surgical management and outcome of 1,113 patients with stage I-II non-small cell lung cancer (NSCLC) in a 20-year cohort.

8045 Background: Surgical resection is the primary therapy for stage I-II NSCLC but not performed in a subset of patients due to comorbidities or self-election, who instead undergo radiation with or without systemic therapy (RT±ST). Little is known about the demographic, tumoral, therapeutic, and quality-of-life (QOL) characteristics of this non-surgical group. Understanding their differences from the surgical group is essential for developing precision treatment strategies and tailored survivorship guidelines. Methods: In a prospectively enrolled (1997-2016) and followed (through 2025) cohort of 20,951 primary lung cancer patients, 6,486 (31%) had stage I-II NSCLC, including 5,359 (83%) treated surgically (Surgical) and 1,113 (17%) otherwise (Non-surgical). Preexisting diseases were grouped into cancer, lung, and other comorbidities. QOL data were available for 40% of all patients. Descriptive analysis of demographics, tumor features, treatment patterns, and QOL metrics, as well as survival analysis (median years and overall survival [OS] rates) were conducted. QOL measures, on overall and 15 symptom and functional domains, were scored 0 (worst) to 10 (best), with 1-unit difference considered clinically and statistically meaningful. Results: At time of diagnosis, compared to the Surgical, the Non-surgical patients were older (median 73 v 68 years), more likely to have smoked cigarettes (91% v 83%), squamous cell and unspecified NSCLC (53% v 28%), stage IIB (19% v 12%), and preexisting lung comorbidities (71% v 58%). Non-surgical patients more frequently received RT±ST than the Surgical (70% v 21%) and had shorter median survival (2.5 v 7.8) years. Within the Non-surgical, 28% had no cancer treatment (No-Tx), 44% RT-only, 7% ST-only, and 19% both (RT+ST); their respective median diagnosis ages were 74, 76, 68, 70 years; median survival were 1.7, 2.7, 2.2, 3.2 years; 5-year OS (95%CI) at 25% (21-31), 25% (21-29), 26% (17-38), 30% (25-37); and 10-year OS at 9% (7-14), 7% (5-10), 10% (5-21), 9% (6-14), respectively. RT-only group had highest rates of comorbidities (37-84%) and the No-Tx the lowest (31-66%). Although the overall QOL scored the same for all groups, RT-only patients reported the worst scores on multiple symptoms burden, and the No-Tx reported the least pain and lung cancer symptoms but the worst on mental well-being and social activities. Conclusions: Non-surgically managed stage I-II NSCLC cases present clinically distinct patients with the shortest median survival in No-Tx group and highest 5-year survival in RT+ST. RT-only patients were oldest, had the most comorbidities, and reported the worst symptom burdens. These differences highlight the need for more in-depth analyses and studies (considering age, histology, comorbidity, QOL, etc.) to support tailored therapeutic strategies and survivorship care for patients who decline or are not suitable for surgery.

Trends in historical response rates: A meta-analysis of KRAS G12C inhibitors in pretreated metastatic pancreatic cancer—Effects on ORR and disease control.

e16443 Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with KRAS mutations present in approximately 90% of cases. Patients with advanced or metastatic PDAC who have progressed after standard chemotherapy face limited treatment options, with historical outcomes showing objective response rates (ORR) below 10% and median progression-free survival (PFS) and overall survival (OS) of approximately 2-4 months and 6-8 months, respectively. The development of covalent KRAS G12C inhibitors—including sotorasib, adagrasib, garsorasib, glecirasib, and divarasib—has opened new therapeutic options for this molecularly defined subset of PDAC patients. Methods: We conducted a systematic review and meta-analysis of clinical trials evaluating KRAS G12C inhibitor monotherapy in patients with advanced/metastatic pancreatic ductal adenocarcinoma. Data were extracted from 3 studies (Strickler 2022, Li J 2025, and Tanios 2023) encompassing a total of 91 patients with KRAS G12C-mutant PDAC who had received 1-2 prior lines of chemotherapy. Pooled estimates were calculated using random-effects meta-analysis models (DerSimonian-Laird method). For proportion outcomes (ORR and DCR), standard errors were calculated using binomial distribution, and for continuous outcomes (PFS and OS), inverse-variance weighting was employed. Heterogeneity was assessed using the I² statistic and Cochran's Q test. All confidence intervals were calculated at the 95% level. Results: The pooled analysis revealed clinically meaningful efficacy across all endpoints. The pooled objective response rate (ORR) was 32.9% (95% CI: 17.0% to 48.9%), with moderate heterogeneity (I² = 64.0%). The pooled disease control rate (DCR) was substantially higher at 88.3% (95% CI: 80.5% to 96.1%), with low heterogeneity (I² = 27.7%), indicating consistent disease stabilization across studies. For survival outcomes, the pooled median progression-free survival (PFS) was 4.98 months (95% CI: 3.62 to 6.34 months), with low heterogeneity (I² = 32.3%). The pooled median overall survival (OS) was 8.73 months (95% CI: 6.07 to 11.39 months), though with substantial heterogeneity (I² = 77.0%). Conclusions: KRAS G12C inhibitor monotherapy demonstrates clinically significant and durable efficacy in pretreated adults with advanced/metastatic PDAC harboring the KRAS G12C mutation. The pooled ORR of approximately one-third, together with a DCR near 90%, indicates substantial tumor control in a population with historically poor outcomes. Median PFS of approximately 5 months and OS of nearly 9 months represent clinically relevant improvements over standard salvage therapies, supporting KRAS G12C inhibitors as a viable option after chemotherapy failure.

OrigAMI-5: A randomized, phase 3 study of amivantamab plus pembrolizumab and carboplatin vs standard of care pembrolizumab plus platinum and 5-fluorouracil as first-line treatment in recurrent/metastatic head and neck cancer.

TPS6127 Background: Recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC) is associated with significant morbidity and mortality. Current first-line standard of care regimens, including combinations of pembrolizumab with platinum-based chemotherapy with/without 5-fluorouracil (5-FU), yield low response rates and poor long-term outcomes, with a median survival of approximately 1 year. Many patients with R/M HNSCC exhibit EGFR and MET overexpression. Amivantamab is an EGFR-MET bispecific antibody with immune cell–directing activity that is FDA-approved in EGFR -mutated advanced non-small cell lung cancer. In a prior report of the phase 1b/2 OrigAMI-4 study (NCT06385080), subcutaneous (SC) amivantamab monotherapy demonstrated a confirmed objective response rate of 45% among participants with HPV-unrelated R/M HNSCC whose disease had previously progressed on immune checkpoint inhibitor and platinum-based chemotherapy (Harrington Oral Oncology 2025). The objective of this phase 3 randomized study is to assess the efficacy of SC amivantamab in addition to pembrolizumab and carboplatin, as compared to the standard of care (pembrolizumab plus carboplatin or cisplatin and 5-FU) as first-line therapy for participants with R/M HNSCC. Methods: The ongoing multicenter, global OrigAMI-5 study (ClinicalTrials.gov identifier: NCT07276399) is planned to open in approximately 205 sites in 22 countries. Eligible participants will have HPV-unrelated R/M HNSCC (primary tumor locations: oral cavity, oropharynx, hypopharynx, or larynx); all primary oropharyngeal tumors must be human papillomavirus (HPV)-negative. All participants, regardless of combined positive score (CPS), are eligible but must have local testing results to determine CPS for stratification and be treatment-naïve in the R/M setting; systemic therapy in the locally advanced setting is allowed if completed &gt;6 months prior. Prior exposure to EGFR or MET targeting agents is exclusionary. Approximately 500 participants will be randomly assigned 1:1 to receive SC amivantamab (co-formulated with recombinant human hyaluronidase [rHuPH20]) with pembrolizumab and carboplatin, or 5-FU plus pembrolizumab and investigator’s choice of carboplatin or cisplatin. Randomization will be stratified by programmed cell death ligand 1 (PD-L1) CPS (&lt;1, 1–19, ≥20) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1). The primary endpoints will be objective response rate and overall survival. Secondary endpoints include progression-free survival, duration of response, and patient-reported outcomes. Safety assessments will include adverse event monitoring and laboratory abnormalities. Clinical trial information: NCT07276399 .

Epidemiology of melanoma in Syria: A retrospective analysis from the national cancer center.

e21524 Background: Epidemiological data on melanoma from conflict-affected regions like Syria are critically scarce, hindering effective disease management and resource allocation. This study aims to address this gap by providing the first analysis of the demographic and clinical characteristics of patients diagnosed with new-onset melanoma at Syria's principal oncology referral center over four years. Methods: We conducted a retrospective, hospital-based epidemiological study at Al-Bairouni University Hospital, the national cancer center serving approximately 70% of Syria's oncology population. All patients with a new histopathological diagnosis of cutaneous melanoma between 1 January 2022 and 31 December 2025 were included. Data on demographics (age, sex, and governorate of residence), clinical characteristics (cancer stage, grade), and smoking status were extracted from medical records. Patients were grouped by diagnosis year to analyze temporal trends. The study was approved by the local institutional review board. Results: A total of 175 patients were diagnosed with Melanoma during the study period: 33 in 2022, 32 in 2023, 57 in 2024, and 53 in 2025 (Table 1). Across all years, a consistent male predominance was observed (60.1%). The average age at diagnosis was 56.1 years, 40.1% of patients were smokers, and 64.5% of all cases had advanced/metastatic disease at diagnosis. The highest patient loads originated from Damascus (16.5%) and Rural Damascus (9%), followed by central governorates such as Homs (14.7%) and Hama (16.5%). Notably, patients from more distant and underserved governorates such as Deir ez-Zor (4.1%), Aleppo (12.2%), and Al-Hasakeh (4.1%) accounted for a significant proportion of the melanoma presenting to our center. Men presented with advanced-stage melanoma significantly more often than women (75% vs. 52%, p = 0.01), which was the only significant predictor in multivariate regression analysis. Age was not associated with disease stage (p &gt; 0.05). Conclusions: This study presents the first multi-year, nationwide dataset on melanoma in Syria, encompassing all 14 governorates. Our findings reveal a critical burden of disease, with close to half of all patients diagnosed at an advanced stage and over one-third identified as smokers. These actionable insights underscore the critical need for targeted public health strategies focused on tobacco control and enhanced early detection programs. This dataset provides a vital foundation for guiding these interventions and future research in the region. Diagnosis 2022 Cases 2023 Cases 2024 Cases 2025 Cases Total cases Average Age SexMale (%) Smokers (%) High grade Advanced/Metastatic at diagnosis melanoma 33 32 57 53 175 56.1 55.7% 40.1% 86.8% 64.5%

Placing oncology and conflicts of interest in a global context: Evidence from the large international ONCOTRUST-2 study.

9042 Background: Conflicts of interest (COIs) arising from relationships between pharmaceutical industry and oncologists can influence clinical practice and research. Still, global patterns of COIs and disclosure practices remain unexplored. In this interim analysis of ONCOTRUST-2 study, we compared self-reported COI-related practices and financial relationships among oncologists practicing in high-income countries (HICs) versus low-/middle-income countries (LMICs). Methods: ONCOTRUST-2 is a multinational cross-sectional survey (January 2024–January 2026) targeting oncologists with at &gt;1 year of experience from LMICs and HICs. Data were collected using snowball sampling through established professional networks and scientific societies. Multivariable logistic regression models were fitted, adjusting for years of professional experience, specialty, current position/seniority, frequency of pharmaceutical industry visits, and the presence of local COI regulations/policies. We report adjusted odds ratios (aORs) with 95% confidence intervals, using a significance threshold of p &lt; 0.05. Findings are reported in accordance with the CROSS guidelines. Results: A total of 678 oncologists responded to the survey (LMICs: 63.9; HICs: 36.1%) mainly in medical oncology (48.7%), clinical oncology (15.9%) and radiation oncology specialties (15.5%). After adjustment for experience, specialty, position, pharma-visit frequency, and local COI policy presence, HIC oncologists reported higher prevalence of higher-profile industry relationships, including consulting/advisory roles (aOR 2.13, CI: 1.45–3.13; p &lt; 0.001) and honoraria/consulting payments (aOR 2.77, CI: 1.29–5.98; p = 0.009). Trips/accommodation support was also more common in HICs (aOR 1.52, CI:1.07–2.17; p = 0.021). A marked gradient was observed for payment magnitude. HICs oncologists were less likely to report no money received (aOR 0.37, CI 0.25–0.54; p &lt; 0.001) and more likely to report receiving $2,000–$5,000 (aOR 6.96, 95% CI 3.08–15.75; p &lt; 0.001) or &gt; $5,000 (aOR 17.23, 95% CI 4.92–60.32; p &lt; 0.001). HICs oncologists reported better COIs disclosure in key academic settings. COIs disclosure before presentations was more common in HICs (aOR 2.72, 95% CI 1.81–4.09; p &lt; 0.001), and disclosure in publications was also higher (aOR 1.92, CI: 1.32–2.79; p &lt; 0.001) than in LMICs. Reporting non-disclosure was also less frequent in HICs (aOR 0.44, 95% CI 0.25–0.77; p = 0.004). Conclusions: Oncologists in HICs reported both greater engagement with and better COI disclosure compared with LMICs. These findings suggest that global COI policies and disclosure infrastructures may differ by national economic context and should be strengthened, with attention to equitable, context-appropriate implementation, regulation governance of COI in LMIC settings.

Inpatient chemotherapy and immunotherapy encounters in the United States: Recent trends, acute complications, and palliative care utilization.

e23144 Background: Most chemotherapy and immunotherapy treatments are administered in the ambulatory setting, while inpatient systemic therapies are often reserved for high-acuity and complex cases. National data on inpatient chemotherapy and immunotherapy hospitalizations in the modern immunotherapy era remain limited. We aimed to examine acute severe inpatient complications, palliative care utilization, and outcomes among hospitalizations with chemotherapy and immunotherapy. Methods: We conducted a retrospective study using the National Inpatient Sample (NIS) from 2016 to 2022. Hospitalizations with a diagnosis indicating inpatient chemotherapy (Z51.11) and/or immunotherapy encounter (Z51.12) were queried. Acute inpatient complications were identified using ICD-10 codes. Survey-weighted descriptive analyses and multivariable survey-weighted regression models were performed. Results: The cohort included 190,676 unweighted admissions representing around 953,380 weighted hospitalizations, with an average age of 41.5 years old and average length of stay (LOS) 5.9 days. 61.8% of encounters were hematologic malignancies and 35.2 % were solid organ malignancies. Encounter type distribution was chemo-only 96.1%, immune-only 2.50%, and both 1.45%. There was a steady increase in immunotherapy encounters since 2018 with 12.54% of the hospitalizations of 2018 compared to 20.92% in 2022. There was low incidence of sepsis (1.74%), acute respiratory failure (ARF, 1.54%), tumor-lysis syndrome (TLS, 1.19%). Acute kidney injury (AKI, 5.66%). Septic shock (0.55%), ventricular fibrillation/ventricular tachycardia (0.36%), cardiac arrest (0.01%), and death (0.62%) were rare events. Inpatient palliative care use occurred in 2.35% of these hospitalizations. In weighted multivariate regression analyses of palliative care utilization, acute inpatient complications were the strongest independent predictors. Palliative care use was significantly associated with sepsis (OR 4.44, 95% CI 3.83–5.14), AKI (OR 2.25, 95% CI 2.04–2.49), TLS (OR 2.04, 95% CI 1.69–2.47), and catastrophic cardiovascular events (OR 1.57, 95% CI 1.17–2.11). In adjusted log-linear models, palliative care involvement was associated with an 18% longer LOS (95% CI 14%–22%) and 35% higher total hospital charges (95% CI 30%–40%, both p &lt; 0.001), likely reflecting greater illness severity among patients receiving palliative care. Conclusions: Inpatient chemotherapy and immunotherapy hospitalizations represent a high-acuity population with infrequent but severe complications, in which palliative care utilization remains uncommon and is primarily driven by acute severe clinical complications. These findings highlight opportunities for earlier palliative integration and improved risk stratification in hospitalized patients receiving systemic cancer therapies.