Browse Articles

First-in-class DIO3 inhibitor as a novel treatment strategy in ovarian cancer.

3101 Background: Ovarian cancer carries high mortality, driven in part by platinum resistance and a scarcity of actionable therapeutic targets. Thyroid hormone signaling via triiodothyronine (T3) exerts tumor-suppressive effects, including inhibition of proliferative and DNA-damage stress pathways. Iodothyronine deiodinase type 3 (DIO3) is a clinically expressed T3-inactivating enzyme associated with aggressive disease biology, therapeutic resistance, and poor patient outcomes. DioTree Ltd is the first biotech company that developed ITYR-DBRMD, a first-in-class small-molecule DIO3 inhibitor for cancer treatment. Methods: DIO3 target engagement was evaluated using enzymatic mimic assays, intracellular T3 quantification (ELISA), and cellular thermal shift assays (CETSA). Pharmacokinetics (PK) were characterized across clinically relevant delivery routes (IV, IP, SC) with development of a dedicated bioanalytical quantification method. Antitumor efficacy was tested in nude mice bearing homologous recombination-proficient (HRP), carboplatin-resistant ovarian cancer xenografts. Mice received vehicle, ITYR-DBRMD, carboplatin, or their combination for three weeks. Tumor growth inhibition (TGI) and safety were assessed. Results: ITYR-DBRMD achieved selective and durable inhibition of DIO3 activity with direct cellular binding confirmation, robust increases in intracellular T3 levels, and consistent PK exposure across all administration routes tested. Monotherapy TGI was 43% for carboplatin and 50% for ITYR-DBRMD. Combination therapy produced a clinically meaningful efficacy increase, reaching 68% TGI, with no observed treatment-related toxicity or weight loss, supporting a favorable therapeutic index. Albumin-based tumor delivery and drug retention in tumors was established. Conclusions: These data support advancement of ITYR-DBRMD toward early-phase clinical testing, with potential application in ovarian cancer patients, a population lacking targeted therapeutic options.

Symbiotic-GI-03: A randomized, double-blind, phase 3 study of first-line PF-08634404, a PD-1/VEGF bispecific antibody, in combination with mFOLFOX6 in patients with metastatic colorectal cancer (mCRC).

TPS3675 Background: Multi-agent chemotherapy regimens (eg, mFOLFOX6) ± anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor regimens are currently the standard of care for patients (pts) with mCRC without targetable mutations. However, the 5-year survival rate remains low at approximately 16% (SEER, 2025). The addition of biological therapies (eg, bevacizumab [bev], an anti-VEGF monoclonal antibody) to immune checkpoint inhibitors (ICIs) has demonstrated a synergistic antitumor effect in solid tumors. However, ICI monotherapy has limited activity in mismatch repair proficient (pMMR)/microsatellite stable (MSS) mCRC. Simultaneous bispecific targeting of programmed death 1 (PD-1) and VEGF in conjunction with cytotoxic chemotherapy has the potential to enhance antitumor activity. PF-08634404 is a fully human immunoglobulin G4 (IgG4) bispecific antibody targeting PD-1 and VEGF. A phase 2 study of PF-08634404 with XELOX or mFOLFOX6 demonstrated promising antitumor activity with a manageable safety profile in first-line (1L) mCRC (Xu X, ESMO 2025; Abstract 796P). Methods: Symbiotic-GI-03 (NCT07222800) is an ongoing, double-blind, randomized, phase 3 study evaluating the efficacy and safety of 1L PF-08634404 + mFOLFOX6 vs bev + mFOLFOX6. Inclusion criteria are age ≥18 y; mCRC with measurable disease per RECIST 1.1; no prior systemic therapy for metastatic disease; ECOG PS 0 or 1; and adequate hematologic, hepatic, and renal function. Pts with BRAF V600E-mutant or mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) CRC, active central nervous system metastases, or clinically significant risk of hemorrhage/fistula will be excluded. Approximately 800 pts will be randomized 1:1 to receive PF-08634404 + mFOLFOX6 or bev + mFOLFOX6 until disease progression, unacceptable toxicity, withdrawal of consent, or death. Randomization will be stratified by region (North America, Europe, or rest of world), RAS status (mutant or wildtype), and presence of liver metastasis (yes or no). The dual primary endpoints are progression-free survival (PFS) by blinded independent central review and overall survival; for each, a stratified log-rank test will be used to compare arms. Hazard ratios with corresponding 2-sided 95% CIs will be estimated using a stratified Cox proportional hazards model, and medians will be estimated using the Kaplan-Meier method with corresponding 2-sided 95% CIs calculated using the log(-log) method. Secondary endpoints include PFS by investigator, objective response rate, duration of response, PFS after next-line therapy, safety/tolerability, pharmacokinetics, immunogenicity, and patient-reported outcomes. Enrollment began in December 2025. Clinical trial information: NCT07222800 .

Early recurrence and outcome determinants in NF1-associated malignant peripheral nerve sheath tumors: A single-center retrospective analysis.

e23563 Background: Malignant peripheral nerve sheath tumors (MPNST) are rare but highly aggressive malignancies in patients with neurofibromatosis type 1 (NF1). Compared with sporadic MPNST, NF1-associated tumors are characterized by earlier onset, biological heterogeneity, and poor local disease control. Real-world data on recurrence patterns, metastatic disease, and prognostic factors in this population remain limited. Methods: We performed a retrospective single-center analysis of 12 adult patients with NF1-associated MPNST treated between 2022 and 2025. Clinical, pathological, and treatment-related variables were collected. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Associations between clinicopathologic factors and outcomes were assessed using non-parametric and exact statistical tests ( p < 0.05). Results: Median age was 36 years (Q1–Q3: 31.0–46.5). High-grade tumors accounted for 58.3% of cases. Distant metastases at diagnosis were present in 25.0%. Median tumor size was 10.5 cm (Q1–Q3: 6.35–13.25). A high rate of early recurrence was observed, with 58.3% of patients developing relapse. Median RFS was 15 months (95% CI: 4–22), and recurrence risk increased from 20.5% at 5 months to 81.8% at 20 months, indicating early postoperative disease failure. Metastatic status was strongly associated with mortality: 100% of deaths occurred in patients with distant metastases ( p = 0.045). Recurrence occurred exclusively in patients without metastases, reflecting competing-risk dynamics in this small cohort. No significant associations were identified between recurrence and tumor size, grade, resection margins, chemotherapy, or tumor localization. A non-significant trend toward an association between higher grade and positive resection margins was observed ( p = 0.076). Median OS was not reached; estimated 5-year OS was 82.5% (95% CI: 46.1–95.3). Conclusions: NF1-associated MPNST is characterized by a high risk of early postoperative recurrence, representing a major clinical challenge. Metastatic disease emerged as the clearest determinant of mortality, while conventional clinicopathologic factors showed limited prognostic value. These findings highlight the need for larger NF1-MPNST cohorts and direct comparison with sporadic MPNST to better define biological differences, refine risk stratification, and guide translational and surveillance strategies.

Falls among older adults with cancer: A nationwide analysis.

e13759 Background: Falls represent a failure of physiologic reserve rather than a normal consequence of aging. In oncology, fall events are particularly consequential due to frailty, treatment toxicities, and polypharmacy. Falls may lead to serious injury, delay cancer therapy, and alter treatment goals. We examined the prevalence, temporal trends, and predictors of fall-related admissions among older adults with cancer. Methods: Using the National Readmissions Database from 2019–2022, we identified hospital admissions among patients aged ≥60 years with a cancer diagnosis using ICD-10-CM codes. Malignancies were categorized by primary site and metastatic status. Fall-related admissions were identified using validated ICD-10 codes. Baseline characteristics, comorbidities, complications, length of stay (LOS), hospital costs, and discharge disposition were analyzed. Multivariable logistic regression was used to identify independent predictors of fall-related admission. Adjusted odds ratios (aOR) are reported with 95% confidence intervals, and P value < 0.05 was considered statistically significant. Results: Among an estimated 5.17 million weighted cancer admissions, 5.55% were fall-related. The proportion increased significantly from 5.09% in 2019 to 6.10% in 2022 (P trend < 0.001). Patients with falls were older (mean age 77 vs 73 years), and 53% were male. Among cancer types, multiple myeloma conferred the highest odds of fall-related admission (aOR 1.28, P < 0.001). While metastatic disease overall was associated with lower odds (aOR 0.94), site specific analyses showed increased risk with brain metastases (aOR 1.27) and bone metastases (aOR 1.22) (all P < 0.001). Geriatric syndromes were the strongest predictors, including prior falls (aOR 4.67), orthostatic hypotension (aOR 3.04), dementia (aOR 1.69), and urinary incontinence (aOR 1.30). Sensory impairments including neuropathy (aOR 1.32), vision loss (aOR 1.17), and hearing loss (aOR 1.15) were independently associated with higher odds of falls. Laboratory abnormalities including anemia (aOR 1.16), hypercalcemia (aOR 1.14), and hyponatremia (aOR 1.08) were significant predictors (all P < 0.001). Falls resulted in substantial morbidity: 16.3% sustained hip fractures, 7.0% spine fractures, 21.2% other major fractures, and 9.4% intracranial hemorrhage. Mean LOS was 7.97 days, mean costs were $95,175, and discharge to skilled nursing facilities was markedly higher among patients who had falls (43.5% vs 17.4%). Conclusions: Fall-related admissions among older adults with cancer increased steadily over time and were associated with severe complications, prolonged hospitalization, and frequent discharge to post-acute care. Many identified risk factors are directly related to cancer or its treatment and may be modifiable. These findings highlight the need for systematic fall-risk screening and preventive interventions as a core component of geriatric oncology care.

A prospective trial of single-dose neoadjuvant PD-1 blockade with or without a CD40 agonist in HPV-negative HNSCC.

6087 Background: Neoadjuvant PD-1 blockade is approved for resectable locally advanced HPV-negative HNSCC, but major pathologic response rates are <10%, underscoring the need for effective combination strategies. Agonists of the TNF receptor superfamily member CD40 can reverse dendritic cell dysfunction, a key mediator of immune resistance, and may combine with PD-1 blockade to enhance anti-tumor T cell recruitment. We investigated the safety and immunologic effects of combination neoadjuvant PD-1 blockade with CD40 agonism. Methods: We enrolled 20 patients with resectable HPV-negative HNSCC; 10 received a single intravenous dose of PD-1 inhibitor (LVGN3616, 300mg), and 10 received a PD-1 inhibitor (LVGN3616, 300mg) in combination with a CD40 agonist (LVGN7409, 1mg/kg), administered prior to surgical resection (window, 4-28 days). Pre-treatment biopsies, post-treatment surgical specimens, and peripheral blood samples were collected. The primary endpoint was safety, with secondary endpoints including pharmacodynamic immune changes and pathologic responses. Results: Median age was 65 years (range, 39-79); 16 (80%) were male; 16 (80%) were White; 18 (90%) had oral cavity cancer (2 larynx); and 17 (85%) had PD-L1 CPS ≥1. Baseline demographics and PD-L1 were well-balanced between arms. Neoadjuvant immunotherapy was administered a median of 9 days (range, 5-19) before surgery, with no surgical delays observed. Treatment was well tolerated; grade 3/4 events occurred in 12/20 patients, nearly all attributable to post-surgical complications and unrelated to study drug. The only treatment-related grade 3/4 events were transient elevations in liver enzymes seen in two patients in the PD-1+CD40 arm. With a minimum of 6 months' follow-up, 3/20 patients (1 in PD1 arm, 2 in PD1+CD40 arm) had progressed. Serum analyses revealed that combined PD-1 and CD40 agonist therapy induced significant increases in multiple cytokines including IL-15 (p=0.0084), IP-10 (p=0.0379), MCP-1 (p=0.0002), MDC (p<0.0001), and MIG (p=0.0178) at 24 hours, indicating enhanced immune activation. A biomarker-driven inflammatory score based on baseline LCN2 and SAA levels predicted pathological response with 85% accuracy, 71.4% sensitivity, and 92.3% specificity (Fisher’s exact p=0.0072). Pathologic tumor response (pTR) was observed in 3/10 patients in the PD-1 arm (pTR1, 10-49%) and 4/10 patients in the PD-1+CD40 arm (including one pTR2 with 85% regression. Multiplex IHC was performed on tissue samples using CD3, Ki67, PD-L1, CD8, FOXP3, CD68, and panCK markers; quantitative spatial analyses are ongoing and results will be presented. Conclusions: Single-dose neoadjuvant PD-1 blockade combined with a CD40 agonist for HPV-negative HNSCC was safe, did not delay surgery, and produced modestly improved pathologic regressions that correlated with a cytokine-based baseline inflammatory score. Clinical trial information: NCT06159621 .

Circulating tumor DNA to enhance detection of high-risk minimal residual disease in ovarian cancer relative to second look laparoscopy.

5567 Background: Minimal residual disease (MRD) following frontline treatment of ovarian cancer has been established as a predictor of recurrence and survival. Historically, second look laparoscopy (SLL) has served as the gold-standard method to assess MRD; however the need for surgical evaluation limits widespread adoption and clinical applicability. Circulating tumor DNA (ctDNA) offers a non-invasive alternative for MRD detection and enables longitudinal monitoring with the potential for early identification of recurrence. Presently, the concordance between ctDNA-based detection and surgical assessment remains incompletely characterized. In this retrospective cohort study, we compare the predictive performance of ctDNA versus SLL for detecting clinically significant MRD after frontline treatment for high-grade ovarian cancer. Methods: This retrospective, single-institution study included patients with high-grade epithelial ovarian cancer who completed frontline chemotherapy and surgery. All patients underwent SLL to determine surgical MRD status. At the time of SLL, plasma was collected and profiled using NeXT Personal. Using whole-genome sequencing, this ultrasensitive, tumor-informed assay tracks up to 1,800 tumor-specific variants to detect ctDNA at levels down to ~1 part per million. Statistical analyses were conducted using RStudio (version 2026.01.0.392). Results: The cohort consisted of 72 patients (median follow up 38.9 months) with high-grade epithelial ovarian cancer, of whom 69 patients (95.8%) were in clinical remission by Ca-125 and imaging. Despite this, 30 patients (41.7%) were positive for MRD by ctDNA and 33 patients (45.8%) were positive for MRD by SLL. On multivariable analysis, ctDNA positivity independently predicted worse PFS (HR 4.35, 95% CI 2.17-8.72, p<0.001). The results of MRD and SLL were concordant in 53 (73.6%) of cases. There were 8 cases in which ctDNA was positive and SLL was negative. To date, 6/8 patients (75%) have recurred. There were 11 cases in which SLL was positive and ctDNA was negative. To date, 6/11 (54.5%) have recurred. Among these discordant cases, individuals with positive ctDNA but negative SLL had significantly worse PFS than cases with concordant negative results (HR 3.03, 95% CI 1.13-8.14, p=0.03). Whereas among cases with positive SLL and negative ctDNA, there was not a significant difference compared with concordant negative cases (HR 1.54, 95% CI 0.58-4.12, p=0.39). Conclusions: In this cohort where nearly all patients were in clinical remission, ctDNA was an independent predictor of PFS after frontline therapy in high-grade ovarian cancer. Although discordance occurs between ctDNA and SLL, these data suggest that ctDNA may detect clinically meaningful MRD not captured by SLL and could represent a more clinically relevant prognostic tool in this setting.

The therapeutic potential of orphan adhesion G-protein-coupled receptors

Supramolecular‐Covalent Hybrid Chiral Polymers with Strong Circular Dichroism and Unattenuated Dynamic Spectral Shift

ABSTRACT Optically active chiral polymers have been fuelling advances in chiroptics, optoelectronics and sensors. However, achieving strong circular dichroism (CD) intensity and highly tunable chiroptical responses remains a critical yet challenging goal for chiral polymers. Here we report a supramolecular–covalent hybrid chiral polymer that exhibits dynamically tunable CD spectra with large spectral shifts while retaining high intensity. Supramolecular polymerization of a two‐chain chiral monomer in solution yields gels composed of twisted fibrils of stacked nanoribbons. The diacetylene groups on the monomer chains align in long‐range chiral order and undergo in situ topochemical polymerization, resulting in a supramolecular‐covalent hybrid polymer. The polymer material appears dark blue and displays strong CD exceeding 1° at 670 nm. Remarkably, along with a blue‐to‐red chromatic transition upon heating, the CD peak shifts to 565 nm without attenuation of its magnitude. Mechanism study indicates the covalent polymer with a heat‐responsive conjugated backbone is responsible for the dynamic spectral shift, whereas the supramolecular polymer contributes to the persistent high intensity. The unusual CD responses enable the use of the polymer in high‐security information storage based on circular polarizations. The integration of supramolecular and covalent polymerizations provides strategies to create functional chiral polymers for advanced optical applications and beyond.

Molecular alterations to inform anatomical-based prognosis for recurrence prediction in HNSCC.

e18040 Background: Head and neck squamous cell carcinoma (HNSCC) remains a biologically heterogeneous malignancy with poor survival outcomes, primarily due to high recurrence rates and limited predictive biomarkers. The TP53 gene, a critical genomic gatekeeper, is frequently mutated in aggressive oral cavity cancers. The choice of personalized treatment modalities can be enhanced significantly by identifying accurate and reliable methods to predict which HNSCC patients are most likely to recur and consequently improve survival of patients. This stratification of patients has been difficult to obtain due to the numerous anatomic sites, the unpredictable clinical behavior and heterogeneous molecular features of these tumors. In this study we compared the prevalence of molecular alterations of TP53 and its co-occurring genes with anatomical features like depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), extranodal extension (ENE) to evaluate the most consistent indicator disease-recurrence in the HNSCC patients. Methods: A total of 22 patients with histologically confirmed HNSCC were retrospectively analyzed for genomic alterations and clinical/anatomical attributes such as TNM stage, DOI, LVI, PNI, ENE, Disease Free Survival (DFS), and Overall Survival (OS). Next generation sequencing in these patient samples was performed using OncoIndx panel. Correlations of TP53, its co-occurring genomic alterations and the clinical/anatomical attributes of patients with their recurrence pattern was investigated. Results: Our analysis identified a total of 63.63% of patients (n=14/22) to be affected by disease recurrence of whom 85.71% (12/14) harbored TP53 mutations. Further, with respect to individual anatomical features of these disease-recurred patients, 42.85% (n=6/14) showed DOI >=1.0 cm, 7.14% (n=1/14) were LVI positive, 28.57% (n=4/14) were PNI positive, and 21.42% (n=3/14) were ENE positive. Further, 71.42% (n=10/14) of the patients were found to be positive for all the anatomical features together (DOI+LVI+PNI+ENE). Conclusions: TP53-enriched Indian HNSCC cohort demonstrates that molecular determinants (TP53/CDKN2A/MYC/PIK3CA signatures) supersede anatomic staging in predicting recurrence and immunotherapy response. The combined positivity for all anatomical features (71.42%) still fell short of the recurrence-prediction percentage associated with TP53-mutation status (85.71%), highlighting TP53 mutation status as a stronger predictor of recurrence in this HNSCC cohort.

Use of electronic patient reported outcomes (ePRO) to characterize patients with acute myeloid leukemia (AML) receiving intense and less intense treatment.

e18555 Background: Among adults ages 20 and older with Acute Myeloid Leukemia (AML), 5-year relative survival is 30% and less for older patients. 1 With the average age at diagnosis of 68 years, less intense therapies are increasingly being used. 2 The decision for more-or less-intensive initial induction is largely based on chronological age and performance status. However, comorbidity indices have been shown to more accurately predict outcome. Patient reported outcomes (PRO) are needed to provide additional insight into treatment (TX) outcomes. This retrospective study sought to characterize patients using an electronic PRO (ePRO) system receiving intense and less intense treatment. Methods: Patients starting AML TX were enrolled in an ePRO system from 9/2020 to 9/2025. Baseline surveys included demographic data, symptoms (PRO-CTCAE), physical activity (PROMIS 4a), frailty (Cancer and Aging Resilience Evaluation Survey, CARES), and smoking status. TX data was sourced from the electronic medical record or entered directly into the platform. Symptom (SX) surveys were completed weekly throughout TX. Treatment bother (TXB) was measured by FACT-GP5 (“I am bothered by side effects of TX”). Biomarkers were characterized as high or favorable risk. SX reports at baseline, 6 and 12 weeks were analyzed using Fishers Exact Test. Results were stratified by intensive treatment (IT) defined as receiving idarubicin or daunorubicin plus cytarabine or less Intensive treatment (LIT) defined as azacitidine or decitabine plus venetoclax. Results: Eligible participants (n=164) were median age 68 (range=24-88), 52% (n=85) male, 79% (n=130) white, and 45% (n=28) current/former smokers. Of those completing CARE, 29% (n=36) were Frail/preFail and of 56 completing PROMIS 4a, 31% (n=17) reported altered mobility. 48% (n=74) received IT and 52% (n=85) received LIT. The IT group were median 61 years (range=24-74), 51% (n=40) male, 80% (n=63) white, and 33% (10 of 27) current/former smokers. Physically, 23% (13 of 57) were Frail/preFail and 25% (8 of 32) reported altered mobility. The LIT group were median 75 years (range=37-88), 53% (n=45) male, 52% (n=67) white and 52% (18 of 35) were current/former smokers. Physically, 33% (23 of 67) were Frail/preFail and 33% (9 of 24) reported altered mobility. The LIT group had more vomiting (p=.001) at baseline and more general pain and fatigue at 12 w (p=.04 for both.) The high-risk biomarker group was associated with receipt of LIT (p=0.004). The favorable risk group showed a non-significant trend towards receiving IT (p=0.069). Conclusions: Although the LIT group was older, more minority, more current/former smokers and were frailer and with more reported altered mobility, symptom prevalence and TB was similar to the IT group at three timepoints. Further examination of symptom severity and TB over the entire treatment period is warranted.

Efficacy of probiotics combined with glutamine compound for acute radiation enteritis during neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A randomized controlled trial (NCT05406882).

3624 Background: Acute radiation enteritis (ARE) occurs in up to 80% of patients undergoing abdominal-pelvic radiotherapy, with severe ARE causing treatment interruption in 20%. Current prophylactic strategies remain inadequate. Small-sample studies suggest probiotics and glutamine may reduce radiation-induced mucosal injury and intestinal syndrome (e.g., diarrhea), but evidence-based validation is insufficient. This study investigated the efficacy of probiotics combined with glutamine compound preparation in preventing and alleviating ARE in locally advanced rectal cancer (LARC) patients receiving chemoradiotherapy. Methods: This prospective randomized trial enrolled 176 stage II-III rectal adenocarcinoma patients receiving preoperative chemoradiotherapy, randomized 1:1 to prophylactic (group A, n=86) versus therapeutic (group B, n=84) (treatment started when patients had ≥ 2° ARE) administration of probiotics combined with glutamine compound. Concurrent chemoradiotherapy consisted of pelvic radiation 50-50.4 Gy/25-28 fractions plus oxaliplatin/capecitabine. Weekly assessments documented ARE (including anal tenesmus/pain, diarrhea, constipation, hematochezia) basing on RTOG and CTCAE v5.0 criteria. Primary endpoints: incidence of grade ≥2 ARE and diarrhea. Chi-square or Fisher's exact tests were used for analysis through R version 4.4.2. P<0.05 indicated statistical significance. Results: The enrollment was completed on August 5, 2025. Six patients withdrew consent (group A: 1; group B: 5). Ultimately, there were 170 patients who completed concurrent chemoradiotherapy (84 control, 86 treatment), including 105 males (61.8%). The incidence rate of ≥ 2° ARE in group A was significantly lower than that in group B (44.2% vs 73.8%, P<0.001; RR=0.60, 95%CI: 0.46-0.78). The incidence rate of ≥ 2° diarrhea was also significantly lower in group A (34.9% vs 54.8%, P=0.01). There was 1.2% (1/86) and 3.6% (3/84) of grade 3 ARE in the two groups, respectively; and all these four patients experienced grade 3 diarrhea. The incidence rate of ≥ 2° ARE increased with higher doses of pelvic radiotherapy in both groups, with the peak incidence occurring in the fifth week (24.1%) of group A and the fourth week (35.7%) of group B, respectively. Conclusions: Prophylactic probiotics combined with glutamine compound has a preventive effect of severe radiation enteritis and diarrhea during concurrent chemoradiotherapy for rectal cancer. Clinical trial information: NCT05406882 .

Spatial heterogeneity of structural inequities in diagnostic delay and survival in early-onset colorectal cancer in a large urban catchment area.

1586 Background: Disparities in early-onset colorectal cancer (EO-CRC) stage at diagnosis and survival persist despite expanding specialty care, suggesting that structural and neighborhood-level factors, beyond traditional access measures, influence timeliness of cancer detection and treatment. We applied geospatial modeling integrating clinical data with census-based Social Vulnerability Index (SVI) and historical redlining to characterize geographic variation in diagnostic delay and median overall survival (mOS). Methods: We retrospectively analyzed 214 patients diagnosed with EO-CRC (<50 years) treated an urban tertiary center (2018-2025), identified via ICD-10 codes. Geocoded addresses were linked to census-tract level SVI and Home Owners’ Loan Corporation redlining grades (A/B vs C/D). Access was quantified using network drive-time and Euclidean distance to colorectal surgery and gastroenterology. Spatial analyses in ArcGISPro included hotspot mapping, tract-level aggregation, and Geographically Weighted Regression (GWR) to model spatially varying associations between race, stage, access, and OS. GWR residuals >±2 standard deviations (SD) identified clusters of excess risk. Results: Among 214 patients: 32% were non-White; 62% were stage III/IV; 49% lived in redlined neighborhoods. Time from symptom onset to diagnosis was non-linear with access: patients living <5 miles (89 days) and >20 miles (101 days) from specialty care experienced longer delays than those 5-10 miles (67 days) or 10-20 miles (72 days) away (p<0.01), consistent across drive-time and Euclidean measures. GWR demonstrated that the effects of race and stage on diagnostic delay (median local R²=0.52, range 0.28–0.67) and OS (median local R²=0.46, range 0.23–0.60) varied by location. High-residual clusters (>2 SD above predicted delay) localized to the Southeast and East neighborhoods of the catchment area, where non-White patients experienced 48-82 excess days of diagnostic delay after adjustment for stage, access, and SVI. High-residual areas had higher emergency or inpatient index presentation than in low-residual areas (42% vs 21%, p=0.01). The mOS was significantly lower in high-SVI vs low-SVI tracts (22 vs 38 mo; HR 1.9, p<0.01), in redlined versus non-redlined neighborhoods (24 vs 50 mo; HR 2.1, p<0.002). Within low-SVI areas, non-White patients had inferior mOS compared to White patients (28 vs 37 mo, HR 1.5, p=0.001). Conclusions: Spatial modeling suggests that EO-CRC disparities reflect place-based structural factors beyond clinical stage or proximity to care. Clustering of excess diagnostic delay and inferior survival in historically redlined and high-SVI neighborhoods identifies priority geographies for future studies integrating clinical and population data to design targeted, place-based navigation and early-detection interventions.

Disparities in supportive care access and financial burden associated with chemotherapy-induced alopecia in women with breast cancer.

e13748 Background: Chemotherapy-induced alopecia (CIA) remains one of the most visible and psychologically distressing toxicities of breast cancer therapy. Despite its high prevalence and impact on treatment experience, CIA management is inconsistently integrated into oncology supportive care pathways, and access to mitigation strategies may vary across demographic and treatment-related factors. Methods: A cross-sectional survey was administered between July and October 2025 to women with breast cancer who received chemotherapy or endocrine therapy at two academic centers in the United States. Data collected included demographic characteristics, chemotherapy regimen, hair loss severity and management strategies, out-of-pocket costs, treatment avoidance, and perceived healthcare support. Outcomes were analyzed by Fitzpatrick skin phototype, chemotherapy regimen, hair texture, and household income. Results: Among 63 respondents (mean age 57.1 years), 43% received-taxane based chemotherapy. Nearly all participants reported chemotherapy-associated hair loss; however, only 11.1% had dermatologic involvement in management. Patients with Fitzpatrick skin types IV-VI were significantly more likely to delay or forgo CIA treatment due to cost compared with those with types I-III (68.4% vs. 34.2%; RR = 2.00; p = 0.023). Patients receiving taxane-based chemotherapy reported greater financial burden related to CIA management compared with non-taxane regimens (64.0% vs 45.5%; RR = 1.41) and were less likely to feel adequately supported by the healthcare team (7.4% vs 27.8%; p = 0.055). Cost-related treatment avoidance was highest among middle-income patients ($25,000-$74,999; 56.0%) compared with both lower- and higher-income groups, consistent with a supportive-care coverage gap. Hair texture was not significantly associated with treatment-seeking behavior or access. Conclusions: CIA represents a clinically meaningful toxicity with disproportionate financial and supportive-care burden among patients receiving taxane-based therapy and those with darker skin phototypes. These findings suggest that disparities in CIA management are driven by structural gaps in oncology supportive care. Improved integration of alopecia prevention counseling, referral pathways, and equitable access strategies is warranted within comprehensive breast cancer care.

Immunotherapy rechallenge in extensive-stage small-cell lung cancer: A real-world retrospective study.

e20130 Background: Although extensive-stage small-cell lung cancer (ES-SCLC) is highly sensitive to first-line immunotherapy combined with chemotherapy, most patients experience relapse and resistance after initial treatment. The median overall survival (mOS) with second-line chemotherapy is only 4–6 months. To date, there is a lack of prospective clinical trial data with a sufficient sample size to support the safety and efficacy of ICI rechallenge after progression on first-line immunotherapy in patients with ES-SCLC. Methods: This study retrospectively analyzed the clinical data of 151 patients with ES-SCLC who received first-line immunotherapy at Hunan Cancer Hospital between September 2019 and April 2025. We compared the efficacy and safety between patients who received ICI rechallenge (ICI rechallenge group, N = 100) and those who did not (non-ICI group, N = 51). The assessed endpoints included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: The ICI rechallenge group showed significantly higher ORR and DCR compared with the non-ICI group (ORR: 26.00% vs. 11.76%, p = 0.043; DCR: 75.00% vs. 47.06%, p < 0.001). The ICI rechallenge group also showed significantly longer PFS and OS compared with the non-ICI group (median progression-free survival [mPFS]: 3.98 vs. 2.43 months, p < 0.001; mOS: 9.43 vs. 6.23 months, p < 0.001). Subgroup analyses indicated that patients benefited from ICI rechallenge, regardless of the ICI rechallenge mode, ICI type, or combination regimen, compared with the non-ICI group. Multivariate Cox regression analysis confirmed that first-line PFS (1L-PFS) > 6 months and ICI rechallenge were independent protective factors (PFS: HR = 0.35, p < 0.001; OS: HR = 0.37, p < 0.001). Regarding safety, the incidence of grade ≥ 3 treatment-related adverse events (TRAEs) was not significantly different between the two groups (18.0% vs. 15.7%, p = 0.722). In the ICI rechallenge group, immune-related adverse events (irAEs) were predominantly grade 1–2. Grade ≥ 3 irAEs occurred in only 2.0% of patients. Conclusions: This real-world evidence confirms that ICI rechallenge significantly improves efficacy and prognosis in patients with ES-SCLC who progress after first-line immunotherapy combined with chemotherapy. The safety profile of ICI rechallenge is manageable. Regardless of the ICI rechallenge mode, ICI type, or combination regimen, patients with ES-SCLC can benefit from ICI rechallenge. This study provides critical evidence for clinical decision-making.

Impact of cirrhosis on the metabolic profile, tumor presentation, and management of MASLD-associated hepatocellular carcinoma: A systematic review and meta-analysis.

e16306 Background: Metabolically-dysfunction-associated steatotic liver disease (MASLD) affects nearly 38% of the adult world population and is a rapidly growing contributor to hepatocellular carcinoma. Unlike viral hepatitis–related HCC, MASLD-associated HCC frequently occurs in both cirrhotic and non-cirrhotic patients, creating uncertainty regarding risk stratification, presentation, and treatment eligibility. We conducted a systematic review and meta-analysis to evaluate the impact of cirrhosis on metabolic risk factors, tumor presentation, and treatment plan in MASLD-related HCC. Methods: We followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and performed a comprehensive literature search using PubMed, Cochrane, and Scopus. Data were extracted and pooled using random-effects models and Review Manager (V.5.4). Heterogeneity was assessed using the I² statistic. Results: Among the 2,873 article abstracts screened, 13 studies were analyzed. Cirrhotic MASLD-HCC patients had significantly higher odds of diabetes compared with non-cirrhotic patients (OR 2.16, 95% CI 1.84-2.54), while no significant associations were observed for obesity (OR 2.34, 95% CI 0.78-7.01), hyperlipidemia (OR 0.78, 95% CI 0.48-1.27), or hypertension (OR 1.07, 95% CI 0.90-1.27). At diagnosis, cirrhotic patients had greater tumor burden with higher odds of multifocal disease (OR 1.62, 95% Cl 1.09-2.42). Cirrhosis was strongly associated with reduced likelihood of surgical resection (OR 0.20, 95% Cl 0.13-0.29). Mortality did not differ significantly between cirrhotic and non-cirrhotic groups (OR 1.63, 95% Cl 0.94-2.81). Conclusions: Cirrhosis is associated with a distinct background metabolic risk profile in MASLD-associated HCC, affecting tumor presentation and treatment strategies. Differences in treatment patterns and metabolic risk factors emphasize the need for individualized surveillance and therapeutic protocols for this growing population. Further studies are warranted to improve risk stratification and to optimize a personalized treatment plan. Pooled odds ratio for metabolic risk factors, disease presentation, mortality, and treatment outcomes associated with HCC in cirrhotic MASLD compared to non-cirrhotic MASLD patients. Risk Factors, Presentation, Mortality and Treatment Pooled Odds Ratio (OR) 95% Cl Diabetes 2.16 1.84-2.54 Obesity 2.34 0.78-7.01* Hyperlipidemia 0.78 0.48-1.27* Hypertension 1.07 0.90-1.27* Number of Lesions: 1 0.61 0.41-0.89 Number of Lesions: 2-3 1.62 1.09-2.42 Mortality 1.63 0.94-2.81* Surgical Resection 0.20 0.13-0.29 All p<0.005 unless noted with *.

LLM-generated serious illness conversation summaries to improve care for hospitalized patients: A pilot clinical trial.

1519 Background: Patients with cancer often receive intensive care near the end of life that does not align with their goals and preferences. Hospitalization is a critical opportunity to engage in serious illness conversations (SICs) that can align care with preferences, but SICs rarely occur. Large language model (LLM)-generated SIC summaries may help busy inpatient clinicians by identifying patient preferences in fragmented SIC documentation in voluminous electronic health record (EHR) notes. Methods: This randomized pilot clinical trial enrolled adults with solid tumors admitted to an academic hospital with a 90-day predicted mortality > 40%. Patients were randomized 3:1 (intervention:control) to usual care or to an intervention consisting of an LLM-generated summary of SIC documentation in EHR notes from the last 6 months emailed to their inpatient and outpatient oncology and palliative care teams within 16 hours of admission. Summaries included 8 SIC topics and up to 18 bullet points, and emails included a message encouraging SICs and incorporation of patients’ preferences into care plans. The primary outcome was SIC summary accuracy: manual review determined whether each summary bullet point accurately reflected the source note, and the proportion of accurate bullet points were calculated. Other outcomes included user perspectives from day 3 patient interviews and day 7 clinician surveys and 90-day care delivery outcomes (days in the hospital, number of hospitalizations, hospital re-admission). Results: 58 enrolled patients were 55% female, 76% White, 91% non-Hispanic and had a mean 90-day predicted mortality of 57.7%. 902 of 936 (96.4%) summary bullet points accurately reflected underlying documentation. Inaccuracies were typically not clinically significant and related to overstating the strength of preferences (e.g., documentation stating a plan to start treatment to improve symptoms might be summarized to state the patient is “focused on improving symptoms”) and misattribution of clinician concerns to the patient. 32 patients participated in interviews. They were generally supportive of the intervention and felt it would improve patient-clinician understanding and communication around preferences. 31 clinicians completed surveys and evaluated SIC summaries as “moderately” to “extremely accurate.” 90-day outcomes were mature for 24 patients. In 90 days after enrollment, preliminary mean hospital days (20.9 vs 13.2), mean number of hospitalizations including index admission (2.3 vs 1.5) and re-admission (42.9% vs 23.5%) were all lower in the intervention arm. Full trial data will be available in March. Conclusions: LLM-generated SIC summaries can be accurately generated, delivered within 16 hours of hospital admission, are received favorably by patients and clinicians, and may reduce care utilization. An effectiveness clinical trial starts May 2026. Clinical trial information: NCT07147023 .

Pyrotinib versus pertuzumab plus trastuzumab and taxane as first-line therapy for HER2-positive advanced breast cancer: A retrospective cohort study using propensity score overlap weighting.

e13024 Background: Trastuzumab–pertuzumab–taxane (THP) and trastuzumab–pyrotinib–taxane (PyHT) are both accessible first-line options for HER2-positive advanced breast cancer (HER2+ ABC) in China. However, direct comparative evidence between these strategies remains limited, particularly regarding central nervous system (CNS) evolution—whether introducing a TKI-containing regimen upfront can delay the development of new brain metastases. Methods: We conducted a single-center retrospective cohort study at the First Affiliated Hospital of Xi'an Jiaotong University including patients with HER2+ ABC treated with first-line THP or PyHT (Jan 2018–Jan 2025). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), brain metastasis–free survival (BMFS), and adverse events (AEs). BMFS was evaluated among patients without baseline brain metastases and defined as the time from treatment initiation to radiologically confirmed new brain metastases (CT/MRI) or death. To emulate a randomized comparison in the overlap population without discarding patients, propensity score overlap weighting (OW) was applied. Robustness was assessed by sensitivity analyses. Results: A total of 143 patients were included (THP n = 93; PyHT n = 50) with a median follow-up of 43.0 months. Data cutoff was Nov 1, 2025. All covariates achieved adequate balance after OW (absolute standardized differences < 0.10). After OW analysis, PFS and OS did not differ significantly between groups, while PyHT was associated with a higher ORR (84.1% vs 55.6%). Among patients without baseline brain metastases (n = 125), PyHT was associated with longer BMFS (HR = 0.47；95% CI 0.23–0.96). PyHT was associated with a higher burden of grade ≥3 AEs (36.0% vs 22.6%). Grade ≥3 diarrhea occurred in 30.0% with PyHT, whereas THP was characterized mainly by hematologic toxicity. Conclusions: This long-term retrospective study suggests comparable systemic disease control (PFS/OS) between THP and PyHT. PyHT was associated with a higher response rate and a signal toward delayed CNS evolution (longer BMFS ), at the cost of increased gastrointestinal toxicity. These hypothesis-generating findings may inform individualized first-line selection and support prospective validation focusing on CNS prevention. Overlap-weighted efficacy outcomes of first-line THP vs PyHT. THP (n=93) PyHT (n=50) Effect estimate (PyHT vs THP) Median PFS (mo) 17.0 25.0 HR 0.82 (95% CI 0.55–1.24); p=0.55 Median OS (mo) 83.0 75.0 HR 0.76 (95% CI 0.37–1.55); p=0.60 ORR (%) 55.6 84.1 p=0.03 Median BMFS (mo)* 68.0 80.0 HR 0.47 (95% CI 0.23–0.96); p=0.04 *BMFS evaluated among patients without baseline brain metastases (n=125; THP n=81; PyHT n=44).

Utility of a modified geriatric assessment to identify impairments in adults of all ages with lymphoma: A prospective observational cohort study.

7091 Background: Performance status assessments may overlook important health vulnerabilities in adults with cancer. While geriatric assessment (GA) systematically evaluates multiple domains including physical function, cognition, psychological health, comorbidity, and nutrition, it has been predominantly studied in older adults. We evaluated the prevalence and patterns of GA-identified deficits among adults of all ages initiating systemic therapy for lymphoma. Methods: Adults with lymphoma enrolled in a prospective registry at an academic cancer center from 2018-2025 completed a modified Cancer and Aging Research Group (CARG) GA at treatment initiation. The assessment included validated measures across eight domains: mobility (Timed Up and Go), falls history, instrumental activities of daily living (IADLs), medication burden, comorbidities, weight loss, cognition (Blessed Orientation-Memory-Concentration test), and psychological health (Mental Health Index-13). Karnofsky Performance Status (KPS) was documented. Prevalence of deficits was compared between adults <65 and ≥65 years. Results: Among 97 participants (mean age 57 years, range 22-84; 39% ≥65 years), 94% had normal KPS (≥80). Despite preserved performance status, 56% had multiple (≥2) GA-identified deficits, and only 21% had zero deficits. The most common deficit was unintentional weight loss (43% overall). Among younger adults (<65 years), substantial proportions reported weight loss (34%), falls (27%), IADL impairment (27%), and anxiety or depression (45%). Most deficits did not differ significantly between age groups, though weight loss, multimorbidity (≥4 comorbidities), and severe polypharmacy (≥10 medications) were more prevalent in older adults. Conclusions: GA reveals high prevalence of health-related deficits across multiple domains in adults with lymphoma regardless of age, despite preserved performance status. These findings support a shift toward needs-based rather than age-based approaches to identify individuals who may benefit from supportive care interventions. Functional measures among adults treated for lymphoma, stratified by age. Deficit Domain Full Cohort % (95% CI) Age < 65 % (95% CI) Age ≥ 65 % (95% CI) p** Weight Loss 43 (33-53) 34 (23-47) 57 (41-71) 0.035 Mental Health 37 (28-46) 45 (33-58) 24 (13-39) 0.051 IADL Impairment 29.9 (21.7-39.6) 27.1 (17.4-39.6) 34.2 (21.2-50.1) 0.50 Falls (≥ 1 in past 6 months) 24 (16-33) 27 (17-40) 18 (9-33) 0.46 Polypharmacy (≥ 10 medications) 17 (11-25) 7 (3-16) 32 (20-49) 0.002 Cognitive Impairment (BOMC ≥ 5) 32 (23-43) 28 (18-42) 38 (24-54) 0.36 High Comorbidity (≥ 4 conditions) 10 (6-18) 5 (2-14) 18 (9-33) 0.047 TUG >14 seconds 5 (2-12) 4 (1-14) 6 (2-19) 1.0 *Reflects missing values (1 each for weight loss, MHI13, daily medications, and comorbid conditions, 10 for BOMC, and 16 for TUG). **P-values from Fisher's exact test.

Efficacy and safety of antibody-drug conjugates in HR+/HER2− advanced breast cancer: A systematic review and meta-analysis of phase III randomized trials.

e13038 Background: Hormone receptor–positive (HR+)/HER2- advanced breast cancer is characterized by disease progression after initial endocrine and targeted therapies, with modest benefit from conventional chemotherapy. Antibody–drug conjugates (ADCs) are a promising therapeutic class in this setting following initial approval for HER2+ disease. We performed a systematic review and meta-analysis of Phase III ADC efficacy and safety in HR+/HER2- (including HER2-low) breast cancer. Methods: PubMed, Cochrane CENTRAL, ESMO, and major conference proceedings through December 2025 were systematically searched. Phase III randomized controlled trials of ADCs versus standard-of-care (SOC) therapy in HR+/HER2- unresectable/metastatic breast cancer were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and Grade ≥3 treatment-related adverse events (TRAEs). Pooled hazard ratios (HRs) were estimated using inverse-variance random-effects models; risk ratios (RR) were synthesized for binary endpoints. Heterogeneity was assessed with sensitivity analyses performed. Results: Five Phase III RCTs with nearly 3000 total patients were assessed. Median PFS and OS across ADC-treated populations were 6.9 months (range: 4.3–13.2) and 19.8 months (range: 14.5–23.9), respectively. ADCs significantly improved PFS compared with SOC (pooled HR 0.58, 95% CI 0.47–0.72) and showed an OS benefit (pooled HR 0.69, 95% CI 0.49–0.98). Significantly higher ORR (pooled RR 1.81, 95% CI 1.43–2.29; RD +17.5%, 95% CI +6.7%-+28.4%) with favorable DCR (pooled RR 1.21, RD +11.5%) and DOR (median 8.1 vs. 5.7 months; pooled RoM 1.44 [95% CI 1.23–1.68]) trends were seen with ADC treatment. Grade ≥3 TRAEs showed a higher trial-level median rate with ADCs (61.0% vs 55.4%) but were comparable overall versus SOC (pooled RR 0.97, 95% CI 0.73–1.29). Despite heterogeneity in effect magnitude (I² 81-92% for PFS/OS), between-study variance was modest for PFS (τ²≈0.05) and moderate for OS (τ²≈0.15), reflective of inter-trial differences in follow-up maturity and post-progression therapy. Conclusions: Collectively, ADCs demonstrated a consistent clinically meaningful improvement in PFS with an OS benefit as compared with SOC despite trial-level variability. ADC efficacy measures showed earlier and more sustained anti-tumor activity with improved overall disease control, supportive of more rapid symptom relief and as well as time to subsequent-line therapy. The observed toxicity profile highlights regimen-dependent effects and the importance of patient selection and monitoring. These findings support the use of ADCs as a more efficacious alternative to chemotherapy in pre-treated HR+/HER2- advanced breast cancer.

Real-world EGFR, ALK, and PD-L1 testing performance and end-to-end intervals in Colombian patients with non–small cell lung cancer.

11091 Background: Timely and comprehensive EGFR, ALK, and PD-L1 testing underpins effective precision oncology care in NSCLC, yet real-world data on testing completeness and integration into care pathways remain scarce in Latin America. Methods: We conducted a retrospective cohort study of adults with pathologically confirmed NSCLC treated at Fundación Santa Fe de Bogotá (2018–2025). EGFR/ALK/PD-L1 testing completeness, complete-panel availability, biomarker distributions, and turnaround times (order-to-report and diagnosis-to-report) were assessed. Stage III–IV sub analysis was performed. Results: A total of 242 patients were included. Most were female (53.3%), never-smokers (45.0%), and had adenocarcinoma histology (82.2%). EGFR, ALK, and PD-L1 results were available in 84.3%, 80.6%, and 80.6% of cases, respectively. Complete-panel availability was 74.4% and improved over time (adjusted OR per year, 1.28; 95% CI, 1.10–1.50; p=0.002). Turnaround times were favorable, with a median order-to-report time of 5 days (IQR, 2–8), and 68.0% completed within 7 days. The median diagnosis-to-report time was 12 days (IQR, 6–28.5), with 54.3% completed within 14 days. Activating EGFR mutations occurred in 38.7%, ALK fusions in 9.7%, and PD-L1 TPS ≥50% in 21.0%. In exploratory multivariable models, EGFR positivity was less frequent in ever-smokers (OR 0.26; 95% CI 0.13–0.51) and non-adenocarcinoma histology (OR 0.26; 95% CI 0.07–0.96). Guideline-concordant first-line targeted therapy was used in >80% of systemically treated patients with actionable alterations. In the stage III–IV subset (median age, 71.3 years; 53.8% female), median intervals were 13 days for imaging-to-diagnosis and 27 days for diagnosis-to-treatment (IQR, 16–52), with 33% exceeding 30 days and higher rates among patients referred after extra-institutional diagnosis. Median diagnosis-to-molecular report and report-to-treatment intervals were 11 days (IQR, 5–21) and 14 days, respectively. Requirement for EBUS was associated with longer imaging-to-diagnosis delays (75% >30 days; p=0.01). Conclusions: This study provides Latin American benchmarks for precision oncology delivery in NSCLC, showing high and improving molecular testing completeness with rapid turnaround. While molecular readiness was favorable, treatment initiation—especially for referred patients—represented the principal optimization gap. Standardized diagnosis-initiated testing and navigation workflows may improve end-to-end pathway performance. Temporal trends in biomarker testing completeness in NSCLC (2018–2025). Metric 2018–2020 (n=87) 2021–2023 (n=93) 2024–2025 (n=59) Overall (N=242) EGFR available, % 77.0 86.0 93.2 84.3 ALK available, % 73.6 80.6 91.5 80.6 PD-L1 available, % 71.3 83.9 89.8 80.6 Complete panel available, % 65.5 74.2 88.1 74.4