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Enhanced surveillance modalities and biopsy outcomes.
e12749 Background: Breast cancer (BC) survivors are at higher risk for recurrence or new primary disease and often require complex surveillance imaging. Use of contrast enhanced surveillance imaging modalities with contrast-enhanced digital mammography (CEM) and magnetic resonance imaging (MRI) has increased in recent years. This study evaluates characteristics of those BC survivors who receive contrast enhanced imaging and whether the addition of contrast enhanced imaging affects biopsy outcomes in BC survivors. Methods: An IRB-approved retrospective chart review identified female BC survivors who underwent breast surgery and subsequent surveillance imaging at a single academic center between 2016 and 2025. Surveillance episodes were categorized as mammography alone versus mammography with addition of CEM and/or MRI. Multivariable generalized estimating equations were used to compare patient and tumor characteristics associated with enhanced imaging modality use. Similarly rates of biopsy and cancer were evaluated with enhanced imaging use. Results: A total of 4,050 surveillance imaging episodes in 861 patients were identified and 54 resulted in biopsy-proven malignancy. Mammography alone was performed in 3,459 episodes, while enhanced imaging with CEM or MRI was used in 591 (14.6%) episodes. Use of CEM or MRI for surveillance imaging increased over time. In 2016, surveillance imaging consisted predominantly of mammography alone (93.3%) with 6.6% incorporating MRI or CEM. By 2025, mammography only surveillance decreased to 78.4% while use of MRI or CEM increased to 21.6%. Use of contrast enhanced imaging was associated with higher incidence rate ratios (IRR) for dense breast tissue [IRR 2.33; 95% CI 1.92, 2.82), p < 0.001] and less frequently used among patients aged 65–79 years [IRR 0.60, 95% CI 0.49, 0.74; p < 0.0001] and > = 80 years of age [IRR 0.40; 95% CI 0.24, 0.66; p < 0.001]. Ductal carcinoma in situ (DCIS) (IRR 3.09, p = 0.0061), and immunotherapy use (IRR 2.56, p = 0.0006) also were associated with increased use of CEM/MRI enhanced imaging. Biopsies were performed in 146 (4.2%) mammography alone episodes and 55 (9.3%) enhanced imaging episodes [IRR 2.20; 95% CI 1.63, 2.96; p < 0.001]. Surveillance with mammography yielded malignant biopsy results in 39 (1.1%) episodes, compared with 15 (2.5%) episodes using enhanced imaging [IRR 2.25; 95% CI 1.25, 4.06; p = 0.007). Conclusions: In breast cancer surveillance at our institution, the addition of contrast enhanced imaging modalities were utilized in a minority of surveillance episodes but did increase over time and were higher in patients with dense breasts. CEM or MRI usage demonstrated higher biopsy rates and increased malignancy detection compared with mammography alone, but the incidence of a positive biopsy was low. These findings suggest and are in keeping with 2023 ACR guidelines that enhanced imaging may improve cancer detection in select breast cancer survivors.
Sequencing ivosidenib post–first-line immunotherapy in biliary tract cancer: A real-world matched analysis.
e16249 Background: The TOPAZ-1 trial established Gemcitabine-Cisplatin plus Durvalumab as the preferred first-line therapy for advanced biliary tract cancer (BTC) raising and important question regarding optimal sequencing of subsequent therapies. The pivotal ClarIDHy trial, which established Ivosidenib’s efficacy, was conducted in an immunotherapy-naïve population. It remains unclear whether immunotherapy sensitizes the tumor via 2-hydroxyglutarate suppression ("priming”) or selects for resistant, immune-exhausted phenotypes ("selection"). This study evaluated if the real-world efficacy of second-line Ivosidenib is altered by prior ICI exposure. Methods: We utilized the TriNetX global health research network to identify patients with IDH1 -mutated cholangiocarcinoma treated with Ivosidenib in the second line setting. Patients were stratified into two cohorts: Cohort A (Post-IO, n = 81)received prior Gemcitabine-Cisplatin plus an ICI, and Cohort B (IO-Naïve, n = 106) received prior chemotherapy alone. 1:1 propensity score matching (PSM) was performed for age, sex, ECOG performance status proxies, baseline liver function, albumin, chronic liver diseases and metastatic burden. Outcomes were 1-year overall survival (OS) and hepatic decompensation (composite for ascites, hepatic failure, ERCP, hepatopulmonary syndrome) calculated from the initiation of Ivosidenib. Kaplan-Meier survival analysis and Cox proportional hazards models were used to compare outcomes. Results: The final matched cohort included 124 patients (62 per arm) with well-balanced baseline characteristics. 1-year OS did not differ significantly between Post IO vs IO naïve cohorts (49.64% vs 44.20%; median survival 10.8 vs 10.4 months; p = 0.79). Rates of hepatic decompensation were also comparable, with a non-significant trend toward lower risk in the post-ICI group (43.55% vs. 51.61%; HR 0.84, 95% CI 0.58–1.22; p = 0.37). Conclusions: Prior exposure to immune checkpoint inhibitors did not diminish the survival benefit of second-line Ivosidenib. Our findings suggest that the metabolic benefit of IDH1 inhibition is independent of prior immune modulation, refuting the "Selection" hypothesis while also failing to demonstrate the synergistic "Priming" effect. This data provides providing real-world reassurance that Ivosidenib remains an effective second-line option in the post–TOPAZ-1 treatment landscape. Impact of ICI on survival and hepatic outcomes with ivosidenib (propensity-matched). Outcome POST IO cohort (n= 62) IO NAIVE cohort (n= 62) Hazard Ratio/ Risk Ratio (95% CI) p-value 1 year Survival Probability 49.64% 44.20% 0.92 (0.54, 1.57) 0.79 Hepatic Decompensation 43.55% 51.61% 0.84 (0.58, 1.22) 0.37
Multi-omic ctDNA-based MRD for predicting clinical outcomes in advanced NSCLC receiving chemoimmunotherapy.
8576 Background: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for advanced non–small cell lung cancer (aNSCLC); however, many patients achieving radiographic partial or complete response (PR/CR) relapse early. This underscores the need for more precise risk stratification after an initial response. We investigated whether circulating tumor DNA -based minimal residual disease (ctDNA-MRD) assessment could stratify patients with durable benefit versus those at risk of early progression after chemoimmunotherapy (Chemo-IO). Methods: We analyzed 152 retrospective and 60 prospective aNSCLC patients who achieved PR/CR after first-line (1L) PD-1-based Chemo-IO. Plasma was collected at the first imaging-confirmed PR/CR (retrospective) or at baseline and Cycle 5 Day 1 (C5D1; prospective). ctDNA-MRD was assessed using a tumor-naïve, mutation-based panel and a fragmentomics model derived from low-pass whole-genome sequencing (LP-WGS). In the retrospective cohort, 89 patients were used for LP-WGS model training and 63 for validation. Risk stratification was evaluated using progression-free (PFS) and overall survival (OS). Results: In the retrospective validation cohort (n = 63), both the mutation- and fragmentomic-based assays stratified PFS and OS. For the mutation-based assay, median PFS (mPFS) was 27.0 vs. 10.1 months (negative vs. positive; Hazard ratios [HR] 0.414, 95% confidence intervals [CI] 0.211‒0.814, p = 0.008) and median OS (mOS) was not reached (NR) vs. 17.5 months (HR 0.341, 95% CI 0.151‒0.768, p = 0.007). For the LP-WGS-based model, mPFS was 27.0 vs. 13.8 months (HR 0.412, 95% CI 0.216‒0.785, p = 0.005) and mOS was NR vs. 25.1 months (HR 0.355, 95% CI 0.158‒0.795, p = 0.009). Integration using an either-assay-positive definition further improved prognostic discrimination, with mPFS NR vs. 13.8 months (HR 0.379, 95% CI 0.201‒0.714, p = 0.002) and mOS NR vs. 25.1 months (HR 0.324, 95% CI 0.143‒0.730, p = 0.004). In the prospective cohort (n = 60), both assays at C5D1 identified patients at higher risk of progression: mutation-based mPFS 18.3 vs. 6.1 months (HR 0.184, 95% CI 0.075‒0.457, p < 0.0001); LP-WGS-based mPFS NR vs. 5.3 months (HR 0.178, 95% CI 0.070‒0.456, p < 0.0001). Integration-based mPFS was NR vs. 6.5 months (HR 0.130, 95% CI 0.039‒0.440, p = 0.0001). Multivariable analysis confirmed the independent and complementary prognostic value of both approaches across cohorts. Conclusions: Both mutation- and fragmentation-based ctDNA-MRD assays effectively stratified risk among aNSCLC patients with radiographic response to 1L Chemo-IO. Their integration further improved prognostic performance, refining risk beyond imaging-defined PR/CR and informing post-response management decisions.
Fixed-duration glofitamab monotherapy in relapsed/refractory (R/R) mantle cell lymphoma (MCL) with/without prior Bruton's tyrosine kinase inhibitor (BTKi) exposure: Updated data after a 3.5-year follow-up.
7006 Background: Patients (pts) with advanced R/R MCL have poor outcomes, especially pts with high-risk features or those progressing after BTKi therapies. Glofitamab is a CD20xCD3 2:1 bispecific antibody that redirects T cells to eliminate malignant B cells. A Phase 1/2 trial (NCT03075696) evaluated glofitamab monotherapy, given with step-up dosing (SUD) after obinutuzumab pretreatment (Gpt), in pts with R/R MCL. Prior analyses showed high response rates and manageable safety, regardless of prior BTKi exposure (Phillips, et al. ASCO 2024). We report longer follow-up data from this MCL cohort. Methods: Pts with R/R MCL after ≥1 prior line of systemic therapy received Gpt (single 1000 mg dose or 2000 mg split over 2 days, as needed) on cycle (C)1 day (D)1. Glofitamab SUD was given on C1D8 (2.5 mg) and C1D15 (10 mg), then the target dose of 16 or 30 mg every 3 weeks on D1 of C2–12. Efficacy endpoints included investigator-assessed complete response (CR) rate, overall response rate (ORR), duration of CR (DoCR), duration of response (DoR), progression free survival (PFS), and overall survival (OS). Results: As of Sept 8, 2025, 61 pts with R/R MCL were enrolled (Gpt: 1000 mg, n=17; 2000 mg, n=44); 60 pts were treated. The median number of prior lines of therapy was 2 (range 1–5), median age was 72.0 years (range 41–86), 86.9% of pts had Ann Arbor stage III/IV, and 26.3% had a simplified MCL International Prognostic Index score of ≥6. Pts had high-risk disease features such as Ki-67 proliferation index ≥30% (62.3%), blastoid/pleomorphic variants (9.8%), and TP53 mutation (19.7%). The median number of glofitamab cycles received was 12 (range 1–13). With a median OS follow-up of 41.5 months (mo; 95% CI: 37.4–48.7), the ORR and CR rate were 82% and 77%, respectively. Median DoCR was 40.8 mo (95% CI: 14.1–NE); 48.9% of pts had ongoing CRs at the data cut-off. Estimated 33-mo DoCR and DoR rates were 50.5% and 47.4%, respectively. Median (95% CI) PFS was 18 mo (11.3–42.8) and OS was NE (26.9–NE). For pts who received prior BTKi therapy (n=34 [55.7%]), the ORR and CR rate were 73.5% and 70.6%, respectively. Median (95% CI) DoCR was 15.4 mo (8.3–NE), PFS was 11.3 mo (5.1–32.6), and OS was 29.9 mo (11.3–NE). Estimated 33-mo DoCR and DoR rates were 42.7% and 41.0%, respectively. No new safety signals were observed. Cytokine release syndrome remained the most common adverse event (n=42/60, 70%; Grade 1–2, 58.3%; Grade 3–4, 11.6%), with lower rates in the 2000 mg (n=28/44, 63.6%) vs 1000 mg (n=14/16, 87.5%) Gpt cohorts. Conclusions: Updated data on fixed-duration glofitamab monotherapy in heavily pretreated pts with R/R MCL show robust efficacy and manageable safety, including in BTKi-exposed pts. Glofitamab monotherapy is a suitable treatment for pts with R/R MCL in need of rapid disease control and is under investigation in the Phase 3 GLOBRYTE trial. Clinical trial information: NCT03075696 .
Substance use disorders following cancer diagnosis in adolescents and young adults: A Canadian population-based study.
e23102 Background: Substance use disorders (SUDs) can adversely affect cancer treatment and survivorship outcomes, including the risk of secondary malignancies among adolescents and young adults (AYAs) with cancer. However, data on the burden of SUDs and associated risk factors in this population remain limited. This study examined the five-year cumulative incidence of SUDs following cancer diagnosis and factors associated with its development among AYAs with cancer. Methods: This retrospective, population-based cohort study used the Manitoba Cancer Registry to identify AYAs aged 15–39 years diagnosed with invasive cancer between 1989 and 2019. Incident SUDs were identified using validated administrative definitions based on one or more hospitalizations or physician visits with diagnoses of alcohol- or drug-related psychoses, dependence, or non-dependent substance abuse (ICD-9 codes 291–305; ICD-10 codes F10–F19, F55, Z50.2, Z50.3). Competing risks regression was used to assess the five-year cumulative incidence of SUDs and the association of age, sex, comorbidities, income, residence, tumor type (sex-specific vs non–sex-specific), calendar year, and receipt of chemotherapy, surgery, or radiation with SUDs. Sex-specific cancers included breast, ovarian, uterine, and cervical cancers in females, and prostate and testicular cancers in males. Results: Among 3,818 AYAs with cancer (mean age at diagnosis, 30.7 years), 2,125 (56%) were female, and 3124 (81%) had solid tumors. The unadjusted 5-year cumulative incidence of SUDs post cancer diagnosis was 4.1% [95% Confidence Interval (CI), 3.5–4.8]. In competing-risk regression analyses, those in the highest income quintile had the lowest risk of developing SUDs compared to those in the lowest income quintile [sub-Hazard ratio (sHR), 0.40; 95% CI 0.25–0.66)] (Table 1). Receipt of chemotherapy (sHR, 1.53; 95% CI 1.07–2.28) and radiation therapy (sHR, 1.60; 95% CI 1.10–2.34) were independently associated with increased SUDs risk, whereas the presence of one or more comorbidities at diagnosis (sHR, 0.62; 95% CI 0.41–0.93) and more recent calendar year of diagnosis (sHR per year, 0.97; 95% CI 0.95–0.99) were associated with reduced risk. Conclusions: SUDs among AYAs with cancer post cancer diagnosis are higher among those in lower income quintiles and those receiving chemotherapy or radiation therapy. These findings support the integration of early, targeted substance use screening and equity-informed interventions into routine AYA oncology care for patients undergoing intensive treatment and those from socioeconomically disadvantaged backgrounds. Five-year adjusted cumulative incidence of substance use disorders by income quintile. Income Quintile 5-Year Adjusted Cumulative Incidence (%) Q1 (lowest income) 6.3 Q2 3.4 Q3 3.6 Q4 2.0 Q5 (highest income) 2.7
Beyond geography: The intersecting impact of rurality, race, and depression on breast cancer survival.
11137 Background: Rural–urban disparities in breast cancer outcomes are well-documented, with rural populations typically experiencing worse survival due to limited access to screening and specialty care. However, the role of integrated healthcare systems in mitigating these disparities and the impact of psychosocial factors, such as depression, on survival remain underexplored. This study evaluated the survival outcomes of breast cancer patients treated within an integrated, academic health system, focusing on the intersecting effects of geographic residence, race, and antidepressant therapy. Methods: We conducted a retrospective cohort study of 6,788 female breast cancer patients diagnosed between 2014 and 2024 at MUSC-affiliated facilities in urban and rural South Carolina. Data on patient demographics, cancer stage, hormone receptor status, depression diagnosis, and antidepressant use were extracted from electronic medical records. We used Kaplan-Meier survival analysis with log-rank tests and multivariable Cox proportional hazards models to assess the association of geographic location, race, and antidepressant use with overall survival, while adjusting for clinical and demographic confounders. Results: Contrary to national trends, rural patients demonstrated superior overall survival compared to urban patients (5-year survival: 92.1% vs. 85.3%, p < 0.001). In a multivariable model, rural residence was an independent protective factor (HR = 0.72, 95% CI: 0.61–0.85, p < 0.001). Antidepressant treatment was also associated with significantly improved survival (HR = 0.78, 95% CI: 0.65–0.93, p = 0.006). This survival benefit was consistent across urban and rural subgroups. While African American race showed a borderline increased risk of mortality (HR = 1.18, 95% CI: 0.98–1.42, p = 0.081), the rural survival advantage was maintained within both African American and non-African American subgroups. Triple-negative breast cancer (TNBC) was an independent and significant predictor of mortality (HR = 1.34, 95% CI: 1.15–1.57, p < 0.001), and was more prevalent in the urban cohort. Conclusions: Our findings suggest that a coordinated, academic-affiliated care model can effectively address geographic barriers to care. The study also highlights the critical role of psychosocial health, demonstrating that antidepressant therapy is an independent predictor of improved survival, reinforcing the need for integrated mental health support in oncology. Furthermore, the higher prevalence of aggressive triple-negative breast cancer in the urban cohort, coupled with the potential for the urban facilities to receive more complicated referrals, may contribute to the observed urban survival disadvantage, underscoring the interplay of tumor biology and patient referral patterns within integrated systems.
National mortality trends of malignant melanoma associated with cerebrovascular diseases in the United States (1999-2023).
e21518 Background: Malignant melanoma and cerebrovascular diseases (CVDs) pose major U.S. public health burdens, with melanoma mortality of 2.0–2.7 per 100,000 and > 160,000 annual cerebrovascular deaths. Linked through hypercoagulability, vascular disruption, and frequent brain metastases in advanced melanoma, their combined mortality patterns remain poorly defined despite therapeutic advances. This study examines national trends from 1999 to 2023 to identify vulnerable populations that require targeted interventions. Methods: This population-based study analyzed U.S. mortality data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) were calculated for malignant melanoma (ICD-10 C43) associated with cerebrovascular diseases (ICD-10 I60–I69) among decedents aged ≥45 years from 1999 to 2023. Trends were stratified by age, sex, race/ethnicity, urbanization, and Census region using Joinpoint regression. Analyses were conducted between December 2025 and January 2026. Results: Nationally, melanoma-associated cerebrovascular mortality increased by 1.4% annually from 1999 to 2023 (P < .05). Rates rose more steeply among individuals aged ≥65 years (AAPC, 1.59%; post-2012 APC, 3.46%; P < .001) compared with those aged 45–64 years. Non-Hispanic White individuals experienced the largest increase (AAPC, 2.8%; post-2018 APC, 6.5%; P < .001). Mortality rates were higher among males than females, though trends were parallel. Nonmetropolitan areas (AAPC, 2.05%) and the South and Midwest showed faster increases than metropolitan, Northeastern, or Western regions. Conclusions: Despite overall declines in isolated melanoma and cerebrovascular mortality, combined melanoma-associated cerebrovascular deaths increased steadily over two decades. Older adults, non-Hispanic White individuals, men, rural residents, and populations in the South and Midwest bear a disproportionate burden. These findings highlight the need for integrated vascular-oncologic care, enhanced surveillance, and equitable access to advanced therapies. Age-adjusted mortality trends for melanoma-related cerebrovascular deaths in U.S. adults ≥45 years (1999–2023). S. No. Characteristic AAMR (1999-2023) AAPC (95%CI) P Value JP, No. 1. Overall 0.30-0.40 1.37 (0.92–1.81) <0.001 1 2. Female 0.21-0.26 1.13 (0.22–2.05) 0.023 1 3. Male 0.50-0.60 1.38 (0.88–1.88) 0.000 1 4. Hispanic 0.31-0.45 1.50 (1.01–1.99) 0.000 1 5. Non-Hispanic - White 0.37-0.54 1.59 (1.12–2.06) 0.000 1 6. 45-64 years 0.10-0.14 1.07 (0.04–2.10) 0.053 0 7. ≥65 years 0.66-0.87 1.52 (1.05–1.99) 0.000 1 8. Census Region- Midwest 0.21-0.42 1.97 (1.12–2.82) 0.000 1 9. Census Region- West 0.38-0.48 1.45 (0.72–2.19) 0.001 1
Optimal timing of circulating tumor DNA (ctDNA) dynamics to prognosticate immune checkpoint inhibitors (ICI) efficacy in patients with advanced stage melanoma.
9534 Background: ctDNA predicts relapse in resected tumors, but its role in advanced disease is less defined. We previously reported that early ctDNA changes at 3-4 weeks after ICI initiation can inform treatment response and survival. In this study, we attempt to identify the optimal timing of ctDNA dynamics within 90 days at various windows to better associate with ORR, PFS, and OS outcomes in patients (pts) with advanced stage melanoma treated with ICI. Methods: We performed a multicenter retrospective analysis using a personalized tumor-informed ctDNA assay (Natera) on prospectively collected plasma from pts with unresectable stage III/IV melanoma treated with anti-PD-1-based therapy. ctDNA was assessed at baseline and within 90 days of ICI initiation, stratified by ≤30, 31-60, and 61-90 days. Logistic regression evaluated associations between ctDNA change (decrease/stable vs increase) and ORR. Cox proportional hazards models assessed PFS and OS. Pearson (ORR) and Spearman (PFS, OS) correlations were used for continuous ctDNA analyses. Results: Among 182 pts, 80% had cutaneous, 11% mucosal, and 9% unknown primary melanoma; 23% had unresectable stage III and 77% stage IV disease. Treatments included ipilimumab/nivolumab (55%), nivolumab/relatlimab (24%), and anti–PD-1 monotherapy (20%). Median follow-up was 12.1 months. Decreasing/stable ctDNA at all timepoints was strongly associated with ORR (p<0.0001), with the greatest effect at 31-60 days (OR 25.38, 95% CI 7.12-90.45). Similar patterns were observed for survival, with improved PFS across all windows and strongest separation at 61-90 days (HR 0.170, 0.101-0.288). OS was likewise improved, most notably at 61-90 days (HR 0.137, 0.058-0.321). Continuous ctDNA change correlated with ORR (r -0.51 to -0.63) and PFS (ρ -0.35 to -0.47); OS correlations were weaker but significant at 61-90 days (ρ -0.21). See Table 1. Conclusions: While ctDNA dynamics within 30 days showed prognostic value, associations with ORR, PFS, and OS were strongest and most consistent at 31–60 and 61–90 days. Prospective studies are needed to validate ctDNA for ICI treatment monitoring. Association of ctDNA dynamics with outcomes by time interval. ≤30 days 31-60 days 61-90 days ORR (OR, 95% CI) 15.28 (5.58–41.78), p<0.0001 25.38 (7.12–90.45), p<0.0001 17.82 (5.66–56.08), p<0.0001 PFS (HR, 95% CI) 0.373 (0.224-0.621), p<0.0001 0.233 (95% CI 0.139-0.388), p<0.0001 0.170 (0.101-0.288), p<0.0001 OS (HR, 95% CI) 0.477 (0.237-0.961), p=0.038 0.392 (95% CI 0.185-0.831), p<0.015 0.137 (0.058-0.321), p<0.0001 ORR (Pearson, r) -0.553, p<0.0001 -0.628, p<0.0001 -0.513, p<0.0001 PFS (Spearman, ρ) -0.352, p<0.0001 -0.438, p<0.0001 -0.473, p<0.0001 OS (Spearman, ρ) -0.128, p=0.168 -0.104, p=0.240 -0.210, p=0.0171
Prognostic biomarkers in retroperitoneal dedifferentiated liposarcoma and their clinical impact on patient management.
11546 Background: The prognosis of patients (pts) with retroperitoneal dedifferentiated liposarcoma (DDLPS) is mainly driven by tumor size, grade, patient age, and completeness of resection. Furthermore, the expression of myogenic markers has been associated with poorer outcomes. Prognostic nomograms, such as Sarculator, and transcriptomic signatures—most notably the Complexity INdex in SARComas (CINSARC)—have improved risk stratification. However, given the rarity of DDLPS and the limited evidence guiding treatment, identifying robust prognostic biomarkers remains a major challenge. This study evaluated the prognostic impact of clinical, morphological, and molecular features and assessed the performance of Sarculator and CINSARC in retroperitoneal DDLPS. Methods: A retrospective observational study was conducted on pts with retroperitoneal DDLPS treated at the Veneto Institute of Oncology (IOV)-IRCCS between 2004 and 2024. Tumor samples with adequate material underwent morphological, immunohistochemical, and molecular analyses, including CINSARC assessment. Disease-free survival (DFS) and overall survival (OS) were evaluated in surgically treated pts (Cohort 1), while progression-free survival (PFS) and OS were assessed in pts receiving first-line chemotherapy (Cohort 2). Sarculator was applied to Cohort 1, and its discriminative ability was evaluated using ROC curves. Concordance between CINSARC and Sarculator was also examined. Results: A total of 119 pts were included. In the overall population, tumor grade (3 vs 2: HR, 2.23; 95% CI 1.06 - 4.70; p = 0.03) and age (<65 vs ≥65: HR, 0.43; 95% CI 0.22 - 0.85; p = 0.02) were the most significant predictors of OS. In Cohort 1, these variables remained determinants of survival. In Cohort 2, sex, tumor size and differentiation significantly affected survival, with rhabdomyoblastic differentiation conferring the worst prognosis (p = 0.04). When Sarculator was applied to Cohort 1, a moderate discriminative ability was observed for OS (AUC = 0.75), with a lower performance for DFS (AUC = 0.64). Molecular analyses were performed on 32 samples; MYOG transcripts, indicative of rhabdomyoblastic differentiation, were detected in 8 cases. Based on CINSARC, 11 pts (34.4%) were low risk and 21 (65.6%) high risk. Agreement between Sarculator and CINSARC was moderate for both OS (Cohen’s Kappa, κ = 0.40) and DFS (κ = 0.55). Conclusions: To our knowledge, our study is among the largest conducted in retroperitoneal DDLPS specifically evaluating clinico-pathological features and the performance of Sarculator and CINSARC. Our findings support the negative prognostic impact of rhabdomyoblastic differentiation. Further investigation of differentiation patterns, combined with prognostic nomograms and transcriptomic signatures, may improve the identification of high-risk pts and support more personalized therapeutic strategies.
Family cancer history and perceived value of multi-cancer early detection tests in a national U.S. sample.
10519 Background: Family history of cancer has a strong influence on individuals’ perceived cancer risk and has been shown to be a key determinant of cancer prevention behaviors. As novel precision-screening technologies such as Multi-Cancer Early Detection (MCED) blood tests emerge, understanding how familial cancer experience shapes public awareness and openness to adoption is essential for equitable implementation. Methods: We analyzed data from a nationally representative survey (Health Information National Trends Survey 7), of U.S. adults aged ≥18 years (N = 5,789). Weighted analyses accounted for complex survey design and population structure. The prevalence of awareness and perceived value of MCED tests among individuals with a family history of cancer, as well as population characteristics, including socio-demographics, family history of cancer, and cancer-related beliefs were estimated. Weighted multivariable logistic regression models evaluated associations between family history and two primary outcomes: awareness and perceived acceptability of MCED adjusting for sociodemographic factors, personal cancer beliefs, and perceived cancer risk. Results: Of the overall study sample, 74.3% reported a family history of cancer. The sample was 50.6% female, 63.3% Non-Hispanic White, 10.9% Black, 16.1% Hispanic, and 4.9% Asian. In total, 17.3% reported prior awareness of MCED tests and 74.2% perceived MCED as valuable. After adjustment, family history of cancer was not associated with MCED awareness (OR = 0.94; 95% CI = 0.66 –1.34; p = 0.71). However, family history was significantly associated with higher acceptability of MCED testing (OR = 1.50; 95% CI = 1.15–1.96; p = 0.004). Conclusions: Adults with a family history of cancer are more willing to adopt Multi-Cancer Early Detection blood tests even without prior awareness. In this study, family history was not associated with MCED awareness but was significantly associated with higher perceived value and acceptability. This contrast suggests that receptivity to MCED may be driven more by perceived risk in the form of prior family history than by knowledge alone. Increasing general awareness may therefore be insufficient to promote broad uptake, highlighting the need to consider differences in risk perception when designing communication strategies as MCED moves toward clinical integration.
Genotype–anatomic correlates and survival outcomes in a molecularly validated 90-patient cohort of skeletal and extraskeletal Ewing sarcomas and mimics.
e23501 Background: Ewing sarcoma (ES)—defined by FET::ETS rearrangements—and Ewing-like small round-cell mimics represent a heterogeneous group of aggressive tumors with distinct genotypes and prognostic profiles. Clarifying genotype–anatomic correlations and their relationship to survival outcomes is clinically essential. Methods: Ninety small round-cell sarcomas of bone and soft tissue at a tertiary cancer center (2016–2025) were retrospectively analyzed. All cases underwent molecular confirmation using targeted RNA sequencing (Archer FusionPlex Sarcoma Panel) and/or break-apart FISH for EWSR1 and FUS. Genotypic subsets (Ewing vs Ewing-like) were compared across skeletal and extraskeletal sites. Associations with stage, treatment patterns, and overall survival were evaluated using univariate analysis. Results: Among 90 patients (median age 18.5 years), 76 (84%) harbored classical ES genetics, mainly EWSR1::FLI1 (89%), and 14 (16%) were Ewing-like with alternative (e.g., CIC::DUX4) or no detectable fusions. ES peaked in adolescence and showed a skeletal predilection (63%), particularly axial (p&lt;0.001), whereas Ewing-like tumors spanned a broader age range—including infantile cases—and were significantly enriched at extraskeletal sites (p&lt;0.001). Stage did not differ between ES and Ewing-like tumors or across skeletal and extraskeletal presentations. Most received multimodal therapy; VDC/IE was the predominant regimen. Neoadjuvant chemotherapy was more common in skeletal tumors, while upfront excision predominated in extraskeletal and visceral lesions. Overall survival was comparable across skeletal and extraskeletal tumors and between diagnostic categories; median OS not reached. Metastatic presentation, frequently involving the lungs, remained the dominant adverse prognostic factor (p=0.007). Ewing-like tumors demonstrated higher metastatic rates—particularly to lymph nodes—than ES. Visceral primaries showed a markedly elevated metastatic risk (p=0.004). Conclusions: ES and Ewing-like small round-cell tumors differ markedly in genotype, anatomic distribution, and age profile. Skeletal versus extraskeletal origin does not independently influence survival, underscoring the central prognostic importance of metastatic presentation. Ewing-like sarcomas exhibit more aggressive clinical behavior.
Trends in gastric cancer-related mortality across world bank income groups, 1980–2023: A retrospective analysis.
e16043 Background: Gastric cancer is a major global health concern and a leading cause of cancer-related mortality worldwide. This study examines trends in age-standardized death rates (ASDR) from 1980 to 2023 across countries stratified by World Bank income levels using data from the Global Burden of Disease (GBD) study. Methods: The GBD (2023) database was used to obtain the data. We included income based regions as classified by the world bank. ASDRs per 100,000 population among high income, lower income, lower middle income and upper middle income countries were assessed. We employed joinpoint regression analysis and estimated Average Annual Percentage Change (AAPC) values of the study period. A p value of less than 0.05 was considered statistically significant. Results: From 1980 to 2023, the largest decline in ASDR was observed in upper-middle-income countries, decreasing from 38.96 per 100,000 to 13.79 (AAPC: −2.44; 95% CI: −2.80 to −2.07; p < 0.000001). High-income countries also showed a consistent decline, from 24.16 per 100,000 to 7.25 (AAPC: −2.76; 95% CI: −2.90 to −2.61; p < 0.000001). Low-income countries maintained relatively stable ASDRs, from 13.37 per 100,000 to 11.50 (AAPC: −0.34; 95% CI: −0.44 to −0.24; p < 0.000001). In Lower-middle-income countries, the ASDR decreased from 9.69 per 100,000 to 6.90 (AAPC: −0.74; 95% CI: −0.93 to −0.56; p < 0.000001). Conclusions: Gastric cancer remains a major global health burden, with stark income-based disparities. Although ASDRs have declined in high- and upper-middle-income countries, progress is limited in low- and lower-middle-income settings. Expanding screening, improving early diagnosis, and ensuring equitable access to effective treatment are essential to further reduce global mortality. Gastric cancer mortality trends by world bank income groups: Age-Standardized Death Rate (ASDR) with 95% Uncertainty Interval (UI) in 2023 and Annual Percent Change (APC) with 95% Confidence Interval (CI). The (*) sign indicates p<0.05. Region APC (95% CI) ASDR 2023 (per 100,000) with 95% UI High Income 1980–1984: -1.98* (-2.48 – -1.47)1984–1987: -3.42* (-4.99 – -1.82)1987–1993: -2.23* (-2.59 – -1.87)1993–2021: -3.10* (-3.13 – -3.07)2021–2023: -0.06 (-1.69 – 1.58) 7.25 (6.45 to 7.89) Low Income 1980–1993: -0.51* (-0.59 – -0.44)1993–1998: -1.34* (-1.79 – -0.88)1998–2016: -0.69* (-0.74 – -0.64)2016–2020: 0.66 (-0.06 – 1.39)2020–2023: 2.85* (2.10 – 3.60) 11.50 (7.89 to 14.62) Lower Middle Income 1980–1989: -0.44* (-0.8145 – -0.07)1989–2010: -0.87* (-0.9863 – -0.76)2010–2015: -2.3539* (-3.5991 – -1.09)2015–2023: 0.25 (-0.18 – 0.70) 6.90 (5.15 to 8.82) Upper Middle Income 1980–1986: -1.80* (-2.85 – -0.74)1986–1990: 1.24 (-1.91 – 4.50)1990–2003: -1.80* (-2.17 – -1.44)2003–2014: -4.78* (-5.25 – -4.30)2014–2023: -2.49* (-3.06 – -1.93) 13.79 (11.48 to 16.74)
Adjuvant donafenib plus anti–PD-1 therapy in hepatocellular carcinoma with high-risk features after curative resection: A real-world study.
e16254 Background: Patients with hepatocellular carcinoma (HCC) and high-risk pathological features have a substantial risk of recurrence after curative resection, and effective adjuvant systemic therapies remain an unmet need. Evidence for postoperative combination therapy in real-world settings is limited. We conducted a real-world study to evaluate the efficacy and safety of adjuvant donafenib plus anti–PD-1 therapy in this population. Methods: This single-center retrospective study included HCC patients who underwent R0 resection followed by adjuvant donafenib plus anti–PD-1 therapy. Eligible patients had ECOG 0–1, Child–Pugh ≤7, and at least one high-risk feature, including tumor diameter ≥5 cm, tumor number ≥2, microvascular invasion (MVI), satellite nodules, or surgical margin <1 cm. The primary endpoint was 1-year recurrence-free survival (RFS). Secondary endpoints included overall survival (OS) and safety. Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were explored using Cox regression. Results: Seventy-seven patients were included. Overall, 26% had BCLC stage B or C disease, and 70.2% presented with two or more high-risk features. MVI was observed in 53.2% of patients, and most MVI-positive patients had additional high-risk factors. Median follow-up was 29.35 months. Median time from surgery to initiation of adjuvant therapy was 0.99 months. At data cutoff, 28 patients experienced recurrence and 5 patients died, all after recurrence. Median RFS was not reached; the 1- and 2-year RFS rates were 79.7% and 60.9%, respectively. Among patients with recurrence, intrahepatic recurrence predominated (n=16), followed by extrahepatic recurrence (n=6) and combined intrahepatic and extrahepatic recurrence (n=5); one recurrence pattern was unknown. OS outcomes were favorable, with 1- and 2-year OS rates of 98.5% and 94.8%, respectively, and median OS not reached. In multivariate analysis, portal vein tumor thrombosis (PVTT) was an independent adverse prognostic factor for RFS (HR 4.59, 95% CI 1.53–13.78; P=0.007). MVI showed a consistent trend toward poorer RFS (HR 2.01, 95% CI 0.89–4.57; P=0.094). Patients with two or more high-risk features tended to have shorter RFS than those with one high-risk feature (HR 2.59, 95% CI 0.98–6.84; P=0.054).Treatment-related adverse events occurred in 75% of patients. Grade 3 adverse events were reported in 10%, with no grade 4 or 5 events. Conclusions: In this real-world study of resected HCC patients with substantial recurrence risk, adjuvant donafenib combined with anti–PD-1 therapy demonstrated encouraging RFS outcomes with manageable safety. Recurrence was predominantly intrahepatic, and PVTT and MVI remained key adverse prognostic factors. These findings support further prospective evaluation of this postoperative adjuvant strategy.
Trends and factors associated with glucagon-like peptide 1 receptor agonists prescription for cancer populations with type 2 diabetes.
11181 Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in cancer survivors with Type 2 Diabetes (T2D) given its efficacy, yet concerns regarding treatment tolerance, weight loss, and limited oncology-specific guidance during active treatment and survivorship may influence prescribing patterns. To date, little evidence exists regarding the trends and factors associated with GLP-1RA use in cancer populations with T2D. Methods: We conducted a retrospective cohort study using SEER–Medicare data to identify patients newly diagnosed with seven most common cancers in 2010-2021 with pre-existing T2D. Pre-existing T2D was defined by relevant diagnosis codes within 12 months prior to cancer diagnosis. Patients with continuous Medicare Parts A & B and Part D enrollment were followed annually from diagnosis until death or end of follow-up (12/31/2022) to assess GLP-1RA use. A non-cancer cohort with T2D was identified using a 5% random sample of Medicare beneficiaries without cancer. We calculated annual proportions of beneficiaries with any GLP-1RA use, stratified by Traditional Medicare (TM) and Medicare Advantage (MA, data available in 2016-2021). Multivariable logistic regression models evaluated patient sociodemographic and clinical characteristics associated with GLP-1RA use in 2021. Results: We included 482,878 and 542,285 Medicare beneficiaries with T2D in the cancer and non-cancer cohort respectively (1,927,771 and 3,265,774 person-years in 2010-2022). Among TM beneficiaries, GLP-1RA use in the cancer cohort increased from 0.5% to 8.2% in 2010-2022, compared to an increase from 0.4% to 6.4% among non-cancer cohort; similarly higher GLP-1RA use was observed in cancer than non-cancer cohort among MA beneficiaries in 2016-2021 (1.8% to 6.8% vs. 1.3% to 5.7%; unadjusted p-values < 0.001). Rapid uptake was observed for dulaglutide and semaglutide from 2015, while liraglutide use declined modestly after peaking in 2018. In adjusted analyses within the cancer cohort, patients with breast (0.87 percentage points [ppts], p < 0.001), female genital (1.08 ppts, p < 0.001), and prostate cancers (0.62 ppts, p = 0.001) were more likely to receive GLP-1RAs than those with colorectal cancer. More advanced cancer stage was associated with lower likelihoods of GLP-1RA use; Non-Hispanic White, higher socioeconomic neighborhoods, and dual eligibility were associated with higher likelihoods of GLP-1RAs use. Conclusions: GLP-1RA use increased substantially among Medicare beneficiaries with cancer and T2D, and was consistently higher than those without cancer, which may reflect greater clinical engagement and cardiometabolic risk burden following a cancer diagnosis. Variation by cancer site, stage, and socioeconomic factors suggest that both clinical complexity and structural determinants shape GLP-1RA use in cancer survivors.
A phase 1/2 study of mRNA-2808 in participants with relapsed or refractory multiple myeloma.
TPS7580 Background: Multiple myeloma (MM) remains mostly incurable despite therapeutic advances and relapsed or refractory multiple myeloma (RRMM) remains a significant unmet need. mRNA-2808 is an intravenously (IV) administered mRNA-encoded, multiplexed T-cell engager (TCE) that delivers in vivo translation of three distinct TCEs targeting BCMA, GPRC5D, and FcRH5. This multiplexed approach aims to enhance immune-mediated cytotoxicity, overcome tumor heterogeneity and target-mediated resistance. Previous preclinical studies of mRNA-2808 have demonstrated efficient in vivo translation of TCEs, potent activity against both primary MM cells ex vivo and murine tumor xenografts in vivo , and target-cell depletion in non-human primates. Taken together, this supports the clinical evaluation of mRNA-2808. Methods: This ongoing, first-in-human, open-label, multicenter Phase 1/2 study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mRNA-2808 administered to participants with RRMM. Key eligibility criteria include RRMM with prior exposure to a proteasome inhibitor, an IMiD, and an anti-CD38 monoclonal antibody and are either triple-class refractory or have progressed on or within 60 days of their last line of therapy, have measurable disease including bone marrow plasma cells >30% or plasmacytoma ≥2cm in size, and ECOG PS 0-2. Prior exposure to BCMA, GPRC5D, or FcRH5 targeted therapies is allowed. The study comprises two parts: Part 1 (dose escalation) to determine the recommended Phase 2 dose(s) (RP2D) and Part 2 (dose expansion) to further assess safety and efficacy of selected RP2D(s). The dose-escalation in Part 1 will proceed in 2 phases: Accelerated Titration Phase (single participant per dose level (DL)) and Standard Titration Phase (at least 3 participants per DL). The Accelerated Titration Phase will continue until a dose limiting toxicity (DLT) or a clinically significant AE of ≥Grade 2 is observed. If a ≥Grade 2 CRS and/or ≥Grade 2 neurotoxicity including ICANS occurs, step-up dosing will be implemented. During the Standard Titration Phase, dosing decisions will be guided by a Bayesian Optimal Interval design based on the observed DLT rate from the current cohort and recommendations from the Safety Review Committee. During Cycle 1 (28-day cycles), mRNA-2808 will be administered IV weekly, and during Cycles 2-12 every 2 weeks. Treatment with mRNA-2808 will continue for up to 12 cycles. Participants who achieve at least a partial response by the end of Cycle 5 may transition to a 4-week dosing schedule at the Investigator’s discretion. Additional exploratory endpoints will evaluate surrogates of efficacy, mechanism of action, and characterize exposure. Dose Levels 1 and 2 have been completed without DLT and dose escalation is ongoing (NCT07116616). Clinical trial information: NCT07116616 .
Treatment patterns and outcomes in pacritinib-treated patients with MF and higher platelet count: MY-PAC study.
6575 Background: Pacritinib (PAC), a JAK1-sparing JAK2/IRAK1/ACVR1 inhibitor has shown spleen volume and symptom improvement in clinical trials of in patients (pts) with myelofibrosis (MF) with similar benefits in the real-world. This analysis evaluated real-world outcomes in pts with MF and platelet counts (PLT) ≥50 x10 9 /L at PAC initiation. Methods: This was a multisite chart review of pts with MF treated with PAC for ≥1 month between 06/01/2022 and 07/31/2024 with ≥6 months of follow-up through 01/31/2025. Pts were followed from PAC initiation (index) until the earliest of end of the study, the end of data availability for the pt, or death. Evaluated data included Pt characteristics, treatment patterns, palpable spleen length (total spleen length minus 10cm) and spleen size category based on palpation or palpable spleen length below costal margin (not palpable/minimally palpable <5 cm below costal margin; mild: 5-10 cm palpable; moderate: 11-20 cm palpable; severe: >20 cm palpable), PLT, hemoglobin (Hb), MF-related symptoms, and overall survival through Day 180. Results for pts with PTL ≥50 x10 9 /L at index are described using counts and percentages, medians and interquartile range (IQR), and survival probabilities. Results: Of 169 pts with MF treated with PAC, 27% (45/169) had PLT ≥50 x 10 9 /L at index. Median age was 67 years (IQR: 62-74) at diagnosis and median time from diagnosis to index was 6 months (IQR: 1.3-14.3). The median duration of follow-up from index was 7.6 months (IQR: 6.7-11.0) and 82% of pts (n=37) were still on PAC at end of follow-up. Of 12 pts with spleen length measured by ultrasound at index and Day 180, median spleen length reduction (SLR) was 39% (IQR: 30.4-48.3) with 83% (10/12) achieving SLR ≥25% by Day 180. Among those with categorical spleen size based on palpation (n=5) or ultrasound (n=12), 53% (9/17) achieved a reduction in spleen size category. No pts had a worsening in spleen size category, and spleen size category remained stable for 47% (8/17) of pts. At index, all but one pt had ≥1 MF-related symptom. By Day 180, 80% (35/44) experienced a reduction in the number of symptoms, with a median reduction of 67% (IQR: 33-75). Median PLT at index was 72 x 10 9 /L (IQR: 53-110) and from index to Day 180, median increase in PLT was 14% (n=38, IQR: 0-30). Among pts with PLT ≤100 x10 9 /L at index 20% (6/30) achieved an increase of ≥30x10 9 /L. At index, median Hb was 8.8 g/dL (IQR: 8.0-9.7). Among 29 pts with Hb <10 g/dL at index and Hb at Day 180, Hb increased by a median of 0.8 g/dL (IQR: -0.1-1.0), with 31% (9/29) achieving an increase ≥1.0 g/dL. Overall survival by the end of follow-up was 89% (40/45), and 6-month survival probability was 93% (95% confidence interval: 81, 98). Conclusions: Similar to clinical trials, pts with MF and higher PLT counts treated with PAC in the real-world also experienced reduction or stabilization in spleen size category, decreased MF-symptom burden, PLT stability, and improved Hb.
Real-world outcomes among Medicare beneficiaries treated with first-line (1L) Bruton tyrosine kinase inhibitors (BTKis) for chronic lymphocytic leukemia (CLL).
7047 Background: Covalent BTKi monotherapies are standard of care for 1L CLL in the US. However, there is a lack of head-to-head BTKi trials in the 1L setting, and previous real-world studies had limited sample size and follow-up time. We used a large US database to evaluate clinical outcomes among patients (pts) treated with BTKis for 1L CLL. Methods: This retrospective cohort study utilized the de-identified Medicare Fee-For-Services database. Eligible pts included those with a CLL/SLL diagnosis at age ≥65 y who started 1L BTKi monotherapy between 01/01/2020 and 06/30/2025 and ≥12 months (mos) enrollment pre-1L. Outcomes included real-world overall survival (OS), time to next treatment (tx) or death (TTNT), and time to tx discontinuation or death (TTD) from 1L start. Landmark tx and survival probabilities at 12 and 24 mos were estimated using Kaplan–Meier methods. Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox proportional hazard models, adjusting for age, sex, race/ethnicity, Charlson Comorbidity Index (CCI) and year of 1L start. Subgroup analysis was performed by age groups (65-74, 75-84, ≥85 y). Results: A total of 10,523 pts were included (zanubrutinib [zanu]:3006; acalabrutinib [acala]:4309; ibrutinib [ibr]:3208). Median age at 1L was 77 y for zanu and acala, and 76 y for ibr. Most pts were male (58%), non-Hispanic White (91%), and resided in urban areas (78%). Median CCI score was 4 for zanu and acala, and 3 for ibr. At baseline, hypertension was 65% overall, and atrial fibrillation was 17% for zanu and acala, and 12% for ibru. Median follow-up was 16 mos (range: 0-61) for zanu, 21 mos (0-69) for acala and 35 mos (0-69) for ibr. Median OS was not reached (NR) for all groups. Median TTNT was NR for zanu (95% CI, 45-NR), 40 mos (38-42) for acala, and 30 mos (29-32) for ibr. Median TTD was NR (NR-NR) for zanu, 24 mos (22-25) for acala, and 14 mos (13-15) for ibr. Pts on zanu had higher probability of survival, not advancing to next line of therapy and not discontinuing tx at 12 and 24 mos, than those receiving acala and ibr (Table; with 95% CIs). After adjusting for baseline factors and year of 1L, pts on zanu had a statistically significantly lower risk of death, advancing to next line, or discontinuing tx, than those on ibr or acala. Similar results were observed across age subgroups. Conclusions: In this large cohort of pts aged ≥65 yrs with longest follow up to date, zanu monotherapy was associated with better survival and tx outcomes, compared to ibr and acala. Tx OS TTNT TTD 12 mos % 24 mos % aHR 12 mos % 24 mos % aHR 12 mos % 24 mos % aHR Zanu 91(90-92) 86(84-87) 82(81-94) 71(69-74) 72(71-74) 63(61-65) Ibr (ref) 85(84-86) 75(74-77) 0.64(0.54-0.77) 74(72-75) 56(55-58) 0.63(0.55-0.71) 53(51-55) 35(33-37) 0.57(0.51-0.64) Acala (ref) 87(86-88) 80(78-81) 0.77(0.66-0.88) 78(77-80) 67(65-68) 0.87(0.78-0.96) 63(61-64) 49(47-51) 0.86(0.78-0.94)
GLP-1 receptor agonist utilization and survival outcomes in a large U.S. community oncology cohort.
11017 Background: GLP1 use has increased with 12.4% of U.S. adults reported using these treatments, driven in part by the 2021 approval of semaglutide for chronic weight management without diabetes. Beyond established metabolic benefits, emerging preclinical and observational data suggest potential anticancer effects of GLP1 therapy. However, no study to date has characterized GLP1 use among cancer patients treated in a large-scale population. This study provides an essential step towards describing real-world world GLP1 treatment patterns and clinical outcomes. Methods: Structured EHR data from The US Oncology Network were used to identify GLP1 users (dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, and tirzepatide) and nonusers between January 2021 and October 2024, with follow-up through October 2025. Overall survival (OS) was assessed from initial cancer diagnosis to death from any cause. Nonusers were matched to GLP1 users by cancer type and diagnosis year. To address immortal time bias, each nonuser was assigned the matched user’s GLP1 medication start date as the anchor date; nonusers who died or were lost to follow-up prior to that date were excluded. Multivariable Cox proportional hazards models evaluated factors associated with OS among patients diagnosed with breast, prostate, lung, hepatocellular, or renal cancer. Results: A total of 1,121 GLP1 users and 471,580 non GLP1 users with cancer were identified. GLP1 users had a median age of 63 years, were 63% White, and 69% had BMI ≥30 kg/m 2 semaglutide was the most commonly used agent (64%). Non GLP1 users had a median age of 68 years, were 61% White, and 30% had BMI ≥30 kg/m 2 . Among GLP1 users, 74% were prescribed GLP1 therapy after initial cancer diagnosis, of those 7% after metastatic diagnosis; the most common cancers were breast (27%) and prostate (13%). OS at 24 months was higher among GLP1 users versus nonusers for both breast cancer (97.9% [95% CI 93.7–99.3] vs 92.6% [92.4–92.8]) and prostate cancer (97.9% [93.7–99.3] vs 92.6% [92.4–92.8]). After adjustment for age, BMI, stage, and cancer type, GLP1 use was significantly associated with improved OS (HR 0.58, 95% CI 0.40–0.84; p = 0.0036). Conclusions: In this large real-world cohort, GLP1 use was most frequently observed among younger patients with obesity and was commonly prescribed after cancer diagnosis, with semaglutide accounting for the majority of prescriptions. Breast and prostate cancers were the most prevalent malignancies among GLP1 users, reflecting early adoption across common solid tumor types in routine practice. Despite limitations inherent to structured real-world data, including potential underreporting of GLP1 exposure, GLP1 use was associated with improved OS compared with nonuse, supporting the need for future studies using robust causal inference approaches.
Large cell carcinoma with rhabdoid phenotype: Demographics, treatment, and survival in the NCDB.
e20078 Background: Large cell carcinoma with rhabdoid phenotype (LCC-RP) constitutes <1% of lung malignancies and is associated with a poorer prognosis than classic LCC, characterized by aggressive biologic behavior with early widespread metastasis and rapid progression. The median survival and five-year survival rate among LCC patients are eight months and 15.6%, respectively. Case series report LCC-RP patients as primarily male (ages 35-70) and often presenting with advanced disease stages (n=11). Since comprehensive survival data remain unreported, this study uses the NCDB to analyze the demographic profile and survival outcomes of patients with LCC-RP. Methods: A retrospective cohort study using the 2004–2020 National Cancer Database to identify patients with histologically confirmed LCC-RP (ICD-O-3 code 8014). Variables included demographics (age, sex, race, Hispanic origin, educational attainment, insurance status, treatment facility type, Charlson-Deyo comorbidity score), clinical characteristics (stage at diagnosis, primary tumor site), treatment modalities (surgical resection, chemotherapy, radiation therapy), and survival outcomes. Incidence patterns were evaluated using regression analysis. Results: The study cohort included 293 patients with LCC-RP. No substantial temporal trend in annual incidence was observed (R² = 0.033). Stage IV disease was most common at diagnosis (37.5%), with upper lobe predominance (31.1%). Most patients were male (60.8%), non-Hispanic (93.2%), and White (83.3%), with a mean age of 65.4 years. Patients predominantly resided in metropolitan areas (84.7%) and were evenly distributed across income quartiles, with the largest proportion in the ≥$74,063 quartile (28.2%). Most were insured by Medicare (51.9%), and comprehensive community cancer programs treated the plurality of patients (42.5%). Most patients (64.8%) did not undergo surgical resection. Chemotherapy was the most common treatment (42%), followed by radiation therapy (35.2%). Median survival was 62.7 months, with five-year and ten-year survival rates of 34.1% and 26.7%, respectively. Conclusions: This is the first NCDB analysis of large cell carcinoma with rhabdoid phenotype, providing demographic, treatment, and overall survival data from a large national cohort. Most patients were male, non-Hispanic, and white, consistent with the gender distributions in prior case series. Patients were evenly distributed across income quartiles, with the largest proportion in the highest quartile. They predominantly lived in metropolitan areas and were most commonly treated at comprehensive community cancer programs. Median survival (62.7 months) dramatically exceeded survival estimates reported in prior case series. Further research is needed to analyze factors contributing to improved survival and the impact of demographic, socioeconomic, and treatment variables on outcomes.
Phase 2 trial of lisocabtagene maraleucel for minimal residual disease in patients with large B-cell lymphoma.
TPS7107 Background: Patients with relapsed/refractory large B-cell lymphoma (LBCL) have a poor prognosis. Identifying patients at high risk of recurrence after completion of first line (1L) treatment is crucial to enable early intervention with further treatments that may improve outcomes. Recent studies have shown that detectable minimal residual disease (MRD) by circulating tumor DNA (ctDNA) assay after 1L chemoimmunotherapy is prognostic for risk of recurrence. We hypothesize that lisocabtagene maraleucel (liso-cel) will eradicate the MRD in patients with LBCL who have detectable ctDNA at the end of 1L treatment will lead to improved long-term outcomes relative to historical results with liso-cel in second line treatment for patients with radiologically-detected disease. Methods: This is an open-label, phase 2, single-arm, multicenter, investigator-sponsored trial designed to evaluate the efficacy and safety of lisocabtagene maraleucel (liso-cel) in patients with LBCL who have achieved a response to 1L standard-of-care therapy but have detectable MRD. The trial will enroll 50 evaluable patients. Eligible participants are adults with LBCL, including DLBCL-NOS and HGBCL, who received 1L anthracycline-based chemoimmunotherapy (R-CHOP, DA-EPOCH-R, or polatuzumab-R-CHP) for six cycles, with or without an additional two cycles of rituximab, for previously untreated disease. Patients must have achieved a CR, or a PR with a negative biopsy or biopsy not feasible, and must demonstrate detectable MRD as assessed by the Foresight CLARITY ctDNA-MRD assay following completion of 1L therapy. The primary endpoint is event-free survival rate at 12 months, and secondary endpoints include rate of undetectable MRD. Correlative studies are designed to build a holistic model for understanding the tumor-intrinsic and immune features that contribute to response, as well as treatment-associated toxicities following liso-cel in patients with LBCL and detectable MD, a population at high risk of recurrence. Enrolment to the trial is planned at five centers in the US: MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center, City of Hope and Massachusetts General Hospital (NCT07316010). Clinical trial information: NCT07316010 .