Browse Articles

Real-world biomarker testing rates, targeted therapy use, and clinical outcomes in patients with advanced gastric or GEJ cancer in the United States.

e16039 Background: Guidelines endorse testing patients (pts) with advanced (adv) gastric cancer (GC) or gastroesophageal junction cancer (GEJC) for HER2, PD-L1, MMR/MSI, and CLDN18 to guide first-line (1L) treatment (tx) decisions. Tx decisions in cases of multiple targets are not well defined in real-world (rw) practice. This study evaluated the alignment between biomarker results and rw-1L tx and its association with clinical outcomes. Methods: This retrospective cohort study of adult pts with adv GC/GEJC used the US-based, electronic health record (EHR)-derived deidentified Flatiron Health Research Database. Pt follow-up started from the first EHR activity after January 1, 2011, and spanned to September 30, 2025. Pts were included if they received 1L tx on or after September 1, 2017. Biomarker testing was assessed before and up to 30d post 1L start. 1L regimens included immunotherapy (IO) + chemotherapy (Chemo) + HER2, IO + Chemo, HER2, Chemo, and Other. Pts were further categorized into received “guideline concordant tx” or not according to biomarker test results and 1L tx received. Cox proportional hazard models estimated time to next tx or death (rwTTNTD) associated with guideline concordance tx, adjusting for demographics, clinical characteristics, and biomarker results. To account for non-proportional hazards, a piecewise Cox model with a time split at 20 months was used. Results: Of 3,828 pts (58% GC, 42% GEJC, 60% ≥65 years, 57% diagnosis stage IV/IVB), testing rates for HER2, MMR/MSI, PD-L1, and CLDN18 were 78%, 58%, 50%, and 6%, with positivity rates of 17%, 7%, 66%, and 47%, respectively. 13.4% (n = 322) of pts tested for > 2 biomarkers had > 2 actionable biomarkers (eg, HER2+ & PD-L1+). Concordance between biomarker status and 1L tx was high for HER2+ disease, with 62% of HER2+ pts receiving HER2-directed therapy. In contrast, concordance was lower for PD-L1+ and CLDN18+ disease, with < 37% of pts receiving IO or targeted tx in concordance with each positive biomarker. Among pts with ≥2 actionable biomarkers, IO therapy was not prioritized as consistently as HER2-directed therapy (32% received IO + Chemo + HER2, 34% HER2, 34% other tx groups). Pts receiving non-concordant tx had a 16% increased risk of next tx or death during the first 20 months after 1L start vs pts receiving concordant tx (HR [95% CI], 1.16 [1.07-1.26]); P < .001). No significant association was observed beyond 20 months (0.76 [0.55-1.04]). HER2+ status was independently associated with reduced risk (0.85 [0.76-0.95]; P = .003). Conclusions: In rw-practice, tx decisions were more often discordant with biomarker results for PD-L1+ or CLDN18+ compared with HER2+. Concordant first-line tx showed an early rwTTNTD benefit without sustained risk reduction after about 20 months. Broader biomarker testing and clearer tx-prioritization frameworks are needed to advance precision medicine in adv GC and GEJC.

Mechanistic study of iron oxide nanoparticles synthesized from sapota leaves extract for the removal of crystal violet from model industrial effluent: Experimental, simulation and RSM modelling

Dynamic Circular Sulfur‐Rich Polymer Glasses From Elemental Sulfur

ABSTRACT Elemental sulfur (S 8 ) is a commodity‐priced petroleum byproduct suitable for upcycling as a neat molten medium for sustainable polymer synthesis. Inverse vulcanization is an attractive approach for converting S 8 into sulfur‐rich plastics, yet scalable manufacturing remains challenging. The chemistry of molten sulfur is poorly understood, limiting progress using this unconventional medium. Herein, molten sulfur homogeneity is identified as a critical parameter for accessing sulfur‐rich (70–80 wt.%) polymer glasses, termed inverse vulcanized glass (IVG). Application of ultra‐high‐purity sulfur melts uncovers a hidden boundary condition governing sulfur plastic manufacturing, enabling fabrication of large IVG precision optics with high refractive index and landmark broadband transparency across the visible–infrared spectrum. The inclusion of S–S bonds afford covalent adaptable networks with rheology dominated by dynamic bond reorganization. IVG functions as an affordable, broadband Vis–IR optical glass whose damaged components can be melt‐reprocessed, providing a circular advantage over traditional inorganic optical materials.

Impact of chronic kidney disease on toxicity patterns and economic burden in CAR T-cell therapy for multiple myeloma: A national analysis.

e19536 Background: Chronic kidney disease (CKD) may impair physiologic resilience during chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM). While cytokine response syndrome (CRS) and immune cell-associated neurotoxicity syndromes (ICANS) have been described in MM CAR-T recipients with CKD, the broader cardiopulmonary, infectious, renal, and economic implications of CKD remain insufficiently defined. We examined the national impact of CKD on mortality, immune cell effector toxicities, organ dysfunction, infections and resource utilization. Methods: Adult MM hospitalizations receiving CAR T-cell therapy were identified from the National Inpatient Sample (2018–2022) using ICD-10-PCS codes. Patients with ESRD were excluded. CKD was categorized as CKD3a+ (eGFR <60 mL/min) versus no CKD/CKD1–2. Outcomes included in-hospital mortality, CRS (2021–2022), ICANS (2022), cardiac arrhythmias, acute kidney injury (AKI), renal replacement therapy, respiratory failure, infections and total hospitalization cost (calculated using TOTCHG variable and adjusted cost to charge ratio). Comparative analysis was done using chi-square testing. Multivariate analysis adjusted for demographics, comorbidities, and hospital characteristics. Results: Among 2,045 weighted MM CAR-T hospitalizations, 7.6% had CKD3a+. Overall CRS rates were similar (66.7% vs 64.9%; p=0.839) between CKD3a+ vs no/CKD1-2. Overall ICANS rates were also comparable (16.7% vs 17.3%; p=0.941). Differences in CRS/ICANS grades were not significant. CKD3a+ patients experienced sharply higher AKI (58.1% vs 13.0%; p<0.001; adjusted odds ratio [OR] 9.2, p<0.001). Renal replacement therapy was more frequent in CKD3a+ but non-significant (3.2% vs 0.8%; p=0.196). Acute respiratory failure was more frequent (9.7% vs 2.9%; p=0.045) in patients with CKD. Cardiac arrhythmias were numerically higher but non-significant (25.8% vs 20.6%; p=0.527; adjusted OR 1.3, 95% CI 0.4–4.9; p=0.673). Infections were amplified, including gram-negative bacteremia (3.2% vs 0.3%; p=0.026), sepsis (9.7% vs 2.6%; p=0.040), and septic shock (3.2% vs 0.3%; p=0.027) in patients with CKD. Inpatient mortality was numerically higher (6.5% vs 1.9%; p=0.101), though nonsignificant after adjustment (OR 6.9; p=0.319). Hospital costs were substantially higher in CKD3a+ (USD 346,769 vs 239,175; p=0.006), though not significant in adjusted models (OR 1.3; p=0.120). Conclusions: CKD3a+ is associated with markedly increased AKI, higher respiratory failure and infections, with a trend towards higher hospitalization costs. Inpatient mortality, CRS and ICANS rates were similar. CKD3a+ represents a significant vulnerability that amplifies downstream complications in MM CAR-T recipients, warranting enhanced pre-treatment risk stratification, infection surveillance and renal-preserving strategies.

Decomposing the co-mutational landscape of NSCLC by unsupervised learning to unveil components with impact on overall survival.

8041 Background: The molecular characterization of non-small cell lung cancer (NSCLC) and targeting therapies are improving outcomes for many patients. However, about 40% remain without identifiable molecular drivers. Understanding the co-mutational landscape of NSCLC may contribute to close that gap but has not yet been sufficiently characterized beyond e.g. TP53 co-mutations that associated with adverse outcome (Galina et al. J. Thor. Onc . 2024). Previously, the hierarchical Dirichlet mixture model (HDMM) provided important insight into acute leukemia biology (Papaemmanuil et al. NEJM 2016, Turki et al. EHA plenary abstract 2025), reason why we adopted this method for the first time to decompose the NSCLC genetics landscape. Methods: Here, we leveraged the HDMM with multinomial distribution for unsupervised learning of NSCLC genetics on the large AACR GENIE BPC NSCLC cohort (n = 1,846 patients, Choudhury et al. Clin. Can. Res . 2023) including 300 features for 60 genes. Preprocessing excluded columns with < 5 mutations, features duplicating information or with high rates of missingness, leaving the most relevant 85 genetic features for HDMM analysis including single mutations, gene amplifications and deletions. Within UICC stages I, II-III and IV, overall survival (OS) was analyzed with the Kaplan Meier method comparing the new components with the logrank test. Results: Among 1926 genetically distinct tumors of 1785 NSCLC patients with detectable genetic alterations, the HDMM identified four components assembling patients with similar landscape. Their driver patterns involved either co-mutated TP53/KRAS , TP53/EGFR or PDGFR/KDR and other mutations including established risk groups, i.e. with amplifications in ALK , BRAFV600E, cMET exon 14 or single EGFR or KRAS mutations, ROS1 or NTRK translocations. As expected, UICC stages I-IV stratified this cohort significantly for OS. Next, we tested whether genetic components refined outcomes within the same UICC stage. Indeed, for stage I NSCLC the genetic components associated with significant OS differences (p = 0.0065). Patients with PDGFR/KDR had the highest OS, while patients of the TP53/KRAS component had the lowest median OS with a Kaplan Meier estimate of 82.4 months as compared to 116.7 in the TP53/EGFR cluster. Also, among patients with stage II-III NSCLC, the three components associated with significant differences in OS (p = 0.023). Not taking into account other driver mutations, the components also associated with distinct OS in patients with stage IV NSCLC (p = 0.0001). Conclusions: This analysis of the co-mutational landscape is complementing existing genetic classes in NSCLC. We identified a new PDGFR / KDR component and support the relevance of previously described co-occurring TP53 / EGFR and TP53 / KRAS . The significantly distinct OS in resectable NSCLC may open new risk adapted treatment strategies.

Enhanced pre-biopsy risk stratification for aggressive prostate cancer using prostate density in an EHR-derived cohort.

e17127 Background: Total prostate-specific antigen (PSA) lacks specificity for distinguishing aggressive prostate cancer (Gleason score ≥7) from indolent/benign disease, leading to unnecessary biopsies. Prostate-specific antigen density (PSAD), incorporating prostate volume, may improve diagnostic prediction. We developed and internally validated prediction models comparing PSAD-based versus PSA-based approaches using electronic health record (EHR) data. Methods: We conducted a retrospective cohort study using EHR data from Rush University Medical Center. Men aged > 30 years who underwent prostate biopsy between 2017-2024 were included if they had PSA ≤1 year pre-biopsy, prostate volume from mpMRI/TRUS, and pathologic confirmation. The outcome was aggressive prostate cancer (Gleason ≥7) versus indolent/benign disease. Candidate predictors included demographics, comorbidities, medications, and PSA or PSAD (log 2 -transformed). Logistic regression and random forest models were developed, evaluating PSA and PSAD alone and in combination with clinical predictors. Data were randomly split 80/20 for training/testing with 5-fold cross-validation for internal validation. Results: 673 men total were included, of whom 333 (49%) had aggressive prostate cancer, with a median age of 65 years. PSAD consistently outperformed total PSA across all models. In multivariable logistic regression, PSAD showed a significant association with aggressive cancer (OR per doubling 2.87; 95% CI 2.32–3.61). Age was independently associated with aggressive cancer, whereas race and ethnicity were not significant. Overall, PSAD-based models improved area under the curve (AUC) by an average of 0.10 in training and 0.12 in testing compared with PSA-based models. Conclusions: PSAD significantly improves prediction of aggressive prostate cancer compared with total PSA alone. Incorporating PSAD into pre-biopsy risk stratification algorithms may reduce unnecessary biopsies while maintaining detection of clinically significant disease. EHR-derived clinical notes represent a valuable data source for algorithm development and highlight the importance of integrating structured and unstructured data sources in oncology decision support. Comparison of model performance for aggressive prostate cancer discrimination. Model Predictors Train AUC (95% CI) Test AUC (95% CI) Logistic Regression Total PSA 0.67 (0.63–0.72) 0.56 (0.46–0.66) Logistic Regression Total PSA + Demographics 0.70 (0.66–0.74) 0.57 (0.47–0.67) Logistic Regression PSAD 0.78 (0.74–0.82) 0.67 (0.57–0.76) Logistic Regression PSAD + Demographics 0.79 (0.76–0.83) 0.67 (0.58–0.77) Random Forest Total PSA + Demographics 0.67 (0.63–0.72) 0.50 (0.39–0.60) Random Forest PSAD + Demographics 0.78 (0.74–0.81) 0.65 (0.55–0.75) Demographics included age, race, and ethnicity, based on a p-value < 0.10 in univariable modeling.

TroFuse-022/ENGOT-ov84/GOG-3103 part 2: A phase 3 study of maintenance therapy with sacituzumab tirumotecan ± bevacizumab vs standard of care following second-line platinum-based doublet chemotherapy for platinum-sensitive recurrent ovarian cancer.

TPS5636 Background: There is an unmet clinical need for novel therapies for patients with platinum-sensitive recurrent ovarian cancer (PSROC). Trophoblast cell-surface antigen 2 (TROP2) is highly expressed in multiple tumor types, including ovarian cancer. Sacituzumab tirumotecan (sac-TMT) is a TROP2-directed antibody-drug conjugate with a unique, bifunctional linker that maximizes delivery of a belotecan-derived topoisomerase 1 inhibitor payload to tumor cells. The current TroFuse-022/ENGOT-ov84/GOG-3103 study (NCT06824467) is evaluating maintenance therapy with sac-TMT ± bevacizumab (bev) vs standard of care (SoC) following second-line (2L) platinum-based doublet chemotherapy (chemo) in participants (pts) with PSROC. The study includes a safety run-in part (part 1) and a phase 3 part (part 2). We present the trial design for part 2 of this study. Methods: Part 2 is enrolling ~750 pts aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with PSROC (radiographic evidence of PD >180 d after the last dose of first-line [1L] platinum-based doublet chemo ± bev); pts with BRCA mutation or homologous recombination deficiency-positive status with no evidence of disease (NED), CR, or PR after 1L chemo must have received a PARP inhibitor as 1L maintenance therapy. All pts must have received 6 cycles of 2L carboplatin-based doublet chemo ± bev and achieved NED, CR, PR, or SD per investigator assessment; pts with SD must have received bev in combination with 2L chemo and be eligible to continue treatment with bev. Other inclusion criteria are an ECOG PS of 0 or 1 and an available tumor sample for central testing of TROP2 and BRCA status. Candidates for curative-intent surgery or radiotherapy at enrollment are not eligible. Pts are randomized 1:1 to receive maintenance therapy with sac-TMT 4 mg/kg IV Q2W ± bev 15 mg/kg IV Q3W (arm 1) or SoC treatment with observation ± bev 15 mg/kg IV Q3W (arm 2). Use of bev is at the investigator’s discretion and can only be given to eligible pts who received ≥2 doses of bev 15 mg/kg Q3W or equivalent dose (with no dose reductions) in combination with 2L chemo; pts with SD after 2L chemo must receive bev (pts with SD not receiving bev are ineligible). Treatment with sac-TMT (arm 1) and bev (if elected, arms 1 and 2) continues until PD, unacceptable toxicity, or other protocol-defined reason for discontinuation. Pts in arm 2 are not permitted to cross over to arm 1. The primary endpoint is PFS per RECIST version 1.1 as assessed by blinded independent central review. Secondary endpoints include OS, safety and tolerability, and patient-reported outcomes. PFS and OS will be assessed in pts with medium/high TROP2 expression tumors and all pts. The study is ongoing, and enrollment in part 2 is open. Clinical trial information: NCT06824467; EU CT, 2023-508015-23; UTN, U1111-1297-4489.

Knowledge, attitudes, and factors influencing clinical trial participation among breast cancer patients in Brazil: The LACOG 1123 (ASTRAL) study.

e23209 Background: Despite Brazil’s growing participation in clinical cancer research, data on knowledge, attitudes, and factors influencing clinical trial participation remain limited. The LACOG 1123 (ASTRAL) study evaluated these aspects among Brazilian patients with breast cancer (BC). Methods: Patients ≥18 years diagnosed with stage I-IV BC within the previous five years and receiving active treatment or having completed treatment within two years were invited by their treating physicians to complete an electronic survey. The questionnaire included sociodemographic and clinical characteristics, as well as questions related to clinical research adapted from previously published surveys. Results: A total of 350 responses were received from all regions of Brazil. Most physicians worked both in private and public setting (52%). Median age was 49.0 years (IQR 42-60), 54.6% were white, and 85.3% had private health insurance. The majority had initial disease (32.5%) and 89.1% were receiving active treatment. Regarding previous knowledge on clinical research, 63.1% reported having heard about clinical trials, most of them learned through some kind of media (68%); however, 65.5% were unaware of the existence of research centers at their treatment sites. Only 13.1% had ever been invited to participate in a clinical trial. The main motivation to participate was contributing to science (38.8%), followed by contributing to the hospital and care team (25.1%). Physicians’ opinions were reported to play a central role in decision-making by 76.2% of participants, and 74.5% reported that refusing participation would not compromise the quality of care. Regarding perceptions of clinical research, 79.1% agreed that clinical trials benefit patients and society, 67.2% reported willingness to participate if invited, and 61.6% would encourage relatives or friends to participate. Regarding concerns to participation, 18% reported fear of being treated as a “guinea pig,” whereas 39.4% reported no fear of participating. Conclusions: Brazilian BC patients demonstrate strong altruistic and pro-science attitudes, with high willingness to participate in and encourage clinical trial enrollment. Although overall awareness levels were relatively high, access to clinical trials remains substantially lower than that reported in high-income settings. Moreover, the study population was skewed toward higher socioeconomic status, despite balanced representation of physicians from private and public institutions, likely overestimating levels of research awareness. Persistently low invitation rates likely reflect not only limited physician engagement, but also restricted trial availability and insufficient awareness of ongoing studies among care teams, highlighting key opportunities to expand equitable access and strengthen patient confidence in clinical research.

Real-world outcome of low-frequency outpatient monitoring for venetoclax initiation in CLL: Single-center experience.

e19026 Background: Venetoclax (Ven) is a potential treatment for CLL/SLL. However, tumor lysis syndrome (TLS) concerns and the need for inpatient monitoring have limited its use in the community setting. This is noteworthy as a great proportion of CLL patients are treated in the community. We implemented a novel, low-frequency-monitoring protocol for outpatient Ven initiation in our CLL population and report our experience. Methods: Between 2023 and 2026, we implemented an outpatient Ven initiation ramp up. All patients were initiated on cytoreductive therapy before Ven and continued for 2 weeks post Ven initiation. Ven was initiated when the following criteria were met: 1) absolute lymphocyte count <20,000 K/mL, 2) adenopathy <5 cm by exam, 3) resolution of splenomegaly if present, per exam and 4) CrCl >45mL/min. Once meeting criteria, Ven dosing followed the standard five-week(W) dose escalation protocol. Prophylactic allopurinol was initiated one day prior to W1 during the escalation period. Patients self-administered the initial Ven dose on W1D1 no earlier than 8:00 PM. The following morning (W1D2), patients presented for outpatient evaluation 12 hours after dose administration. Laboratory monitoring included CBC, BMP, calcium, uric acid, and phosphorus levels. If laboratory parameters were without TLS, defined as uric acid >8 mg/dL, potassium >6 mmol/L, phosphorus>4.5 mg/dL, or calcium <7 mg/dL- dose escalation proceeded on W2D1 with repeat laboratory evaluation on W2D2. This monitoring and dose escalation process was repeated weekly through five weeks. The primary endpoint of this study was to assess the safety and tolerability of Ven dose escalation in the outpatient setting. Results: Thirty patients were transitioned to Ven. The median age was 71 years. 30% were IgVH mutated; 60% were unmutated. Cytogenetics classified 53% as low risk and 44% as high-risk. 80% were heavily pre-treated with ≥ 2 prior lines of therapy. 80% received single-agent BTKi as cytoreductive therapy. There was 100% compliance with treatment appointments. No laboratories suggestive of TLS, hospitalizations, treatment/dose escalation interruptions, nor deaths. occurred. 68% of patients had MRD testing within 3 to 11 months after initiation with 24% of patients achieving uMRD. Conclusions: Real world data shows community-based practitioners are more likely to endorse continuous BTKi as compared to fixed-duration Ven. Importantly, depth of response is greater with ven-based therapy as compared to BTKi-based therapy. Our approach demonstrates real-world evidence regarding the ease and safety of initiating single agent Ven in the outpatient setting across a heterogeneous population. Ven-based therapy should be considered a safe, easy to initiate viable option. Additional reporting of similar experiences is encouraged.

Routine targeted NGS testing to guide treatment decisions in all-stage NSCLC: Public hospital implementation.

e20752 Background: Next-generation sequencing (NGS) is central to the diagnostic work-up in NSCLC by enabling identification of actionable genomic alterations. We report the first pilot experience of NGS testing in routine practice in a state-funded public hospital in Russia. Methods: We retrospectively analyzed consecutive patients with NSCLC treated at Moscow City Oncology Hospital No. 62 who underwent NGS testing prior to multidisciplinary tumor board discussion between August 2024 and December 2025. Demographic, clinical characteristics and NGS results were collected. Categorical variables were compared using χ² or Fisher’s exact test. Results: The cohort included 466 patients (median age 69 years; 56% male; 60% smokers; 89% adenocarcinoma). Median turnaround time was 11 days (IQR 7–14). NGS results were practice-changing in 25% of cases. The most frequent alterations were EGFR 21.9% (L858R = 46 [40%], Ex19del = 34 [29.5%], G719X = 9 [7.8%]), KRAS 20.6% (G12C 36 [36%], G12V 24 [24%], G12A 12 [12%]) and BRAF 3.0% (V600E 6 [40%], non-V600E 9 [60%]); fusions included ALK (4.1%), ROS1 (2.4%), RET (1.0%) and NTRK (0.24%). All MET alterations were exon 14 skipping mutations (3.2%). Overall, 61.2% of patients had no actionable driver mutations. EGFR mutations were more frequent in females than males (40% vs 7.3%, p < 0.001) and in non-smokers than smokers (47% vs 5.5%, p < 0.001), whereas KRAS mutations predominated in males (26.7% vs 13.2%, p < 0.001) and smokers (27.6% vs 10.1%, p < 0.001). ROS1 (5.3% vs 0.4%, p = 0.001) and MET (5.3% vs 0.8%, p = 0.008) alterations were significantly enriched in non-smokers. Conclusions: Universal targeted multigene NGS was feasible in a state-funded public hospital, with short turnaround time and clinically meaningful impact on treatment decisions. These data support implementation of NGS testing within publicly funded healthcare systems. . Alteration Frequency% p53% Male/Female Smoking No/Yes (p) Stage I–III/IV (p) EGFR 102(21.9) 45.1 19(7.3)/ 81(40) (p<0.001) 79(47.9)/ 14(5.4) (p<0.001) 61(24.5)/ 41(19.0) (p=0.167) KRAS 96(20.6) 45.4 70(26.7)/ 27(13.2) (p<0.001) 17(10.1)/ 71(27.6) (p<0.001) 45(18.1)/ 52(24.1) (p=0.101) ALK 19(4.1) 15.8 9(3.4)/ 10(4.9) (p=0.594) 12(7.1)/ 6(2.3) (p=0.017) 13(5.2)/ 6(2.8) (p=0.191) ERBB2 15(3.6) 46.7 4(1.5)/ 11(5.4) (p=0.020) 11(6.5)/ 3(1.2) (p=0.002) 7(2.8)/ 8(3.7) (p=0.574) PIK3CA 15(3.6) 66.7 7(2.7)/ 8(3.9) (p=0.462) 7(4.1)/ 8(3.1) (p=0.765) 10(4.0)/ 5(2.3) (p=0.309) BRAF 14(3.0) 53.3 11(4.2)/ 4(2.0) (p=0.168) 2(1.2)/ 12(4.7) (p=0.049) 6(2.4)/ 9(4.2) (p=0.277) MET 14(3.0) 28.6 5(1.9)/ 9(4.4) (p=0.119) 9(5.3)/ 2(0.8) (p=0.008) 9(3.6)/ 5(2.3) (p=0.428) ROS1 11(2.4) 45.5 3(1.1)/ 8(3.9) (p=0.067) 9(5.3)/ 1(0.4) (p=0.001) 6(2.4)/ 5(2.3) (p=0.959)

National burden and outcomes of CAR-T therapy toxicities in DLBCL, multiple myeloma, and B-ALL: A retrospective analysis of the Nationwide Inpatient Sample.

e19108 Background: Chimeric antigen receptor (CAR) T-cell therapy achieves durable responses in diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and B-cell acute lymphoblastic leukemia (B-ALL). However, toxicities including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) complicate care and strain resources. Population-based estimates of toxicity rates across indications remain limited. We performed a national retrospective analysis to compare toxicity incidence and burden, aiming to inform risk stratification and resource planning. Methods: Using the Nationwide Inpatient Sample (NIS) 2020–2022, we identified adult hospitalizations receiving CAR-T for DLBCL, MM, or B-ALL (ICD-10 codes). We collected sociogeographic data, inpatient outcomes (mortality, length of stay [LOS], total charges), and complications including CRS, ICANS, sepsis, acute renal failure (ARF), and others. Analyses used Stata 18.5 with survey weighting. Multivariable logistic regression evaluated associations between indication and outcomes. p<0.05 was significant. Results: Among 10,650 CAR-T recipients, DLBCL (46.5%) and MM (19.6%) cohorts were older (mean age 62.7 and 63.6 years), whereas B-ALL (10.9%) patients were younger (mean 26 years). Median LOS was longest in B-ALL (19.2 days), followed by DLBCL (16.9) and MM (13.5; p<0.0001). Mean hospital charges were highest in DLBCL ($1,346,614), exceeding MM ($973,800) and B-ALL ($973,134; p<0.0001). Inpatient mortality was similar: MM 3.8%, B-ALL 3.0%, DLBCL 2.8% (p=0.61). CRS occurred in 47.1% overall, highest in MM (53.96%), then DLBCL (46.91%) and B-ALL (35.62%; p<0.001). On multivariable analysis, MM had higher odds of CRS vs. DLBCL (OR 1.33; 95%CI 1.05–1.67; p=0.016), while B-ALL had lower odds (OR 0.63; 95%CI 0.47–0.84; p=0.002). ICANS occurred in 14.7% overall, most in DLBCL (16.41%), then B-ALL (13.73%), and least in MM (11.03%; p=0.03). MM had lower odds vs. DLBCL (OR 0.63; 95%CI 0.45–0.90; p=0.01). Any complication was common across groups (MM 67.4%, DLBCL 66.0%, B-ALL 56.2%; p=0.01); B-ALL had lower adjusted odds vs. DLBCL (OR 0.66; 95%CI 0.50–0.89; p=0.006). ARF was most frequent in MM (21.6% vs. DLBCL 13.9%, B-ALL 9.4%; p<0.0001), with higher odds vs. DLBCL (OR 1.71; 95%CI 1.27–2.29; p=0.000). Rates of sepsis, mechanical ventilation, and vasopressor use did not differ significantly by indication. Conclusions: In this national cohort, CAR-T toxicities are common and confer substantial clinical and economic burden. DLBCL carries the highest costs; MM is associated with increased CRS and ARF but lower ICANS vs. DLBCL; and B-ALL, despite younger age and fewer complications, has the longest hospitalizations. These data support indication-specific toxicity mitigation, risk stratification, and resource planning as CAR-T use expands.

A feasibility study of ApricityCarefor early detection and management of immune-related adverse events in cancer patients receiving immune checkpoint therapies.

e13711 Background: Immune-related adverse events (irAEs) is a leading cause of immune checkpoint therapy (ICT) interruption or discontinuation. Earlier detection of irAEs can improve outcomes and extend ICT continuation. ApricityCare is a HIPAA-compliant AI-powered remote symptom monitoring platform designed to facilitate early irAE detection and standardize management. Hypothesis: ApricityCare in a routine care setting can enable remote patient symptom monitoring and irAE detection. Methods: This prospective, single-center pilot feasibility study was conducted Feb 1, 2019 to Feb 1, 2020. Enrolled patients receiving ICT were instructed to report symptoms and biometric data via ApricityCare over a 12-week period. Pre-specified algorithms based off inputted data generated alerts categorized by suspected irAE type and severity: green (no concerning symptoms), yellow (mild-moderate symptoms), and red (moderate-severe symptoms). The co-primary endpoints were frequency of symptom reporting and educational video access. Feasibility was defined as 80% of patients reporting ≥3 times per week. Secondary endpoints included distribution of generated alerts. Post-hoc exploratory analysis was performed to assess irAE incidence based off documentation and lab results, detection accuracy, and interventions. Results: 44.4% of participants (n = 18) checked in via ApricityCare ≥ 3 times per week, and 38% chose to continue ApricityCare after the trial. Of the 705 total alerts recorded, 72% were green, 24% yellow, and 5% red. Ten confirmed or suspected irAEs were documented, of which 6 were detected via ApricityCare: dermatitis Grade (G) 1, dermatitis G2, thyroiditis G2, myositis G2, arthralgia G2, and colitis G1. All received or initiated treatment within 48 hours of alert with no delays in ICT. The 4 irAEs not detected included hepatitis G2, 2 cases of thyroiditis G2, and pneumonitis G3 which required ICT discontinuation. Rate of irAE incidence was 50% (4/8) for patients who frequently checked in and 30% (3/10) for those who did not. Out of 8 patients who prematurely stopped check-ins prior trial completion, one experienced a subsequent irAE. Conclusions: While frequency of remote symptom reporting via ApricityCare did not meet its co-primary endpoint, a subset of patients showed high engagement and majority of irAEs were captured. Lessons learned included: (1) patient adherence and accurate data input are critical; (2) rigid check-in schedules limit patient uptake, especially when asymptomatic; (3) proactive monitoring creates primarily non-urgent alerts that increase clinic workload. Building on these, ApricityCare was revised with flexible check-ins and first-response triage by remote nurses. A prospective clinical trial is underway to evaluate the updated ApricityCare program in routine care and clinical trial populations (NCT06693687).

Addressing barriers to FRα-directed therapy integration in platinum-resistant ovarian cancer: A multi-phase, community-informed initiative.

5601 Background: Antibody–drug conjugates (ADCs) targeting folate receptor alpha (FRα) represent an important therapeutic advancement in ovarian cancer, introducing a new standard of care (SOC) for patients with FRα–positive platinum-resistant ovarian cancer (PROC). Despite this progress, real-world integration of FRα biomarker testing and FRα-directed therapies into clinical practice remains variable, particularly in community settings where most patients receive care. This multi-phase initiative was designed to assess real-world practice patterns and barriers related to FRα-directed care and to evaluate outcomes from an educational intervention addressing these gaps. Methods: Phase 1 formative research included a national claims data analysis, a community-based practice pattern analysis survey (n=100), and a clinician case crowdsourcing survey (n=100) examining biomarker testing practices, treatment sequencing, and perceived challenges in PROC care. Findings from Phase 1 informed development of a 60-minute, on-demand CME activity (Phase 2) targeting oncologists, gynecologic oncologists and pathologists, and APPs. Educational outcomes were assessed using pre-/post-activity knowledge and confidence measures, polling, and post-activity evaluations. Interim Phase 2 outcomes are reported. Results: Phase 1 analyses demonstrated variable use of FRα biomarker testing across the patient journey, with testing more frequently performed at initial diagnosis. Clinicians cited barriers including testing access and turnaround time, tissue adequacy, uncertainty around eligibility thresholds for FRα-directed therapy, and challenges in sequencing FRα-directed agents relative to other targeted options. Claims data showed continued predominance of cytotoxic regimens at first PROC progression. As of 2.5 months post-launch, over 5,100 clinicians have engaged with the education. Pre- to post-activity assessments demonstrated the largest gains in knowledge related to limitations of the current SOC in PROC and in understanding the role of FRα biomarker testing in informing treatment decisions. Confidence in appropriately incorporating FRα-directed therapies into treatment plans remained low at post-test. Intended practice changes included increased use of comprehensive biomarker testing (36%), reassessment of the role of PFI in treatment selection (41%), and routine FRα testing at recurrence (37%). Conclusions: This multi-phase initiative identified persistent gaps in FRα biomarker testing and therapeutic integration in PROC and demonstrated early educational gains in knowledge, with ongoing needs related to clinical application and confidence. These findings highlight the value of outcomes-driven education in addressing real-world barriers and supporting informed integration of FRα-directed therapies into PROC care.

Real-world PSA kinetics and depth of response with ARPI-based triplet therapy in metastatic hormone-sensitive prostate cancer: A single-center retrospective cohort analysis.

e17089 Background: Triplet therapy combining an androgen receptor pathway inhibitor (ARPI) with androgen deprivation therapy (ADT) and docetaxel has demonstrated survival benefits in phase III trials (ARASENS, PEACE-1) for metastatic hormone-sensitive prostate cancer (mHSPC). However, real-world evidence on the pace and depth of prostate-specific antigen (PSA) response remains sparse, especially in clinical practice settings outside trials. This study aimed to describe PSA kinetics and response rates in patients receiving darolutamide- or abiraterone-based triplet therapy in routine care. Methods: In this retrospective single-center cohort study, patients with mHSPC who initiated darolutamide- or abiraterone-based triplet therapy and had serial PSA measurements were included. PSA50 (≥50% decline), PSA90 (≥90% decline), and PSA < 0.2 ng/mL were evaluated. Time-to-event endpoints were estimated using Kaplan–Meier analysis. Subgroup analyses were performed by ARPI type. Results: Among 36 eligible patients (darolutamide: n = 26; abiraterone: n = 10), median age was 67 years, all had Gleason score ≥8, and baseline median PSA was 423.4 ng/mL. Metastatic burden was high: 100% bone, 80.6% lymph node, and 38.9% visceral involvement. With a median follow-up of 7.5 months, 94.4% achieved both PSA50 and PSA90, and 58.3% attained PSA < 0.2 ng/mL. Median time to PSA50 was 0.8 months (95%CI 0.6–1.0), to PSA90 was 1.1 months (95%CI 0.8–1.4), and to PSA < 0.2 ng/mL was 6.0 months (95%CI 4.0–8.0). In ARPI-specific analyses, darolutamide-treated patients (n = 26) all achieved PSA50/90, with 61.5% reaching PSA < 0.2 ng/mL at a median of 6.0 months (95%CI 4.1-7.9). In the abiraterone group (n = 10), 80% achieved PSA50/90 and 50% reached PSA < 0.2 ng/mL. Conclusions: In this real-world cohort of mHSPC patients with high-volume disease, ARPI-based triplet therapy induced rapid and deep PSA responses, consistent with clinical trial data. PSA kinetics appeared to differ between ARPI subtypes, with darolutamide associated with numerically faster and higher rates of deep PSA decline. These findings underscore the clinical activity of triplet regimens in practice and highlight PSA monitoring as a potential early indicator of treatment response. These findings are descriptive and limited by the retrospective design and small sample size.

TBCRC 050: A phase 1b/2 trial of niraparib and trastuzumab in HER2-positive metastatic breast cancer (MBC): Efficacy and correlative analyses.

1056 Background: Resistance to HER2-directed therapies remains a major challenge in HER2-positiveMBC. In preclinical models, HER2+ tumors overexpress poly (ADP-ribose) polymerase (PARP), and PARP inhibition induces apoptosis through NF-κB suppression even in the absence of pathogenic mutations in BRCA 1/2 . We evaluated the safety, efficacy, and translational correlates of niraparib combined with trastuzumab in patients (pts) with refractory HER2+ MBC. Methods: This open-label Phase 1b/2 trial (NCT03368729) enrolled pts with HER2+ MBC (IHC 3+ and/or FISH amplified), measurable disease, LVEF ≥50%, and progression on ≥1 prior HER2-targeted therapy; stable CNS disease was allowed. Pts with germline BRCA1/2 mutations or prior PARP inhibitor exposure were excluded. Niraparib 300 mg orally was administered on Days 1–21 of a 21-day cycle with trastuzumab 6 mg/kg IV every 3 weeks (loading dose 8 mg/kg on cycle 1). The Phase 2 portion used a Gehan/Simon two-stage design with early stopping for futility (P0=24%); ≥1 response among the first 20 patients triggered expansion to 40 patients. ORR was assessed by RECIST v1.1, meeting the primary endpoint and allowing response rate estimation with <7% standard error and a two-sided 95% exact CI width of 0.28. Gene expression profiling of paired tumor tissue and peripheral blood mononuclear cells (PBMCs) was performed using the NanoString nCounter Tumor Signaling 360 panel at pretreatment compared to cycle 2. Results: Forty-six pts were enrolled (9/2019–2/2025); 41 were evaluable for response. Pts were heavily pretreated (median 3 prior regimens), including trastuzumab deruxtecan in 22 pts; 33% had brain metastases. Treatment-related adverse events were predominantly grade 1–2 and manageable. Clinical benefit rate (CBR) was 44% (18/41) including 1 complete response, 2 partial responses, and 15 stable disease. Eleven patients achieved disease control ≥ 6 months; 1 patient remained on treatment at data cutoff. Tumor profiling revealed enrichment of a B-cell–driven tertiary lymphoid structure signature with reduced hypoxia signaling in responders. Matched PBMC analyses demonstrated coordinated downregulation of interferon signaling, DNA damage response, metabolic activation, angiogenesis, and resistance pathways in clinical responders, whereas non-responders retained signatures of chronic stress and immune exhaustion. Conclusions: Niraparib plus trastuzumab demonstrated a favorable safety profile and durable clinical benefit in heavily pretreated HER2+ MBC. Integrated tumor and blood-based analyses identify immune-organized tumor microenvironments and systemic immune normalization as key correlates of prolonged response, supporting further investigation of PARP inhibition strategies. Clinical trial information: NCT03368729 .

An actionable machine learning–driven clinicogenomic model as a predictor of brain metastasis risk in breast cancer.

106 Background: Brain metastasis (BM) is a frequent site of disease progression for patients living with metastatic breast cancer (MBC). Guidelines do not recommend routine MRI brain surveillance in asymptomatic patients. Consequently, patients with MBC who develop BM often present with extensive disease, leading to lasting neurological damage or death. Methods: This study included MBC patients without known BM at presentation who underwent genomic sequencing of a non-BM specimen with MSK-IMPACT, a custom tumor-normal next-generation sequencing assay, within one year of M1 diagnosis. We developed an ensemble time-dependent LASSO machine learning (ML) model with BM-free survival (BMFS) as the primary endpoint, integrating baseline clinical, pathologic, and genomic features for risk stratification, using a cross-validation framework. Benchmarking was conducted using a time-dependent neural network designed to model competing risks (DeepHit), and further validation was performed using an independent clinical trial dataset. Results: 1594 MBC patients were divided into a training set (n=1118) and a test set (n=476), with 320 events over a median follow-up of 39.7 months. The ensemble ML model identified distinct clinicogenomic features associated with shorter BMFS, including receptor subtype, ER/PR percent positivity, menopausal status, metastatic burden, metastatic site distribution, disease-free interval, and alterations in TP53 , ERBB2 , and RB1 . The model stratified patients into low-, intermediate-, and high-risk groups (training C-index: 0.690; test C-index: 0.696). In the test cohort, 24-month BMFS was 68%, 89%, and 98% in high, intermediate, and low risk groups (HR 19.2, p<0.001 high vs. low risk; HR 6.5, p<0.001 intermediate vs. low risk), with model predictions retaining robust predictive ability beyond 24 months (time-dependent AUC at 10 years of 0.79). These results were confirmed using DeepHit, a competing-risk-specific neural network (training C-index 0.71; test C-index 0.61). The model similarly identified high-risk patients within a single-arm phase II clinical trial dataset utilizing MRI screening in patients with MBC. Conclusions: We developed an actionable ML-driven clinicogenomic model that accurately identifies MBC patients at high risk of developing BM. Biologically plausible and readily available features defined a high-risk patient category with a >30% risk of developing BM within 2 years and would likely benefit from MRI screening. The results will be prospectively validated in BRAINSTORM (Breast Cancer Radiologic Assessment and Intervention for Neurological Surveillance, Tracking, and Optimized Risk Management), a phase II randomized clinical trial of intensified MRI surveillance versus standard symptom-based screening in high-risk MBC patients.

Population-level forecasting of CAR-T–related toxicities using meta-analytic data.

e18602 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of hematologic malignancies but is frequently complicated by cytokine release syndrome (CRS) and immune-mediated neurotoxicity (NS). As CAR-T programs expand, population-level projections of treatment-related toxicities are essential for program planning and risk mitigation, yet remain poorly characterized. Methods: We performed a cohort-based forecasting analysis using pooled incidence rates of CRS and NS derived from published meta-analyses of CAR-T clinical trials. Expected numbers of toxicity events were projected for hypothetical cohorts of 100, 500, and 1,000 CAR-T–treated patients. Uncertainty was quantified using binomial 95% confidence intervals. Disease-specific projections were generated by applying stratified pooled toxicity rates for hematologic malignancies and solid tumors. Results: For a projected cohort of 1,000 CAR-T–treated patients, forecasts estimated approximately 770 patients would experience CRS of any grade, 290 would develop grade ≥3 CRS, 400 would experience NS of any grade, and 280 would develop grade ≥3 NS. Toxicity counts increased proportionally with cohort size and demonstrated predictable uncertainty bounds. When stratified by disease type, hematologic malignancies exhibited substantially higher toxicity burdens than solid tumors across all endpoints. At a cohort size of 1,000 patients, hematologic malignancies were associated with markedly higher rates of both CRS and severe neurotoxicity, whereas solid tumors demonstrated consistently lower toxicity burdens. Conclusions: Using pooled clinical trial data, this forecasting model provides quantitative estimates of CAR-T–associated toxicity burdens at the population level. Severe CRS and neurotoxicity remain common and scale predictably with program size, particularly in hematologic malignancies. These findings offer a pragmatic framework for anticipating resource utilization, toxicity management needs, and safety planning as CAR-T therapy continues to expand.

Contemporary trends in early-stage non–small cell lung cancer diagnosis and disparities, 2018–2022.

10550 Background: Early detection of non-small cell lung cancer (NSCLC) improves survival. We evaluated stage trends in adults aged 50-80 with NSCLC in SEER 2018-2022 after the 2021 screening expansion and the COVID-19 pandemic. Methods: We included 112,183 SEER cases aged 50-80 with primary NSCLC from 2018-2022. Histology was classified as adenocarcinoma, squamous, large cell or other/unknown. Stage at diagnosis was categorized as early (0-II) versus late (III-IV). Early-stage proportions were calculated by year, sex, race, age, income quartile, rurality and histology. Trends were tested using the Cochran–Armitage test. Multivariable logistic regression evaluated associations with early-stage diagnosis. To adjust for changing eligibility, NHIS 2018-2022 data were used to estimate screening-eligible shares by age-sex-race strata and standardize stage distributions. Results: Among 112,183 patients (median age 69; 56% male), 39,023 (34.9%) were early stage. Early-stage diagnoses increased modestly from 34.4% in 2018 to 35.6% in 2022, with a dip to 33.8% in 2020 (Table 1). Women had higher early-stage rates (~38%) than men (~32%), and White patients had higher rates (~37%) than Black or American Indian/Alaska Native patients (~29%). Logistic regression showed male sex (OR 0.78) and non-adenocarcinoma histology (ORs 0.16-0.25) were associated with lower odds of early detection; income quartile and rurality were not significant. Eligibility-standardized analyses produced similar trends, suggesting limited impact of the 2021 screening expansion to date. Conclusions: Between 2018 and 2022, early-stage NSCLC detection in SEER improved only slightly. Sex and racial disparities persisted. Enhanced outreach, particularly to men and racial/ethnic minorities, and broader low-dose computed tomography implementation are needed to accelerate stage migration. Early-stage NSCLC diagnoses by year (ages 50–80). Year Total cases Early-stage cases Early-stage proportion* 2018 23,482 8,069 34.36% 2019 24,061 8,427 35.02% 2020 20,633 6,965 33.76% 2021 22,099 7,772 35.17% 2022 21,908 7,790 35.56% *The Cochran–Armitage test indicated a statistically significant upward trend (p < 0.05), but the absolute increase was modest.

Real-world evaluation of CXCL9/10 with PD-L1 and TMB as predictors of pembrolizumab benefit in triple-negative breast cancer (TNBC).

1125 Background: Pembrolizumab is approved for TNBC; however, current biomarkers PD-L1 and tumor mutational burden (TMB) have limited predictive accuracy and show weak correlation with clinical benefit. We evaluated whether chemokines (CXCL9 and CXCL10) that recruit cytotoxic T cells into the tumor microenvironment (TME) may improve prediction of pembrolizumab benefit beyond PD-L1 and TMB. Methods: TNBC tumors (n=3662) were profiled by next-generation sequencing (592 NextSeq; WES/WTS NovaSeq; Caris Life Sciences, Phoenix, AZ). Chemokine expression was classified as high vs low based on 50 th percentile. Immune cells were estimated using WTS deconvolution (Quantiseq). PD-L1 was assessed by immunohistochemistry (22C3 ≥10%), and TMB by nonsynonymous mutations/Mb (high ≥10). Real-world median overall survival (mOS) was derived from insurance claims and calculated from pembrolizumab initiation to last contact. Associations were tested using chi-square and Mann-Whitney U with multiple comparison adjustment ( q<0.05 ). Results: CXCL9/ 10- high expression showed increased fraction of CD8⁺ T, dendritic cells and higher IFN-γ signatures ( CXCL9-high vs low : 1.3% vs 0%, 3.1% vs 2.8%, –0.09 vs –0.47; CXCL10 -high vs low: 1.1% vs 0%, 3.1% vs 2.7%, –0.1 vs –0.46), respectively all q<0.05 . Among patients treated with pembrolizumab (n=750), CXCL9 / 10- high expression was associated with improved mOS ( CXCL9-high : 24.5 months (m) vs 15.8 m; CXCL10-high : 23.4 m vs 17 m; all p<0.05 ) compared to CXCL9/10 -low; PD-L1+ tumors had improved mOS (24.3 m vs 18.6 m, p=0.007 ) compared with PD-L1-negative; and TMB-low tumors had numerically improved mOS (21.7 m vs 17.5, p=0.08 ) compared with TMB-high. Combining CXCL9 / 10 with PD-L1 or TMB identified subgroups of tumors with PD-L1-negative and TMB-high expression that showed better OS with pembrolizumab (Table). In multivariable cox analysis, adjusting for TMB and PD-L1, CXCL9 [HR 0.67 (95% CI 0.54-0.83)] and CXCL10 [HR 0.79 (95% CI 0.64-0.97)] remained independent predictors of pembrolizumab benefit, all p<0.05 . Conclusions: In this large real-world study, PD-L1 but not TMB predicted pembrolizumab benefit in TNBC. CXCL9 / 10-high define an immune-active TME and are independent predictors of pembrolizumab response. When integrated with PD-L1 and TMB, these chemokines help identify additional patients with TNBC who may derive benefit from pembrolizumab, supporting their inclusion as biomarkers in prospective studies. PD-L1 Chemokine CXCL9 mOS (in months) (95% CI) p CXCL10 mOS (in months) (95% CI) p + High 25.7 (22.1 - 32.1) <0.01 25.7 (22.2 - 34.1) <0.01 – High 26.9 (17.8 - 39.2) 21.7 (17.5 - 28.2) + Low 18.5 (11.9 - NR) 20.7 (13.3 - 30.1) – Low 15.8 (12.2 - 19.2) 16.7 (13.1 - 21.5) TMB Low High 25.0 (22.1 - 30.1) <0.01 23.7 (20.9 - 28.2) <0.01 High High 20.6 (17.5 -37.1) 19.5 (16.3 - NR) Low Low 18.3 (14.1 - 21.3) 18.6 (15.7 - 22.2) High Low 6.6 (3.6 - 13.7) 7.6 (5.1 - 16.2)

Rural and urban disparities in cancer mortality in Texas during the COVID-19 pandemic.

e22504 Background: Populations residing in rural regions (in comparison to urban) often experience higher cancer mortality rates. The COVID-19 pandemic introduced significant disruptions to healthcare systems and mortality patterns. This study investigates the differential impact of the COVID-19 pandemic on cancer mortality trends in Texas, specifically examining shifts in rural-urban disparities stratified by age and sex. Methods: We conducted a retrospective population-based analysis of malignant cancer (C00-C97) deaths in counties of Texas from 2018 to 2023 using CDC WONDER mortality data; stratified by sex, age [middle-aged (45-64 yrs), older adults (65-84 years)], and county’s classification (rural or urban). The study period was divided into pre-COVID (2018-2019) and COVID (2020-2023) eras. Annual estimated populations were ascertained by county, age, and sex-to document mortality rates per 100,000 persons. We computed ratios between rural-to-urban mortality rates for both periods (pre vs during COVID). Statistical significance for the time-periods and geographic differences in mean mortality rate ratios were assessed using generalized linear models, where P<0.05 was deemed significant. Results: Throughout the six-year study period there were a total of 185,949 cancer deaths [55% male, 69.1% older adults] in Texas US. In the pre-COVID era, average annual number of deaths were 29,788, whereas the COVID era experienced on average 41,124 deaths per year. Significant declines in cancer mortality rates were observed across all demographic groups in rural and urban counties during the COVID period compared to the pre-COVID period, with steeper declines observed in rural populations (P<0.001). Furthermore, older males the rural-urban ratio was 1.36 pre-COVID vs 1.07 during COVID (ratio differences, P<0.001). Whereas, for older females the rural-urban ratio was 1.33 pre-COVID vs 0.99 during COVID (ratio differences, P<0.001). Hence the largest narrowing of cancer mortality rural-urban rate ratios from pre-COVID to COVID era was observed among older adults, where the rural-urban ratio is approximately one-to-one. Conclusions: While cancer mortality rates appeared to decrease during the pandemic, the significant narrowing of the rural-urban gap approaching parity in older populations likely reflects the competing risk of COVID-19 mortality, which disproportionately affected rural and older populations, alongside potential under-diagnosis due to screening disruptions. These findings suggest a “masking” of cancer burdens in rural Texas rather than a true improvement in oncologic equity. Future research must account for excess death modeling to understand the true latent burden of cancer in the post-pandemic rural landscape.