Puig, Carlos A.

8077 Background: Small cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis. This study evaluates national trends in surgical management of early-stage SCLC using the National Cancer Database (NCDB), aiming to identify factors associated with improved outcomes and assess the survival benefit of surgical resection. Methods: Patients diagnosed with clinical stage T1–T3 N0 M0 SCLC between 2004 and 2022 were identified from the NCDB. Exclusions included non-SCLC histologies, advanced or missing staging, non-lobectomy surgeries, and incomplete survival data. Propensity score matching (1:1) was used to balance surgical and non-surgical cohorts based on demographic, clinical, and socioeconomic variables. Kaplan-Meier and Cox regression analyses were used to evaluate overall survival, stratified by T stage. Results: Among 17,762 patients with early-stage SCLC, 3,234 (18.2%) underwent lobectomy with mediastinal lymph node dissection. Surgical rates increased from 5% in 2004, 17% in 2013 to 24% in 2021. Surgery was more common in T1 (26.5%) than T2 (11.4%) or T3 (4.6%) disease. After matching, surgery was associated with improved survival across all T stages, with no significant interaction between T stage and surgical benefit (p=0.43). Older age, male sex, and higher comorbidity scores predicted worse outcomes. Among surgical patients, 2.3% received neoadjuvant therapy and 71.6% received adjuvant treatment. Systemic therapy-both neoadjuvant (HR 0.63) and adjuvant (HR 0.69)-was significantly associated with improved survival. Conclusions: Lobectomy remains underutilized in early-stage SCLC but is linked to significantly improved survival. Albeit small patient's number, neoadjuvant systemic therapy further enhanced survival, supporting broader use of surgery and multimodal treatment in appropriately selected patients Univariable results 1 Multivariable results 2 Characteristic No. deaths Person-months HR (95% CI) p-value HR (95% CI) p-value Charlson score <0.001 <0.001 0 761 77727 1.00 (ref) 1.00 (ref) 1 623 60483 1.06 (0.95,1.18) 1.07 (0.96,1.20) 2 or more 350 27025 1.30 (1.15,1.48) 1.30 (1.13,1.48) Clinical T-stage 0.011 0.014 cT1N0M0 1266 124916 1.00 (ref) 1.00 (ref) cT2N0M0 406 33924 1.18 (1.06,1.32) 1.20 (1.06,1.35) cT3N0M0 62 6393 0.96 (0.75,1.24) 1.00 (0.76,1.31) Residual disease <0.001 <0.001 No residual tumor 1626 158838 1.00 (ref) 1.00 (ref) Residual tumor 92 4699 1.91 (1.55,2.36) 1.91 (1.52,2.40) Neoadjuvant systemic treatment 0.253 0.034 No 1629 154116 1.00 (ref) 1.00 (ref) Yes 30 3495 0.81 (0.56,1.16) 0.63 (0.41,0.97) Adjuvant radiation 0.067 <0.001 No 1209 118925 1.00 (ref) 1.00 (ref) Yes 452 40471 1.11 (0.99,1.23) 1.33 (1.18,1.51) Adjuvant systemic treatment <0.001 <0.001 No 563 44045 1.00 (ref) 1.00 (ref) Yes 1096 113566 0.75 (0.68,0.83) 0.69 (0.62,0.78)

334 Background: Sarcopenia, or decreased skeletal muscle mass, has been associated with worse surgical and oncologic outcomes across multiple malignancies. This study investigates the impact of sarcopenia on outcomes after multimodal therapy for esophageal cancer. Methods: Retrospective observational cohort study including adult patients who underwent neoadjuvant therapy followed by esophagectomy for primary esophageal cancer from January 2000 - December 2021. A fully automated abdominal segmentation using deep convolutional neural network was utilized to calculate skeletal muscle index (SMI) from preoperative CT scans performed at our institution. Males with SMI <52.4 cm 2 /m 2 and females with SMI <38.5 cm 2 /m 2 at any point before surgery were classified as sarcopenic. The relationship between sarcopenia and patient demographics, operative details, and complications were explored using chi-square tests. The relationship between sarcopenia and disease-free survival and overall survival were investigated using parsimonious multivariable analysis retaining variables with p-value <0.05 using backward selection method. Results: We identified 200 patients meeting the study criteria with 142 (71%) having sarcopenia at any time prior to surgery. Patients with sarcopenia were significantly older [65.2 (59.6, 71.2) vs 63 (53.6, 67.5), p = .023] and more likely to have had open surgery [129 (90.8%) vs 46 (79.3%), p = .034]. There were no significant differences in sex, history of diabetes, coronary artery disease, renal disease, smoking, cancer type, cancer stage, tumor size, tumor location, or margin status between sarcopenic groups ( p > .05). Sarcopenic patients were significantly more likely to require blood transfusion ≥3 units after esophagectomy [79 (55.6%) vs 8 (13.8%), p < .001] or to experience complications requiring surgical intervention [36 (24.6%) vs 7 (12.1%), p = .048]. Multivariate analysis revealed that sarcopenia was associated with disease-free and overall survival (Table). Conclusions: Sarcopenia is a prognostic factor in patients undergoing multimodal therapy for esophageal cancer. Interventions that aim to prevent decreases in SMI after initiating neoadjuvant therapy should be investigated. Multivariate analysis with sarcopenia predicting outcomes. Disease free survivalHR (95% CI) p-value Overall survivalHR (95% CI) p-value Age 1.04 (1.02, 1.06) < .001 1.04 (1.02, 1.07) < .001 Epicenter Middle Upper 1.88 (1.21, 2.86)3.16 (1.67, 5.98) .001.005< .001 1.96 (1.26, 3.04)4.00 (1.90, 8.44) < .001.003< .001 Stage Stage II Stage III Stage IV 1.88 (0.95, 3.71)2.90 (1.46, 5.75)16.02 (6.12, 41.93) < .001.069.002< .001 1.65 (0.83, 3.25)2.76 (1.37, 5.55)10.14 (4.03, 25.53) < .001.151.005< .001 Cancer type - - 1.76 (1.03, 3.02) .039 Transfusion > 3 pRBC - - 1.54 (0.99, 2.40) .057 BMI prior to cancer diagnosis - - 0.98 (0.94, 1.01 .208 Sarcopenic 1.76 (1.16, 2.67) .007 1.64 (1.04, 2.60) .033