Abstract

Abstract Introduction: Sarcopenia, progressive and generalized loss of skeletal muscle mass, is difficult and labor intensive to directly measure as it requires manual segmentations by radiologists from computed tomography (CT) scans. Sarcopenia has been shown to be a prognostic factor in some metastatic cancers. We evaluated the impact of sarcopenia derived via an automated segmentation algorithm on outcomes in the Phase 3 NSCLC clinical trial, CheckMate 227 (NCT02477826) Methods: The sarcopenia score assessment involves automated selection of the L3 vertebra level slice from abdominal or chest, abdomen, and pelvis (CAP) CT scans, followed by automated segmentation of the muscle area from that slice. Sarcopenia scores were derived from previously established definitions of sarcopenia, with values below 41 cm2/m2 for female patients (regardless of BMI) and below 43 cm2/m2 or 53 cm2/m2 for male (based on BMI < 25 kg/m2 or ≥ 25 kg/m2). Among the 967 patients with evaluable scans, sarcopenia at baseline was identified in 68.39% (n=329/481) patients receiving nivolumab (NIVO) with ipilimumab (IPI) and 70.2% (n=341/486) receiving chemotherapy (Chemo). Results: There was a trend of worse overall survival (OS) in patients with baseline sarcopenia across both treatment arms (minimum follow up 49.4 months). In patients with baseline sarcopenia vs ITT, median OS was 16.5 mo vs. 21.8 mo (p= 0.219) within the NIVO + IPI arm and 12.9 mo vs.15.0 mo (p= 0.273) within the Chemo arm respectively. Any increase in muscle mass from baseline to week 12 was associated with better OS for patients treated with NIVO+IPI (n=98) with sarcopenia at baseline compared to those without an increase in muscle mass (median OS 45.3 mo vs.19.5 mo, p= 0.012). This was not seen in those who received Chemo (n=87). Weight and muscle mass were moderately correlated at baseline (r=0.60). Conclusions: We found that in CheckMate 227, baseline sarcopenia is associated with numerically worse OS, regardless of treatment, leading to potential use as a negative prognostic biomarker. Patients with NSCLC receiving immunotherapy might benefit from changes in muscle mass being monitored during treatment. Validation of these findings in other studies and other tumor types is warranted. Citation Format: Wiem Safta, Rafael Santana-Davila, David Paulucci, William J. Geese, Diederik J. Grootendorst. An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7650.

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