Impact of muscle mass loss on survival during neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma: A multi-center retrospective study in China (TIMES study).

e16106 Background: The value of excessive muscle loss (EML) during neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) is controversial. The objective of this study is to evaluate the prognostic significance of dynamic and longitudinal EMLin patients with LA-ESCC receiving NCRT and surgery. Methods: This study retrospectively included consecutive LA-ESCC patients with NCRT and surgery at three institutions in China between 2014 and 2023. The skeletal muscle mass was measured using computed tomography (CT) scans on L3 vertebra at three longitudinal time points (pre-NCRT, post-NCRT, and pre-surgery), with stage A and B defined as from pre-NCRT to post-NCRT, and post-NCRT to pre-surgery, respectively. Univariate and multivariate Cox proportional hazards models were used for prognostic analysis, and survival curves were constructed using the Kaplan–Meier method. Statistical significance was defined as P < 0.05. Results: A total of 421 patients were included. With a median follow-up of 39.1 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 60% and 53.9%, respectively. There were 112 (26.6%) and 156 (37.1%) EML events at stage A and B, respectively. After multivariate analysis, EML at stage A (hazard ratio [HR] 1.5, P < 0.05) and B (HR 1.63, P = 0.01) was identified as an independent adverse prognostic factor for OS. For subgroup patients without EML at stage A, increased muscle mass at the subsequent stage B could significantly improve OS (HR 0.48, P < 0.01). Conversely, for patients with EML at stage A, no survival benefit was observed after muscle mass increase at stage B ( P > 0.05). Conclusions: EML occurring at stage A or B was an independent adverse prognostic factor for OS in LA-ESCC patients receiving NCRT and esophagectomy. For patients without EML during NCRT, intensified nutritional support and improved muscle mass after NCRT, during the waiting time for surgery, were associated with prolonged survival. Baseline characteristics of patients. Characteristics Total (n = 421) n (%) Age, years < 65 ≥ 65 265 (62.9)156 (37.1) Gender Male Female 347 (82.4)74 (17.6) BMI Underweight Normal Overweight Obese 34 (8.1)208 (49.4)80 (19.0)99 (23.5) Malnutrition No Yes 175 (41.6)246 (58.4) Nutritional support Normal diet PEN/PPN 184 (43.7)237 (56.3) KPS 90-100 70-80 349 (82.9)72 (17.1) Tumor location Upper 1/3 Middle 1/3 Lower 1/3 48 (11.4)172 (40.9)201 (47.7) Clinical TNM stage II III IV 32 (7.6)298 (70.8)91 (21.6) SMI (pre-NCRT) Normal Low 159 (37.8)262 (62.2) Abbreviations: BMI = body mass index; KPS = Karnofsky performance status; NCRT = neoadjuvant chemoradiotherapy; PPN = partial parenteral nutrition; PEN = partial enteral nutrition; SMI = skeletal muscle index.