Prognostic Impact of Sarcopenia and Skeletal Muscle Loss During Neoadjuvant Chemoradiotherapy in Esophageal Cancer

Abstract

Backgrounds: The relationship between sarcopenia, characterized by loss of muscle mass and strength, and survival outcomes of esophageal cancer is controversial. This study aimed to assess the effect of sarcopenia and skeletal muscle loss on overall survival (OS) and recurrence-free survival (RFS) of esophageal cancer patients. Methods: We retrospectively collected the medical records of 248 male patients diagnosed with squamous cell esophageal cancer and who underwent neoadjuvant chemoradiotherapy (NACRT) followed by surgery. We measured the cross-sectional area of the skeletal muscle at the L3 vertebra level using computed tomography images and calculated the skeletal muscle index (SMI). Sarcopenia was defined as SMI <52.4 cm2/m2, and excessive muscle loss was defined as SMI change <−10.0%/50 days during NACRT. Moreover, laboratory test results, such as albumin, prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) before and after NACRT, were collected. Results: In the univariable Cox analysis, pre- (p = 0.689) and post-radiotherapy (RT) sarcopenia (p = 0.669) were not associated with OS. However, excessive muscle loss had a significant association with OS in both the univariable and multivariable analyses (all p = 0.001). Excessive muscle loss was also related to RFS in both the univariable (p = 0.011) and multivariable (p = 0.022) Cox analysis. Patients with excessive muscle loss had significantly lower levels of post-RT albumin (p < 0.001) and PNI (p < 0.001), higher levels of post-RT NLR (p = 0.031) and PLR (p = 0.071), larger decrease in albumin (p < 0.001) and PNI (p < 0.001) after NACRT, and larger increase in NLR (p = 0.051) and PLR (p = 0.088) after NACRT than in those with non-excessive muscle loss. Conclusion: Excessive muscle loss rather than pre- and post-RT sarcopenia was a significant prognostic factor for OS and RFS, and it was also related to nutritional and inflammatory markers.

The Impact of Preoperative Sarcopenia on Survival Prognosis in Patients Receiving Neoadjuvant Therapy for Esophageal Cancer: A Systematic Review and Meta-Analysis

“…This meta-analysis found that sarcopenia following NAT had an adverse impact on long-term survival outcomes of EC patients, which was consistent with other reports ( 9 , 32 , 33 ). However, there was a novel additional suggestion in the study.…”

Cross-sectional analysis of the association between serum uric acid levels and handgrip strength among Chinese adults over 45 years of age

“…Among Chinese individuals aged 50-74, Wu et al (25) reported that a higher UA level was independently related to better HGS. A cross- (29)(30)(31). In this study, however, additional adjustment for hs-CRP did not alter the results showing the association between the serum UA level and HGS; this suggests that inflammation is not the primary mechanism for this association among Chinese adults older than 45.…”

Prognostic significance of nutritional markers in metastatic gastric and esophageal adenocarcinoma

“…A few groups have reported that the loss of skeletal muscle mass and development of sarcopenia during disease course carries prognostic impact on oncologic outcomes, rather than just the presence of sarcopenia at baseline 26,29,30 . Yoon et al recently reported that although the presence of sarcopenia prior to neoadjuvant chemoradiotherapy and surgery was not prognostic, a 10% decrease in SMI during treatment was significantly associated with overall survival 30 .…”

“…A few groups have reported that the loss of skeletal muscle mass and development of sarcopenia during disease course carries prognostic impact on oncologic outcomes, rather than just the presence of sarcopenia at baseline 26,29,30 . Yoon et al recently reported that although the presence of sarcopenia prior to neoadjuvant chemoradiotherapy and surgery was not prognostic, a 10% decrease in SMI during treatment was significantly associated with overall survival 30 . Similarly, in the metastatic setting, Sugiyama et al studied 231 patients with metastatic gastric cancer receiving platinum‐based chemotherapy, and found that though pretreatment sarcopenia was not associated with time to treatment failure or overall survival, muscle loss during treatment was associated with inferior survival outcomes 20 .…”