Skeletal muscle mass correlates with increased toxicity during neoadjuvant radiochemotherapy in locally advanced esophageal cancer: A SAKK 75/08 substudy

Abstract

Background Sarcopenia, the critical depletion of skeletal muscle mass, is an independent prognostic factor in several tumor entities for treatment-related toxicity and survival. In esophageal cancer, there have been conflicting results regarding the value of sarcopenia as prognostic factor, which may be attributed to the heterogeneous patient populations and the retrospective nature of previous studies. The aim of our study was therefore to determine the impact of sarcopenia on prospectively collected specific outcomes in a subgroup of patients treated within the phase III study SAKK 75/08 with trimodality therapy (induction chemotherapy, radiochemotherapy and surgery) for locally advanced esophageal cancer. Methods Sarcopenia was assessed by skeletal muscle index at the 3rd lumbar vertebra (L3) in cross-sectional computed tomography scans before induction chemotherapy, before radiochemotherapy and after neoadjuvant therapy in a subgroup of 61 patients from four centers in Switzerland. Sarcopenia was determined by previously established cut-off values (Martin et al., PMID: 23530101) and correlated with prospectively collected outcomes including treatment-related toxicity, postoperative morbidity, treatment feasibility and survival. Results Using the published cut-off values, the prevalence of sarcopenia increased from 29.5% before treatment to 63.9% during neoadjuvant therapy (p < 0.001). Feasibility of neoadjuvant therapy and surgery was not different in initially sarcopenic and non-sarcopenic patients. We observed in sarcopenic patients significantly increased grade ≥ 3 toxicities during chemoradiation (83.3% vs 52.4%, p = 0.04) and a non-significant trend towards increased postoperative complications (66.7% vs 42.9%, p = 0.16). No difference in survival according to sarcopenia could be observed in this small study population. Conclusions Trimodality therapy in locally advanced esophageal cancer is feasible in selected patients with sarcopenia. Neoadjuvant chemoradiation increased the percentage of sarcopenia. Sarcopenic patients are at higher risk for increased toxicity during neoadjuvant radiochemotherapy and showed a non-significant trend to more postoperative morbidity.

The Predictive Value of Low Skeletal Muscle Mass Assessed on Cross-Sectional Imaging for Anti-Cancer Drug Toxicity: A Systematic Review and Meta-Analysis

“…The results of the QUIPS assessment of all included studies are summarized in Figure 2. Out of the 31 included studies, seven studies had a low risk of bias [6,16,19,24,25,34,38], 16 studies had a moderate risk of bias [5,7,8,[21][22][23]26,[28][29][30][31][32]35,37,43,44], and eight had a high risk of bias [20,27,33,36,[39][40][41][42]. The domains study participation, study confounding, and statistical analysis and reporting were most frequently assessed as having a high risk of bias.…”

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

“…However, skeletal muscle mass and strength may furtherly be reduced during NAT (9), because of chemotherapy-related toxicities (10), disease progression (11) and adverse postoperative complications (12). Until now, whether sarcopenia would influence the survival rate of EC patients remains controversial (13,14). Therefore, we aim to assess the effects of sarcopenia on the prognosis of EC patients undergoing NAT in this meta-analysis.…”

The prevalence and the impact of sarcopenia in digestive cancers. A systematic review

“…[18] Also, in stage III TNM esophageal cancer treated with neoadjuvant chemoradiotherapy followed by esophagectomy, the presence of sarcopenia was not associated with negative short-and longterm outcome. [13,50] Conversely, one study showed that patients with gastric cancer who had preoperative sarcopenia and were converted to non-sarcopenic status did not present major postoperative complications. [51] Also, the phenotype of sarcopenia may play a role.…”