Sarcopenia in Esophageal Cancer: Evaluation of the Short-Term and Long-Term Prognostic Utility of Muscle Loss Among Patients with Locally Advanced Esophageal Cancer
Creators: Jogiat, Uzair Muhammad
Publisher: name: University of Alberta Library
Year: 2024

<p>The purpose of this research was to understand the effect of sarcopenia on short-term and long-term clinical outcomes among patients with locally advanced esophageal cancer.   Study 1 was a systematic review and meta-analysis on sarcopenia in resectable esophageal cancer. The primary outcome was overall survival. In total, 21 studies were identified. Sarcopenia was present in 1940 (48.1%) patients and was associated with lower overall survival (hazard ratio (HR): 1.56 95% CI:  1.04 -2.87; p = 0.03, I2 ¬= 71%) and disease-free survival (HR: 1.73, 95% CI: 1.04-2.87; p = 0.005; I2 = 51%). A decrease in skeletal muscle index was associated with lower overall survival (HR: 1.81; 95% CI: 1.20-2.73; P =0.005; I2 =92%). Sarcopenia was associated with increased odds of pulmonary complications (odds ratio (OR): 1.86; 95% CI: 1.29-2.66; P =0.0008; I2 =41%) and increased odds of anastomotic leak (AL) (OR 1.46; 95% CI: 1.11-1.93; P =0.008; I2 =0%). Study 2 was a systematic review and meta-analysis on sarcopenia in unresectable esophageal cancer. The primary outcome was overall survival. In total, five studies met the inclusion criteria with data evaluating the effect of sarcopenia defined by SMI on overall survival. Sarcopenia, as determined by SMI using pre-defined cut-off values, was reported in 517 patients (66%). Meta-analysis demonstrated decreased overall survival in the sarcopenia group compared with the non-sarcopenia group (HR = 1.51; 95% CI 1.21-1.89; P = 0.0003; I2 = 0%).     Study 3 was a retrospective cohort study with the objective of obtaining insight into how changes in sarcopenia influence survival. In total, 141 patients were included. The median disease-free survival (DFS) and overall survival (OS) were 33.2 [95% confidence interval (CI) 19.1-73.7] and 34.5 (95% CI 23.1-57.6) months, respectively. Sarcopenia classified by the staging CT was present in 20 (17.0%) patients. This changed to 45 (38.1%) patients by the post-neoadjuvant scan, and 44 (37.3%) by the surveillance scan. In multivariable analysis, sarcopenia at the post-neoadjuvant scan was significantly associated with OS [hazards ratio (HR) 2.65, 95% CI 1.59-4.40; p &lt; 0.001] and DFS (HR 1.80, 95% CI 1.03-3.13; p = 0.038). The net change in skeletal muscle index was associated with OS (HR 0.93, 95% CI 0.90-0.97; p &lt; 0.001) and DFS (HR 0.94, 95% CI 0.91-0.98; p = 0.001).     Study 4 was a comparative analysis of body composition at the T4 and L3 levels. Of the 120 patients included, eight (8.2%) patients had T4-sarcopenia at the staging CT which increased to 25 (25.8%) at the post-neoadjuvant CT. On multivariable analysis, T4-sarcopenia was associated with worse OS (HR 2.51, 95% CI 1.47-4.29, p = 0.001) and DFS (HR 1.88, 95% CI 1.09-3.24, p = 0.022). The correlation (R-value) between T4 and L3 SMI was greater than 0.6 (0.62-0.81) for all staging intervals. These findings support the use of T4-sarcopenia as a prognostic indicator for OS and DFS.    Study 5 was a prospective cohort study evaluating the impact of nutritional parameters and sarcopenia on adverse clinical outcomes among patients with locally advanced esophageal cancer undergoing tri-modality therapy. Of the 140 patients, sarcopenia was present among 79 (56.43%) patients at the staging scan and 103 (73.57%) patients at the re-staging scan. Sarcopenia was associated with increased odds of AL (OR 2.89, 95% CI 1.19-7.00, p = 0.019). Patients who received a pre-operative feeding tube and were sarcopenic did not have a significant increase in odds of anastomotic leak (AL; OR 2.40 95% CI 0.67-8.53, p = 0.176). Patients who did not receive a pre-operative feeding tube and were sarcopenic did have a significant increase in odds of AL (OR 3.60 95% CI 1.20-10.83, p = 0.023). These findings suggest that sarcopenic patients who receive pre-operative nutritional intervention experience decreased morbidity. Sarcopenia status may improve patient selection for pre-operative nutritional intervention.    These studies have demonstrated that sarcopenia is prevalent among patients with locally advanced esophageal cancer and increases with receipt of neoadjuvant chemoradiation. Patients who experience sarcopenia are at increased risk of post-operative complications such as anastomotic leak and have worse survival. Nutritional parameters, such as the use of pre-operative tube feeding, may attenuate the risk of post-operative morbidity among sarcopenic patients. </p>