High Loss of Adipose Tissue During Neoadjuvant Chemotherapy Predicts Poor Prognosis in Patients With Gastric Cancer

Gastric cancer (GC) patients often have nutritional risks or malnutrition, and neoadjuvant chemotherapy (NAC) tends to exacerbate malnutrition. Body composition parameters are associated with the prognosis of GC patients. Little is known about body composition changes during NAC and its role in clinical outcomes.

This was a secondary analysis of a Phase 3, open-label, multicentre, randomized clinical trial (RCT) (NCT01364376), assessing the usefulness, safety and efficacy of S-1 plus oxaliplatin (SOX) vs. fluorouracil, leucovorin and oxaliplatin (FOLFOX) as a perioperative chemotherapy regimen for patients with locally advanced GC. Pre-NAC and post-NAC computer tomography (CT) were collected to evaluate the prognostic role of skeletal muscle, adipose tissue and their dynamic change. Overall survival (OS) and progression-free survival (PFS) rates were calculated using the Kaplan-Meier method.

A total of 583 patients from 12 Chinese hospitals were enrolled. After exclusion, 423 patients who proceeded to surgery were used for further analysis. The median age was 60 (IQR: 54, 66) years, and 133 patients (31.4%) were female. Prior to NAC, 132 (31.2%) patients were diagnosed with sarcopenia. There was no significant difference in overall survival between sarcopenia and non-sarcopenia patients (p = 0.363). During NAC, most patients suffered skeletal muscle (SM) loss (n = 268, 63.4%), subcutaneous adipose tissue (SAT) loss (n = 236, 55.8%) and visceral adipose tissue (VAT) loss (n = 254, 60.0%). Patients with SAT loss > 12.5% had significantly worse PFS (p = 0.005) and OS (p = 0.003) than those without. Patients with VAT loss > 15% had significantly worse PFS (p = 0.003) and OS (p = 0.004) than the stable or gain group. Patients with SMI loss > 4.7% had significantly worse PFS (p = 0.043) and showed a tendency of reduced OS (p = 0.181) than those without. In patients without sarcopenia, the incidence of grade 3/4 neutropenia in the FOLFOX group was higher than that of the SOX group (p = 0.019). In patients with myosteatosis, the incidence of Grade 3/4 thrombocytopenia in the SOX group was higher than that of the FOLFOX group (p < 0.001).

In this RCT study, patients with GC experience significant losses of muscle and adipose tissue during NAC. A high level of adipose tissue or muscle loss during NAC is prognostic of reduced survival in patients with locally advanced GC. Assessing and monitoring body composition can predict prognosis and effectively guide individual nutrition intervention and the prevention of complications.