Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer.

Background: Pancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy.

Methods: The diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values.

Results: Seventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03-1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08-1.35, p = 0.001).

Conclusions: Sarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.