Muscle and Adipose Wasting despite Disease Control: Unaddressed Side Effects of Palliative Chemotherapy for Pancreatic Cancer

Abstract

Muscle and adipose wasting during chemotherapy for advanced pancreatic cancer (aPC) are associated with poor outcomes. We aimed to quantify the contributions of chemotherapy regimen and tumour progression to muscle and adipose wasting and evaluate the prognostic value of each tissue loss. Of all patients treated for aPC from 2013–2019 in Alberta, Canada (n = 504), computed-tomography (CT)-defined muscle and adipose tissue index changes (∆SMI, ∆ATI, cm2/m2) were measured for patients with CT images available both prior to and 12 ± 4 weeks after chemotherapy initiation (n = 210). Contributions of regimen and tumour response to tissue change were assessed with multivariable linear regression. Survival impacts were assessed with multivariable Cox’s proportional hazards models. Tissue changes varied widely (∆SMI: −17.8 to +7.3 cm2/m2, ∆ATI: −106.1 to +37.7 cm2/m2) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (−3.2 cm2/m2, p 2/m2, p = 0.001). FOLFIRINOX was associated with greater muscle loss (−1.6 cm2/m2, p = 0.013) and GEM/NAB with greater adipose loss (−11.2 cm2/m2, p = 0.002). The greatest muscle and adipose losses were independently associated with reduced survival (muscle: HR 1.72, p = 0.007; adipose: HR 1.73, p = 0.012; tertile 1 versus tertile 3). Muscle and adipose losses are adverse effects of chemotherapy and may require regimen-specific management strategies.

Keywords

• pancreatic ductal adenocarcinoma
• cancer cachexia
• skeletal muscle
• adipose
• chemotherapy
• wasting