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

SIMPLE SUMMARY: Muscle and fat losses during chemotherapy for advanced pancreatic cancer are highly prevalent and associated with tumour progression during treatment. Whether chemotherapy treatment also drives these losses is unknown. This retrospective study aimed to define the effects of chemotherapy and tumour progression on muscle and fat loss and determine the relevance of these losses to overall survival. In a cohort of 210 patients over a standardised scan interval, we demonstrated that tumour progression was associated with greater loss of each tissue compared to tumour control. Furthermore, fluorouracil-based triplet chemotherapy was associated with more muscle loss, while gemcitabine-based doublet chemotherapy was associated with more fat loss. Independent of tumour response, patients with the most muscle or fat loss by tertiles had 72–73% greater hazard of death compared to those with the smallest losses. Muscle and adipose losses are adverse effects of chemotherapy treatment that require targeted management strategies. 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, cm(2)/m(2)) 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 cm(2)/m(2), ∆ATI: −106.1 to +37.7 cm(2)/m(2)) over 116 (27) days. Tumour progression contributed to both muscle and adipose loss (−3.2 cm(2)/m(2), p < 0.001; −12.4 cm(2)/m(2), p = 0.001). FOLFIRINOX was associated with greater muscle loss (−1.6 cm(2)/m(2), p = 0.013) and GEM/NAB with greater adipose loss (−11.2 cm(2)/m(2), 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.