Prognosis Based on Early Loss of Muscle and Fat In Patients with Pancreatic Ductal Adenocarcinoma (PDAC) Treated with Chemotherapy +/- Radiotherapy
Abstract
Purpose
Early body composition (BC) loss after chemotherapy associates with poor outcomes in PDAC, but its implications for treatment strategy remain unclear. Radiotherapy (RT) is sometimes considered after 6 months of chemotherapy for patients with unresectable disease. We focused on patients with intermediate to good prognosis to determine whether early changes in BC may aid in guiding therapy.
Methods
Using a 7-month landmark from chemotherapy initiation to mitigate immortal-time bias, we analyzed unresectable PDAC patients who survived beyond the landmark, representing a moderate-to-good-prognosis cohort. Using TotalSegmentator on L3-center axial CT at baseline and ~3months from chemotherapy, we calculated skeletal muscle (SKM), subcutaneous abdominal fat (SAF), visceral abdominal fat, and intermuscular fat and percentage loss from baseline were calculated. Inverse probability of treatment weighting (IPTW) anchored to the chemotherapy-alone group assessed survival with versus without RT. Weighted Kaplan-Meier and weighted-Cox regression characterized BC changes for risk stratification.
Results
Among total 107 patients (chemoradiotherapy n=55), early loss of SKM and SAF after 3-months from chemotherapy occurred in 62.6% and 74.8% of patients and was more pronounced among short-term survivors, with greater declines (SKM: -1.9vs-1.0 cm2/mo., p=0.04; SAF: -8.9vs-5.1, p=0.01; Wilcoxon rank-sum test). IPTW improved baseline balance (maximum absolute SMD: from 0.39 to 0.08). Use of RT was not associated with improved survival (median OS: 7.2 vs 9.8 months for chemotherapy alone vs RT; P=0.46), with no differential benefit across body-composition risk groups. In weighted Cox regression, greater early SKM and SAF loss was associated with worse survival (univariable: SKM HR=2.15, p<0.001; SAF HR=1.77, p<0.01; multivariable: SKM HR=2.07, p<0.01; SAF HR=1.54, p=0.057).
Conclusion
Early post-chemotherapy SKM and SAF loss was common and associated with poorer survival in this moderate-to-good-prognosis PDAC cohort. Ongoing work will investigate corresponding poor prognosis patients to determine the impact on the use of this biomarker to guide treatment.