Emmanuel Salinas-Miranda1,2, Dominik Deniffel1,2,3, Xin Dong1, Gerard M Healy1,2, Farzad Khalvati1,2, Grainne M O'Kane4,5, Jennifer Knox4,5, Oliver F Bathe6, Vickie E Baracos7, Steven Gallinger5,8, Masoom A Haider9,10,11. 1. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. 2. Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada. 3. Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 4. Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada. 5. Ontario Institute for Cancer Research, Toronto, ON, Canada. 6. Departments of Surgery and Oncology, University of Calgary, Calgary, AB, Canada. 7. Department of Oncology, University of Alberta, Edmonton, AB, Canada. 8. Hepatobiliary Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON, Canada. 9. Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. mahaider@radfiler.com. 10. Joint Department of Medical Imaging, University Health Network, Sinai Health System and University of Toronto, Toronto, ON, Canada. mahaider@radfiler.com. 11. Ontario Institute for Cancer Research, Toronto, ON, Canada. mahaider@radfiler.com.
Abstract
OBJECTIVES: Skeletal muscle mass is a prognostic factor in pancreatic ductal adenocarcinoma (PDAC). However, it remains unclear whether changes in body composition provide an incremental prognostic value to established risk factors, especially the Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). The aim of this study was to determine the prognostic value of CT-quantified body composition changes in patients with unresectable PDAC starting chemotherapy. METHODS: We retrospectively evaluated 105 patients with unresectable (locally advanced or metastatic) PDAC treated with FOLFIRINOX (n = 64) or gemcitabine-based (n = 41) first-line chemotherapy within a multicenter prospective trial. Changes (Δ) in skeletal muscle index (SMI), subcutaneous (SATI), and visceral adipose tissue index (VATI) between pre-chemotherapy and first follow-up CT were assessed. Cox regression models and covariate-adjusted survival curves were used to identify predictors of overall survival (OS). RESULTS: At multivariable analysis, adjusting for RECISTv1.1-response at first follow-up, ΔSMI was prognostic for OS with a hazard ratio (HR) of 1.2 (95% CI: 1.08-1.33, p = 0.001). No significant association with OS was observed for ΔSATI (HR: 1, 95% CI: 0.97-1.04, p = 0.88) and ΔVATI (HR: 1.01, 95% CI: 0.99-1.04, p = 0.33). At an optimal cutoff of 2.8 cm2/m2 per 30 days, the median survival of patients with high versus low ΔSMI was 143 versus 233 days (p < 0.001). CONCLUSIONS: Patients with a lower rate of skeletal muscle loss at first follow-up demonstrated improved survival for unresectable PDAC, regardless of their RECISTv1.1-category. Assessing ΔSMI at the first follow-up CT may be useful for prognostication, in addition to routine radiological assessment. KEY POINTS: • In patients with unresectable pancreatic ductal adenocarcinoma, change of skeletal muscle index (ΔSMI) in the early phase of chemotherapy is prognostic for overall survival, even after adjusting for Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) assessment at first follow-up. • Changes in adipose tissue compartments at first follow-up demonstrated no significant association with overall survival. • Integrating ΔSMI into routine radiological assessment may improve prognostic stratification and impact treatment decision-making at the first follow-up.
OBJECTIVES: Skeletal muscle mass is a prognostic factor in pancreatic ductal adenocarcinoma (PDAC). However, it remains unclear whether changes in body composition provide an incremental prognostic value to established risk factors, especially the Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). The aim of this study was to determine the prognostic value of CT-quantified body composition changes in patients with unresectable PDAC starting chemotherapy. METHODS: We retrospectively evaluated 105 patients with unresectable (locally advanced or metastatic) PDAC treated with FOLFIRINOX (n = 64) or gemcitabine-based (n = 41) first-line chemotherapy within a multicenter prospective trial. Changes (Δ) in skeletal muscle index (SMI), subcutaneous (SATI), and visceral adipose tissue index (VATI) between pre-chemotherapy and first follow-up CT were assessed. Cox regression models and covariate-adjusted survival curves were used to identify predictors of overall survival (OS). RESULTS: At multivariable analysis, adjusting for RECISTv1.1-response at first follow-up, ΔSMI was prognostic for OS with a hazard ratio (HR) of 1.2 (95% CI: 1.08-1.33, p = 0.001). No significant association with OS was observed for ΔSATI (HR: 1, 95% CI: 0.97-1.04, p = 0.88) and ΔVATI (HR: 1.01, 95% CI: 0.99-1.04, p = 0.33). At an optimal cutoff of 2.8 cm2/m2 per 30 days, the median survival of patients with high versus low ΔSMI was 143 versus 233 days (p < 0.001). CONCLUSIONS: Patients with a lower rate of skeletal muscle loss at first follow-up demonstrated improved survival for unresectable PDAC, regardless of their RECISTv1.1-category. Assessing ΔSMI at the first follow-up CT may be useful for prognostication, in addition to routine radiological assessment. KEY POINTS: • In patients with unresectable pancreatic ductal adenocarcinoma, change of skeletal muscle index (ΔSMI) in the early phase of chemotherapy is prognostic for overall survival, even after adjusting for Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) assessment at first follow-up. • Changes in adipose tissue compartments at first follow-up demonstrated no significant association with overall survival. • Integrating ΔSMI into routine radiological assessment may improve prognostic stratification and impact treatment decision-making at the first follow-up.
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