O048
MUSCLE LOSS DURING NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITHIN THE PREOPANC-2 STUDY PREDICTS OVERALL SURVIVAL
N. Hildebrand1,2,3,*, E. N. Dekker4, A. S. Bryce5,6, J. W. Wilmink7,8, S. van Kujk9, J. T. Siveke10,11, J. L. van Dam4, L. Wee12, S. A. Bouwense2,3, U. P. Neumann1,3, C. H. van Eijck4, H. C. van Santvoort13, D. P. van Dijk2,3, M. den Dulk2,3, M. G. Besselink8,14, J. de Vos-Geelen15, D. K. Chang5,6, B. Groot Koerkamp4, S. W. Olde Damink1,2,3 on behalf of Dutch Pancreatic Cancer Group (DPCG) and West of Scotland HPB Unit
1Department of General-, Visceral-, Vascular-, and Transplantation Surgery, University Medicine Essen, Essen, Germany, 2Department of Surgery, Maastricht University, 3Department of Surgery, Maastricht University Medical Center+, Maastricht, 4Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands, 5Wolfson Wohl Cancer Research Centre, School of Cancer Sciences, University of Glasgow, 6West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom, 7Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, 8Cancer Center Amsterdam, Amsterdam, 9Department of Clinical Epidemiology and Medical Technology Assessment (KEMTA), Maastricht University Medical Center+, Maastricht, Netherlands, 10Bridge Institute of Experimental Tumor Therapy (BIT), 11Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), West German Cancer Center, University Medicine Essen, Essen, Germany, 12Department of Radiotherapy (MAASTRO), Maastricht University, Maastricht, 13Department of Surgery, Regional Academic Cancer Center Utrecht, Utrecht, 14Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, 15Department of Internal Medicine, Division of Medical Oncology, GROW-Research Institute for Oncology & Reproduction, Maastricht University Medical Center+, Maastricht, Netherlands
Rationale: Prognosis of pancreatic ductal adenocarcinoma (PDAC) remains poor. The PREOPANC-2 trial found no difference in overall survival (OS) between neoadjuvant FOLFIRINOX (FFX) and gemcitabine-based chemoradiotherapy (CRT) in (borderline) resectable PDAC. Current prognostic tools disregard tumor-host interaction.
Methods: In this post-hoc analysis, we tested associations between body composition (BC) and OS. BC (skeletal muscle index [SMI], adipose tissue) was analyzed at baseline, after four (FU1)/eight cycles (FU2) of FFX, or three cycles of CRT using automated segmentation. Multivariable Cox-regression analysis was performed. Results were externally validated in patients receiving six cycles FFX (N=119).
Results: 330 patients were included (160 FFX, 170 CRT). SMI and fat mass decreased significantly during neoadjuvant therapy. Loss of SMI between baseline and FU1 was more pronounced during FFX than CRT (p≤0.01: males: -9% vs -4%; females: -5% vs -2%). Sex-specific cut-offs for significant muscle loss (cm2/m2 ; SML) were defined: males: -4.1 (FFX), -1.7 (CRT); females: -1.8 (FFX), -0.8 (CRT). SML was associated with shorter OS independent of TNM and biochemical response (aHR 1.86, p<0.01). This was attenuated in the CRT arm. Median OS in the entire cohort differed significantly (19.7 months with SML; 28.3 months without SML). In the external validation cohort, SML was identically associated with OS independent of TNM (aHR 2.72, p=0.03). Confirmatory, patients with SML had significantly shorter median OS, compared to those without SML (15.1 vs. 23.1 months, p=0.02).
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Conclusion: Skeletal muscle loss during neoadjuvant therapy is a strong predictor of OS in (borderline) resectable PDAC. This highlights the need to investigate and integrate muscle-preserving strategies, including nutritional interventions and exercise, into neoadjuvant treatment pathways.
Disclosure of Interest: None declared