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Clinical Trial
. 2025 Feb;16(1):e13595.
doi: 10.1002/jcsm.13595. Epub 2025 Jan 17.

Muscle Loss During First-Line Chemotherapy Impairs Survival in Advanced Pancreatic Cancer Despite Adapted Physical Activity

Pauline Parent  1   2 , Frédéric Pigneur  3 , Marc Hilmi  4   5 , Aurélien Carnot  6 , Marie-Line Garcia Larnicol  5 , Dewi Vernerey  7   8 , Alain Luciani  3 , Pascal Hammel  9 , Julie Henriques  7   8 , Cindy Neuzillet  4   5 , Anthony Turpin  1   5   10
Affiliations
Clinical Trial

Muscle Loss During First-Line Chemotherapy Impairs Survival in Advanced Pancreatic Cancer Despite Adapted Physical Activity

Pauline Parent et al. J Cachexia Sarcopenia Muscle. 2025 Feb.

Abstract

Background: Advanced pancreatic ductal adenocarcinoma (aPDAC) is often accompanied by significant muscle mass loss, contributing to poor prognosis. SarcAPACaP, an ancillary study of the GERCOR-APACaP phase III trial, evaluated the role of adapted physical activity (APA) in aPDAC Western patients receiving first-line chemotherapy. The study aimed to assess (1) the potential impact of computed tomography (CT)-quantified muscle mass before and during treatments on health-related quality of life (HRQoL) and overall survival (OS) and (2) the role of APA in mitigating muscle mass loss.

Methods: In the APACaP trial, aPDAC patients with ECOG performance status (PS) 0-2 were randomized 1:1 to usual care including first-line chemotherapy or usual care plus a 16-week home-based APA program. In the SarcAPACaP study, the surface muscular index (SMI) was determined from L3 CT scan slices. Two patient populations were analysed: those with CT scan available at baseline (modified[m] intent-to-treat [ITT]1-W0) and those with CT scans available at both W0 and W16 (mITT2 W0-W16). Low muscle mass was defined by low SMI with SMI < 41 cm2/m2 for women and < 43 and < 53 cm2/m2 for men with body max index < 25.0 and ≥ 25.0 kg/m2, respectively. Muscle loss was defined by the relative difference of SMI between W0 and W16 (100*[SMI W16-SMI W0]/SMI W0). In mITT2 W0-W16, patients were stratified into three groups based on the severity of muscle loss: none, moderate (0%-10%) and high (≥ 10%). Associations between muscle mass loss and OS, time until definitive deterioration (TUDD) of HRQoL and the effect of APA on loss of muscle mass were assessed.

Results: Between October 2014 and May 2020, 313 patients were prospectively enrolled, with 225 in mITT1 W0 and 128 in mITT2 W0-W16, with 65 assigned to the APA arm. Both groups had similar baseline characteristics with comparable OS and TUDD. A low SMI at W0 was not associated with OS and TUDD of HRQoL in either group. Among mITT2 W0-W16 patients, high muscle mass loss (n = 27) independently predicted OS (p = 0.012) and showed a trend toward negatively affecting TUDD of HRQoL. Notably, APA did not mitigate muscle loss in our study population.

Conclusions: Longitudinal muscle mass loss emerged as a predictive factor for both OS and HRQoL in aPDAC patients undergoing chemotherapy, while a low SMI at diagnosis did not provide prognostic value. APA did not impact muscle mass loss in this population.

Keywords: CT scan; adapted physical activity; muscular mass loss; pancreatic cancer; quality of life; sarcopenia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Two lumbar L3 CT scan slices at W0 (A and B) and at W16 (C and D) depict a male patient included in mITT2 population (APA arm), exhibiting a 20.6% decrease in muscle mass between W0 and W16. The patient main characteristics included an ECOG performance status of 0, moderately active GPAC score, a BMI of 24.9 kg/m2, the presences of liver metastasis, with SMI of 48.9 cm2/m2 at W0 and of 37.82 cm2/m2 at W16 SMI, OS of 4.5 months and TUDD of global health status of 0.82 months.
FIGURE 2
FIGURE 2
Flow‐chart of patient selection for the SarcAPACaP ancillary study.
FIGURE 3
FIGURE 3
Overall survival (OS) and time until definitive deterioration of global health status (TUDD) according to the SMI status. OS in the mITT1 W0 (A) and mITT2 W0–W16 (B) populations. TUDD in the mITT1 W0 (C) and mITT2 W0–W16 (D) populations.
FIGURE 4
FIGURE 4
Overall survival according to evolution of muscle mass between W0 and W16 in the mITT2 W0–W16 population (A). Time until definitive deterioration of global health status (B), physical functioning (C) and fatigue (D) according to evolution of muscle mass between W0 and W16 in the mITT2 W0–W16 population.
FIGURE 5
FIGURE 5
Evolution of SMI at W16 in patients with normal SMI at W0 according to treatment arm (A). Evolution of SMI at W16 in patients with low SMI at W0 according to treatment arm (B).
FIGURE 6
FIGURE 6
Forest plot of the impact of APA on OS and HRQoL according to muscle mass evolution between W0 and W16.
See this image and copyright information in PMC

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