Parent Pauline, Pigneur Frédéric, Hilmi Marc, Carnot Aurélien, Garcia Larnicol Marie-Line, Vernerey Dewi, Luciani Alain, Hammel Pascal, Henriques Julie, Neuzillet Cindy, Turpin Anthony
Department of Medical Oncology, Lille University Hospital, Lille, France.
University of Lille, Lille, France.
J Cachexia Sarcopenia Muscle. 2025 Feb;16(1):e13595. doi: 10.1002/jcsm.13595. Epub 2025 Jan 17.
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.
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 cm/m for women and < 43 and < 53 cm/m for men with body max index < 25.0 and ≥ 25.0 kg/m, 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.
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.
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.
晚期胰腺导管腺癌（aPDAC）常伴有显著的肌肉量流失，这导致预后不良。SarcAPACaP是GERCOR-APACaP III期试验的一项辅助研究，评估了适应性体育活动（APA）在接受一线化疗的西方aPDAC患者中的作用。该研究旨在评估：（1）治疗前和治疗期间计算机断层扫描（CT）量化的肌肉量对健康相关生活质量（HRQoL）和总生存期（OS）的潜在影响；（2）APA在减轻肌肉量流失方面的作用。
在APACaP试验中，东部肿瘤协作组（ECOG）体能状态（PS）为0-2的aPDAC患者按1:1随机分组，分别接受包括一线化疗的常规护理或常规护理加为期16周的居家APA项目。在SarcAPACaP研究中，从L3水平的CT扫描切片确定表面肌肉指数（SMI）。分析了两个患者群体：基线时有CT扫描结果的患者（改良[m]意向性治疗[ITT]1-W0）以及在W0和W16时均有CT扫描结果的患者（mITT2 W0-W16）。肌肉量低的定义为SMI低，对于身体质量指数（BMI）<25.0 kg/m的女性，SMI<41 cm/m；对于BMI≥25.0 kg/m的男性，SMI<43 cm/m和<53 cm/m。肌肉量流失定义为W0和W16之间SMI的相对差异（100×[SMI W16 - SMI W0]/SMI W0）。在mITT2 W0-W16中，根据肌肉量流失的严重程度将患者分为三组：无、中度（0%-10%）和重度（≥10%）。评估了肌肉量流失与OS、HRQoL直至明确恶化的时间（TUDD）之间的关联以及APA对肌肉量流失的影响。
2014年10月至2020年5月，前瞻性纳入了313例患者，其中225例属于mITT1 W0，128例属于mITT2 W0-W16，65例被分配到APA组。两组具有相似的基线特征，OS和TUDD相当。W0时低SMI与两组中HRQoL的OS和TUDD均无关。在mITT2 W0-W16患者中，高肌肉量流失（n = 27）独立预测OS（p = 0.012），并显示出对HRQoL的TUDD产生负面影响的趋势。值得注意的是，在我们的研究人群中，APA并未减轻肌肉量流失。
在接受化疗的aPDAC患者中，纵向肌肉量流失是OS和HRQoL的预测因素，而诊断时低SMI不具有预后价值。APA对该人群的肌肉量流失没有影响。
