Skeletal muscle is independently associated with grade 3–4 toxicity in advanced stage pancreatic ductal adenocarcinoma patients receiving chemotherapy

IF 2.9 Q3 NUTRITION & DIETETICS

Clinical nutrition ESPEN Pub Date : 2024-11-21 DOI:10.1016/j.clnesp.2024.11.004

Merel R. Aberle , Mariëlle M.E. Coolsen , Gilles Wenmaekers , Leroy Volmer , Ralph Brecheisen , David van Dijk , Leonard Wee , Ronald M. Van Dam , Judith de Vos-Geelen , Sander S. Rensen , Steven W.M. Olde Damink

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引用次数: 0

Abstract

Background

Patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) are regularly treated with FOLFIRINOX, a chemotherapy regimen based on 5-fluorouracil, irinotecan and oxaliplatin, which is associated with high toxicity. Dosing of FOLFIRINOX is based on body surface area, risking under- or overdosing caused by altered pharmacokinetics due to interindividual differences in body composition. This study aimed to investigate the relationship between body composition and treatment toxicity in advanced stage PDAC patients treated with FOLFIRINOX.

Methods

Data from patients treated at the Maastricht University Medical Centre + between 2012 and 2020 were collected retrospectively (n = 65). Skeletal muscle-, visceral adipose tissue, subcutaneous adipose tissue-, (SM-Index, VAT-Index, SAT-Index resp.) and Skeletal Muscle Radiation Attenuation (SM-RA) were calculated after segmentation of computed tomography (CT) images at the third lumbar level using a validated deep learning method. Lean body mass (LBM) was estimated using SM-Index. Toxicities were scored and grade 3-4 adverse events were considered dose-limiting toxicities (DLTs).

Results

Sixty-seven DLTs were reported during the median follow-up of 51.4 (95%CI 39.2–63.7) weeks. Patients who experienced at least one DLT had significantly higher dose intensity per LBM for all separate cytotoxics of FOLFIRINOX. Independent prognostic factors for the number of DLTs per cycle were: sarcopenia (β = 0.292; 95%CI 0.013 to 0.065; p = 0.013), SM-Index change (% per 30 days, β = −0.045; 95%CI −0.079 to −0.011; p = 0.011), VAT-Index change (% per 30 days, β = −0.006; 95%CI −0.012 to 0.000; p = 0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80 % (β = −0.315; 95 % CI −0.543 to −0.087; p = 0.008).

Conclusion

Sarcopenia and early muscle and fat wasting during FOLFIRINOX treatment were associated with treatment-related toxicity, warranting exploration of body composition guided personalized dosing of chemotherapeutics to limit DLTs.

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在接受化疗的晚期胰腺导管腺癌患者中，骨骼肌与 3-4 级毒性密切相关。

背景：晚期胰腺导管腺癌（PDAC）患者定期接受 FOLFIRINOX 治疗，这是一种基于 5-氟尿嘧啶、伊立替康和奥沙利铂的化疗方案，具有较高毒性。FOLFIRINOX 的剂量是根据体表面积计算的，由于个体间身体成分的差异，药代动力学可能会发生变化，从而导致剂量不足或过量的风险。本研究旨在调查接受 FOLFIRINOX 治疗的晚期 PDAC 患者的身体成分与治疗毒性之间的关系：回顾性收集了 2012-2020 年间在马斯特里赫特大学医学中心+接受治疗的患者数据（n=65）。使用经过验证的深度学习方法对第三腰椎水平的计算机断层扫描（CT）图像进行分割后，计算骨骼肌、内脏脂肪组织、皮下脂肪组织（SM-Index、VAT-Index、SAT-Index）和骨骼肌辐射衰减（SM-RA）。使用SM-Index估算瘦体重（LBM）。对毒性进行评分，3-4级不良事件被视为剂量限制性毒性（DLT）：中位随访 51.4 周（95%CI 39.2 - 63.7 周），共报告 67 例 DLT。至少出现过一次DLT的患者，其FOLFIRINOX所有独立细胞毒性药物的单位LBM剂量强度明显更高。每个周期 DLT 数量的独立预后因素包括：肌无力（β=0.292；95%CI 0.013 - 0.065；p=0.013）、SM-Index 变化（每 30 天的百分比，β=-0.045；95%CI -0.079 - 0.011；p=0.011), VAT-Index change (% per 30 days, β=-0.006; 95%CI -0.012 - 0.000; p=0.040) between diagnosis and the first follow follow-up CT scan, and cumulative relative dose intensity >80% (β=-0.315; 95%CI -0.543 -0.087; p=0.008).结论：结论：FOLFIRINOX治疗期间的肌少症和早期肌肉与脂肪消瘦与治疗相关毒性有关，因此有必要探索以身体成分为指导的个性化化疗剂量，以限制DLT。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical nutrition ESPEN NUTRITION & DIETETICS-

CiteScore

4.90

自引率

3.30%

发文量

512

期刊介绍： Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.