TY - JOUR
T1 - Skeletal muscle is independently associated with grade 3-4 toxicity in advanced stage pancreatic ductal adenocarcinoma patients receiving chemotherapy
AU - Aberle, Merel R
AU - Coolsen, Mariëlle M E
AU - Wenmaekers, Gilles
AU - Volmer, Leroy
AU - Brecheisen, Ralph
AU - van Dijk, David
AU - Wee, Leonard
AU - Van Dam, Ronald M
AU - de Vos-Geelen, Judith
AU - Rensen, Sander S
AU - Damink, Steven W M Olde
PY - 2025/2
Y1 - 2025/2
N2 - 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 2012-2020 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 (ß=0.292; 95%CI 0.013 - 0.065; p=0.013), SM-Index change (% per 30 days, ß=-0.045; 95%CI -0.079 - -0.011; p=0.011), VAT-Index change (% per 30 days, ß=-0.006; 95%CI -0.012 - 0.000; p=0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80% (ß=-0.315; 95% CI -0.543 - -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.
AB - 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 2012-2020 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 (ß=0.292; 95%CI 0.013 - 0.065; p=0.013), SM-Index change (% per 30 days, ß=-0.045; 95%CI -0.079 - -0.011; p=0.011), VAT-Index change (% per 30 days, ß=-0.006; 95%CI -0.012 - 0.000; p=0.040) between diagnosis and the first follow-up CT scan, and cumulative relative dose intensity >80% (ß=-0.315; 95% CI -0.543 - -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.
KW - Personalized medicine
KW - chemotherapy
KW - pancreatic cancer
KW - systemic therapy
KW - toxicity
U2 - 10.1016/j.clnesp.2024.11.004
DO - 10.1016/j.clnesp.2024.11.004
M3 - Article
SN - 2405-4577
VL - 65
SP - 134
EP - 143
JO - Clinical Nutrition ESPEN
JF - Clinical Nutrition ESPEN
ER -