Impact of Baseline Muscle Mass and Myosteatosis on the Development of Early Toxicity During First-Line Chemotherapy in Patients With Initially Metastatic Pancreatic Cancer

Abstract

ObjectivesAlthough chemotherapy is the only treatment option for metastatic pancreatic cancer (PDAC), patients frequently encounter adverse events during chemotherapy leading deterioration of patients’ quality of life and treatment interruption. We evaluated the role of baseline CT-assessed body composition in predicting early toxicity during first cycle of the first-line chemotherapy in patients with metastatic PDAC.MethodsThis retrospective study included 636 patients with initially metastatic PDAC who underwent first-line chemotherapy from January 2009 to December 2019. Chemotherapy regimen, baseline laboratory data, and body composition parameters acquired from baseline CT were obtained. The skeletal muscle index (SMI) was used to identify patients with a low muscle mass (SMI < 41 cm2/m2 for women, and < 43 cm2/m2 [body mass index < 25 cm/kg2] or < 53 cm2/m2 [body mass index ≥ 25 cm/kg2] for men), and myosteatosis was defined as low-attenuated muscle area divided by skeletal muscle area (LAMA/SMA index) ≥ 20%. Univariate and multivariable binary logistic regression analyses were performed using bootstrapping with 500 interactions to identify predictors of grade 3–4 toxicity and any treatment-modifying toxicity which led to a dose reduction, delayed administration, drug skip or discontinuation.ResultsDuring the first cycle of the first-line chemotherapy, grade 3–4 toxicity and treatment-modifying toxicity occurred in 160 patients (25.2%) and in 247 patients (38.8%), respectively. The presence of both low muscle mass and myosteatosis was significantly associated with the occurrence of both grade 3-4 toxicity (odd ratio [OR], 1.73; 95% confidence interval [CI], 1.14–2.63) and treatment-modifying toxicity (OR, 1.83; 95% CI, 1.26–2.66) whereas low muscle mass alone did not.ConclusionsThe presence of both low muscle mass and myosteatosis assessed on baseline CT may be used to predict early chemotherapy-related toxicity in patients with metastatic PDAC.

Mechanisms Underlying the Rarity of Skeletal Muscle Cancers

“…A higher SKM mass, often measured using the SKM index, is correlated with improved prognosis in patients with cancers of various origins, including biliary tract, brain, breast, esophageal, gastric, liver, small-cell lung, ovarian, pancreatic, urothelial, and pediatric malignant solid cancers [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. For example, a 2010 meta-analysis demonstrated that lower muscle mass was associated with an all-cause mortality hazard ratio of 1.44 in patients with solid cancers [ 60 ], although the effect is likely at least partially due to better resistance to chemotherapy-induced dysfunction supported by increased SKM mass.…”

Mechanisms Underlying the Rarity of Skeletal Muscle Cancers

“…A higher SKM mass, often measured using the SKM index, is correlated with improved prognosis in patients with cancers of various origins, including biliary tract, brain, breast, esophageal, gastric, liver, small-cell lung, ovarian, pancreatic, urothelial, and pediatric malignant solid cancers [26][27][28][29][30][31][32][33]. For example, a 2010 meta-analysis demonstrated that lower muscle mass was associated with an all-cause mortality hazard ratio of 1.44 in patients with solid cancers [34], although the effect is likely at least partially due to better resistance to chemotherapy-induced dysfunction supported by increased SKM mass.…”

Skeletal Muscle Proteome Modifications following Antibiotic-Induced Microbial Disturbances in Cancer Cachexia

“…Cancer cachexia is a multifactorial disorder characterized by the involuntary loss of body weight that results predominantly from loss of skeletal muscle and fat mass. 1 In this situation, skeletal muscle atrophy is recognized as an independent risk factor for the impairment of quality of life 2 and poor survival in cancer patients, 3 because it contributes to reduced chemotherapy treatment tolerance 4 and increased surgical complications. 5 The loss of skeletal muscle mass results, in part, from an imbalance between muscle protein breakdown and synthesis.…”