Prognostic value of initial and longitudinal changes in body composition in metastatic pancreatic cancer

Abstract

Background: Sarcopenia or visceral adipose tissue has been reported to be related to pancreatic cancer prognosis. However, clinical relevance of the comprehensive analysis of body compositions and their longitudinal changes is lacking. This study analysed the association between body composition changes after chemotherapy and survival in patients with metastatic pancreatic cancer.

Methods: We retrospectively included 456 patients (mean age ± standard deviation, 61.2 ± 10.0 years; 272 males and 184 females) with metastatic pancreatic cancer who received palliative chemotherapy from May 2011 to December 2019. Using deep learning-based, fully automated segmentation of contrast-enhanced computed tomography (CT) at the time of diagnosis, cross-sectional areas of muscle, subcutaneous adipose tissue and visceral adipose tissue were extracted from a single axial image of the portal venous phase at L3 level. Skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI) and mean skeletal muscle attenuation (MA) were calculated, and their effect on overall survival (OS) was analysed. Longitudinal changes in body composition and prognostic values were also analysed in a subgroup of patients with 2- and 6-month follow-up CT (n = 349).

Results: A total of 452 deaths occurred during follow-up in the entire cohort. The survival rate was 49.3% (95% confidence interval [CI], 44.9-54.2) at 1 year and 3.7% (95% CI, 2.0-6.8) at 5 years. In multivariable analysis, higher MA (≥44.4 HU in males and ≥34.8 HU in females) at initial CT was significantly associated with better OS in both males and females (adjusted hazard ratio [HR], 0.706; 95% CI, 0.538-0.925; P = 0.012 for males, and HR, 0.656; 95% CI, 0.475-0.906; P = 0.010 for females), whereas higher SATI (≥42.8 cm²/m² in males and ≥65.8 cm²/m² in females) was significantly associated with better OS in female patients only (adjusted HR, 0.568; 95% CI, 0.388-0.830; P = 0.003). In longitudinal analysis, SMI, VATI and SATI significantly decreased between initial and 2-month follow-up CT, whereas mean MA significantly decreased between 2- and 6-month follow-up CT. In multivariable Cox regression analysis of longitudinal changes, which was stratified by disease control state, SATI change was significantly associated with OS in male patients (adjusted HR, 0.513; 95% CI, 0.354-0.745; P < 0.001), while other body composition parameters were not.

Conclusions: In patients with metastatic pancreatic cancer, body composition mostly changed during the first 2 months after starting chemotherapy, and the prognostic factors associated with OS differed between males and females. Initial and longitudinal changes of body composition are associated with OS of metastatic pancreatic cancer.

Keywords: body composition analysis; deep learning; pancreatic cancer; survival.

Figure 1

Study population. CT, computed tomography; EUS‐FNA, endoscopic ultrasound‐guided fine needle aspiration; PDAC, pancreatic ductal adenocarcinoma. *Inappropriate CT scan: Difficult to calculate visceral adipose tissue index and subcutaneous adipose tissue index due to ascites and subcutaneous oedema.

Figure 2

Longitudinal changes of body composition parameters. Longitudinal changes of (A) skeletal muscle index (SMI; cm²/m²), (B) muscle attenuation (MA; HU), (C) visceral adipose tissue index (VATI; cm²/m²) and (D) subcutaneous adipose tissue index (SATI; cm²/m²). SMI, VATI and SATI significantly decreased between initial and 2 months (A, C, D). Skeletal MA significantly decreased between 2 and 6 months (B). *Post hoc analysis—not significant (ns): >0.05, *: <0.05, **: <0.01, ***: <0.001, ****: <0.0001.

Figure 3

(A–D) Survival analysis with initial body composition parameters. MA, muscle attenuation; SATI, subcutaneous adipose tissue index; SMI, skeletal muscle index; VATI, visceral adipose tissue index.