Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial

Abstract

Background Body fat and/or muscle composition influences prognosis in several cancer types. For advanced gastric and gastroesophageal junction cancer, we investigated which body composition parameters carry prognostic information beyond well‐established clinical parameters using robust model selection strategy such that parameters identified can be expected to generalize and to be reproducible beyond our particular data set. Then we modelled how differences in these parameters translate into survival outcomes. Methods Fat and muscle parameters were measured on baseline computed tomography scans in 761 patients with advanced gastric or gastroesophageal junction cancer from the phase III EXPAND trial, undergoing first‐line chemotherapy. Cox regression analysis for overall survival (OS) and progression‐free survival (PFS) included body composition parameters and clinical prognostic factors. All continuous variables were entered linearly into the model as there was no evidence of non‐linear prognostic impact. For transferability, the final model included only parameters that were picked by Bayesian information criterion model selection followed by bootstrap analysis to identify the most robust model. Results Muscle and fat parameters formed correlation clusters without relevant between‐cluster correlation. Mean muscle attenuation (MA) clusters with the fat parameters. In multivariate analysis, MA was prognostic for OS (P < 0.0001) but not for PFS, while skeletal muscle index was prognostic for PFS (P = 0.02) but not for OS. Worse performance status Eastern Cooperative Oncology Group (ECOG 1/0), younger age (on a linear scale), and the number of metastatic sites were strong negative clinical prognostic factors for both OS and PFS. MA remained in the model for OS (P = 0.0001) following Bayesian information criterion model selection in contrast to skeletal muscle index that remained prognostic for PFS (P = 0.009). Applying stricter criteria for transferability, MA represented the only prognostic body composition parameter for OS, selected in >80% of bootstrap replicates. Finally, Cox model‐derived survival curves indicated that large differences in MA translate into only moderate differences in expected OS in this cohort. Conclusions Among body composition parameters, only MA has robust prognostic impact for OS. Data suggest that treatment approaches targeting muscle quality are unlikely to prolong OS noticeably on their own in advanced gastric cancer patients, indicating that multimodal approaches should be pursued in the future.

Clinical Significance of Paraspinal Muscle Parameters as a prognostic factor for survival in Gastric Cancer Patients who underwent Curative Surgical Resection

“…The role of PMI as a prognostic factor for survival has been reported recently in gastrointestinal tumors. In Hacker's study on advanced gastric and gastroesophageal junction cancers, PMI was shown to be a significant predictor for OS (p = 0.003) but not for DFS using the multivariate Cox model [17]. In our study, PMI was a significant prognostic factor for OS and DFS when applying univariate Cox model; however, PMI was not an independent prognostic factor for OS or DFS when the multivariate Cox model was used.…”

“…In studies by Dohzono and Deng, it was suggested that paraspinal muscle was composed of multifidus and erector spinae [19,20]. In other studies, multifidus and erector spinae combined with either psoas muscle [27], quadratus lumborum [17], or psoas muscle/quadratus lumborum [15,25,26] were defined as paraspinal muscles.…”

“…The advent of CT also enables explorations of changes in muscle fat avoiding invasive muscle biopsy [14]. Low muscle attenuation (MA), at the level of L3, has been reported as a poor prognostic factor for survival [15][16][17][18].…”

“…Recently, a paraspinal muscle area (PMA) adjusted for height squared (such as the paraspinal muscle index, PMI) and MA in paraspinal muscle (PMMA) at the level of L3 have been reported as independent prognostic factors for survival in patients with gastrointestinal tumors [17,19,20]. However, there is no available study considering the clinical significance of paraspinal muscle parameters on long-term survival outcome in localized gastric cancer patients.…”

Preoperative nutritional risk index and postoperative one-year skeletal muscle loss can predict the prognosis of patients with gastric cancer: a registry based study

“…A number of patient variables such as age, performance status, and neutrophil/lymphocyte ratio have been identi ed as prognostic factors for overall survival in the last decade [5][6][7] . Recently, the prognostic value of preoperative sarcopenia and nutritional status have been gaining emphasis 8,9 . However, we have been impressed that progressive skeletal muscle loss after gastrectomy might also be a powerful prognostic indicator based on thousands of cases of practice in our dedicated gastric cancer center.…”