Combined Effect of Sarcopenia and Systemic Inflammation on Survival in Patients with Advanced Stage Cancer Treated with Immunotherapy

Abstract

Background Sarcopenia and inflammation have been associated with poor survival in patients with cancer. We explored the combined effects of these variables on survival in patients with cancer treated with immunotherapy. Methods We performed a retrospective review of 90 patients enrolled on immunotherapy‐based phase I clinical trials at Emory University from 2009 to 2017. Baseline neutrophil‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio (PLR) were used as surrogates of inflammation. The skeletal muscle index (SMI) was derived from the skeletal muscle density calculated from baseline abdominal computed tomography images. Optimal cutoffs for continuous inflammation biomarkers and SMI were determined by bias‐adjusted log‐rank test. A four‐level risk stratification was used to create low‐risk (PLR <242 and nonsarcopenic), intermediate‐risk (PLR <242 and sarcopenic), high‐risk (PLR ≥242 and nonsarcopenic), and very‐high‐risk (PLR ≥242 and sarcopenic) groups with subsequent association with survival. Results Most patients (59%) were male, and the most common cancers were melanoma (33%) and gastrointestinal (22%). Very high‐risk, high‐risk, and intermediate‐risk patients had significantly shorter overall survival (hazard ratio [HR], 8.46; 95% confidence interval [CI], 2.65–27.01; p < .001; HR, 5.32; CI, 1.96–14.43; p = .001; and HR, 4.01; CI, 1.66–9.68; p = .002, respectively) and progression‐free survival (HR, 12.29; CI, 5.15–29.32; p < .001; HR, 3.51; CI, 1.37–9.02; p = .009; and HR, 2.14; CI, 1.12–4.10; p = .022, respectively) compared with low‐risk patients. Conclusion Baseline sarcopenia and elevated inflammatory biomarkers may have a combined effect on decreasing survival in immunotherapy‐treated patients in phase I trials. These data may be immediately applicable for medical oncologists for the risk stratification of patients beginning immunotherapeutic agents. Implications for Practice Sarcopenia and inflammation have been associated with poor survival in patients with cancer, but it is unclear how to apply this information to patient care. The authors created a risk‐stratification system that combined sarcopenia and platelet‐to‐lymphocyte ratio as a marker of systemic inflammation. The presence of sarcopenia and systemic inflammation decreased progression‐free survival and overall survival in our cohort of 90 patients who received immunotherapy in phase I clinical trials. The data presented in this study may be immediately applicable for medical oncologists as a way to risk‐stratify patients who are beginning treatment with immunotherapy.

Reply to Body fat indices and survival in immunotherapy‐treated patients with cancer

“…In their final point, Orlandella et al inquire whether we quantified sarcopenia in this analysis because the IFI was associated with worse outcomes in patients with a high SFI in our study. In a recently published article,3 our group shows that the presence of sarcopenia and systemic inflammation, measured by the platelet‐to‐lymphocyte ratio, was associated with decreased OS and PFS in this cohort of patients. In conclusion, we appreciate the thoughtful commentary from Orlandella et al and agree that the field of oncology would benefit from large, comprehensive studies elucidating the impact of host adiposity, including the different compartments, on survival in patients with cancer treated with immunotherapy.…”

Significance of Glasgow prognostic scores in NSCLC patients treated with immunotherapy after platinum-based cytotoxic chemotherapy

“…Several studies demonstrated that systemic in ammatory biomarkers in peripheral blood were predictive markers for treatment outcomes in different solid tumors including prostate, colorectal, and esophageal cancer, melanoma, and NSCLC [15][16][17][18][19]. Although the exact biological basis for these ndings has not been thoroughly elucidated, in ammatory cells such as neutrophils play a signi cant role in tumor development and progression via effects on tumor cells or other components of the tumor microenvironment by secreting chemokines and cytokines such as transforming growth factor-ß, interleukin-6 (IL-6), and matrix metalloproteinase [20,21].…”

Dietary inflammatory potential and risk of sarcopenia: data from national health and nutrition examination surveys

“…Sarcopenia has been associated with increased levels of myostatin, a negative regulator of muscle mass [ 19 ], and skeletal muscle inflammation [ 20 ]. Sarcopenia has been observed in patients with chronic inflammatory conditions [ 21 ], and anti-inflammatory therapy reduces inflammation-induced muscle weakness [ 22 ]. Previous studies have suggested that inflammation parameters inversely correlate with muscle strength [ 23 , 24 ].…”