Impact of Sarcopenia, BMI, and Inflammatory Biomarkers on Survival in Advanced Hepatocellular Carcinoma Treated With Anti-PD-1 Antibody

Abstract

Background: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of sarcopenia, body mass index (BMI), and inflammatory biomarkers on survival in advanced hepatocellular carcinoma (HCC) patients treated with anti-PD-1 antibody-based immunotherapy. Methods: A retrospective review of advanced HCC patients treated with immunotherapy at Winship Cancer Institute between 2015 and 2019 was performed. Baseline computed tomography and magnetic resonance images were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m2). Sex-specific sarcopenia was defined by the median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall survival (OS) was set as primary outcome and Cox proportional hazard model was used for association with survival. Results: A total of 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% Eastern Cooperative Oncology Group performance status 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9% of patients. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 versus 14.3 months in sarcopenic versus nonsarcopenic patients (Log-rank P=0.054). Median OS was 5 and 17.5 months in patients with BMI <25 and BMI ≥25, respectively (Log-rank P=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil-to-lymphocyte ratio (NLR) ≥5.15 versus NLR <5.15 (Log-rank P<0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (hazard ratio [HR]: 4.17, 95% confidence interval [CI]: 1.52-11.39, P=0.005). Sex-specific sarcopenia showed a trend of worse OS (HR: 1.71, 95% CI: 0.73-4.00, P=0.215) but was not statistically significant. BMI<25 was associated with worse OS (HR: 2.28, 95% CI: 0.92-5.65, P=0.076). In the association with progression free survival, neither baseline BMI nor sex-specific sarcopenia showed statistical significance. Conclusion: After controlling for baseline Child Pugh score and NLR, sex-specific sarcopenia does not predict OS. Baseline BMI and NLR together may predict OS in advanced HCC patients treated with anti-PD-1 antibody.

Comparison of the Prognostic Value of Inflammation-Based Scores in Patients with Hepatocellular Carcinoma After Anti-PD-1 Therapy

“… 27 However, the practicability of the model is insufficient in clinical practice. For HCC, the NLR and PLR were reported to have strong predictive roles in anti-PD-1 therapy, 20 , 28 , 29 which was verified in our study. With the combination of albumin and lymphocytes, our study suggested that the presence of the systemic inflammatory response revealed by PNI was the optimal tool in the assessment of survival in HCC patients treated with PD-1 inhibitors compared with the other inflammation-based scores.…”

Post treatment NLR is a predictor of response to immune checkpoint inhibitor therapy in patients with esophageal squamous cell carcinoma

“…In previous study, peripheral blood parameters can reflect the system state of human bodies [ 15 – 17 ]. NLR and other hematologic parameters have become biomarkers to predict the overall survival (OS) and anti-PD-1 / PD-L1 treatment effect of diverse types of cancer [ 18 , 19 ]. PLR, MLR and SII were also reported to be potential biomarkers for predicting OS and the response to anti-PD-1/PD-L1 antibody treatment in different types of cancer [ 20 – 23 ].…”

Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort

“…Indeed, in a recent study of 976 patients, 65% of whom treated for NSCLC, a median OS of 26.6 months (95% CI: 21.4–36.8) was reported, and median OS was higher in patients with a BMI ≥ 25 (HR= 0.33 95% CI: 0.28–0.41) [ 13 ]. Most of the other studies demonstrating a relationship between BMI and outcome on immunotherapy [ 17 , 20 , 21 , 22 , 23 ] were also performed on patients with NSCLC [ 16 , 24 , 25 ], renal carcinoma, or melanoma [ 12 , 26 , 27 ]. Moreover, two studies, including patients treated by immunotherapy or chemotherapy, demonstrated a prognostic effect of BMI exclusively in patients on immunotherapy.…”

“…Multivariate Cox regression models were generated by a backward approach after testing in univariate models to estimate patient survival in association with BMI adjusted for covariates, including toxicity, performance status during first-line immunotherapy (0 to 4), and MSI. A landmark analysis was then performed to deal with the survivor bias resulting from patients responding to immunotherapy being exposed to immunotherapy for longer, and therefore being more likely to develop irAEs than non-responder patients, in whom immunotherapy was stopped earlier [ 20 ]. These analyses considered only toxicities occurring in the first three months of immunotherapy for the classification of groups, with the exclusion of patients who died or were censured before three months of treatment.…”