The relation between tumor mutation burden (TMB) and outcome of cancer patients receiving immunotherapy has been reported. This study aimed to evaluate the prognostic role of TMB in cancer patients receiving immunotherapy. Databases including Embase, PubMed, and the Cochrane library were systematically searched to identify potentially eligible studies until Sep 2018 without language limitation. Studies assessing high versus low TMB in predicting survival of various cancer patients were selected. The pooled analyses were conducted using hazard ratio (HR) of high versus low TMB for overall survival (OS) and progression-free survival (PFS), and the odds ratio (OR) for overall response rate (ORR). The primary endpoint was OS. Secondary outcomes were PFS and ORR. A total of 45 studies consisting of 103078 cancer patients were included. The combined results showed that high TMB was associated with better OS (HR = 0.40; 95% confidence interval (CI):0.30–0.53; p< .00001), PFS (HR = 0.37; 95% CI: 0.26–0.53; p< .00001) and ORR (OR = 4.62; 95%CI: 2.90–7.34; p< .0001) when treated with immunotherapy. In studying patients with high TMB, these patients had improved OS (HR = 0.69; 95%CI: 0.47–1.03; p= .07) when comparing immunotherapy to chemotherapy. Subgroup analyses suggested that the prognostic role of TMB was independent of cancer types and TMB detection methods (all p< .05). Our findings suggest that high TMB is associated with better survival in cancer patients receiving immunotherapy. For cancer patients with high TMB, immunotherapy could be considered.

Objective: Nivolumab has been used for treating non-small cell lung cancer (NSCLC) worldwide. Whether neutrophil-lymphocyte ratio (NLR) can predict the prognosis of NSCLC treated with Nivolumab is still under debate. This meta-analysis was to assess the significance of NLR as a predictive factor in NSCLC patients receiving Nivolumab. Methods: Databases including PubMed, Embase, and the Cochrane library were searched to identify eligible studies evaluating the role of NLR in predicting prognosis of NSCLC treated with Nivolumab until March 2018 without language restrictions. The meta-analysis was performed using hazard ratio (HR) of progression free survival (PFS) and overall survival (OS) in NSCLC patients with various NLR. Results: A total of 14 retrospective studies consisting of 1225 NSCLC patients were included. The combined results showed that relatively higher baseline NLR was associated with poor PFS (HR = 1.44; 95% confidence interval (CI):1.18–1.77; p < 0.05) and OS (HR = 1.75; 95% CI: 1.33–2.30; p < 0.05) after treatment of Nivolumab. Subgroup analysis suggested that NLR ≥ 5 was more reliable for PFS (HR = 1.73; 95%CI: 1.14, 2.62; p < 0.05) and OS (HR = 1.76; 95%CI: 1.47, 2.10; p < 0.05). In addition, post-treatment NLR also had predictive roles for PFS (HR = 3.17; 95%CI: 1.48, 6.82; p < 0.05) and OS (HR = 2.26; 95%CI: 1.05, 4.86; p < 0.05). Conclusion: Our findings suggest that NLR can be used as a prognostic biomarker for NSCLC treating with Nivolumab, and the recommended cutoff value of NLR is 5.

Recent studies suggest obesity is associated with improved survival of cancer patients treated with immune checkpoint inhibitors (ICIs). We performed this meta-analysis to evaluate the impact of obesity on survival of these patients with regard to the cutoff value of body mass index (BMI) as well as sex. Electronic databases including Pubmed, Emabse, and the Cochrane library were systematically searched until April 2019, without language limitation. Clinical studies evaluating the association between BMI and survival of cancer patients treated with ICIs were included. The main endpoints were overall survival (OS) and progression-free survival (PFS). Data from individual studies were extracted by two researchers, independently. RevMan 5.3 and Stata 11 software were used to perform the analysis. 16 retrospective studies met the inclusion criteria, with a total of 4090 patients. The OS (HR = 0.72, 95% CI: 0.51-1.02; P = 0.06) and PFS (HR = 0.67, 95% CI: 0.48-0.95; P = 0.02) of the high BMI group were improved compared with the low BMI group. Dose-response analysis showed that the risk of death decreased by 3.6% when the BMI increased every 1 kg/m2. Subgroup analysis revealed that BMI > 30 was a reliable value for determining significantly better OS (HR = 0.64; 95%CI: 0.43-0.96; P = 0.03). The prognostic effect of BMI on OS was significant regardless of gender (For male, HR = 0.73, 95% CI: 0.61-0.86; P < 0.01. For female, HR = 0.63, 95% CI: 0.43-0.92; P = 0.02). Obesity is associated with better outcomes in cancer patients treated with ICIs, and this clinical benefit may be independent of sex.

Whether platelet-lymphocyte ratio (PLR) is a prognostic factor for cancer patients treated with immunotherapy is under debate. In this study, we aimed to evaluate the relationship between PLR and survival of cancer patients treated with immune checkpoint inhibitors (ICIs). A systematical search was performed in databases including PubMed, Embase, and the Cochrane library to retrieve potential eligible clinical studies assessing the prognosis of cancer patients with high versus low PLR after immunotherapy, from the establishment of the database to June 2019. Quality evaluation of included studies was performed, and meta-analyses with regards to overall survival (OS) and progression-free survival (PFS) were conducted using RevMan 5.3 and STATA 11. A total of 12 eligible studies with 1340 cancer patients were included. Combined results showed that elevated PLR was a negative factor affecting the efficacy of ICIs in cancer patients. Patients with high PLR had a significantly shorter OS compared to those with low PLR (hazard ratio (HR) = 2.02, 95% confidence interval (CI): 1.46 to 2.80, P < 0.0001), as well as PFS (HR = 1.74, 95%CI: 1.27 to 2.38, P = 0.0006). Similar results were observed in sensitivity analyses. Subgroup analyses revealed that the prognostic role of PLR on OS and PFS was dependent on cancer type, region, and cutoff value. For NSCLC patients, the disease stage, ICIs agent, and line of treatment may not influence the prognostic role of PLR. PLR could be a routinely potential prognostic factor for ICIs. Low PLR may be associated with better survival for cancer patients when treated with immunotherapy.