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Yuan Zhuang, Bao-Ying Yuan, Yong Hu, Gen-Wen Chen, Li Zhang, Xiao-Mei Zhao, Yi-Xing Chen,* Zhao-Chong Zeng* Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi-Xing Chen; Zhao-Chong ZengDepartment of Radiation Oncology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, People’s Republic of ChinaTel +86-139-1605-6575Fax +86-21-6404-8472Email chen.yixing@zs-hospital.sh.cn; zeng.zhaochong@zs-hospital.sh.cnPurpose: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT).Patients and methods: Sixty patients who received SBRT were retrospectively reviewed. NLR and PLR were calculated by division of neutrophil and platelet counts, respectively, by lymphocyte counts. Independent factors for progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan–Meier method, log-rank test, and Cox multivariate regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated.Results: The median follow-up was 36.9 (range: 4.1–73.5) months. Median PFS was 21.4 (range: 1.8–66.9) months. The 1-year and 2-year PFS rates were 76.7% and 55.0%, respectively. The 1-year and 2-year OS rates were 95.0% and 78.3%, respectively. In multivariate analysis, post-treatment PLR ≥263.0 indicated both poor PFS (HR: 3.70; 95% CI: 1.07–12.76, p=0.038) and OS (HR: 3.23; 95% CI: 1.01–9.11, p=0.043) for sHCC patients treated with SBRT. In addition, the presence of hepatitis infection and a low level of red blood cell count were also proved to be significantly associated with patients’ poor prognosis (pp=0.029).Conclusion: High post-treatment PLR and change in NLR ≥2.7-fold were associated with poor prognosis in patients treated with SBRT and might be considered as reliable and independent prognostic biomarkers for patients with sHCC.Keywords: stereotactic body radiation therapy, hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, progression-free survival

Liang Zhao,1,* Xiyi Liao,1,* Ganji Hong,1 Yanzhen Zhuang,2 Kaili Fu,1 Peiqiong Chen,2 Yuhuan Wang,2 Haojun Chen,3 Qin Lin1 1Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 2Department of Pathology, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China; 3Department of Nuclear Medicine & Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China *These authors contributed equally to this work Purpose: To analyze the mismatch repair (MMR) status and PD-L1 expression in nasopharyngeal carcinoma (NPC), and investigate whether PD-L1 and MMR status could be used as a biomarker for predicting response of immune checkpoint blockades (ICBs) treatment.Patients and methods: A total of 108 patients were initially histopathologically diagnosed with NPC between December 2017 and September 2018. All tissue specimens were collected before any treatment. Tumor tissue MMR status was determined by both immunohistochemistry and PCR. The expression of PD-L1 in NPC tissue was analyzed immunohistochemically. High PD-L1 expression in tumor cells (TC) or tumor-infiltrating immune cells (TIIC) was defined as ≥50% of corresponding cells with membranous staining.Results: Tissue samples were obtained from 102 patients after written informed consent was obtained. Seventy-one (69.6%) patients were treated in our hospital after diagnosis. Disease in stages I–III accounted for 35 (49.3%) cases, while stage IVa–IVb was identified in 36 (50.7%) cases. Only two of 102 patients were identified as MMR-deficient (dMMR) by IHC and PCR. High PD-L1 expression in TC was confirmed in 77 of the 102 (75.5%) NPC cases, while only 13 of the 102 (12.7%) NPC cases were considered to exhibit high PD-L1 expression in TIIC. PD-L1 expression in TC was positively correlated with T stage (P=0.033), while PD-L1 expression in TIIC was negatively associated with plasma Epstein–Barr virus DNA load (P=0.021), N stage (P=0.009), M stage (P=0.014), and clinical stage (P=0.001).Conclusion: dMMR is a rare event in NPC and may not be a prospective biomarker to predict the effectiveness of treatment with ICBs in clinical practice. It was also determined that high PD-L1 expression in NPC is quite common and the importance of distinguishing PD-L1 expression in TC and TIIC was highlighted. Keywords: immunotherapy, biomarker, microsatellite instability, PD-L1, tumor-infiltrating immune cells

Purpose: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT)., Patients and Methods: Sixty patients who received SBRT were retrospectively reviewed. NLR and PLR were calculated by division of neutrophil and platelet counts, respectively, by lymphocyte counts. Independent factors for progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method, log-rank test, and Cox multivariate regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated., Results: The median follow-up was 36.9 (range: 4.1-73.5) months. Median PFS was 21.4 (range: 1.8-66.9) months. The 1-year and 2-year PFS rates were 76.7% and 55.0%, respectively. The 1-year and 2-year OS rates were 95.0% and 78.3%, respectively. In multivariate analysis, post-treatment PLR ≥263.0 indicated both poor PFS (HR: 3.70; 95% CI: 1.07-12.76, p =0.038) and OS (HR: 3.23; 95% CI: 1.01-9.11, p =0.043) for sHCC patients treated with SBRT. In addition, the presence of hepatitis infection and a low level of red blood cell count were also proved to be significantly associated with patients' poor prognosis ( p <0.05 for each). Post-treatment increase in NLR ≥2.7-fold was shown to be a negative independent predictor of inferior OS (HR: 3.43; 95% CI: 1.14-10.38, p =0.029)., Conclusion: High post-treatment PLR and change in NLR ≥2.7-fold were associated with poor prognosis in patients treated with SBRT and might be considered as reliable and independent prognostic biomarkers for patients with sHCC., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Zhuang et al.)