Ming Cui

Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer.

The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1–1.52, p = 0.001; I2 = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88–2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC.

Increased programmed death ligand-1 expression predicts poor prognosis in hepatocellular carcinoma patients

Purpose Accumulating studies have investigated the prognostic and clinical significance of programmed death ligand-1 (PD-L1) expression in patients with hepatocellular carcinoma (HCC); however, the results were conflicting and inconclusive. We conducted a meta-analysis to combine controversial data to precisely evaluate this issue. Methods Relevant studies were thoroughly searched on PubMed, Web of Science, and Embase until April 2016. Eligible studies were evaluated by selection criteria. Hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the prognostic role of PD-L1 for overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Odds ratio (OR) with 95% CI were selected to assess the relationship between PD-L1 and clinicopathological features of HCC patients. Publication bias was tested using Begg’s funnel plot. Results A total of seven studies published from 2009 to 2016 were included for meta-analysis. The data showed that high PD-L1 expression was correlated to shorter OS (HR =2.09, 95% CI: 1.66–2.64, P<0.001) as well as poor DFS/RFS (HR =2.3, 95% CI: 1.46–3.62, P<0.001). In addition, increased PD-L1 expression was also associated with tumor differentiation (HR =1.51, 95% CI: 1–2.29, P=0.05), vascular invasion (HR =2.16, 95% CI: 1.43–3.27, P<0.001), and α-fetoprotein (AFP; HR =1.46, 95% CI: 1–2.14, P=0.05), but had no association with tumor stage, tumor size, hepatitis history, sex, age, or tumor multiplicity. No publication bias was found for all analyses. Conclusion This meta-analysis revealed that overexpression of PD-L1 was predictive for shortened OS and DFS/RFS in HCC. Furthermore, increased PD-L1 expression was associated with less differentiation, vascular invasion, and AFP elevation.

BRCA2 mutations should be screened early and routinely as markers of poor prognosis: evidence from 8,988 patients with prostate cancer

The aim of this study was to focus on clinicopathological characteristics and prognosis in men with prostate cancer (PCa) harboring a breast cancer 2 (BRCA2) gene mutation and to offer convincing evidence to consider BRCA2 mutation as a marker of poor prognosis in the molecular classification of PCa. We searched relevant articles from PubMed, Embase, Web of Science, and the Cochrane Library databases to evaluate the differences in the overall survival (OS) and cancer-specific survival (CSS) between BRCA2 mutation carriers and non-carriers in patients with PCa. We included 525 BRCA2 mutation-carriers and 8,463 non-carriers in total from 10 studies in our meta-analysis. The results showed that carrying a BRCA2 mutation was correlated with a reduced CSS and OS when compared with that of non-carriers, with pooled Hazard Ratios (HRs) of 2.53 (95% confidence interval (CI): 2.10–3.06, P < 0.001) and 2.21 (95% CI: 1.64–2.99, P < 0.001), respectively. The results also demonstrated that BRCA2 mutation-carriers harbored a higher Gleason Score (GS) (> 7), TNM stage (> T3, N1, M1), and risk level than non-carriers. Our meta-analysis showed that a BRCA2 mutation predicted poor survival outcomes in patients with prostate cancer, especially in those undergoing treatments with radiotherapy. Therefore, the use of BRCA2 mutation as a clinical prognostic factor could help stratify the high-risk patients and provide clinical strategies for more effective targeted treatments for patients with prostate cancer.

The role of definitive chemoradiotherapy versus surgery as initial treatments for potentially resectable esophageal carcinoma

BackgroundWe performed a meta-analysis to compare the efficacy of definitive chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially resectable esophageal cancer.MethodsTo assess both strategies, the combined odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen studies (Nu2009=u20092071; dCRTu2009=u2009869 and surgeryu2009=u20091202) were included. In all, 90.39% of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC).ResultsThe 2-year (ORu2009=u20091.199, 95% CI 0.922–1.560; Pu2009=u20090.177) and 5-year overall survival (OS) rates (ORu2009=u20090.947, 95% CI 0.628–1.429; Pu2009=u20090.796) were not significantly different. No significant differences were identified in the 2-year OS among patients with stage I disease (ORu2009=u20091.397, 95% CI 0.740–2.638; Pu2009=u20090.303) or stage II–III (ORu2009=u20090.418, 95% CI 0.022–7.833; Pu2009=u20090.560). Patients with lymph node metastases tended to have a better 5-year OS when treated with dCRT than with surgery (ORu2009=u20090.226, 95% CI 0.044–1.169; Pu2009=u20090.076); however, the difference between the two methods was not significant. Western patients who received dCRT had poorer prognoses than patients who underwent surgery (ORu2009=u20091.522, 95% CI 1.035–2.238; Pu2009=u20090.033). dCRT and surgery led to similar 5-year progression-free survival rates (ORu2009=u20091.06, 95% CI 0.79–1.42; Pu2009=u20090.70).ConclusionsdCRT and surgery are equally effective as initial treatments for potentially resectable esophageal cancer. These results apply primarily to Asian populations as they have an increased incidence of ESCC.

Partial stereotactic ablative boost radiotherapy in bulky non-small cell lung cancer: a retrospective study

Purpose Bulky non-small cell lung cancer (NSCLC) is difficult to achieve effective local control by conventionally fractionated radiotherapy (CRT). The present work aims to evaluate the safety and efficacy of partial stereotactic ablative boost radiotherapy (P-SABR) in bulky NSCLC. Patients and methods From December 2012 through August 2017, 30 patients with bulky NSCLC treated with P-SABR technique were analyzed. The P-SABR plan consisted of one partial SABR plan (5–9 Gy/f, 3–6 fractions) to gross tumor boost (GTVb), followed by one CRT plan to the planning target volume (PTV). GTVb was the max volume receiving SABR to guarantee the dose of organs-at-risks (OARs) falloff to about 3 Gy/f. The total dose of PTV margin was planned to above 60 Gy. The simply CRT plans were created using the same planning parameters as the original plan, with the goal to achieve comparable OARs doses and PTV margin dose to the P-SABR plan. Dosimetric variables were acquired in both P-SABR and compared CRT plans. Toxicity, local control, and survival were also evaluated. Results Median follow-up in survivors was 10.3 months (range=2.3–39.4 months). Eleven patients (36.7%) had partial response (PR) and ten patients (33.3%) had stable disease (SD). Two-year overall survival was 55.6%. Two-year local control rate was 85.7%. No severe acute side effects >CTCAE Grade III were observed. Compared to the simply CRT plan, P-SABR plans achieved similar doses to the OARs and Dmin, but increased dose at the isocenter, Dmean, Dmax, and biological equivalent dose (BED) significantly (P<0.05). BED in the tumor center could reach 107.3 Gy (93.2–132 Gy). Patients with B90≥65% achieved a higher local control rate than those with B90<65% (P=0.010). Conclusion This retrospective study suggests that P-SABR is feasible and well tolerated in bulky NSCLC. Local control rate is encouraging, especially for the B90≥65% group, which may due to the ability of P-SABR to optimize BED with equivalent toxicity.

Methyl jasmonate enhances the radiation sensitivity of esophageal carcinoma cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3

Purpose In our previous study, we found that AKR1C3 was a radioresistance gene in KY170R cells. Downregulating the expression of AKR1C3 could enhance the radiosensitivity of esophageal carcinoma cells. In this study, we investigated whether methyl jasmonate (MeJ), an inhibitor of Aldo-keto reductase family1 member C3 (AKR1C3), could overcome radiation resistance in AKR1C3 highly expressed cells. Patients and methods We used clone formation assays to detect radiosensitivity effects. Flow cytometry assays were used to detect reactive oxygen species (ROS) accumulation and apoptosis. Enzyme linked immunosorbent assays (ELISAs) were used to detect the concentrations of prostaglandin F2 (PGF2) and prostaglandin D2 (PGD2) in the cells after incubation with MeJ. Western blotting was used to detect AKR1C3 and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Results We found that AKR1C3 was highly expressed in radioresistant esophageal carcinoma cells. MeJ inhibited the expression of AKR1C3 and enhanced the radiation sensitivity of esophageal carcinoma cells expressing high levels of AKR1C3 (P<0.05). MeJ could inhibit the 11-ketoprostaglandin reductase activity of AKR1C3 in a dose-dependent manner in KY170R cells. Incubation of KY170R cells with 200 µmol/L of MeJ for 24 h reduced the expression of PGF2 by roughly 30% (P<0.05). The PPAR pathway inhibitor GW9662 prevented the radiation sensitivity enhancement imparted by MeJ. After adding GW9662, there were no significant differences between the radiation sensitivities of MeJ-treated and -untreated KY170R cells (P>0.05). The radiation sensitivity effect of MeJ also depended upon the generation of ROS in KY170R cells; 48 h after irradiation, ROS levels in the MeJ group was twofold higher than in the untreated KY170R cells (P<0.05). The ROS scavenger, N-acetyl cysteine, could reverse the radiosensitivity effects of MeJ (P>0.05). Conclusion Our results indicate that MeJ can increase the radiation sensitivity of AKR1C3-overexpressing KY170R cells by inhibiting the 11-ketoprostaglandin reductase activity of AKR1C3 and increasing cellular ROS levels.

Survival outcomes of radical prostatectomy and external beam radiotherapy in clinically localized high-risk prostate cancer: a population-based, propensity score matched study

Objective This study was aimed to compare survival outcomes in high-risk prostate cancer (PCa) patients receiving external beam radiotherapy (EBRT) or radical prostatectomy (RP). Materials and methods The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCa patients with high-risk features who received RP alone or EBRT alone from 2004 to 2008. Propensity-score matching (PSM) was performed. Kaplan–Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS). Multivariate Cox regression analysis was used to identify independent prognostic factors. Results A total of 24,293 patients were identified, 14,460 patients receiving RP and 9833 patients receiving EBRT. Through PSM, 3828 patients were identified in each group. The mean CSS was 128.6 and 126.7 months for RP and EBRT groups, respectively (P<0.001). The subgroup analyses showed that CSS of the RP group was better than that of the EBRT group for patients aged <65 years (P<0.001), White race (P<0.001), and married status (P<0.001). However, there was no significant difference in CSS for patients aged ≥65 years, Black race, other race, and unmarried status. Similar trends were observed for OS. Multivariate analysis showed that EBRT treatment modality, T3–T4 stage, Gleason score 8–10, and prostate-specific antigen >20 ng/mL were significant risk factors for both CSS and OS. Conclusion This study suggested that survival outcomes might be better with RP than EBRT in high-risk PCa patients aged <65 years; however, RP and EBRT provided equivalent survival outcomes in older patients, which argues for primary radiotherapy in this older cohort.