A validation study on the lung immune prognostic index for prognostic value in patients with locally advanced non-small cell lung cancer.

BACKGROUND: Baseline lung immune prognostic index (LIPI) was reported as a potential predictive biomarker of immune checkpoint inhibitor treatment and a prognostic biomarker for metastatic non-small cell lung cancer (NSCLC). However, it remains unclear whether LIPI is associated with outcomes in locally advanced NSCLC (LA-NSCLC). MATERIALS/METHODS: Patients with LA-NSCLC receiving radiotherapy between 2000 to 2017 were retrospectively reviewed. Based on pretreatment dNLR and LDH level made up LIPI per previous publications, patients were divided into good group (0 score) and intermediate-poor group (1 or 2 scores). Propensity score matching (PSM) was conducted to balance confounding variables. RESULTS: A total of 1079 patients were eligible for analysis. Patients with intermediate-poor pretreatment LIPI had inferior overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) than those with good LIPI. Multivariate analysis suggested that LIPI was an independent prognostic marker for OS (hazard ratio [HR] = 1.19, 95% CI: 1.02-1.40), PFS (HR = 1.18, 95% CI: 1.02-1.36), and LRRFS (HR = 1.22, 95% CI: 1.05-1.41) in patients with inoperable LA-NSCLC. PSM analysis further verified that intermediate-poor LIPI was an independent prognostic factor for shorter survivals (OS, PFS and LRRFS). CONCLUSIONS: LIPI is a simple and promising prognostic marker for patients with unresectable LA-NSCLC. Further prospected studies are warranted to validated these findings.

Complete response induced by anti-PD-1-based immunotherapy with toripalimab in a patient with locally advanced lung adenocarcinoma who failed rapidly after concurrent chemoradiotherapy: A case report.

WHAT IS KNOWN AND OBJECTIVE: Several immune checkpoint inhibitors (ICIs) are now available for treatment of non-small cell lung cancer (NSCLC). However, not all patients benefit from ICI therapy, and the choice of ICIs is limited. CASE SUMMARY: A 54-year-old man with locally advanced NSCLC achieved partial response after definitive chemoradiotherapy. When he opted for consolidation therapy, metastatic lesions were found. Surprisingly, after immunotherapy with toripalimab, he quickly achieved complete response. WHAT IS NEW AND CONCLUSION: As a PD-1 inhibitor, toripalimab may be an effective option for subsequent therapy of patients with locally advanced NSCLC after concurrent chemoradiotherapy.

Comparison of efficacy and safety between simultaneous integrated boost intensity-modulated radiotherapy and conventional intensity-modulated radiotherapy in locally advanced non-small-cell lung cancer: a retrospective study.

BACKGROUND: Consistent results are lacking as regards the comparative effectiveness of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) versus conventional intensity-modulated radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Therefore, we conducted a retrospective analysis to demonstrate the role of SIB-IMRT for patients. METHODS: Patients who had histologically confirmed NSCLC, stage III disease and received thoracic IMRT between 2014 and 2016 were retrospectively reviewed. The survival, toxicities and dose to organs at risk (OAR) were compared among patients irradiated with different techniques. The SIB-IMRT plans were designed to deliver 45-59.4Gy (median: 50.4Gy) to PTV while simultaneously delivering 50-70Gy (median: 59.92Gy) to PGTV. As for conventional IMRT plans, a total dose of 50-70Gy (median: 60Gy) was delivered to PTV. RESULTS: 426 patients with stage III NSCLC were eligible for analysis, including 128 with SIB-IMRT and 298 with conventional IMRT. The SIB-IMRT group had more stage IIIB disease (69.5% vs. 53%, P = 0.002), larger planning treatment volumes (median: 504 ml vs. 402 ml, P<0.001), and a larger planning treatment volume/volume of lung ratio (median, 0.18 vs. 0.12, P<0.001). The median OS of the SIB-IMRT and conventional IMRT groups were 34.5 and 31.7 months, with the 2-year rate of 60.4 and 59%, respectively (P = 0.797). No difference in PFS, LRFS or DMFS was observed between the two techniques. Patients treated with SIB-IMRT got similar lung and esophageal toxicities versus those with conventional IMRT. CONCLUSIONS: SIB-IMRT may be an effective and safe option for patients with locally advanced NSCLC, especially for those with large mass or wide lymph node metastasis.

The VEGFR-2 protein and the VEGFR-2 rs1870377 A>T genetic polymorphism are prognostic factors for gastric cancer.

OBJECTIVE: Angiogenesis is one of the key processes in the development of malignant tumors. The vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) signaling pathway regulates branching angiogenesis in cancer. In this study, we analyzed the associations of VEGF/VEGFR-2 proteins and VEGFR-2 genetic variations with the prognosis of gastric cancer (GC). METHOD: We collected the clinical information of patients with GC and extracted genomic DNA from paraffin-embedded tissues. Immunohistochemical methods were used to detect the expression of VEGF and VEGFR-2 in GC tissues. Four single nucleotide polymorphisms of VEGFR-2 were detected by the TaqMan assay. The Kaplan-Meier method and Cox regression model were applied to analyze the associations between clinicopathological characteristics, VEGFR-2 polymorphisms and GC prognosis. RESULTS: A total of 256 cases of GC were included in our study. VEGFR-2 (+) and VEGFR-2 (++/+++) protein expression levels were detected in 83 and 135 cases, respectively. High expression of the VEGFR-2 protein was associated with the poor prognosis of GC (log-rank test P = 0.026). No statistical significance was observed for the association between VEGF and the prognosis of GC. The VEGFR-2 rs1870377 A > T genetic polymorphism was discovered to be associated with the prognosis of GC (AA vs. AT, HR = 1.69, 95% CI = 1.06-2.68, P = 0.027). CONCLUSION: Our study suggested that the high expression of VEGFR-2, as well as the VEGFR-2 rs1870377 A > T genetic polymorphism, may be prognostic markers for GC.

Genetic Variants Within MTORC1 Genes Predict Gastric Cancer Prognosis in Chinese Populations.

Objective: Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions in gastric cancer (GC). Previous studies demonstrated genetic variants within mTORC1 genes were associated with GC risk. However, no studies reported the associations between genetic variants within mTORC1 genes and GC prognosis. Herein, we firstly assessed the associations of genetic variants of mTORC1 genes with overall survival (OS) of GC in Chinese populations. Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in mTORC1 genes (i.e., rs2536 T>C and rs1883965 G>A for mTOR, rs3160 T>C and rs26865 A>G for MLST8, rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A for RPTOR) by the TaqMan method in 197 Chinese GC patients who had surgical resection in Xinhua Hospital. We conducted Kaplan-Meier survival plots and Cox hazards regression analysis to explore the associations of these SNPs with OS. Results: The single-locus analysis indicated that RPTOR rs1062935 T>C was associated with an increased risk of poor GC prognosis (CC vs. TT/TC: adjusted Hazard ratio (HR) = 1.71, 95% confidence interval (CI) = 1.04-2.82). The combined analysis of all eight SNPs showed that patients with more than three risk genotypes significantly increased risk of death (adjusted HR = 2.44, 95% CI = 1.30-4.58), when compared to those with three or less risk genotypes. Conclusions: Our findings indicated that genetic variants within mTORC1 genes may predict GC prognosis in Chinese populations. The results need to be validated in future studies with larger sample sizes.

Deficiency of hMLH1 and hMSH2 expression is a poor prognostic factor in Early Gastric Cancer (EGC).

Purpose: The aim of the study was to investigate the effect of deficiency of hMLH1 and hMSH2 expression on the prognosis of early gastric cancer (EGC) in Chinese populations. Methods: A total of 160 EGC patients who underwent curative gastrectomy with lymphadenectomy from January 2011 to July 2014 at Xinhua Hospital were evaluated. The expression rates of hMLH1 and hMSH2 were examined using tissues preserved in paraffin blocks by immunohistochemical staining. The clinicopathological characteristics and prognosis of EGC with deficient hMLH1 and hMSH2 were analyzed. Results: On immunohistochemical staining, the loss expression of hMLH1 and hMSH2 were observed in 89 (55.6%) and 45 (28.1%), respectively. The hMLH1 deficiency was associated with the middle third of tumor location (P = 0.041). According to Kaplan-Meier survival analysis and Log-Rank test, the loss expression of hMLH1 and hMSH2 were associated with worse survival than positive hMLH1 (HR = 0.247, 95% CI = 0.078-0.781, P = 0.017) and hMSH2 (HR = 0.174, 95% CI = 0.051-0.601, P = 0.006) in EGC. Conclusion: The main conclusions were as follows: The hMLH1 deficiency was preferred to the middle third of EGC. Lymph node metastasis (LNM) was a prognostic factor of EGC. And the prognosis of EGC patients with deficient mismatch repair (dMMR, mainly including deficient hMLH1 and hMSH2) was obviously worse than proficient mismatch repair (pMMR).

A case report of targeted therapy with apatinib in a patient with advanced gastric cancer and high serum level of alpha-fetoprotein.

BACKGROUND: Alpha-fetoprotein (AFP) is an important marker for hepatocellular carcinoma, and the detection of serum AFP is currently the principle method for the diagnosis of hepatocellular carcinoma. The prevalence of gastric cancer (GC) with high level of serum AFP is extremely rare, but has unique clinical features. CASE SUMMARY: We herein present a rare case with GC and high level of serum AFP. A 64-year-old Chinese female underwent gastrectomy was diagnosed as gastric adenocarcinoma and the pathological stage was T1bN0M0, IA. With the progression of disease, the tumor widely metastasized and the serum AFP level increased progressively with the highest level of 3396 ng/mL. She successively entered into 3 lines palliative systematic chemotherapy and fourth-line targeted therapy of apatinib, a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. Although previous studies suggested that the prognosis of this special type of GC was poor, this patient lived for 22 months after tumor transfer. Apatinib kept her progression-free survival for 5 months, and the overall survival was 4.5 years. CONCLUSION: So, we speculate that maybe we can focus apatinib on serum AFP elevated GC patients.

Associations between CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer risk: Proof from 26 case-control studies.

Cytochrome P450 1A1 (CYP1A1) enzyme is one of the most important metabolizing enzymes responsible for the metabolism of numerous xenobiotics. Numerous individual case-control studies have investigated the associations between the CYP1A1 rs1048943 A > G and rs4646903 T > C genetic variations and colorectal cancer (CRC) risk, but the conclusions were controversial. To obtain a scientific conclusion, we performed a meta-analysis based on a total of 26 publications, including 20 studies with 8665 cases and 9953 controls on rs1048943 A > G and 19 studies with 6416 cases and 7551 controls on rs4646903 T > C, respectively. The pooled analysis indicated that rs1048943 A > G was associated with an increased risk of CRC (G vs. A: OR = 1.28, 95% CI = 1.08-1.52; GG vs. AA: OR = 1.54, 95% CI = 1.25-1.91; GA vs. AA: OR = 1.26, 95% CI = 1.00-1.60; GG/GA vs. AA: OR = 1.31, 95% CI = 1.05-1.64; GG vs. GA/AA. OR = 1.56, 95% CI = 1.26-1.91). Stratification analysis showed the association between rs1048943 A > G and CRC risk was more obvious in studies with the population-based (PB) design or high quality score. The association between rs4646903 T > C and CRC risk did not reach statistical significance in the pooled analysis as well as stratification analysis. This meta-analysis demonstrated CYP1A1 rs1048943 A > G may increase the susceptibility to CRC instead of rs4646903 T > C. This conclusion suggested CYP1A1 may contribute to the pathogenesis of CRC.

Predictable factors for lymph node metastasis in early gastric cancer analysis of clinicopathologic factors and biological markers.

Predicting lymph node metastasis (LNM) accurately is very important to decide treatment strategies preoperatively. The aim of this study was to explore risk factors that predict the presence of LNM in early gastric cancer (EGC). A total of 230 patients with EGC who underwent curative gastrectomy with lymph adenectomy at Xinhua Hospital from January 2006 to July 2014 were retrospectively reviewed. We studied the relationship between clinicopathological factors, biological markers (p53, ki67, nm23, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), E-cadherin (E-cad), beta-catenin (b-catenin), glutathione S-transferase (GST), and topoisomerase II (Topo II)), and LNM of EGC patients by chi-square test and logistic regression analysis. Meta-analyses were further conducted to review the effects of the proteins (P53, ki67, E-cad, and b-catenin) on LNM in ECG patients. LNM was detected in 42 (18.3 %) of 230 patients. Incidences of LNM was distinct in different tumor size (p = 0.044), depth of submucosal invasion (p < 0.0001), and P53 overexpression (p = 0.004). Multivariate analysis further indentified that large tumor size (≥20 mm, odds ratio (OR) = 2.168, p = 0.041), submucosa (OR = 4.000, p = 0.0005), and P53 overexpression (OR = 3.010, p = 0.022) were independent risk factors of LNM in EGC patients. The meta-analysis revealed a significantly statistical association of P53, ki67, and b-catenin with an increased risk of LNM in EGC patients (P53, OR = 1.81, p = 0.017; ki67, OR = 2.53, p = 0.0003; b-catenin, OR = 0.53, p = 0.01). Tumor size (≥20 mm), the depth of invasion (submucosa), and P53 overexpression may be helpful predictors of LNM in EGC patients. Furthermore, the results of meta-analysis revealed that P53, ki67 overexpression, and abnormal expression of b-catenin may be associated with LNM in EGC. The results need further validation in single large studies.

SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients.

BACKGROUND: Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship. METHODS: The meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. RESULTS: Eight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01-1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00-1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00-1.21). CONCLUSION: SHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.

Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof from a meta-analysis.

Phospholipase C epsilon 1 (PLCE1) plays an important role in cell growth, differentiation and oncogenesis. An increasing number of individual studies have investigated the association between PLCE1 rs2274223 polymorphism and cancer risk, but the conclusions are inconclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 22 studies with 13188 cases and 14666 controls. The pooled results indicated that PLCE1 rs2274223 A > G polymorphism was associated with an increased risk of overall cancer (G vs. A: OR = 1.15, 95% CI = 1.06-1.25; GG vs. AA: OR = 1.30, 95% CI = 1.10-1.55; GA vs. AA: OR = 1.18, 95% CI = 1.08-1.30; GG/GA vs. AA: OR = 1.20, 95% CI = 1.08-1.32; GG vs. GA/AA: OR = 1.22, 95% CI = 1.04-1.42). The stratification analysis showed the polymorphism was significantly associated with an increased risk of esophageal squamous cell carcinoma (ESCC) other than gastric cancer (GC), especially among the subgroups of Asian, high quality score, sample size > 1000 and the studies consistent with Hardy-Weinberg equilibrium (HWE). This meta-analysis demonstrated that PLCE1 rs2274223 A > G polymorphism may be associated with increased susceptibility to cancer, especially for ESCC. However, due to the substantial heterogeneities across the studies, the conclusion might be not conclusive that need more studies to confirm.