The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Background: Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. Objective: This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. Material and Methods: In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. Results: The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). Conclusions: We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

PD-L1 Expression in Colorectal Adenocarcinoma Is Associated With the Tumor Immune Microenvironment and Epithelial-Mesenchymal Transition.

OBJECTIVES: Colorectal carcinomas are the third-most common tumors in the world, and colorectal cancer ranks second in cancer-related deaths. Our aim in this study was to investigate the correlation between programmed cell death ligand 1 (PD-L1) expression and clinicopathologic parameters in colorectal carcinomas and their relationship to the tumor immune microenvironment, epithelial-mesenchymal transition (EMT), and microsatellite instability. We also investigated the predictive and prognostic role of PD-L1. METHODS: One hundred patients with a diagnosis of colorectal adenocarcinoma who did not receive neoadjuvant therapy were included in the study. The relationships among the altered expression of PD-L1; vimentin; E-cadherin; mismatch repair status; and pathologic microenvironmental features, including the presence of tumor budding and CD8-positive tumor infiltrating lymphocytes (TILs), were assessed. RESULTS: Increased PD-L1 expression in tumor cells was associated with increased TILs (P = .013), high histologic grade (P = .011), advanced pathologic T stage (P = .007), lymph node metastasis (P = .002), distant metastasis (P < .001), perineural invasion (P = .009), high bud score (P = .023), EMT (P < .001), and shorter disease-free survival (P = .029). CONCLUSIONS: Overall, PD-L1 expression in colorectal carcinoma tumor cells is a marker of poor prognosis, and the positive correlation detected between EMT status and PD-L1 expression suggests that patients with the mesenchymal phenotype may be more likely to benefit from programmed cell death 1 protein/PD-L1 immunotherapy.

Should a fourth category be added to the international tumor budding consensus conference tumor budding scoring system in colorectal adenocarcinomas?

The aim of this study was to investigate the relationship between tumor budding (TB) and clinicopathologic prognostic criteria in colorectal adenocarcinomas and to discuss the inclusion of the fourth group in the scoring system. A total of 131 cases were included in the study. TB was scored according to the classical 3-tiered scoring system and our proposed 4-tiered scoring system: BD0 (no buds), BD1* (1-4 buds), BD2 (5-9 buds), and BD3 (≥10 buds). Cytokeratin staining was applied to 80 randomly selected cases and TB scoring was re-evaluated. TB was not observed in 31 (23.7%) of 131 cases and was categorized as BD0. Patients with BD0 budding had lower pT category, AJCC stage, tumor grade, less lymph node metastasis, lymphovascular invasion, tumor deposits (p < 0.05), and longer overall survival than BD1* patients (log-Rank p: 0.018). There was significant compatibility between the evaluation of TB with H&E and cytokeratin (kappa: 0.727, p < 0.001). In conclusion, we think it is valuable to add the "BD0" category to the International Tumor Budding Consensus Conference (ITBCC) scores. However, more research with larger cohorts is needed for clinical applicability. H&E staining is sufficient for the assessment of budding, except in conditions such as increased inflammation where the tumor-stroma interface may be obscured.

Prognostic value of the neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 in estimating survival in patients with metastatic pancreatic cancer.

BACKGROUND: The predictive value of different prognostic biomarkers has been studied in various cancer types. AIMS AND OBJECTIVES: The purpose of this study was to examine the degree of risk and prognostic significance of pretreatment neutrophil-to-lymphocyte ratio (NLR) and carbohydrate antigen (CA) 19-9 levels in patients with metastatic pancreatic cancer (PC) and reveal its relevance with survival. MATERIALS AND METHODS: Clinical and laboratory data of 118 patients with metastatic PC at the time of diagnosis were retrospectively analyzed. The overall survival (OS) was estimated according to the Kaplan-Meier method. To determine the prognostic factors affecting PC, the Cox regression analysis was performed. RESULTS: The average age of the patients was 67 ± 9.57 years. The patients were analyzed during the follow-up period, and their average OS was 12 months (95% confidence interval [CI] = 9.73-14.26). The cutoff value was 3.54 (area under the curve [AUC] = 0.653, 95% CI = 0.56-0.73, P = 0.006) for NLR and 437 (AUC = 0.670, 95% CI = 0.57-0.75, P = 0.002) for CA19-9. Statistically significant difference was found between CA19-9 (P < 000.1) and NLR (P < 000.1) and OS. Analysis of multivariate Cox regression showed that NLR (hazard ratio [HR] = 2.17, 95% CI = 1.17-4.03, P = 0.013) and CA19-9 (HR = 1.81, 95% CI = 1.08-3.03, P = 0.022) were important prognostic factors in OS analysis. CONCLUSION: Pretreatment NLR and CA19-9 levels were found to be reliable estimative markers for poor prognosis in patients with metastatic PC. Our findings revealed that NLR and CA19-9 levels can be used to estimate the survival of patients with PC. We believe that our findings will shed light on the management of treatment protocols for patients diagnosed with metastatic PC.

Comparison of Gemcitabine monotherapy with Gemcitabine and Cisplatin combination in metastatic pancreatic cancer: a retrospective analysis.

PURPOSE: Gemcitabine is among the standard first-line agents for the treatment of metastatic pancreatic cancer. However, as the median survival with gemcitabine monotherapy is 6 months, different combinations are being studied for better, prolonged survival. In this multicenter study, we aimed to compare the results of gemcitabine monotherapy with those of gemcitabine and cisplatin combination therapy as first-line treatments for metastatic pancreatic cancer. METHODS: Data of 664 patients diagnosed with metastatic pancreatic cancer between January 2007 and December 2016 from seven oncology centers in Turkey were retrospectively evaluated, and 319 patients with gemcitabine alone (n=138) or gemcitabine and cisplatin combination (n=181) as first-line treatment were included. RESULTS: The median patient age was 62 years (range 42-79), being 60 years (42-75) in the gemcitabine/cisplatin arm and 67 years (52-79) in gemcitabine alone arm. no complete response was observed in either arm, whereas partial response rates were 30.1% in gemcitabine/cisplatin arm and 15.3% in gemcitabine alone arm (p=0.001). median overall survival was 8 months (95% CI:7.7-10.2) and was significantly longer in the gemcitabine/cisplatin arm than in the gemcitabine alone arm (10 vs. 6 months, p=0.004). CONCLUSION: The cemcitabine and cisplatin combination therapy as first-line treatment of metastatic pancreatic cancer yields significantly prolonged survival over gemcitabine monotherapy. In patients with favorable performance conditions, the combination therapy should be preferred.

Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study.

BACKGROUND: We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS). RESULTS: The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months. CONCLUSION: This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma.

Prognostic value of ERCC1, ERCC2, XRCC1, and TP53 single nucleotide polymorphisms in patients with early-stage non-small cell lung cancer.

Identification of biomarkers used for the prognostic evaluation of non-small cell lung cancer (NSCLC) patients is important. The aim of this study was to evaluate the potential prognostic value of XRCC1, ERCC1, ERCC2, and TP53 single nucleotide polymorphisms (SNPs) in completely resected NSCLC patients. In total, 130 patients, surgically treated for NSCLC between 2000 and 2012, were included. An analysis of SNPs from peripheral blood cells was performed by polymerase chain reaction. XRCC1 Arg399Gln, ERCC1 Asn118Asn, ERCC2 Lys751Gln, and TP53 Arg72Pro polymorphisms were evaluated in conjunction with clinical and pathological parameters and survival. Kaplan-Meier method and Cox regression analysis were used. Median age rate was 59.3, ranging between 36 and 78 years. Median relapse-free survival duration (RFS) was found as 46.2 months. In those with ERCC2 CC allele, median RFS was detected as 28.3 months (95 % confidence interval (CI), 20.8-35.8), 46.9 months in those with CT heterozygous (95 % CI, 18.6-75.2), and 80.1 months for those with TT mutant allel (95 % CI, 33.0-127.2). Median RFS was seen to be longer in mutant group and also statistically significant (P = 0.018). Additionally, upon evaluating CC normal group with CT + TT alleles including mutant alleles, median RFS was found as 56.5 months (95 % CI, 24.6-88.4) in CT + TT group, and this was statistically significant (P = 0.005) Also, median RFS was 15.1 months in those including ERCC2 CC allele and 56.5 months in CT + TT allele in the group with no adjuvant treatment (P = 0.001). In conclusion, our study showed that ERCC2/XPD polymorphism is an independent prognostic factor in operated NSCLC patients, and these findings should be supported with prospective studies.

Sunitinib for patients with metastatic non-clear cell renal cell carcinoma: a Multicenter Retrospective Turkish Oncology Group trial.

AIM: This study aimed to assess the clinical efficacy and toxicity of sunitinib, a targeted-agent, for non-clear cell renal cell carcinoma. PATIENTS AND METHODS: Sixty-three patients with complete clinical data from 13 oncology Centers were retrospectively evaluated. Outcomes analyzed were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse events. RESULTS: The median age of all patients, 38 men (60.3%) and 25 women (39.7%), was 63 years (range=25-82 years). Histological subtypes included 46 (88%) cases of papillary RCC, 10 of chromophobe, and 7 unclassified cases. Median treatment duration was seven months (range=2-86 months). At the time of this analysis, 52 patients had discontinued treatment, 33 of whom had died. Treatment discontinuation was due to disease progression in 43 patients, and toxicity in nine. Dose interruption was necessary in 22 (34.9%) patients, and dose reduction in 27 (42.9%). The objective response rate and disease control rate were 11.1% and 63.5%, respectively. The median PFS and OS were 7.6 months (95% confidence interval (CI)=5.5-9.7 months) and 22.0 months (95% CI=13.4-30.6 months), respectively, with 1-year rates of 64.7% and 33.7%, respectively. CONCLUSION: Clinical outcome of the metastatic non-clear cell RCC patients with sunitinib treatment seemed to be worse than the historical data of clear cell RCC patients, in terms of PFS, OS and objective response. New and more effective targeted-therapies and better understanding of the underlying molecular processes are necessary to improve survival outcome for these patients.