Relationship between Epidermal Growth Factor Receptor Gene Mutations and Clinicopathological Features in Patients with Non-Small Cell Lung Cancer in Western Turkey EGFR mutations;non small cell lung cancer;clinical features;Western Turkey; Background: To investigate epidermal growth factor receptor (EGFR) gene mutations in patients with non-small cell lung cancer (NSCLC) and to analyze any relationship with clinicopathological features and prognosis. Materials and Methods: EGFR gene exons 18-21 in 48 specimens of paraffin-embedded tumor tissue from NSCLC patients were amplified by PCR, followed by direct sequencing and analysis of links to clinicopathological features and prognosis. Results: EGFR mutations were detected in 18 of 48 (42.6%) patients with NSCLC. There were 9 cases of mutations in exon 20, 7 in exon 19 and 2 in exon 21. Mutations were more frequently observed in women (5/7 pts, 71.4%) than in men (13/41 pts, 31.7%) (p=0.086) and in non-smokers (5/5 pts, 100%) than smokers (13/43 pts, 30.2%). There was negative correlation of EGFR mutations with smoking status (p=0.005). EGFR mutations were more frequently observed with adenocarcinoma histology (13/32 pts, 40.6%) than in other types (5/16 pts, 31.3%) (p=0.527). The patients with EGFR mutations had better survival than those with wild-type EGFR (p=0.08). There was no association of EGFR mutations with metastatic spread. Conclusions: EGFR mutations in NSCLC were here demonstrated more frequently in females, non-smokers and adenocarcinoma histology in the western region of Turkey. Patients with EGFR mutations have a better prognosis.

Fluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect of dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR) polymorphisms in colorectal cancer patients. Eighty-five patients who were administered fluoropyrimidine-based treatment were included in the study. The DPYD, TYMS and MTHFR polymorphisms were scanned by a next generation Sequenom MassARRAY. Fluoropyrimidine toxicities were observed in 92% of all patients. The following polymorphisms were detected: DPYD 85T>C (29.4% heterozygote mutants, 7.1% homozygote mutants), DPYD IVS 14+1G>A (1.2% heterozygote mutants), TYMS 1494del TTAAAG (38.4% heterozygote mutants, 24.7% homozygote mutants), MTHFR 677C>T (43.5% heterozygote mutants, 9.4% homozygote mutants) and MTHFR 1298A>C (8.2% heterozygote mutants, 2.4% homozygote mutants). A statistically significant association was demonstrated between MTHFR 677C>T and fluoropyrimidine-related toxicity (p value = 0.007). Furthermore, MTHFR 1298A>C was associated with hematopoietic toxicity (p value = 0.008). MTHFR polymorphisms may be considered as related factors of fluoropyrimidine toxicity and may be useful as predictive biomarkers for the determination of the colorectal cancer patients who can receive the greatest benefit from fluoropyrimidine-based treatments.

Background & aims: Prognostic factors of metastatic rectal cancer are not well known. We aim to determine prognostic factors affecting survival for metastatic rectal cancer patients and also to investigate the effect of tumor localization on overall survival.Methods: Metastatic rectal cancer patients who received treatment in 5 different centers between 2012 and 2022 were included. Prognostic factors for survival were evaluated using univariate and multivariate analysis. The statistical methods included Pearson’s chi-square test, Fisher exact test, Log-rank test, and Cox regression model.Results: A total of 283 patients with metastatic rectal cancer were included in the study. The median OS was not significantly different among the three groups (upper rectum 30.1 months, middle rectum 28.3 months, and low rectum cancer 24.8 months; log-rank p = 0.25). In univariate analysis, Grade 3, ECOG performance status 2, the presence of multiple metastatic sites, the presence of KRAS mutation, the presence of liver metastases, the presence of nonregional lymph node metastases, and the presence of bone metastases were significant predictors of poor survival. In multivariate analysis, Grade 3, ECOG performance status 2, and the presence of multiple metastatic sites were determined as indicators of worse prognosis.Conclusion: Our findings, primary tumor location did not affect survival in metastatic rectal cancer. The most important factors affecting survival were multiple metastatic sites, tumor grade, and ECOG performance status.

Introduction: Information regarding HER2-low tumors in metastatic gastric cancer is sparse. Our aim here was to determine the frequency of low HER2 expression in metastatic gastric cancer and to compare the clinicopathological characteristics, survival, and treatment response of HER2-low patients with HER2-zero patients. Methods: The clinicopathological features, treatment responses, and survival of HER2-low tumors and HER2-zero tumors were compared. Results: Of 226 patients, 71 (31.4%) had low HER2 expression and 155 (68.6%) had zero HER2 expression. HER2-low tumors were detected more frequently in older patients and in low-grade tumors than HER2-zero tumors (69% vs. 47.7%, p = 0.003, 16.9% vs. 3.8%, p < 0.001). On the contrary, HER2-zero tumors were more likely to be poor grade than HER2-low tumors (47% vs. 22.2%, p < 0.001). All patients received a first-line chemotherapy regimen. The disease control rate was not statistically different between both groups (40% vs. 46.4%, p = 0.11). The median survival was 12.05 (95% CI, 8.09–16.02) months in HER2-low patients and 10.41 (95% CI, 8.52–12.3) months in HER2-zero patients with no statistical difference (p = 0.73). Conclusion: HER2-low metastatic gastric cancer has a higher rate of being low grade than HER2-zero tumors. HER2-low metastatic gastric cancer is similar to HER2 zero in terms of chemotherapy response and survival.

Background and Objectives: A recent clinical trial has demonstrated that breast cancer with low-HER2 expression levels responds to trastuzumab deruxtecan treatment. This has prompted a re-evaluation of HER2-targeted therapies in the HER2-negative group. Further research is required in the form of more detailed information about HER2-negative breast cancers with HER2-null, HER2-ultralow, and HER2-low subgroups. This study represents a novel approach to this field. Materials and Methods: HER2-negative breast cancer patients were classified into three groups as HER2-null, HER2-ultralow, and HER2-low. A comparison of clinicopathological features was analyzed retrospectively. Results: Of 722 patients, 22.3% were HER2-null, 23.7% were HER2-ultralow, 54.0% were HER2-low. While two-thirds of all the patients were evaluated as having T2 tumors, T4 tumors constituted 2.4%. Among HER2-negative cases, 11.8% were triple-negative and 88.2% were hormone-positive. The mean tumor diameter was 0.57 cm larger in the HER2-ultralow group than in the HER2-null group and 0.34 cm larger in the HER2-low group than in the HER2-null group. HER2-null tumors tend to be smaller. The HER2-low group was more likely to relapse than the HER2-null group. There were no significant differences in the distribution of hormone positivity or negativity (TNBC) among the groups; they accounted for 89.2% and 10.8% of all cases, respectively. Conclusions: HER2-negative breast cancer is a heterogeneous disease and deserves a detailed review in terms of diagnosis and treatment. HER2-ultralow tumors are larger in size and have a prognosis comparable to HER2-null tumors. HER2-low tumors tend to recur much more frequently and with poorer outcomes. In this field, new therapeutic approaches may result in better outcomes.

Two-Week Combination Chemotherapy with Gemcitabine, High-Dose Folinic Acid and 5 Fluorouracil (GEMFUFOL) as First-Line Treatment of Metastatic Biliary Tract Cancers Metastatic biliary tract cancer;gemcitabine;5-fluorouracil;high-dose folinic acid; Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. Materials and Methods: All patients received folinic acid $400mg/m^2$ on day 1, 5-fluorouracil bolus $400mg/m^2$ on day 1, IV infusion of 5-fluorouracil $2400mg/m^2$ over 46 hours, and gemcitabine $1250mg/m^2$ on day 1. Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstline treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.