Effects of hormone receptor status on patient clinic and survival in HER2 positive breast cancer.

BACKGROUND: In the current study, the effect of hormone receptor (HR) status on clinical and survival in early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer was investigated. METHODS: Two hundred ninety-one patients with HER2- positive were examined in two categories as HR-positive and HR-negative. RESULTS: Of these, 197 (68%) were HR-positive and 94 (32%) were HR-negative with a mean follow-up period of 68 ± 2.7 months. The groups were found to be similar in terms of age, menopausal status, comorbidity, pathologic type, stage, T stage, N stage, lymphovascular invasion, presence and percentage of intraductal component, multicentricity/focality and extracapsular invasion. Family history (P = 0.038), stage 2 tumor rate (P < 0.001), and perineural invasion (P = 0.005) were significantly higher in the HR-positive group. In the HR-negative group, mean Ki-67 value (P = 0.014), stage 3 tumor rate (P < 0.001), tumor necrosis (P = 0.004) and strong (3+) HER2 staining on immunohistochemical staining (P = 0.003) were higher. The incidence of relapse and metastasis, and the localization of metastasis were similar in both patient groups. The rate of locoregional relapse during the first 2 years was higher in the HR-negative patients than in the HR-positive patients (P = 0.023). Overall survival (OS) and disease-free survival (DFS) did not differ between the groups in univariate analysis. However, HR status was determined as an independent prognostic factor (HR: 2.11, 95% CI: 1.17-3.79; P = 0.012) for OS was not found to be significant for DFS in multivariate analysis. CONCLUSION: Both clinicopathologic features and OS outcomes of HR-negative patients were worse than those of HR-positive patients.

The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

The effect of the change in hemoglobin-albumin-lymphocyte-platelet scores occurring with neoadjuvant chemotherapy on clinical and pathological responses in breast cancer.

INTRODUCTION: Breast-cancer is a common-cause of death in women.(1) We investigated the effects of before/after-NACT on hemoglobin-albumin-lymphocyte-platelet (HALP) scores and of changes therein on clinical/pathological-responses. MATERIALS AND METHODS: One-hundred-twenty-seven breast-cancer-patients receiving-NACT between December 2009 - January 2019 were investigated retrospectively. RESULTS: The mean - age was 50.3±12.3 (min 27 - max 79), and 125 patients (98.4 %) were women. Fifty-four (42.5 %) were premenopausal and 71 (55.9 %) postmenopausal. Invasive-ductal-carcinoma was present in 111 patients (92.5 %). Eighty patients (70.2 %) were ≤ T2 and 34 (29.8 %) > T2. Lymph-node-status was positive in 99 patients (83.2 %) and negative in 20 (16.8 %). Ki-67 was ≤ 10 % in 22 (28.9 %), 11-20 % in 23 (30.3 %), and > 20 % in 31 (40.8 %). Complete clinical response was observed in 27 (21.3 %), partial-response in 76 (59.8 %), stable-disease in 21 (16.5 %), and progressive-disease in 3 patients (2.4 %). The objective-response-rate (ORR) was 103 (81.1 %). Pathological-complete-response (pCR) was observed in 24 patients (18.9 %). ORR was higher in Ki-67 > 20 % compared to ≤ 10 % and 10-20 % (90.3 % vs 59.0 % / 78.3 %, respectively, p: 0.027), but no difference occurred in pCR. Neutrophil-lymphocyte-ratio (NLR), platelet-lymphocyte-ratio (PLR), prognostic-nutritional-index (PNI), and HALP were measured before/after NACT. Associations with ORR and pCR were investigated via changes in these with NACT (excepting-PNI), but no-significant results emerged. CONCLUSIONS: Higher ORR occurred post-NACT in patients with Ki-67 >20 %, while NLR, PLR, PNI, and HALP before/after-NACT and post-NACT-changes (excepting-PNI) had no-effect on ORR/pCR (Tab. 5, Ref. 21). Text in PDF www.elis.sk Keywords: breast cancer, objective response rate (ORR), pathological complete response (pCR), hemoglobin-albumin-lymphocyte-platelet (HALP) score.

The effects of thymoquinone on pancreatic cancer and immune cells.

OBJECTIVES: Black cumin is widely used as a spice and as a traditional treatment. The active ingredient in black cumin seeds is thymoquinone. Thymoquinone has shown anticancer effects in some cancers. We planned to investigate its anticancer effect on pancreatic cancer cell lines. METHODS: Thymoquinone chemical component in various doses was prepared and inoculated on pancreatic cancer cell culture, healthy mesenchymal stem cells, and peripheral blood mononuclear cell culture. IC50 values were calculated by absorbance data and measuring cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide staining of cells incubated with thymoquinone at 24, 48, and 72 h. RESULTS: There was dose-related cytotoxicity. Maximal cytotoxicity was observed at 24 h and 100 µM thymoquinone concentrations in pancreatic cancer cell culture and mesenchymal stem cells. Any concentration of thymoquinone was not cytotoxic to peripheral blood mononuclear cell. Thymoquinone even caused proliferation at a concentration of 6.25 µM. CONCLUSIONS: Since the cytotoxic concentration of thymoquinone on pancreatic cancer cell culture and mesenchymal stem cells is the same, it is not appropriate to use thymoquinone to achieve cytotoxicity in pancreatic cancer. However, since thymoquinone provides proliferation in peripheral blood mononuclear cell at a noncytotoxic dose, it may have an immune activator effect. Therefore, in vivo studies are needed to investigate the effect of thymoquinone on the immune system.

The association between the lymph node ratio, surgical margin, and survival in patients with colon cancer receiving adjuvant chemotherapy.

Objectives: To investigate the prognostic significant of lymph node ratio and surgical margins in patients with colon cancer undergoing surgery. Methods: This observational and retrospective study was conducted at Karadeniz Technical University Medical Faculty, between 1 January, 2010 and 31 November, 2020. A series of 137 patients who had undergone surgical resection of colon carcinoma were included in this study. mLNR, defined as the ratio of the number of mLNs to the number of examined lymph nodes, was calculated in colorectal cancer cases with lymph node metastasis. Patients were divided into three groups; LNR1 (< 0.25), LNR2 (0.25-0.6) and LNR3 (> 0.6). Results: Mean disease-free survival was 79.2 months (95% CI 71.0-87.4). The mean expected survival time was 73.5 months (95% CI: 65.9-81.0). As the metastatic LN ratio increased, the rate of local recurrence or distant metastasis increased statistically significantly (p=0.007). As the metastatic LN ratio increased, the death rate increased statistically significantly (p=0.036). Metastatic lymph node ratio did not have a statistically significant effect on overall survival in patients with stage-3 and more than 12 LNs removed (p=0.069). There was no statistically significant association between the closeness of the surgical margin and disease-free survival in stage 1 (p=0.505) and stage-2 (p=0.161). There was no statistically significant association between the closeness of the surgical margin and overall survival among patients with stage 1 (p=0.494) and stage 2 (p=0.265). Conclusion: A high metastatic LNR is associated with poorer overall and disease-free survival.

Amlodipine improves the outcomes of regorafenib in metastatic colorectal cancer.

Regorafenib is a multikinase inhibitor. It is used for metastatic colorectal cancer (mCRC) treatment. It has a mild effect. Regorafenib outcomes, and side effects may vary across patients. This study was aimed to evaluate the factors that affect regorafenib outcomes in mCRC patients. We conducted a single-center and retrospective study. Fifty-six patients were included. All patients had received regorafenib for mCRC. Some clinical and pathological factors and the effects of these factors on overall survival (OS), progression-free survival (PFS), and disease control rates (DCR) were analyzed. Concomitant amlodipine intake with regorafenib improved OS [14.26 vs. 6.97 months; 95% confidence interval, 4.04-20.84; P = 0.031] and DCR at 12th week (90% vs. 46%; P = 0.012). Hepatic metastasis was found as the poorest prognostic factor in both univariate and multivariate analyses. Patients who received chemotherapy after regorafenib had better OS. Good performance status was the strongest indicator of better OS. Patients taking amlodipine for arterial hypertension at the same time with regorafenib had numerically better OS and PFS and statistically better DCR. Amlodipine itself already has anticancer effects, and it has additive anticancer effects with regorafenib. The presence of hepatic metastases was found to be the most important prognostic factor for OS. There were not any predictive factors of side effects to regorafenib.

Prognostic Factors in Gastrointestinal Stromal Tumors (GIST): Could Prognostic Nutritional Index (PNI) be a New Prognostic Factor?

OBJECTIVE: To investigate factors that may affect prognosis in gastrointestinal stromal tumors (GISTs). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Karadeniz Technical University Hospital, Trabzon, Turkey from 2000 to 2019. METHODOLOGY: All the patients diagnosed with GIST and followed-up in this centre were included. Those who were not followed-up in this centre were excluded. The Chi-square test for differences between variables in independent groups; and the Kaplan-Meier method for survival rates were used. RESULTS: Median tumor size was larger in patients with recurrence, compared to those without (8cm vs. 5 cm, p <0.001). Recurrence rates were higher with mitosis ≥5 in 50 high-power-fields than with low mitosis (52.6% vs. 23.4%, p = 0.021). Median Ki-67 percentages were higher in patients with recurrence than without (5 vs. 2, p = 0.031). Recurrence rates were higher with necrosis and bleeding than without (57.7% vs. 14.3%, p = <0.001; 50% vs. 13.8%, p = 0.003). Median overall-survival (OS) was shorter in with mitotic counts ≥5 compared to <5 (52.0 vs. 110.0 months, p = 0.051) and with ulceration than without (36.0 vs. 110.0 months, p = 0.017). The groups below (<43.5) and above (>43.5) the median prognostic-nutritional-index (PNI) value were similar in terms of OS and disease-free survival (DFS) (52 vs. 70 months, p = 0.174; 82 vs. 100 months, p = 0.411). Median DFS was shorter with ulceration than without (27 vs. 100 months, p = 0.048). CONCLUSION: While necrosis, bleeding, ulceration, mitosis, size, and Ki-67 significantly affect the prognosis in GIST, PNI has no significant effect. Key Words: Gastrointestinal stromal tumors (GIST), Survival, Prognosis, Recurrence, Prognostic Nutrition Index (PNI).

Repurposing calcium channel blockers: may be sensible combination with erlotinib for non-small cell lung cancer.

Erlotinib is a tyrosine kinase inhibitor that inhibits epidermal growth factor receptor. It is being used for metastatic non-small cell lung cancer patients (NSCLC). Repurposing noncancer drugs for cancer treatment is a current issue and it has many advantages. We planned to reveal the effects of noncancer drugs [calcium channel blockers (CCBs) and others] on erlotinib. We scanned the files of NSCLC patients retrospectively who were applied to Karadeniz Technical University between January 2013 and April 2019 and used erlotinib. There were 63 patients, 9 of them were taking CCB simultaneously for arterial hypertension. We analyzed some parameters of these patients and their effects on overall survival (OS) and progression-free survival (PFS). A χ2 or Fisher's exact test, Kaplan-Meier and Cox regressions were used in the statistical analysis. 12-month OS rates of CCB user and nonuser were 78.3 and 39.7%, respectively, [odds ratio (OR),0.14; 95% confidence interval (CI), 0.27-0.75; P = 0.023]. 24-month PFS rates of CCB user and nonuser were 44.4 and 8.3%, respectively (OR,0.11; 95% CI, 0.02-0.60; P = 0.016). There was 12-month OS and 24-month PFS advantage with simultaneously taking CCBs and erlotinib, they have an additive effect for NSCLC. This study will be inspiring future prospective studies.

Hepatitis B Virus Screening and Real Life Data in Patients with Solid Tumor Receiving Chemotherapy.

BACKGROUND: Reactivation of the hepatitis B virus (HBV) either during or after chemotherapy may cause serious and sometimes fatal hepatitis. All patients undergoing chemotherapy should therefore be screened in terms of HBV before chemotherapy. The purpose of this research was to identify HBV screening rates in patients with solid cancer undergoing parenteral chemotherapy and to determine the outcomes of patients undergoing HBV screening. METHODS: Data for patients undergoing parenteral chemotherapy for solid cancer from January 1, 2012 to December 30, 2018 were retrieved from our electronic health record patient files in this retrospective study. Screening was defined as hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) tests carried out within six months prior the first chemotherapy session. RESULTS: Four thousand fifty-eight (63%) of the 6440 patients who underwent parenteral chemotherapy were screened for HBsAg and/or HBcAb. The proportions of patients screened for HBsAg and HBcAb improved from 38.8% (2012) to 76.3% (2018), and from 0.2% (2012) to 43% (2018), respectively (P<0.001). The HBsAg and HBcAb positivity rates were 2.9% and 36.5%, respectively. Antiviral prophylaxis was started in 11.8% of HBsAg-negative/HBcAb-positive patients and 40.5% of HBsAg-positive patients. HBV reactivation did not occur in patients receiving antiviral prophylaxis, but was identified in 7.2% of HBsAg-positive patients and 0.6% of HBsAg-negative/HBcAb-positive patients without antiviral prophylaxis. CONCLUSION: Although HBV screening rates before chemotherapy are increasing among solid cancer patients, the rate of initiation of antiviral prophylaxis is still low. It is therefore important to raise awareness regarding HBV reactivation during/after chemotherapy.

Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.

PURPOSE: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting. METHODS: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included. RESULTS: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85). CONCLUSION: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.