Prognostic significance of mucinous histology in left­sided metastatic colorectal cancers with wild­type RAS and evaluation of backbone chemotherapy regimens.

Mucinous colorectal adenocarcinoma (MCAC) is a distinct subtype of colorectal carcinoma (CRC). The prognostic and predictive significance of mucinous histology remains controversial. It was aimed to investigate the prognostic and/or predictive role of mucinous histology in left-sided metastatic CRC (mCRC) with wild-type RAS. This is a retrospective multicenter study of mCRC treated with first line anti-EGFR combined 5-fluorouracil based chemotherapy (CT). Patients were stratified according to presence (>50% extracellular mucin) or absence of mucinous histology. Survival analyses were performed firstly regardless of treatment options and then performed as separating according to CT regimens. Additional analyses were performed for MCAC patients considering backbone CT regimens. A total of 125 patients were included, consisting of 40 (32.0%) patients with MCAC and 85 (68.0%) patients with non-MCAC. Median follow-up time was 19.7 months. Median progression-free survival (PFS) was 10.7 months in all patients, and PFS was lower in MCAC than non-MCAC (9.9 vs. 12.0 months, respectively, P=0.005). Median overall survival (OS) was 25.7 months in all patients. OS was lower in MCAC than non-MCAC (22.8 vs. 29.7 months, respectively, P=0.005). When considering backbone CT regimens, in multivariate analyses, mucinous histology was an independent prognostic factor for OS in both for mFOLFOX6 (HR: 1.92, P=0.04) and FOLFIRI (HR: 2.04, P=0.04) groups and was associated with poor PFS in only mFOLFOX6 (HR: 3.86, P<0.001) group. When outcomes were analyzed for the MCAC group, median OS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 22.47 and 14.22 months, respectively (P=0.41). Median PFS of MCAC patients receiving mFOLFOX6 and FOLFIRI was 10.15 and 8.11 months, respectively (P=0.73). The study revealed poor prognosis of mucinous histology, both in whole study population and in backbone CT groups. Moreover, lower PFS of MCAC patients was revealed in only mFOLFOX6 group and this finding may be a valuable issue for the future research. However, considering all analyses, the present results did not indicate a special benefit of any backbone CT regimen for MCAC patients.

The Predictive Importance of Body Mass Index on Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer.

Purpose: The aim of the study was to investigate the effects of body mass index (BMI) on the response to neoadjuvant chemotherapy (NACT) in Turkish patients with local and locally advanced breast cancer. Methods: The pathological responses for the breast and axilla were assessed according to the Miller-Payne grading (MPG) system. Tumors were grouped into molecular phenotypes and classified as response rates according to the MPG system after the completion of NACT. A 90% or greater reduction in tumor cellularity was considered a good response to treatment. Additionally, patients were grouped according to BMI into <25 (group A) and ≥25 (group B). Results: In total, 647 Turkish women with breast cancer were included in the study. In the univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and BMI were assessed to determine which of these factors were associated with a ≥90% response rate. Stage, HER2 positivity, triple-negative breast cancer (TNBC; ER-negative, PR-negative, and HER2-negative breast cancer), grade, Ki-67 levels, and BMI were found to be the statistically significant factors for a ≥90% response rate. In the multivariate analysis, grade III disease, HER2 positivity, and TNBC were found to be the factors associated with a high pathological response. Meanwhile, hormone receptor (HR) positivity and a higher BMI were associated with a decreased pathological response in patients receiving NACT for breast cancer. Conclusion: Our results show that a high BMI and HR positivity are associated with a poor response to NACT in Turkish patients with breast cancer. The findings presented in this study may guide novel studies to examine the NACT response in obese patients with and without insulin resistance.

The impact of adjuvant oxaliplatin and tumor sidedness on the overall survival of stage IIB colon cancer patients: a multicentre study.

The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.

Is adipose tissue metabolic activity a predictor of pathological responses to neoadjuvant treatment in breast cancer.

INTRODUCTION AND OBJECTIVE: Prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer is essential for optimal treatment strategy. The current approach of adjuvant or neoadjuvant treatment is based on the molecular subtype. Obesity may have affected chemotherapy response. This study aims to evaluate the relationship between metabolic activity of adipose tissue (AT) and pathological responses to NAC. And to define the association with body mass index (BMI) and metabolic parameters of standardized uptake value (SUV) of adipose tissue measured by positron emission computed tomography (PET/CT). MATERIAL AND METHODS: One-hundred and sixteen consecutive patients with stage II and III breast cancer who underwent PET/CT before receiving NAC, were evaluated in the study. Metabolic parameters of visceral adipose tissue (VAT-SUV), subcutaneous adipose tissue (SAT-SUV), and calculated SUV of visceral-to-subcutaneous ratio (V/S-ratio) were regarded. The relationship between SUV of AT and pathologic response was evaluated from medical records retrospectively. RESULTS: Univariate-analysis revealed that good pathological response was significantly associated with clinical stage (P<.001), HER-2 positivity (P<.001), VAT-SUV (P=.037), VAT-density (P=.043) and V/S-ratio (P=.003). In multivariate-analysis clinical stage, HER-2 positivity and V/S-ratio were found to have statistically effect on pathological response. VAT-volume (P<.001), VAT-SUV (P=.016), SAT-volume (P<.001) and SAT-SUV (P<.001) has positive correlation with BMI value. On the other hand, V/S-ratio (P=.039) and SAT-density (P=.003) has negative correlation with BMI. CONCLUSION: Metabolic activity of AT is associated with BMI and effected chemotherapy responses. LowV/S ratio was associated with high BMI and poor pathological response to NAC. V/S ratio may be a useful marker for the prediction of NAC responses.

Is the benefit of using adjuvant capecitabine in patients with residual triple-negative breast cancer related to pathological response to neoadjuvant chemotherapy?

BACKGROUND: Triple-negative-breast-cancer (TNBC) has a poor prognosis if pathologic complete response (pCR) cannot be achieved following neoadjuvant chemotherapy (NAC). The group of patients that benefit most from adjuvant capecitabine remains unclear. MATERIALS AND METHODS: We analyzed data of 160 consecutive patients with residual TNBC from eight cancer-center. Pathologic response was defined into two groups as having good-pathologic-response (MillerPayneGrading (MPG) IV-III) or poor-pathologic-response (MPG I-II). The characteristics of patients were compared regarding adjuvant capecitabine usage. RESULTS: Univariate-analysis revealed that age, histology, clinical-stage, tumor-size, lymph-nodes number, menopausal status, and pathological-stage were significantly different between two groups. In multivariate-analysis, menopausal status (p = 0.043) and residual tumor-size (p < 0.001) were found to be independent prognostic factors for pathological response. The hazard-ratio for disease recurrence and death in the poor-response group with adjuvant capecitabine was 2.94 (95% confidence-interval (CI), 1.21 to 7.10; p = 0.016) and 4.080 (95% CI, 1.22 to 13.64; p = 0.022), respectively. DFS (p = 0.58) and OS (p = 0.89) improvements with adjuvant capecitabine were not demonstrated in good-response groups. CONCLUSION: This multicenter-study suggested that only the poor-response group to NAC achieved benefit from adjuvant capecitabine. Postmenopausal status and residual tumor-size were related to poor prognosis.

FOLFIRINOX versus gemcitabine plus nab-paclitaxel as the first-line chemotherapy in metastatic pancreatic cancer.

Pancreas cancer (PCa) is one of the mortal cancer types with ranking as fourth leading cancer death in both sexes together. FOLFIRINOX (FFX) and Gemcitabine plus nab-paclitaxel (GNP) are approved as first-line metastatic treatment in PCa. The aim of this study was to compare the clinical outcomes, treated with FFX and GNP as first-line metastatic PCa. Medical records of patients diagnosed with metastatic PCa, from January 2010 to December 2020 were analyzed. This study was a retrospective cohort, multi-institution analysis. The focus of the present study was to compare the efficiency of FFX and GNP chemotherapy combinations in the first-line treatment of PCa. Efficacy had been measured by progression-free survival (PFS) and overall survival (OS). 182 patients diagnosed with PCa receiving metastatic first-line treatment were retrospectively analyzed. Patients were divided into two groups one hundred and three (56.6%) patients treated with FFX and seventy-nine (43.4%) patients treated with GNP. Patients in the FFX group were younger and had a better ECOG performance status. Overall response rate (ORR) was 69.9% in FFX and 37.9% in GNP group (p: 0.000). Disease control rate (DCR) was 73.7% in patients treated with FFX and 39.2% in GNP group (p: 0.000). The median PFS was 8.3 months (FFX 9.1 vs. GNP 6.7, HR = 0.25, 95% CI: 0.16-0.38) the median OS was 12.2 months (FFX 14.1 vs. GNP 9.6, HR = 0.48, 95% CI: 0.31-0.72). Guidelines recommend both FFX and GNP regimens as a first-line treatment of metastatic PCa. In clinical routine, it is still unclear which regiment is more effective. The present study showed increased survival parameters with FFX versus GNP with similar toxicity profiles.

The role of mean platelet volume in nonalcoholic fatty liver disease without cardiovascular comorbidities, obesity and diabetes mellitus.

BACKGROUND: While the relation of mean platelet volume (MPV) with inflammatory diseases is obvious, its role in nonalcoholic fatty liver disease (NAFLD) without cardiovascular comorbidities, obesity and diabetes mellitus is not clear. METHODS: A total of 249 patients (nonobese, nondiabetic and not having cardiac diseases) who underwent an abdominal ultrasonography assessment were enrolled. They were divided according to the absence (group 1) or presence (group 2) of hepatic steatosis. The patients with steatosis were further divided according to the severity of steatosis as group 2a (grade 1), 2b (grade 2) and 2c (grade 3). The demographic and laboratory features were compared between groups. RESULTS: Hepatic steatosis was absent in 120 patients and detected in 129 patients (grade 1, 2, 3 hepatic steatosis in 75, 49 and 5 patients, respectively). BMI, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and serum AST, ALT, triglyceride levels were significantly higher in group 2 than in group 1 (P < 0.001, P < 0.001, P < 0.001, P = 0.005, P < 0.001, respectively). BMI, serum AST and triglyceride levels were significant factors for NAFLD (P < 0.001, P = 0.018, P = 0.001). MPV was neither different between groups (P > 0.05) nor a predictor factor for NAFLD (P > 0.05). CONCLUSION: MPV is a useless parameter to detect NAFLD without cardiovascular comorbidities, obesity and diabetes mellitus.

Efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer.

Aim: To evaluate the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer. Methods: We retrospectively included 138 patients who were given trastuzumab-based chemotherapy as first-line treatment and analyzed the relationship between clinical response rates and maintenance treatment status and survival outcomes. Results: In the whole group, the median progression-free survival and overall survival were 10.2 and 16 months, respectively. Clinical response was obtained in 79% of patients. The median overall survival was 16.9 months in follow-up group and 19.0 months in the maintenance group in patients with clinical response. Continuation of maintenance trastuzumab created a significant survival advantage (p = 0.021). Eastern Cooperative Oncology Group performance status 2 (hazard ratio [HR]: 2.02), grade 3 (HR: 1.78) and more than four metastatic lesions (HR: 1.67) were determined as risk factors for death. Conclusion: We recommend the continuation of maintenance trastuzumab in patients with clinical response, but those with identified risk factors may not benefit from treatment because life expectancy may be low.

Gastric cancer has a poor prognosis despite available treatments. Inclusive studies are still needed with real-life data. Our research retrospectively evaluated the efficacy of trastuzumab and potential risk factors on survival in patients with HER2-positive metastatic gastric cancer who received trastuzumab-based chemotherapy as first-line therapy. In total, 138 patients were included in this study. Clinical response to trastuzumab-based chemotherapy was obtained in 79% of the patients. We also divided the patients who had a clinical response into two groups according to whether they received maintenance therapy. In the present study, trastuzumab administration had compatible survival outcomes with recent studies. Continuation of trastuzumab maintenance treatment provided a survival advantage in patients with clinical response. We suppose that maintenance trastuzumab may be recommended in patients with clinical responses to the first-line treatment. Furthermore, Eastern Cooperative Oncology Group Performance Status 2, grade 3 and having more than four metastatic lesions were determined as risk factors for death. Therefore, although we recommend maintenance of trastuzumab in patients with clinical response, those with identified risk factors may not benefit from treatment.

Role of tumor location on high-grade serous ovarian cancer prognosis.

OBJECTIVES: Ovarian cancer is associated with the highest mortality of gynecologic cancers. Epidemiological and genetic factors of ovarian cancer development are clearly defined but prognostic factors have not been adequately identified. Right and left ovarian cancers seem to act different behaviors at high-grade serous ovarian cancer (HGSOC) prognosis. The aim of this study is to explain this prognostic role of its sidedness. The aim of this study is to explain this prognostic role of its sidedness. MATERIAL AND METHODS: We reviewed 160 consecutive patients with Figo stage 1-3 HGSOCs and undergone surgery at two high-volume hospitals. Prognostic effects of primary tumor location onset were evaluated in terms of 5-year disease free survival and overall survival rate. RESULTS: One hundred-sixty patients with ovarian cancer records were analyzed using the Kaplan-Meier method, that demonstrated a significant difference in the 5-year disease-free survival rates between right and left-sided cancers for all stages (44.6% vs 78.5%, p < 0.001). Also, there was significant difference in the 5-year overall survival rates between the two groups (71.1% vs 91.9%, p = 0.020). CONCLUSIONS: Tumor location within the HGSOC seems to be a compelling prognostic factor ovarian cancer. Further prospective studies are needed in order to support our hypothesis.

Initial Ca 125 Value as a Predictive Marker for High-grade Serous Ovarian Cancer.

OBJECTIVE: To determine the relevance between the cut-off level of cancer antigen 125 (CA 125) level and long-term prognosis in high-grade serous ovarian cancer (HGSCs). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Departments of Oncology, Medeniyet University Goztepe Education and Research Hospital, and Kartal Lutfi Kirdar Education and Research Hospital, Istanbul, Turkey, from January 2017 to June 2019. METHODOLOGY: Medical records of 230 women with HGSC were reviewed randomly from two Oncology Clinics. Descriptive analysis and CA 125 marker levels were evaluated with five years of disease-free survival rate (DFS) and overall survival rate (OS). Patients were divided into groups of high and low initial CA 125 levels (cut-off ≥385U/ml). The ability of initial serum CA 125 levels in predicting the presence of marker-recurrence of ovarian cancer were analysed using ROC (Receiver operating characteristics) curve analysis. RESULTS: Statistically significant predictive value of initial CA 125 level was calculated as 385U/ml (p=0.008). The 5-year DFS of high and low CA 125 levels for all stages in HGSC was statistically significant (p<0.001). The sub-group analysis demonstrated that the significant survival difference was especially in FIGO stage III. Patients with HGSC <385 U/ml had a significantly improved 5-year DFS and OS rates within stage III disease: 5-year DFS (p = 0.008) and 5-year OS (p = 0.004) according to the stratification of CA 125 level. CONCLUSION: Initial CA 125 level appeared to be of beneficial clinical predictive value for HGSC. Key Words: Initial CA 125, Tumor marker, High-grade serous ovarian cancer, Disease-free survival, Overall survival, Predictive value.

Clinical and Pathological Characteristics of Patients with High-Risk Breast Cancer Based on BRCA Mutation Profiles: A Retrospective Study.

OBJECTIVE: This study aimed to determine the differences in clinicopathological features of Turkish patients with high-risk breast cancer based on the mutation status of two breast cancer susceptibility genes (BRCA1/2) . MATERIALS AND METHODS: This study enrolled patients with invasive breast cancer who have been evaluated for BRCA1/2 mutations due to the presence of high-risk factors admitted to two tertiary referral centers in Turkey. Clinical and histopathological features were analyzed in BRCA1 mutation carriers, BRCA2 mutation carriers, and non-carriers. RESULTS: A total of 302 patients with a mean age of 44.2±9.9 (22-82) years were included. BRCA1/2 mutation was found in 75 (24%) patients, of whom 41 (13.6%) were BRCA1 mutation carriers and 37 (12.3%) were BRCA2 mutation carriers. Moreover, 104 (34.4%) and 4 (1.3%) patients had family history of breast and ovarian carcinoma, respectively. The rates of triple negativity (56.1%), histologic grade 3 (65.9%), and lymphovascular invasion (78%) were significantly higher in BRCA1 mutation carriers than in non-carriers and BRCA2 mutation carriers. Furthermore, 87% of triple-negative BRCA1 mutation carriers had histologic grade 3 tumors compared with 38.9% in non-triple-negative BRCA1 mutation carriers, and the difference was significant. CONCLUSION: Findings of this study showed that BRCA1-related breast cancers represent a distinct group with unique pathological features, which are usually associated with a poor prognosis.

Prognostic factors of ado-trastuzumab emtansine treatment in patients with metastatic HER-2 positive breast cancer.

BACKGROUND: Ado-trastuzumab emtansine is an antibody-drug conjugate that combines the cytotoxic activity of emtansine with human epidermal growth factor receptor 2-targeted antitumor features of trastuzumab. OBJECTIVE: We conducted a study of metastatic breast cancer patients treated with trastuzumab emtansine. By evaluating progression-free survival, overall survival, and response rates, we aimed to find prognostic factors of trastuzumab emtansine treatment. METHODS: Our study is a single-center, retrospective, observational study. We have clinical data from 78 patients treated with trastuzumab emtansine for metastatic breast cancer, from May 2016 through May 2019, at Kartal Dr Lutfi Kirdar Education and Research Hospital, Medical Oncology Department. Our objective is to assess the survival and response rates in trastuzumab emtansine-treated individuals and the factors associated with survival. The factors we analyzed were cancer antigen 15-3 sensitivity, Eastern Cooperative Oncology Group-Performance Status, presence or absence of visceral metastases, presence or absence of cranial metastases, and treatment-associated thrombocytopenia. RESULTS: Among 78 patients, median progression-free survival was 7.8 months, and overall survival was 21.1 months. Twenty of the patients had an objective tumor response. The results showed that trastuzumab emtansine was tolerable with a manageable safety profile and consistent with the results of the previous literature. Mostly seen adverse events were anemia, thrombocytopenia, fatigue, and increased levels of alkaline phosphatase. Patients with Eastern Cooperative Oncology Group-Performance Status = 2 had worse progression-free survival and overall survival compared to ones with Eastern Cooperative Oncology Group-Performance Status < 2; progression-free survival and overall survival are worse in cancer antigen 15-3-sensitive breast cancer patients. According to our findings, treatment-associated thrombocytopenia was a significant prognostic factor for survival. Patients with thrombocytopenia had 12 months progression-free survival, whereas patients without thrombocytopenia had only 4.1 months progression-free survival. In like manner, overall survival was much better in the thrombocytopenia-experienced patients as 29.5 versus 11.8 months. CONCLUSIONS: Trastuzumab emtansine prolongs progression-free survival and overall survival with a manageable safety profile. Thrombocytopenia, Eastern Cooperative Oncology Group-Performance Status, and cancer antigen 15-3 are correlated with progression-free survival and/or overall survival.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

OBJECTIVE: Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). MATERIAL AND METHOD: We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. RESULTS: Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. CONCLUSION: TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Evaluation of pharmacist interventions and commonly used medications in the geriatric ward of a teaching hospital in Turkey: a retrospective study.

PURPOSE: Aging increases the prevalence of diseases. The elderly population is consequently often exposed to complex medication regimens. Increased drug use is one of the main reasons for drug-related problems (DRPs). The primary objective of this study was to define and classify DRPs, pharmacist interventions, and frequently prescribed medications in relation to possible DRPs in patients admitted to the geriatric ward of a teaching hospital in Turkey. PATIENTS AND METHODS: Pharmacist medication review reports for 200 orders of 91 patients (mean age: 80.33±0.46) were analyzed retrospectively. RESULTS: A total of 1,632 medications were assessed and 329 interventions were proposed for possible DRPs in 156 orders. A total of 87.5% of the patients used five or more drugs (mean: 8.17±0.23). The number of DRPs per order was higher when polypharmacy was present (1.04±0.15 vs 1.66±0.11, P<0.05). In 71.31% of the cases, adverse drug events were recognized as the problem. The principal cause of possible DRPs was determined as drug interactions (40.12%). Only 22 potentially inappropriate medications were prescribed. The most common interventions included monitoring drug therapy (31.0%), stopping the drug (20.06%), and changing dosage (13.98%). The acceptance rate of pharmacist interventions by treating geriatrician was 85.41%. The most frequently prescribed drugs were for the nervous system, alimentary tract and metabolism, and cardiovascular system (n=358, 314, and 304, respectively). The pharmaceutical forms of 23 drugs were deemed inappropriate by pharmacists. CONCLUSION: Clinical pharmacy services are still not properly implemented in Turkey. The study highlights ways in which clinical pharmacy services can be instrumental in a geriatric ward. The high acceptance rates of pharmacist recommendations concerning a wide variety of DRPs and different classes of drugs indicate that advanced collaboration among geriatricians and pharmacists is possible in interdisciplinary geriatric assessment teams in Turkey.