Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Impact of 68Ga-PSMA PET/CT on Survival and Management in Prostate Cancer.

BACKGROUND: 68Ga-labeled prostate-specific membrane antigen positron emission tomography-computed tomography (68Ga-PSMA PET/CT) has led to altered treatment plans for prostate cancer (PCa) patients. OBJECTIVE: This study aimed to investigate the impact of 68Ga-PSMA PET/CT on overall survival (OS) and management in PCa. METHODS: Consecutive 100 patients who had 68Ga-PSMA PET/CT and conventional imaging (CI) were included in this retrospective study. Disease stages and treatment plans according to both CI and 68Ga-PSMA PET/CT were compared. The effect of 68Ga-PSMA PET/CT on OS was assessed. RESULTS: After 68Ga-PSMA PET/CT, the stage changed in 64 patients (64%). By the reason of 68Ga-PSMA PET/CT findings, treatment plans based on CI were changed in 73 patients (73%). According to the ROC analysis, patients with a PSA value below 8 had higher rates of change in staging (p<0.0001) and treatment (p=0.034). Both a PSA below 8 (OR 8.79 95% CI (2.72-28.43), p<0.001), and having a hormone-sensitive disease at the time of imaging (OR 5.6 95% CI (1.35-23.08), p=0.017) were significant independent factors predicting change in staging with 68Ga-PSMA PET/CT. The results of a phi correlation coefficient analysis showed a significant relationship between therapy and changes in staging (ϕ=0.638, p<0.0001). Two-year OS was statistically different in hormone-sensitive patients with and without treatment change (95% vs 81%, p=0.006). CONCLUSION: 68Ga-PSMA PET/CT has the effect of changing the treatment in 73% of PCa patients. There is a positive correlation between the changes in staging and treatment. Survival of hormone sensitive patients has improved due to treatment changes based on PET/CT findings.

Simple and easily accessible prognostic markers in ewing sarcoma; neutrophil-lymphocyte ratio, neutrophil-platelet score and systemic-inflammation index.

Background: Inflammation markers are the new point of view in cancer due to increasing data on the interaction of immune system with tumor cells and their prognostic and predictive importance were found in many different types of solid tumors. Therefore, we aimed to evaluate the prognostic value of neutrophil-lymphocyte ratio (NLR), neutrophil-platelet score (NPS), and systemic inflammation index (SII) in Ewing sarcoma patients in which risk groups are still not clearly defined. Methods and Results: A total of 64 patients were evaluated retrospectively. Receiver operating characteristic analysis was performed to find cut-off values for NLR and SII. Survival analysis was calculated by using Kaplan-Meier method. Cox regression analysis was performed to determine prognostic factors such as age, stage, and neoadjuvant chemotherapy were statistically significant prognostic factors for OS in multivariate analysis. While patients with low NLR and SII had longer OS (P = 0.003 and P = 0.018), patients with high NPS score had shorter OS (67.7 vs 21.7 months, P = 0.001). Conclusion: Patients with lower NLR, NPS, and SII score have a better prognosis compared with those with higher NLR, NPS, and SII score and these simple parameters may be monitoring tools of the tumor microenvironment.

Treatment Outcomes and Prognostic Factors in N3 Stage Gastric Cancer After Curative Resection: A Real World Data.

Purpose: N3 gastric cancer is characterized by a fairly high lymph node metastasis burden and poor outcome despite optimal therapy. Given the limitations of TNM classification, a comprehensive evaluation tool is necessary to predict the prognosis of patients with N3 gastric cancer who underwent curative surgery. This study aims to explore the outcomes and clinicopathologic prognostic factors affecting the overall survival (OS) of patients with N3 gastric cancer after surgery. Methods: Data on patients with N3 gastric cancer who underwent (sub)total gastrectomy and regional lymph node dissection between November 2005 and September 2018 (n = 169) were analyzed by Cox regression to determine the independent prognostic factors for OS. Results: The multivariable analysis established that gender, patient performance status, metastatic lymph node ratio (MLNR), tumor grade, and adjuvant chemotherapy are significantly associated with OS. The five-year OS of the study population was 15%. Adjuvant chemoradiotherapy was applied to 72% of the patients, which resulted in an improvement in recurrence-free survival but not OS. Recurrence occurred in 103 (75%) patients, in which the most frequent recurrence site was distant metastasis. Conclusion: Male gender, poor performance status, grade 3 tumor, MLNR > 0.37, and not receiving adjuvant chemotherapy are predictors of poor prognosis in N3 gastric cancer after curative resection. Considering the high recurrence rates of this group, prospective studies are needed to optimize treatment strategies.

The Prognostic and Functional Impact of Sprouty 2 Expression in Non-small Cell Lung Cancer.

OBJECTIVE: We represent Sprouty 2 (Spry2) expression analysis and its association with key driver mutations and clinical features of patients with non-small cell lung cancer as the largest ex vivo data. METHODS: The strength of Spry2 expression was evaluated using the immunoreactivity score (IRS), which was calculated using the following formula: IRS=(staining intensity score) SI×(percentage of positively stained cells) PP. The median IRS score was defined as the cutoff value. Patients were grouped as "weak immunoreactivity score" (IRS: 0 to 4) or "strong immunoreactivity score" (IRS: ≥4) with respect to the IRS score. RESULTS: The intensity and percentage of Spry2 staining were significantly lower in tumor tissues than in normal lung tissues ( P <0.0001). Patients' characteristics were similar for both groups, except for smoking status and, brain and lymph node metastasis. Overall survival of patients with a strong immunoreactivity score was significantly lower than those with a weak immunoreactivity score among metastatic patients (6.9 mo vs. 13.6, P =0.023) and adenocarcinoma histology (7.0 mo vs. not reached, P =0.003). CONCLUSION: Spry2 expression was lower in tumor tissues than in normal lung parenchyma. Increased expression of Spry2 is associated with poor prognosis. There were no significant associations between epidermal growth factor receptor, anaplastic lymphoma kinase, or c-ros oncogene 1 rearrangement and Spry2 expression. Despite the absence of KRAS mutational analysis, the clinical and epidemiological features of patients suggested that KRAS mutation might be an underlying determinant factor of the functional role of Spry2 in non-small cell lung cancer.

The effectiveness of adjuvant treatment approaches for resectable esophageal cancer: A single-center experience.

AIMS AND BACKGROUND: In general, neoadjuvant treatment is the standard for clinical stage II/III esophageal cancer (EC), whereas the effect of adjuvant treatment on survival still remains controversial. The aim of this study was to investigate the efficacy of adjuvant treatment modalities on the survival of EC patients. PATIENTS AND METHODS: A total of 63 patients with stage II-IVA EC who had undergone curative surgery between the years 2002 and 2020 were included in the study. Patients' data were retrospectively collected from oncologic follow-up files. Various treatment regimens were administered during this period, including chemotherapy and chemoradiotherapy. RESULTS: The median age was 56 years (24-73), and the number of males was slightly higher than females (male/female: 33/30). While 32 (51%) patients received postoperative adjuvant treatment, the remaining 31 (49%) patients underwent surgery alone. The median overall survival (OS) was 45.9 months (95% confidence interval [CI]: 25.1-66.8) in patients receiving adjuvant therapy and 37.6 months (95% CI: 20.9-54.4) in patients not receiving adjuvant therapy. The 8.3-month survival difference was statistically insignificant (P = 0.54). The 1-, 3-, and 5-year OS rates were 87.5% versus 77.4%, 58.4% versus 51.6%, and 40.8% versus 27.6% for patients with and without adjuvant therapy, respectively. Pathological stage (P = 0.028) and lymph node status (P = 0.044) were significant prognostic factors for survival. CONCLUSIONS: This study did not support the benefit of adjuvant treatment compared with surgery alone in completely resected EC patients. The reason for this result may be related to the small sample size and different treatment regimens due to the change in treatment options over time.

The Comparison of mDCF and mFOLFOX-6 as First-Line Treatment in Metastatic Gastric Cancer.

INTRODUCTION: Fluoropyrimidine and platinum-based chemotherapy regimens are widely accepted for metastatic gastric cancer (GC). Because of drug toxicity, a combined two-drug cytotoxic drug regimen is recommended for first-line therapy, while three-drug cytotoxic regimens are recommended for patients with medically fit and better performance status. In this study, it was aimed to compare modified FOLFOX-6 (mFOLFOX-6) and modified DCF (mDCF) regimens in terms of survival and side effects in first-line treatment in metastatic GC. METHODS:  We retrospectively reviewed the clinical record of patients with metastatic gastric or gastro-esophageal junction cancer who had received mDCF or mFOLFOX-6 as the first-line treatment, and followed up in our center between February 2013 and December 2020. The data were collected from the patients' registration database of the hospital and oncologic follow-up files of our center. In the mDCF arm, docetaxel 60 mg/m2 and cisplatin 60 mg/m2 on day 1 intravenous (i.v.) infusion, and 600 mg/m2 5-fluorouracil (FU) as a continuous infusion for five days were administrated every three weeks for up to six cycles. In the mFOLFOX-6 arm, 85 mg/m2 oxaliplatin and 400 mg/m2 LV as an i.v. infusion over two hours and a 5-FU bolus of 400 mg/m2 as a 10-minute infusion, followed by 2.400 mg/m2 5-FU as a 46-hour continuous infusion were administrated every two weeks for up to six cycles. Univariate and multivariate analyses for overall survival (OS) were performed by Cox proportional hazards regression model. Survival analysis was performed by the Kaplan-Meier method with the Long-rank test. P-value <0.05 was considered statistically significant. RESULTS: A total of 70 patients included into the study. Of those, 40 (57%) patients had received mDCF and 30 (43%) had received FOLFOX-6 regimens as first-line treatment. There were no complete responses in both groups. The partial response rate was 28% and 27% for mDCF and mFOLFOX-6, respectively. There was no statistically significant difference regarding treatment response for both groups (p=0.787). The median OS was 13.9 months (95% CI: 7.5-20.4) in the mDCF arm, and 10.4 months (95% CI: 6.4-14.4) in the mFOLFOX-6 arm (p=0.409). The median progression-free survival (PFS) was 5.2 months (95% CI: 3.6-6.9) in the mDCF arm, and 6.4 months (3.2-9.6) in the FOLFOX-6 arm (p=0.126). The ratio of dose reduction, treatment delay, and neutropenic fever were not statistically different between treatment arms. CONCLUSION: The present study demonstrated that proper patient selection for metastatic GC may give rise to comparable survival rates without increased toxicity. mFOLFOX-6 and mDCF had similar response rates, OS, PFS, and side effect profiles.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

The evaluation of the role of BMI and insulin resistance on inflammatory markers, PAI-1 levels and arterial stiffness in newly diagnosed type 2 diabetes mellitus patients.

BACKGROUND: Increased cardiovascular risk, represented by endothelial inflammation, probably starts with the very first course of type-2 diabetes (T2DM). Almost 85.2% of all T2DM patients are overweight or obese. Thrombosis accounts 80% of all deaths in patients with diabetes. The thrombotic-fibrinolytic equilibrium shifts in favor of thrombosis by plasminogen activator inhibitor-1 (PAI-1). PAI-1 secretion is induced primarily by CRP. PAI-1 overexpression predisposes unstable plaque development. The contribution of obesity and diabetes to this process is not clearly understood. In this study, we aimed to investigate comparison of inflammatory markers, PAI-1 levels and arterial stiffness according to BMI and impaired glucose metabolism in patient with newly diagnosed T2DM. METHODS: Newly diagnosed 60 T2DM patients were enrolled. Demographics and measurements were noted. Liver (AST, ALT), kidney (urea, creatinine, albumin/creatinine ratio), metabolic (fasting blood glucose, post-prandial blood glucose, insulin, c-peptide, HbA1c, total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglyceride) parameters, inflammatory markers [hsCRP, fibrinogen]), PAI-1 levels and pulse wave velocity was measured from all participants. The results were compared. RESULTS: Inflammatory markers and PAI-1 levels were significantly elevated in obese group compared to overweight participants. The correlation analysis showed that waist and hip circumferences, high-sensitive CRP, fibrinogen and PAI-1 levels were positively correlated with BMI but not with HbA1c levels. CONCLUSIONS: The results of our study showed that lipid levels, glycemic and blood pressure values of the obese and overweight patients were similar. BMI affects inflammatory markers and PAI-1 levels independent of glucose regulation and insulin resistance in newly diagnosed T2DM. According to the current study BMI is found to be more prominent in terms of inflammatory markers and PAI-1 levels compared to insulin resistance and impaired glucose metabolism in newly diagnosed T2DM.

Is there any clinical or laboratory predictive factor for cetuximab-induced skin toxicity?

BACKGROUND: We aim to explore the predictive role of clinical and hematological parameters for cetuximab-induced skin toxicity (CI-ST) and survival outcomes in patients according to risk categories.RESEARCH DESIGN AND METHODS: The optimal cut-off values for hematological parameters were assessed by the Receiver Operating Characteristic (ROC) analysis. Patients were classified as High risk, Intermediate risk and Low risk subgroups with respect to platelet to lymphocyte ratio (PLR) and red blood cell count (RBC) values. Kaplan-Meier test was used for survival analysis, and outcomes were analyzed by Log-rank test. P-value <0.05 considered as statistically significant.RESULTS: Among hematological parameters, only PLR and RBC were statistically significant prognostic factors.Optimal cut-off value for PLR was 196.2 (82.9% sensitivity and 61.1% specificity), and 4.610x106/µL for RBC count (65.9% sensitivity and 81.1% specificity). Patients in high risk group had increased risk with an OR:69.34 (p<0.0001), and in the intermediate risk group had an OR:28.73 (p=0.002) for CI-ST. De novo metastatic patients had 9.11-fold increased risk for CI-ST compared to recurrent metastatic patients (p=0.028).CONCLUSION: Our study indicates that risk categories based on PLR and RBC can predict CI-ST and de novo metastatic patients had higher risk for CI-ST.

A Comparison of Osseous and Extraosseous Ewing Sarcoma.

OBJECTIVE: To compare the clinicopathological characteristics, treatment responses, survival analysis of osseous Ewing sarcoma (OES) and extraosseous ES (EES). STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Ankara City Hospital and Ankara Numune Training Research Hospital Medical Oncology Clinics from January 2005 to February 2020. METHODOLOGY: Clinicopathological characteristics of histologically confirmed ES/PNET and followed up, and treatment modalities were recorded from patients' registration data-base of the hospital. Lactate dehydrogenase (LDH), alkaline phosphatase (ALP), hemoglobin were measured before chemotherapy or surgery. The patients with a second cancer, gall bladder/biliary tract diseases, viral hepatitis and other bone diseases were excluded. RESULTS: Sixty seven patients evaluated retrospectively. Out of the total patients, 56.7% consisted of OES, and 43.3% consisted of EES. The median age of the EES group (26 years) was significantly higher than that of the OES group (22 years, p = 0.008). The most common metastasis region was lung in both the groups. Age, LDH levels and stage of the disease were found to be statistically significant prognostic factors in univariate and multivariate analysis. The median OS of patients who started with local treatment (surgical, surgical ± radiotherapy) and followed up with chemotherapy was 82.6 months (95% CI, 55.2-110.1), while the median OS of patients who received local treatment between or after chemotherapy was 43.4 months (95% CI, 13.2-73.6, p = 0.042). CONCLUSION: Patients with extrosseus ES were significantly older. Age, LDH levels, stage of disease, local treatment followed by systemic therapy are important associated factors. Key Words: Osseous ewing sarcoma, Extraosseous ewing sarcoma, Chemotherapy, Local treatment.

"Swords and Shields" against COVID-19 for patients with cancer at "clean" and "pandemic" hospitals: are we ready for the second wave?

PURPOSE: COVID-19 will continue to disrupt the diagnosis-treatment process of cancer patients. Dr. Abdurrahman Yurtaslan Ankara Oncology Hospital has been considered as a 'non-pandemic' center ('clean') in Ankara, the capital city of Turkey. The other state hospitals that also take care of cancer patients in Ankara were defined as 'pandemic' centers. This study aimed to evaluate hospital admission changes and the precautionary measures in clean and pandemic centers during the pandemic. The effect of these measures and changes on COVID-19 spreading among cancer patients was also evaluated. METHODS: The patients admitted to the medical oncology follow-up, new diagnosis, or chemotherapy (CT) outpatient clinics during the first quarter of pandemic period (March 15-June 1, 2020) of each center were determined and compared with the admissions of the same frame of previous year (March 15-June 1, 2019). COVID-19 PCR test results in clean and pandemic centers were compared with each other. Telemedicine was preffered in the clean hospital to keep on follow-up of the cancer patients as 'noninfected'. RESULTS: In the clean hospital, COVID-19-infected patients that needed to be hospitalized were referred to pandemic hospitals. COVID-19 test positivity rate was eight-fold higher for outpatient clinic admissions in pandemic hospitals (p < 0.001). The number of patients admitted new diagnosis outpatient clinics in both clean and pandemic hospitals decreased significantly during the pandemic compared with the previous year. CONCLUSION: We consider that local strategic modifications and defining 'clean' hospital model during infectious pandemic may contribute to protect and treat cancer patients during pandemic.

Albumin-to-Alkaline Phosphatase Ratio: Does It Predict Survival in Grade 1 and Grade 2 Neuroendocrine Tumors?

OBJECTIVES: Neuroendocrine tumors (NETs) are very heterogeneous tumors. This study aimed to evaluate prognostic value of an albumin-to-alkaline phosphatase (ALP) ratio (AAPR) in well-differentiated NETs. METHODS: A total of 110 patients were included in this study. Albumin-to-alkaline phosphatase ratio was calculated by dividing albumin concentration (g/dL) to ALP level (U/L). Cutoff value for AAPR was determined by receiver operating characteristic analysis. Survival analysis was performed by Kaplan-Meier method with the log-rank test. A P value of less than 0.05 was considered statistically significant. RESULTS: The optimum cutoff value for AAPR was 0.028. Patients were divided into 2 groups as patients with AAPR of 0.028 or less (n = 22, 20%) and with AAPR of greater than 0.028 (n = 88, 80%). Patients with AAPR of greater than 0.028 had statistically longer overall survival compared with patients with 0.028 or less (not reached vs 96.8 months, P = 0.001). In addition, AAPR has been shown to be an independent prognostic factor for overall survival in multivariate analysis (hazard ratio, 3.99; 95% confidence interval, 1.26-12.61, P = 0.018). CONCLUSIONS: Patients with higher AAPR had more favorable prognosis compared with patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.

Systemic treatment options for growing teratoma syndrome: A single-center experience with a comprehensive review of the literature.

BACKGROUND: Growing teratoma syndrome (GTS) is a very uncommon phenomena. Given its lower prevalence, there is little data about clinichopathological features and management of GTS. Literature about disease mostly composed of case reports. In this study, we aimed to report patients characteristics and treatment modalities in our center within a relatively large cohort. PATIENTS AND METHODS: We retrospectively reviewed the clinical records 21 patients who fulfilled criteria of GTS. Survival analysis was performed by using the Kaplan-Meier method with the Long-rank test. p<0.05 was considered statistically significant. RESULTS: The median age at diagnosis was 25 (range 17-51). A total of 12 patients could have undergone surgery. Of patients who underwent surgery, 5 patients remained fully disease free, and 7 patients had experienced disease recurrences. Nine patients had unresectable disease, and treated with either platin-based chemotherapy or interferone α2b. Of those, 5 patients eventually had undergone autologous stem cell transplantation (ASCT) with surprisingly promising response rates. One patient had complete response and three patients had partial response. One patient died soon after ASCT due to infectious complication. CONCLUSION: GTS is an unique entity with regard to its clinicopathological features and available treatment options as we mentioned in the text. Despite various agents reported to have efficacy in case reports, surgery remains as the mainstay of treatment. According to result of our study, ASCT and platin-based chemotherapy regimens may be feasible options for patients with unresectable disease.

The prognostic value of tumor/lymph node standardized uptake value max ratio and correlation with hematologic parameters in stage III nonsmall cell lung cancer.

Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous subtype of lung cancer. There are still no widely accepted prognostic parameters for stage III NSCLC. In this study, we evaluated the prognostic value of the standardized uptake value (SUV) max ratio of primary tumor to lymph node (T/N SUV max) and its correlation with various hematological parameters.Patient data were reviewed from the hospital database retrospectively. The T/N SUV max ratio was calculated by dividing the SUV max of the primary tumor by the maximal SUV max of the lymph node. The cut-off value for T/N SUV max ratio was determined by receiver operating characteristic analysis. Survival analysis was performed by Kaplan-Meier method with the Long-rank test. P value < .05 was considered statistically significant.A total of 52 patients were included in this study. The optimal cut-off value for T/N SUV max was 1.96 (area under the curve: 0.74; 72.7% sensitivity and 73.7% specificity). Patients with T/N SUV max ≤1.96 were defined as high risk patients and those with >1.96 were defined as low risk patients. The median event (recurrence or progression) free survival was 24.3 months (95% confidence interval: 12.0-36.6) for low risk patients, and 9.2 months (95% confidence interval: 6.1-12.4) for high risk patients (P = .0015). There was an inverse correlation between T/N SUV max and hemoglobin concentration and mean corpuscular volume (rho: -0.349, P = .011; rho: -0.312, P = .025, respectively).Low risk patients had a more favorable prognosis compared to high risk patients. We demonstrated that T/N SUV max can be of prognostic value in stage III NSCLC. T/N SUV max correlated only with hemoglobin and mean corpuscular volume.

Sunitinib or Pazopanib: Is There Any Difference Between Tyrosine Kinase Inhibitors in the Pre-Nivolumab Setting in Metastatic Renal Cell Carcinoma?

Introduction Treatment options for metastatic renal cell carcinoma disease have been improved in recent years. However, there is still no optimal treatment sequence or combination for metastatic disease. We aimed to investigate whether patients differed in terms of disease outcomes regarding pre-nivolumab tyrosine kinase inhibitors (TKIs). Material and methods The analysis of patients was performed after all cohorts were sub-grouped into two groups according to pre-nivolumab TKIs as following the sunitinib arm and the pazopanib arm. Result A total of 75 patients were included in this study. The median follow-up time was eight months for all cohorts. The objective response rate was statistically significantly higher in the pazopanib arm as compared to the sunitinib arm (56% vs 30%, p=0.02). Progression-free survival was significantly higher in pazopanib than sunitinib (10.3 months vs 5.3 months, p=0.02). Multivariate analysis revealed that pazopanib treatment was associated with better progression-free survival (HR: 0.44, 95 CI; 0.22-0.91, p=0.02). While the median overall survival for patients who had received sunitinib was 11.0 months, it has not been reached the median in the pazopanib arm (11.0 months vs NR, p=0.051). Discussion We demonstrated significantly better progression-free survival and a higher objective response rate with nivolumab treatment in patients who had received pazopanib as compared with patients who received sunitinib in the pre-nivolumab period.

Prognostic and predictive value of KRAS mutation number in metastatic colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world and is the second leading cause of cancer-related deaths. Several mutations are involved in the development of CRC. The prognostic significance of the KRAS mutation has been discussed in many studies. We aimed to investigate the prognostic significance of the number of KRAS mutations in metastatic CRC (mCRC).Patients with mutations in the KRAS gene were included in the study. They were divided into 2 groups as single mutation and multiple mutations in the KRAS gene.For the study, 425 CRC patients were screened. KRAS mutation was positive in 191 patients (45%). One hundred ninety-one patients were included in the study, 171 patients (90%) had single mutations and 20 patients (10%) had multiple mutations. Median progression-free survival was 12.8 months in patients with multiple mutations, while it was 8.8 months in patients with single mutations (P: .05). The median overall survival of patients with multiple mutations was 40.7 months, while it was 22.7 months for patients with single mutations (P = .01)We found that the presence of multiple mutations in KRAS mutant patients was associated with better overall survival and progression-free survival than a single mutation.

Is there any correlation among MKK4 (mitogen-activated protein kinase kinase 4) expression, clinicopathological features, and KRAS/NRAS mutation in colorectal cancer.

BACKGROUND: We aimed to evaluate the correlation between MKK4 expression and clinicopathological features, KRAS/NRAS mutation in colorectal cancer. METHODS: MKK4 expression was assessed by immunoreactivity score (IRS). Staining intensity(SI) and percentage of positively stained cells (PP) were used for IRS (IRS = SI×PP). Cutoffs were explored with ROC analysis. Patients were grouped as WIR ('weak immunoreactive'; IRS:0-2) and SIR ('strong immunoreactive'; IRS: >3). RESULTS: We enrolled 95 patients. 63.2% had metastasis. Median follow-up was 31.4 months. KRAS/NRAS mutation rate was 45.2%. Median values for OS, DFS, and PFS were as 31.6, 17.2, and 10.3 months. WIR group had longer OS (p = 0.03). Recurrence rate was 36.8%. Median DFS was longer for recurrent patients in WIR group (p = 0.055). KRAS or NRAS wild-type patients and those with left-sided tumors in WIR group had longer OS (p = 0.029, p = 0.024, p = 0.03). There was no PFS difference (p: 0.15). In correlation analysis, there was a negative correlation between MKK4 expression and KRAS mutation, NRAS mutation, OS, PFS, DFS (r: -0,06; r: -0,02; r: -0,10; r: -0,06; r: -0,34). Only the correlation for MKK4 expression and DFS was significant (p = 0.04). CONCLUSION: MKK4 expression inversely correlates with survival outcomes. Patients with KRAS/NRAS wild-type, left-sided tumors with WIR had longer OS.

Does primary tumor resection contribute to overall survival in unresectable synchronous metastatic colorectal cancer?

BACKGROUND: Primary tumor resection (PTR) in metastatic colorectal cancer (mCRC) has not been suggested by guidelines, since new systemic chemotherapy options have improved overall survival. However, the effect of PTR is still controversial in mCRC. In this study, we aimed to evaluate the effect of PTR on survival in unresectable mCRC. MATERIALS AND METHODS: Two hundred and fifty-two patients with unresectable mCRC were screened retrospectively between January 2007 and December 2017 and a total of 147 patients who met inclusion criteria were included. The patients with emergency or elective PTR and the patients without surgery were compared for baseline features and overall survival. RESULTS: The median follow-up time was 15.6 months (range; 1.2-78.9) in whole patients. There were 91 patients in nonsurgical (NS) group and 56 patients in PTR group. The median overall survival was significantly longer in PTR group compared NS group (21.8 vs. 17.0 months, P = 0.01), but it was not associated to better overall survival in multivariate Cox analysis (hazard ratio: 0.65, 95% confidence interval: 0.41-1.02, P = 0.06). There was no significant difference in overall survival between emergency and elective surgery subgroups (22.9 vs. 16.1 months, respectively, P = 0.9). CONCLUSION: PTR did not offer an overall survival benefit in this study. Although it is debated, we think that it is better to start treatment with chemotherapy and biological agent combinations in patients with asymptomatic mCRC. Thus, the patients can be protected from the morbidity and mortality of the surgery.

Long-term outcomes of prolonged bisphosphonates more than 2 years in bone metastatic breast cancer: risk vs benefit.

BACKGROUND: Bisphosphonates are the mainstay therapeutic options for prevention of skeletal-related events and generally used for up to 2 years in bone metastatic cancer patients. AIM: We aimed to evaluate the long-term outcomes of prolonged (> 2 years) bisphosphonate usage in bone metastatic breast cancer (BMBC) patients. METHODS: Ninety-nine BMBC patients who had prolonged bisphosphonates were evaluated retrospectively for long-term outcomes and survival rates. RESULTS: Median duration of bisphosphonate therapy was 46.8 (24-198) months. Seven patients had bisphosphonate-related adverse events (osteonecrosis of the jaw (ONJ) (n = 6), ONJ and renal failure (n = 1)). Bisphosphonate was switched to another one because of bone metastasis progression in more than one-third of the patients (n = 36, 36.3%). The patients who had bisphosphonate switch therapy had statistically significant longer overall survival (p < 0.01). Neither duration nor type of bisphosphonates had effect on frequency of bisphosphonate-related adverse events. CONCLUSION: Bisphosphonates might be prolonged for more than 2 years in BMBC patients with an acceptable toxicity profile. In addition, bisphosphonates switch therapy should be preferred in those with progressive bone metastasis since it might contribute to better survival despite bisphosphonates could not have been shown to have survival benefit in previous studies.