Predictive and prognostic effect of ABO blood group on immune checkpoint inhibitors.

BACKGROUND: The relationship of the ABO blood group system with the immune response is known, but its relationship with immune checkpoint inhibitors (ICIs) has not been clearly investigated until now. OBJECTIVE: In this study, the relationship between different blood groups and nivolumab treatment response in patients with advanced malignant melanoma was investigated. METHODS: The data of patients who used nivolumab for advanced malignant melanoma between April 2018 and April 2021 were retrospectively reviewed. RESULTS: A total of 73 patients were included in the study. In the progression-free survival (PFS) analysis according to blood groups, it was 3.9 months, 16.1 months, 20.0 months and 3.0 months for A, B, AB and O, respectively (p= 0.1). Overall survival (OS) analysis according to blood groups was 5.1 months, 25.0 months, 20.0 months and 9.3 months for A, B, AB and O, respectively (p= 0.1). The B antigen group (B or AB) had significantly longer PFS and OS than the non-B antigen group (A or O) (16.1 vs. 3.5 months for PFS, respectively, p= 0.03; 20.0 vs. 7.4 months for OS, respectively, p= 0.02). CONCLUSIONS: The presence of B antigen provides a significant advantage in terms of survival in patients using ICIs for advanced melanoma.

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.

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.

Association of illness perception with chemotherapy-induced nausea and vomiting: a Turkish Oncology Group (TOG) study.

Chemotherapy-induced nausea and vomiting (CINV) may be linked to the psychological status of cancer patients. Therefore, the authors aimed to better understand the underlying risk factors for CINV using the Brief Illness Perception Questionnaire. A total of 238 patients were recruited during three cycles of chemotherapy. Patient, disease and treatment characteristics were noted at the onset of chemotherapy. The Brief Illness Perception Questionnaire was administered face-to-face prior to chemotherapy. The relationship between illness perceptions and CINV was analyzed using Spearman's rank correlation. Positive illness perception parameters, including personal and treatment control, were negatively correlated, whereas negative illness perception parameters, including consequences, timeline, identity, concern and emotions, were positively correlated with CINV after adjusting for age, sex and emetogenic potential of chemotherapy (p < 0.001). Illness perception may be an underlying risk factor for CINV.

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.

Prognostic and Predictive Value of NAR Score in Gastric Cancer.

INTRODUCTION: Neoadjuvant treatment is a widely accepted approach for locally advanced rectum cancer. Efforts to explore a surrogate endpoint for clinical trials revealed a new prognostic scoring system which is named as neoadjuvant rectal score (NAR) in patients who received neoadjuvant treatment for rectal cancer. MATERIAL AND METHODS: 88 patients who met inclusion criteria were included in the study. The optimal cutoff value of the NAR score was 17.6 with 71% sensitivity and 63% specificity. Patients with NAR score > 17.6 (n: 48, 54%) were defined as the high-risk group and those with NAR score ≤ 17.6 (n: 40, 56%) as the low-risk group. RESULT: Survival analysis according to the NAR score group (low-risk vs high-risk) revealed that there was a statistically significant difference between groups regarding OS and DFS. The median OS for high-risk patients was 27.3 months (95% CI, 15.0-39.6); it was 76.6 months (47.3-106.0) for low-risk patients (p < 0.0001). The median DFS was 15.1 months (11.8-18.4) for high-risk patients; it was 44.3 months (95% CI, 4.1-84.6) in the low-risk group (p = 0.002). DISCUSSION: As a result, we interpreted our findings as supporting data about the utility of NAR score not only as a surrogate endpoint for the clinical trial of rectal cancer but also as a prognostic marker in patients with gastric cancer who received neoadjuvant treatment.

Prediction of Peritoneal Recurrence in Patients with Gastric Cancer: a Multicenter Study.

PURPOSE: The peritoneum is the common recurrence site of gastric cancer (GC) presenting with worse survival. Although some predictive clinicopathological factors have been identified, there is no comprehensive assessment of peritoneal recurrence risk prediction for patients treated with adjuvant chemotherapy (CR) or chemoradiotherapy (CRT) after surgery. We aimed to predict peritoneal recurrence and develop a new scoring model in GC. METHODS: This retrospective study included 274 GC patients who presented with recurrence after curative gastrectomy followed by adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). Risk factors for peritoneal recurrence were analyzed using the following parameters: age, gender, tumor location and characteristics, and differences between treatment modalities. All parameters were assessed by binary logistic regression analysis to compare the patients with and without peritoneal recurrence. Then, a new risk scoring model was developed. RESULTS: Peritoneal recurrence was observed in 115 (44.1%) patients. Peritoneal recurrence was higher in female gender (odds ratio (OR), 1.93; 1.07-3.49, P = 0.030, 1 point), T4a-b stage (OR, 2.47; 1.14-5.36, P = 0.022, 1 point), poor/undifferentiated (OR, 2.04; 1.31-4.06, P = 0.004, 1 point), and signet cell carcinoma (OR, 2.04; 1.04-4.02, P = 0.038, 1 point) after adjusted for resection and dissection types. The risk scoring model was developed using the related parameters: Peritoneal recurrence rates were 24.6%, 42.6%, and 71.4% for group 1 (0 point), group 2 (1-2 points), and group 3 (3-4 points), respectively. CONCLUSION: Female gender, T4 tumor stage, undifferentiated histopathology, and signet cell type had a tendency to peritoneal recurrence after adjusted for treatment modalities. Patients with 3 or 4 risk factors had an 8.8-fold increased risk for the development of peritoneal recurrence.

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.

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.

KRAS codon 12 and 13 mutations may guide the selection of irinotecan or oxaliplatin in first-line treatment of metastatic colorectal cancer.

Background: In this study, we aimed to investigate the frequency, prognostic effect of codon, and amino acid-specific KRAS mutations in patients with metastatic colorectal cancer (mCRC) and their predictive effect on irinotecan and oxaliplatin during first-line treatment.Methods: The data of 304 mCRC patients were retrospectively evaluated between 2010 and 2018. Patients were categorized according to the most prominent codon and amino acid mutation and their prognostic features were analyzed.Results: In total, 274 patients were included in the study and 128 patients (47%) revealed KRAS mutation. Median follow-up time was 19.8 months (range; 1.6-96). The median overall survival rates for patients with codons 12 and 13 mutations were 25.4 and 22.2 months, respectively (p = 0.4). Moreover, the median overall survival for the codon 12 mutant patients who received irinotecan-based chemotherapy in the first-line treatment was 42.7 months, whereas for the codon 13 mutant and KRAS wild-type patients, it was 18.3 and 23.9 months, respectively (codon 12 vs. codon 13; HR: 0.31, p = 0.03, codon 12 vs. wild-type; HR: 0.45, p = 0.03).Conclusion: The significant survival advantage was observed in patients with codon 12 mutations who received irinotecan-based chemotherapy as a first-line treatment.