Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study.

OBJECTIVE: To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). METHODS: A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. RESULTS: The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. CONCLUSION: In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

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 effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

Nutritional Health in Premenopausal Women: A Cross-Sectional Study from Turkey.

Background: The aim of this study was to evaluate the nutritional habits of premenopausal women using the Food Consumption Frequency Questionnaire (FCFQ) and to evaluate the relationship between anthropometric measurements, lipid parameters, and the presence of anemia with the findings obtained. Methods: This study was carried out in the internal medicine outpatient clinics of the Health Sciences University Bursa Yüksek Ihtisas Training Research Hospital (located in Yildirim districts) and Gürsu State Hospital (located in Gürsu districts) of Bursa province between 1 June-31 August 2019. We used clustered sampling in patient selection. One hundred seventy-one premenopausal participants aged between 18 and 55 who were known to be healthy and who came for routine control to the internal medicine outpatient clinics were included in the study. The FCFQ was used to determine how often the participants consumed different food groups in the last 1 month. Results: Overweight participants were 29.20% and 17% were obese. 43.90% of the women had anemia and 65.50% of the women had iron deficiency. The milk-dairy products nutrition score of the group with triglycerides (TG) <150 mg/dL was higher than the group with TG ≥150 mg/dL (P = 0.029). The meat-egg-legumes nutrition score (2.11 ± 0.57) of the group with high density lipoprotein (HDL) ≥50 mg/dL was higher than the group with HDL <50 mg/dL (1.91 ± 0.58) (P = 0.04). Conclusions: Anemia and obesity are high in premenopausal women. Community-based screening programs are needed to evaluate premenopausal women for anemia and obesity. Scales to assess the nutritional habits of the population are also needed in screening programs.

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.

Immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy.

Aim: To evaluate the immunogenicity and safety of the CoronaVac vaccine in patients with cancer receiving active systemic therapy. Methods: This multicenter, prospective, observational study was conducted with 47 patients receiving active systemic therapy for cancer. CoronaVac was administered as two doses (3 µg/day) on days 0 and 28. Antibody level higher than 1 IU/ml was defined as 'immunogenicity.' Results: The immunogenicity rate was 63.8% (30/47) in the entire patient group, 59.5% (25/42) in those receiving at least one cytotoxic drug and 100% (five of five) in those receiving monoclonal antibody or immunotherapy alone. Age was an independent predictive factor for immunogenicity (odds ratio: 0.830; p = 0.043). Conclusion: More than half of cancer patients receiving active systemic therapy developed immunogenicity.

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.

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.

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.

The Comparison Spondin 2 Levels in Primary Glomerular Diseases.

Spondin 2 (SPON2) plays an important role in multiple processes and is a member of the Spondin 2/F-spondin family of extracellular matrix proteins. We investigated serum SPON2 levels and its correlation with renal functions and urine protein excretion in different glomerular diseases. The cohort included 97 consecutive adults with persistant proteinuria (>300 mg/day) with the diagnosis of focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MN), IgA nephropathy (IgAN), membranoproliferative glomerulonephritis (MPGN), and AA amyloidosis and the control groups with 15 polycystic kidney disease (PKD) and 32 healthy people. Serum SPON2 levels in MN (64.6 ng/mL), FSGS (47.8 ng/mL), IgAN (52.6 ng/mL), MPGN (54.6 ng/mL), and AA amyloidosis (60.7 ng/mL) groups were higher than those of the control (26.4 ng/mL) and nonglomerular disease groups (PKD) (15.3 ng/mL). Only serum SPON2 levels were correlated with serum uric acid and triglyceride levels in patients with glomerular disease. This is the first study to show that serum SPON2 levels are similar in different glomerular diseases and that there is no correlation between SPON2 and proteinuria grade.

Effects of the Disease Characteristics and the Treatment on Psychological Status in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis.

INTRODUCTION: Various psychiatric disorders, especially depression and anxiety, are seen in 2/3 of the chronic rheumatic diseases with chronic pain. In this study, we aimed to define anxiety and depression rates in Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) patients (under treatment) with similar age and gender; to compare the obtained data with each other and healthy control group; and also we aimed to investigate the relationship between human leukocyte antigen B27(HLA-B27) in AS, Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in RA with anxiety and depression. METHOD: 46 patients with RA, 43 patients with AS and 29 healthy volunteers were evaluated with Beck Depression Inventory (BAI) and Beck Anxiety Inventory (BAI). Participants were also noted for their educational status, occupation status, family history of illness, duration of the disease and their current treatments. Then we compared the obtained data with the healthy control group. SPSS (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.p=0. Armonk, NY: IBM Corp.) was used for performing statistical analysis. RESULTS: There was no difference between the groups according to age, sex, duration of illness (p=0.104, p=0.767, p=0.377). A significant difference between groups in terms of BAI values were determined (p=0.018). In subgroup analyzes, the median BAI value of AS group was found to be higher than the control group (p=0.020). There were no differences in BAI values between AS and RA groups or between RA and the control groups (p>0.05, p>0.05 respectively). Also, there were no differences between the groups in terms of BDI values (p=0.055). CONCLUSIONS: Especially, chronic pain-related diseases are often associated with mental disorders, especially depression and anxiety. As a result, a multidisciplinary approach including psychiatric support should be used when planning treatment for these patients.