Comparison of efficacy and safety of 5-FU or capecitabine combined with cisplatin and docetaxel (mDCF and mDCX) as a first-line chemotherapy regimen in her 2-negative metastatic gastric cancer patients: A retrospective study.

The prognosis of metastatic gastric cancer (GC) is poor, with a median survival time of less than a year. Capecitabine is a prodrug, metabolized by thymidine phosphorylase to its cytotoxic metabolite (5-FU). Few studies have compared capecitabine and 5-FU in mGC. In this retrospective study, we compared the efficacy and safety of modified DCF (mDCF) (docetaxel, cisplatin, and 5-FU) and modified DCX (mDCX) (docetaxel, cisplatin, and capecitabine) regimens for first-line treatment in patients with mGC. The study included 112 mGC patients treated with either mDCF (n = 69) or mDCX (n = 43) between 2010 and 2021. Demographic data, response rate, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. The complete response rate in the mDCF group was 10.1%, whereas the complete response rate in the mDCX group was 2.3%. The partial response rate for mDCF and mDCX were 29% and 37%, respectively. The 2 treatment arms of the study had the same objective rate of response and disease control rate (DCR). PFS and OS rates were comparable between the 2 groups. The median PFS in the mDCF and mDCX arms were 6.0 months (95% CI, 4.87-7.14) and 5.0 months (95% CI, 4.10-5.90) respectively (P = .08). The median OS in the mDCF and mDCX arms were 9.0 months (95% CI, 7.53-10.47) and 9.0 months (95% CI, 6.87-11.11) respectively (P = .07). Neutropenia, asthenia, stomatitis, and nausea/vomiting were the most frequently reported grade 3 to 4 adverse events (AEs). The rates of grade 3/4 AEs and dose reduction were comparable between the 2 groups. There was no treatment discontinuation due to grade 3 to 4 AE. As a first-line treatment for patients with mGC, mDCX and mDCF regimens have comparable efficacy and tolerability profiles.

Investigation of the potential of miRNA candidates as non-invasive biomarkers for the diagnosis and follow-up of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, and despite advances in treatment, molecular biomarkers are needed for both early diagnosis and prognosis monitoring. It is known that microRNAs (miRNA), one of the epigenetic mechanisms, are effective in the initiation and development of cancer by regulating the activity of tumor suppressors and/or oncogenes. In this study, the potential of the molecules let-7, miRNA125b, and miRNA30a, which are known to play a role in cellular processes, as biomarkers for colorectal cancer and their molecular mechanisms were investigated in this model. The aim was to evaluate the diagnostic, prognostic, and predictive utility of the target miRNAs in colorectal cancer patients. MATERIAL AND METHODS: The expression changes of miRNAs let-7, miRNA125b, and miRNA30a were investigated by miRNAs isolation and cDNA synthesis from the serum samples of 60 patients diagnosed with CRC or from the serum samples of 20 healthy individuals. The calculation was performed using the quantitative real-time polymerase chain reaction method to determine the expression level. The results were compared with clinical parameters. RESULT: An 8-fold decrease in the expression of let-7 and miRNA125b and a 60-fold decrease in the expression of miRNA30a were found in the serum samples of patients diagnosed with colorectal cancer (CRC) compared to the healthy group. A decrease in let-7 was observed in 53.3%, miRNA125b in 58.3%, and miRNA30a in 55% of patients. A significant correlation was found between the reduced expression status and the stage, lymph nodes, local recurrence, and metastasis (p < 0.05). The ROC analysis showed that the miRNA30a level could be a diagnostic biomarker for CRC (p < 0.001). No significant impact of target miRNA expression changes on overall disease survival was observed. CONCLUSION: It is thought that the target miRNA30a can be used for early diagnosis and screening and that the target miRNA let-7, miRNA125b, and miRNA30a can be used as non-invasive biomarkers for disease follow-up, with larger patient studies being conducted on CRC patients.

Disease characteristics and prognostic factors of colorectal cancer patients with bone metastasis: A real-world data from Turkey.

BACKGROUND: Bone metastasis is rarely seen in colorectal cancer (CRC) patients, and there is insufficient data available regarding such cases. The study aimed to identify the prognostic factors and characteristics associated with overall survival in patients with bone metastatic CRC. METHOD: Data from bone metastatic CRC patients referred to a high-volume tertiary cancer center in Turkey, between January 2018 and April 2021, were retrospectively collected. The records of 150 consecutive patients treated for bone metastases due to CRC were reviewed. Overall survival curves were generated by the Kaplan-Meier method and analyzed using the log-rank test. RESULTS: Median age was 55 years (19-86 years). Bone metastases were more common in men and those with metachronous metastases. The axial skeleton was the most commonly involved site, and patients were frequently presented with single bone metastasis. Peritoneal metastases were significantly correlated with extra-axial metastases (P = 0.002), and radiotherapy was applied to axial metastases significantly, more frequently (P = 0.02). Lung metastasis was also more prevalent in K-RAS mutated patients (P = 0.008). The median survival time from diagnosis of bone metastasis was 8.3 months (95% confidence interval (CI), 5.5-10.6), and the three-year survival rate was 76.9% (95% CI, 69.8-84.0). Multivariate analysis revealed that brain metastases, right-sided colon tumor, high serum ALP, and Ca 19-9 levels were independent poor prognostic factors (P = 0.01, 0.02, <0.001, and 0.04, respectively). CONCLUSIONS: The location of CRC correlates significantly with the site of bone metastasis; the prognosis of CRC patients with bone metastasis is very poor, and the significant poor prognostic factors are brain metastases, right-sidedness, high serum ALP, and Ca 19-9 levels. More attention should be paid to bone metastasis in CRC patients.

Is there any diagnostic value of serum caveolin-1 levels on the determination of pancreatic adenocarcinoma?

BACKGROUND: Caveolin-1 (CAV-1) is a vital component in cancer pathogenesis, as its expression determines the survival of patients with cancer. This study investigates CAV-1 serum levels in pancreatic adenocarcinoma (PA) patients and their role in tumor progression and prognostic factors. METHOD: The trial included 33 patients with pathologically confirmed pancreatic cancer (PC). The enzyme-linked immunosorbent assay (ELISA) method was used to measure the concentrations of CAV-1 in the blood. The study also included 20 healthy subjects. The statistical analysis was two-sided, and a P value of ≤ 0.05 was determined as statistically significant. RESULTS: The median age of the subjects was 59 years (32-84 years) at the time of diagnosis. There were 13 (39%) female participants. In 21 (63%) patients, the primary focus was the pancreatic head. In 23 stage IV patients, hepatic metastasis (n = 19, 83%) was observed. Only one patient (3%) was still alive at the end of the study period. Palliative chemotherapy (CTx) was provided, with 39% of the 23 patients responding to it. The overall survival (OS) rate in this cohort was 41.3 ± 8.3 weeks at a 95% confidence interval (CI), after 25-58 weeks. Serum baseline CAV-1 values among patients with PA were significantly higher compared with controls (p = 0.009). Patients with poor performance status, a pancreatic head tumor, lower albumin levels, higher serum carcinoembryonic antigen (CEA) levels, and higher CA 19.9 levels had significantly higher serum CAV-1 levels (p = 0.01, P = 0.05, P = 0.03, P = 0.02, and P = 0.04, respectively). However, CAV-1 did not show any prognostic value (p = 0.75). CONCLUSION: Although serum CAV-1 is a useful diagnostic marker in PC patients, it is not a prognostic or predictive marker.

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

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

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.

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) regimen in the first-line treatment of metastatic gastric cancer: A single-center experience.

Objective: The median survival time for metastatic gastric cancer that has a poor prognosis is usually shorter than 1 year. The fluorouracil, oxaliplatin, and docetaxel (FLOT) regimen is observed to be effective in the neo-adjuvant treatment of gastric cancer. However, data on the FLOT regimen in metastatic gastric cancer are limited. The current study aims to evaluate the safety and efficacy of the FLOT regimen in metastatic gastric cancer in real life. Study Design: Retrospective study. Place and Duration of Study: The study was performed in an Institute of Oncology of a university and included the patients diagnosed between January 2015 and December 2020. Methodology: In addition to the clinicopathological data of patients with human epidermal growth factor receptor 2 (HER-2)-negative metastatic gastric cancer, we retrospectively evaluated the survival and treatment-related toxicities. The FLOT regimen (Fluorouracil 2600 mg/m2 24 hours continuous intravenous infusion, leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2 on day 1) every 2 weeks was used in all patients. Results: The study included 94 patients who were followed up for a median of 11.1 (min-max: 1.5-65.8) months. The number of male patients was 60 (63.4%), and the median age was 58 (min-max: 27-78) years. The primary tumor was located in the stomach (72.3%) and gastroesophageal junction (27.7%). The objective response rate was observed in 64.8% of the patients. The median overall survival was 13.5 (95% CI: 9.2-17.8) months, whereas the progression-free survival was 7 (95% CI: 5.7-8.3) months. The 1-year survival rate was 53.6%. Complete response was detected in 7.4% of the patients. Among grade 3-4 toxicities, neutropenia (44.6%), leukopenia (27.6%), neuropathy (12.7%), and fatigue (9.5%) were the most common observed toxicities. Conclusion: FLOT is a highly active option in the first-line treatment of metastatic gastric cancer, with a favorable safety profile.

Serum fetuin-A and RANKL levels in patients with early stage breast cancer.

Background: Breast cancer (BC) is the primary cause of mortality due to cancer in females around the world. Fetuin-A is known to increase metastases over signals and peroxisomes related with growing. Receptor activator of nuclear factor-kB ligand (RANKL) takes part in cell adhesion, and RANKL inhibition is used in the management of cancer. We aimed to examine the relationship between serum fetuin-A, RANKL levels, other laboratory parameters and clinical findings in women diagnosed with early stage BC, in our population. Methods: Women having early stage BC (n=117) met our study inclusion criteria as they had no any anti-cancer therapy before. Thirty-seven healthy women controls were also confirmed with breast examination and ultrasonography and/or mammography according to their ages. Serum samples were stored at -80°C and analysed via ELISA. Results: Median age of the patients was 53 (range: 57-86) while it was 47 (range: 23-74) in the healthy group. Patients had lower high-density lipoprotein levels (p=0.002) and higher neutrophil counts (p=0.014). Fetuin-A and RANKL levels did not differ between the groups (p=0.116 and p=0.439, respectively) but RANKL leves were found to be lower in the favorable histological subtypes (p=0.04). Conclusions: In this study, we found no correlation between serum fetuin-A levels and clinical findings in patients diagnosed with early stage BC. However, RANKL levels are found to be lower in subgroups with favorable histopathologic subtypes such as tubular, papillary and mucinous BC and there was statistically significant difference.

Distributions and prognostic effects of ABO/Rh blood groups in patients with HER2/neu positive gastric and gastroesophageal junction cancer.

BACKGROUND: The aim of study was to look at ABO/Rh blood types frequency and prognostic significance in patients with HER2/neu positive gastric cancer. METHODS: The study was designed retrospectively. Clinicopathological characteristics, treatment approaches, and the ABO/Rh blood groups features were noted. The ABO/Rh blood types for patients and healthy donors were compared by the Chi-square method. RESULTS: The average age was 61 years. The average survival time was 17.9 months (13.2-22.5). ABO blood types frequencies were not similar between patients (25.9% O, 6.3% AB, 57.1% A, and 10.7% B) and control group (34.9% O, 7.9% AB, 41.9% A, and 15.3% B) (P = 0.01). Patients and controls had the same Rh factor distribution (P = 0.07). CONCLUSIONS: We showed that A blood group frequency was increased in patients with HER2/neu receptor-positive gastric cancer than in a healthy population. Also, we detected that the frequency of O blood type was decreased. ABO/Rh blood types were not linked with prognosis for overall survival.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Capecitabine and temozolomide (CAPTEM) is effective in metastatic well-differentiated gastrointestinal neuroendocrine tumors.

OBJECTIVE: The aim of this study was to investigate the outcomes and prognostic factors of patients with metastatic gastrointestinal neuroendocrine tumor (mGI-NET) who were treated with capecitabine and temozolomide (CAPTEM) and somatostatin receptor ligand (octreotide or lanreotide). METHODS: Clinicopathological characteristics and treatment outcomes of 43 patients with mGI-NET were retrospectively evaluated. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier curve. Cox-regression analysis was used to assess prognostic variables. RESULTS: There were 23 (53.5%) men and 20 women (46.5%) with a median age of 59 years (range 27-85 y). Patients were given octreotide (86.0%) or lanreotide (14.0%) with CAPTEM. In patients with well-differentiated mGI-NET, median PFS was 17.4 months, and the disease control rate was 71.1%. Patients with poorly differentiated mGI-NET showed no response, and the median PFS was 4.5 months. Four (9.3%) discontinued the medication due to toxicity. Anemia (37.2%), thrombocytopenia (25.6%), and fatigue (16.3%) were the most prevalent adverse events. The 5-year OS rate was 61.0% in all patients during a median follow-up of 33.8 months. In multivariate analysis, age (P = 0.014) and tumor differentiation (P < 0.001) were statistically significant factors for OS. CONCLUSIONS: CAPTEM plus somatostatin receptor ligands were efficacious and well tolerated in individuals with well-differentiated mGI-NET. However, it was ineffective for those with poorly differentiated tumors. Age of 60 years or elder and poorly differentiated tumors were related to a poor patient prognosis.

Evaluation of Prognostic Factors and Trastuzumab-based Treatments in HER2/Neu-positive Metastatic Gastric Cancer.

OBJECTIVE: To determine the efficacy of trastuzumab-based treatment in patients with HER2/neu-positive metastatic gastric cancer. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Istanbul University, Institute of Oncology, Istanbul, Turkey, between January 2014 and December 2020. METHODOLOGY: The clinicopathological characteristic and treatment data of patients with HER2/neu-positive metastatic gastric cancer were recorded retrospectively. Kaplan-Meier analysis was performed to compare the chemotherapy regimens. RESULTS: Sixty-three patients were included in the study. The average age was 61. Female patients accounted for 27% of the total, while male patients accounted for 73%. De novo metastatic cases accounted for 44 (69.8%) of the total number of patients. The median survival time was 13.6 (8-19.3) months. Complete response was 6.3%, partial response was 39.7%, and the stable response was 9.5% with trastuzumab-based chemotherapy. The overall survival (p= 0.45) and progression-free survival (p=0.893) were similar for different chemotherapy regimens. The grade 1-2 to grade 3-4 toxicity ratio was 79.6% and 20.6%, respectively. The patients' performance (p<0.001) and the number of metastatic sites (p=0.001) were both shown to be unfavourable predictive variables for OS in multivariate analysis. CONCLUSION: The addition of taxane to trastuzumab-based combinations (with platinum and fluoropyrimidine) did not affect overall and progression-free survival in this research. Three or more metastatic sites and poor performance status were found as the unfavourable prognostic variables for overall survival. KEY WORDS: Gastric cancer, Trastuzumab, Chemotherapy, Prognostic factors.

Prognostic value of FDG PET-CT in suspected recurrence of colorectal carcinoma: survival outcomes of a 10-year follow-up : FDG PET in recurrent colorectal CA.

OBJECTIVE: We aimed to evaluate the predictive value of FDG PET-CT scan and CEA measurements in recurrent colorectal cancer (CRC) patients. METHODS: The records of 211 CRC patients who had FDG PET-CT scans between April 2009 and June 2011 due to suspicion of recurrence were extracted from the data of our previous report of 235 patients after 24 patients were excluded from the study due to lack of follow-up data or death unrelated to CRC. FDG PET-CT findings, simultaneous CEA levels, and survival data were evaluated retrospectively to determine the prognostic factors that affected the overall survival (OS) of the patients. RESULTS: The mean age of 211 patients was 60.2 ± 12.8 years. The median follow-up time was 39 months (CI 95%: 4-123 months). The CRC-related death rate was 71.6% and the median OS time was measured 39 months (CI 95%: 27-50 months) for 211 patients. The median OS time for the patients with positive findings for recurrence in PET scans was 28 months (CI 95%: 22-33 months) which was significantly shorter (p < 0.001) than that of PET-negative patients (median OS was not reached; mean OS: 105 months; CI 95%: 95-116 months). CEA positivity also had a significant negative effect on survival (p < 0.001). Median OS times in patients with elevated and normal levels of CEA were 24 months (CI 95%: 17-30 months) and 85 months (CI 95%: 62-107 months), respectively. When the effect of CEA positivity was evaluated in patients with negative PET scans for recurrence, no statistically significant difference was determined (p = 0.209), but PET positivity had a significant negative effect on OS in patients with normal levels of CEA (p < 0.001). On the other hand, PET negativity had a significant positive effect on OS in patients with elevated CEA levels (p = 0.002). The extend of recurrent disease had also a significant effect on OS. The patients with distant metastasis had less favorable OS than those patients with only local recurrence (p < 0.001). The presence of liver metastasis also diminished the OS, but this effect was not statistically significant (p = 0.177). CONCLUSION: FDG PET-CT scan which is a reliable imaging method to detect recurrence in CRC patients, regardless of CEA levels, can also provide valuable prognostic information, even superior to that of CEA measurement.

Does nutritional status affect treatment tolerability, chemotherapy response and survival in metastatic gastric cancer patients? Results of a prospective multicenter study in Turkey.

BACKGROUND: The possible impact of malnutrition on the efficacy and tolerability of modern chemotherapy for metastatic gastic adenocarcinoma (mGC) patients is unclear. With this study, we aimed to represent the possible impact of malnutrition on the efficacy and tolerability of chemotherapy, and also on the overall survival of mGC patients. METHODS: In this prospective multicenter study, we collected demographic, oncological and nutritional data of our mGC patients. The nutritional status of patients were assessed with the Nutritional Risk Index (NRI), Body Mass Index (BMI) and weight loss percentage within 21-day period, between the chemotherapy cycles. All of these parameters along with toxicity assessment were evaluated after each courses of chemotherapy in order to determine inter-treatment weight loss. NRIs were calculated with a formula as follows; [1.519 × serum albumin level(g/L) + 41.7 × current weight/basic weight]. Patients were classified as having 'no malnutrition' (NRI > 97.5), 'moderate malnutrition' (97.5 ≥ NRI ≥ 83.5) or 'severe malnutrition' (NRI < 83.5). Drug-induced toxicities and treatment responses were evaluated via National Cancer Institute CTCAE version 4.0 and RECIST Criteria 1.1, respectively. RESULTS: One hundred and sixteen mGC patients were enrolled into the study. Median age was 60 years with range 32-83. Primary location of the tumor was antrum in 40% of the patients and of which 24% had undergone primary tumor resection. Ninety-eight percent of the patients had WHO performance status 0 or 1. Malnutrition was diagnosed in 67% of the patients and was severe in 31% of them. All patients received chemotherapy as first-line setting. Severe malnutrition was not associated with chemotherapy responses (p = 0.57). Moderate/severe malnutrition was associated with more cytopenia, nausea/vomiting, diarrhea, neuropathy, (p < 0.05 for all parameters). Moderate/severe malnutrition is associated with worser non-hematological toxicities (p = 0.038). Forty-one percent of patients died during the follow up period (Median: 138 days, range: 21-378). Malnutritional level was associated with significantly reduced overall survival. Severe malnutrition was associated with shorter median overall survival (74 days (95% CI, 20.7-111.0) vs. 237 (95% CI, 148.4-325.6) in none/moderate groups, p = 0.007). CONCLUSIONS: In mGC patients, moderate/severe malnutrition is associated with worse non-hematological toxicities. Severe malnutrition is also associated with reduced overall survival.

Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study.

BACKGROUND: The role of radiotherapy in the adjuvant treatment of gastric cancer (GC) remains to be elucidated. This study aimed to assess the additional benefit of radiotherapy in the adjuvant treatment of GC. MATERIALS AND METHODS: In this retrospective cohort study, we included 230 gastric adenocarcinoma patients who underwent D2 dissection between January 2004 and December 2019. Patients without R0 resection, who underwent metastasectomy at surgery, and treated with the neoadjuvant treatment were excluded. The co-primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were the locoregional and distant metastasis risk and adverse events (AEs) leading to treatment discontinuation. RESULTS: One hundred and sixty-six and 64 patients were included in the chemoradiotherapy (CRT) and chemotherapy (ChT) arms, respectively. The median OS was 135.8 months [interquartile range (IQR): 99.4-172.2] and 97 months (IQR: 59.7-134.3) in the CRT and the ChT arms, respectively. No statistical significance was observed between the arms in OS (p = 0.3). Locoregional or distant recurrence rates were similar in each group. AEs leading to treatment discontinuation were higher in the CRT arm than in the ChT arm (13.2 vs 9.3%), and the difference between the arms was not statistically significant (p = 0.4). CONCLUSION: In this real-life study, we established that there was no additional benefit of RT in GC patients who underwent D2 dissection. HOW TO CITE THIS ARTICLE: Yekedüz E, Dogan I, Birgi SD, et al. Adjuvant Treatment of Gastric Cancer in the D2 Dissection Era: A Real-life Experience from a Multicenter Retrospective Cohort Study. Euroasian J Hepato-Gastroenterol 2021;11(2):51-58.

Does nutritional status affect treatment tolarability, response and survival in metastatic colorectal cancer patients? Results of a prospective multicenter study.

BACKGROUND: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. METHODS: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI (Nutritional Risk Assessment), BMI (Body Mass Index) and WL (Weight Loss) before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. NRIs were examined in 3 categories as 'no malnutrition' (NRI >97.5), 'moderate malnutrition' (97.5 ≥NRI ≥83.5) or 'severe malnutrition' (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively. RESULTS: One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p = 0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS (World Health Organization Performance Status) of 1, over the median value of CEA/CA 19-9 (carcinoembryonic antigen/carbohydate antigen 19-9) levels (p = 0.003, p = 0.03, p < 0.001, and p = 0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p < 0.001 and p < 0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p = 0.02 and p = 0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p < 0.001]. CONCLUSIONS: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.

Circulating annexin A2 as a biomarker in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) is a highly lethal malignancy. There are only few predictive or prognostic markers for PC. This study was conducted to investigate the serum levels of annexin A2 (AnxA2) in patients with PC and its relationship with tumor progression and known prognostic parameters. MATERIALS AND METHODS: Serum samples were obtained on the first admission before any treatment. Serum AnxA2 levels were determined using enzyme-linked immunosorbent assay. Age- and sex-matched healthy controls were included in the analysis. All statistical tests were carried out using two-sided test, and P ≤ 0.05 was considered statistically significant. RESULTS: The median age at diagnosis was 59 years. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). At the end of the observation period, thirty-two patients (97%) were dead. Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx responsive. Median overall survival of the whole group was 41.3 ± 8.3 weeks (95% confidence interval = 25-58 weeks). The baseline serum AnxA2 levels were significantly higher in patients with PC than in the control group (P = 0.01). Serum AnxA2 levels were significantly higher in the patients with high erythrocyte sedimentation rate (P = 0.04). Conversely, serum AnxA2 concentration had no prognostic role on survival (P = 0.18). CONCLUSIONS: AnxA2 is identified as a novel secretory biomarker for PC, but it has no role as a prognostic or predictive marker.

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

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