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.

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.

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.

Role of mir-33a, mir-203b, mir361-3p, and mir-424 in hepatocellular carcinoma

Background/aim: Hepatocellular carcinoma (HCC) is one of the most aggressive cancer types. MicroRNAs (miRNAs) are small noncoding regulatory RNAs that function posttranscriptionally. miRNA deregulation was observed in the development and progression of HCC. In this study, we aimed to investigate the expression levels of four miRNAs (mir-33a, mir-203b, mir361-3p, and mir-424) in HCC patients in comparison to healthy individuals. Materials and methods: Venous blood samples were collected from both HCC patients and healthy individuals. In order to determine the relative expression levels of mir-33a, mir-203b, mir361-3p, and hsa-mir-424 in HCC patients, probe-based quantitative real time PCR (qRT-PCR) was performed. The cycle threshold (Ct) results were analyzed according to the 2−∆∆Ct method and statistical analyses were performed by SPSS Statistics version 15 for Windows. Results: qRT-PCR analysis revealed that the expression levels of mir-33a (fold change: 7.3 and P < 0.001), mir-203b (fold change: 4.6 and P < 0.001), and mir361-3p (fold change: 5.1 and P < 0.001)were downregulated compared to healthy individuals and mir-424 did not show any significant change between HCC patients and controls. Conclusion: Our results indicated that mir-33a, mir-203b, and mir-361-3p may significantly contribute to tumor pathogenesis in HCC and have potential to be used as a noninvasive biomarker for cancer therapy.

Clinical significance of serum interleukin-29, interleukin-32, and tumor necrosis factor alpha levels in patients with gastric cancer.

Many studies suggested that cytokines interleukin (IL)-29, IL-32, and tumor necrosis factor alpha (TNF-α) are implicated in the pathogenesis of malignancies. The purpose of this study was to determine the clinical significance of the serum levels of IL-29, IL-32, and TNF-α in gastric cancer (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy controls were enrolled into this study. The median age at diagnosis was 59.5 years (range 32-82 years). Tumor localization of the majority of the patients was antrum (n = 42, 72.4 %), and tumor histopathology of the majority of the patients was diffuse (n = 43, 74.1 %). The majority of the patients had stage IV disease (n = 41, 70.7 %). Thirty-six (62.1 %) patients had lymph node involvement. The median follow-up time was 66 months (range 1 to 97.2 months). The baseline serum IL-29 concentrations were not different between patients and controls (p = 0.627). The baseline serum IL-32 and TNF-α concentrations of the GC patients were significantly higher (for IL-32, p = 0.014; for TNF-α, p = 0.001). Gender, localization, histopathology, tumor, and lymph node involvement were not found to be correlated with serum IL-29, IL-32, and TNF-α concentrations (p > 0.05). Patients without metastasis (p = 0.01) and patients who responded to chemotherapy (p = 0.04) had higher serum IL-29 concentrations. Patients older than 60 years had higher serum IL-32 (p = 0.002). Serum IL-29, IL-32, and TNF-α levels were not associated with outcome (p = 0.30, p = 0.51, and p = 0.41, respectively). In conclusion, serum levels of IL-32 and TNF-α may be diagnostic markers, and serum IL-29 levels may be associated with good prognosis in patients with GC.

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

PURPOSE: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA. METHODS: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC). RESULTS: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001). CONCLUSIONS: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.

Serum transforming growth factor-beta1 levels may have predictive and prognostic roles in patients with gastric cancer.

Transforming growth factor-beta1 (TGF-beta1) plays an important role in the pathogenesis of multiple malignancies, and also, its expression strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of TGF-beta1 in gastric cancer patients. A total of 63 patients with a pathologically confirmed diagnosis of gastric cancer were enrolled into this study. Serum TGF-beta1 concentrations were determined by the solid-phase sandwich ELISA method. Thirty healthy age- and sex-matched controls were included in the analysis. The median age at diagnosis was 62 years, range 28 to 82 years. There was no significant difference in baseline serum TGF-beta1 levels between gastric cancer patients and the healthy control group (p = 0.08). The known clinical variables including age of patient, gender, site of lesion, histology, histological grade, stage of disease, and serum levels of lactate dehydrogenase (LDH), CEA, and carbohydrate antigen (CA) 19.9 were not found to be correlated with serum TGF-beta1 concentrations (p > 0.05). However, the chemotherapy-responsive patients had higher serum TGF-beta1 levels compared with chemotherapy-unresponsive ones (median values 330.50 v 49.54 pg/mL, respectively, p = 0.01). Moreover, patients with elevated serum TGF-beta1 concentrations had significantly favorable overall survival compared with those with lower levels (median 71.1 v 39.9 weeks, respectively, p = 0.04). In conclusion, serum levels of TGF-beta1 may have predictive and prognostic roles in patients with gastric cancer.

Radioprotectant and Cytotoxic Effects of Spirulina in Relapsed Verrucous Vulvar Cancer: A Case Report.

CONTEXT: The treatment of relapsed verrucous vulvar cancer (VVC) is difficult. When vulvar cancer relapses, the treatment response is low for second-line treatments. Conversely, toxicity is high. Therefore, scientists need to identify different treatment methods. OBJECTIVES: The case study was intended to examine the benefits of combining treatment with microalgae and metronidazole with radiotherapy to increase the response to treatment. SETTING: The study took place in the Department of Radiation Oncology at Bezmialem Vakif University, in Istanbul, Turkey. PARTICIPANT: The case study involved an 81-y-old female patient whose vulvar tumor was excised and who came to the research team's radiation oncology service for postoperative radiation. She had 2 comorbid disorders: Alzheimer's disease and cardiovascular disease. INTERVENTION: A relapse had occurred in the 15-d postoperative period. Because of the patient's age and comorbid disorders, the research team decided to treat the new tumor only with concurrent radiochemotherapy and a weekly dose of cisplatin that contained chemoradiotherapy, for a total of 25 mg. At the 52.2 Gy dose level, grade 3 radiation skin toxicity occurred in the radiated area, although the research team had obtained an 80% response to the radiochemotherapy. The treatment was interrupted because of toxicity but also due to a deterioration in the patient's general health. Progression of the tumor continued, and the tumor's diameter increased to 7 cm after a 4-mo period. The research team then initiated radiotherapy again, combining it with spirulina in a 750 mg/dose at 2 doses/d and metronidazole in a 500 mg/dose at 3 doses/d, to decrease radiation toxicity and increase radiosensitivity. Radiotherapy was applied at 200 cGy per fraction with a total dose of 2400 cGy, with only 1 anterior local-tumor field. RESULTS: The patient showed a complete response to radiotherapy, and the tumor disappeared at the 2400 cGy radiation dose. No toxicity occurred related to the skin or the woman's general health. Her Karnofsky performance score increased to 90% from 50%, which was the initial score of the second treatment.

Progesterone receptor status in determining the prognosis of estrogen receptor positive/ HER2 negative breast carcinoma patients.

PURPOSE: To evaluate the impact of progesterone receptor (PR) status on estrogen receptor (ER)-positive and HER2-negative breast cancer. METHODS: A total of 1673 operable breast cancer patients, diagnosed from June 1984 to June 2011 were retrospectively reviewed and 400 patients with ER-positive and HER2-negative tumors were identified and evaluated. ER-positive and HER2-negative patients were classified into two groups: group A: ER+/PR-/HER2- and group B : ER+/PR+/HER2- according to PR status. RESULTS: Median follow-up was 14.2 years (range 10.1-18.2). The ratio of postmenopausal patients was significantly higher in group A (68.2%, p=0.015). Grade 1 tumor and stage I disease were significantly higher in group B (15%, p=0.007 and 15%, p=0.005, respectively). Mean overall survival (OS) and disease free survival (DFS) were significantly better in group B (15.3±1.5 years vs 8.7±0.8 years, p=0.032; 10.5±1.6 years vs 5.7±0.5 years, p=0.022) as compared with group A. Relative risk for recurrence and death were two-fold higher in group A (p=0.05 and p=0.01, respectively). CONCLUSION: PR status exerts a significant impact on prognosis of ER+/HER2- breast cancer.

Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.

PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC. METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities. CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

Clinical significance of serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with breast cancer.

Insulin-like growth factor-1 (IGF-1) and its primary binding protein-3 (IGFBP-3) play an important role in cellular proliferation, differentiation and apoptosis in many tumors, including breast cancer (BC). The objective of this study was to determine the clinical significance of the serum levels of IGF-1 and IGFBP-3 in BC patients. A total of 96 patients with a pathologically confirmed diagnosis of BC were enrolled into this study. Serum IGF-1 and IGFBP-3 levels were determined by the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) methods. Age- and sex-matched 30 healthy controls were included in the analysis. The median age of diagnosis was 48 years (range: 29-80). Thirty-seven (39 %) consisted of metastatic disease. No significant difference in baseline serum was found in both IGF-1 and IGFBP-3 levels between BC patients and healthy controls (p = 0.92 and p = 0.26, respectively). None of the prognostic parameters analyzed was correlated significantly with the serum assay concentrations. Likewise, no correlations were also found between these serum concentrations and response to chemotherapy. No significant correlation was found between serum IGF-1 and IGFBP-3 levels in BC patients (r s = 0.048, p = 0.66).The patients with elevated serum IGF-1 levels had favorable in survival than those with lower levels (p = 0.05). However, serum IGFBP-3 concentrations were found no prognostic role for outcome (p = 0.35). In conclusion, elevated serum IGF-1 level is afavorable prognostic factor for overall survival in BC patients.

Synuclein-gamma predicts poor clinical outcome in esophageal cancer patients.

The synuclein gamma (SNCG) protein, a member of neuronal protein family synuclein, has been considered as a promising potential biomarker as an indicator of cancer stage and survival in patients with cancer. The present study was conducted to evaluate the prognostic value of SNCG in patients with esophageal carcinoma (EC). SNCG levels were assessed immunohistochemically in cancer tissues from 73 EC patients. Median age was 57 (range, 29-78) years old. Forty-seven percent of the patients were male. Thirty-seven percent of the patients had upper or middle localized tumor whereas 59 % had epidermoid carcinoma. More than half of the patients (61 %) had undergone operation where 57 % received adjuvant treatment including chemotherapy or chemotherapy plus radiotherapy. Median overall survival was 11.3 ± 1.8 months (95% confidence interval (CI): 7.7-14.9 months). SNCG positivity was significantly associated with the histological type of EC and inoperability (for SNCG positive vs. negative group; epidermoid 80 vs. 53 %; p = 0.05 and inoperable 59 vs.32 %; p = 0.04, respectively). Lymph node metastasis, inoperability and receiving no adjuvant treatment had significantly adverse effect on survival in the univariate analysis (p = 0.01, p < 0.001, and p = 0.001, respectively). SNCG positivity had significantly adverse effect on survival in both univariate and multivariate analysis (p = 0.02 and p = 0.01, respectively). Our results are the first to suggest that SNCG is a new independent predictor for poor prognosis in EC patients in the literature.

Treatment modalities in primary gastric lymphoma: the effect of rituximab and surgical treatment. A study by the Anatolian Society of Medical Oncology.

AIM OF THE STUDY: Gastrointestinal lymphoma is the most common type of extranodal lymphoma and commonly involved site is the stomach. We have compared the superiority between treatment modalities for primary gastric lymphoma and we want to investigate efficacy of rituximab in gastric lymphoma. MATERIAL AND METHODS: Between April 2002 and December 2011, 146 patients with a histologically confirmed primary gastric lymphoma, initially diagnosed at eight different Cancer Centers within Turkey were evaluated retrospectively. According to the treatment modality, the patients were divided into chemotherapy (CT) alone, chemotherapy and radiotherapy (CRT), surgery and chemotherapy (SCT), surgery along with chemotherapy and radiotherapy (SCRT), and surgery (S) alone groups. RESULTS: Median follow-up period was 25.5 months. The 5-year EFS (event free survival) and OS (overall survival) rates for the patients were 55% and 62.3% respectively. In Log rank analysis of OS and EFS, we have identified levels of albumin and hemoglobine, IPI score, stage at diagnosis as factors influencing survival. In multivariate analysis of OS and EFS, only albumin and stage at diagnosis were factors independently contributing to survival. There was no statistically significant difference in terms of survival between different treatment modalities (p = 0.707 in EFS and p = 0.124 in OS). In analysis of patients treated with chemotherapy alone, there was no a statistically significant difference in terms of EFS and OS between chemotherapy regimens with or without rituximab in localized and advanced stage groups (p = 0.264 and p = 0.639). There was no statistical difference in survival rate (EFS and OS) between surgical or non-surgical treatment modalities for localized/advanced stage gastric lymphoma groups (p = 0.519 / p = 0.165). CONCLUSIONS: There are several treatment options due to similar results in different treatment modalities. Also benefit of rituximab treatment in gastric lymphoma is still a controversial subject. Additional prospective trials are definitely required in order to clarify use of rituximab in treatment of extranodal gastric lymphoma.

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.

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.

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.

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.