Efficacy of adjuvant capecitabine in residual triple negative breast cancer: a multicenter observational Turkish Oncology Group (TOG) study.

BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

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.

The Prognostic Utility of the Metastatic Lymph Node Ratio and the Number of Regional Lymph Nodes Removed from Patients with Small Bowel Adenocarcinomas.

Background and Objectives: Small bowel adenocarcinomas (SBAs) are rare tumors of the gastrointestinal system. Lymph node metastasis in patients with curatively resected SBAs is associated with poor prognosis. In this study, we determined the prognostic utility of the number of removed lymph nodes and the metastatic lymph node ratio (the N ratio). Materials and Methods: The data of 97 patients who underwent curative SBA resection in nine hospitals of Turkey were retrospectively evaluated. Univariate and multivariate analyses of potentially prognostic factors including the N ratio and the numbers of regional lymph nodes removed were evaluated. Results: Univariate analysis showed that perineural and vascular invasion, metastatic lymph nodes, advanced TNM stage, and a high N ratio were significant predictors of poor survival. Multivariate analysis revealed that the N ratio was a significant independent predictor of disease-specific survival (DSS). The group with the lowest N ratio exhibited the longest disease-free survival (DFS) and DSS; these decreased significantly as the N ratio increased (both, p < 0.001). There was no significant difference in either DFS or DSS between groups with low and high numbers of dissected lymph nodes (i.e., <13 and ≥13) (both, p = 0.075). Conclusions: We found that the N ratio was independently prognostic of DSS in patients with radically resected SBAs. The N ratio is a convenient and accurate measure of the severity of lymph node metastasis.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study).

INTRODUCTION: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI. MATERIALS AND METHODS: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells. RESULTS: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group. CONCLUSION: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs.

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.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Efficacy of adding pain neuroscience education to a multimodal treatment in fibromyalgia: A systematic review and meta-analysis.

The aim of this study was to investigate whether adding pain neuroscience education (PNE) to a multimodal approach has additional benefits in patients with fibromyalgia (FM). The methodology of this study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The methods and strategies applied in the study were registered in PROSPERO (CRD42021272246). A systematic search with related search terms in the PubMed, Ebsco (Academic Search Ultimate), Cochrane Library, Physiotherapy Evidence Database (PEDro), Medline (Ebsco), Cinahl (Ebsco), Scopus and Web of Science was conducted up to June 2021. Statistical analysis was performed with Comprehensive Meta-Analysis (CMA) software Version 3 (CMA V3, Biostat Inc) comparing before and after values of mean ± standard deviation (SD) data in both groups. The primary outcome of interest was severity of FM (Fibromyalgia Impact Questionnaire), whereas secondary outcomes were pain intensity (visual analog scale, numeric pain rating scale), catastrophizing (Pain Catastrophizing Scale), depression (Hospital Anxiety and Depression Scale [HADS]) and anxiety (HADS). The initial search strategy based on the range and language yielded 274 relevant studies and 4 of these studies met the final eligibility criteria for this study. A total of 612 patients were enrolled in the included studies. The meta-analysis showed that PNE groups were statistically more effective than the interventions applied in the control groups on severity of FM (standard mean difference [SMD] = -1.051; 95% CI = -1.309, -0.793; P < .000), pain intensity (SMD = -1.049; 95% CI = -1.400, -0.698; P < .000), catastrophizing (SMD = -0.893; 95% CI = -1.437, -0.348; P = .001), depression (SMD = -0.686; 95% CI = -0.849, -0.523; P < .000) and anxiety (SMD = -0.711; 95% CI = -0.869, -0.552; P < .000). This review demonstrates that adding PNE to a multimodal treatment including exercise therapy might be an effective approach for improving functional status, pain-related symptoms, anxiety and depression for patients with FM. There is a need for further studies, especially on the optimum duration and dosage of PNE sessions in FM.

Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study.

PURPOSE: Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population. MATERIALS AND METHODS: We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed. RESULTS: The median age was 50 years (range, 38-58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder. CONCLUSION: Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas.

Prognostic Factors for Operated Gallbladder Cancer.

PURPOSE: The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer. MATERIAL AND METHOD: We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS. CONCLUSION: Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer.

Immunohistochemical Profile of Tumor Pathways and Prognostic Significance in Colon Adenocarcinomas.

The current study examined the immunohistochemical expression levels of molecules on carcinogenesis pathway and evaluated their clinicopathologic significance in colorectal adenocarcinoma (CRA). A total of 189 CRA and 20 colonic mucosal tissue samples were evaluated by immunohistochemical staining using 38 antibodies targeting the known molecules that play roles in developmental pathways of various tumors. The immunoexpression data of the patients were compared to clinicopathologic parameters. Expression loss of MLH1, MSH2, MSH6, PMS2, PTEN, Smad4 and E-cadherin, and overexpression of ALDH1, CD44, CAIX, P504S (AMACR), TGFΒ, and ZEB1 were statistically significant in CRA compared to normal colon mucosa. Long-term clinical follow-up findings in our cases suggested that AMACR, CAIX, ALDH1, TGFΒ, ZEB1 overexpression, and cyclinD1, p53, E-cadherin, and PTEN inactivity might be useful markers of a poor prognosis in CRA. In survival analyses, the expression of CAIX and AMACR were significantly associated with overall survival in both the univariate and multivariate analyses (log-rank test; p < 0.01 and p < 0.05, respectively).

Correlation of Caveolin-1 Expression with Prognosis in Patients with Gastric Cancer after Gastrectomy.

BACKGROUND: Upregulation of caveolin-1 (Cav-1) expression is correlated with histopathological grade and poor prognosis in several human cancers. However, in gastric cancer, its clinical utility as a useful prognostic molecular marker remains unclear. METHODS: The prognostic importance of Cav-1 expression was retrospectively analyzed by immunohistochemistry in 148 patients with gastric cancer who had undergone radical gastrectomy. RESULTS: Cav-1 expression was positive in 23 (15.5%) patients and negative in 125 (84.5%) patients. Tumor location, tumor grade, lymph node involvement, pT stage, pTNM stage, and the presence of recurrence were found to be significantly associated with Cav-1 expression. The median disease-free survival (DFS) of patients with negative Cav-1 expression was significantly better than that of patients with positive Cav-1 expression (not reached vs. 10.2 months, p < 0.001). Moreover, patients with positive Cav-1 expression had a worse median overall survival (OS) compared to patients with negative Cav-1 expression (14.2 vs. 40.3 months, p = 0.004). In the multivariate analysis, Cav-1 expression (positive vs. negative) was an independent prognostic factor for DFS (p < 0.001, hazard ratio (HR) 2.58) and OS (p = 0.031, HR 1.87), as was lymph node metastasis. CONCLUSION: Our results suggest that positive Cav-1 expression is associated with progression and poor prognosis in gastric cancer patients after radical gastrectomy. Targeting Cav-1 would be a potential option for future gastric cancer treatment.

Evaluation of Bevacizumab in Advanced Small Bowel Adenocarcinoma.

BACKGROUND: Small bowel adenocarcinomas (SBAs) are rarely seen tumors. Data regarding the use of chemotherapy together with bevacizumab in patients with advanced SBA are lacking. The aim of this study was the evaluation of treatment with bevacizumab in advanced SBA. MATERIALS AND METHODS: Twenty-eight patients from 5 centers with a diagnosis of advanced SBA who received first-line treatments with modified FOLFOX6 (mFOLFOX6; oxaliplatin, leucovorin, and 5-fluorouracil) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) chemotherapy regimens were involved in the study. All patients were divided into 2 groups; those who received bevacizumab together with these chemotherapy regimens (Chemo+Bev group) and those who did not receive bevacizumab (Chemo group). RESULTS: The median progression-free survival (PFS) and overall survival (OS) times of all population were 8.7 months and 16.9 months, respectively. The overall response rate was 43.7% in the Chemo group and 58.3% in the Chemo+Bev group. The median PFSs in the Chemo and Chemo+Bev groups were found to be 7.7 months and 9.6 months, respectively, and the median OSs were 14.8 months and 18.5 months, respectively. There was not a significant difference between the groups in terms of overall response rate, PFS, and OS. CONCLUSION: Although there was no significant difference in any of the outcomes, use of bevacizumab together with chemotherapy is a more effective treatment approach compared with chemotherapy alone, and it does not cause an excess of significant toxicity.

Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA. MATERIALS AND METHODS: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates. RESULTS: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts. CONCLUSIONS: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.

Gastric Adenocarcinoma Biomarker Expression Profiles and their Prognostic Value.

Expression levels of several molecules implicated in carcinogenesis were examined by immunohistochemical staining, and the prognostic significance of their expression levels in gastric adenocarcinoma (GA) was evaluated. A total of 115 GA and 20 control gastric tissue samples were evaluated by immunohistochemistry using 33 antibodies targeting molecules known to play a part in the development of various tumors. Overexpression of carbonic anhydrase IX (CAIX) and loss of AT-rich interactive domain-containing protein 1A (ARID1A), aldehyde dehydrogenase 1 (ALDH1), and CD44 expression in GA patients were significantly correlated with lymph node (LN) metastasis, advanced tumor stage, and poor prognosis. The results demonstrated that ALDH1A and ARID1A may be strong independent prognostic factors associated with overall survival and recurrence-free survival (p < 0.01 and p < 0.05, respectively). Our results demonstrated that ALDH1, CD44, ARID1A, and CAIX in immunoreactive GA tumor cells exhibit different expression profiles compared with control cells and that these differences are associated with patient survival. The molecules with differential expression profiles were associated with some common functions, including hypoxia, epithelial-to-mesenchymal transition, and SW1/SNF-mediated chromatin remodeling. In addition, the loss of ALDH1, ARID1A, and CD44 and the overexpression of CAIX are important for tumor invasion and metastasis; therefore, they may serve as useful prognostic indicators of long-term survival in patients with GA. In conclusion, our study found that abnormal expression of some of the proteins evaluated in GA tumor cells might have an important role in carcinogenesis and tumor progression and thus may influence the prognosis of patients with GA.

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.

Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastric pH in extensive metabolizer patients with gastroesophageal reflux disease.

BACKGROUND/AIMS: Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype. MATERIALS AND METHODS: Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients. RESULTS: On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment. CONCLUSION: Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.

Retrospective multicenter evaluation of patients diagnosed with mucosal melanoma: a study of Anatolian Society of Medical Oncology.

Mucosal melanoma (MM) is a rare type of cancer that differs significantly from cutaneous melanoma. In this study, we aimed to evaluate clinical and demographical characteristics, prognoses and factors influencing survival, treatment alternatives, and features of different subtypes of the patients. The patients were followed up with and treated in different centers due to their diagnoses of MM. We retrospectively analyzed data of 107 patients who were diagnosed with MM in 14 different institutions in Turkey. The mean age of the patients was 64.5 years. Of the patients, 47 % were female and 53 % were male. The median overall survival (OS) was 17 months, and the mean follow-up duration was 27 months. The 2-year survival rate was 42 %, and the 5-year survival rate was 23 %. The best survival rate appeared in those patients with MM in the head-neck region (median survival rate was 27 months, P = 0.034). The most common anatomical site was the head-neck region. In a univariate analysis, variables including age ≥65 years, the anatomical site of the primary lesion other than head and neck region, the metastatic stage of the disease, high levels of lactate dehydrogenase (LDH), and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 were found to be associated with poor survival (P < 0.05). However, in a multivariate analysis, only advanced stage disease (HR = 2.70; 95 % CI, 1.64-4.45; P = 0.000) and high LDH levels (HR = 2.31; 95 % CI, 1.40-3.80; P = 0.001) were determined to be adverse prognostic variables. Primary MM presents a more aggressive behavior and offers a poorer prognosis compared to cutaneous melanoma. Because the disease is rarely seen, is heterogeneous, and lacks randomized studies, issues concerning optimal treatment approaches and management and clinical characteristics of the disease have not been clarified yet.