Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

The impact of tamoxifen treatment on voice parameters in premenopausal women with breast cancer.

OBJECTIVE: The study aims to investigate the estrogen-agonistic effects of tamoxifen on voice parameters in premenopausal women diagnosed with breast cancer. METHODS: A total of 108 premenopausal women were included, segmented into distinct treatment groups and a control group. Objective sound analysis was conducted using robust statistical methods, employing SPSS 25.0 for data analysis. RESULTS: The study identified a statistically significant reduction in Jitter values across all treatment groups compared to the control group. No significant changes were observed in other voice quality parameters such as F0, Shimmer, NHR, and HNR. CONCLUSIONS: The findings suggest that tamoxifen may have an estrogen-agonistic effect on voice quality, thereby potentially influencing future treatment protocols. This research fills a critical void in existing literature and sets the stage for more comprehensive studies that consider affects of hormonal therapies to voice.

Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: PD-1 inhibitors combined with chemotherapy have shown efficacy in gastric or gastro-esophageal junction cancer. We compared the efficacy and safety of pembrolizumab plus chemotherapy with placebo plus chemotherapy in participants with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. METHODS: KEYNOTE-859 is a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial, done at 207 medical centres across 33 countries. Eligible participants were aged 18 years and older with previously untreated histologically or cytologically confirmed locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to receive pembrolizumab or placebo 200 mg, administered intravenously every 3 weeks for up to 35 cycles. All participants received investigator's choice of fluorouracil (intravenous, 800 mg/m2 per day) administered continuously on days 1-5 of each 3-week cycle plus cisplatin (intravenous, 80 mg/m2) administered on day 1 of each 3-week cycle or capecitabine (oral, 1000 mg/m2) administered twice daily on days 1-14 of each 3-week cycle plus oxaliplatin (intravenous, 130 mg/m2) administered on day 1 of each 3-week cycle. Randomisation was done using a central interactive voice-response system and stratified by geographical region, PD-L1 status, and chemotherapy in permuted block sizes of four. The primary endpoint was overall survival, assessed in the intention-to-treat (ITT) population, and the populations with a PD-L1 combined positive score (CPS) of 1 or higher, and PD-L1 CPS of 10 or higher. Safety was assessed in the as-treated population, which included all randomly assigned participants who received at least one dose of study intervention. Here, we report the results of the interim analysis. This study is registered with ClinicalTrials.gov, NCT03675737, and recruitment is complete. FINDINGS: Between Nov 8, 2018, and June 11, 2021, 1579 (66%) of 2409 screened participants were randomly assigned to receive pembrolizumab plus chemotherapy (pembrolizumab group; n=790) or placebo plus chemotherapy (placebo group; n=789). Most participants were male (527 [67%] of 790 participants in the pembrolizumab plus chemotherapy group; 544 [69%] of 789 participants in the placebo plus chemotherapy group) and White (426 [54%]; 435 [55%]). Median follow-up at the data cutoff was 31·0 months (IQR 23·0-38·3). Median overall survival was longer in the pembrolizumab group than in the placebo group in the ITT population (12·9 months [95% CI 11·9-14·0] vs 11·5 months [10·6-12·1]; hazard ratio [HR] 0·78 [95% CI 0·70-0·87]; p<0·0001), in participants with a PD-L1 CPS of 1 or higher (13·0 months [11·6-14·2] vs 11·4 months [10·5-12·0]; 0·74 [0·65-0·84]; p<0·0001), and in participants with a PD-L1 CPS of 10 or higher (15·7 months [13·8-19·3] vs 11·8 months [10·3-12·7]; 0·65 [0·53-0·79]; p<0·0001). The most common grade 3-5 adverse events of any cause were anaemia (95 [12%] of 785 participants in the pembrolizumab group vs 76 [10%] of 787 participants in the placebo group) and decreased neutrophil count (77 [10%] vs 64 [8%]). Serious treatment-related adverse events occurred in 184 (23%) participants in the pembrolizumab group and 146 (19%) participants in the placebo group. Treatment-related deaths occurred in eight (1%) participants in the pembrolizumab group and 16 (2%) participants in the placebo group. No new safety signals were identified. INTERPRETATION: Participants in the pembrolizumab plus chemotherapy group had a significant and clinically meaningful improvement in overall survival with manageable toxicity compared with participants in the placebo plus chemotherapy group. Therefore, pembrolizumab with chemotherapy might be a first-line treatment option for patients with locally advanced or metastatic HER2-negative gastric or gastro-esophageal junction adenocarcinoma. FUNDING: Merck Sharp and Dohme.

Brigatinib-associated autoimmune hepatitis: A case report.

INTRODUCTION: Brigatinib is a next-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a wide variety of ALK mutations and ROS1 rearrangements. While pancreatic enzyme elevations due to brigatinib are well known, we wanted to present a case that caused liver toxicity. CASE REPORT: ALK and ROS1 translocations were detected in a 58-year-old patient diagnosed with metastatic lung adenocarcinoma. In the patient who had a good response with brigatinib, more than 5-fold elevation was detected in liver enzymes at the fifth month of treatment. MANAGEMENT & OUTCOME: After excluding other hepatitis factors, the patient was thought to have autoimmune hepatitis, and methylprednisolone was started and liver enzymes were decreased. DISCUSSION: Increased creatine kinase and lipase levels are common side effects associated with brigatinib, while liver toxicity is rare. Autoimmune hepatitis due to brigatinib was considered because of hepatic toxicity that developed in the fifth month of treatment and responded well to steroids.

Effect of Microsatellite Status and Pan-Immune-Inflammation Score on Pathological Response in Patients with Clinical Stage III Stomach Cancer Treated with Perioperative Chemotherapy.

Background and Objective: This study evaluated the relationship between microsatellite status (MSI) and pan-immune-inflammation score (PIV) in tumor response to neoadjuvant chemotherapy (NAC) in patients with clinical stage III gastric cancer (cStage III GC). Materials and Methods: Microsatellite instability (MSI) status was evaluated based on pathology preparations. Pan-immune-inflammation score (PIV) was obtained from pre-treatment blood tests. The relationship of both parameters with pathological complete response (pCR) was evaluated. Results: A total of 104 patients were included in this study. All the patients were stage III GC patients receiving perioperative treatment. There were 13 patients in total who achieved a pCR response. While CNS was detected in 11 of the patients who achieved a pCR, the MSI status of the other two patients was unknown. No pCR was observed in any patient with MSI-H. According to the cut-off value for PIV, 25 (24%) patients were in the PIV-low (≤53.9) group, while 79 (76%) were in the PIV-high (>53.9) group. Based on univariate analysis, a higher PIV was associated with worse outcomes for pathological response, disease recurrence, and survival (p < 0.05). Conclusions: In patients with clinically stage III GC, the presence of MSI-H may predict no benefit from perioperative treatment. Conversely, a pre-treatment PIV score using specific cut-off values may provide a positive prediction of pathological response and survival.

Evaluation of antibody response after two doses of the Sinovac vaccine and the potential need for booster doses in cancer patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is more severe in some specific patient groups, such as cancer patients with a mortality rate of 26.5%. The main way of protection is vaccination. In this study, we aimed to evaluate the antibody responses of our cancer patients who received two doses of the inactivated COVID-19 vaccine manufactured by Sinovac Life Sciences. Patients over the age of 18, who had not been suspected or polymerase chain reaction-confirmed COVID-19 positive, who received two doses of the vaccine, and at least 28 days passed after the second dose, and who received at least one dose of cancer treatment before the vaccination-were included in the study. Immunoglobulin class G antibodies against the receptor binding region (S-RBD) of the spike protein S1 subunit of SARS-CoV-2 were studied. A total of 200 patients with a diagnosis of cancer were included in the study. The median time between the second dose of the Sinovac vaccine and the time of blood collection was 3.44 (3.20-3.84) months. SARS-CoV-2 antibody positivity was detected in 110 (55%) patients. The two subgroups with the highest antibody levels were gynecological cancers and breast cancers, with median 158.5 AU/ml (38.4-764.5) and 106.3 AU/ml (61.9-162.9) levels, respectively. Antibody positivity rate was 46.8% in patients who received chemotherapy at any time between the first dose of the vaccine and the date of blood collection; and it was 73.8% in the group that did not receive chemotherapy (p < 0.001). As a result, the expected antibody response was not obtained with two doses of the Sinovac vaccine. Therefore, if the Sinovac vaccine is to be preferred for these patients, the appropriate booster time for the third dose should be determined or other vaccines, such as messenger RNA vaccines, with reported higher antibody responses should be considered.

Proton pump inhibitors may reduce the efficacy of ribociclib and palbociclib in metastatic breast cancer patients based on an observational study.

INTRODUCTION: Approximately 20-33% of all cancer patients are treated with acid-reducing agents (ARAs), most commonly proton pump inhibitors (PPIs), to reduce gastroesophageal reflux disease symptoms. Palbociclib and ribociclib are weak bases so their solubility depends on different pH. The solubility of palbociclib dramatically decreases to < 0.5 mg/ml when pH is above 4,5 but ribociclibs' solubility decreases when pH increases above 6,5. In the current study, we aimed to investigate the effects of concurrent PPIs on palbociclib and ribociclib efficacy in terms of progression-free survival in metastatic breast cancer (mBC) patients. PATIENTS AND METHODS: We enrolled hormone receptor-positive, HER2-negative mBC patients treated with endocrine treatment (letrozole or fulvestrant) combined palbociclib or ribociclib alone or with PPI accompanying our observational study. During palbociclib/ribociclib therapy, patients should be treated with "concurrent PPIs" defined as all or more than half of treatment with palbociclib/ribociclib, If no PPI was applied, it was defined as 'no concurrent PPI', those who used PPI but less than half were excluded from the study. All data was collected from real-life retrospectively. RESULTS: Our study included 217 patients, 105 of whom received palbociclib and 112 received ribociclib treatment. In the study population CDK inhibitor treatment was added to fulvestrant 102 patients ( 47%), to letrozole 115 patients (53%). In the Palbociclib arm fulvestrant/letrozole ratio was 53.3/46.7%, in the ribociclib arm it was 41.07/58.93%. Of 105 patients who received palbociclib, 65 were on concomitant PPI therapy, 40 were not. Of the 112 patients who received ribociclib, 61 were on concomitant PPI therapy, 51 were not. In the palbociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (13.04 months vs. unreachable, p < 0.001). It was determined that taking PPIs was an independent predictor of shortening PFS (p < 0.001) in the multivariate analysis, In the ribociclib group, the PFS of the patients using PPIs was shorter than the PFS of the patients not using (12.64 months vs. unreachable, p = 0.003). It was determined that taking PPIs was single statistically independent predictor of shortening PFS (p = 0.003, univariate analysis). CONCLUSIONS: Our study demonstrated that concomitant usage of PPIs was associated with shorter PFS in mBC treated with both ribociclib and especially palbociclib. If it needs to be used, PPI selection should be made carefully and low-strength PPI or other ARAs (eg H2 antagonists, antacids) should be preferred.

Prognostic Importance of Inflammatory Indexes in Patients Treated by Pazopanib for Soft Tissue Sarcoma.

BACKGROUND: The goal of this study was to evaluate the predictive and prognostic importance of the lymphocyte to monocyte ratio (LMR), neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (DNLR), and systemic immune inflammation index (SSI) in STS cases treated with pazopanib. METHODS: Thirty STS patients treated with pazopanib were included in this study. SSI, DNLR, LMR, and NLR values were calculated at baseline and in the first month. Median values of these predictors in these patients (SSI (944), DNLR (1.8), LMR (2.7), and NLR (3.0)) were taken as cutoff values. The associations between the survival time (both overall survival (OS) and progression-free survival (PFS)) and cutoff values were evaluated using Kaplan Meier curves and Cox regression models. RESULTS: Patients with low SSI, NLR, and DNLR values at pretreatment and after the initial response had longer OS (for OS - p = 0.024, p = 0.015, and p = 0.041, respectively). Longer OS was also found in patients who showed increasing LMR and decreasing NLR after one month of therapy (for ΔLMR, p = 0.016; for ΔNLR, p = 0.016). Pa-tients with low SSI and NLR values at pretreatment and after the initial response had longer PFS (for PFS, p = 0.014, p = 0.04, p ˂ 0.001, respectively). In terms of initial responses to treatment, SSI, NLR, DNLR, and increased LMR were detected as independent risk factors in univariate analysis, but initial response was found to be the only independent risk factor for PFS in multivariate analysis. CONCLUSIONS: Low values of SSI, NLR, and DNLR at pretreatment and at initial response may predict long-term survival rates. After one month of treatment with pazopanib, decreased NLR and increased LMR are predictive of favorable outcomes in these cases.

Panitumumab Associated Acute Pancreatitis.

INTRODUCTION: The addition of panitumumab to chemotherapy in wild-type metastatic colon cancer contributes to survival. While the skin related side effects of panitumumab are well known, we wanted to present a case where it was a possible cause of acute pancreatitis. CASE REPORT: The FOLFOX regimen was started in a 67-year-old patient with sigmoid colon cancer and multiple liver metastases. After 2 cycles, genetic tests were concluded and panitumumab 6 mg/kg was added to the treatment. The patient who presented with abdominal pain 2 days after the treatment was hospitalized with acute pancreaatitis. MANAGEMENT & OUTCOME: Abdominal tomography of the patient was compatible with acute pancreatitis. Oral intake was stopped, IV hydration was started. The patient, whose complaints regressed, was discharged on the 3rd day of hospitalization. DISCUSSION: Skin side effects related to panitumumab are observed quite frequently. Although panitumumab related gastrointestinal side effects have been reported, there is no data on acute pancreatitis. Panitumumab was added to the chemotherapy regimen he received, and it was thought that panitumumab might be the etiological factor in the case who developed pancreatitis.

Steatohepatitis due to FOLFIRINOX regimen in adjuvant pancreas cancer treatment mimicking liver metastasis.

INTRODUCTION: The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is more toxic than gemcitabine, but it is a safe regimen with manageable toxicities. CASE REPORT: We report a case with steatohepatitis mimicking liver metastasis as toxicity that was not seen in study patient population.Management and outcome: In the adjuvant statement with FOLFIRINOX due to biopsy, we give the same regimen by excluding metastasis. DISCUSSION: The adverse events of drugs are important predictive factor for treatment management, as important as efficacy. Especially the new lesion and metastasis is the most important factor for changing treatment. The clinicians must be careful about adverse events of regimens. CONCLUSION: FOLFIRINOX regimen is the most important combination in pancreas cancer adjuvant setting. This case shows us the different presentation of usual adverse event.

Enteral nutrition consensus report from KEPAN: Indications, choice, practical application, and follow-up.

OBJECTIVES: Clinicians are in need of guidance that will ease the application of medical nutrition therapy. In order to facilitate the application and success of medical nutrition therapy, the Turkish Clinical Enteral & Parenteral Nutrition Society (KEPAN) planned a report that is short, is clear, and has clear-cut recommendations that will guide health care professionals in the indications, choice, practical application, follow-up, and stopping of enteral nutrition. METHODS: The enteral nutrition consensus report on enteral nutrition use in medical nutrition therapy was developed by a study group (12 working group academicians and 17 expert group academicians) under the organization of KEPAN. The enteral nutrition consensus report was generated in 5 online and face-to-face phases from December 2019 through October 2022. At the end (Delphi rounds), a total of 24 questions and subjects, recommendations, and comments were sent to the enteral nutrition working group and the expert group via e-mail. They were asked to score the criteria by using the Likert scale. RESULTS: The first round of the study resulted in acceptance of all 24 recommendations. None of the criteria was rejected. Only some minor editing for wording was recommended by the panelists during the first and second rounds of the Delphi study. The final report was sent to all 29 panelists and was approved without any revision suggestions. CONCLUSION: This report provides 24 clear-cut recommendations in a question-answer format. We believe that this report could have a significant effect on the optimum use of enteral nutrition in the context of medical nutrition therapy when clinicians manage everyday patients.

Bintrafusp Alfa With CCRT Followed by Bintrafusp Alfa Versus Placebo With CCRT Followed by Durvalumab in Patients With Unresectable Stage III NSCLC: A Phase 2 Randomized Study.

INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment. METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point). RESULTS: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression-free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69-3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any-grade treatment-emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%). CONCLUSIONS: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC.

Efficacy and safety of the proposed bevacizumab biosimilar BAT1706 compared with reference bevacizumab in patients with advanced nonsquamous non-small cell lung cancer: A randomized, double-blind, phase III study.

BACKGROUND: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU-sourced reference bevacizumab (EU-bevacizumab) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). METHODS: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU-bevacizumab plus paclitaxel and carboplatin (EU-bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU-bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU-bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75-1.33 (China National Medical Products Administration requirements), or 0.73-1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of -0.12 to 0.15 (EMA requirements). RESULTS: In total, 649 randomized patients (BAT1706, n = 325; EU-bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU-bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94-1.24) and the ORR18 risk difference of 0.03 (95% CI: -0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU-bevacizumab. The safety profile of BAT1706 was consistent with that of EU-bevacizumab and no new safety signals were observed. CONCLUSION: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.

Can LMWH improve the outcome of patients with inoperable stage III non-small cell lung cancer?

AIM OF THE STUDY: Lung cancer is the most common malignancy, accounting for one-third of all deaths from cancer. Some studies have shown that low molecular weight heparin (LMWH) significantly prolongs the survival of patients with non-small cell lung cancer (NSCLC). The aim of this study was to determine the effects of treating inoperable stage III NSCLC with LMWH in addition to concurrent chemoradiotherapy. MATERIAL AND METHODS: Eighty-two patients with inoperable stage III NSCLC were evaluated at Dicle University's Medical Oncology Department between 2005 and 2010. All patients were treated with concurrent chemoradiotherapy (CRT) with or without LMWH (enoxaparin 4000 IU/day) depending on the patient's risk of thrombosis. The primary objectives were to determine disease-free survival (DFS) and overall survival (OS) for patients treated with LMWH. RESULTS: A total of 38 patients in the LMWH negative group and 44 patients in the LMWH positive group were included in the study. The median OS was 11.2 months for the enoxaparin recipients and 12.7 months for the non-enoxaparin group (p = 0.4). The median DFS was 9.3 months with CRT alone and 10.0 months with CRT plus enoxaparin (p = 0.9). The one-year OS rates were 47% and 34% for groups treated with CRT and enoxaparin plus CRT, respectively, while the two-year OS rates were 23% and 21%, respectively. No significant difference was noted between the two groups in terms of grade 3-4 hematologic toxicity and mucositis (p = 0.3). CONCLUSIONS: This study did not demonstrate improvements in survival for patients with NSCLC treated with enoxaparin. LMWH's positive contribution is still controversial.

Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.

Background and objective Male breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients. Materials and methods We retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded. Results The mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4. Conclusion The hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.

Predictors of Survival in Turkish Patients with Primary Glioblastoma.

AIM: An increasing number of biomarkers of primary glioblastoma (GBM) have recently been described. We aimed to investigate the biological and clinical factors that affect survival in Turkish patients with primary GBM. MATERIAL AND METHODS: The clinical and demographic data of all patients with primary GBM diagnosed between 2007 and 2016 were evaluated. In all the patients? pathological specimens, O6 methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH) 1 mutation were detected retrospectively by immunohistochemistry. Kaplan-Meier survival analysis, log-rank test, and multivariate analyses of the Cox hazard proportional model for all the variables were performed using the SPSS statistical package. The treatment details and other patient-related factors were identified, and their correlations were analyzed. RESULTS: We enrolled 137 primary GBM patients to the study. Median progression free survival (PFS) was 8.57 months (95% CI:6.8-9.5) and median overall survival (OS) was 12 months (95% CI:10.8-13.3). IDH-1 mutations were detected in 21 primary GBMs (15.3%). PFS was 15.43 ± 1.95 months. Survival rates were higher, but no statistically significant difference (p=0.074). MGMT methylation was detected in 40 primary GBMs (29.2%). OS and PFS of MGMT (+) cases were higher than MGMT(-) cases (p=0.001; p=0.001 respectively). Ki67 (%) measurement (10%-90%) average is 32.64 ± 16.56. No statistically significant between higher and lower ki67 levels (p=0.510, p=0.505 respectively). KPS (%) more than 70 at the time of diagnosis statistically significant longer median OS and PFS (p=0.001). PFS and OS were higher in all treatment modalities. CONCLUSION: The most important factors that affected survival were performance score, MGMT methylation status, systemic oncologic therapy, and IDH mutation in the Turkish population with primary GBM. We demonstrated that MGMT methylation and higher KPS levels were associated with significiantly longer OS and PFS.

Low dose vincristine-induced severe polyneuropathy in a Hodgkin lymphoma patient: a case report (vincristine-induced severe polyneuropathy).

Chemotherapeutic drugs are the most common toxic agents for peripheral nerves. Vincristine is a vinca alkaloid drug that is used for the treatment of several malignancies in combination with other chemotherapeutic agents. Treatment with intravenous (IV) vincristine at doses above 5 mg leads to a dose-dependent neuropathy with sensory symptoms but higher cumulative doses at around 30 to 50 mg are needed for the development of motor symptoms. The standard maximum adult IV vincristine dose is 2 mg IV per dose given at weekly intervals. However, administration of a single 2-mg dose IV vincristine may rarely result in the development of peripheral neuropathy. Few case reports have been presented on vincristine-associated severe paralysis in patients with preexisting hereditary neuropathy like Charcot-Marie Tooth (CMT) disease, who received doses even lower than 2 mg. Herein, we reported a Hodgkin lymphoma patient who developed severe polyneuropathy after receiving 2 mg vincristine treatment and was subsequently found to carry the CMT1A duplication responsible for CMT disease.

The efficacy of rituximab in patients with splenectomized refractory chronic idiopathic thrombocythopenic purpura.

The most difficult problem a physician encounters is the management of patients with idiopathic thrombocytopenic purpura (ITP), who has persistent severe thrombocytopenia after failure of initial treatment with glucocorticoids and splenectomy. Most of the patients refractory to corticosteroids and splenectomy will become refractory to other available agents, such as intravenous immunoglobulin (IVIg), danazol or chemotherapy. In this study, we investigated the effect of rituximab on 17 splenectomized refractory chronic ITP patients. Here, we showed that the anti-CD20 antibody, rituximab, induces a clinically significant response in severe chronic ITP patients, who are unresponsive to other therapeutic options. After sixth month, 10 out of 14 responders were still maintaining their durable and significant platelet responses (platelet counts >50 x 10(9)/l), without requirement to any other ITP medication. Therefore, we suggest that, rituximab is an effective treatment option in splenectomized refractory or relapsed ITP patients. Rituximab was well tolerated without severe side effects.

A case of essential mixed cryoglobulinemia and associated acquired von-Willebrand disease treated with rituximab.

Current treatment options of essential mixed cryoglobulinemia (EMC); include immunosuppressive approaches, such as corticosteroids, cyclophosphamide, plasma exchange, other cytotoxic drugs in moderate to severe manifestations. Some controlled studies have been carried out to assess the efficacy of anti-CD20 monoclonal antibody, rituximab in patients with hepatitis C (HCV) related cryoglobulinemia (CG) and in patients with autoimmune disorders. Recent trials and some case reports demonstrate a beneficial role for rituximab in HCV related mixed CG. Although, the published evidence for treatment of EMC with rituximab is restricted to case reports, which have shown positive results. Several diseases include lymphoproliferative and myeloproliferative disorders, solid tumors, immunological disorders, cardiovascular disorders and some drugs associated with acquired von Willebrand disease (avWD). CG, which is a kind of immune complex disease, may be related with development of autoantibodies to various autoantigens. In this present case report, we showed the efficacy of rituximab in a 21-year-old female patient, suffered from neuropathy and arthralgia related with EMC, and developed avWD, presented with mucosal bleeding associated with CG. von Willebrand factor activity of our patient also increased with controlling the underlying disease, EMC by rituximab. This case demonstrate that rituximab may be an effective treatment option in EMC and avWD mainly related to CG.

The effects of nonsteroidal anti-inflammatory drugs on platelet function and severity of upper gastrointestinal haemorrhage.

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) damage primarily due to the inhibition of prostaglandin synthesis in gastric mucosa, which is an important factor in mucosa protection. Platelets are a cardinal feature of vascular repair. A variety of angiogenic stimulators are stored in platelets and are released during clotting at the wound. When there is a defect in any of these functions and/or platelet number, haemostasis is usually impaired and there may be an associated increased risk and severity of bleeding. While the mechanism of mucosal injury and bleeding are well documented with the use of NSAIDs, very little is known about the platelet function abnormalities and their effects on severity of upper GI bleedings. We performed a prospective analysis of 49 patients who had a history of NSAIDs use to investigate the association between the platelet function impairment associated with NSAIDs and severity of upper GI haemorrhages. Thirty-six of 49 patients (73.5%) had deteriorated platelet function. Mean severity score of patients with deteriorated platelet functions was 3.39, and that of patients with normal platelet functions was 2.46. Mean severity score was statistically significantly higher in patients with deteriorated platelet functions. In conclusion, impaired platelet functions associated with NSAIDs may cause more severe upper GI bleeding. Clinicians should be alert for GI complications especially in older patients and in those with a history of ulcer bleeding.