Search

Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Objective: Colorectal cancers (CRCs) are among the most common cancers all over the world with a high mortality rate. Many prognostic factors have been identified for these cancers, one of which is the lymph node ratio (LNR). The purpose of this study was to reveal the prognostic importance of the LNR in stage III CRCs. Material and Methods:The records of stage III colorectal patients who received adjuvant chemotherapy between January 1998 and May 2014 were examined retrospectively. Similar to the literature, the patients were divided into three groups according to their LNRs. Those with a ratio of 0–0.20 were in the 1st group, with 0.21–0.50 were in the 2nd group, and with 0.51–1 were in the 3rd group. Demographic characteristics of the patients, number of positive and total lymph nodes removed, lymph node positivity rate, presence of free tumor nodules, and survival were evaluated. Results: A total of 263 patients were included in the study. While 163 (61.9%) of the patients were male, the median age was 62 (min: 25–max: 85). The mean number of lymph nodes removed was 17.46 (±11.55), and the mean number of positive lymph nodes was 3.48 (±5.13). The mean duration of disease-free survival (DFS) was 65.2 (±46.07) months (min = 6, max = 223). The mean overall survival time (OS) was 70.9 (±44.4) months (min = 6, max = 223). In univariate analysis, it was observed that as the LNR increased, recurrence and mortality increased statistically significantly (P < 0.001). According to the results of multivariate analysis, the relationship of DFS and OS with the LNR groups was statistically significant (P = 0.030 and P = 0.019, respectively). Conclusion: The LNR in operated stage III CRC is an effective prognostic factor on DFS and OS

Dünyanın farklı bölgelerinde birçok kompozit travers teknolojisi geliştirilmiştir. Bu teknolojiler geleneksel traversler olarak nitelenen çelik travers, ahşap travers ve beton traverslere potansiyel bir alternatif olarak ortaya çıkmıştır. Çelik ve betondan farklı olarak kompozit traversler, ahşap travers davranışını taklit edecek şekilde tasarlanabilir ve neredeyse bakım gerektirmeyip, çevresel açıdan daha üstündürler. Bu çalışma kapsamında demiryollarında farklı miktar ve uzunluklarda fiber içeren Tip 1, Tip 2 ve Tip 3 gibi kompozit traversler hakkında bilgi verilerek bu traverslerin kullanımı ve performans karşılaştırılması detaylı olarak yapılmıştır. Kompozit traversler ile konvansiyonel tip olan ahşap, çelik ve beton traverslerin karşılaştırılması yapılmış olup kompozit traverslerin kullanımı sırasında meydana gelen zorluklardan bahsedilerek bu traverslerin demiryollarında geniş çapta kullanım alanı bulabilmesi için hem teknik hem de maliyet açısından ne gibi hususları karşılamaları gerektiği hakkında tavsiyelerde bulunulmuştur.

Objective The successful results obtained in trials may not necessarily translate into prolonged survival of metastatic colorectal cancer (mCRC) patients in real life. This multinational registry study aimed to evaluate the real-life data effecting the survival of patients with mCRC. Methods This is a multinational, retrospective registry study. Turkish and Greek mCRC patients diagnosed between 2005 and 2012, with at least 3 years of follow-up data or who died before 3 years of follow-up were included in the study. Results A total of 364 were included in the study. RAS and BRAF mutation rates were found to be 36% and 39%, respectively. As first-line therapy, 196 (54%) patients received bevacizumab and Anti-EGFR treatments in combination with chemotherapy. The objective response rate was 42% (n = 152) and 32% (n = 78) for 1(st) line and 2(nd) line treatments, respectively. While the median progression-free survival (PFS) with the 1(st) line treatment was 10 months, it was 7 months with the 2(nd) line treatments. In the total study population median PFS and overall survival (OS) were 10 (95% CI, 8.3-11.6) and 35 (95% CI, 30.7-39.2) months, respectively. In Turkish and Greek patients, median OS (36 months versus 29 months, p = .81) and PFS (10.2 versus 9.2, p = .42) were not different. In multivariate analysis, ECOG PS of >= 2 and having metastases in more than one region decreased overall survival (p = .002 and p = .003), it was found that wild RAS and BRAF mutations and second metastasectomy contributed to overall survival (p = .047 and p < .001). Conclusion In conclusion, it seems that the patient's performance status, tumor location, number of metastatic lesions at the time of diagnosis affect the prognosis of mCRC. Although access to molecular tests and first-line treatments differ between Greece and Turkey, no significant difference was found in survival times.

We aimed to compare the efficacy and the safety of the FOLFOX and the FLOT regimens in metastatic gastric cancer (mGC) as first-line treatment. It was a retrospective multicenter observational study. The comparisons between groups were conducted in terms of progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and hematologic adverse events. Seventy-nine patients, diagnosed with mGC between March 2012 and December 2019, treated with FOLFOX (n = 43) or FLOT (n = 36) regimens as first-line treatment were included in the study. The mPFS was 10.9 months [95% confidence interval (CI), 5.8-16.1] in the FLOT arm and 7.1 months (95% CI, 5.1-9.1) in the FOLFOX arm (P < 0.001). The ORR was 63.9% in the FLOT arm and 30.2% in the FOLFOX arm (P = 0.003). The mOS was 13.3 months (95% CI, 11.3-15.4) in the FLOT arm and 10.9 months (95% CI, 8.2-13.5) in the FOLFOX arm (P = 0.103). The hematologic adverse events in all grades were 88.4% (n = 38) in the FOLFOX arm compared with 80.6% (n = 29) in the FLOT arm (P = 0.335). The FLOT regimen might be a preferred option in mGC with an improved PFS and ORR compared with the FOLFOX regimen.

We present a Lagrangian formulation for the general modified chiral model. Weuse it to discuss the Hamiltonian formalism for this model and to derive thecommutation relations for the chiral field. We look at some explicit examplesand show that the Hamiltonian, containing a contribution involving aWess-Zumino term, is conserved, as required.

Background: The aim of our study was to compare the efficacy and the safety of the FLOT and the modified DCF (mDCF) regimens in patients with metastatic gastric (GC) and gastroesophageal junction (GEJ) adenocarcinoma as first-line treatment. Methods: The medical records of 72 patients were retrospectively reviewed. Survivals and hematological adverse events of the patients were examined. Factors affecting survivals were analyzed in univariate analysis. A multivariate analysis was performed with the factors contributing to survivals in univariate analysis. Results: The median PFS (mPFS) was 10.1 months (95% CI, 6.8-13.4) in the FLOT arm (n = 33) and 7.4 months (95% CI, 9.1-21.6) in the mDCF arm (n = 39) (p = 0.041). The median OS (mOS) was 12.9 months (95% CI, 9.7-16.1) in the FLOT arm and 15.4 months (95% CI, 9.1-21.6) in the mDCF arm (p = 0.622). It was found that all grade neutropenia was 51.3% vs. 72.7% (p = 0.063), febrile neutropenia was 8.3% vs. 6.3% (p = 0.743), and thrombocytopenia was 48.7% vs. 51.5% (p = 0.813) in the FLOT and mDCF arms, respectively. Anemia was 59% in the FLOT arm and 100% in the mDCF arm (p < 0.001). Grade 3-4 anemia was 7.7% in the FLOT arm and 24.2% in the mDCF arm (p = 0.052). Discussion: It was shown that the mPFS was significantly increased in the FLOT arm compared to the mDCF arm as the first-line treatment in patients with metastatic GC and GEJC. Hematological adverse events were more favorable in the FLOT arm than in the mDCF arm.

Introduction: Gastrointestinal Stromal Tumors mostly located in the stomach and esophageal GIST is extremely rare. Various genetic disorders increase the risk of developing GIST, among these, NF-1 is the most common. A case of posterior mediastial GIST developing in the neurofibromatosis patient has not been reported yet.Case: A 48-year-old male patient is being evaluated with complaints of dyspnea and progressive dysphagia. Computed tomography detected a cystic, lobulated contour mass that was located at the posterior mediastinum and measuring 11 x 14x12 cm. The giant semisolid mass has been dissected from adjacent the vertebra, the esophagus, pericardium and inferior pulmonary vein and Histopathological examination revealed GİST. Pathological examination of skin lesions confirmed NF-1. Finally, NF-1-associated posterior mediastinal GIST was diagnosed and adjuvant imatinib treatment was initiated. Conclusion: To the best our knowledge, this patient was the first case, who diagnosed with posterior mediastinal GIST developing on the basis of NF-1.

Amaç: Trastuzumabın meme kanserinde neoadjuvan tedaviye eklenmesiyle patolojik tam yanıt (PTY) oranını arttırdığı bilinmektedir ancak trastuzumabın kullanım sırasıyla ilgili kısıtlı veri bulunmaktadır. HER2 pozitif lokal ileri meme kanserinde neoadjuvan trastuzumab uygulama sırasının PTY üzerine etkisi olup olmadığını incelemeyi amaçladık. Materyal ve metod: 2010-2018 yılları arasında HER2 pozitif evre 2 ve 3 meme kanseri nedeniyle neoadjuvan trastuzumab kullanan hastaların verileri retrospektif incelenmiş olup antrasiklin bazlı tedavi sonrası trastuzumab alan 30 hasta ile tam tersi sıralama ile tedavi alan 16 hasta çalışmaya alındı. Bulgular: Çalışmaya toplam 46 hasta alınmış olup ortanca takip süresi 31 aydı (7-98). Hastaların ortanca yaşı 51 yıldı (19-72). Tüm hastaların %52 si postmenopozal, %67'si hormon reseptör pozitifti. Tüm hastalarda klinik nod pozitifliği olup %54'ü cN1 idi. Hastalar trastuzumab sıralamasına göre gruplandırıldığında bazal özellikler açısından anlamlı fark yoktu. PTY oranları trastuzumab ile tedaviye başlayanlarda %63 olup diğer grupta %37 (p=0.1) olup 3 yıllık kümülatif hastalıksız sağ kalım oranları ise sırasıyla %100 ve %80’di (p=0.2). Tek değişkenli analizde evre 2 ve VKI

Objective: In this study, our aim was to identify the main predictive factors associated with pathologic complete response (pCR) to neoadjuvantchemoradiotherapy (nCRT) in patients with locally advanced rectal cancer. Methods: The patients who had locally advanced rectal cancer and underwent a long-course nCRT, followed by curative surgery between January 2009 and December 2015 at two-center were included. The clinical factors associated with pCR or non-pCR were analyzed by Logistic regression. Results: Two hundred and three patients were included in this study. Forty-six patients (22.7%) had pCR and 157 patients (77.3%) had non-pCR. In the univariate analysis, no smoking history, clinically negative lymp node (cN-), well-differentiated tumor, tumor size of ≤5 cm, pre-nCRT CEA level of ≤5 (ng/mL) and median interval to surgery>8 week were associated with an increased rate of pCR. No smoking history [odds ratio (OR) = 3.382, P = .008], endoscopic tumor size of ≤5 [OR = 2.608, P = .03], cN- [OR = 3.800, P = .002], well-differentiated tumor [OR = 3.566, P = .002], median interval to surgery of >8 week [OR = 2.981, P = .014], and pre-nCRT CEA level of ≤5 (ng/mL) [OR = 3.067, P = .008] were determined to be independent predictive factors of pCR with logistic regression model analysis. Conclusion: No smoking history, cN-, tumor size of ≤5 cm, well-differentiated tumor, pre-nCRT CEA level of ≤5 (ng/mL) and median interval to surgery of >8 weeks were independent clinical predictors for pCR in rectal cancer patients treated with long course of nCRT. This factors may help clinicians predict the prognosis of patients and develop proper treatment approach. Keywords: Pathologic complete response, Neoadjuvant chemoradiotherapy, Locally advanced rectal cancer, Leukocyte/lymphocyte ratio, Platelet/lymphocyte ratio

This study is related to investigation of effect of different processing temperatures on tribological behaviours of high power diode laser treated samples. Laser treatment was applied to R260 grade rail steel specimens with the initial laser power of 1.750 W and a constant scanning speed of 6 mm/s at the different processing temperatures of 1.100 °C, 1.200 °C and 1.300 °C. As a conclusion 0.4, 0.56, 0.53 and 0.57 friction coefficient values were found for untreated and laser treated samples at 1.100 °C, 1.200 °C and 1.300 °C respectively. While it was expected that raise in surface hardness depending on increasing processing temperatures to result in reduction in wear rate and friction coefficient in laser treated samples, contrary an opposite situation in tribological behaviours was found.

The aim of this study was to evaluate the efficacy and toxicity profile of oral etoposide (50mg/day, days 1-14, every 3 weeks) in recurrent platinum-resistant epithelial ovarian cancer (EOC). 52 recurrent platinum-resistant EOC patients followed up in four centres between April 2000 and December 2013 were analysed retrospectively. There was response in a total of 21 patients [partial response (PR) and stable disease (SD)], 12 of them used etoposide in second and third, and 9 of them used it in fourth- to fifth-lines of treatment. The overall response rate was 19.2% and clinical benefit rate was 40.4% [PR (19.2%), SD (21.2%)]. Median overall survival (OS) and progression-free survival (PFS) was 9.95 months (95%CI, 0.2-19.7 months) and 3.2 months (95%CI 2.6-3.8 months), respectively. Grade III-IV haematologic and non-haematologic adverse events were observed in 7 (13.4%) patients. We consider that oral etoposide (50mg/day, days 1-14, every 3 weeks) is an effective treatment with a manageable adverse effect profile in recurrent platinum-resistant EOC patients.Impact statementWhat is already known on this subject: Oral etoposide is an effective option for recurrent EOC patients at a dose of 50-100mg/m(2)/day (1-21 days, every 28 days) regimen. However, it has a high toxicity rate.What the results of this study add: Oral etoposide at a dose of 50mg/kg (1-14 days, every 21 days) is an effective treatment with a manageable toxicity profile in platinum- resistant ovarian cancer patients when it is used as 4th-line palliative setting.What the implications are of these findings for clinical practice and/or further research: We need trials evaluating the effect of low-dose oral etoposide combination with bevacizumab or other chemotherapy agents (irinotecan and gemcitabine) in platinum-resistant EOC patients.

Tyrosine kinase inhibitors (TKIs) are frequently used drugs in oncology practice. Although oral administration is an advantage, long-term use increases potential drug-drug interaction risk. The purpose of this study was to assess the prevalence of potential TKI-drug interaction (PTDI) in patients who used TKIs and increase awareness of this subject.We retrospectively evaluated the data of 310 patients collected from four different oncology centers, where TKIs were administered for solid organ cancer, between January 2007 and December 2017. The potential interaction between TKI and any other prescribed drug was determined using ''Lexicomp® Drug Interactions, App Version 1.1'' software.Overall, 310 patients were included; among those, 301 (97.1%) were using another drug with TKI and 147 (47.4%) experienced PTDI at least once. The median number of additional drugs was 4 (range 1-12). We detected 250 PTDIs, of which 30.8% were major interactions. The most frequently interacting TKI was imatinib (29.6%), and the additional drug group was antibiotics (21.2%). We observed that PTDIs caused the following effects: TKI concentration was increased or decreased owing to 14.4% or 22.8% PTDIs, respectively, and electrocardiographic QT prolongation occurred in 22% of all PTDIs. Multivariate analysis demonstrated that use of higher number of additional drugs (odds ratio/OR=1.63), pre-existing lung cancer (OR=8.82), and use of pazopanib (OR=9.22) were potential risk factors.The rate of PTDI is quite high in patients using TKIs. Effort must be made to increase awareness of this subject. Increasing awareness aids in lowering toxicity rates and providing efficient antitumor therapy.

Amac: Literaturde evre III kucuk hucreli disi akciger kanseri (KHDAK) tedavisi ile ilgili tartismalar halen surmektedir. Radyoterapi ve cerrahideki gelismeler ile evre III KHDAK gercek yasamdaki verilerin degerlendirilmesi onem arz etmektedir. Evre IIIA ve IIIB lokal ileri KHDAK’nde tedavi yaklasimlarinin ve gercek yasam verilerinin degerlendirilmesi amaclanmistir. Yontem: Subat 2016 – Mayis 2018 tarihleri arasinda Gazi Universitesi Tip Fakultesi Medikal Onkoloji kliniginde takip edilen lokal ileri evre IIIA ve IIIB KHDAK 47 hastanin dosyalari retrospektif olarak degerlendirildi. Bulgular: Primer tedavi olarak 27 (%57) hasta definitif kemoradyoterapi (KRT), 20 (%43) hastaya cerrahi tedavisi uygulanmisti. KRT uygulanan hastalarin, performans durumunun (p=0.010) istatistiksel olarak anlamli derecede daha kotuydu, aktif sigara iciminin (p=0.033) daha fazla oldugu ve daha ileri lenf nodu evresine (p=0.052) sahip oldugu gorulmustur. Tek degiskenli analizde lenf nodu durumu (p=0.011), hastalarin performans durumu (p=0.0247) ve hastalarin tedavi modalitesi (p=0.001) sag kalimi etkileyen prognostik faktorler olarak tespit edilmistir. Hastalarin 1 yillik genel sag kalim oranlari ve medyan sag kalimi, cerrahi uygulanan grupta sirasiyla 85% ve 23 ay, definitif KRT uygulananlarda 41% ve 10 ay olarak tespit edilmistir. Cok degiskenli analizde cerrahi yapilmasi KRT’ye gore bagimsiz daha iyi prognostik faktor olarak belirlenmistir (HR: 2.72, 95% CI: 1.27-5.82, p=0.010). Sonuc: Evre III KHDAK hasta grubunda klinik deneyimimiz sonucunda rezektabl olan hastalarin sonuclarinin daha iyi oldugu gorulmektedir. Mediasten lenf nodu tutulum bolgesi ozellikle N3 lenf nodu bolgesi ve hasta performansi evre III KHDAK’ inde prognozu belirleyen onemli faktorlerdendir.

Coexistence of two or more primary cancers is a relatively rare case. Not with standing that the coexistence of multiple primary cancers is often discussed in the literature, there is a small number of publications concerning the coexistence of squamous cell lung carcinoma and renal cancer. In this case report, detection of both squamous cell lung carcinoma and primary renal cancer in one male patient is going to be discussed.

The cancer burden is rising globally, exerting significant strain on populations and health systems at all income levels. In May 2017, world governments made a commitment to further invest in cancer control as a public health priority, passing the World Health Assembly Resolution 70.12 on cancer prevention and control within an integrated approach. In this manuscript, the 2016 European Society for Medical Oncology Leadership Generation Programme participants propose a strategic framework that is in line with the 2017 WHO Cancer Resolution and consistent with the principle of universal health coverage, which ensures access to optimal cancer care for all people because health is a basic human right. The time for action is now to reduce barriers and provide the highest possible quality cancer care to everyone regardless of circumstance, precondition or geographic location. The national actions and the policy recommendations in this paper set forth the vision of its authors for the future of global cancer control at the national level, where the WHO Cancer Resolution must be implemented if we are to reduce the cancer burden, avoid unnecessary suffering and save as many lives as possible.

Background: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. Patients and methods: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. Results: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (2; pConclusions: The time from the initial diagnosis of systemic metastasis to the development of BMs (2) were independent risk factors for a poor prognosis.

BACKGROUND The potential prognostic value of survivin is variably reported depending on the gastric cancer. OBJECTIVE Evaluation of the prognostic and predictive significance of serum survivin and its relation with survival and treatment response rates in patients with locally advanced gastric cancer (LAGC). METHODS Serum samples were prospectively collected from 50 patients with newly diagnosed LAGC. Serum samples of 32 healthy subjects were also collected as control groups for survivin levels. Serum survivin levels were evaluated at baseline and after three cycles of neoadjuvant chemotherapy in LAGC patients. RESULTS Median survivin level was 147 IU/L (range = 4.4-4936) at baseline and was 27 IU/L (range = 4.2-4737) after neoadjuvant chemotherapy. The difference between survivin levels of the control group (26 IU/L, range = 3.8-1430) and pre-treatment patient group was statistically significant (p< 0.001). Clinical response to mDCF regimen was classified as progressive (progressive disease) and non-progressive groups (partial response + stable disease). Baseline survivin levels were similar between patients in progressive and non-progressive groups (p= 0.55). Survivin levels were significantly reduced after chemotherapy in non-progressive group (p< 0.001). In contrast, serum survivin levels increased in a stepwise fashion from baseline to post-chemotherapy in patients with progressive disease (p= 0.06). Patients were divided into low and high survivin groups according to baseline median survivin levels. Median DFS was 12.4 and 14.6 months for low and high groups, respectively (p= 0.18). Moreover, median OS was 14.4 and 24.9 months for low and high group, respectively (p= 0.14). CONCLUSION It can be suggested that serum survivin can be used as a predictor of response to chemotherapy- but not survival- in LAGC patients receiving neoadjuvant mDCF chemotherapy. However, large multicenter prospective studies are required to confirm these results.

Objectives: The purpose of this study is to investigate bone marrow metastasis in patients with Gastric cancer.

Studies on the effects of third-line chemotherapy (CT) in advanced gastric cancer (GC) patients are still scarce. The aim of this study was to evaluate the efficacy and safety of the modified 5-fluorouracil, leucovorin, and irinotecan (mFOLFIRI) regimen as a third-line CT in metastatic GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. After failure of first-and second-line therapies, 42 patients received third-line FOLFIRI (180 mg/m(2) irinotecan and 400 mg/m(2) leucovorin administered concomitantly as a 90-minute intravenous (IV) infusion on day 1, followed by a 400 mg/m(2) 5-fluorouracil IV bolus then 2600 mg/m(2) continuous infusion over 46 hours), between January 2009 and December 2015. FOLFIRI was administered for a median of 6 cycles (range 4-12 cycles). Eight patients achieved partial response, while 13 patients showed stable disease, resulting in the overall response rate (ORR) of 19% and disease control rate (DCR) of 50%. The most frequent grade 3-4 hematological and non-hematological toxicities were neutropenia (14.2%) and diarrhea (7.1%). The median progression-free survival (PFS) and overall survival (OS) from the start of third-line CT were 3.8 months (95% confidence interval [CI], 3.0-4.5) and 6.8 months (95% CI, 5.6-7.9), respectively. According to the multivariate analysis, two factors were independently predictive of the poor OS: > 2 regions of metastasis (relative risk [RR], 2.6; 95% CI, 1.3-5.4) and a high level of carcinoembryonic antigen [CEA] (RR, 3.4; 95% CI, 1.6-7.4). In conclusion, FOLFIRI was well tolerated as third-line CT and showed promising PFS and OS in advanced GC patients, after failure of fluoropyrimidine, platinum, anthracycline, and taxane.

WOS: 000399505100004 PubMed ID: 28333566 Background: There are insufficient predictive markers for renal cell carcinoma (RCC). Methods: A total of 308 metastatic RCC patients were analyzed retrospectively. Results: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35months (p < .001) and 21.0 versus 11.36months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively. Conclusions: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.

Trastuzumab is the first anti-HER-2 humanized monoclonal antibody. The benefit of adjuvant trastuzumab has been shown in randomized phase III trials. Despite trastuzumab being recommended for 52 weeks in the adjuvant treatment of HER-2 positive breast cancer according to the current breast cancer guidelines, there is still no consensus on the optimal duration of adjuvant trastuzumab. The aim of our study is to investigate the efficacy and safety of adjuvant trastuzumab for 9 weeks and 52 weeks in axillary lymph node positive HER-2 positive breast cancer patients.A total of 271 HER-2 and axillary node positive breast cancer patients who received trastuzumab in adjuvant treatment between the years 2005 and 2013 were retrospectively analyzed. Patients with axillary node positive HER-2 positive breast cancer who were non-metastatic were enrolled to the study. Patients were allocated to the 9 week trastuzumab group (n = 155) or the 52 week trastuzumab group (n = 116). Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). Two-sided p values of0.05 were considered statistically significant. The most important limitation of our manuscript is the retrospective design.The median follow-up time for this analysis was 34 (4-95) months. Patients' clinical and pathological characteristics were well balanced between the two treatment arms. In the 9 week trastuzumab treatment group, the DFS rate was 96.7%, 84.8% and 74.9% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 94.3%, 80.0% and 80.0% (P = 0.76). In the 9 week trastuzumab treatment group, the OS rate was 99.3%, 92.2% and 88.3% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 99.0%, 94.7% and 78.6% (P = 0.99). In both groups, symptomatic heart failure was not reported but asymptomatic left ventricular ejection fraction (LVEF) decline was observed 3 (1.9%) and 18 (15.5%) patients in the 9 week and 52 week trastuzumab treatment groups, respectively (P0.001).In our study, the efficacy of trastuzumab for 52 weeks and 9 weeks was similar in node-positive HER-2 positive breast cancer. Cardiotoxicity was significantly increased in the 52 week trastuzumab arm compared to the 9 week trastuzumab arm.

Background: The development of brain metastases (BMs) was associated with poor prognosis in melanoma patients. Patients with BMs have a median survival of 4 mm) (p = 0.008), ulceration (p = 0.007), and pathologically N2 and N3 diseases (p = 0.001) were found to be significantly associated with the development of BMs. In univariate analysis, tumor thickness and performance status had a significant influence on post-BMs survival. In multivariate analysis, these clinicopathologic factors were not remained as significant predictive factors. Conclusions: Our results revealed the importance of primary tumor characteristics associated with the development of BMs. Ulceration, primary tumor thickness, anatomic site, and pathologic ≥N2 disease were found to be significant predictors of BMs development. © 2013 Springer-Verlag Berlin Heidelberg.

To determine whether there are any clinicopathological or prognostic differences between mucinous gastric carcinoma (MGC) and signet ring cell carcinoma (SRCC).Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with MGC and SRCC.In total, 193 patients (51 with MGC and 142 with SRCC) were included in this study. Patients with SRCC in particular had notably higher lymphovascular invasion, perineural invasion, rate of Borrmann types III and IV, and stage III-IV cancer (according to its TNM stage) compared with patients with MGC. However, tumor size was larger in patients with MGC (tumor size ≥5 cm). Median overall survival (OS) was 29.8 months in the MGC group and 16.6 months in the SRCC group (p = .04). The median OS in stage I-III patients was 59.9 and 42.5 months in the MGC and SRCC groups, respectively (p = .35). Comparing OS between MGC and SRCC stage IV patients revealed that the median OS was 10.1 and 8.8 months, respectively (p = .96). Multivariate analysis of the entire patient group revealed that the presence of weight loss at diagnosis, distant metastasis, and lymph node involvement were significantly related to OS. Multivariate analysis also revealed that weight loss at the diagnosis and T3-4 tumors were significant factors influencing OS in the stage I-III group.Patients with SRCC had generally poorer prognosis and lower survival rates compared with patients with MGC. Further studies on the prognosis and treatment plan based on the pathological subtypes of SRCC and MGC are still needed.

Alpha-fetoprotein producing gastric carcinoma (AFP-PGC) is a rare cancer for which limited data on the clinicopathological features and treatment modalities exist. The aim of this study was to compare the efficacy of modified docetaxel-cisplatin-5-fluorouracil (mDCF) as the first-line chemotherapy regimen in metastatic AFP-PGC and non-AFP-PGC. The patients diagnosed with metastatic gastric cancer who were given mDCF as first-line therapy were retrospectively reviewed. The patients with a basal serum AFP level over 9 ng/ml were defined as AFP-PGC patients. In total, 169 patients (34 with AFP-PGC and 135 with non-AFP-PGC) were included in this study. AFP-PGC patients had more liver metastases than non-AFP-PGC patients (p < 0.001). A decrease in basal AFP levels after three cycles of chemotherapy was significantly different in AFP-PGC group (p = 0.001). Overall disease control rate was 79.4% (partial response [PR] - 44.1%, stable disease [SD] - 35.3%), and 82.2% (complete response - 3%, PR - 36.2%, SD - 43%) in AFP-PGC and non-AFP-PGC patients, respectively. There was no difference between AFP-PGC and non-AFP-PGC groups in overall and progression-free survival rates (11.3 versus 11.4 months and 7.7 versus 7.1 months, respectively). Rates of grade 3-4 hematologic toxicity were 8.8% and 6.7% for neutropenia in AFP-PGC and non-AFP-PGC group, respectively and 5.9% and 7.4% for anemia. In conclusion, mDCF regimen is well-tolerated with acceptable toxicity outcomes in both AFP-PGC and non-AFP-PGC patients. A statistically significant decrease in AFP levels after mDCF regimen indicate that AFP might be considered as a supplemental marker of response to mDCF chemotherapy in AFP-PGC patients. However, further prospective clinical trials are required in this area.

Chemerin is expressed mainly in the adipose tissue. It is an agonist of chemokine-like receptor-1, which is expressed by the immune system cells. Chemerin stimulates the chemotaxis of the immune system cells, and this indicates the function of chemerin and chemokine-like receptor-1 in the immune response. The tumor microenvironment is very important for determining cancer cell growth and spreading. Therefore, we aimed to investigate the association between colorectal cancer, inflammation, and adipokines including chemerin, adiponectin, and vaspin. The study group consisted of patients with colon cancer, whereas the control subjects consisted of patients with benign conditions, diagnosed with colonoscopy. The two groups were compared in terms of the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, adiponectin, chemerin, and vaspin. A total of 41 (28 men, 13 women) patients with confirmed colon cancer, and 27 (15 men, 12 women) controls without, confirmed by colonoscopy, were enrolled. The median chemerin levels were found significantly higher in the study group than the controls (390 vs. 340 ng/mL, p = 0.032), whereas the mean vaspin and adiponectin levels were not significantly different. The median values for the CRP, fibrinogen, and ESR were significantly higher in the patients with colon cancer, when compared to the control group (6.08 vs. 1.4 mg/L, p

Obesity has been confirmed to be an adverse prognostic factor in patients who were treated with aromatase inhibitors; however, such relationship has never been thoroughly investigated in patients treated with tamoxifen. The purpose of this study was to examine the effect of body mass index (BMI) on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.Newly diagnosed premenopausal and non-metastatic hormone receptor-positive breast cancer patients were enrolled in the study. Patients with BMI ranging between 18.5 and 24.9 kg/m(2) were considered as normal weight patients (Arm A, n = 408), and/patients with a BMI ≥ 25 kg/m(2) were considered as overweight and obese patients (Arm B, n = 418).In both normal weight and overweight patients, the baseline clinicopathologic properties and the treatment history with radiotherapy and chemotherapy were similar and no statistical significant difference could be detected. Tamoxifen in combination with luteinizing hormone-releasing hormone (LHRH) agonist was used in 33% (136/408) of the patients in Arm A and in 22% (91/418) of patients in Arm B (p0.001). Three-year disease free survival (DFS) rates were 89% and 87% in arm A and arm B, respectively (p=0.39). Three-year overall survival (OS) rates were 99% in arm A and 94% in arm B which appeared to be of significance (p=0.028). In univariate analysis no statistical significant effect of LHRH agonist usage on DFS (p=0.58) and OS (p=0.96) was found.Although BMI had no negative effect on recurrence risk, poor OS was observed in overweight and obese premenopausal breast cancer patients with hormone-receptor positive tumors who were treated with tamoxifen.

Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I - II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.

Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. Methods: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. Results: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.

WOS: 000368937200011, PubMed ID: 26775722, Aim: To investigate the role of surgical resection of primary tumor on overall survival (OS) in advanced gastric cancer patients at the time of diagnosis. Patients & methods: The survival rates of metastatic gastric cancer patients whose gastric primary tumor was resected at time of diagnosis were compared with metastatic gastric cancer patients whose primary tumor was nonresected. Results: The median progression-free survival and OS in operated and nonoperated group were 10 versus 6, 14 versus 9 months, respectively (p < 0.001). In multivariate analysis, gastric resection of primary tumor, Eastern Cooperative Oncology Group performance status, second-line chemotherapy had a significant effect on OS (hazard ratio [HR]: 0.52 [95% CI: 0.38-0.71], HR: 0.57 [95% CI: 0.42-0.78], HR: 1.48 [1.09-2.01]; p