Evaluating the effectiveness of the Charlson Comorbidity Index in predicting immune checkpoint inhibitor-related adverse events.

Aims: Our study aimed to evaluate the effectiveness of the Charlson Comorbidity Index (CCI) in predicting immune-related adverse events (irAEs) in solid tumor patients receiving immunotherapy. Patients & methods/materials: The CCI score at the time of initiation of immunotherapy was calculated in 164 solid tumor patients receiving immunotherapy and the correlation between the CCI score and immune toxicity was evaluated. Results: A significant relationship was found between CCI score and irAEs in lung cancer and renal cell cancer patients. In malignant melanoma, no significant relationship was found between the CCI score and the occurrence of irAEs. Conclusion: We argue that CCI can be used to predict irAEs, but we believe that a specific comorbidity index that includes autoimmune diseases should be developed.

The aim of our study was to find a scale that can predict which patients are most likely to develop side effects of immunotherapy drugs, which work by stimulating the immune system. We evaluated whether the Charlson Comorbidity Index ­ a scale which already exists to predict the mortality of patients with serious conditions ­ was able to predict whether people with cancer experienced negative side effects from immunotherapy drugs. We found that it may be useful to predict these negative reactions in patients receiving immunotherapy to treat lung and kidney cancer. This means that the Charlson Comorbidity Index might be useful for patients with these types of cancers, to help predict whether they will experience negative side effects. This could help doctors and patients to take better precautions and be more prepared in the event that these side effects do occur.

Tumor Volume Is a Better Prognostic Factor than Greatest Tumor Diameter in Operated Stage I-III Non-Small-Cell Lung Cancer.

INTRODUCTION: The aim of this study was to investigate the prognostic impact of tumor volume (TV, recorded from surgical specimens) on patients with stage I-III non-small-cell lung cancer (NSCLC) after complete resection. MATERIALS AND METHODS: A total of 129 patients with stage I-III NSCLC diagnosed and underwent curative resection from 2007 to 2014 in our center were included in the study. Their clinico-pathological factors were retrospectively reviewed. Overall survival (OS) and disease-free survival (DFS) analyses were performed with the Kaplan-Meier method and Cox's hazard model. According to the ROC analysis, patients were divided into 2 groups (Group 1: 58 patients <30.3 cm3 and Group 2: 71 patients ≥30.3 cm3) and the OS and DFS values were compared. RESULTS: Median TVs and greatest tumor diameter were 12 cm3 (0.1-30) / 3 cm (0.4-6.5) in Group 1 and 98 cm3 (30.6-1521) / 6 cm (3.5-21) in Group 2. Median OS was 53 (5-177) months in Group 1 and 38 (2-200) months in Group 2 (P < .001). DFS was similar in both group (28 [1-140] vs. 24 [1-155] months, Introduction P = .489). Kaplan-Meier curves showed significantly higher OS rates in Group 1 than Group 2 (P = .04). In multivariable analysis (TV, tumor T stage, tumor N stage, receiving adjuvant radiotherapy) showed that TV (HR: 0.293, 95% CI: 0.121-0.707, P = .006) and tumor N stage (HR: 0.013, 95% CI: 0.001-0.191, P = .02) were independent factors associated with OS. CONCLUSION: Tumor volume, not considered in the routine TNM classification, may improve prediction accuracy of overall OS in operated Stage I-III NSCLC.

Clinical outcomes of cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors in patients with male breast cancer: A multicenter study.

BACKGROUND: Since breast cancer is less common in men than in women, data on the use of new therapeutic agents, including cyclin-dependent kinase 4-6 (CDK 4-6) inhibitors, are limited in patients with metastatic hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) male breast cancer. Therefore; we aimed to investigate the treatment responses of metastatic HR+, HER2-male breast cancer patients treated with CDK 4-6 inhibitors in a multicenter real-life cohort. METHODS: Male patients with a diagnosis of HR+ and HER2-metastatic breast cancer, treated with any CDK 4-6 inhibitor, were included in the study. Demographic and clinical characteristics of the patients were recorded. We aimed to determine progression-free survival (PFS) time, response rates and drug related side effects. RESULTS: A total 25 patients from 14 institutions were recruited. The mean age at diagnosis was 57 years. Median follow-up was 19.53 (95% CI: 14.04-25.02) months. The overall response rate was 60%. While the median PFS was 20.6 months in the whole cohort, it wasn't reached in those using CDK 4-6 inhibitors in first line and 10 months in the subsequent lines (p:0.009). No new adverse events were encountered. CONCLUSION: In our study, we found that CDK 4-6 inhibitors are effective and safe options in men with HR+ and HER2-metastatic breast cancer as in women. Our results support the use of CDK 4-6 inhibitor-based combinations in the first-line treatment of HR+ and HER2-metastatic male breast cancer.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

The Efficacy and Safety of Treatment Regimens Used in the First-Line Setting in Metastatic Pancreatic Cancer Patients: A Multicenter Real-Life Study.

OBJECTIVE: The aim of the study is to compare the efficacy and safety of 3 chemotherapy regimens used as first-line treatments in the real-life management of metastatic pancreatic cancer. METHODS: A total of 218 patients were included in this multicenter study. Gemcitabine (Gem, n = 71), gemcitabine-cisplatin (Gem-Cis, n = 91), and FOLFIRINOX (a combination of leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin [FFX], n = 56) treatments were compared. RESULTS: Overall response rate was significantly higher in the FFX group (50.0%) than in the Gem (28.2%) and Gem-Cis (27.5%) groups (P = 0.010). Median progression-free survival (8.4 vs 4.6 and 5.5 months, respectively, P < 0.001) and overall survival (16.4 vs 8.1 and 8.7 months, respectively, P = 0.002) were significantly longer in the FFX group than in the Gem and Gem-Cis groups. Toxicity of any grade was noted in 46 (64.8%), 56 (61.5%), and 49 (87.5%) patients in the Gem, Gem-Cis, and FFX groups, respectively (P = 0.003). CONCLUSIONS: In our study, FFX regimen provides a significant advantage over the other treatment regimens in terms of response rates and survival. Treatment toxicity was more frequent but manageable with the FFX regimen.

The Effect of Gene Mutations on Metastasis and Overall Survival in Metastatic and Nonmetastatic Colon Cancers.

OBJECTIVE: It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers. METHODS: A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated. RESULTS: The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05). CONCLUSION: We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.

Is SUVmax of 18F-FDG PET/CT Predictive Factor for Malignancy in Gastrointestinal Tract?

BACKGROUND: Increasing use of 18F-FDG PET/CT in cancer patients, has led to more common detection of 18F- FDG uptake in the gastrointestinal tract (GIT). AIMS: The objective of this study was to assess 18F-FDG uptake in incidental and known GIT malignancy. METHODS: A total of 6500 patients followed-up in a single and tertiary center between January 2010 and September 2016 were retrospectively reviewed. Of 2850 patients assessed with 18FDG-PET/CT, known GIT malignancy and 18F-FDG uptake cases during follow-up were included in the study. RESULTS: Of 658 patients with 18F-FDG uptake, 150 patients who underwent endoscopy were included in the study. Seventy-seven of these patients had known GIT malignancy and 73 had incidental 18F-FDG uptake. Among these 73 patients; 7 (9.6%) had malignancy, 20 (27,2%) adenoma and 24 (32.9%) inflammation that were confirmed. Endoscopy was normal in 22 (30.2%) patients. One hundred forty-three (95.3%) patients had focal and 7 (4.7%) had diffuse uptake. While no malignancy was detected in patients with diffuse uptake, 58.7% (84/143) of the patients with focal uptake presented malignancy. Mean the standardized uptake value (SUV) max values were found as 15.0 ± 10.6 (range, 3.8-56.5) in malignant disease, 10.2 ± 4.3 (range, 2.4-19.7) in adenoma, 7.3 ± 3.6 (range, 3.6-18.7) in inflammation, and 9.8 ± 4.2 (range, 3.8-19.9) in normal endoscopy groups (p < 0.001, rho = 0.378). CONCLUSION: Although this study demonstrated high probability of malignant disease with increased 18F-FDG uptake in the GIT, it would be a more appropriate approach to confirm all patients with 18F-FDG uptake through endoscopy as SUVmax values vary in a wide range.

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

PURPOSE: We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). METHODS: Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. RESULTS: Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). CONCLUSION: In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

Efficacy and safety of bevacizumab in Turkish patients with metastatic and recurrent cervical cancer.

OBJECTIVE: To evaluate the efficacy of bevacizumab a monoclonal, antivascular endothelial growth factor antibody in combination with cytotoxic chemotherapy in Turkish patients with recurrent and metastatic cervical cancer. MATERIALS AND METHODS: Data of 64 patients with metastatic or recurrent cervical cancer, receiving bevacizumab with first-line cisplatin or carboplatin and paclitaxel chemotherapy between 2013 and 2017 were retrospectively evaluated. RESULTS: The mean age of the patients was 49 years (range, 28-68), the median follow-up time was 12 months (range, 2-53), the median progression-free survival (PFS) was eight months, and the median overall survival (OS) was 23 months. All 64 patients received a median of 6 (range, 1-12) bevacizumab and 6 (range, 2-12) chemotherapy cycles. The chemotherapy regimens used with bevacizumab were cisplatin and paclitaxel in 31 (48%) and carboplatin and paclitaxel in 33 (52%) patients. The survival in patients treated with bevacizumab and cisplatin plus paclitaxel was better-particularly in patients with no previous cisplatin-based radiosensitizer therapy-than those treated with carboplatin, paclitaxel, and bevacizumab (p=0.023). The bevacizumab dose was 7.5 mg/kg in 30 patients (47%) and 15 mg/kg in 34 patients (53%) every 21 days. No significant difference was reported in the OS and the PFS between the two groups. While the most common all-grades adverse events were nausea, neutropenia, anemia, and peripheral sensory neuropathy, the most common grade ≥3 adverse events were neutropenia, anemia, and peripheral sensory neuropathy. CONCLUSION: Adding bevacizumab to platinum and paclitaxel chemotherapy in a case of metastatic or recurrent cervical cancer is an effective and tolerable treatment for Turkish patients.

The prognostic importance of VEGF-A, PDGF-BB and c-MET in patients with metastatic colorectal cancer.

INTRODUCTION: We aimed to assess the effect of VEGF-A, PDGF-BB, and c-Met expression levels on survival in patients with metastatic colorectal cancer receiving bevacizumab therapies. PATIENTS AND METHODS: A total of 105 patients diagnosed with metastatic colorectal cancer between the years 2006 and 2016 were included in the research retrospectively. RESULTS: The progression-free survival (PFS) durations of patients with high expression levels of VEGF-A and with low expression levels of VEGF-A were 11 months and 10 months (p = 0.44), respectively. The PFS durations of patients with high PDGF-BB expression and low PDGF-BB expression were 12 months and 10 months (p = 0.16), respectively, while the PFS durations of patients with high and low c-Met expression were 8 months and 13 months (p = 0.005), respectively. Metastatic overall survival was 27 months and 18 months (p = 0.05) in patients with high and low VEGF-A expression levels, respectively, 31 months and 21 months (p = 0.16) in patients with high and low PDGF-BB expression levels, respectively, and 21 months and 26 months (p = 0.11) in patients with high and low c-Met expression levels, respectively. CONCLUSION: The results of this research revealed a high c-Met expression relationship with worse PFS and low VEGF-A expression associated with poor metastatic overall survival in patients with metastatic colorectal cancer receiving bevacizumab therapies.

Efficacy of second-line targeted agents in kras wild metastatic colorectal cancer patients who received prior targeted agent: First anti-epidermal growth factor receptor or vascular endothelial growth factor in right and left colon?

INTRODUCTION: We aimed to investigate the impact of first biological agents on second-line biological agents in kras wild-type metastatic colon patients in right and left colon. PATIENTS AND METHODS: The patients received anti-EGFR compared with anti-VEGF in right and left colon separately according to progression-free survival and overall survival in second line. RESULTS: A total of 84 patients were included in the study. In left colon, progression-free survival and overall survival were 9 and 14 months for anti-EGFR and 9 and 16 months for anti-VEGF in the second line. In right colon, progression-free survival and overall survival were 5 and 9 months for anti-EGFR and 4 and 6 months for anti-VEGF in the second line. CONCLUSIONS: Progression-free survival was higher in patients who received bevacizumab first followed by anti-EGFR than reverse sequencing in right colon. Overall survival was similar between two groups.

The prognostic value of the change in neutrophil-to-lymphocyte ratio during first-line palliative chemotherapy in patients with metastatic gastric cancer: A retrospective study.

PURPOSE: Metastatic gastric cancer (mGC) is linked with worse prognosis, and tools are needed for predicting disease course and chemotherapy response. The value of the change in the neutrophil-to-lymphocyte ratio (NLR) during first-line palliative chemotherapy on the outcomes in patients with mGC is not fully explained. This study aimed to investigate the importance of changes in NLR in predicting disease course and chemotherapy response in mGC. METHODS: We retrospectively reviewed 194 patients diagnosed with mGC between August 2005 and November 2016. The NLR was assessed before and after chemotherapy to evaluate its relationship with survival. According to threshold values determined by receiver operating characteristics (ROC) analysis, the NLR was divided into two groups with <2.6 and ≥2.6. RESULTS: Elevated prechemotherapy NLR was significantly correlated with worse overall survival (OS) on univariate analysis (p=0.01). On multivariate analysis, elevated prechemotherapy NLR (HR 1.43, p=0.036) was an independent prognostic element for worse OS, but not for progression-free survival (PFS). Constantly elevated NLR or an increase in NLR after chemotherapy was correlated with poor OS, PFS and chemotherapy response. In the multivariate analysis, constantly elevated NLR was identified to be independent predictor of reduced OS and PFS. CONCLUSION: NLR change during chemotherapy is a better index than prechemotherapy NLR for predicting survival in patients with mCG.

Impact of neutrophil-lymphocyte and platelet-lymphocyte ratio on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer.

PURPOSE: The purpose of this study was to determine the influence of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer patients. METHODS: All metastatic colorectal cancer patients who had received chemotherapy and biological agents as first-line treatment at Erciyes University Hospital were retrospectively reviewed. NLR and PLR were each divided into two groups, as high and low. The NLR high group was compared with the low group and the PLR high group was compared with the low group in patients in terms of progression-free survival (PFS) and overall survival (OS), separately. Cox regression and the Kaplan Meier method were used. RESULTS: One hundred and thirty (58%) of the patients had received bevacizumab and 94 (42%) had received antiEGFR therapy (cetuximab or panitumumab). In the bevacizumab group, PFS was 9 months in the NLR high group and 11 months in the NLR low group (p=0.013). OS was 23 months in the NLR high group and 27 months in the NLR low group (p=0.734). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to NLR. There was no statistically significant PFS difference in patients who received bevacizumab according to PLR. In the antiEGFR group, PFS was 9 months (95% CI, 8.07-13.55) in the PLR high group and 18 months (95% CI, 12.02-18.68) in the PLR low group, with statistically significant difference (p=0.040). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to PLR. CONCLUSIONS: NLR and PLR are important inflammatory markers. In patients who had received bevacizumab, PFS was longer in the NLR low group than in the high group. In patients who had received antiEGFR, PFS was longer in the PLR low group than in the high group.

Sarcoidosis with Multiorgan Involvement and Cutaneous Manifestations after Colonic Adenocarcinoma Resection.

Sarcoidosis is a systemic chronic granulomatous disease. It mostly involves the lungs and hilar lymph nodes and produces epithelioid granulomas. Granulomatous (sarcoid) reaction is known to be associated with malignancies; however, it is uncommonly seen with colon carcinomas. Furthermore, systemic sarcoidosis following cancer diagnosis is less commonly seen. To the best of our knowledge, cutaneous sarcoidosis related with an underlying colon carcinoma has not been reported previously in the literature. In this report, we present a very rare case with sarcoidosis development after resection of sigmoid adenocarcinoma, presenting with multiorgan involvement including the skin, eye, joints, and lymph nodes. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) images showed the skin, lung, spleen, mediastinal, and hilar lymph node involvement. Histopathological examination of skin lesions demonstrated granulomatous dermatitis. This case demonstrates that sarcoidosis can cause intensely FDG-avid lesions on 18F-FDG-PET/CT scans, mimicking metastasis in colon cancer patients. Histopathological evaluation is essential for confirming the diagnosis. 18F-FDG-PET/CT scan provides important information for evaluation of disease extension, progression, and clinical follow-up.

Biweekly cisplatin and gemcitabine with two different doses in non small cell lung cancer patients: A retrospective singlecenter experience.

PURPOSE: Non-small-cell lung cancer (NSCLC) constitutes 80-85% of all lung cancers. Patients with advanced-stage NSCLC may benefit from chemotherapy. Gemcitabine and cisplatin is a well-established therapy for this malignancy. Recently, biweekly administration is becoming more acceptable, but the most effective and tolerable dose remains unclear. The purpose of this study was to compare the toxicity and efficacy of 1000 mg/m2 gemcitabine (GEM 1000) and 1500 mg/m2 gemcitabine (GEM 1500) in combination with 50 mg/m2 cisplatin. METHODS: Gemcitabine was administered at a dose of 1000 or 1500 mg/m2 with cisplatin administered at a dose of 50 mg/m2 on day 1. The treatment was repeated every 2 weeks for a total of 4 courses. Response rates, progression-free survival (PFS), overall survival (OS) and toxicities were assessed. RESULTS: 114 patients with IIIB and IV stages of NSCLC were included. Seventy two patients (63%) received GEM 1000 and 42 (37%) received GEM 1500. The overall reponse rate (ORR), PFS and OS were 24%, 6 months and 13 months respectively in the GEM 1000 group and 36%, 6 months and 15 months in the GEM 1500 group, respectively. Grade 3-4 neutropenia and thrombocytopenia were observed in 4% of the GEM 1000 group and 9% of the GEM 1500 group (p=0.41). CONCLUSION: Biweekly administration of GEM 1000 and 1500 is a well tolerated regimen. Although the GEM 1000 group showed a lower response rate than the GEM 1500 group, PFS and OS were similar.

Retrospective evaluation of premenopausal hormone-sensitive breast cancer patients treated with adjuvant gonadotropin-releasing hormone analogue: Anatolian Society of Medical Oncology (ASMO) study.

AIM: The goal of this study is to evaluate possible factors affecting the survival of patients treated with gonadotropin-releasing hormone (GnRH) analogues. METHODS: Demographic characteristics, treatment modalities, overall survival (OS) and the possible factors affecting the survival a total of 554 premenopausal breast cancer patients in Turkey evaluated retrospectively. RESULTS: The median duration of GnRH analogues use was 22 ± 13.6 (range, 1-87) months. Patients were divided into three groups according to the duration of GNRH analogues use; 4-12 months (Group A), 13-24 months (Group B) and ≥25 months (Group C). Overall, 530 patients were analyzed; 23.2%, 45.8%, 30.9% of the patients were in Group A, B and C, respectively. The median follow-up duration was 34 ± 30.3 (range, 4-188) months. The OS in patients ≤35 years of age was found to be significantly longer than that of patients >35 years of age in Group B (log rank, P = 0.023). The disease-free survival of the patients in Group A was significantly shorter than that of patients in Group C (log rank, P = 0.003). The OS of Group A patients was significantly shorter in comparison to that of Group B and Group C patients (log rank, P = 0.000) and the OS of Group B patients was significantly shorter than Group C (log rank, P = 0,000). CONCLUSION: There is currently no definite data on the optimal duration of GnRH analogues use. One of the important results of this study that will provide an insight to the future studies is the improvement gained in OS by the increase in the duration of GnRH analogues use.

Efficacy and safety of cetuximab plus FOLFOX in second-line and third-line therapy in metastatic colorectal cancer.

PURPOSE: To evaluate the efficacy and adverse events with cetuximab plus FOLFOX administered as second- and third-line therapy in metastatic colorectal cancer (mCRC) patients. METHODS: IPatients were administered cetuximab plus FOLFOX as second- and third-line therapy from January 2010 through October 2015. mCRC patients with wild type KRAS were alsï given irinïtecan and/ïr ïxaliplatin cïmbined with fluorïpyrimidine±bevacizumab. Tumor respïnse and survival were evaluated using RECIST and Kaplan-Meier methïd respectively. RESULTS: Sixty patients were included this study. Cetuximab plus FOLFOX was administered to 40 (66.7%) patients as second-line and to 20 (33.3%) as third-line therapy. The majority of the patients had a good ECOG performance status (PS) (0 or 1). Clinical benefit was partial plus stable disease and it was 75.0% for both of these two lines. The median progression free survival (PFS) was 7.1 months (95% CI=3.2-10.9) and 6.0 months (95% CI=2.4-9.6), in the second-and third-line (p=0.484). The median ïverall survival (ÏS) was 14.3 and 9.2 mïnths in secïnd-and third-line therapy respectively (p=0.071). The common toxicities were haematologic and gastrointestinal, mostly grade 1 and 2. CONCLUSION: The addition of cetuximab to FOLFOX was well-tolerated and had antitumor activity both in second- and third-line therapy in patients with mCRC.

Prognostic Value of Cancer Stem Cell Markers CD44 and ALDH1/2 in Gastric Cancer Cases

Purpose: To determine expression levels of CD44 and ALDH1/2, known cancer stem cell (CSC) markers, in stomach adenocarcinomas and assess relationships with clinicopathologic parameters and prognosis. Methods: Eighty patients diagnosed with gastric cancer between the years 2011-2015 were included in this study of clinicopathologic characteristics, postoperative prognostic indexes and stem cell marker CD44 and ALDH1/2 expression in paraffin-embedded tumour sections analyzed immunohistochemically. Clinicopathologic parameters were evaluated using the chi-square test and t-test. Survival analyses were conducted using Kaplan-Meier statistics. Results: We observed positive CD44 and ALDH1/2 staining in 45.0 % and 67.5% of tumour tissues, respectively, but not in normal gastric mucosa. Recurrence-free survival (RFS) was found to be shorter in cases with high levels of CD44 expression (p=0.004). Similarly, short RFS was observed in patients with high levels of CD44 and ALDH1/2 co-expression (p=0.004). Furthermore, tumour invasion depth was found to correlate with high CD44 and ALDH1/2 co-expression (p=0.028). Conclusion: The cancer stem cell markers CD44 and ALDH1/2 may indicate poor patient prognosis and play a role in tumour development and invasion.

Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology).

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.

The relationship between plasma hyaluronan levels and anthracycline-related cardiotoxicity in breast cancer patients.

AIM: Anthracycline-derived antineoplastic agents are used as the main form of treatment in many malignant diseases, including breast cancer and childhood cancers. Cardiotoxicity is one of the most feared life-threatening complications of cancer therapy. In the present study, we aimed to investigate the relationship between plasma hyaluronan (HA) levels and anthracycline-induced cardiotoxicity. MATERIALS AND METHODS: Fifty eight of 73 female patients who were diagnosed with breast cancer and treated with a chemotherapy regimen including anthracycline were enrolled in this study. Anamneses were taken from each patient before and after chemotherapy. Further, physical examinations, electrocardiography, and transthoracic echocardiography were performed, and plasma hyaluronan levels were determined by using ELISA assay for each patient before and after treatment. RESULTS: Following anthracycline-based chemotherapy, the average left ventricular ejection fraction decreased (62.6±3.7% vs. 58.6±4.4%, p<0.001), and diastolic functions significantly deteriorated (p<0.001). However, troponin and hyaluronan levels significantly increased following chemotherapy [Troponin (ng/ml, mean±SD): before 0.01±0.002, after 0.037±0.02, p<0.001], [Plasma HA (ng/ml, mean±SD): before 41.3±5.4, after 70±8.5, p<0.001]. The increase in troponin values correlated with systolic dysfunction (p=0.002), but did not correlate with diastolic dysfunction (p=0.661). Significant correlations were found between systolic/diastolic dysfunction and plasma HA levels (r=0.417, p=0.001; r=0.339, p=0.009, respectively). CONCLUSIONS: Both systolic and diastolic functions were significantly deteriorated after chemotherapy. In addition, plasma levels of HA and troponin increased after treatment. Further, both systolic and diastolic dysfunctions were found to correlate with serum HA levels. All these data suggest that HA might have a function on anthracycline-induced cardiotoxicity.