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Objective: The current study assesss programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and to associate our results with neoadjuvant chemotherapy history and disease prognosis. Materials and Methods: We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher’s Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1. Results: Univariate analysis demonstrated that optimal debulking (p

Purpose Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. Methods This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. Results A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. Conclusion This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

Background: atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. Patients and methods: in this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. Results The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS >= 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. Conclusions: our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy., NA

Introduction: There is a lack of evidence of the outcomes in elderly patients advanced stage biliary tract cancer due to the patients aged over 65 years are less than 25% in many prospective trials. We designed a retrospective multicenter study to evaluate the factors affecting treatment and survival in elderly patients with advanced-stage biliary tract cancer. Materials and methods: A total of 116 patients with advanced stage biliary tract cancer aged ≥65 years were included, and the treatment responses, survival, and toxicity rates were evaluated with respect to age groups Results: There was no significant difference between age and response to treatment, survival, or toxicity. The median progression-free survival and overall survival were 5.3, and 11.8 months respectively. Multivariate analysis indicated that ECOG PS (p

Aim:Leptomeningeal metastasis (LM), which can be seen in all types of cancer, is a rare condition with poor prognosis. Diagnosis and treatment are important components of the management of the disease. We aimed to reveal clues for early diagnosis by examining the clinical and laboratory features of LM.Methods:Sixteen patients who received the diagnosis of LM between 2018 and 2020 were included in the study retrospectively. The cerebrospinal fluid (CSF) samples and cranial magnetic resonance imaging of the patients were examined. In addition, the patients were divided into two groups according to the presence of papilledema.Results:The mean age of the patients was 49 (19-73) and 37.5% were women. The most common histological tumor type was adenocarcinoma. The most common clinical finding was multiple cranial neuropathy. The mean time to the diagnosis of LM was 20 months. Eleven of the 16 patients had solid tumors, five had hematological malignancies. Nine patients had papilledema. Headache was significantly more common in the group with papilledema (p=0.01). The average lifespan after the diagnosis of LM was 8 months (1-48 months). Malignant cells were detected in the CSF cytology of four patients (30%).Conclusion:LM is a condition with poor prognosis and difficult to diagnose in oncology patients, despite all tests being performed under appropriate conditions. Presence of papilledema is thought to contribute to the diagnosis since the evaluation of intracranial in LM patients is a non-invasive evaluation method.

Objective: To evaluate the outcomes of patients who were followed up and treated for serous epithelial ovarian tumor. Materials and Methods: This retrospective study included 260 patients who were diagnosed with serous epithelial ovarian cancer, treated and followed up at Kanuni Sultan Suleyman Training and Research Hospital between January 2002 and December 2019. Results: The mean age of the patients participated in the study was 53.4±11.6 years. Of the patients, 79.7% had advance stage and 82.4% had grade 3 tumors. The rate of complete or optimal surgery was 88.2%, while the rate of suboptimal surgery was 11.2%. While 82% of the patients received adjuvant chemotherapy, 15.7% received neoadjuvant chemotherapy. Of the patients, 80.2% had a Ca 125 value higher than 35. Despite primary cytoreductive surgery and platinum-based adjuvant chemotherapy, the recurrence rate was 66.2%, and the PFS and OS rates were 34.7±41.0 and 50.5±40.0 months, respectively. Conclusion: The majority of serous epithelial ovarian cancers are diagnosed at an advanced stage. Despite primary situ reductive surgery and subsequent platinum-based chemotherapy, the recurrence rates are quite high.

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. Results: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37–86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ?), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673–5.761; p < (0.001), ECOG PS (1 ?) HR 2.184; 95% CI 1.120–4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558–4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031–4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1–3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer. © 2021, Japan Society of Clinical Oncology.

Tüm dünyada meme kanseri kadınlarda kanserin ve kanser ilişkili ölümlerin en sık nedenidir. Meme kanserli hastaların %17–30 HER2 overekspresyonu olup hastalık kötü prognoz, hastalık progresyon riskinde artış, genel sağkalım ve progresyona kadar geçen sürenin her ikisinde azalma ile birliktedir. Lapatinib, HER2 ve epidermal büyüme faktör reseptör(EGFR) ün ilk dual tirozin kinaz inhibitörüdür. Bu çalışma da antrasiklin, taksan ve trastuzumab tedavisi sonrasında progrese olan metastatik meme kanserli hastalarda kapesitabin ve lapatinib kombinasyonunun etkisini ve tolerabilitesini inceledik. Medyan yaş 56 (34-76) olan toplam 24 hasta dosyası Eylül 2010-Mayıs 2018 arasında 3 merkezde retrospektif olarak incelendi. Tüm hastalar taksan ve antrasiklin içeren kemoterapi ve trastuzumab sonrası progrese olan HER2 pozitif metastatik meme kanseri hastalardı. Genel cevap oranı %29.1, 2 komplet yanıt (CR, 8.3%), 5 parsiyel yanıt (PR, 20.8%), ve 7 stabil hastalık (SD, 29.1%) olmak üzere sağlandı. Kapesitabin ve lapatinib kombinasyon tedavisi antrasiklin, taksan ve trastuzumab tedavisi sonrasında progrese olan metastatik meme kanserli hastalarda etkili ve iyi tolere edilmiştir.

Background: Endocrine treatment and chemotherapy are a treatment options for patients with hormone receptor (HR) positive and HER2-negative metastatic breast cancer (MBC). However, response to first-line hormone treatment could not obtained in all patients, and even patients who havea response will eventually relapse. After disease progression, second-line hormonal treatmentoptions are used sequentially. Everolimus with exemestane has demonstrated promising activity in patients with HR-positive HER2-negative endocrine-resistant MBC with respect to the results of the BOLERO-2 study. In the present study, we aimed to evaluate the efficacy and safety of this combination in the real-life clinical setting for the unselected population in Turkey. Material and Methods: One hundred and one patients with HR-positive HER-2 negative MBC progressing after prior endocrine treatment who were treated with everolimus with exemestane were retrospectively analyzed. The tolerability and efficacy of this combination were evaluated in the unselected Turkish patients. Results: Among 101 patients, 45% of patients had visceral and %50 patients had only bone metastasis. Everolimus with exemestane treatment was administered as a second-line in 21.3% of patients, third-line in 40.4% and forth-line and later in 38.2%. The objective response rate was 24.7% (CR+PR) and stable disease was obtained in 37.7% of patients. At the median follow-up time of 13.5 months, the median progression-free survival (PFS) time and 1-year PFS were 13.8 months and 57.2%, while the median overall survival (OS) interval and 1-year OS were 40 months and 85%. The median treatment duration was 8.3 and 6.5 months for exemestane and everolimus, respectively. The most frequent reason for discontinuation of treatment were disease progression (39%). Moreover, the most common advers events (AE) causing permanent discontinuation were stomatitis (3%) and pneumonitis (3%). A total of 81 % of patients experienced at least one AE of any grade, 25% of patients at least one grade 3 or 4 AE. Due to AEs, everolimus dosage was reduced to 5 mg in 16 (15.8%) of patients. Conclusions: Our findings confirmed that the combination of everolimus with exemestane was the safe and effective treatment options for patients with HR-positive HER-2 negative MBC after second or later lines treatments. Citation Format: Bilici A, Menekse S, Akin S, Degirmenci M, Olmez OF, Avci N, Sakalar T, Tural D, Kaplan MA, Tanriverdi O, Bilgetekin I, Uslu R. The efficacy and safety analysis of the treatments of everolimus and exemestane combination in 101 metastatic breast cancer patients: Real-life experience from Turkey [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-37.

Background Atezolizumab (ATZ) has demonstrated antitumor activity in the previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. Patients and Methods In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher’s exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. Results The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experience clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases (Hazard Ratio [HR] = 1.9; p = 0.04), ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p

WOS:000617829700001 PMID: 33586012 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.

A 34-year-old woman had a history of breast cancer and underwent a right-sided nipple-sparing mastectomy and axillary dissection in 2014. She was staged as pT2N2aM0, IIIA, and the histopathological type was TNBC, grade 3. Ki-67 index was 35%-40%. The patient received four cycles of adjuvant dose-dense doxorubicin and cyclophosphamide followed by four cycles of docetaxel. Radiotherapy to her chest wall and regional lymph node was performed with 60 Gy in 30 fractions as adjuvant therapy, and she was followed without any recurrence until February 2019.

[No abstract available], Amer Soc Clin Oncol

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. the FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1( + ) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. Results: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. the ALK( + ) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 +/- 1.6 months and median overall survival (mOS) was 89.1 +/- 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 +/- 2.5 months and mOS of 90.3 +/- 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. the most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. the observed mOS of 89 +/- 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 +/- 24 months is unprecedented for ROS1( + ) NSCLC., PfizerPfizer [IIS 53234545], We grateful to Pfizer for the funding of the grant IIS 53234545.

409 Background: In the current study, we evaluated whether the response first-line chemotherapy could impact atezolizumab benefit in terms of response rate and overall survival in patients with metastatic urothelial carcinoma. Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. The association between response to first-line chemotherapy and ATZ was assessed using Fisher’s exact test. Overall survival (OS) was estimated by using the Kaplan-Meier method. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p˂0.1) and then included the final model if p˂0.05. Results: Best response to first-line chemotherapy was complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 5(4.8%), 38(36.2%), 16(15.2%), 46(43.8%) patients, respectively. Best response to atezolizumab was CR, PR, SD, PD in 9(8.6%), 22(21%), 23(21,9%), 51(48,5%). Forty (74.1%) of patients who benefited from first-line chemotherapy also benefited from atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with atezolizumab (Fisher’s exact test, p=0.001). Patients with clinical benefit from first-line chemotherapy had a higher OS. The median OS of atezolizumab were 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (log-rank p=0.001). In univariate analysis, Patients with clinical benefit from first-line chemotherapy, liver metastases, baseline creatinine clearance less (GFR)than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent factor of short survival: liver metastases (Hazard Ratio [HR]= 0.6; 95% CI 0.174-0.60; p=0.04), ECOG PS≥1 (HR= 0.36; 95% CI 0.2-0.66; p=0.001), and Hemoglobin level below 10 mg/dl (HR= 0.36; 95% CI 0.2-0.66; p

Background The prognostic importance of platelet-to-lymphocyte ratio(PLR)has been also investigated in some cancer types including colorectal cancer (CRC).Several studies have found that PLR is associated with poor prognosis in patients with CRC,but,the results are controversial.The aim of this study was to investigate the predictive and prognostic value of PLR,and the relationship between PLR and tumor localization. Methods A total of 201 patients with metastatic CRC and candidate to systemic treatments were retrospectively analyzed.Pretreatment complete blood cell count was evaluated to calculate PLR.The cutoff value for PLR was defined by the receiver operating characteristic(ROC)curve analysis and threshold value of 205.5 as best cut-off value was found.The prognostic and predictive significance of PLR was evaluated by univariate and logistic regression analysis. Results Significant relationship was detected between PLR and BRAF mutation,tumor localization.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh(> 205.5)compared to those with PLRlow(

Background: Lymph node involvement is an important prognostic factor in patients with gastric cancer. The aim of this study was to determine the prognostic significance of metastatic lymph node ratio (MLNR) and compare it to the number of lymph node metastasis in pN3 gastric cancer. Methods: We retrospectively analyzed 207 patients with pN3 gastric cancer who had undergone radical gastrectomy. Prognostic factors and MLNR were evaluated by univariate and multivariate analysis. Results: An MLNR of 0.75 was found to be the best cut-off value to determine the prognosis of patients with pN3 gastric cancer (p = 0.001). The MLNR was significantly higher in patients with large-sized and undifferentiated tumors, vascular, lymphatic and perineural invasion, and total gastrectomy. In multivariate analysis, MLNR (p = 0.041), tumor differentiation (p = 0.046), and vascular invasion (p = 0.012) were found to be independent prognostic factors for disease-free survival, while both MLNR (p 0.75 compared to the MLNR Conclusion: Our results showed that MLNR was a useful indicator to determine the prognosis and recurrence patterns of patients with radically resected gastric cancer. Moreover, MLNR is a beneficial and reliable technique for evaluating lymph node metastasis.

451 Background: Anti-tumor activity and manageable safety profile of atezolizumab (ATZ) has been demonstrated in the previous clinical trials in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. In this study, we reported the results of real-life data of urothelial carcinoma patients in Turkey who were treated with ATZ. Methods: Data of the patients with metastatic urothelial carcinoma registered to ATZ Expanded-Access Program and treated with at least one course of ATZ from 36 oncology centers in Turkey were collected. The primary endpoint was the overall response rate (ORR); secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of the ATZ treatment and safety. Results: Data of 115 eligible patients were analyzed. Of the patients, 100 (87%) were male and 13% were female. The median age was 65.3 years (37-86). Most of the patients (92.3%) had received only one chemotherapy regimen prior to ATZ. The median follow-up time was 23.5 months. The complete response rate to ATZ, partial response rate, and ORR were 8.7% (n=10), 20.0% (n=23), and 28.7% (n=33), respectively. The median duration of response was 20.4 months (95% CI 6.47–28.8). Of the thirty-three patients who responded to treatment, 20 (60%) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 months (95% 2.25–5.49) and 9.8 months (95% 6.7–12.9), respectively. The 12-month PFS rate was 22.3% and the 24-month PFS rate was 16.9%. The 12-month OS rate was 42.2% and the 24-month OS rate was 23.5%, respectively. Sixty-four percent of patients experienced a treatment-related adverse event of any grade, and 24 (20%) of patients had a grade 3–4 treatment-related adverse event. Because of treatment-related side effects, dose reduction was performed in 9 (7.8%) patients and ATZ was discontinued in 8 patients (7.0%). Adverse event that required systemic steroid use was reported in only 7 (6.1%) patients. Four patients (3.5%) died due to treatment-related causes. Conclusions: ATZ is an effective and tolerable treatment for patients with metastatic platinum-resistant urothelial carcinoma.

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus–myoclonus–ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%–25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus–myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.

WOS: 000360385400050 PubMed ID: 26156886 Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case-control design the association between the functional -1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case-control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 -1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR = 0.89, 95 % confidence interval [CI] = 0.44-1.82, P = 0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR = 0.81, 95 % CI = 0.40-1.94, P = 0.84). When the MMP-9 -1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjects with the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9 -1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects.

PubMed ID: 25743846 Background: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/ amplified (HER2+), the efficacy of trastuzumab treatment and survival results. Materials and Methods: Patients with HER2- positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model. Results: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0 ). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p

Introduction Triple-negative breast cancers (TNBCs) – which lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) – have no established markers that can be used for prognostic stratification. As adiponectin has been previously implicated in a more aggressive phenotype of primary breast cancer, we explored the relation between adiponectin immunohistochemical expression and prognosis in TNBCs. Material and methods Immunohistochemical staining for adiponectin was performed in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served as the main outcome measures. Results Of the 38 TNBC patients, 18 (47%) had negative and 20 (53%) positive adiponectin immunohistochemical expression. We did not find any significant association between adiponectin immunohistochemical expression and the baseline characteristics. In addition, there were no associations between adiponectin immunohistochemical expression and prognosis. Conclusions Although our results suggest that adiponectin immunohistochemical expression is not of prognostic significance in TNBCs, further studies are warranted to determine the role of this adipokine in breast cancer biology.

Background: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. Methods: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. Conclusions: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.

43rd ESMO Congress (ESMO) -- OCT 19-23, 2018 -- Munich, GERMANY WOS: 000459277303171 … European Society for Medical Oncology, Japanese Society of Medical Oncology

Purpose: Surgery is the definitive treatment for early colon cancers. Adjuvant therapies are used with the aim of eradicating micrometastases and improving cure rates. Recent studies have proposed that adiponectin might be responsible for obesity-related malignancies. We investigated the prognostic value of this cytokine. Materials and Methods: Patients who underwent surgical removal of stage II or III (TNM staging) primary tumors and were followed for at least three years were included in the study given adequate specimen for immunohistochemical evaluation. Based on these criteria, 53 patients were included. Results: Mean age was 58.3 ± 10.1 years (35-78 years). The mean follow-up time was 41 months (10-96 months). Immunohistochemical evaluation identified 21 patients (39.6%) with cytoplasmic adiponectin present in their specimens. The rates of recurrence were 42.9% (9/21) and 34.4% (11/32) in patients with and without adiponectin expression, respectively. In cases with adiponectin expression, mean disease - free survival was 60.3 ± 9.03 months, and in cases without adiponectin expression, mean disease - free survival was 68.7 ± 6.67 months (P = 0.414). Mean overall survival of patients with adiponectin expression was 65 months compared to 67 months for patients without (P = 0.786). Conclusion: Adiponectin, which is secreted by adipose tissue, may have a role in the development and progression of cancer via its pro-apoptotic and/or anti-proliferative effects. Adiponectin expression in tumor tissues is likely to have a negative effect on disease - free survival in patients with stage II/III colon cancer; however, no statistically significant effect was demonstrated.

Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, has been associated with prognosis and response to therapy in several solid tumors. This study was designed to test whether c-erb-B2 overexpression can be related to prognosis of patients with metastatic gastric cancer. Between 2005 and 2010, 46 cases of metastatic gastric cancer were evaluated immunohistochemically for c-erb-B2 overexpression. Overall survival (OS) and time-to-progression (TTP) served as the main outcome measures. c-erbB2 was overexpressed in 19 (41.3 %) cases and 8 patients (17.4 %) had a c-erbB2 score of 3+ (a strong complete membrane staining observed in > 10 % of the tumor cells). c-erbB2 expression was not associated with the clinicohistological characteristics of the study participants. The mean OS was 11.48 +/- A 1.03 months, whereas the mean TTP was 8.28 +/- A 0.8 months. Compared with patients with a score of 2+ or less (n = 38), those with a c-erbB2 score of 3+ (n = 8) had both a significantly lower OS (15.55 +/- A 1.63 vs. 8.22 +/- A 0.88 months, respectively, p < 0.05) and TTP (10.72 +/- A 1.81 vs. 6.11 +/- A 0.61 months, respectively, p < 0.05). After allowance for potential confounders, Cox regression analysis identified a c-erbB2 score of 3+ as an independent predictor of both OS (hazard ratio = 1.9; 95 % confidence interval = 1.1-3.7, p < 0.05) and TTP (hazard ratio = 1.8; 95 % confidence interval = 1.1-4.1, p < 0.05). Our results suggest that c-erbB-2 overexpression may have a prognostic significance in patients with metastatic gastric cancer.

Background: Suppressor of cytokine signaling (SOCS)-1 acts as a key regulator of many cytokine signaling pathways and its abnormal expression has been identified in several human malignancies, suggesting potential roles in carcinogenesis. The aim of this study was to investigate any association between the functional SOCS-1 -1478CA>del polymorphism and colorectal cancer (CC) as well as age at onset in a Turkish clinical sample. Materials and Methods: A total of 122 subjects were enrolled in this case-control study (70 CC cases and 52 controls). The SOCS-1 -1478CA>del polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The odds ratio of the del allele for CC relative to the CA allele was not significantly different between the groups (OR=0.71, 95% CI=0.41-1.22, p=0.27). This result did not change after adjustment for age and sex on multivariable regression analysis (OR=0.84, 95% CI=0.59-1.34, p=0.53). When the SOCS-1 -1478CA>del polymorphism was analyzed among CC patients in relation to the age at disease onset, we found no significant differences between subjects with the del/del, CA/del, and CA/CA genotypes. Conclusions: The results of our study did not point towards a major role of the SOCS-1 -1478CA>del polymorphism in the pathogenesis of CC in Turkish subjects.

Background: Pulmonary actinomycosis may create a diagnostic and therapeutic dilemma especially in cancer patients. Case Report: A 64-year-old male patient presented with a productive cough, bloody sputum, and weight loss. Thoracic computed tomography (CT) showed a 5-cm mass in the upper lobe of the right lung, and a 2-cm mass in the lower lobe of the left lung. Bronchoscopic examination did not show any endobronchial lesions. CT-guided needle biopsy of the right pulmonary lesion showed lung adenocarcinoma. Whole-body positron emission tomography/CT revealed an increase in fluorodeoxyglucose accumulation in the upper lobe of the right lung, in the lower lobe of the left lung, and in the right hilar and paratracheal lymph nodes. Before chemotherapy was initiated, the patient had to be admitted to the hospital because of massive hemoptysis. Bronchoscopic examination indicated persistent bleeding in the left lower lobe bronchus. The patient underwent diagnostic left thoracotomy, and wedge resection of the lower lobe mass. The diagnosis was pulmonary actinomycosis, and the patient received oral amoxicillin. He underwent successful surgery for the primary disease following 6 cycles of chemotherapy. Conclusion: Oncologists should be aware of rare diseases that may affect management approaches in the treatment of cancer.

Objectives Iron is deemed to play a crucial role in the pathophysiology of liver damage in patients with chronic viral hepatitis. Hepcidin has recently emerged as the key hormone in the regulation of iron balance and recycling. We assessed plasma prohepcidin levels in patients with chronic viral hepatitis and investigated the association of this molecule with iron parameters, histologic activity index, and liver fibrosis scores. Methods We enrolled 35 patients with chronic hepatitis C, 27 with chronic hepatitis B, and 21 healthy controls. Plasma levels of prohepcidin were measured by enzyme-linked immunosorbent assay. Results Mean prohepcidin levels were significantly lower in patients with chronic hepatitis B than in those with chronic hepatitis C (P < 0.001) and healthy comparison controls (P < 0.05). In patients with chronic hepatitis C, prohepcidin was independently associated with liver fibrosis scores (beta = -0.009, standard error = 0.003, P < 0.05). No association of prohepcidin with iron parameters was found. Conclusion Significantly lower prohepcidin levels are frequently found in patients with chronic hepatitis B. Levels of this molecule may represent a biochemical correlate of fibrosis in chronic hepatitis C virus infection.

Arsenic is a classical poison that has been historically used since ancient times for homicidal purposes. More recently, episodes of deliberate or unintentional arsenic self-poisoning have been increasingly reported. We describe here a case of a 77-year old male patient with a history of major depression, who attempted suicide by ingestion of 4 g of arsenic trioxide. The man, a dentist by profession, used arsenic preparations for pulp devitalization. The patient was admitted to our hospital 5 h after arsenic ingestion with nausea and vomiting. Plain radiograph of the abdomen showed radio-opaque material in the stomach and small intestine. Nasogastric lavage, activated charcoal, and chelators were used to remove arsenic. On day 3, endoscopy disclosed the presence of gastritis and superficial ulcers. The patient developed significant anemia (Hb: 8.7 g/dL on day 7) without significant signs of hemolysis. He gradually recovered from anemia within 5 months. The patient did not suffer any adverse outcome in spite of having ingesting 4 g of arsenic, approximately 20 times the lethal dose.

Objective The modified Early Warning Score (mEWS) is a triage instrument that promises to predict patient disposition and clinical outcome in emergency departments (EDs). We investigated whether mEWS can predict death, hospital admission, intensive care unit (ICU) admission, and in-hospital deaths in a Turkish setting. Methods We conducted an ED-based prospective study of 309 patients who presented to an academic medical center. The mEWS was recorded in all patients on ED admission. A mEWS >4 was used to define patients at high-risk for the study outcomes. Results Patients categorized as being at high-risk either were admitted to ICU (n = 23) or to hospital (n = 37) 56.6% of the time, or died in ED (n = 16) or in hospital (n = 29) 42.4% of the time. Patients categorized as being at low-risk either were admitted to ICU (n = 25) or to hospital (n = 52) 37.4% of the time, or died in ED (n = 1) or in hospital (n = 4) 2.5% of the time. In multivariate regression analysis, patients with a mEWS of 5 or more were 1.95 times more likely to be admitted to ICU than those with a score less than 5. Patients with high-risk mEWS were 35 times more likely to die in ED and 14 times more likely to die in hospital than those presenting with a low-risk score. Conclusion We conclude that scores on the mEWS predict ICU admission as well as ICU and in-hospital deaths.

AIM: To investigate prognostic factors of survival following curative, non-palliative surgical removal of lung metastases secondary to colorectal cancer (CRC). METHODS: Between 1999 and 2009, a radical metastasectomy with curative intent was performed on lung metastases in 21 patients with CRC (15 male and 6 female; mean age: 57.4 +/- 11.8 years; age range: 29-74 years) who had already undergone primary tumour resection. RESULTS: The mean number of lung metastases ranged from one to five. The mean overall survival was 71 +/- 35 mo (median: 25 mo). After adjusting for potential confounders, multivariable Cox regression analyses predicted only the number of lung metastases (1 vs >= 2; hazard ratio: 7.60, 95% confidence interval: 1.18-17.2, P = 0.03) as an independent predictor of poor survival following lung resection for metastatic CRC. CONCLUSION: Resection of lung metastases is a safe and effective treatment in selected CRC patients with single lung metastases. (C) 2012 Baishideng. All rights reserved.