Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

Uncu, Dogan,Bayoglu, Ibrahim Vedat,Arslan, Ulku Yalcintas,Kucukoner, Mehmet,Artac, Mehmet,Koca, Dogan,Oguz, Arzu,Demirci, Umut,Arpaci, Erkan,Dogan, Mutlu,Kucukzeybek, Yuksel,Turker, Ibrahim,Isikdogan, Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer

Kos, Fahriye Tugba,Hocazade, Cemil,Kos, Mehmet,Uncu, Dogan,Karakas, Esra,Dogan, Mutlu,Uncu, Hikmet Gulsen,Ozdemir, Nuriye,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. Results: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ${\geq}3.24$) and PNI (<49.5 or ${\geq}49.5$). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). Conclusions: NLR (${\geq}3.24$) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

Acupuncture as a Complementary Treatment for Cancer Patients Receiving Chemotherapy

Tas, Demet,Uncu, Dogan,Sendur, Mehmet Ali,Koca, Nuran,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.7

Background: Medical treatment for eliminating the side effects of cancer therapy may not always be efficacious. Acupuncture is one of the most widely accepted alternative and complementary therapies in use today. In this study, we investigated the efficacy of acupuncture in patients experiencing cancer treatment side effects, including nausea, vomiting, pain, poor sleep quality and anxiety. Materials and Methods: A total of 45 inpatients who underwent chemotherapy between February and April 2013 in the Oncology Department of Numune Hospital were included in our study. Acupuncture was administered to the patients one day prior to chemotherapy, on the day of chemotherapy and one day after chemotherapy. The patients were evaluated on nausea, vomiting, pain, sleep quality and anxiety before the chemotherapy and on the $4^{th}$ day of chemotherapy. Results: Of the 45 patients included in the study, 18 (40%) were female and 27 (60%) were male. A total of 25 (55.6%) had an elementary school education; 32 patients (71%) had stage 4 cancer and were treated with palliative chemotherapy (the patient characteristics are shown in Table 1). Statistically significant decreases (p<0.001) in pain, nausea, vomiting, insomnia and anxiety scores were observed after the acupuncture treatment compared to baseline. There were no differences in the age, gender, education level, stage or metastasis levels between the patient groups whose symptoms improved or were unchanged. Conclusions: Our study showed that acupuncture has positive effects in cancer treatment patients who experience nausea, vomiting, pain, poor sleep quality and anxiety as side effects of chemotherapy. Chemotherapy-related side effects in cancer patients could be decreased by the concurrent use of acupuncture.

Elevated Serum Galectin-1 and Galectin-3 Levels in Children With Specific Learning Disorder: A Case Control Study

Yaşar Tanır,Zeynep Nur Gülle,Gökçe Sultan Uncu,Adile Merve Baki,Pervin Vural,Nusret Soylu,Abdurrahman Cahid Örengül 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.7

Objective Specific learning disorder (SLD) is a neurodevelopmental disorder in which underlying pathogenesis and etiological factors are not fully understood. Neuroinflammatory response (measured with serum levels of galectin-1 and galectin-3), which is associated with learning and memory, may play an important role in the etiopathogenesis of SLD. Aim of the present study is to examine whether serum galectin-1 and galectin-3 levels are related to SLD.Methods The current study consisted of 42 treatment-naive children with SLD and 42 control subjects. All of the subjects were assessed using semi-structured psychiatric examination to diagnose SLD and exclude attention-deficit hyperactivity disorder. Serum galectin-1 and galectin-3 levels were measured via venous blood samples.Results The SLD and control group did not differ significantly in terms of age, sex, and body mass index (BMI). The SLD group had significantly higher serum levels of galectin-1 (8.78±2.97 vs. 7.40±2.03, p=0.019) and galectin-3 (1.86±0.93 vs. 1.32±0.69, p=0.003) than the control group when controlled for age, sex, and BMI.Conclusion Higher serum levels of galectin-1 and galectin-3 in children with SLD may indicate the role of neuroinflammatory response in the pathogenesis of SLD. Other mechanisms involving galectin-1 and galectin-3 related to learning may play a part in the etiology of SLD.

Clinicopathologic Features and Prognosis of Osteosarcoma in Turkish Adults

Seker, Mehmet Metin,Seker, Ayse,Aksoy, Sercan,Ozdemir, Nuriye,Uncu, Dogan,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.8

Background: Osteosarcomas are the most common solid malignancies of bone. In the last two decades there have been no concrete developments in their systemic treatment. In this trial we aimed to present our osteosarcoma patient clinical and demographic outcomes. Materials and Methods: Patients treated and followed up for osteosarcoma in Ankara Numune Education and Research Hospital from 2002 to 2012 were reviewed retrospectively. Results: A total of 21 patients (15 male, 6 female) were diagnosed with osteosarcoma. The disease was located at extremities in 76% and in 14% was metastatic at the time of diagnosis. Median disease free survival (DFS) was 36 months in non-metastatic patients and median progression free survival (PFS) was 2 months in metastatic patients (p<0.0001). Median overall survival (OS) was 80 months and 4 months, respectively (p=0.012). There were no survival differences in terms of presentation with pathological fracture, tumor size, tumor grade, alkaline phosphatase and lactate dehydrogenase level and type of chemotherapy regimen. Conclusions: Tumor site and stages are the most important prognostic factors for osteosarcoma. Extremity primary tumors have beter survival rates than non-extremity tumors. As a result of the use of effective chemotherapy the long term survival rates have improved from 10-20% to 60-70% in the last decades but we need more active agents, especially for metastatic cases.

Is There an Association between Blood Group and Survival in Pancreatic Cancer?

Kos, F. Tugba,Civelek, Burak,Seker, M. Metin,Arik, Zafer,Aksoy, Sercan,Uncu, Dogan,Ozdemir, Nuriye,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Background: An association between the ABO groups and pancreatic cancer has been shown previously, group A being significantly commoner in affected patients. We conducted the present study to investigate the prognostic effect of ABO blood group on overall survival of pancreas cancer patients. Methods: Patients who were diagnosed between 2005 and 2010 with pancreas cancer at Ankara Numune Education and Research Hospital were analyzed retrospectively. Patient demographics and ABO blood groups were obtained from medical charts. Results: Fifty pancreas cancer patients with known ABO blood group were included, 26 (52%) group A, 12 patients (24%) group 0, 9 (18%) group B, and 3 (6%) group AB. Blood group A pancreas cancer patient median age was 61.5 (39-80) years, with the median age of the other blood groups (B, AB,O) being 55.5 (32-74) years (p=0.14). 18% of patients with blood group A and 11% of the other blood group patients had metastasis (p=0.17) at the time of diagnosis. The median overall survival of blood group A pancreas patients was significantly lower than the other blood group patients, 7.6 (95%CI: 5.0-10.2) months versus 29.0 (95%CI: 0.0-68.8) months (p=0.05). Conclusions: Acccording to previously published cohort studies a relation may exist between ABO blood groups and cancer of pancreas. In this study we observed that pancreas cancer patients with blood group A have significantly worse overall survival than other blood groups.

Effects of Vitamin E Supplementation on Oxidative Stress in Streptozotocin Induced Diabetic Rats: Investigation of Liver and Plasma

Arzu Seven,Sava Guzel,Oktay Seymen,Sabiha Civelek,Murat Bolayirli,Murat Uncu,Gulden Burcak 연세대학교의과대학 2004 Yonsei medical journal Vol.45 No.4

This experimental study was designed to investigate the effects of vitamin E supplementation, especially on lipid peroxidation and antioxidant status elements¾ namely, glutathione (GSH), CuZn superoxide dismutase (CuZn SOD), and glutathione peroxidase (GSH Px), both in blood and liver tissues of streptozotocin (STZ) diabetic rats. The extent to which blood can be used to reflect the oxidative stress of the liver is also investigated. In diabetic rats, plasma lipid peroxide values were not significantly different,from control,whereas erythrocyte CuZn SOD (p<0.01), GSH Px (p<0.001) activities and plasma vitamin E levels (p<0.001), were significantly more elevated than controls. Vitamin E supplementation caused significant decreases of erythrocyte GSH level (p<0.01) in control rats and of erythrocyte GSH Px activity (p<0.05) in diabetic rats. Liver findings revealed significantly higher lipid peroxide (p<0.001) and vitamin E (p<0.01) levels and lower GSH (p<0.001), CuZn SOD (p<0.001) and GSH Px (p<0.01) levels in diabetic rats. A decreased hepatic lipid peroxide level (p<0.01) and increased vitamin E/lipid peroxide ratio (p<0.001) were observed in vitamin E supplemented, diabetic rats. A vitamin E supplementation level which did not cause any increase in the concentration of the vitamin in the liver or blood, was sufficient to lower lipid peroxidation in the liver. Vitamin E/lipid peroxide ratio is suggested as an appropriate index to evaluate the efficiency of vitamin E activity,independent of tissue lipid values. Further, the antioxidant components GSH, GSH Px and CuZn SOD and the relationships among them, were affected differently in the liver and blood by diabetes or vitamin E supplementation.

Treatment and Outcomes of Ewing Sarcoma in Turkish Adults: A Single Centre Experience

Seker, Mehmet Metin,Kos, Tugba,Ozdemir, Nuriye,Seker, Ayse,Aksoy, Sercan,Uncu, Dogan,Zengin, Nurullah Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1

Background: Ewing sarcoma is a small round cell tumor arising from soft tissue and bone that predominantly affects children and adolescents. The most unfavorable prognostic factor is the presence of distant metastasis at the time of diagnosis. Materials and Methods: The records of 26 Ewing sarcoma patients (14 male, 12 female) were re-evaluated retrospectively. Results: The median age was 26.5 (19-42) years. Eight patients (31%) showed a primary tumor in their extremities, 8 (31%) in the thorax, 4 (15%) at the vertebra, 4 (15%) in the head and neck, and 2 (8%) in the abdomen. Five patients (19%) had distant metastasis at diagnosis. The median progression-free survival was 72 months and 10 months in localized and metastatic disease, respectively (p=0.005). The overall survival rate was 19 months in metastatic disease, and the 5-year overall survival rate was 64% in localized disease (p=0.006). Patients who had localized disease in the extremities and were under age 30 had a favorable prognosis. Conclusions: Although Ewing sarcoma is a tumor affecting children and adolescents, it may be seen in adults, where the prognosis is generally worse. Although it is a highly malignant tumor, it is possible to achieve improved survival with combined modality treatments.

Predictors of 3-month mortality with muscle ultrasound and palliative prognostic tools among patients admitted to palliative care units

Zeynep Irmak Kaya,Yelda Öztürk,Sinem Gürcü,Gülgün Uncu,Anıl Uçan,Mert Eşme,Berrin Yalınbaş Kaya,Cafer Balci 대한내과학회 2023 The Korean Journal of Internal Medicine Vol.38 No.4

Background/Aims: Prognostic factors are an important issue in progressive and life-limiting diseases. This study evaluate 3-month mortality in patients admitted to the palliative care unit (PCU). Methods: In this study, the patient’s demographics, comorbidities, nutritional status, and laboratory values were recorded. The palliative performance scale (PPS), the palliative prognostic index (PPI), and the palliative prognostic (PaP) score were calculated. The rectus femoris (RF) cross-sectional area (CSA), RF muscle thickness, gastrocnemius (GC) medialis muscle thickness, pennation angle and fascicle length of the GC were measured by ultrasound for survival prediction. Results: A total of 88 patients enrolled during the study period, with a mean age of 73.6 ± 13.3 years and a 3-month mortality rate of 59.1%. The findings of a multivariable Cox proportional hazards regression model based on age, gender, C-reactive protein level and Nutrition Risk Screening 2002 scores as covariates revealed the PPI and the PaP score to be significant predictors of 3-month mortality. In addition, in the unadjusted Cox proportional hazard regression analysis, the CSA of the RF muscle was also found to be a significant predictor of 3-month mortality. Conclusions: Findings revealed that the combined use of the CSA of the RF, the PPI, and the PaP score are reliable predictors of mortality in patients admitted to the PCU.

Clinicopathological Features in Bilateral Breast Cancer

Baykara, Meltem,Ozturk, Selcuk Cemil,Buyukberber, Suleyman,Helvaci, Kaan,Ozdemir, Nuriye,Alkis, Necati,Berk, Veli,Koca, Dogan,Coskun, Ugur,Oksuzoglu, Berna,Uncu, Dogan,Arpaci, Erkan,Ustaalioglu, Basak Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.9

Introduction and Purpose: The frequency of bilateral breast cancer is 1.4-11.0% among all breast cancers. It can present as synchronous (SC) or metachronous (MC). Data regarding clinical course of bilateral breast cancer are scarce. In this study, we therefore evaluated demographic, pathological and clinical characteristics, treatments and responses in bilateral breast cancer cases; making distinctions between metachronous-synchronous and comparing with historic one-sided data for the same parameters. Materials and Methods: One hundred fifty bilateral breast cancer cases from ten different centers between 2000 and 2011 were retrospectively scanned. Age of the cases, family history, menopausal status, pathological features, pathological stages, neoadjuvant, surgery, adjuvant and palliative chemotherapy/radiotherapy were examined in the context of the first and second occurrence and discussed with reference to the literature. Results: Metachronous and synchronous groups showed similar age, menopausal status, tumor type, HER2/neu expression; the family history tumor grade, tumor stage, ER-negativity rate, local and distant metastases rates, surgery, adjuvant chemotherapy application rates were identified as significantly different. Palliative chemotherapy response rate was greater in the metachronous group but median PFS rates did not differ between the groups. Conclusion: Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis.