A multicenter, retrospective archive study of radiological and clinical features of ALK-positive non-small cell lung cancer patients and crizotinib efficacy.

To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.

Clinical significance of postoperatif controlling nutritional status (CONUT) score in glioblastoma multiforme.

PURPOSE: The Controlling Nutritional Status (CONUT) Score, a new parameter that reflects the immuno-nutritional status, has been closely associated with prognosis in many cancer types. However, the prognostic significance of the CONUT score in Glioblastoma Multiforme (GBM) is not known. In this study, we aimed to show the prognostic significance of the CONUT score in the postoperative period in patients with GBM. METHODS: 120 patients followed up with GBM were included in the study, retrospectively. According to the receiver operating characteristic (ROC) curve analysis, the optimal cut-off values were determined for the CONUT score, and the patients were divided into low (<2.5) and high (≥2.5) CONUT groups. Systemic immune inflammation index (SII), prognostic nutritional index (PNI), and neutrophil-lymphocyte ratio (NLR) were grouped according to the cut-off point of 1111, 46.5, and 4.48, respectively. Cox regression analyzes were used to assess their prognostic significance for progression-free survival (PFS) and overall survival (OS). RESULTS: The high CONUT score group was found to have worse PFS and OS than the low CONUT score group (p < 0.001, p < 0.001). In univariate analysis, age, gender, comorbidity, CONUT score, SII, PNI, NLR were found to be significant for both PFS and OS. In multivariate analysis, only age and CONUT score were found as independent prognostic factors for both PFS (p: 0.040, p < 0,001) and OS (p: 0,041, p < 0,001). CONCLUSION: The CONUT score in the postoperative period in patients with GBM is an independent prognostic parameter that predicts progression and survival.

Tyrosine kinase inhibitors in the treatment of metastatic renal cell cancer patients with early cytokine intolerance: TURCOS, a Turkish national, prospective observational study.

OBJECTIVE: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients. METHODS: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded. RESULTS: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4-10.4) and 27.3 months (95%CI: 17.6-27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity. CONCLUSIONS: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS.Trial registration: TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients.

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 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯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 ±â€¯2.5 months and mOS of 90.3 ±â€¯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 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.

Molecular subtypes are prognostic for N3 breast cancer patients in the modern therapeutic era.

Nodal (N) status and molecular subtypes are well-known prognostic factors for breast cancer patients. The aim of the present study was to evaluate whether there was a prognostic role of molecular subtypes for pN3a breast cancer patients in the modern therapeutic era. The present study retrospectively evaluated a total of 521 breast cancer patients who had 10 or more metastatic lymph nodes and received adjuvant systemic therapy at the Oncology Department of four different centers in Turkey between 2000-2015. Patients were divided into four molecular subtypes by immunohistochemical staining. There were no significant differences in relapse rates according to the molecular subtypes (P=0.07). The five year disease free survival rate was 62% for the whole study population, 67% for Luminal A tumors, 53% for Luminal B tumors, 64% for human epidermal growth factor receptor 2-positive tumors and 56% for triple negative tumors. Luminal A patients had a better progression free survival when compared with Luminal B (P=0.026) and triple negative (P=0.07) patients. pT stage (P<0.001), and breast cancer subtype (P<0.001), remained significant independent factors for disease free survival. Therefore, breast cancer subtypes are still prognostic for patients with pN3 breast cancer.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

Arterial Stiffness in Breast Cancer Patients Treated with Anthracycline and Trastuzumab-Based Regimens.

AIMS: Cardiovascular diseases are the primary cause of premature morbidity and mortality in early breast cancer patients after treatment with cardiotoxic chemotherapeutic agents. Arterial stiffness is an independent risk factor for future cardiovascular diseases and can be used as a predictive marker of subclinical cardiac damage. The aim of this study is to analyze the arterial stiffness in breast cancer patients who are in the follow-up period after receiving anthracycline-based chemotherapy regimens with trastuzumab. METHODS AND MATERIAL: We enrolled 45 HER2-positive breast cancer patients who are on follow-up at least for six months after completion of adjuvant chemotherapy with trastuzumab, and cardiovascular risk matched 30 control volunteers. The measurements were done with pulse wave analyzing machine. RESULTS: Mean pulse wave velocity was higher in breast cancer patients compared to controls. The pulse wave velocity was significantly higher in patients receiving aromatase inhibitors compared to patients under tamoxifen. It was also significantly higher in postmenopausal breast cancer patients than postmenopausal controls. CONCLUSIONS: Arterial stiffness measurements may predict the breast cancer survivors with higher risk for cardiovascular events earlier in the follow-up period, and necessary preventive approaches and/or treatments can be applied.

Role of increased mean platelet volume (MPV) and decreased MPV/platelet count ratio as poor prognostic factors in lung cancer.

OBJECTIVES: In this study, they investigated whether mean thrombocyte volume (MPV) and MPV/platelet count ratio have a prognostic significance in advanced NSCLC or not. METHODS: A total of 496 NSCLC patients at stage IIIB/IV and did not meet exclusion criteria were included in the study. The demographic features (age, gender, smoking habit), clinical characteristics (performance status, weight loss, disease stage, first-line treatment regimen), laboratory tests (levels of hemoglobin, lactate dehydrogenase and calcium as well as MPV, MPV/platelet count ratio and counts of white blood cell, platelet), and histological features (histologic type, tumor grade) were recorded. RESULTS: The MPV levels of all patients were determined as 10.2 {plus minus} 3.4 (range, 6.4-14.1 fL). With ROC curve analysis, the MPV/PC ratio was associated with a sensitivity of 67.8% and a specificity of 84.8% at a cutoff value of 0.47424 for presence of brain metastasis at the time of diagnosis. Univariate analysis showed that OS was significantly shorter in the group with an increased MPV level than in the other group (median OS time 6.8 months vs. 11.5 months, log-rank, P = .032). Multivariate analysis confirmed that an increased MPV level was an independent poor prognostic factor for OS (HR: 1.704, 95% CI: 1.274-3.415, P = .014). CONCLUSIONS: Unlike results of previous studies, the study showed that increased MPV was an important prognostic factor in patients with NSCLC. Hence, an increased MPV level may be used as a prognostic biomarker to estimate for poor overall survival in patients with NSCLC.

Pretreatment Serum Albumin Level is an Independent Prognostic Factor in Patients with Stage IIIB Non-Small Cell Lung Cancer: A Study of the Turkish Descriptive Oncological Researches Group.

BACKGROUND: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. MATERIALS AND METHODS: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. RESULTS: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. CONCLUSIONS: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.

Epidemiology of colorectal cancer in Turkey: A cross-sectional disease registry study (A Turkish Oncology Group trial).

BACKGROUND/AIMS: This study aimed to determine the epidemiological characteristics of colorectal cancer in Turkey. MATERIALS AND METHODS: In this multicenter, prospective, and cross-sectional registry study, data for 968 patients with colorectal cancer from 21 centers in 7 geographic regions were analyzed. RESULTS: Diagnosis was colon cancer in 662 (68.4%) and rectum cancer in 306 (31.6%) patients. In total, 60.9% of patients was male; mean age was 58.9±12.6 years. Among patients, 15.0% was drinking alcohol, 17.5% was smoking, 1.5% had familial history of polyposis, 15.0% had diabetes mellitus, 1.0% had inflammatory bowel disease. Fruit and vegetable consumption was low (<3 times/week) in 35.5% and red meat consumption was high (≥3 times/week) in 47.4% of the patients. Median time-to diagnosis was 3.0 months and 4.0 months for patients with colon and rectum cancer, respectively. Mean body mass index was >25 in all group of patients. Distal rectum (61.3%) and sigmoid colon (36.8%) were the most common locations of cancer, for rectum and colon respectively. In total, 85.6% of patients were operated; 25.8% had emergency surgery. Low anterior resection rate was 64.2% in rectum cancer. In majority (89.8%) of the patients with rectum cancer who received preoperative treatment, conventional chemo-radiotherapy regimen was given. pTNM staging at diagnosis showed that stage III and IV patients were in majority (35.9% and 29.7%, respectively). CONCLUSION: Colon cancer is more frequent than rectum cancer in Turkey. Colorectal cancer patients are diagnosed at later stages. Most of the cases were operated. Interregional differences for risk factors are worthwhile for evaluation in future trials.

Prognostic significance of the baseline serum uric acid level in non-small cell lung cancer patients treated with first-line chemotherapy: a study of the Turkish Descriptive Oncological Researches Group.

Non-small cell lung cancer (NSCLC) is one of the most common cancers. Most of the patients are inoperable at the time of diagnosis, and the prognosis is poor. Many prognostic factors have been identified in prior studies. However, it is not clear which factor is more useful. In this study, we investigated whether uric acid, the last breakdown product of purine metabolism in humans, has a prognostic significance in advanced NSCLC. A total of 384 NSCLC patients at stage IIIB/IV and who did not meet exclusion criteria were included in this retrospective cross-sectional study. The patients' serum uric acid levels before first-line chemotherapy and demographic (age, gender, smoking), clinical (performance status, weight loss, disease stage, first-line treatment regimen), laboratory (hemoglobin, lactate dehydrogenase), and histologic (histologic type, tumor grade) characteristics were recorded. First, a cut-off value was determined for serum uric acid level. Then, the patients were stratified into four groups (quartiles) based on their serum uric acid levels. Descriptive statistics, univariate and multivariate analyses, and survival analyses were used. Majority of the patients were males, smokers and metastatic at time of diagnosis and had history of weight loss and adenocarcinoma upon pathological examination. The serum uric acid levels of all patients were determined as 4.9±2.9 (range 1.9-11.3). The patients were stratified according to quartiles of serum uric acid concentration with cutoff values defined as <3.08 mg/dL (lowest quartile, Group 1), 3.09-5.91 mg/dL (Group 2), 5.92-7.48 mg/dL (Group 3), and >7.49 mg/dL (highest quartile, Group 4). Among the patients who had serum uric acid levels over 7.49, it was observed that those who also had squamous cell carcinoma had a greater rate of brain metastasis, a shorter time lapse until brain metastasis, and lower overall survival rate. It can be assumed that NSCLC patients who had histologically shown squamous cell carcinoma display brain metastasis and poor prognosis. It can be recommended to repeat this study with larger patient series including immunohistochemical, molecular, and wider laboratory investigations.

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG).

Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.

Tumor characteristics and metastatic sites may predict bevacizumab efficacy in the first-line treatment of metastatic colorectal cancer.

Colorectal cancer (CRC) is among the most frequently diagnosed cancers and a major cause of cancer-related mortality worldwide. The aim of the present study was to determine whether there was an improvement in the time to disease progression (TTP) in patients with metastatic colorectal cancer (mCRC) treated with first-line bevacizumab plus chemotherapy, according to tumor characteristics and metastatic sites. Tumor characteristics and tumor burden were considered to be predictive markers of the therapeutic efficacy of bevacizumab. The medical records of 705 patients with mCRC were retrospectively reviewed in three oncology centers between January, 2005 and September, 2012. A total of 101 patients completed their first-line bevacizumab-containing treatment. The median TTP was 6.93 months [interquartile range (IQR)=4.20-9.80 months] in patients treated with irinotecan, 5-fluorouracil (5-FU) and bevacizumab vs. 7.42 months (IQR=6.08-10.68 months) in those treated with oxaliplatin, 5-FU and bevacizumab (P=0.589). When we compared patients with pulmonary metastases (median TTP, 9.9000 months) or other metastatic patients without pulmonary metastasis (median TTP, 6.9000 months), we observed a statistically significant difference (P=0.046). However, when the efficacy of bevacizumab was compared in terms of other tumor characteristics (tumor grade, size and lymph node involvement) and metastatic sites, the differences were not significant (P>0.05). We concluded that bevacizumab may be effective in all subgroups of patients with mCRC. Furthermore, bevacizumab with combination chemotherapy may be superior to combination chemotherapy only as the first-line treatment of patients with mCRC and pulmonary metastasis.

Reconsideration of clinical and histopathological prognostic factors in breast cancer patients: a single center experience.

BACKGROUND: The clinical course of the neoplasm may vary due to both patient and tumor cell characteristics. AIM: The aim of this study was to research the influence of certain clinical and pathological features on the prognosis of early stage breast cancer. MATERIALS AND METHODS: This study included 117 women that were treated and followed-up in between the years 2001-2011. The demographic, clinical and histopathological features of the cases were reviewed retrospectively. STATISTICAL ANALYSIS: In categorical comparisons between groups, cross-tab statistics were provided and significance levels were estimated using chi-square test. Cox regression analysis, Pearson and Spearman correlation tests, and the Kaplan-Meier test were also used. RESULTS: With an average of 35-months follow-up, the mean disease-free survival of patients was 91 months and the mean overall survival time was 132 months. In the whole study group, the disease-free survival rates were 88, 84, 83 and 52%, while the overall survival rates 95, 94, 83, and 83% within the first, third, fifth and tenth years, respectively. The disease- free and overall survival rates were decreased with increasing tumor grades, though this was not statistically significant. The presence of lymphovascular invasion, positive staining with Ki67 and postmenopausal status were associated with shorter disease-free and overall survival times. In multivariate analysis, only age and Her2/ neu receptor status influenced the prognosis significantly. CONCLUSIONS: In parallel to clinical, histopathological, and immunohistochemical prognostic features in breast cancer, in this study positive Her2/neu receptor status, a previously accepted poor prognostic factor, was found to have positive influence after trastuzumab treatment.

Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation.

Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an effective treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine.

Cutaneous metastasis of gallbladder adenocarcinoma in a patient with chronic lymphocytic leukemia: a case report and review of the literature.

Skin metastasis of primary gallbladder tumors is extremely rare with a reported incidence of 0.7~9% and it usually involves the thorax, abdomen, the extremities, neck, head region, and scalp. Cutaneous metastasis may occur synchronously or metatochronously. In the present case, the patient had chronic lymphocytic leukemia, which was being treated with an alkylating agent (chlorambucil) when the patient developed skin metastasis from gallbladder adenocarcinoma during post- cholecystectomy follow-up. Given the fact that secondary malignancies occur in chronic lymphocytic leukemia; this clinical setting warrants attention. We aimed to discuss secondary malignancy in chronic lymphocytic leukemia patients and gallbladder adenocarcinoma with skin metastasis, based on a review of the literature and the presented case.

Anti-Yo antibody-mediated paraneoplastic cerebellar degeneration in a female patient with pleural malignant mesothelioma.

Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.

Long-term effect of trastuzumab on QT dispersion in adjuvant treatment for patients with Her2 receptor positive breast cancer: a pilot study.

We investigated the long-term effect of trastuzumab, a monoclonal antibody against the Her2 signalling pathway, on QT dispersion in female patients with early-stage breast cancer. A total of 46 eligible patients with early-stage breast cancer were divided into two groups according to whether they were treated with trastuzumab: Group 1 (n = 32, patients with Her2-positive tumours who were treated with trastuzumab) and Group 2 (n = 14, patients with Her2-negative tumours who were not treated with trastuzumab). The both groups were compared using QT interval measurements. Patients with breast cancer treated with trastuzumab after an anthracycline-based regimen exhibited a significantly higher QTd than non-treated patients (0.064 ± 0.023 s vs. 0.051 ± 0.016 s, respectively) (P = 0.034). The mean increases in QTd and QTcd for Group 1 patients after paclitaxel-trastuzumab combination treatment (0.021 ± 0.011 and 0.022 ± 0.014 s, respectively) are significantly different than the mean increases in QT and QTcd after an anthracycline-based regimen (0.005 ± 0.003 and 0.006 ± 0.008 s) in the same group (P = 0.0246), compared with initial measurements. It has been concluded that the relationship between increased QTd measurements and trastuzumab treatment for 12 weeks in an adjuvant setting for patients with early-stage breast cancer is independent from other study variables. We suggested that long-term treatment with trastuzumab significantly prolonged the QT interval and increased QTd in patients with breast cancer.

Imatinib-associated bilateral gynecomastia and unilateral testicular hydrocele in male patient with metastatic gastrointestinal stromal tumor: a literature review.

Imatinib mesylate is a drug that has been approved for treatment of advanced gastrointestinal stromal tumors (GISTs) and patients with leukemia such as chronic myeloid or Philadelphia chromosome-positive acute lymphoblastic. Although it has been described only in one patient with testicular hydrocele and gynecomastia in the literature, several cases of male gynecomastia have been reported with the use of imatinib mesylate in chronic myeloid leukemia (GML). Generally, male mastoplasia resolves after discontinuation of imatinib treatment. We report a 73-year-old male with metastatic GISTs who developed gynecomastia and unilateral testicular hydrocele while receiving imatinib mesylate. Nine months after commencing imatinib treatment, gynecomastia and testicular hydrocele were determined. Hormone analyses requested showed serum testosterone levels below and serum estrogen levels above normal limits. During the first month after discontinuing imatinib mesylate treatment, serum testosterone level was normal and there was a partial regression in gynecomastia and testicular hydrocele. To our knowledge, this is the second report of male gynecomastia following imatinib mesylate treatment of a patient with GIST. In conclusion, male patients who are to receive treatment with imatinib mesylate may be monitored for serum testosterone levels and for other reproductive hormone profiles before initiation of the treatment and their breasts may be examined during follow-up visits.