Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Correlation between 18F-FDG Positron-Emission Tomography 18F-FDG Uptake Levels at Diagnosis and Histopathologic and Immunohistochemical Factors in Patients with Breast Cancer.

OBJECTIVE: In this study, we aimed to determine the correlation between pretreatment-staging 18F-FDG total body positron-emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) levels and histopathologic and immunohistochemical predictive and prognostic factors in patients with breast cancer. MATERIALS AND METHODS: One hundred thirty-nine women with breast cancer who were treated between 2009 and 2015 at our hospital and who had pretreatment-staging PET/CT were included in the study. SUVmax levels and histopathologic and immunohistochemical results were compared. RESULTS: The median age was 48 years (range, 29-79 years). The mean tumor diameter was 33.4 mm (range, 7-120 mm). The histology was invasive ductal carcinoma in 80.6% of the patients. In the univariate analysis, SUVmax levels were significantly higher in patients with invasive ductal carcinoma; in patients with a maximum tumor diameter more than 2 cm; patients who were estrogen, progesterone, and combined hormone receptor-negative, triple-negative patients, and in tumors with higher grades (p<0.05). In HER2-positive patients, SUVmax levels were higher even if it was not statistically significant. There was no correlation between lymph node metastases and pathologic stage. In multivariate analysis, tumor diameter was an independent factor. CONCLUSION: SUVmax levels are correlated with known histopathologic and immunohistochemical prognostic factors. PET/CT could be useful in preoperative evaluation of patients with breast cancer to predict biologic characteristics of tumors and prognosis.

Staging with PET-CT in patients with locally advanced non small cell lung cancer is superior to conventional staging methods in terms of survival.

BACKGROUND: Of patients with non small cell lung cancer (NSCLC), around one third are locally advanced at the time of diagnosis. Because only a proprotion of stage III patients can be cured by surgery, in order to improve the outcomes, sequential or concurrent chemoradiation, or concurrent chemoradiation with induction or consolidation is offered to the patients with locally advanced NSCLC. Today, PET combined with computerized tomography (PET-CT) is accepted as the most sensitive technique for detecting mediastinal lymph node and extracranial metastases from NSCLC. We aimed to compare PET-CT and conventional staging procedures for decisions regarding curative treatment of locally advanced NSCLC. MATERIALS AND METHODS: A total of 168 consecutive patients were included from Acibadem Kayseri Hospital, Acibadem Adana Hospital and Kayseri Research and Training Hospital in this study. RESULTS: While the median PFS was 13.0 ± 1.9 months in the PET-CT group, it was only 6.0 ± 0.9 in the others (p<0.001). The median OS values were 20.5 ± 15.6 and 11.5 ± 1.5 months, respectively (p<0.001). DISCUSSION: As a result, we found that staging with PET CT has better results in terms of survival staging. This superiority leads to survival advantage in patients with locally advanced NSCLC.

Sunlight may increase the FDG uptake value in primary tumors of patients with non-small cell lung cancer.

Currently, positron emission tomography with computerized tomography (PET-CT) is the most sensitive technique for detecting extracranial metastases in non-small cell lung cancer (NSCLC). It has been reported that there is a correlation between the maximal standardized uptake value (SUV(max)) of primary tumors and prognosis in patients with NSCLC. The effect of sunlight exposure on PET-CT SUV(max) value is not known. Therefore, we aimed to evaluate the effect of sunlight exposure on PET-CT SUV(max) value in patients with NSCLC. A total of 290 patients with NSCLC from two different regions of Turkey (Kayseri, n=168 and Adana, n=122) that have different climate and sunlight exposure intensity, were included in the study. Age, gender, histology of cancer, cancer stage, smoking status, comorbidity and SUV(max) of the primary tumor area at the time of staging were evaluated as prognostic factors. In the multivariate analysis, we detected that the region was the only independent factor affecting SUV(max) (P=0.019). We identified that warmer climate and more sunlight exposure significantly increases the SUV(max) value of the primary tumor area in patients with NSCLC. Further studies are warranted to clarify the issue.

Does sunlight exposure improve survival in patients with non-small cell lung cancer?

BACKGROUND: Some epidemiological studies reported that sunlight exposure and highvitamin D levels may decrease the morbidity and mortality related to cancer. We aimed to evaluate whether sunlight exposure has an impact on survival in patients with non small cell lung cancer. MATERIALS AND METHODS: A total of 546 patients with NSCLC from two different regions (Kayseri and Adana) differing according to sunlight exposure were analysed retrospectively. RESULTS: The median overall survival (OS) rates were 11. 6 (CI: 9.50-13.6) and 15.6 months (CI: 12.4-18.8) for Kayseri and Adana, respectively, in all patients (p=0.880). CONCLUSIONS: There were no differences between groups in terms of OS. While there is strong evidence regarding inverse relationship between cancer incidence and sunlight exposure, it is still controversial whether sunlight exposure is a good prognostic factor for survival in patients with lung cancer.

Management of elderly patients with advanced non-small cell lung cancer in Turkey.

OBJECTIVE: Non-small cell lung cancer is a disease that affects the elderly. However, most patients older than 70 years are less likely to receive standard therapy than their younger counterparts and the aim of the present study was to determine age-dependent variation in efficacy. SUBJECTS AND METHODS: Between 2004-2008, 40 consecutive patients older than 70 years received treatment for advanced non-small cell lung cancer. All were evaluated for response and toxicity. Chemotherapy was either with cisplatin or carboplatin and double or single agents (vinorelbine, gemcitabine). Docetaxel was used as a second line therapy in selected cases. Patients were grouped according to age: group 1 (70-74 years), group 2 (>or= 75 years). RESULTS: Except for 4 cases, all received chemotherapy, and 61 % were given a cisplatin-containing regimen. Second-line therapy was given to 42.5% and grades 3-4 neutropenia was seen in 17 (42.5%). Only one patient died due to neutropenic fever. Nephrotoxicity was observed in 2 (5%) and one underwent hemodialysis. Overall survival was 10 months, with median survival periods for groups 1 and 2 of 13 and 10 months, respectively (p> 0.05). No differences were found regarding type of chemotherapy administered or adverse events between the 2 groups. CONCLUSION: Patients older than 75 years appear to deserve the same standard therapy for non-small cell lung cancer as that given to younger cases.

Prognostic significance of the C-erbB-2 expression in turkish non-small cell lung cancer patients.

BACKGROUND: The prognostic value of c-erbB-2 expression in patients with non-small cell lung cancer (NSCLC) remains controversial. The prevalence of c-erbB-2 expression in NSCLC and relation to disease prognosis were therefore investigated. METHODS: Eighty-nine patients with NSCLC diagnosed at Baskent University, Adana Hospital, Medical Oncology Department, between 2000-2005 were investigated. Expression of c-erbB-2 was evaluated by immunohistochemistry in paraffin-embedded sections. Characteristics of patients, histology and stage of the disease were obtained from clinical records. RESULTS: C-erbB-2 expression was detected in 18 patients (20.2%). Median survival of the patients with c-erbB-2 negative was 13 months, as compared to 6 months for c-erbB-2 positive cases (p=0.02), the relative risk of death being 1.96 times higher. No correlation was found between c-erbB-2 positivity and stage of the disease or histology of the tumor (p> 0.05). CONCLUSIONS: C-erbB-2 positivity may indicate shorter survival and can be regarded as an unfavorable prognostic factor in NSCLC. Immunohistochemistry seems to be a readily applicable, inexpensive methodology for determining c-erbB-2 expression in NSCLCs.

The effect of HER2 expression on cisplatin-based chemotherapy in advanced non-small cell lung cancer patients.

INTRODUCTION: The prognostic value of HER2 expression in patients with advanced non-small cell lung cancer remains controversial. The relationship between HER2 expression, and platinum resistance and patient survival, was investigated. METHODS: Seventy-three consecutive patients (median age, 61 years) with stage IIIB and IV non-small cell lung cancer, admitted between February 2004 and December 2006, were included in this study. Sixty-one patients received gemcitabine, given as two 1250 mg/m2 doses on days 1 and 8 and, cisplatin, given as a 75 mg/m2 dose on day 8. Twelve patients received vinorelbine, given as two 25 mg/m2 doses on day 1 and 8, and cisplatin, given as a 75 mg/m2 dose on day 1. Both treatment paradigms were repeated on a 21-day cycle. Tumor response was evaluated by comparing tumor size on computerized tomography scans before and after three cycles of chemotherapy. HER2 status was examined by immunohistochemical analysis of paraffin-embedded specimens. RESULTS: HER2 was positive in 21 of 73 patients (28.8%). Of the 21 patients with HER2 positivity, 13 (61.9%) responded to chemotherapy with either a complete response, partial remission, or evidence of stable disease. Of 52 HER2-negative patients, 48 (92.3%) exhibited a response to chemotherapy. The difference in response to therapy between HER2-positive and -negative patients was statistically significant (p = 0.003). The median overall survival duration for all patients was 13 months. Median overall survival time was 14 months for HER2-negative patients and 10 months for HER2-positive patients (log-rank p = 0.007). CONCLUSION: Non-small cell lung cancer patients with high expression of HER2 exhibited resistance to cisplatin-based chemotherapies that are the standard treatment for this disease. Our results indicate that HER2 status may be a predictive and prognostic factor for cisplatin- based therapy response and disease survival.

Micronucleus analysis in patients with colorectal adenocarcinoma and colorectal polyps.

AIM: To determine, by counting micronucleus (MN) frequencies, whether chromosomal or DNA damage have an effect on the pathogenesis of early colorectal adenocarcinoma (CRC). METHODS: We analyzed MN frequencies in 21 patients with CRC, 24 patients with colon polyps [10 neoplastic polyps (NP) and 14 non-neoplastic polyps (NNP)] and 20 normal controls. RESULTS: MN frequency was significantly increased in CRC patients and in NP patients compared with controls (3.72 +/- 1.34, 3.58 +/- 1.21 vs 1.97 +/- 0.81, P < 0.001). However, there was no difference in the MN frequency between CRC patients and NP patients (P > 0.05). Similarly, there was no difference in the MN frequency between NNP patients (2.06 +/- 0.85) and controls (P > 0.05). CONCLUSION: Our results suggest increased chromosome/DNA instabilities may be associated with the pathogenesis of early CRC.

Gemcitabine and cisplatin treatment of advanced-stage non-small-cell lung cancer in patients given cisplatin on day 8.

AIMS AND BACKGROUND: Gemcitabine and cisplatin treatment were administered to patients with advanced-stage, non-small-cell lung cancer. During phase II studies, the treatment is performed using a 28-day cycle, with gemcitabine administered on days 1, 8, and 15. Although it is advised that cisplatin not be administered on the first day, gemcitabine and cisplatin treatment is usually performed using a 21-day cycle, with gemcitabine administered on days 1 and 8, and cisplatin is given on the first day in most phase III studies. In contrast with previous phase III studies, cisplatin was administered on day 8 in our study. Dose density, drug toxicity, and efficacy were analyzed. METHODS AND STUDY DESIGN: Chemonaive patients with stage IIIB or stage IV nonsmall-cell lung cancer received gemcitabine (1250 mg/m2) on days 1 and 8 plus cisplatin (75 mg/m2) on day 8 every 3 weeks (1 cycle contained 2 applications). RESULTS: Sixty-seven patients received a total of 293 applications. Dose densities were 92.3% for gemcitabine and 93.9% for cisplatin. The types and rates of grade 3 and grade 4 hematologic toxicities were anemia (6%), granulocytopenia (46%), and thrombocytopenia (6%). Complete remission was seen in 2 patients (3%); partial remission was 40%, stable disease was 39%, and progression of disease, 10%. The median overall survival time was 13 months. The median progression-free survival time was 9.5 months. One-year survival rate was 54% and 2-year survival, 10.4%. CONCLUSIONS: In this 21-day treatment regimen, overall survival was longer than 1 year and the 1-year survival rate was more than 50%. Both the severity and rate of observed thrombocytopenia in the study were very low. Other adverse effects in the current study were comparable to those reported in the literature.