Onur Esbah

Metaplastic Breast Carcinoma: Case Series and Review of the Literature

Metaplastic breast carcinoma (MpBC) is a rare disease entity, accounting for less than 1% of all breast carcinomas. Furthermore, it is a heterogenous disease with different subgroups, including malignant epithelial (carcinoma) and stromal (sarcoma) features. Here we evaluated, retrospectively, 14 female MpBC patients admitted to Ankara Oncology Training and Research Hospital between 2005 and 2011. Median age was 45.5 (range:16.0-76.0) and tumor size 57.5 mm (range: 20.0-80.0 mm). Histopathological subtypes were as follows: 5 carcinosarcoma, 5 squamous and 4 adenosquamous carcinoma. All but one with upfront lung metastasis, had their primary breast tumor operated. Axillary lymph nodes were involved in 64.3%. The most common sites of metastasis were lungs and brain. Chemotherapy including antracycline, taxane and even platinium was planned for adjuvant, neoadjuvant and palliative purposes in 9, 3 and 1 patient, respectively. Median cycles of chemotherapy was 6 (range:4-8). Median follow-up of the patients was 52 months (95%CI 10.4-93.6 month). Median 3 year progression free survival (PFS) and overall survival (OS) in this patients cohort were 33% and 56%, respectively. In conclusion, MpBC is a rare and orphan disease without standardized treatment approaches and the prognosis is poor so that larger studies to investigate different treatment schedules are urgently needed.

Bone Metastasis from Gastric Cancer: The Incidence, Clinicopathological Features, and Influence on Survival

Purpose To evaluate the incidence, clinicopathological characteristics, treatment outcomes, prognostic factors, and survival of gastric cancer patients with bone metastases. Materials and Methods Of 4,617 gastric cancer patients who were treated between 2001 and 2013, 176 patients with bone metastases were analyzed. Results The incidence of bone metastasis was 3.8%. The most common histopathological subtype was adenocarcinoma (79%) with poor differentiation (60.8%). The median interval from the diagnosis to bone metastasis was 11 months. The median survival time after bone metastasis was 5.4 months. Factors that were associated with longer median survival times included the following: isolated bone metastasis (P=0.004), well-differentiated tumors (P=0.002), palliative chemotherapy (P=0.003), zoledronic acid treatment (P<0.001), no smoking history (P=0.007), and no metastatic gastric cancer at the time of diagnosis (P=0.01). On the other hand, high levels of lactate dehydrogenase (LDH) (hazard ratio [HR]: 1.86; P=0.015), carcinoembryonic antigen (CEA) (HR: 2.04; P=0.002), and carbohydrate antigen (CA) 19-9 (HR: 2.94; P<0.001) were associated with shorter survival times. In multivariate analysis, receiving zoledronic acid (P<0.001) and performance status (P=0.013) were independent prognostic factors. Conclusions Smoking history, poor performance status, poorly differentiated adenocarcinoma, and high levels of LDH, CEA, and CA 19-9 were shown to be poor prognostic factors, while receiving chemotherapy and zoledronic acid were associated with prolonged survival in gastric cancer patients with bone metastases.

Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

PURPOSE To assess the safety and efficacy of a gemcitabine plus docetaxel regimen as a second line therapy for patients with advanced soft tissue sarcoma (STS) resistant to doxorubicin and ifosfamide-based therapy. PATIENTS AND METHODS Medical records of 64 patients with advanced STS who received gemcitabine plus docetaxel regimen as a second line treatment between May 2006 and June 2011 were examined. All patients had been previously treated with doxorubicin plus ifosfamide-based regimen at first line setting. Patients received gemcitabine 900 mg/m2 on days one and eight intravenously over 90 minutes, followed by docetaxel 75 mg/m2 on day eight intravenously over one hour. Cycles were repeated every 3 weeks. RESULTS The male-to-female ratio was 37/27 and the median age was 44 years (range; 19-67 years). Objective responses were observed in 13 (20.3%) patients (2 CR, 11 PR) and stable disease in 21 (32.8%). Total clinical benefit (CR+PR+SD) was observed in 34 (53.1%). Median overall survival (OS) was 18 months (95% confidence interval (CI):12.1-23.9) and Median time to progression (TTP) was 4.8 months (95% CI: 3.6-6). A total of 243 cycles of chemotherapy were administered. The median number of cycle was 3 (range; 1-11). The most common grade 3-4 hematologic toxicity was neutropenia (35.9%). The most common nonhematologic toxicities consisted of nausea/vomiting (37.5%), mucositis (32.8%), peripheral neuropathy (29.7%), and fatigue (26%). There was no toxicity-related death. CONCLUSION The combination of gemcitabine plus docetaxel is an active and tolerable regimen as a second line therapy for patients with advanced soft tissue sarcoma who have failed doxorubicin and ifosfamide-based therapy.

Gastric carcinoma with bone marrow metastasis: a case series.

Gastric cancer is a major cause of cancer-related mortality. At the time of diagnosis, majority of the patients usually have unresectable or metastatic disease. The most common sites of metastases are the liver and the peritoneum, but in the advanced stages, there may be metastases to any region of the body. Bone marrow is an important metastatic site for solid tumors, and the prognosis in such cases is poor. In gastric cancer cases, bone marrow metastasis is usually observed in younger patients and in those with poorly differentiated tumors. Prognosis is worsened owing to the poor histomorphology as well as the occurrence of pancytopenia. The effect of standard chemotherapy is unknown, as survival is limited to a few weeks. This report aimed to evaluate 5 gastric cancer patients with bone marrow metastases to emphasize the importance of this condition.

Sunitinib-induced severe hypoglycemia in a diabetic patient.

Introduction: Sunitinib is an oral inhibitor of tyrosine kinase that was used for the treatment of mRCC. The general side effects are fatigue, asthenia, diarrhea, mucositis, nausea, vomiting, skin changes, hypertension, hypothyroidism and hematologic side effects. In addition, sunitinib-induced hypoglycemia has also been reported. There are limited number of case reports related to sunitinib-induced hypoglycemia. Case presentation: In this case report, we have presented a patient with type 2 diabetes mellitus (DM) with emerging severe hypoglycemia after sunitinib treatment. It was shown that blood glucose levels were normalized two weeks after the interruption of sunitinib. Conclusion: Although the underlying mechanism of sunitinib-induced hypoglycemia is not completely understood, sunitinib can be regarded to have an antidiabetic effect. In the literature, there are some reports about sunitinib/other TKI induced hypoglycemia; however, life threatening hypoglycemia is rare. There is no case report of severe hypoglycemia due to imatinib; however, there are two case reports with severe hypoglycemia due to sunitinib treatment. Symptomatic hypoglycemic episodes due to sunitinib may lead to hospital admission. Diabetic patients may develop severe hypoglycaemia and it should be kept in mind that the discontinuation of antihyperglycemic treatment may be required. Therefore, blood glucose levels should be closely monitored in diabetic patients with mRCC during sunitinib therapy.

Multicenter evaluation of patients with cutaneous malignant melanoma in Turkey: MELAS study.

BACKGROUND Malignant melanoma is a cancer that demonstrates rapid progression and atypical clinically features with a poor prognosis. AIM This study was performed to determine the clinical characteristics and treatment outcomes of patients with malignant melanoma in Turkey. METHODS The medical records of 98 patients between 2007- 2012 at our centers were retrieved from the patient registry. Overall survival (OS) was calculated using the Kaplan-Meier method. RESULTS In our study, with the median follow-up of all patients with cutaneous MM of 46.3 months, the median OS rate of all cases was 43.6 months and 5-year OS was 48.6%. However, five-year OS rates of patients with localized disease (stage I-II) and node involvement (stage III) were 60.3% and 39.6%, respectively. The median OS of stage IV patients was 8.7 months and 1-year OS rate was 26.2%. We showed that advanced stage, male gender, and advanced age in all patients with MM were significant prognostic factors of OS. CONCLUSIONS Compared with the results of current studies from Western countries, we found similar findings concerning demographical features, histological variables and survival analyses for our patients with cutaneous MM in Turkey.

Outcomes of Adolescent and Adult Patients with Lung Metastatic Osteosarcoma and Comparison of Synchronous and Metachronous Lung Metastatic Groups

Osteosarcomas with lung metastases are rather heterogenous group. We aimed to evaluate the clinicopathological characteristics and outcomes of osteosarcoma patients with lung metastases and to compare the synchronous and metachronous lung metastatic groups. A total of 93 adolescent and adult patients with lung metastatic osteosarcoma, from March 1995 to July 2011, in a single center, were included. Sixty-five patients (69.9%) were male. The median age was 19 years (range, 14–74). Thirty-nine patients (41.9%) had synchronous lung metastases (Group A) and 54 patients (58.1%) had metachronous lung metastases (Group B). The 5-year and 10-year post-lung metastases overall survival (PLM-OS) was 17% and 15%, respectively. In multivariate analysis for PLM-OS, time to lung metastases (p = 0.010), number of metastatic pulmonary nodules (p = 0.020), presence of pulmonary metastasectomy (p = 0.007) and presence of chemotherapy for lung metastases (p< 0.001) were found to be independent prognostic factors. The median PLM-OS of Group A and Group B was 16 months and 9 months, respectively. In Group B, the median PLM-OS of the patients who developed lung metastases within 12 months was 6 months, whereas that of the patients who developed lung metastases later was 16 months. Time to lung metastases, number and laterality of metastatic pulmonary nodules, chemotherapy for lung metastatic disease and pulmonary metastasectomy were independent prognostic factors for patients with lung metastatic osteosarcoma. The best PLM-OS was in the subgroup of patients treated both surgery and chemotherapy. The prognosis of the patients who developed lung metastases within 12 months after diagnosis was worst.

Effects of comorbidities and functional living activities on survival in geriatric breast cancer patients

Aim of the study We evaluated the possible effects of comorbid diseases and functional capacity on the survival of elderly female patients with breast cancer. Material and methods The study included 159 breast cancer patients aged 65 years or older. Functional status of the patients was evaluated using Katzs index of activities of daily living (ADL) and Lawton and Brodys Instrumental ADL (IADL) scale. Results ADL-based evaluation revealed 121 patients (76.1%) were independent, 34 (21.4%) semi-dependent and 4 (2.5%) dependent whereas IADL-based evaluation showed 69 patients (43.4%) were independent, 67 patients (42.1%) semi-dependent and 23 patients (14.5%) dependent. Among the patients, 69 (43.4%) had one comorbid disease, 62 (39.0%) had two and 26 (16.4%) had three or more. Of the entire cohort, 60.4% received adjuvant chemotherapy. Based on ADL index, overall survival (OS) was significantly better in semi-dependent and independent patients than in dependent patients (p = 0.001). In the upfront non-metastatic patient subgroup, disease-free survival (DFS) was favourable in the independent patients according to ADL index (p = 0.001). Having more than one comorbid disease had an unfavourable effect on OS. In the multiple regression analysis of non-metastatic patients, stage, triple-negative histology and ADL index remained significant in terms of OS (p = 0.008, HR: 3.17, CI: 1.35–7.44; p = 0.027, HR: 2.78, CI: 1.172–6.91; and p = 0.006, HR: 0.29, CI: 0.12–0.70, respectively). Conclusions In elderly patients with breast cancer, evaluation of daily living activities and comorbid diseases are as important as staging and subclassification of breast cancer in the determination of prognosis and survival.

Prognostic Factors in Operated Stage IIIC, Pathological N3a Breast Cancer Patients

Background: The aim of this retrospective study was to evaluate the prognostic factors in patients operated for stage IIIC breast carcinoma who had > 10 positive axillary lymph nodes (pN3a). Patients and Methods: The medical records of 302 operated N3a breast cancer patients without distant metastasis followed up in 2 medical oncology clinics in Ankara between January 1998 and June 2013 were evaluated retrospectively. Results: The median age was 50 (21-83) years. The median follow-up time was 43 (5-191) months. The patients were divided into 4 subgroups according to hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. There were 151 (50.0%) patients in the HR+/HER2- group, 80 (26.5%) patients in the HR+/HER2+ group, 42 (13.9%) patients in the HR-/HER2+ group, and 29 (9.6%) patients in the triple negative (TN) group. At the time of analysis, 155 (51.3%) patients had recurrent disease and 117 (38.7%) patients had died. The median disease-free survival (DFS) and overall survival (OS) times were 46.0 and 78.0 months, respectively. Both the DFS and OS in the HR+/HER2- group were longer than in the other groups (log-rank p = 0.034 and p = 0.016, respectively). Menopausal status, progesterone receptor (PgR) status, and lymph node ratio (LNR; defined as the number of positive lymph nodes compared to the total number of removed lymph nodes) were found to be independent prognostic factors (p = 0.019, p = 0.001, and p = 0.012, respectively). Conclusion: Menopausal status, PgR status, and LNR were independent prognostic factors in operated N3a breast cancer patients, who are underrepresented in breast cancer trials.

Prognostic & predictive factors for planning adjuvant chemotherapy of early-stage breast cancer

Breast cancer is a heterogeneous disease and may present with different clinical and biological characteristics. At present, breast cancer is divided into molecular subgroups besides its histopathological classification. Decision for adjuvant chemotherapy is made based on not only histopathological characteristics but also molecular and genomic characteristics using indices, guidelines and calculators in early-stage breast cancer. Making a treatment plan through all these prognostic and predictive methods according to risk categories aims at preventing unnecessary or useless treatments. In this review, an attempt to make a general assessment of prognostic and predictive methods is made which may be used for planning individualized therapy and also the comments of the guidelines used by the oncologists worldwide on these methods.