Berna Oksuzoglu

Breast cancer subtypes and outcomes of central nervous system metastases

Central nervous system (CNS) metastases are detected in up to one third of patients with advanced breast cancer, but their incidence and outcomes by breast cancer subtypes are not precisely documented. Herein, we retrospectively analyzed clinicopathologic data of 259 breast cancer patients with CNS metastases to evaluate the association between breast cancer subtypes and CNS metastasis. The patient groups were classified according to their hormone receptor status and HER-2 expression. Median follow-up time among the patients was 42 months and median survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing group, median time period between the diagnosis of breast cancer and the detection of CNS metastasis (15.9 months) was significantly shorter compared to the other groups (p = 0.01). The triple negative group had the shortest median survival time after CNS metastasis (6.6 months), although statistically not significant (p = 0.3). In multivariate Cox regression analyses, having solitary CNS metastasis (HR 0.4, 95% CI; 0.2-0.7, p = 0.004), and receiving chemotherapy after CNS metastasis (HR 0.4, 95% CI; 0.287-0.772, p = 0.003) were independent prognostic factors for increasing survival after CNS metastasis. In conclusion, new and effective treatment strategies are required for breast carcinoma patients with brain metastasis considering the positive effect of the treatment on survival.

Metastasis to the breast from nonmammarian solid neoplasms: a report of five cases.

Primary breast carcinoma is the commonest neoplasm in women. Although rare, metastases of solid tumors from elsewhere to the breast may occur. Apart from cross-lymphatic metastasis from contralateral primary breast carcinoma, hematopoietic neoplasms occasionally involve the breast. As far as we know, less than 500 patients with secondary extramammary solid neoplasms involving the breasts have been reported in the English literature, of which malignant melanoma and lung tumors constitute the leading cause. Herein, five additional adult cases are reported and literature is reviewed. Two of the patients had primary rhabdomyosarcomas, two ovarian carcinomas, and one colon carcinoma. In one case with ovarian carcinoma, breast mass was the only manifestations of the disease relapse. All, except one with disseminated disease, had pathological diagnosis. Two of the patients died soon after the detection of breast metastasis. As a result, breast mass can be the first manifestation of relapse or part of a disseminated disease, and usually predicts poor survival.

A laboratory prognostic index model for patients with advanced non-small cell lung cancer.

Purpose We aimed to establish a laboratory prognostic index (LPI) in advanced non-small cell lung cancer (NSCLC) patients based on hematologic and biochemical parameters and to analyze the predictive value of LPI on NSCLC survival. Patients and Methods The study retrospectively reviewed 462 patients with advanced NSCLC diagnosed between 2000 and 2010 in a single institution. We developed an LPI that included serum levels of white blood cells (WBC), lactate dehydrogenase (LDH), albumin, calcium, and alkaline phosphatase (ALP), based on the results of a Cox regression analysis. The patients were classified into 3 LPI groups as follows: LPI 0: normal; LPI 1: one abnormal laboratory finding; and LPI 2: at least 2 abnormal laboratory findings. Results The median follow up period was 44 months; the median overall survival (OS) and median progression-free survival (PFS) were 11 and 6 months, respectively. A multivariate analysis revealed that the following could be used as independent prognostic factors: an Eastern Cooperative Oncology Group performance status score (ECOG PS) ≥2, a high LDH level, serum albumin <3 g/dL, serum calcium>10.5 g/dL, number of metastases>2, presence of liver metastases, malignant pleural effusion, or receiving chemotherapy ≥4 cycles. The 1-year OS rates according to LPI 0, LPI 1, and LPI 2 were 54%, 34%, and 17% (p<0.001), respectively and 6-month PFS rates were 44%, 27%, and 15% (p<0.001), respectively. The LPI was a significant predictor for OS (Hazard Ratio (HR): 1.41; 1.05–1.88, p<0.001) and PFS (HR: 1.48; 1.14–1.93, p<0.001). Conclusion An LPI is an inexpensive, easily accessible and independent prognostic index for advanced NSCLC and may be helpful in making individualized treatment plans and predicting survival rates when combined with clinical parameters.

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.

Comparison of ICE (Ifosfamide-Carboplatin-Etoposide) Versus DHAP (Cytosine Arabinoside-Cisplatin-Dexamethasone) as Salvage Chemotherapy in Patients with Relapsed or Refractory Lymphoma

Background: High dose chemotherapy with autologous stem cell transplantation is currently the treatment of choice for relapsed or refractory lymphoma patients. However, its applicability is mostly restricted to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP (cytosine arabinoside, cisplatin and dexamethasone) and ICE (ifosfamide, carboplatin and etoposide) regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and Methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkins disease (HD) (n = 13) or non-Hodgkin lymphoma (NHL) (n = 40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 (39,6%) were female and the median age was 43 years. A total of 73 courses of ICE and 59 courses of DHAP were administered. Response could be evaluated in 49 patients (36 NHL and 13 HD). Of 49 patients, 11 (22.5%) achieved complete remission (CR) and 17 (35%) achieved partial remission (PR), leading to an overall response rate (ORR: CR + PR) of 57.5%. In the evaluable ICE group (n = 22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n = 27) rates of CR, PR, and ORR were 18%, 30% and 48% (p = 0.24, for ORR). Toxicity with both regimens was within acceptable limits. The major grade III–IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to have higher rates of response than DHAP regimen does.

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

BACKGROUND Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. MATERIALS AND METHODS Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). RESULTS A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. CONCLUSIONS This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

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.

Capecitabine and Cisplatin Combination Is an Active and Well-Tolerated Doublet in the Treatment of Metastatic Breast Carcinoma Patients Pretreated with Anthracycline and Taxanes

Our aim was to evaluate the activity and toxicity of capecitabine and cisplatin (CapCisp) combination in anthracycline- and taxane-pretreated metastatic breast cancer patients. Thirty-three patients, 20–61 years of age (median 41), were included. They received Cap 2,000 mg/m2 on days 1–14 and Cisp 60 mg/m2 on day 1, repeated every 3 weeks. Twelve nonprogressive patients continued single-agent Cap therapy until progression or until intolerable toxicity after Cisp cessation. The disease control rate in 154 cycles was 81.8%: complete response 3.0% (n = 1), partial response 48.5% (n = 16) and stable disease 30.3% (n = 10). The median time to disease progression was 6.3 months (95% CI 3.8–8.8). The median overall survival was 11.5 months (95% CI 6.9–16.1). The only grade 3 toxicity was neutropenia, observed in 4 patients (12.1%). CapCisp has an encouraging anti-tumor activity with a low toxicity rate in anthracycline- and taxane-pretreated metastatic breast cancer patients.

Comparison of Cisplatin-5-Fluorouracil-Folinic Acid versus Modified Docetaxel-Cisplatin-5-Fluorouracil Regimens in the First-Line Treatment of Metastatic Gastric Cancer

Objective: Prognosis of metastatic gastric cancer is poor and median survival is between 3 and 5 months. Response rates of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in first-line treatment have been found to be 20–25% in the English literature. It has been demonstrated that adding docetaxel to combination chemotherapy improved time to progression and overall survival. However, the toxicity rates of the docetaxel-cisplatin-5-FU protocol were high. In our study we compared efficacy and toxicity of cisplatin-5-FU-folinic acid (CFF) and modified docetaxel-cisplatin-5-FU (mDCF) regimens in the first-line treatment of metastatic gastric cancer. Patients and Methods: Between June 2004 and October 2008, 70 patients with previously untreated metastatic gastric cancer treated with CFF (n = 30) and mDCF (n = 40) were retrospectively evaluated in the study. Survival and toxicity data were compared. Results: Median age of the patients was 53 years (range 23–69). Forty-eight percent of the patients were male and 75.7% had an ECOG performance status of 0–1. Prognostic factors including age, ECOG performance status, histopathological grade, and number and sites of metastases were similar between the groups. Objective response rates (complete and partial response) were higher in the mDCF group (30.0 vs. 13.3%, p = 0.19). While toxicity was acceptable in both groups, the most common grade 3–4 toxicities were anemia in 3.3 and 5.0%, neutropenia in 20 and 7.5%, febrile neutropenia in 6.7 and 5.0%, and diarrhea in 3.3 and 5.0% in the CFF and mDCF groups, respectively. Median follow-up was 10.3 (1.5–59.6) months. During that period 90 and 97.5% of the patients were dead in the CFF and mDCF groups, respectively. Median time to progression was 4.4 (95% CI 1.8–7.0) and 6.2 months (95% CI 5.6–6.8) (p = 0.85), median overall survival was 6.5 (95% CI 1.8–11.2) and 8.7 months (95% CI 6.7–10.7) (p = 0.88) in the CFF and mDCF groups, respectively. Conclusion: The mDCF regimen has been found to be more favorable than the CFF regimen with an acceptable toxicity profile in the first-line treatment of metastatic gastric cancer.

Lapatinib plus Capecitabine for HER2-Positive Advanced-Stage Breast Cancer in Elderly Women: Review of the Anatolian Society of Medical Oncology (ASMO) Experience.

Background: The efficacy and safety of the lapatinib and capecitabine combination remain elusive in elderly patients with metastatic breast cancer (MBC), who progress after trastuzumab-based therapy. Patients and Methods: A total of 26 patients with HER2-positive MBC were included in this retrospective multicenter study. Median age was 69 years (range 65-82 years). All patients were treated with the combination of lapatinib (1,250 mg/day, continuously) and capecitabine (2,000 mg/m2 on days 1-14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. Results: The median follow-up was 10 months (range 2-31 months). An overall response rate of 33.4% was achieved, including 1 complete response (3.8%), and 8 partial responses (30.8%). Median progression-free survival was 7 months (95% confidence interval (CI) 5-8), and the median overall survival was 15 months (95% CI 11-19). Most common side effects were fatigue (53.8%), diarrhea (46%), vomiting (36.3%), hand-foot syndrome (34.5%), and anorexia (34.6%). Grade 3-4 toxicities were identified as hand-foot syndrome (3.8%), diarrhea (7.6%), and fatigue (11.5%). There were no symptomatic cardiac events. Conclusion: Lapatinib and capecitabine combination therapy was effective and well tolerated in elderly patients with MBC, who had progressive disease after trastuzumab-based therapy.