Ozge Gumusay

Diagnostic potential of serum direct markers and non-invasive fibrosis models in patients with chronic hepatitis B

Aim:  Liver biopsy is recommended in the majority of patients with chronic viral hepatitis for fibrosis evaluation. Because of the disadvantages of liver biopsy, many studies related to non‐invasive biomarkers and scores have been performed. In this study, we aimed to assess the diagnostic value of serum direct markers and non‐invasive fibrosis models to predict liver fibrosis in the treatment‐naive chronic hepatitis B (CHB) patients and to compare their diagnostic performance.

Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.

Oral Etoposide for Platinum-Resistant and Recurrent Epithelial Ovarian Cancer: a Study by the Anatolian Society of Medical Oncology

BACKGROUND The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. MATERIALS AND METHODS For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). RESULTS Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8-20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). CONCLUSIONS Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme: Carbonic anhydrase IX and glioblastoma multiforme

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA‐IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA‐IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA‐IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan–Meier curves and log‐rank tests were used for analysis of progression‐free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA‐IX expression (18 months) compared to patients overexpressing CA‐IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA‐IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA‐IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross‐total resection (HR, 1.956; P = 0.034). Our findings indicated that CA‐IX may be a potential prognostic biomarker in the treatment of GBM.

Pazopanib-Induced Hepatotoxicity in an Experimental Rat Model

Pazopanib is an effective treatment for advanced renal cell carcinoma and soft tissue sarcoma. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. The aim of the present study was to evaluate the effect of pazopanib on the liver in an experimental rat model. Sixteen Wistar albino rats were divided into 3 groups: experimental toxicity was induced with pazopanib (10 mg/kg) administered for 28 days (group 2) or 56 days (group 3) orally by gavage. Group 1 (control group) received only distilled water. Rats in groups 2 and 3 were sacrificed after the collection of blood and tissue samples on the 28th and 56th days, respectively. We found significant differences in bilirubin, alkaline phosphatase, lactate dehydrogenase, glucose, triglyceride, very-low-density lipoprotein, and iron values (p < 0.050 for all) but none in any other parameter (p > 0.050). All rats in the control group had normal histological features; however, none of the rats in groups 2 and 3 showed normal histology. In group 2, we observed mild sinusoidal dilatation, congestion, enlarged Kupffer cells, accumulation of yellow-brown-black pigment in the Kupffer cells and the accumulation of hemosiderin with Prussian blue reaction in the hepatocytes. In group 3, the findings mentioned above were more prominent, and besides these findings focal acinar transformation and macrovesicular steatosis were also observed. In group 3, mild inflammation within the portal areas was observed consisting of lymphocytes, neutrophils, and eosinophils. This study is the first that reports the biochemical and histopathological evaluation of pazopanib-related hepatic toxicity.

Liver metastases from adenocarcinomas of unknown primary site: management and prognosis in 68 consecutive patients.

SummaryBackgroundIn this retrospective study, we aimed to evaluate the clinicopathological characteristics of the patients presenting with liver metastases from unknown primary site besides survival rates, treatment outcomes, and prognostic factors.MethodsIn all, 68 patients followed-up at our center with adenocarcinoma of unknown primary (ACUP) metastatic to the liver between 2005 and 2013 were enrolled. All of the liver metastases were proven by liver biopsy and all yielded diagnosis of adenocarcinoma.ResultsMedian age was 61 years (29–90) and most of the patients were male (male/female: 43/25). The liver was the only metastatic site in 2 (3 %) patients whilst 66 patients (97 %) had extrahepatic metastases. The most common extrahepatic metastatic sites were lymph nodes (89.7 %), lungs (32.4 %), bones (25 %), peritoneum (11.8 %), brain (4.4 %), and adrenal glands (2.9 %). Of all 68 patients, 39 (57.4 %) were treated with chemotherapy. Median overall survival (OS) was significantly higher in ACUP patients treated with chemotherapy [12.5 months (95 % CI 8.3–16.7) vs. 4 months (95 % CI 1.2–6.8), (p = 0.026), respectively]. In multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status (p = 0.009), chemotherapy (p = 0.024), serum albumin (p = 0.012), and serum CA 19-9 level (p = 0.026) at initial diagnosis were identified as independent prognostic factors influencing survival for the patients with liver metastases from ACUP.ConclusionPatients with liver metastases from ACUP have poor prognosis and chemotherapy improves survival. Decreased serum albumin level, increased CA 19-9 level and poor performance status are independent poor prognostic factors.

Salvage chemotherapy with weekly paclitaxel for metastatic melanoma.

Although new therapeutic strategies have come up in the past few years in metastatic malignant melanoma, salvage therapy option which is systemic chemotherapy has not lost its importance. Therefore, we evaluated 23 patients with metastatic malignant melanoma administrated weekly paclitaxel 80 mg/m2 as salvage therapy from October 2008 to August 2013 in a multicenter Anatolian Society of Medical Oncology (ASMO) study, retrospectively. Tumor responses were evaluated every 2-3 months by the Response Evaluation Criteria in Solid Tumors criteria version 1.1 and toxicities were graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3.0. Before the induction of paclitaxel, all patients had received the combination of temozolamide and cisplatin or temozolamide alone or dacarbazine alone. Targeted therapies were not given because they were not provided at that time in our country. Eighteen patients had received the paclitaxel in second-line and 5 patients in third-line. Median age was 57 (min-max: 29-79) years. Fifteen patients were male and 8 female. In terms of primer tumor site, 8 patients in head-neck, 6 patients in lower limb, 3 patients in upper limb, 3 patients in trunk and 3 patients in uvea. All patients had multiple nodal and/ or visceral metastases at administration of paclitaxel. Complete response were not observed but 2 patients (8.7%) had partial response. Stable disease was observed in 8 patients (34.7%). Response rate (RR) was 8.7% and clinical response rate was 43.4%. Median progression free survival (PFS) was 12 weeks (95% CI: 9.67-14.32) and median overall survival (OS) was 40 weeks (95% CI: 21.22-58.78) (Table 1). Six patients (26%) experienced neuropathy, all grade 1-2. Other dose-limiting toxicities were not observed. The prognosis for advanced metastatic melanoma is poor. Temozolamide and dacarbazine have been the most commonly used cytotoxic agent. However, the objective response rate is under 20% (Patel et al., 2011). The combination of carboplatin and paclitaxel or paclitaxel alone have shown modest activity in advanced melanoma LETTER to the EDITOR