Supratentorial ependymoma, zinc finger translocation-associated fusion positive, with extensive synaptophysin immunoreactivity arising from malignant transformation of clear cell ependymoma: A case report.

Background: We describe a case of a supratentorial ependymoma, zinc finger translocation-associated (ZFTA) fusion positive with extensive synaptophysin immunoreactivity arising from malignant transformation of an ependymoma with clear cell features in a patient with long-term follow-up. Case Description: A 55-year-old woman presented with seizures and ataxia 15 years after an initial resection of a clear cell ependymoma, Grade 2. Imaging demonstrated an enhancing right paracentral mass and the patient underwent biopsy and resection. Microscopic analysis showed regions of the tumor with morphological and immunohistochemical features typical of ependymoma, including perivascular pseudorosettes and focal dot- like epithelial membrane antigen positivity, as well as high-grade features. In addition, the neoplasm contained large nodular regions of clear cells exhibiting extensive synaptophysin immunoreactivity, suggestive of neural differentiation, and only focally positive immunoreactivity for glial markers. Electron microscopy showed poorly formed and ill-defined junctional complexes, but no cilia, microvilli, or dense granules were seen. Molecular profiling revealed the presence of a fusion between ZFTA (previously known as C11orf95) and RELA fusion. Conclusion: We report a case of extensive synaptophysin immunoreactivity in a ZFTA-RELA fusion-positive ependymoma that had undergone malignant transformation from a clear cell ependymoma and has long-term follow-up, contributing to the assessment of prognostic significance of synaptophysin immunoreactivity in supratentorial ependymoma, ZFTA fusion positive.

p53-based strategy to reduce hematological toxicity of chemotherapy: A proof of principle study.

p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity. Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005 mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4, and 6 for objective 2. p53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4, and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as "suppressed" (or "activated") for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used. Twenty-six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the "suppressed" relative to the "activated" group. These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy. This trial is registered in ClinicalTrials.gov. Identifier: NCT01428128.

Initial evaluation of Cyberknife technology for extracorporeal renal tissue ablation.

OBJECTIVES: To determine whether Cyberknife technology can be applied to renal tissue safely and effectively. The goal was to achieve the high efficacy of a surgical treatment, with the low morbidity of a noninvasive intervention. METHODS: The Cyberknife is a frameless, image-guided radiosurgical device. This innovative extracorporeal treatment combines a linear accelerator mounted on a highly maneuverable robotic arm. The Cyberknife is unique in that it divides the high-dose radiation necessary to ablate the lesion completely into up to 1200 beams. Each one of these beams of radiation has a significantly reduced dose. Therefore, the individual dose of each beam is essentially benign to the pathway and surrounding tissue. However, at the focal point of these beams, the dose is additive, and the desired ablative dose is attained. Predetermined "lesions" in 16 kidneys were treated in vivo in the porcine model. Complete treatment was accomplished in one session per animal, with no complications. Gross and histologic evaluations were completed at 4, 6, or 8 weeks. RESULTS: The degree of radiation changes correlated with longer treatment intervals. After 8 weeks, the lesions showed complete fibrosis. The zones of complete fibrosis were characterized by dense, paucicellular connective tissue completely devoid of all normal kidney elements, including tubules and glomeruli. CONCLUSIONS: This initial preclinical evaluation of the Cyberknife for extracorporeal renal tissue ablation appears to be very promising and demonstrated its ability to ablate a targeted area precisely and completely with relative sparing of the surrounding tissue. This innovative technology introduces an exciting approach as a potential treatment option of renal masses in the future.

Results of whole brain radiotherapy in patients with brain metastases from breast cancer: a retrospective study.

PURPOSE: To analyze the factors that affect survival in patients with brain metastases (BM) from breast cancer who were treated with whole brain radiotherapy (WBRT). METHODS AND MATERIALS: We identified 116 women with breast cancer who were treated with WBRT alone between February 1984 and September 2000. All patients had treatment and follow-up data available in their medical charts, which we extracted for this retrospective study. We evaluated a number of potential predictors of survival after WBRT: age, primary tumor stage, control of primary tumor, presence of other systemic metastases, site of systemic metastases, Karnofsky performance status, Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, total dose of WBRT, and number of BM. Eighteen patients received a total dose >3000 cGy and 7 received a partial brain boost. RESULTS: For the entire cohort, the median survival from the start of WBRT was 4.2 months. The 1-year survival rate was 17%, and the 2-year survival rate was 2%. Using univariate analysis, only Karnofsky performance status (p = 0. 0084), recursive partitioning analysis class (p = 0. 0147), and total WBRT dose (p = 0.0001) were predictive of longer survival. In multivariate analysis, Karnofsky performance status was the only significant predictor. CONCLUSION: Overall survival in breast cancer patients with BM treated with WBRT is poor. We recommend breast cancer patients with BM be enrolled in prospective trials to improve results.

Successful Breast Conservation in a Patient with Epidermolysis Bullosa Simplex.

Before breast conservation can be offered to a woman with breast cancer one must understand both the indications and contraindications to such an approach. Factors that play a role in this decision include tumor-related factors and factors related to the expected cosmetic outcome following breast conservation. Here we present a case of a woman with epidermolysis bullosa simplex (EBS), a rare skin disorder that is characterized by blister formation following minor trauma, who underwent successful breast conservation.