Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-Center Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. The effects of radiation parameters of SRS on hearing remain unknown. The goal of this study is to determine the effect of tumor volume, patient demographics, pretreatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration. METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms. RESULTS: Pure tone averages (PTAs) increased and word recognition scores (WRSs) decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS. CONCLUSIONS: Decline of hearing at one year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearingtbrowd preservation at one year is 3 Gy, and the use of 3 fractions instead of one fraction was better at preserving hearing.

Mutations in SZT2 result in early-onset epileptic encephalopathy and leukoencephalopathy.

Early-onset epileptic encephalopathies (EOEEs) are a genetically heterogeneous collection of severe epilepsies often associated with psychomotor regression. Mutations in SZT2, a known seizure threshold regulator gene, are a newly identified cause of EOEE. We present an individual with EOEE, macrocephaly, and developmental regression with compound heterozygous mutations in SZT2 as identified by whole exome sequencing. Serial imaging characterized the novel finding of progressive loss of central myelination. This case expands our clinical understanding of the SZT2-phenotype and emphasizes the role of this gene in the diagnostic investigation for EOEE and leukoencephalopathies.

Evaluating the Prevalence of the Epidermal Growth Factor Receptor in Transitional Cell Carcinoma of Bladder and its Relationship With Other Prognostic Factors.

BACKGROUND: The most common malignancy in the urinary system has been bladder cancer and the most predominant histologic subtype has been transitional cell carcinoma (TCC). There were many molecular risk factors, related with poor prognosis. One of these factors was expression of epidermal growth factor receptor (EGFR). OBJECTIVES: The aim of this study was to evaluate the prevalence of the epidermal growth factor receptor in transitional cell carcinoma of bladder and its relationship with other prognostic factors. PATIENTS AND METHODS: This analytic descriptive study has performed with 61 patients with TCC of bladder after radical cystectomy whom have been hospitalized in Labbafinejad hospital in Tehran, Iran between 2007 and 2010. We have used Chi-square and t-test to analyze our data samples. RESULTS: Records of 61 patients have studied. Fifty three of the total samples were positive for EGFR expression (86.9%). Fifty samples of these fifty-three belonged to men and three others were women's samples (P = 0.46). Among the group with EGFR expression the results were as follows: 25 patients (47.2%) were 60 years old or less and 28 patients (52.8%) were older than 60 (P = 0.023), 16 patients (30.2%) had invasion to lamina properia, and the rest of them had invasion to deeper layers (P = 0.56). For most patients we could not determine the invasion of tumoral cells into the lymph nodes (Nx) (P = 0.067). Thirty four patients (64.2%) had not lymphovascular invasion (P = 0.44) and in forty three of patients (81.1%), perineural invasion have not seen (P = 0.23). Finally, 36 patients (67.9%) were grade 3 (P = 0.27). CONCLUSIONS: In this study we have concluded that most patients had EGFR positive expression. Also, except for the age, there was not any significant relation between expression of EGFR and the other prognostic factors such as, gender, invasion of the tumor into the layers, involving the lymph nodes, lymphovascular or perineural invasion, and grading.

Dose-dense epirubicin and cyclophosphamide followed by docetaxel as adjuvant chemotherapy in node-positive breast cancer.

Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined. Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer. Methods. All Patients first received 4 cycles of epirubicin (100 mg/m(2)) and cyclophosphamide (600 mg/m(2)) at 2-week interval then followed by docetaxel (100 mg/m(2)) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3-10 after each cycle of epirubicin and cyclophosphamide infusion. Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%). Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation.