A phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiation therapy yields high rates of local control for brain metastases, but patients in rural or suburban areas face geographic and socioeconomic barriers to its access. We conducted a phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases in an integrated academic satellite network for patients 18 years of age or older with 4 or fewer brain metastases. Dose was based on gross tumor volume: less than 3.0 cm, 27 Gy in 3 fractions and 3.0 to 3.9 cm, 30 Gy in 5 fractions. Median follow-up was 10 months for 73 evaluable patients, with a median age of 68 years. Median intracranial progression-free survival was 7.1 months (95% confidence interval = 5.3 to not reached), and median survival was 7.2 months (95% confidence interval = 5.4 to not reached); there were no serious adverse events. Outcomes of this trial compare favorably with contemporary trials, and this treatment strategy provides opportunities to expand stereotactic radiation therapy access to underserved populations.

A set of simple methods for detection and extraction of laminarinase.

A carefully designed ammonium sulfate precipitation will simplify extraction of proteins and is considered to be a gold standard among various precipitation methods. Therefore, optimization of ammonium sulfate precipitation can be an important functional step in protein purification. The presence of high amounts of ammonium sulphate precludes direct detection of many enzymatically active proteins including reducing sugar assays (e.g. Nelson-Somogyi, Reissig and 3,5-dinitrosalicylic acid methods) for assessing carbohydrases (e.g. laminarinase (ß (1-3)-glucanohydrolase), cellulases and chitinases). In this study, a simple method was developed using laminarin infused agarose plate for the direct analysis of the ammonium sulphate precipitates from Streptomyces rimosus AFM-1. The developed method is simple and convenient that can give accurate results even in presence of ammonium sulfate in the crude precipitates. Laminarin is a translucent substrate requiring the use of a stain to visualize the zones of hydrolysis in a plate assay. A very low-cost and locally available fluorescent optical fabric brightener Tinopal CBS-X has been used as a stain to detect the zones of hydrolysis. We also report simple methods to prepare colloidal chitin and cell free supernatant in this manuscript.

Statistical Optimization for Coproduction of Chitinase and Beta 1, 4-Endoglucanase by Chitinolytic Paenibacillus elgii PB1 Having Antifungal Activity.

A bacterial strain PB1 with antagonistic activity against pathogenic fungi was isolated from marine soil and was identified as Paenibacillus elgii based on phenotypic and genotypic characterization. The isolate showed good antifungal activity against "Aspergillus niger (MTCC 282), Trichophyton rubrum (MTCC 791), Microsporum gypseum (MTCC 2819), Candida albicans (MTCC 227), and Saccharomyces cerevisiae (MTCC 170)". Chitinase and beta 1, 4-endoglucanase are known for their capability to degrade fungal cell wall, thus we analyzed its productivity in PB1 strain using Plackett-Burman and Central Composite Design. The factors that affect the productivity of chitinase and beta 1, 4-endoglucanase were identified and optimized. A 7.77-fold increase (3.157 to 24.53 ± 1.33 U/mL) in chitinase and 7.422-fold increase (6.476 to 48.066 ± 0.676 U/mL) in beta 1, 4-endoglucanase versus basal medium was achieved. Chitinase and beta 1, 4-endoglucanase produced by Paenibacillus elgii strain PB1 represents the new source for biotechnological, medical, and agricultural applications.

Efficacy of proton therapy in children with high-risk and locally recurrent neuroblastoma.

PURPOSE: Proton therapy is currently used in the management of pediatric tumors to decrease late toxicities. However, one of the criticisms of proton therapy is the limited data regarding efficacy on disease control. The purpose of this study was to examine local and distant control rates after proton therapy for neuroblastoma. METHODS AND MATERIALS: Eighteen patients with high-risk (n = 16) and locally recurrent neuroblastoma (n = 2) were treated with curative intent and received proton therapy to the primary site and up to three post-induction MIBG-avid metastatic sites. Primary sites (n = 18) were treated to 21-36 Gy (relative biological effectiveness [RBE]), and metastatic sites (n = 16) were treated to 21-24 Gy (RBE). Local control and survival rates were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 60.2 months, two- and five-year local control rates at the irradiated primary site were 94% and 87%, respectively. No failures at irradiated distant metastatic sites were observed. The five-year progression-free survival (PFS) was 64%, and the five-year overall survival (OS) was 94%. The extent of surgical resection was not associated with local control, PFS, or OS. No radiation-related nephropathy or hepatopathy was reported. CONCLUSIONS: Excellent local control was achieved using proton therapy to the primary and post-induction MIBG-positive distant sites. The predominant site of failure is progression in post-induction non-MIBG-avid distant sites. Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, further advances in systemic therapy are needed for the improved control of systemic disease.

Radiation for ETMR: Literature review and case series of patients treated with proton therapy.

BACKGROUND AND PURPOSE: Embryonal tumors with multilayered rosettes (ETMRs) are aggressive tumors that typically occur in young children. Radiation is often deferred or delayed for these patients due to late effects; proton therapy may mitigate some of these concerns. This study reviews the role of radiation in ETMR and describes initial results with proton therapy. MATERIALS AND METHODS: Records of patients with embryonal tumor with abundant neuropil and true rosettes (ETANTR), medulloepithelioma (MEP), and ependymoblastoma (EPL) treated with proton therapy at our institution were retrospectively reviewed. A literature review of cases of CNS ETANTR, MEP, and EPL published since 1990 was also conducted. RESULTS: Seven patients were treated with proton therapy. Their median age at diagnosis was 33 months (range 10-57 months) and their median age at radiation start was 42 months (range 17-58 months). Their median overall survival (OS) was 16 months (range 8-64 months), with three patients surviving 36 months or longer. Five patients had disease progression prior to starting radiation; all 5 of these patients failed in the tumor bed. A search of the literature identified 204 cases of ETMR with a median OS of 10 months (range 0.03-161 months). Median OS of 18 long-term survivors (≥36 months) in the literature was 77 months (range 37-184 months). Of these 18 long-term survivors, 17 (94%) received radiotherapy as part of their initial treatment; 14 of them were treated with craniospinal irradiation. CONCLUSIONS: Outcomes of patients with ETMR treated with proton therapy are encouraging compared to historical results. Further study of this rare tumor is warranted to better define the role of radiotherapy.

Reirradiation of Recurrent Pediatric Brain Tumors after Initial Proton Therapy.

PURPOSE: The use of reirradiation for recurrent pediatric brain tumors has been increasing, but the effect of repeat radiation on critical cranial structures is unknown. METHODS AND MATERIALS: Between July 2009 and May 2013, the records of 12 pediatric patients initially treated with proton therapy and then with reirradiation for recurrent brain tumors were retrospectively reviewed for toxicity and outcomes. Initial and repeat radiation dose distributions were deformed and merged to determine the maximum dose to 0.03 cm3 of the optic chiasm, optic nerves, spinal cord, brainstem, cochleae, pituitary, and uninvolved brain, and to 1 cm3 of the brainstem and brain on individual and composite plans. These dosimetric results were compared with auditory, neurocognitive, ophthalmologic, and endocrine outcomes to identify radiation-associated toxicities. RESULTS: Median follow-up was 3.5 years from diagnosis. Median ages at initial and repeat radiation were 4.6 and 6.7 years, respectively. All patients initially received proton radiotherapy to a median tumor dose of 55.8 Gy relative biological effectiveness (RBE) (range, 45 to 60 Gy [RBE]). At progression, patients completed a second course of radiation to local fields (n = 7) or the craniospinal axis (n = 5) with a median tumor dose of 40 Gy (RBE) (range, 20 to 54 Gy [RBE]). Median progression-free survival was 22.7 months from the last day of the second radiation course. No patient developed central nervous system necrosis requiring treatment. Of evaluable patients, none developed radiation-related high-grade hearing loss (n = 11), visual pathway deficit (n = 10), or significant change in pre- and post-reirradiation full-scale intelligence quotient (n = 4). Of 11 evaluable patients, 4 (36.4%) developed secondary hypothyroidism and 1 (9.1%) developed growth hormone deficiency. CONCLUSION: Repeat radiation for recurrent brain tumors after proton therapy may be performed in the pediatric population with acceptable short- and long-term toxicity.