Faculty Bibliography

PURPOSE: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. EXPERIMENTAL DESIGN: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. RESULTS: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. CONCLUSIONS: Both phase 0 and phase II NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics

PURPOSE: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). METHODS AND MATERIALS: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm(2) postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. RESULTS: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% +/- 5% and 52% +/- 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. CONCLUSIONS: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design

We present a case of synchronous involvement of the pineal and suprasellar regions by a mixed germ cell tumor comprising germinoma and yolk sac tumor components, with a predominant angiomatous component. To our knowledge, it is the first case of this nature to be reported in the literature. Usually, synchronous lesions of this kind are pure germinomas, and some clinicians will forgo a biopsy and assume a germinoma histology if the serum beta-human chorionic gonadotrophin (HCG) is <50 IU/l and the alpha-fetoprotein (AFP) is within normal limits. Secondly, if a biopsy is performed on a lesion that has a prominent angiomatous component, the diagnostic germ cell tumor may be missed at the time of the biopsy. In order to alert clinicians and pathologists to this rare entity, the case is discussed with particular reference to difficulties that were encountered in rendering an accurate diagnosis, and the associated management implications

Over the past decades considerable advances have been made in neurosurgery, radiotherapy and chemotherapy resulting in improved survival and cure rates for children with brain tumors. Here we review four of the most common subtypes of pediatric brain tumors, low-grade and high-grade astrocytomas, medulloblastomas and ependymomas, highlighting their molecular features regarding their tumor biology, and promising potential therapeutic targets that may hold promise for finding new 'molecular targeted' drugs. Importantly, appropriate clinical trial design will play a critical role in the evaluation of new and novel treatment approaches for pediatric brain tumors

BACKGROUND: Intramedullary nailing has become a standard treatment for adult tibial shaft fractures. Retained intramedullary nails have been associated with stress shielding, although their long-term effect on decreasing tibial bone mineral density is currently unclear. The purpose of this study was to determine if retained tibial intramedullary nails decrease tibial mineral density in patients with successfully treated fractures. METHODS: Patients treated with statically locked intramedullary nails for isolated, unilateral tibia shaft fractures were studied. Inclusion required that fracture had healed radiographically and that the patient returned to the pre-injury activity level. Data on patient demographic, fracture type, surgical technique, implant, and post-operative functional status were tabulated. Dual energy X-ray absorptiometry was used to measure bone mineral density in selected regions of the affected tibia and the contralateral intact tibia. Image reconstruction software was employed to ensure symmetry of the studied regions. FINDINGS: Twenty patients (mean age 43; range 22-77 years) were studied at a mean of 29 months (range 5-60 months) following intramedullary nailing. There was statistically significant reduction of mean bone mineral density in tibiae with retained intramedullary nails (1.02 g/cm(2) versus 1.06 g/cm(2); P=0.04). A significantly greater decrease in bone mineral density was detected in the reamed versus non-reamed tibiae (-7% versus +6%, respectively; P<0.05). INTERPRETATION: The present study demonstrates a small, but statistically significant overall bone mineral density decrease in healed tibiae with retained nails. Intramedullary reaming appears to be a factor potentiating the reduction of tibia bone mineral density in long-term nail retention.