Faculty Bibliography

Background/Aims. Primary CNS germinoma is readily curable with relatively large volume/high dose radiotherapy with late neuroendocrine/neurocognitive risks. Preradiotherapy chemotherapy with response-based reduced volume/dose radiotherapy may decrease these late effects without compromising survival. We combined the results of two similar trials (NY Germinoma Consortium and COG ACNS0232 - Regimen B) which followed a similar treatment paradigm. Methods. Eligibility included newly diagnosed, histologically confirmed, completely staged CNS germinoma with serum and lumbar CSF H

The anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab has been shown to improve survival in patients with metastatic non-CNS melanoma. The purpose of this study was to investigate the efficacy of CTLA-4 inhibitors in the treatment of metastatic melanoma with limited brain metastases treated with stereotactic radiosurgery (SRS). Between January 2008 and June 2011, 58 patients with limited brain metastases from melanoma were treated with SRS with a median dose of 20 Gy delivered to the 50% isodose line (range, 15-20 Gy). In 25 patients, ipilimumab was administered intravenously at a dose of 3 mg/kg over 90 min every 3 weeks for a median of four doses (range, 1-8). Local control (LC), freedom from new brain metastases, and overall survival (OS) were assessed from the date of the SRS procedure. The median LC, freedom from new brain metastases, and OS for the entire group were 8.7, 4.3, and 5.9 months, respectively. The cause of death was CNS progression in all but eight patients. Six-month LC, freedom from new brain metastases, and OS were 65, 35, and 56%, respectively, for those who received ipilimumab and 63, 47, and 46% for those who did not (P=NS). Intracranial hemorrhage was noted in seven patients who received ipilimumab compared with 10 patients who received SRS alone (P=NS). In this retrospective study, administration of ipilimumab neither increased toxicity nor improved intracerebral disease control in patients with limited brain metastases who received SRS.

Purpose: Associations of radiation therapy (RT) deviations and outcomes in medulloblastoma have not been defined well, particularly in the era of reduced-dose craniospinal irradiation and chemotherapy. The aim of this study is to evaluate the quality of RT on Children's Cancer Group/Pediatric Oncology Group 9961 and analyze associations of RT deviations with outcome. Materials and Methods: Major volume deviations were assessed based on the distance from specified anatomical region to field edge. We investigated associations of RT deviations with progression-free survival (PFS), overall survival (OS), and explored associations with demographics and clinical variables. Results: Of the 308 patients who were evaluable for volume deviations, 101 patients (33%) did not have any. Of the remaining 207 patients, 50% had only minor deviations, 29% had only major deviations, and 21% had both minor and major deviations. Of the patients with major deviations, 73% had a single major deviation. The most common major deviation was in the cribriform plate region, followed by the posterior fossa (PF); PF deviations resulted from treating less than whole PF. There were no significant differences in PFS or OS between patients with deviations and those without. There was no evidence of associations of deviations with patient age. Conclusions: Approximately one-third of patients had major volume deviations. There was no evidence of a significant association between these and outcome. This lack of correlation likely reflects the current high quality of RT delivered in Children's Oncology Group institutions, our strict definition of volume deviations, and the relatively few instances of multiple major deviations in individual patients. In is noteworthy that the types of PF volume deviations observed in this study were not adversely associated with outcome. As we move forward, quality assurance will continue to play an important role to ensure that deviations on study do not influence study outcome.