Faculty Bibliography

OBJECTIVE: Dose-response relationships for meningioma radiosurgery are poorly characterized. We evaluated determinants of local recurrence for meningiomas treated with Gamma Knife radiosurgery (GKRS), to guide future treatment approaches to optimize tumor control. MATERIALS AND METHODS: A total of 101 consecutive patients (108 tumors) who underwent GKRS for benign, atypical, or malignant meningiomas between 1998 and 2011 were studied. Local recurrence was assessed. Cox proportional hazards and logistic regression analyses were used to determine the association of patient-related, tumor-related, and treatment-related characteristics with local recurrence. Acute and late toxicity was evaluated. RESULTS: World Health Organization (2007 classification) tumor grade was I (82%), II (11%), or III (7%). Median dose was 14 Gy (range, 10 to 18 Gy) for grade I tumors and 16 Gy (range, 12 to 20 Gy) for grade II and III tumors. Median follow-up was 25 months (maximum, 17 y). Two- /5-year actuarial local control rates were 100%/98% for grade I tumors and 76%/56% for grade II/III tumors. Higher tumor grade and lower GKRS dose were associated with local failure. In this cohort, there was a 42% relative reduction in local recurrence for each 1 Gy of dose escalation. CONCLUSIONS: Treatment was well tolerated with no moderate or severe toxicity. Tumor control was excellent in benign tumors and suboptimal in higher grade tumors. Because the main determinant of local recurrence was GKRS dose, we recommend dose escalation for atypical or malignant tumors to doses between 16 and 20 Gy where critical structures allow.

PURPOSE: This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. PATIENTS AND METHODS: Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. RESULTS: The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% +/- 4% (SE) and overall survival was 93% +/- 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum alpha-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. CONCLUSION: Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. This regimen should be included as a backbone for further studies.

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.

BACKGROUND: Marked elevations of AFP and bHCG in serum or CSF may serve as surrogate diagnostic markers in lieu of histology for primary CNS mixed, malignant germ cell tumors. There is less information on the diagnostic sensitivity of bHCG assays in germinoma. PROCEDURE: We report baseline serum and lumbar CSF bHCG values in 58 newly diagnosed, histologically confirmed germinoma patients gathered from two prospective clinical trials which required that patients have a normal AFP and bHCG