Boyett, James M.

Abstract Background The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3–21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. Methods Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. Results One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. Conclusions While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.

AbstractBackgroundSurvival rates for children with medulloblastoma have risen over the past decade, in part due to the addition of cisplatin‐containing adjuvant chemotherapy. Total dose of cisplatin required for optimal treatment is unknown. The purpose of this study was to evaluate the survival outcomes based on cumulative cisplatin doses (CCD) in children with newly diagnosed average‐risk medulloblastoma.ProcedureCCD data were reviewed for 363 patients in a prospective study evaluating patients between 3 and 21 years with a newly diagnosed average‐risk medulloblastoma and treated with craniospinal radiation and post‐radiation cisplatin based adjuvant chemotherapy.ResultsEight‐year event‐free survival (EFS) and overall survival (OS) estimates were 78.2 ± 2.6% and 83.9 ± 2.4%, respectively. Only 73 patients received the protocol specified CCD of 600 mg/m2, primarily due to mandated cisplatin toxicity‐related dose reductions. The median CCD given to those without relapse or death on treatment was 487.5 mg/m2. CCD, as a time‐dependent covariate, was not associated with EFS (P = 0.54) or OS (P = 0.11). The 343 patients who completed chemotherapy failure‐free were categorized into four groups according to CCD (n = 10; 75–150 mg/m2), (n = 26; 151–300 mg/m2), (n = 113; 301–450 mg/m2), and (n = 194; 451–600 mg/m2). There were no statistically significant differences in distributions of EFS (P = 0.53) or OS (P = 0.49) among these four groups.ConclusionCCD is not associated with EFS or OS suggesting that lower doses of cisplatin may be incorporated into future medulloblastoma trials, thereby limiting its toxicity profile without affecting survival. If ototoxicity is encountered, more stringent cisplatin dose modification/cessation rules seem warranted. Pediatr Blood Cancer 2014;61:102–106. © 2013 Wiley Periodicals, Inc.