The CR and EFS rates achieved represent a significant improvement over previous results at this institution. Bulky extramedullary disease was an important risk factor in this series, but age and WBC alone inadequately defined risk groups, suggesting that prognostic factors may vary in different world regions.

Reirradiation with chemotherapy may be feasible to improve symptoms and delay progression with minimal toxicity. Patients who are most likely to benefit may be those with prolonged response to initial therapy and a long interval since initial radiation.

Purpose Diffuse intrinsic pontine gliomas (DIPG) typically progress within 6 months after initial radiation therapy. Usually, progression is accompanied with debilitating symptoms and changes in the MRI appearance. Methods We conducted a retrospective chart review of patients with recurrent DIPG at MDAnderson Cancer Center from 1998 to 2010 to asses both, the treatments given and to consider the optimal way to study the benefit of them. Results Thirty one patients were identified who were treated with 61 attempts using 26 different individual treatment elements in 31 different regimens. The most frequently used drugs were etoposide (14), bevacizumab nimotuzumab irinotecan and, valproic acid (13 each). Seven patients had repeat radiation to the primary tumor. Response was recorded after 58 treatment attempts and was categorized as 0/7/20/31 for CR/PR/SD/PD, respectively. The median progression free survival after treatment start was 2 months and was found to be correlated to the prior time to progression but not to the number of previous treatment attempts. Among the various treatments, repeat radiation resulted in the highest response rates (4/7), and longest progression free survival. There was evidence suggestive of benefit of classical chemotherapeutic drugs such as cisplatin and temozolomide. Conclusion The biology of DIPG appears to change from first diagnosis to progression. Repeat radiotherapy, either alone or combined with other therapies, should be tested in a prospective clinical study. An important factor remains previous time to progression for prediction of treatment benefit.

BackgroundHearing loss is common following chemoradiotherapy for children with medulloblastoma. Compared to photons, proton radiotherapy reduces radiation dose to the cochlea for these patients. Here we examine whether this dosimetric advantage leads to a clinical benefit in audiometric outcomes.MethodsFrom 2006-2009, 23 children treated with proton radiotherapy for medulloblastoma were enrolled on a prospective observational study, through which they underwent pre- and 1 year post-radiotherapy pure-tone audiometric testing. Ears with moderate to severe hearing loss prior to therapy were censored, leaving 35 ears in 19 patients available for analysis.ResultsThe predicted mean cochlear radiation dose was 30 60Co-Gy Equivalents (range 19-43), and the mean cumulative cisplatin dose was 303 mg/m2 (range 298-330). Hearing sensitivity significantly declined following radiotherapy across all frequencies analyzed (P < 0.05). There was partial sparing of mean post-radiation hearing thresholds at low-to-midrange frequencies and, consequently, the rate of high-grade (grade 3 or 4) ototoxicity at 1 year was favorable (5%). Ototoxicity did not correlate with predicted dose to the auditory apparatus for proton-treated patients, potentially reflecting a lower-limit threshold for radiation effect on the cochlea.ConclusionsRates of high-grade early post-radiation ototoxicity following proton radiotherapy for pediatric medulloblastoma are low. Preservation of hearing in the audible speech range, as observed here, may improve both quality of life and cognitive functioning for these patients.

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