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AIM: The aim of this study was to evaluate toxicity and response to fractionated reirradiation (FR) of relapsed primary brain tumors in children. BACKGROUND: The treatment options for recurrent brain tumors in children previously irradiated are limited. Reirradiation is performed with fear due to the cumulative late CNS toxicity and the lack of a significant chance of cure. MATERIALS AND METHODS: Between 2008 and 2009, eight children with a median age of 14.5 years with a diagnosis of a recurrent brain tumor underwent reirradiation. Initially, all patients were treated with surgery, chemotherapy and radiotherapy. The median time to the first recurrence after the initial treatment was 19.5 months. Intervals between radiotherapy courses were in the range of 5-51 mos. All retreatments were carried out with 3D image-based conformal methods. The total prescription dose was 40 Gy in a fraction of 5 × 2 Gy/week. The total cumulative dose ranged from 65 to 95 Gy (median: 75 Gy). The median cumulative biologically effective dose was 144 Gy (range: 126-181 Gy). RESULTS: The median overall survival and progression free survival measured from the beginning of reirradiation was 17.5 and 6.5 months, respectively. During the first evaluation, four patients showed a complete or partial response, two did not respond radiologically. Two children were progressive at the time of reirradiation. Among children with progression that occurred during the first year after reirradiation, only two progressed in the treatment area. The repeated irradiation was well tolerated by all patients. No late complications have been observed. CONCLUSION: In the absence of other treatment possibilities, the fractionated reirradiation with highly conformal three-dimensional planning could be a therapeutic choice in case of recurrent brain tumors in children. The control of craniospinal dissemination remains to be the main problem.
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PURPOSE: Medulloblastoma is the most common malignant embryonal brain tumor in children. The current clinical risk stratification to select treatment modalities is not optimal because it does not identify the standard-risk patients with resistant disease or the unknown number of high-risk patients who might be overtreated with current protocols. The aim of this study is to improve the risk stratification of medulloblastoma patients by using the expression of multiple prognostic markers in combination with current clinical parameters. EXPERIMENTAL DESIGN: Candidate prognostic markers were selected from literature or from medulloblastoma expression data. Selected genes were immunohistochemically analyzed for their prognostic value using medulloblastoma tissue arrays containing 124 well-characterized patient samples. RESULTS: Protein expression analyses showed that the combined expression of three genes was able to predict survival in medulloblastoma patients. Low MYC expression identified medulloblastoma patients with a very good outcome. In contrast, concomitant expression of LDHB and CCNB1 characterized patients with a very poor outcome. Multivariate analyses showed that both expression of MYC and the LDHB/CCNB1 gene signature were strong prognostic markers independent of the clinical parameters metastasis and residual disease. Combined analysis of clinical and molecular markers enabled greater resolution of disease risk than clinical factors alone. CONCLUSIONS: A molecular risk stratification model for medulloblastoma patients is proposed based on the signature of MYC, LDHB, and CCNB1 expression. Combined with clinical variables, the model may provide a more accurate basis for targeting therapy in children with this disease.
