Craniospinal Reirradiation Using Proton Beam Radiotherapy in the Treatment of Pediatric Recurrent Medulloblastoma

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<h3>Purpose/Objective(s)</h3> Craniospinal irradiation (CSI) is an essential part of medulloblastoma treatment even without any evidence of leptomeningeal metastasis. In case of recurrence, it is important to assess several factors to consider reirradiation course. These factors include prior radiation doses, time interval between radiotherapy courses and cumulative dose. In cases of leptomeningeal dissemination reirradiation of the entire craniospinal axis is needed, but may be accompanied by severe toxicity. Proton therapy may reduce toxicity without reducing treatment doses. <h3>Materials/Methods</h3> Proton beam craniospinal reirradiation (CSRI) course was conducted to 18 patients with recurrent medulloblastoma. Median dose to craniospinal axis during primary treatment was 30.6 Gy (24-36). Sixteen patients had additional local boost to recurrent and metastatic sites. In all cases we've made a dose gradient in the border zone to avoid irradiation of vertebral bodies. Eight patients had High Dose Chemotherapy (HDCT) before CSRI. The minimal interval between HDCT and CSRI was 2 months. Median dose at primary CSI was 23.7 Gy (23.4-36). Seven patients had reirradiation previously, two of them had CSRI with total dose of 18 Gy. <h3>Results</h3> Median time between two CSI courses was 33 months (19-126). Median follow-up period was 9 months (2-18). Six patients had disease progression, five of them died because of progression during the next 1.5 years after CSRI. Average time to progression was 13.3 ± 1.6 months (95% CI 10.1-16.4). During treatment we observed strong evidence of progressing thrombocytopenia (avg = 95 * 10⁹) with minimal values occurring during third week (p < 0.001). There was a non-significant decrease of hemoglobin and neutrophiles level (p_hemoglobin=0.4, p_neutrophiles=0.07). One patient had severe bone marrow hypoplasia during the treatment which required blood and platelet transfusion and neutrophil stimulation. The rest of the patients' hematological toxicity resolved without medical intervention. Only one patient had interruption during treatment because of COVID-19 infection. All the patients except one received chemotherapy after CSRI. None of them had any evidence of radiation necrosis or other radiological changes during the whole follow-up period. <h3>Conclusion</h3> CSRI is mostly used for medulloblastoma patients with refractory disease and leptomeningeal progression. Proton therapy may help to deliver curative doses with limited hematological toxicity and to minimize or completely avoid gastrointestinal toxicity. Probably it may lead to long-term disease control for such group of patients.