Low-Dose Craniospinal Irradiation (CSI) With Computed Tomographic (CT) Simulation and Ifosfamide, Cisplatin, and Etopiside for Non-Metastatic Embryonal Tumors in the Central Nervous System

Abstract

Purpose/Objective(s): To evaluate the effects of low-dose cranio-spinal irradiation (CSI) with CT simulation combined with chemotherapy for non-metastatic embryonal tumors in the central nervous system. Materials/Methods: All patients were treated with CTsimulation with the help of MRI information. After surgery, patients 5 years received 24Gy/12Fr/3wks CSI. The dose to the primary tumor bed was 39.6-54Gy/22 27Fr/6-7wks. Chemotherapy consisted of ifosfamide (900 mg/m2, day 1-5), cisplatin (20 mg/m2, days 1-5), and etoposide (60 mg/m2, days 1-5). Dose of each agent was modified according to pre-determined dose reduction criteria after second course of chemotherapy. Patients younger than 2.5 years old received the chemotherapy after surgery and radiotherapy was given when they became 2.5 years old. For older patients, the chemotherapy was given once before radiotherapy and subsequently after radiotherapy. Results: Sixteen patients aged 0.5 to 20.4 (median 6.1) years were enrolled and followed for 11 to 172 months with the median of 118 months. Overall survival and progression-free survival for the 8 patients who received 18Gy CSI were both 75 % (CI: 45 100%). Overall survival and progression-free survival for the 8 patients who received 24 Gy CSI were 88% (CI: 64100%) and 75% (CI: 44-100%) respectively. In total, both 5-years actuarial overall survival and progression-free survival were 81 % (CI: 62 100 %) for the 16 patients. Both 5-year actuarial overall and progression-free survival rate were 100% for 6 average risk patients (3 years or older, total resection, posterior fossa) and 70 % (95% confidence interval, CI: 4298%) for 10 poor-risk group (others) (p=0.14). Total intellectual quotient (IQ) was measured in 12 patients with the median follow-up period of 49 months ranged from 3 to 145 months. Total IQ was distributed from 48 103 with the median of 83 at the last follow-up. There was no apparent discrepancy between verbal IQ (median 86, 48 119) and performance IQ (92, 58 113) in 9 patients who could receive the examination for verbal IQ and performance IQ. Apparent deterioration in total IQ more than 10 points was not observed in 6 patients whose total IQ was measured more than 2 times during the follow-up with the median interval of 69 ranged from 19 to 125 months. Deficiency in thyroid hormone, corticosteroid hormone, and growth hormone was observed in 1, 1, and 2 patients, respectively. All were treated with hormonal supplementation. No patients suffered from symptomatic hearing deficiency or required hearing aids. One patient experienced hemangioma in the skull in the irradiated region and received surgical removal of the tumor. Conclusions: Low-dose CSI with CT simulation and ICE chemotherapy may have a role as a treatment option for a subset of patients with non-metastatic embryonal tumors in the central nervous system.