Dose escalation with proton radiation therapy for high-grade meningiomas

Purpose of this study was to determine the toxicity and treatment outcome after dose escalation with proton radiation therapy for patients with World Health Organization (WHO) grade II and grade III meningiomas. Between 1997 and 1999, 6 patients with newly diagnosed or recurrent grade II or III meningioma were treated on a Phase I/II dose escalation trial with combined proton-photon radiotherapy at the Harvard Cyclotron Laboratory/Massachusetts General Hospital. The median age was 46. The sites were sphenoid wing in 2 patients, parasagittal/falcine in 2, parasellar in 1, and olfactory groove in 1. The median gross total volume (GTV) at the time of radiation was 13.3 cc (range: 4.0-129.5). The total dose to the GTV for the grade II and III meningiomas was 68.4 and 72.0 Gy (RBE) in 1.8 Gy (RBE), respectively. The median percentage of proton was 80%. All patients tolerated radiation treatment without any treatment break. None of the patients required steroids or hospitalization during radiation. There was no acute grade 3 to 5 toxicity. With a median follow-up period of 145 months for all surviving patients, one patient developed local recurrence. For the 5 patients with tumor controlled at the primary sites, 3 patients developed new meningioma(s) distantly from the primary sites at a median time of 25 months (range, 9-79). The median survival for grade II and grade III tumors was 145 months and 28 months, respectively. One patient developed late grade 1 dry eye. Two patients developed late grade 2 hypothyroidism and two developed grade 2 hypogonadism. There was no late grade 3-5 toxicity. Dose escalation with proton radiation therapy resulted in low toxicity and high local control rate in patients with high-grade meningiomas. Development of distant meningioma(s) intracranially was the main pattern of failure. Larger prospective studies are necessary to confirm our results.