Treatment Outcomes Following Proton Therapy for High Grade Spinal Cord Ependymoma in Children

Abstract

There is limited information published on the outcome of children treated with radiation for high-grade ependymoma of the spinal cord. Thus, little evidence is available to inform decisions of target volume or prescription dose. Moreover, there is virtually no mature outcome data on proton therapy, despite theoretical advantages in normal tissue exposure. We therefore performed a bicentric retrospective study to better inform treatment of this rare tumor in children.Between 2008 and 2019, 14 consecutive pediatric patients with a non-metastatic grade II or III spinal ependymoma were treated with proton therapy at the University of Florida and Massachusetts General Hospital. The median age of the children at the time of radiation was 14 years old (range, 1.5-18 years). Five tumors arose within the cervical cord (C1-5, C1-2, C1-T1, C3-T1, C4-C6), 3 within the thoracic spine (C7-T4, T7-L1, T11-T12), and 6 within the lumbosacral spine (L3-L5, L3-L5, L4-S2, S2-S5, L2-L3, L2-L3). Six tumors were grade II histology and 8 were grade III. Prior to radiotherapy, 3 patients had undergone a subtotal resection while the other 11 had a gross total or near total resection. One patient received chemotherapy according to the International Society of Pediatric Oncology (SIOP) infant regimen and 1 patient received chemotherapy according to Children's Oncology Group (COG) ACNS0831. For radiation, the gross tumor volume (GTV) was defined by the gross disease and/or tumor bed at the time of radiation. The CTV was defined by the GTV + 5-10 mm. The CTV received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter undergoing boost to just the GTV following the initial 50.4 Gy to respect spinal cord tolerance. For the cohort, the median maximum point dose to the spinal cord was 52.4 Gy (range, 0-53.9 Gy). The median maximum dose to 0.1 cc of spinal cord was 51.3 Gy (range, 0-52.5 Gy). The median volume of cord receiving ≥50.4 Gy was 3.4 cc (range, 0-17.1 cc).With a median follow-up of 6.3 years (range, 1.5 - 14.8 years), no tumors have progressed and all patients are alive. Serious acute toxicity was limited to 1 case of grade 2 nausea. While most patients experienced neurologic sequela following surgery, only 1 patient developed additional neurologic deficits following radiation: An 18-year-old male who received 54 Gy following gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of chronic musculoskeletal toxicity attributable to surgery and radiation in survivors. No patients have developed cardiac, pulmonary, or other visceral organ complications, nor has any patient developed a second malignancy.These outcomes suggest that radiation to a dose of 50-54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with grade II/III spinal cord ependymoma. Proton therapy may reduce the late radiation effects and is not associated with unexpected spinal cord toxicity.