Multidisciplinary treatment of children with recurrent posterior fossa ependymoma

Abstract

Objective: The mainstay of treatment for pediatric posterior fossa ependymoma (PFE) is maximal cytoreductive surgery followed by radiation therapy. PFE, especially posterior fossa group A ependymoma, which is more common in young children, has a high recurrence rate. The aim of this study was to retrospectively investigate the treatment and outcomes of recurrent PFE in children to identify optimal treatment strategies.

Materials and Methods: From 2006 to 2022, 14 pediatric patients with PFE were treated at Kobe Children’s Hospital. Relapse occurred in eight of these patients, the mean interval between first treatment and first recurrence being 23 months. The children’s mean age at the initial treatment was 4.5 years (range, 2 years to 8 years). We retrospectively reviewed the patients’ medical records for clinical course, imaging findings, treatment details and treatment outcomes.

Results: A total of 25 recurrences had occurred in the study cohort, 12 of which were local, nine metastatic or disseminated, and four both. Five of the eight patients were diagnosed histologically as WHO grade 2 ependymoma and three as WHO grade 3 anaplastic ependymoma at the time of initiating treatment. All three patients whose tumors were subjected to DNA methylation analysis had posterior fossa group A ependymomas. A total of 14 surgical procedures were performed for recurrent lesions in seven patients. One patient underwent surgery four times and one five times. The tumors were grossly totally resected in nine surgeries, sub-totally resected in two surgeries, and partially resected in three surgeries. One patient who had not received radiation during the initial treatment received conventional radiotherapy after recurrence, and two patients with metastatic or disseminated disease underwent proton beam therapy. A total of 13 Gamma Knife surgeries (GKSs) were performed on five patients (five to resected cavities, five to disseminated lesions, and three to growing local lesions). The median duration of progression-free survival after GKS was 22 months. The median progression-free survival was 3.5 months for patients with growing lesions who had not undergone prior resection, or local lesions who had undergone prior partial resection. In contrast, the median progression-free survival was 25 months for patients with small and non-aggressive lesions who had not undergone prior resection, or local lesions who had undergone prior subtotal or more resection. Six of eight patients were treated with chemotherapy for relapse: four with combination chemotherapy, five with temozolomide, and two with oral etoposide. The median durations of progression-free survival after combination chemotherapy and temozolomide treatment were 4.5 and 3 months, respectively. Five of eight patients (62.5%) died during the study period. The median survival after the first relapse for all eight patients was 49 months.

Conclusions: Recurrences of pediatric PFEs are difficult to cure and have a dismal prognosis. Tumor resection followed by GKS has some promise for tumor control after recurrence. Chemotherapy for recurrent PFE in children is unlikely to be effective. A treatment strategy that balances tumor control and maintenance of quality of life is essential.