Resection of infantile brain tumors after neoadjuvant chemotherapy: the St. Jude experience

Abstract

Brain tumors in infants are often large, high grade, and vascular, making complete resection difficult and placing children at risk for neurological complications and excessive blood loss. Neoadjuvant chemotherapy may reduce tumor vascularity and volume, which can facilitate resection. The authors evaluated how an ongoing institutional prospective chemotherapy trial would affect patients who did not have a gross-total resection (GTR) immediately and who therefore required further surgical intervention to achieve definitive tumor resection. Thirteen infants (4 girls and 9 boys) who were enrolled in an institutional protocol in which they were treated with multiagent chemotherapy (methotrexate, vincristine, cisplatin, and cyclophosphamide with vinblastine for high-risk patients) subsequently underwent second-look surgery. The primary outcome was extent of resection achieved in postchemotherapy surgery. Secondary outcomes included intraoperative blood loss, radiographic response to the chemotherapy, complications during chemotherapy, and survival. Three infants underwent biopsy, 9 underwent subtotal resection, and 1 patient did not undergo surgery prior to chemotherapy. On subsequent second-look surgery, 11 of 13 patients had a GTR, 1 had a near-total resection, and 1 had a subtotal resection. In each case, a marked reduction in tumor vascularity was observed intraoperatively. The average blood loss was 19% of estimated blood volume, and 6 (46%) of 13 patients required a blood transfusion. Radiographically, chemotherapy induced a reduction in tumor volume in 9 (69%) of 13 patients. Emergency surgery was required in 2 patients during chemotherapy, 1 for intratumoral hemorrhage and 1 for worsening peritumoral edema. The average follow-up period for this cohort was 16.5 months, and at last follow-up, 4 patients (31%) had died, 1 patient had progressive metastatic spinal disease, and the rest had either no evidence of disease or stable disease. A GTR of pediatric brain tumors is one of the most important predictors of outcome. The application of the authors' neoadjuvant induction chemotherapy protocol in a variety of tumor types resulted in devascularization of all tumors and volume regression in the majority, and subsequently facilitated resection, with acceptable intraoperative blood loss. Intracranial complications may occur during chemotherapy, ranging from incidental and asymptomatic to life threatening, necessitating close monitoring of these children.