Van Poppel Mark, Klimo Paul, Dewire Mariko, Sanford Robert A, Boop Frederick, Broniscer Alberto, Wright Karen, Gajjar Amar J
Division of Pediatric Neurosurgery, University of Tennessee College of Medicine, Memphis, Tennessee, USA.
J Neurosurg Pediatr. 2011 Sep;8(3):251-6. doi: 10.3171/2011.6.PEDS11158.
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.
婴儿脑肿瘤通常体积较大、分级较高且血管丰富，这使得完全切除困难，并使儿童面临神经并发症和失血过多的风险。新辅助化疗可能会减少肿瘤血管生成和体积，从而便于切除。作者评估了一项正在进行的机构前瞻性化疗试验将如何影响那些未能立即实现全切除（GTR）、因此需要进一步手术干预以实现肿瘤根治性切除的患者。
13名婴儿（4名女孩和9名男孩）参加了一项机构方案，接受了多药化疗（甲氨蝶呤、长春新碱、顺铂和环磷酰胺，高危患者加用长春碱），随后接受了二次手术。主要结局是化疗后手术的切除范围。次要结局包括术中失血量、化疗的影像学反应、化疗期间的并发症和生存率。
3名婴儿接受了活检，9名接受了次全切除，1名患者在化疗前未接受手术。在随后的二次手术中，13名患者中有11名实现了GTR，1名实现了近全切除，1名实现了次全切除。在每种情况下，术中均观察到肿瘤血管生成明显减少。平均失血量为估计血容量的19%，13名患者中有6名（46%）需要输血。影像学检查显示，13名患者中有9名（69%）化疗后肿瘤体积缩小。化疗期间有2名患者需要急诊手术，1名因肿瘤内出血，1名因瘤周水肿加重。该队列患者的平均随访期为16.5个月，在最后一次随访时，4名患者（31%）死亡，1名患者发生进行性转移性脊柱疾病，其余患者无疾病证据或疾病稳定。
小儿脑肿瘤的GTR是最重要的预后预测指标之一。作者的新辅助诱导化疗方案应用于多种肿瘤类型后，所有肿瘤均出现血管减少，大多数肿瘤体积缩小，随后便于切除，并具有可接受的术中失血量。化疗期间可能会发生颅内并发症，从偶然无症状到危及生命不等，因此需要密切监测这些儿童。
