Faculty Bibliography

PURPOSE: Very young children with CNS primitive neuroectodermal tumors (PNETs) and ependymomas have a poor prognosis and commonly have impairment of growth and cognitive abilities, in part resulting from radiotherapy. Thus, an intensive chemotherapeutic regimen was used to treat children less than 18 months of age at diagnosis. PATIENTS AND METHODS: Children were treated on a Childrens Cancer Group (CCG) protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytarabine, prednisone, and cyclophosphamide) following surgery and postoperative staging. Delayed or reduced-volume radiotherapy was to be administered to all patients, but, in fact, was omitted in most cases. RESULTS: On central review of pathology, 82 children had diagnosis concordant with study entry criteria. Of these, 46 (56%) had posterior fossa (PF) PNET, eight (10%) had pineal PNET, 11 (12%) had nonpineal supratentorial PNET, 15 (18%) had ependymoma, and two had rhabdoid tumors. Fifty percent of tumor resections were complete, as verified by postoperative computed tomographic (CT) scan, and 23% of patients had metastatic disease at the time of diagnosis. Objective tumor response was documented following two cycles of chemotherapy in 28% of assessable patients. Toxicity of chemotherapy was primarily hematopoietic. Five children died of chemotherapy-related complications. Radiotherapy was administered to only nine patients before tumor progression. The 3-year progression-free survival (PFS) rates for PF PNET, pineal PNET, supratentorial nonpineal PNET, and ependymoma are 22% (SE = 6%), 0%, 55% (16%), and 26% (11%), respectively. The 3-year PFS rate for those children without metastatic disease was 29% (6%), as compared with 11% (6%) for those with metastatic disease. The only independent predictors of PFS were metastasis stage and location of the tumor within the pineal region. The median time to progression was 6 months. Twenty-four children completed the chemotherapeutic regimen without tumor progression; 19 are event-free survivors more than 2 years from diagnosis, only three of whom received radiation therapy. CONCLUSION: While overall survival in this group of very young patients is poor, a subset of children who have received only chemotherapy as adjuvant treatment remain free from tumor recurrence

Recurrence is the most common complication of all forms of treatment of craniopharyngioma. Reoperation is the preferred treatment for unsuspected residual tumor after primary radical resection. Surgical resection can be curative in the majority of recurrences, especially those with solid tumor. Scarring from previous surgery, particularly following primary radical removal, may increase the technical difficulty of surgery. Although most patients will have a reasonable functional outcome, the morbidity following operation for recurrence is greater than primary surgery with some degree of new deficit being common. Adjuvant irradiation, interstitial irradiation or bleomycin, and serial aspiration of cystic tumors have lower cure rates than surgical resection but may have lower morbidity in selected patients. They are potential adjuvant or second-line treatments for subsequent recurrence

Patients with medulloblastoma frequently present with hydrocephalus. While not all patients with medulloblastoma will continue to suffer from hydrocephalus after tumor resection, there is a significant proportion who will require a permanent shunt. We have retrospectively reviewed a group of children with medulloblastoma not shunted preoperatively, and have identified several characteristics which are associated with a requirement for permanent shunt. We studied 42 patients and found that 17 patients (40%) required permanent shunts within 4 weeks of craniotomy. The shunted patients were younger (5.4 +/- 2.9 vs. 10.0 +/- 5.7 years; p < 0.01), had larger ventricles (p < 0.05), and had more extensive tumors (Chang's stage T3 and T4; p < 0.01). These variables were all independently significant. In addition, we found that the patients requiring postcraniotomy shunts had a much higher rate of morbidity including a postoperative pseudobulbar syndrome. Of interest, we found that none of our patients without the above characteristics required a shunt. In particular, we found that no patient older than 10 years required a shunt. Thus, we conclude that younger patients with moderate to severe preoperative hydrocephalus and extensive tumors may benefit from perioperative CSF diversion. Other patients not meeting the above criteria can probably be safely managed with perioperative corticosteroids alone

The records of 58 patients with gangliogliomas surgically treated between January 1, 1980, and June 30, 1990, were retrospectively reviewed in order to determine long-term survival, event-free survival, and functional outcome resulting after radical resection and to assess the impact of histological grading on outcome. Tumors were located in the cerebral hemisphere in 19 cases, the spinal cord in 30, and the brain stem in nine. Forty-four patients had gross total resection and 14 had radical subtotal resection. Only six patients underwent postoperative irradiation or chemotherapy and, therefore, the outcome was generally related to surgery alone. Of the 58 gangliogliomas, 40 were classified as histological grade I, 16 were grade II, and two were grade III. The median follow-up period was 56 months. There were no operative deaths, and the operative morbidity rate was 5%, 37%, and 33% for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas, respectively. The 5-year actuarial survival rates for cerebral hemisphere, spinal cord, and brain-stem gangliogliomas were 93%, 84%, and 73%, respectively (p = 0.7). The event-free survival rate at 5 years was 95% for cerebral hemisphere gangliogliomas and 36% for spinal cord gangliogliomas (p < 0.05); for brain-stem gangliogliomas the event-free survival rate at 3 years was 53% (p < 0.05). Neurological function at recent follow-up evaluation was stable or improved in 81% of patients. Multivariate analysis (Cox linear regression) revealed tumor location to be the only variable predictive of outcome, with spinal cord and brain-stem gangliogliomas having a 3.5- and 5-fold increased relative risk of recurrence, respectively, compared to cerebral hemisphere gangliogliomas. Histological grade was not predictive of outcome, although in each location there was a trend for higher-grade tumors to have a shorter time to recurrence. It is concluded that radical surgery leads to long-term survival of patients with gangliogliomas, regardless of location, and adjuvant therapy can probably be reserved for special cases

Vein of Galen malformations may present as congestive heart failure in the neonate and are usually fatal if untreated. Early studies using transcatheter embolization techniques, in a series of 22 patients, had a 50% mortality rate and a 37% incidence of severe mental retardation in survivors. Modifications of embolization techniques and neonatal care have improved the outlook in a more recent series of 11 patients. The diagnosis was established within 3 days of life in 91% of the cases. No mortality occurred, and 6 of the patients were functionally normal at up to 30 months' follow-up. Although two patients had severe neurologic deficits and/or a seizure disorder, only one case was possibly temporally associated with the embolization procedure. Some developmental delay was noted in one other patient. These improvements result, in part, from modifications of the treatment protocol, including earlier diagnosis, avoidance of digoxin, improvement in the application of newer microcatheters and acrylic polymers (n-butylcyanoacrylate), avoidance of overly aggressive neurosurgical procedures, and the use of stable central vascular access for total parenteral nutrition accompanying other general improvements in neonatal care