Results of a pilot study of hyperfractionated radiation therapy for children with brain stem gliomas.

The majority of children with brain stem gliomas develop progressive disease within 18 months of diagnosis and treatment. Radiotherapy (RT) is of transient benefit in most patients and higher total doses of RT have been related to improved survival. The amount of RT which can be given is limited by the tolerance of the surrounding brain. Hyperfractionated RT theoretically allows higher doses of RT to be tolerated by the brain. Sixteen children with brain stem gliomas were treated on a hyperfractionated RT schedule, receiving 120 cGy of RT twice daily, to a total dose of 6480 cGy. All patients tolerated treatment well. Eleven of 15 (73%) evaluable patients had a response to treatment and two (13%) others had stable disease. One patient developed progressive disease during treatment. All patients were tapered off steroids by the completion of treatment. Thirteen of 16 (81%) patients developed progressive disease at a median of 7 months after diagnosis and three remain in remission 8, 12, and 15 months following diagnosis. These results were similar to those of historical controls. Two patients were surgically explored at time of relapse and 5 have had an autopsy. No acute or subacute neurologic toxicity was seen; but long-term detrimental effects on brain could not be assessed. The implications of this study are that escalations of the dose of hyperfractionated RT can be entertained for children with brain stem gliomas.

Quality of life in children with primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa.

We reviewed our experience in 43 consecutive patients with primitive neuroectodermal tumors (medulloblastoma), PNET (MB), treated between 1975 and 1984, to characterize their quality of life and identify factors which impacted on long-term function. Twenty-four of forty-three (56%) of children are alive and free of disease, a median of 4.5 years after diagnosis. The quality of life was analyzed for the 24 long-term survivors. 79% (19 of 24) were functioning well in everyday activities. The median full-scale intelligence quotient (FSIQ), obtained a median of 3.5 years after diagnosis for those tested (n = 17) was 97, with all but 3 (12%) of the patients functioning in the normal range. Specific learning, memory and fine-motor disabilities were found in over one half of patients. Factors associated with poorer performance and lower FSIQ included preoperative obtundation, the need for a permanent shunt, younger age at diagnosis, and a complicated postoperative course. It is concluded that (1) the majority of long-term survivors have 'normal' intellectual function, but may have specific intellectual and academic disabilities, and (2) preoperative and postoperative factors strongly impact on the quality of life of survivors.

Prognostic importance of cellular differentiation in medulloblastoma of childhood.

Medulloblastoma is the most common intracranial primitive neuroectodermal malignancy of childhood. Certain parameters are predictive of survival in children with medulloblastoma; however, tumor histology is of unclear prognostic value. A classification system, proposed by Rorke for all central nervous system (CNS) neoplasms composed of primitive neuroepithelial cells, was utilized in a review of 38 consecutive patients with newly diagnosed medulloblastoma. The classification is based on the concept that medulloblastoma is not unique to the cerebellum but is similar to tumors that may arise elsewhere in the CNS consequent to neoplastic transformation of primitive neuroepithelial cells. Cells forming the tumors may remain in the undifferentiated state or they may exhibit differentiation along glial, and/or ependymal, and/or neuronal lines. For purposes of simplification, the cases were divided into two major groups: those primitive neuroectodermal tumors (PNET's) which showed no evidence of cellular differentiation (PNET-U) and those that were differentiated (PNET-D). There were 20 cases in the PNET-U group and 18 in the PNET-D group. The 4-year survival rate was 70% for PNET-U, compared to 32% for PNET-D (p = 0.004). Only one of 10 children with PNET-D with differentiation along more than one cell line survived. Other factors, including age at diagnosis, tumor metastasis (TM) stage, and extent of surgical resection, were analyzed and were of prognostic importance; but histological features remained statistically significant within each subgroup.

Pineal region tumors of childhood.

The incidence, response to treatment, and outcome of children with pineal region neoplasms is poorly characterized. Since 1975, in one institution, 25 consecutive patients with pineal tumors have undergone biopsy prior to further treatment. This constituted 11% (25/234) of all brain neoplasms seen over this time period. Specific tumors diagnosed included pineal parenchymal tumors ( pineoblastomas , pineocytomas ) in eight patients (32%); germ cell tumors (embryonal cell carcinomas, teratomas, germinomas) in eight patients (32%); glial tumors (astrocytoma, ganglioglioma ) in eight patients (32%); and ganglioneuroblastoma in one patient (4%). Clinical parameters, computed tomographic findings and CSF markers (alphafetoprotein and human chorionic gonadotropin) were unreliable in discriminating between specific tumor types. Response to treatment and patterns of disease relapse were dependent on the type of tumor present. Five of eight children with pineal parenchymal tumors had disease recurrence, and in all leptomeningeal dissemination occurred prior to or concurrent with local relapse. Three of eight children with germ cell tumors and two of eight patients with glial tumors suffered a relapse; in all five children recurrence was initially local. Findings suggest that pineal region neoplasms are not infrequent in childhood; that these tumors vary greatly in histologic type; that contrary to other reports germinomas do not constitute the majority of pineal tumors; and that histologic confirmation is necessary prior to treatment for appropriate management.