Patricia A. Aronin

Low-Stage Medulloblastoma: Final Analysis of Trial Comparing Standard-Dose With Reduced-Dose Neuraxis Irradiation

PURPOSE To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. PATIENTS AND METHODS The Pediatric Oncology Group and Childrens Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed tomography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. RESULTS The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuraxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P =.080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P =.141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. CONCLUSION Reduced-dose neuraxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement.

Prediction of BCNU Pulmonary Toxicity in Patients with Malignant Gliomas: An Assessment of Risk Factors

Symptomatic pulmonary disease occurred in 20 per cent of 93 patients with anaplastic gliomas being treated with carmustine (BCNU). An analysis of the variables has revealed a relation between the occurrence of pulmonary toxicity on the one hand, and the total cumulative dose of BCNU, the number of cycles over which the BCNU was administered, the history of lung disease, the patients age, and the platelet-count nadir after the first course of BCNU on the other. An equation has been generated that allows prediction of pulmonary toxicity during the course of therapy with BCNU with 80 per cent accuracy. Pretreatment analysis of individual cases should allow safe use of BCNU and prevention of most of the serious pulmonary complications caused by this drug.

Desmoplastic infantile gangliogliomas: an approach to therapy.

Desmoplastic infantile gangliogliomas are massive cystic tumors, typically occurring in the cerebral hemispheres of infants. They are remarkable pathologically for a prominent desmoplasia and, in some cases, for a cellular mitotically active component that can be readily interpreted as a malignant neoplasm. Four children less than 1 year of age were diagnosed with desmoplastic infantile gangliogliomas in the Pediatric Oncology Group infant brain tumor study (Protocol number 8633). All had been diagnosed by their respective institutions as having malignant tumors, i.e., Grade III astrocytoma, malignant meningioma, leptomeningeal fibrosarcoma, and gliosarcoma. All had increased intracranial pressure, and two had seizures. The tumors were extremely large, with one measuring 12 x 9 x 9 cm. None had evidence of metastatic disease. One patient had a gross total resection, and the other three had debulking procedures. All four children were treated with chemotherapy (cyclophosphamide, vincristine, cisplatinum, etoposide) for periods ranging from 12 to 24 months. Of those with postoperative measurable disease, one child had a complete response, one a partial response, and one had stable disease at the conclusion of chemotherapy. No child received radiation therapy. All children are alive with progression-free survivals after diagnosis of more than 36, 42, 48, and 60 months, respectively. Although desmoplastic infantile gangliomas are rare, recognition of this tumor type is essential because, despite their massive size and pathologically malignant appearance, they may have a relatively benign clinical course. If total surgical resection can be achieved, further therapy may not be indicated. In those patients in whom residual disease is present, chemotherapy appears to be an effective form of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)