THE POTENTIAL FOR COMPLETE AND DURABLE RESPONSE IN NONGLIAL PRIMARY BRAIN-TUMORS IN CHILDREN AND YOUNG-ADULTS WITH ENHANCED CHEMOTHERAPY DELIVERY

PURPOSE Radiographic tumor response and survival were evaluated in the pediatric and young adult population with germ cell tumor, primary CN S lymphoma, or primitive neuroectodermal tumor receiving intra-arteria l carboplatin-or methotrexate-based chemotherapy with osmotic blood-br ain barrier disruption (BBBD). PATIENTS AND METHODS Thirty-four patien ts with histologically confirmed germ cell tumor (n = 9), primary CNS lymphoma (n = 9), or primitive neuroectodermal tumor (n = 16) were tre ated at the Oregon Health Sciences University from August 1981 through April 1995. Ages ranged from 1 to 30 years (mean, 18 years). Prior tr eatments included cranial radiation (n = 10) and chemotherapy (n = 18) . All patients underwent extensive baseline neuropsychological evaluat ion and follow-up evaluation upon completion of the protocol, except f or two patients who declined follow-up assessment. RESULTS Six hundred and forty-five BBBD procedures were performed with no mortality. Sign ificant complications included one episode of tonsillar herniation wit h no neurologic sequelae, 4% incidence of seizures, and 3% incidence o f sepsis or granulocytopenic fever. Ototoxicity was seen in 61% of pat ients who received carboplatin chemotherapy. Eighty-two percent of the patients had an objective response to treatment, including 62% with c omplete response and 20% with partial response. For most patients, cog nitive functioning was maintained or improved at follow-up; this patte rn was statistically significant. Three of the test scores for the sev en patients who did not receive radiation therapy showed a cognitive d ecline of at least one standard deviation. Among the nine patients who received radiation therapy before or after BBBD chemotherapy, 11 test scores showed a decline in cognitive function at one standard deviati on or more. DISCUSSION Durable responses were seen in patients with ge rm cell tumor and primary CNS lymphoma when treated with BBBD. Primiti ve neuroectodermal tumor requires post-chemotherapy radiotherapy for a durable response to be attained. Ototoxicity was a major form of toxi city in the patients who received carboplatin, but with the recent int roduction of sodium thiosulfate, this problem has been markedly allevi ated. Favorable cognitive outcomes appeared more likely for patients t reated solely with BBBD chemotherapy and not with radiotherapy. Trends in the results for this sample are similar to those of previous resea rch showing that radiotherapy is associated with cognitive decline. Cu rrent alternatives to enhanced drug delivery after BBBD include bone m arrow transplantation; however, the increment in drug delivery is less , the number of courses is limited, and the morbidity and mortality ar e greater for bone marrow transplant than for BBBD. The current result s suggest that in future trials, irradiation may not be needed in lymp homa and may not be necessary in some CNS germ cell tumors and that mo re focal radiotherapy should be further assessed in localized primitiv e neuroectodermal tumors.