Faculty Bibliography

PURPOSE: To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of radiation therapy (RT) and/or chemotherapy. PATIENTS AND METHODS: Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen. RESULTS: Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease. CONCLUSION: (1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure

BACKGROUND. Very young children with central nervous system malignant brain tumors have a poor prognosis. As compared with older children, survival is less likely, and those children who do survive frequently have severe impairment of growth and cognitive abilities, resulting partly from treatment with radiotherapy. Therefore, an intensive chemotherapeutic regimen was used to treat children younger than 2 years of age with a diagnosis of malignant astrocytomas. PATIENTS AND METHODS. Thirty-nine children younger than 24 months of age who were diagnosed with malignant astrocytoma were treated on a Childrens Cancer Group protocol with an eight-drug chemotherapeutic regimen (vincristine, carmustine, procarbazine, hydroxyurea, cisplatin, cytosine arabinoside, prednisone, and dimethyl-triazenoimidazole-carboxamide) after surgery and postoperative staging. Radiation therapy was to be deferred until the completion of chemotherapy. RESULTS. The objective response rate after two cycles of chemotherapy was 24%. Most patients did not receive radiotherapy. Progression-free survival (PFS) and survival at 3 years was 36% (standard error, 8%) and 51% (8%), respectively. The PFS of those children with anaplastic astrocytoma was 44% (11%), significantly better than that of glioblastoma multiforme (GBM) (0%). Extent of resection was not associated significantly with PFS, but tumors within the cerebral hemispheres were associated with a more favorable prognosis. Tumor progression occurred locally in almost all cases and early in treatment (median PFS, 8 months). CONCLUSION. Chemotherapy appears to be effective primary adjuvant treatment for some very young children with anaplastic astrocytomas. Overall, however, survival remains poor, especially for children with GBM. Strategies to improve outcome require early intervention, because tumor progression occurs soon after diagnosis in the majority of patients

We conducted a retrospective analysis of the cases of 122 children operated on for various brain tumors, to determine the incidence and natural history of postoperative diabetes insipidus (DI), and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Abnormalities of water homeostasis were observed in 15 patients (12%). DI, with or without SIADH, was observed in 10 patients (8%), while SIADH alone was seen in five (4%). DI was permanent in five subjects (50%), whereas SIADH resolved completely in all affected individuals. Parenteral desmopressin (dDAVP) was an effective mode of therapy in the postoperative period. The effect did not correlate with a dosage strictly based on body weight

Pathological and clinical data from 56 patients operated on for craniopharyngioma since 1981 were analyzed to determine the utility of dividing patients with this tumor into distinct clinical groups based on recognized pathological type and to determine the prognostic import of brain invasion. Of the tumors in the 30 adult patients, 66% were adamantinomatous, 28% were squamous papillary, and the remainder were mixed. However, of the tumors in the 26 children, 96% were adamantinomatous and none were pure squamous papillary (P < 0.01). Forty-six percent of the children compared with 17% of the adults had brain invasion (P < 0.01). Brain invasion was present in 37% of the adamantinomatous but in only 13% of the squamous papillary tumors. Seventy-seven percent of the children underwent gross total resection (GTR) compared with 27% of the adults (P < 0.01). Sixty-three percent of the squamous papillary tumors underwent GTR compared with 54% of the adamantinomatous and mixed tumors. Follow-up ranged from 7 to 187 months (mean, 49 mo). After subtotal resection, with or without radiation therapy, 58% of the tumors recurred compared with 17% recurrence after GTR (P < 0.01), with a mean time to recurrence of 34 months. In both tumor histological types, subtotal resection was associated with a higher rate of tumor recurrence compared with gross total resection. Among the subtotally resected craniopharyngiomas, 2 of the 3 (67%) squamous papillary and 11 of the 21 (52%) adamantinomatous and mixed tumors recurred. In contrast, among the totally resected tumors, none of the 5 squamous papillary and only 5 of the 25 (20%) adamantinomatous and mixed tumors recurred. There were no significant differences in Karnofsky performance status score, mortality rate, or visual and endocrine outcomes when comparing patients based on histological tumor type. When controlling for age and extent of resection, we found that brain invasion had no significant effect on recurrence rate in totally resected tumors. Based on the limited number of patients in this series, we conclude as follows. 1) Contrary to previous reports, squamous papillary craniopharyngiomas, like adamantinomatous tumors, may recur when subtotally resected. 2) For both tumor variants, the most significant factor associated with craniopharyngioma recurrence is the extent of surgical resection rather than histopathological subtype. 3) Contrary to prior hypotheses, brain invasion in totally resected tumors does not predict higher recurrence. 4) GTR is associated with a significantly lower recurrence rate and can be achieved without sacrificing functional outcome

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

Moyamoya disease is a cerebrovascular disease characterized radiologically by progressive narrowing and occlusion of the arteries contributing to the circle of Willis and its branches. There is formation of an exuberant collateral network of blood vessels at the base of the brain, which is thought to arise in response to chronic ischemia. Clinically, the course is variable, with patients having repeated transient ischemic attacks, strokes, migraine, and seizures. Effective treatment is not available. The etiology and pathophysiology of moyamoya disease are largely unknown. Two patients with arteriographically proven moyamoya disease were identified. Both patients were symptomatic before age 5 years. Despite successful encephaloduroarteriosynangiosis revascularization procedures, they continued to experience an inexorable downhill course. A calcium channel blocker (nicardipine HCl) was introduced in order to prevent further symptoms. After the introduction of nicardipine, no further strokes occurred in either patient. There were no further episodes of transient ischemic attacks, seizures, or headache in one patient and decreased frequency in the other. In patients with moyamoya disease, nicardipine may have a beneficial effect on cerebral hemodynamics and may prevent ischemic sequelae by optimizing existing collateral circulation

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