Faculty Bibliography

Over the last decade, the results of 5 prospective clinical trials of intracranial low-grade glioma (LGG) have been published, 4 in adults with supratentorial LGG and 1 in children with infra- and supratentorial LGG. The data from the more than 1600 patients treated on these studies are summarized herein. European Organization for Research and Treatment of Cancer study 22845 randomized 311 adults to postoperative observation or radiation therapy (RT). There was no difference in the 5-year overall survival (OS) rate between the 2 arms. Irradiated patients had a significantly improved 5-year progression-free survival (PFS) rate. European Organization for Research and Treatment of Cancer study 22844 randomized 379 adults to low-dose (45 Gy) versus high-dose (59.4 Gy) RT. Similarly, an intergroup study conducted by the North Central Cancer Treatment Group, Radiation Therapy Oncology Group, and Eastern Cooperative Group randomized 203 adults to low-dose (50.4 Gy) versus high-dose (64.8 Gy) RT. There was no difference in the 5-year OS or PFS rates between the 2 dose groups in either study. A Southwest Oncology Group study randomized 54 adults with incompletely resected LGG to RT alone or RT plus CCNU (lomustine) chemotherapy. There was no difference in outcome between the 2 treatment arms. Important prognostic factors for OS in these 4 adult trials included extent of surgical resection, histology, tumor size, and age. An intergroup study of the Children's Cancer Group and Pediatric Oncology Group enrolled 660 pediatric patients with management based on the extent of surgical resection: Children who underwent gross total tumor resection were observed postoperatively, whereas those who had subtotal resection or biopsy were either observed or administered RT at the discretion of their physician. Survival was most impacted by several prognostic factors, primarily extent of resection. Besides extent of resection, other prognostic factors that were consistent in predicting survival in these 5 clinical trials included patient age and tumor location, size, and histology. The data from these 5 studies indicate that for intracranial LGG in adults, postoperative RT is associated with improved 5-year PFS but not OS rates compared to postoperative observation. Radiation doses of 45 to 54 Gy result in 5-year OS and PFS rates that are similar to those for higher doses. The strategies of chemotherapy alone and RT plus chemotherapy are under investigation. For pediatric LGG, extent of surgical resection is the most important prognostic factor associated with favorable 5-year OS and PFS. Radiation therapy and chemotherapy are generally used in the settings of incomplete resection and recurrent disease, and these strategies are being investigated in prospective clinical trials. The schemata from recently completed and ongoing studies in both adult and pediatric intracranial LGG are reviewed

PURPOSE: To assess the activity and tolerability of temozolomide in children with progressive low-grade gliomas (LGGs). PATIENTS AND METHODS: The authors reviewed the records of 13 children (6 months to 19 years old) with progressive LGGs and magnetic resonance imaging evidence of unresectable tumors who were treated with temozolomide at the authors' institution since 1999. RESULTS: Four patients received a 5-day regimen of temozolomide (150 mg/m2 per day) repeated every 28 days, and nine patients received a 42-day regimen (75 mg/m2 per day) repeated every 56 days. Three patients demonstrated partial responses to temozolomide, with a median time to maximal response of 5 months (range 4-12 months), and one had a minor response at 9 months. Four patients developed progression while on temozolomide, with a median time to progression of 7 months (range 1-12 months). Five patients had disease stabilization. Among the five patients with prior chemotherapy and/or radiation therapy, temozolomide was associated with disease stabilization in three and tumor response in one. In the three patients with neurofibromatosis type 1, two patients experienced tumor responses and one disease stabilization. Thrombocytopenia, nausea, emesis, and fatigue were the most common toxicities. Four patients discontinued therapy because of the side effects. CONCLUSIONS: Temozolomide is active in children with LGGs. It is effective in previously treated patients and in patients with neurofibromatosis type 1. The 42-day regimen appears less toxic than the 5-day regimen. Any impact on survival for these patients remains to be demonstrated

OBJECT: In this study the authors evaluate the safety, efficacy, and indications for endoscopic third ventriculostomy (ETV) in patients with a history of subarachnoid hemorrhage or intraventricular hemorrhage (IVH) and/or cerebrospinal fluid (CSF) infection. METHODS: The charts of 101 patients from seven international medical centers were retrospectively reviewed; 46 patients had a history of hemorrhage, 42 had a history of CSF infection, and 13 had a history of both disorders. All patients experienced third ventricular hydrocephalus before endoscopy. The success rate for treatment in these three groups was 60.9, 64.3, and 23.1%, respectively. The follow-up period in successfully treated patients ranged from 0.6 to 10 years. Relatively minor complications were observed in 15 patients (14.9%), and there were no deaths. A higher rate of treatment failure was associated with three factors: classification in the combined infection/hemorrhage group, premature birth in the posthemorrhage group, and younger age in the postinfection group. A higher success rate was associated with a history of ventriculoperitoneal (VP) shunt placement before ETV in the posthemorrhage group, even among those who had been born prematurely, who were otherwise more prone to treatment failure. The 13 premature infants who had suffered an IVH and who had undergone VP shunt placement before ETV had a 100% success rate. The procedure was also successful in nine of 10 patients with primary aqueductal stenosis. CONCLUSIONS: Patients with obstructive hydrocephalus and a history of either hemorrhage or infection may be good candidates for ETV, with safety and success rates comparable with those in more general series of patients. Patients who have sustained both hemorrhage and infection are poor candidates for ETV, except in selected cases and as a treatment of last resort. In patients who have previously undergone shunt placement posthemorrhage, ETV is highly successful. It is also highly successful in patients with primary aqueductal stenosis, even in those with a history of hemorrhage or CSF infection

OBJECTIVE: To determine the value of delayed surgical resection in patients with central nervous system germ cell tumors who exhibit less than complete radiographic response despite declining serum and cerebrospinal fluid (CSF) tumor markers after initial chemotherapy. METHODS: We retrospectively analyzed 126 patients enrolled on two international multicenter clinical trials (the First and Second International Central Nervous System Germ Cell Tumor Studies) for patients with newly diagnosed central nervous system germ cell tumors. After at least three cycles of chemotherapy, 10 of these patients underwent delayed surgical resection owing to evidence of residual radiographic abnormalities despite declining or completely normalized serum and CSF levels of alpha-fetoprotein and human chorionic gonadotropin. RESULTS: Eight of these patients demonstrated nongerminomatous germ cell tumor elements at the time of initial diagnosis. In these patients, either serum or CSF tumor markers were elevated initially. Two patients demonstrated pure germinomas with normal levels of serum and CSF tumor markers. After chemotherapy, radiographic evaluation revealed a partial response in seven patients, a minor response in one patient, and stable disease in two patients. All 10 patients had either normal or decreasing levels of serum and CSF tumor markers before second-look surgery. At delayed surgical resection, 7 of the 10 patients underwent gross total resection, and 3 patients underwent subtotal resection of residual lesions. Pathological findings at second-look surgery demonstrated three patients to have mature teratomas, two with immature teratomas, and five with necrotic or scar tissue alone. To date, 7 of the 10 patients have had no recurrence during an average follow-up time of 36.9 months (range, 3-96 mo). Three of four patients with nongerminomatous germ cell tumors who had tumor markers that were decreased, but not normalized, before second-look surgery eventually developed tumor dissemination/progression, and they required subsequent radiation therapy despite having teratoma or necrosis/scar tissue at delayed surgery. In contrast, three of four patients with nongerminomatous germ cell tumors and completely normalized markers did not progress and did not require radiation therapy. CONCLUSION: Delayed surgical resection should be considered in patients with central nervous system germ cell tumors who have residual radiographic abnormalities and normalized tumor markers, because these lesions are likely to be teratoma or necrosis/scar tissue. However, second-look surgery should be avoided in patients whose tumor markers have not normalized completely