Recurrent Adult Brain Tumors

Surgery
Localized Chemotherapy
Systemic Chemotherapy
Radiation Therapy
Current Clinical Trials

Re-resection of recurrent brain tumors is used in some patients. However, the majority of patients do not qualify because of a deteriorating condition or technically inoperable tumors. The evidence is limited to noncontrolled studies and case series on patients who are healthy enough and have small enough tumors to technically debulk. The impact of reoperation versus patient selection on survival is not known.

Carmustine wafers have been investigated in the setting of recurrent malignant gliomas, but the impact on survival is less clear than at the time of initial diagnosis and resection. In a multicenter randomized, placebo-controlled trial, 222 patients with recurrent malignant primary brain tumors requiring reoperation were randomly assigned to receive implanted carmustine wafers or placebo biodegradable wafers.[1] Approximately half of the patients had received prior systemic chemotherapy. The two treatment groups were well balanced at baseline. Median survival was 31 versus 23 weeks in the two groups. The statistical significance between the two overall survival (OS) curves depended upon the method of analysis. The hazard ratio (HR) for risk of dying in the direct intention-to-treat comparison between the two groups was 0.83 (95% confidence interval [CI], 0.63–1.10; P = .19). The baseline characteristics were similar in the two groups, but the investigators did an additional analysis, adjusting for prognostic factors, because they felt that even small differences in baseline characteristics could have a powerful influence on outcomes. In the adjusted proportional hazards model, the HR for risk of death was 0.67 (95% CI, 0.51–0.90, P = .006). The investigators put their emphasis on this latter analysis and reported this as a positive trial.[1][Level of evidence: 1iA] However, a Cochrane Collaboration systematic review of chemotherapeutic wafers for high-grade glioma focused on the unadjusted analysis and reported the same trial as negative.[2]

Systemic therapy (e.g., temozolomide or the combination of procarbazine, a nitrosourea, and vincristine in patients who have not previously received the drugs) has been used at the time of recurrence of primary malignant brain tumors. However, it has not been tested in controlled studies. Patient-selection factors likely play a strong role in determining outcomes, so the impact of therapy on survival is not clear.

Because there are no randomized trials, the role of repeat radiation after disease progression or the development of radiation-induced cancers is also ill defined. Interpretation is difficult because the literature is limited to small retrospective case series.[3] The decision must be made carefully because of the risk of neurocognitive deficits and radiation necrosis.

Patients who have recurrent brain tumors are rarely curable and should be considered candidates for clinical trials when they have exhausted standard therapy. Information about ongoing clinical trials is available from the NCI Web site.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult brain tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1. Brem H, Piantadosi S, Burger PC, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 345 (8956): 1008-12, 1995.  [PUBMED Abstract]
   
   
2. Hart MG, Grant R, Garside R, et al.: Chemotherapeutic wafers for high grade glioma. Cochrane Database Syst Rev (3): CD007294, 2008.  [PUBMED Abstract]
   
   
3. Paulino AC, Mai WY, Chintagumpala M, et al.: Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys 71 (5): 1381-7, 2008.  [PUBMED Abstract]