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Published on: October 27, 2014
Historical controls for phase II surgically based trials requiring gross total resection of glioblastoma multiforme
Nicholas Butowski1, Kathleen R Lamborn, Mitchel S Berger
1Neuro-Oncology Service, Department of Neurological Surgery, University of California, San Francisco, 400 Parnassus Avenue, A808, San Francisco, CA 94143-0350, USA. butowski@neurosurg.ucsf.edu
Abstract:
New treatments for patients with glioblastoma multiforme (GBM) are frequently tested in phase II surgically based clinical trials that require gross total resection (GTR). In order to determine efficacy in such single-arm phase II clinical trials, the results are often compared to those from a historical control group that is not limited to patients with GTR. Recursive partitioning analysis (RPA) can define risk groups within historical control groups; however, RPA analyses to date included patients irrespective of whether a patient had a GTR or not. To provide a more appropriate historical control group for surgically based trials requiring a GTR, we sought to determine survival for a group of patients with newly diagnosed GBM, all of who underwent GTR and were treated on prospective clinical trials. GTR was defined as removal of >90% of the enhancing mass, determined by postoperative magnetic resonance imaging. Of 893 patients with GBM treated during these trials, 153 underwent GTR. The median survival for the GTR group was 71 weeks (95% CI 65-76) which was better than those who did not have a GTR. Within the GTR group, the median age was 54 years (range 25-77 years), and median Karnofsky Performance Score was 90 (range 60-100). Considering only patients with GTR, age at diagnosis continued to be a statistically significant prognostic factor. Patients treated during surgically based phase II studies should be matched with a historical control group restricted to patients with similar pretreatment variables, including GTR.
Insights
For glioblastoma multiforme (GBM) trials, historical controls should include only patients who underwent gross total resection (GTR). This ensures accurate efficacy assessment for new GBM treatments tested in surgically based clinical trials.
Area of Science:
- Neuro-oncology
- Clinical Trial Design
- Surgical Oncology
Background:
- Phase II clinical trials for glioblastoma multiforme (GBM) often require gross total resection (GTR).
- Current historical control groups for these trials include patients with and without GTR, potentially skewing efficacy results.
- Recursive partitioning analysis (RPA) has limitations in defining risk groups when GTR status is not considered.
Purpose of the Study:
- To establish a more appropriate historical control group for phase II clinical trials in GBM that require GTR.
- To determine the survival outcomes for GBM patients who underwent GTR in prospective clinical trials.
Main Methods:
- Retrospective analysis of 153 GBM patients who underwent GTR from a cohort of 893 treated on prospective clinical trials.
- GTR defined as >90% enhancing mass removal via postoperative MRI.
- Survival analysis and prognostic factor assessment (age, Karnofsky Performance Score) within the GTR cohort.
Main Results:
- The median survival for the GTR group was 71 weeks (95% CI 65-76), which was significantly better than for patients without GTR.
- Within the GTR cohort, median age was 54 years, and median Karnofsky Performance Score was 90.
- Age at diagnosis remained a significant prognostic factor for survival within the GTR group.
Conclusions:
- Glioblastoma multiforme (GBM) patients undergoing gross total resection (GTR) have improved survival.
- Future surgically based phase II GBM trials require historical control groups matched for pretreatment variables, specifically including GTR status.
