Multifocal Glioblastoma Multiforme: Prognostic Factors and Patterns of Progression

Purpose

To assess the progression patterns in patients with multifocal glioblastoma multiforme who had undergone whole brain radiotherapy (WBRT), the historical standard, versus three-dimensional conformal radiotherapy, and to identify predictive treatment and pretreatment factors.

Methods and Materials

The records of 50 patients with multifocal glioblastoma multiforme treated with RT were reviewed. Univariate analyses were performed using survival methods and the Cox proportional hazards regression method. Multivariate analyses were performed using the Cox proportional hazards regression method.

Results

The mean age was 61 years, and 71% had a Karnofsky performance status (KPS) score of ≥70. Of the 50 patients, 32% underwent WBRT and 68%, three-dimensional conformal RT. Progression was local in all evaluable patients, as determined by imaging in 38 patients and early neurologic progression in 12. The median time to progression (TTP) was 3.1 months, and the median survival time (MST) was 8.1 months. The significant independent predictors of TTP on multivariate analysis were a KPS score <70 (p = 0.001), the extent of surgery (p = 0.040), a radiation dose <60 Gy (p = 0.027), and the lack of chemotherapy (p = 0.001). The significant independent predictors of a reduced MST were a KPS score <70 (p = 0.022) and the absence of salvage surgery (p = 0.011) and salvage chemotherapy (p = 0.003).

Conclusion

Local progression was observed in all patients. On multivariate analysis, no significant difference was found in the TTP or MST between three-dimensional conformal radiotherapy and WBRT. The KPS was a consistent independent predictor of both TTP and MST. On the basis of the progression pattern, we do not recommend WBRT as a mandatory component of the treatment of multifocal glioblastoma multiforme.

Introduction

Glioblastoma multiforme (GBM) is the most common primary brain tumor encountered in adults. Median survival with optimal treatment is <15 months 1, 2. Although solitary lesions are typical for GBM, multiple synchronous gliomatous foci are found at diagnosis with a reported incidence of 0.5–20% 3, 4, 5, 6, 7. Multiple synchronous gliomas are categorized either as multifocal if a microscopic connection is presumed to exist or as multicentric if a route of dissemination is inapparent 5, 8, 9. Given the diffusely infiltrative nature of GBM, the clinical utility of this classic subcategorization of multiple lesions may be scant (10). Patients with disseminated GBM have inferior survival and a shortened time to recurrence (11).

The standard treatment for GBM includes conformal radiotherapy (RT) encompassing the tumor volume plus margin and concurrent and adjuvant temozolomide 1, 2. Tumor progression or recurrence typically occurs locally within the irradiated volume, despite dose escalation with conformal RT techniques 12, 13. Although the entity of multiple synchronous gliomas has been recognized for decades, no clear consensus has been reached regarding the RT technique for those tumors. In the past, standard therapy for multifocal GBM consisted of whole brain RT (WBRT) with or without a smaller cone-down volume to boost the tumor region (14). The inclusion of whole brain fields in the RT plan for multifocal GBM is controversial because of the consistent pattern of failure within the original tumor volume, as well as the limited doses that can be delivered safely to whole brain fields 3, 5. At our institution, the standard approach changed from the inclusion of WBRT to the use of three-dimensional conformal RT (3D-CRT), with involved-field techniques, allowing for the study of both approaches in this report. This retrospective, single-institution analysis was performed to describe the influence of prognostic and treatment factors on local tumor control and patterns of recurrence.