Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre–bevacizumab era

Abstract

abbreviatioNs ARE = adverse radiation effect; GBM = glioblastoma multiforme; KPS = Karnofsky Performance Scale; MST = median survival time; OS = overall survival; PFS = progression-free survival; RPA = recursive partitioning analysis; RT = radiation therapy; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery. obJect After initial standard of care management of glioblastoma multiforme (GBM), relatively few proven options remain for patients with unresected progressive tumor. Numerous reports describe the value of radiosurgery, yet this modality appears to remain underutilized. The authors analyzed the outcomes of early adjuvant stereotactic radiosurgery (SRS) for unresected tumor or later salvage SRS for progressive GBM. Radiosurgery was performed as part of the multimodality management and was combined with other therapies. Patients continued to receive additional chemotherapy after SRS and prior to progression being documented. In this retrospective analysis, the authors evaluated factors that affected patient overall survival (OS) and progression-free survival. methods Between 1987 and 2008 the authors performed Gamma Knife SRS in 297 patients with histologically proven GBMs. All patients had received prior fractionated radiation therapy, and 66% had undergone one or more chemotherapy regimens. Ninety-six patients with deep-seated unresectable GBMs underwent biopsy only. Of those in whom excision had been possible, resection was considered to be gross total in 68 and subtotal in 133. The median patient age was 58 years (range 23-89 years) and the median tumor volume was 14 cm 3 (range 0.26-84.2 cm 3 ). The median prescription dose delivered to the imaging-defined tumor margin was 15 Gy (range 9-25 Gy). The median follow-up duration was 8.6 months (range 1.1-173 months). Cox regression models were used to analyze survival outcomes. Variables examined included age, residual versus recurrent tumor, prior chemotherapy, time to first recurrence, SRS dose, and gross tumor volume. results The median survival times after radiosurgery and after diagnosis were 9.03 and 18.1 months, respectively. The 1-year and 2-year OS after SRS were 37.9% and 16.7%, respectively. The 1-year and 2-year OS after diagnosis were 76.2% and 30.8%, respectively. Using multivariate analysis, factors associated with improved OS after diagnosis were younger age (< 60 years) at diagnosis (p < 0.0001), tumor volume < 14 cm 3 (p < 0.001), use of prior chemotherapy (p = 0.001), and radiosurgery at the time of recurrence (p < 0.0001). Multivariate analysis showed that younger age (p < 0.0001) and smaller tumor volume (< 14 cm 3 ) (p = 0.001) were significantly associated with increased OS after SRS. Adverse radiation effects were seen in 69 patients (23%). Fifty-eight patients (19.5%) underwent additional resection after SRS. The median survivals after diagnosis for recursive partitioning analysis Classes III, IV and V+VI were 31.6, 20.8, and 16.7 months, respectively. coNclusioNs In this analysis 30% of a heterogeneous cohort ...

Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience

“…52,54 Younger patients may have improved procedural tolerance, but they also have better glioblastoma prognosis, making it challenging to assess true GK treatment impact. However, age independently predicted improved post-GK survival on multivariable modeling, which suggests younger patients may be better candidates.…”

“…We performed sensitivity testing with various size cutoffs but were unable to identify a threshold for significantly poorer outcomes. Numerous reports 54–58 assert that SRS may be most suitable for small, focal, or nodular glioblastoma recurrences. Specifically, one large recent study found post-SRS OS to be significantly better for patients with <14 cm 3 of treatment volume.…”

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

“…Prior to the utilization of combination chemotherapy and radiosurgery, Niranjan et al [16] concluded that patients undergoing SRS had a mean 1- and 2-year OS of 37.9 and 16.7%, respectively. Currently, the treatment paradigm for primary high-grade malignant gliomas consists of maximal safe resection, followed by adjuvant chemoradiation with TMZ in able patients.…”

“…Furthermore, Hudes et al [15] did not report grade 3 toxicity or need for reoperation in their phase I dose-escalation study regarding persistent or recurrent GBM. In a retrospective review, Niranjan et al [16] suggested that combination SRS and bevacizumab may limit the potential toxicity associated with radiotherapy while enhancing its benefit.…”

“…More than 95% of patients, however, fail initial therapy [17]. At recurrence, treatment options for GBM are limited with a vast majority of recurrences occurring at the initial site of disease due to local or marginal failure [16]. Surgical resection is the current standard of care, with median survival time ranging from 3 to 13 months [7, 8, 18, 19].…”