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Patients with recurrent high-grade gliomas who were treated with hypofractionated stereotactic radiation therapy (H-SRT) had survival rates that were comparable to the "best-reported results in the literature" for systemic agents, such as bevacizumab, according to the authors, led by Shannon Fogh, MD, from Thomas Jefferson University in Philadelphia, Pennsylvania.
In this study of 147 recurrent patients treated with H-SRT (median dose, 35.0 Gy in 3.5 Gy fractions), there was a median survival time of 11 months after the salvage H-SRT therapy, the authors report in their study, published online May 17 in the Journal of Clinical Oncology.
H-SRT also had "an improved toxicity profile and decreased cost," compared with systemic maintenance therapy with bevacizumab, which is approved by the US Food and Drug Administration for the treatment of recurrent glioblastomas, Dr. Fogh and coauthors point out.
They emphasize that their study was observational and that any comparisons between H-SRT and other therapies were based on published literature.
Nevertheless, the survival, toxicity, and cost data led the authors to conclude that H-SRT should be evaluated in future studies as the "standard salvage therapy for previously irradiated high-grade gliomas."
Dr. Fogh admitted that many clinicians might find this approach unpalatable.
A concept of brain re-irradiation . . . seems dangerous and prohibitive.
"In the eyes of many patients, neuro-oncologists, and even radiation oncologists who do not treat a large volume of brain patients, the concept of brain re-irradiation, particularly with such large doses given to the area previously treated with radiation therapy, seems dangerous and prohibitive," she told Medscape Oncology.
However, this study, which is the largest series to date on this approach, might change a few minds, suggest the authors.
No standard of care exists in this setting, said Dr. Fogh, but bevacizumab is "commonly given."
"It is important to realize, however, that the population treated with bevacizumab and H-SRT is not always the same; larger and more infiltrative tumors are more likely to get the drug, and those more compact and less infiltrative, the H-SRT. Those 2 approaches to salvage can be looked at as complementary, at least in a proportion of patients," she explained.
Study Rationale and Design
H-SRT seems like a good approach in patients with recurrent gliomas because of "their grim prognosis," say the study authors.
"It is imperative to consider quality of life when evaluating treatment options," they note. Thus, the shorter treatment schedule with hypofractionation (2 weeks vs 3 or 4 weeks) is a plus, they suggest. Also, H-SRT allows for precise treatment and a possible reduction in toxicity.
The authors note that this approach makes economic sense — in a couple of ways.
"Although the cost of re-irradiation is already a fraction of the cost of systemic maintenance therapy, examination of Medicare reimbursement rates for H-SRT demonstrated a cost savings of 20% (i.e., $4498.07 compared with $5705.47) with 10 treatments, compared with the 18 treatments of a typical fractionation schedule," they explain.
With these thoughts in mind, the investigators designed the study.
All the study participants were diagnosed with recurrence on the basis of radiographically identified tumor progression. Clinical judgment was used to define eligibility for H-SRT, the authors explain.
At Thomas Jefferson University, patients are generally eligible for treatment if the tumor volume is within a 10 × 10 cm field, the Karnofsky performance score (KPS) is 60 or higher, and the patients are able to lie flat for treatment planning and delivery.
The 147 patients had either grade 3 astrocytoma (n = 42; 29%) or glioblastoma multiforme (n = 105; 71%), and all had clinical and radiographic evidence of tumor progression.
All patients were followed with magnetic resonance imaging scans, which were obtained 6 to 8 weeks after H-SRT and at 3-month intervals from then on.
All patients had received initial postoperative conformal fractionated radiotherapy to a median dose of 60 Gy in daily 2 Gy fractions.
In all, 110 patients received chemotherapy at the time of initial diagnosis, and 48 received chemotherapy at recurrence with H-SRT.
All patients underwent neurosurgical intervention at initial diagnosis, and 84 patients (60%) had resection at recurrence before salvage H-SRT.
"Overall, the groups with resection plus H-SRT and with H-SRT alone were balanced with respect to initial treatment regimen, time to progression, dose of re-irradiation, and presence of multiple lesions," summarize the authors.
Study Results
Using H-SRT in 3.5 Gy fractions to 35.0 Gy, the investigators reported no grade 3 toxicities or reoperation secondary to toxicity in the patients. This provides "additional support that this dose and fraction size is well tolerated," they write.
There was also no survival benefit when chemotherapy was added to the radiation, report the authors.
"Although it was not a randomized trial, our study did not demonstrate a survival advantage in combining chemotherapy with H-SRT at recurrence compared with patients who received H-SRT alone," they write.
Despite the variability of the participants, their initial treatments, and salvage therapies, the authors observe that "all groups of patients benefited similarly from H-SRT, achieving a uniform" median survival time of 11 months.
The researchers have disclosed no relevant financial relationships.
J Clin Oncol. Published online May 17, 2010. Abstract