In a secondary analysis utilizing the graded prognostic assessment—an improved diagnosis-specific index—patients with one to three brain metastases had no survival advantage when treated with whole-brain radiation therapy and stereotactic radiosurgery, compared with whole-brain radiotherapy alone, according to a study by Paul W. Sperduto, MD, of the Metro-Minnesota CCOP and Minneapolis Radiation Oncology, Minneapolis, and colleagues in the International Journal of Radiation Oncology Biology Physics.1 However, patients with a good prognosis (ie, graded prognostic assessment scores of 3.5–4.0) did have an overall survival advantage with the combined treatment modalities, regardless of the number of brain metastases.
Recently, newer evidence-based guidelines have been published for the management of brain metastases. These guidelines were based on the results of 36 randomized controlled clinical trials. The subject of one of these trials was the comparison of whole-brain radiotherapy with whole-brain radiotherapy plus stereotactic radiosurgery. Although the study results indicated a higher survival rate for patients with one metastatic tumor receiving the combination therapy, the results did not hold true for patients with two or more metastatic tumors.
With that in mind, Sperduto and colleagues decided to revisit the data from this trial to determine whether applying the graded prognostic assessment would result in data indicating a greater survival advantage in patients with two or more metastatic tumors.
The original study (Radiation Therapy Oncology Group [RTOG] 9508) analyzed 331 patients. Of the total number of patients, 252 were deemed evaluable via the graded prognostic assessment. Subgroups defined by graded prognostic assessment class and number of metastases were also compared for treatment effects.
Patients had a median age of 60 years (range, 19–90 years), one to three brain metastases, and no previous cranial radiation therapy. The majority of patients in the study had lung cancer. Other types included gastrointestinal and renal cancers and melanoma.
Findings in Better-Prognosis Patients
Compared with data from the original analysis, patients with graded prognostic assessment scores of 3.5 to 4.0 had better overall survival rates when treated with the combination therapy vs whole-brain radiotherapy alone (median survival of 21.0 months and 2-year overall survival rate of 43% vs median survival of 10.3 months and 2-year overall survival rate of 21%, P = .05).
The investigators noted that most patients (35 of 47) with graded prognostic assessment scores of 3.5 to 4.0 had a single metastasis. However, these patients showed better survival rates regardless of the number of metastases. Among those with two or three metastases who had graded prognostic assessment scores of 3.5 to 4.0, the median survival time for the two arms was 14.1 and 8.9 months, respectively, corresponding to a 5.2-month survival benefit for those patients receiving the combination therapy.
The results of this secondary analysis suggest that the combination of whole-brain radiation therapy and stereotactic radiosurgery may continue to play a role in patients with one or more brain metastases, especially those with a better prognosis. However, this benefit did not extend to patients with lower-graded prognostic assessment scores.
The investigators concluded, “Prospective validation of this survival benefit for patients with graded prognostic assessment scores of 3.5 to 4.0 and one to three brain metastases when treated with whole-brain radiation therapy and stereotactic radiosurgery is warranted.” ■
Disclosure: Senior author Minesh Mehta, MD, is a consultant with Abbott, BMS, Elekta, Merck, Novocure, Novelos, Phillips, and Roche; has stock options with Accuray and Pharmacyclics; has a research grant from Novocure; and is on the Board of Directors of Pharmacyclics. The other authors reported no conflict of interest.
1. Sperduto PW, Shanley R, Luo X, et al: Secondary analysis of RTOG 9508, a phase 3 randomized trial of whole-brain radiation therapy versus WBRT plus stereotactic radiosurgery in patients with 1-3 brain metastases; poststratified by the graded prognostic assessment (GPA). Int J Radiat Oncol Biol Phys 90:526-531, 2014.