BACKGROUND: Several studies have demonstrated that omitting the routine use of adjuvant whole-brain radiation therapy for patients with newly diagnosed brain metastases may be a reasonable first-line strategy. Retrospective evidence suggests that fractionated stereotactic radiotherapy (fSRT) may have a lower level of toxicity with equivalent efficacy in comparison with radiosurgery.
OBJECTIVE: To study the phase II efficacy of using a focally directed treatment strategy for symptomatic brain metastases by the use of fSRT with or without surgery and omitting the routine use of adjuvant whole-brain radiation therapy.
METHODS: We used a Fleming single-stage design of 40 patients. Patients were eligible if they presented with 1 to 3 newly diagnosed symptomatic brain metastases, Karnofsky performance scale (KPS) greater than 60, and histological confirmation of primary disease. Patients underwent fSRT with the use of a dose of 30 Gy in 5 intensity-modulated fractions as primary or adjuvant treatment after surgical resection. The primary end point was the proportion of patients who experienced neurological death. Secondary end points were overall survival, time to KPS <70, and progression-free survival.
RESULTS: Of 40 patients accrued, 39 were eligible for analysis. The proportion of patients dying of neurological causes was 13% (5 patients), which includes 3 patients with an unknown cause of death. Median overall survival, time to KPS <70, and progression-free survival were 16 (95% confidence interval, 9-23), 14 (95% confidence interval, 7-20), and 11 (95% confidence interval, 4-21) months, respectively.
CONCLUSION: A focally directed treatment strategy using fSRT with or without surgery appears to be an effective initial strategy. Based on the results of this phase II clinical trial, further study is warranted.
ABBREVIATIONS: CI, confidence interval
CTV, clinical target volume
fSRT, fractionated stereotactic radiotherapy
GTV, gross tumor volume
KPS, Karnofsky performance status
OS, overall survival
PFS, progression-free survival
PTV, planning target volume
RPA, recursive partition analysis
SRS, stereotactic radiosurgery
WBRT, whole-brain radiation therapy
*Department of Neurological Surgery, Ohio State University Medical Center, Columbus, Ohio;
‡Department of Radiation Oncology, Ohio State University Medical Center, Columbus, Ohio;
§Department of Neurological Surgery, Cleveland Clinic, Cleveland, Ohio;
‖Center for Biostatistics, Ohio State University Medical Center, Columbus, Ohio
Correspondence: Mario Ammirati, MD, MBA, Professor of Neurosurgery and Radiation Oncology, Department of Neurological Surgery, Ohio State University Medical Center, N1025 Doan Hall, 410 W 10th Ave, Columbus, OH 43210. E-mail: Mario.Ammirati@osumc.edu
Received June 30, 2013
Accepted February 10, 2014