The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases.
OBJECTIVE
To better analyze how whole-brain radiotherapy (WBXRT) affects long-term tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for brain metastases, we studied these outcomes in patients who had survived at least 1 year from SRS.


METHODS
We evaluated the results of gamma knife radiosurgery for 160 brain metastases in 110 patients who were followed for a median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a solitary brain metastasis and 28 patients had multiple metastases. Seventy patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas 40 patients (44 lesions) initially received radiosurgery alone. Median treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy).


RESULTS
At 1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%, 68.6% +/- 8.7%, and 68.6% +/- 8.7% with SRS alone compared with 93.1% +/- 2.4%, 87.7% +/- 4.9%, and 65.7% +/- 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found that WBXRT improved local control in patient subsets tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/- 9.4%, and 74.5% +/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/- 8.7%, and 61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend for improved distal intracranial control with WBXRT for only nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in 2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or in any subsets.


CONCLUSIONS
In this retrospective study of 1-year survivors of SRS for brain metastases, the addition of concurrent WBXRT to SRS was associated with an improved local control rate in patient subsets with tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and specifically lung cancer metastases. A trend was noted for improved distal intracranial control for patients having nonradioresistant tumors. Distant intracranial relapse >1 year posttreatment is a significant problem with or without initial WBXRT.
Varlotto
John M
JM
Department of Radiation Oncology, University of Pittsburgh Medical Center and the Center for Image-Guided Neurosurgery, Pittsburgh, PA, USA. jvarlott@bidmc.harvard.edu
Flickinger
John C
JC
Niranjan
Ajay
A
Bhatnagar
Ajay
A
Kondziolka
Douglas
D
Lunsford
L Dade
LD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000379:methods* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016634:Radiosurgery / Q000009:adverse effects / Q000401:mortality; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D017741:Survivors