Elsevier

The Lancet

Volume 363, Issue 9422, 22 May 2004, Pages 1665-1672
The Lancet

Articles
Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial

https://doi.org/10.1016/S0140-6736(04)16250-8Get rights and content

Summary

Background

Brain metastases occur in up to 40% of all patients with systemic cancer. We aimed to assess whether stereotactic radiosurgery provided any therapeutic benefit in a randomised multi-institutional trial directed by the Radiation Therapy Oncology Group (RTOG).

Methods

Patients with one to three newly diagnosed brain metastases were randomly allocated either whole brain radiation therapy (WBRT) or WBRT followed by stereotactic radiosurgery boost. Patients were stratified by number of metastases and status of extracranial disease. Primary outcome was survival; secondary outcomes were tumour response and local rates, overall intracranial recurrence rates, cause of death, and performance measurements.

Findings

From January, 1996, to June, 2001, we enrolled 333 patients from 55 participating RTOG institution—167 were assigned WBRT and stereotactic radiosurgery and 164 were allocated WBRT alone. Univariate analysis showed that there was a survival advantage in the WBRT and stereotactic radiosurgery group for patients with a single brain metastasis (median survival time 6·5 vs 4·9 months, p=0·0393). Patients in the stereotactic surgery group were more likely to have a stable or improved Karnofsky Performance Status (KPS) score at 6 months' follow-up than were patients allocated WBRT alone (43% vs 27%, respectively; p=0·03). By multivariate analysis, survival improved in patients with an RPA class 1 (p<0·0001) or a favourable histological status (p=0·0121).

Interpretation

WBRT and stereotactic boost treatment improved functional autonomy (KPS) for all patients and survival for patients with a single unresectable brain metastasis. WBRT and stereotactic radiosurgery should, therefore, be standard treatment for patients with a single unresectable brain metastasis and considered for patients with two or three brain metastases.

Introduction

Brain metastases occur in 20–40% of patients with systemic cancer;1 30–40% present with a single metastasis.2 Outlook for patients is poor with a median survival time of 1–2 months with corticosteroids,3 which can be extended to 6 months with whole brain radiation therapy (WBRT),4, 5 and some investigators6, 7 report that survival can be further lengthened when WBRT is preceded by surgical resection. Originally developed by the Swedish neurosurgeon Lars Leksell,8 radiosurgery is a technique that involves single treatment radiation precisely focused at intracranial targets. Radiosurgery is frequently used to treat brain metastases, sometimes preferred to surgery as a less invasive alternative. We report results of the first multi-institutional prospective randomised comparison of WBRT with or without stereotactic radiosurgery for patients with one to three brain metastases.

Section snippets

Participants

The study population included patients with confirmed systemic malignant disease. All patients were aged 18 years or older with no previous cranial radiation. Entry criteria included a contrast-enhanced MRI scan showing one to three brain metastases with a maximum diameter of 4 cm for the largest lesion and additional lesions not exceeding 3 cm in diameter.9 Metastases were deemed unresectable if they were located in deep grey matter or in eloquent cortex. Postoperative patients with either

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