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

• Published in: The Lancet (British edition) Vol. 363; no. 9422; pp. 1665 - 1672
• Main Authors: Andrews, David W, Scott, Charles B, Sperduto, Paul W, Flanders, Adam E, Gaspar, Laurie E, Schell, Michael C, Werner-Wasik, Maria, Demas, William, Ryu, Janice, Bahary, Jean-Paul, Souhami, Luis, Rotman, Marvin, Mehta, Minesh P, Curran, Walter J
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 22.05.2004; Lancet; Elsevier Limited
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Brain; Brain Neoplasms - mortality; Brain Neoplasms - radiotherapy; Brain Neoplasms - secondary; Brain Neoplasms - surgery; Cancer; Combined Modality Therapy; Female; General aspects; Humans; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neurology; Prognosis; Radiation; Radiation Injuries; Radiation therapy; Radiosurgery - adverse effects; Radiotherapy Dosage; Surgery; Survival; Survival Rate; Therapy; Tumors; Tumors of the nervous system. Phacomatoses; Phase III trial; Human; Nervous system diseases; Brain cancer; Radiosurgery; Radiation; Stereotaxia; Malignant tumor; Cerebral disorder; Medicine; Treatment; Surgery; Central nervous system disease; Clinical trial
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(04)16250-8

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). 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. 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). 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.