Influence of Whole-Brain Radiotherapy on Remission of Brain Metastases

Abstract

TO THE EDITOR: Schwab et al reported an intriguing therapeutic benefit in a female nonsmoker with multiple brain metastases from lung adenocarcinoma treated with gefitinib 250 mg daily 3 years after thoracic surgery and adjuvant chemotherapy. Gefitinib treatment was initiated 6 weeks after whole-brain radiotherapy (WBRT) with 36 Gy because of a lack of objective response on magnetic resonance imaging and worsening clinical symptoms. After 8 weeks on gefitinib, a major response was seen. Eventually the patient achieved a complete remission. The effects of gefitinib on brain metastases from non–small-cell lung cancer have been reported by several authors, suggesting that objective responses occur in 33% to 43% of patients (Taiwan, Japan) or 10% of patients (Europe). All of these series included less than 80 patients. In comparison, WBRT with 30 Gy to 40 Gy for brain metastases from non–small-cell lung cancer results in objective responses in 38% to 45% of patients (Europe). In the absence of randomized trials comparing WBRT to small receptor tyrosine kinase inhibitors, WBRT should still be considered the first-line treatment of choice for patients with multiple brain metastases. Whether gefitinib has a role in salvage treatment for patients progressing after WBRT should be studied prospectively in patients ineligible for local treatment such as radiosurgery. An important question is when to evaluate remission after WBRT. A previous series suggested that 43% of brain metastases continued to shrink between the first imaging, performed within 2 weeks after WBRT, and the second imaging after 3 months. We have recently confirmed that the best imaging result was evident on scans obtained between 66 days and 120 days after WBRT (median volume reduction 1.5 cm versus, for example, 0.6 cm if the scans were performed within 14 days; P .05). It is therefore important to notice that imaging after 6 weeks does not necessarily reflect the final outcome. In addition, transient demyelination might develop a few weeks after WBRT, leading to clinical symptoms that respond to corticosteroids. These symptoms do not indicate treatment failure.