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Influence of Whole-Brain Radiotherapy on Remission of Brain Metastases

Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany

To the Editor:

Schwab et al¹ 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)^2,3 or 10% of patients (Europe).⁴ 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).^5,6 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.⁷ 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 cm³ versus, for example, 0.6 cm³ if the scans were performed within 14 days; P < .05).⁸ 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.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Schwab R, Pinter F, Moldavy J, et al: Amplification and mutation of the epidermal growth factor receptor in metastatic lung cancer with remission from gefitinib. J Clin Oncol 23:7736-7738, 2005[Free Full Text]

2. Chiu CH, Tsai CM, Chen YM, et al: Gefitinib is active in patients with brain metastases from non-small cell lung cancer and response is related to skin toxicity. Lung Cancer 47:129-138, 2005[CrossRef][Medline]

3. Hotta K, Kiura K, Ueoka H, et al: Effect of gefitinib ('Iressa', ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer. Lung Cancer 46:255-261, 2004[CrossRef][Medline]

4. Ceresoli GL, Cappuzzo F, Gregorc V, et al: Gefitinib in patients with brain metastases from non-small-cell lung cancer: A prospective trial. Ann Oncol 15:1042-1047, 2004[Abstract/Free Full Text]

5. Antoniou D, Kyprianou K, Stathopoulos GP, et al: Response to radiotherapy in brain metastases and survival of patients with non-small cell lung cancer. Oncol Rep 14:733-736, 2005[Medline]

6. Nieder C, Niewald M, Hagen T: Brain metastases in bronchial and breast carcinoma: Differences in metastatic behavior and prognosis (German). Radiologe 35:816-821, 1995[Medline]

7. Nieder C, Berberich W, Schnabel K: Tumor-related prognostic factors for remission of brain metastases after radiotherapy. Int J Radiat Oncol Biol Phys 39:25-30, 1997[CrossRef][Medline]

8. Nieder C, Andratschke NH, Grosu AL, et al: Tumor volume reduction from 3 Gy-fractions in brain metastases and implications for combined treatment. Int J Radiat Oncol Biol Phys 63:S271, 2005 (abstr 2070)

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nieder, C. Search for Related Content PubMed PubMed Citation Articles by Nieder, C. Social Bookmarking                            What's this?