Commentary (Bashir): Management of Brain Metastases

The article by Wen and Loeffler provides a comprehensive, timely, well-written review of the management of cerebral metastases. Both older studies and more recent reports on advances in the surgical, radiotherapeutic, and chemotherapeutic approaches to the treatment of cerebral metastases are covered. Consensus pathways are proposed for the management of patients with cerebral metastases.

Cerebral metastases are an increasingly common problem in the management of cancer patients, for several reasons.[1-3] Better chemotherapeutic agents, radiation, and surgical interventions are achieving good control of systemic cancer.[4] Cerebral metastases are seen as the primary site of disease treatment failure or as a manifestation of poorly controlled disease.[4] The use of head computed tomography (CT) and magnetic resonance imaging (MRI) has also increased the recognition of this problem; many of these metastases were not detected in the past, specifically since postmortem examinations were not performed routinely.[3,5]

External-Beam Radiation Therapy

There is consensus that external-beam radiation is effective in controlling cerebral metastases.[6] Wen and Loeffler elegantly review published studies of this treatment modality. Variations in total radiation doses and fractionation schemes, the inclusion of different types of tumors, and the status of the primary disease site make it difficult to compare many of these studies.[4,7] Studies that include more radioresistant primaries, for example, cannot be compared to trials that include radiosensitive tumors.[4,7,8]

One obvious message of this review is that future studies should be prospective and randomized, and should compare patients of similar age and functional status with similar tumor histology, number of cerebral metastases, and status of the primary disease.[9] All of these factors can be important prognostic indicators, regardless of the radiation dose or fractionation scheme used.

Conventional Surgery, Stereotactic Radiosurgery, and Chemotherapy

Recently introduced diagnostic tools, such as CT/MRI scanning, have made it possible to attempt early surgical resection of a single, isolated cerebral metastasis.[10-12] This intervention has resulted in longer life expectancy.[12]

The addition of postoperative radiation therapy has led to less local disease recurrence and has improved patients’ quality of life.[13,14] It has not, however, improved survival.[14] Again, it is difficult to compare studies because many include a heterogeneous mix of tumors, with their varied degree of responsiveness to radiation.[12-14] Definitive answers to questions about the role of radiation following tumor resection will also require prospective, randomized trials that include patients of comparable age and functional status who have similar tumor histology and status of systemic disease.

Stereotactic radiosurgery is a powerful tool for treating cerebral metastases. It can take the form of a high-energy x-ray produced by linear accelerators, gamma-radiation delivered via the gamma knife, or heavy-particle proton-beam radiation.[15-17]

The roles of radiosurgery in treating cerebral metastases in difficult-to-reach areas, as well as resectable areas, are currently being defined.[17] Early indicators suggest that radiosurgery may be a cost-effective way of treating cerebral metastases.[18] Adequate, prospective, randomized clinical trials (as described earlier) comparing stereotactic radiosurgery to surgical intervention are needed. At present, radiosurgery is a good option for patients with metastases in hard-to-reach areas or those with small metastases from radioresistant primaries, such as melanoma.

The role of chemotherapy in the treatment of cerebral metastases is limited to chemosensitive tumors, such as small-cell carcinoma of the lung, choriocarcinoma, or germ cell tumors.[19] Many cerebral metastases, such as those from non-small-cell lung cancer and melanoma, are not chemosensitive and will not respond to chemotherapy.[19]

Leptomeningeal Metastases With Parenchymal Metastases

One area that this review does not address is the management of concomitant leptomeningeal metastases with parenchymal metastases. This is important for certain types of metastases, such as those from small-cell carcinoma of the lung, systemic lymphoma, or germinoma.[20] Staging with cerebrospinal fluid cytology and MRI scanning of the spinal cord are legitimate concerns in managing these tumors.[20]

Summary

Overall, this review is comprehensive, informative, and timely. It certainly raises issues about the integration of external-beam radiation, conventional surgery, and radiosurgery into the treatment of cerebral metastases. The article also emphasizes the need for more prospective, randomized trials to define the effectiveness of these treatments. Finally, it stresses that stratification of patients according to age, functional status, status of the primary disease, and tumor histology is crucial to making these clinical studies more comparable.

References:

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2. Posner JB: Management of brain metastases. Rev Neurol 148:477-487, 1992.

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15. Flickinger JC, Kondziolka D, Lunsford LD, et al: A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis. Int J Radiat Oncol Biol Phys 28:797-802, 1994.

16. Alexander E III, Moriarty TM, Davis RB, et al: Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases. J Natl Cancer Inst 87:34-49, 1995.

17. Auchter RM, Lamond JP, Alexander E III, et al: A multi-institutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis. Int J Radiat Oncol Biol Phys 35:27-35, 1996.

18. Mehta M, Noyes W, Craig B, et al: A cost-effectiveness and cost-utility analysis of radiosurgery vs resection for single-brain metastases. Int J Radiat Oncol Biol Phys 39:445-454, 1997.

19. Posner JB: Intracranial metastases, in Posner JB (ed): Neurologic Complications of Cancer, pp 77-110. Philadelphia, FA Davis, 1995.

20. Posner JB: Leptomeningeal metastases, in Posner JB (ed): Neurologic Complications of Cancer, pp 143-171. Philadelphia, FA Davis, 1995.