Cancer Treatment Today

Lay Summary: We overview treatment options for brain metastases.

Surgical resection should be considered in patients with single brain metastasis in an accessible location, especially when the size is large, the mass effect is considerable and an obstructive hydrocephalus is present. Surgery is recommended when the systemic disease is absent/controlled and the Karnofsky Performance score is 70 or more (level A recommendation). When the combined resection of a solitary brain metastasis and a non-small cell lung carcinoma (stage I and II) is feasible, surgery for the brain lesion should come first, with a maximum delay between the two surgeries not exceeding 3 weeks. Patients with disseminated but controllable systemic disease (i.e. bone metastases from breast cancer) or with a radioresistant primary tumor (melanoma, renal cell carcinoma, and colon cancer) may benefit from surgery. Surgery at recurrence is useful in selected patients.

Stereotactic radiosurgery (SRS) should be considered in patients with metastases of a diameter of <3–3.5 cm and/or located in eloquent cortical areas, basal ganglia, brain stem or with comorbidities precluding surgery. Gamma-knife or linear accelerator (Linac) are equally effective. SRS may be effective at recurrence after prior radiation treatment.

The role of adjuvant whole-brain radiotherapy (WBRT) after surgery or radiosurgery remains to be clarified. In case of absent/controlled systemic disease and Karnofsky Performance score of 70 or more, one can either withhold initial WBRT if close follow-up with MRI (every 3 to 4 months) is performed or deliver early WBRT with fractions of 1.8–2 Gy to a total dose of 40–55 Gy to avoid late neurotoxicity. Whole-brain radiotherapy alone is the therapy of choice for patients with active systemic disease and/or poor performance status and should employ hypofractionated regimens such as 30 Gy in 10 fractions or 20 Gy in five fractions. For elderly patients with poor performance status WBRT can be withheld and supportive care only employed .

In patients with up to three brain metastases, good performance status (KPS of 70 or more) and controlled systemic disease, SRS is an alternative to WBRT (level B recommendation), whilst surgical resection is an option when the lesions are in an accessible location (level C recommendation). In patients with more than three brain metastases WBRT with hypofractionated regimens is the treatment of choice (level B recommendation). In bedridden patients it should be considered to withhold active radiation treatment and restrict therapy to supportive care.

There appears to not be a role for IMRT since it is neither a good therapy for overall brain like WBRT not specific enought for the tumor alone, like radiosurgery.

The Role of Chemotherapy

Chemotherapy may be the initial treatment for patients with brain metastases from chemosensitive tumors, like small cell lung cancers, lymphomas, germ cell tumors and breast cancers, especially for chemonaive patients or if an effective chemotherapy schedule for the primary is still available. Radiation therapy, with or without chemotherapy, is still the treatment of choice for patients needing a palliation of neurological symptoms

In two phase II trials of temozolomide in heavily pretreated patients with various solid tumor brain metastases, temozolomide was safe and generally well tolerated and showed clinical activity, with three partial responses and 19 disease stabilizations. Results of a third randomized phase II trial of concurrent administration of temozolomide and radiation therapy followed by adjuvant temozolomide therapy compared with radiation alone showed a higher rate of complete and partial responses (objective response of 96% v 67%) and significantly more complete responses (38% v 33%, P =.017), primarily in patients with newly diagnosed brain and lung metastases.

While Avastin does penetrate the blood brain barrier, it’s use specifically to treat brain metastasis is largely unexplored. A 2010 Cochrane panel considered Avastin and did not recommend it. A recent study presented at the ASCO Annual Meeting investigated the use of carboplatin and bevacizumab (Avastin) in progressive brain metastases (including HER2-positive and HER2-negative patients), demonstrating a very promising response rate of 63% in the central nervous system. 3 This remains something that needs to be confirmed.

In terms of surveillance, both NCCN and ACR recommend MRI imaging every three months for one year and no systemic surveillance imaging.

Mintz AP, Perry J, Laperriere N, Cairncross G, Chambers A, Spithoff K, Neuro-oncology Disease Site Group. Management of single brain metastases: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2006 Aug 15. 26 p. (Evidence-based series; no. 9-1). [29 references]

Soffietti R, Cornu P, Delattre JY, Grant R, Graus F, Grisold W, Heimans J, Hildebrand J, Hoskin P, Kalljo M, Krauseneck P, Marosi C, Siegal T, Vecht C. EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. Eur J Neurol 2006 Jul;13(7):674-81. [44 references]

Abrey LE, Christodoulou C. Temozolomide for treating brain metastases.Semin Oncol. 2001 Aug;28(4 Suppl 13):34-42.