As therapies for systemic cancers improve and patients survive longer, the incidence of brain metastases is increasing. Current therapies include varying combinations of surgery, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and in a small subset of patients, systemic therapy. The use of SRS to treat brain metastases has been one of the major successes in neuro-oncology, providing effective local control of even radioresistant brain metastases. Several studies have compared the outcomes of patients with a limited number of brain metastases treated with surgery or radiosurgery alone, with the addition of WBRT.1–4 These studies, which usually included heterogeneous tumor histologies and varying extent of systemic disease, have generally shown improved intracranial control with the addition of WBRT, but no significant improvement in overall survival, and an increased risk of neurocognitive impairment.
Most recently, at the 2015 American Society of Clinical Oncology annual meeting, Brown et al presented the results of the North Central Cancer Treatment Group (NCCTG) (Alliance) N0574 study, a phase III trial comparing SRS+WBRT to SRS alone in patients with 1–3 brain metastases.5 This study for the first time used decline in cognitive function at 3 months as the primary endpoint. Cognitive deterioration at 3 months was significantly more frequent in the WBRT+SRS group than the SRS alone group, involving especially immediate recall, memory, and verbal fluency. As with prior studies, intracranial disease control was improved with WBRT but there was no improvement in overall survival.
This study adds to the growing body of literature addressing this issue. Nonetheless, there is currently no consensus on the value of WBRT and the optimal management of patients with brain metastases remains a dilemma that confronts clinicians looking after these patients. In this issue of Neuro-Oncology, Dr Arjun Sahgal from the University of Toronto discusses the data in favor of omitting WBRT from patients with newly-diagnosed brain metastases, while Dr. Minesh Mehta from the University of Maryland provides the counter-argument of including WBRT for these patients.
References
- 1. Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998;280(17):1485–1489. [DOI] [PubMed] [Google Scholar]
- 2. Aoyama H, Shirato H, Tago M, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295(21):2483–2491. [DOI] [PubMed] [Google Scholar]
- 3. Chang EL, Wefel JS, Hess KR, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009;10(11):1037–1044. [DOI] [PubMed] [Google Scholar]
- 4. Kocher M, Soffietti R, Abacioglu U, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952–26001 study. J Clin Oncol. 2010;29(2):134–141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Brown PD, Asher AL, Ballman KV, et al. NCCTG N0574 (Alliance): A phase III randomized trial of whole brain radiation therapy (WBRT) in addition to radiosurgery (SRS) in patienst with 1–3 brain metastases. In: Proc American Society of Clinical Oncology2015 Abstract LBA#4. [Google Scholar]