ASCO has endorsed the recommendations put forth in a new guideline, developed by the American Society for Radiation Oncology (ASTRO), on the use of radiation therapy for the management of brain metastases.1,2 Although ASTRO—in conjunction with ASCO and the Society for Neuro-Oncology (SNO)—recently spearheaded a joint practice guideline on the treatment of brain metastases, this new publication provides more detailed guidance about various aspects of radiation care, such as indications for surgical resection and the rapidly evolving literature on the use of targeted chemotherapy and immunotherapy for brain metastases.3
David Schiff, MD
“Complementary to the joint guidelines, the ASTRO project went into much greater depth on issues of radiation and radiosurgery dose, fractionation schemes, and the risk of radiation necrosis. It also allowed ASTRO to select a task force principally composed of radiation oncologists to maximize expertise to address these topics,” said David Schiff, MD, of the University of Virginia Medical Center and Co-Chair of the ASCO expert panel that reviewed the ASTRO guideline. “Several members of the ASTRO task force were members of the ASCO/SNO/ASTRO expert panel. This overlap between the two groups helped ensure harmonious recommendations. That both groups were performing essentially simultaneous systematic literature reviews was an additional benefit. So, this really is a win-win.”
Refining the Treatment Roadmap
Rapid advances in brain metastases management over the past 20 years have expanded oncologists’ armamentarium, but consequently, decision-making for patients has become more complicated. For instance, rather than immediately referring patients to radiation therapy—which was standard practice 2 decades ago—radiosurgery or resection or even systemic therapy must now be considered as first steps, depending on the patient’s case.
As a result, there is a need for consensus among expert subspecialists in metastatic brain disease, who can give oncologists a general roadmap on patient management and help them understand which types of therapies or referrals should be considered and when.
“ASTRO took a deeper dive into this topic because the details really do matter,” said Expert Panel Co-Chair Michael A. Vogelbaum, MD, PhD, of Moffitt Cancer Center. “Within the field of radiation oncology, you have different techniques for delivering radiation to the brain, which include conventional fractionated methods, like whole-brain radiotherapy, as opposed to single-fraction or multiple-fraction stereotactic radiosurgery. So, ASTRO is trying to make recommendations regarding the specific techniques used in specific situations.”
Michael A. Vogelbaum, MD, PhD
The ASTRO guideline underscores the benefits of localized, single—or, for larger lesions, hypofractionated—radiation over whole-brain radiotherapy for both local control and reducing neurotoxicity. This is true in the setting of both intact and resected brain metastases.
ASTRO’s recommendations also reflect advances to improve the safety of whole-brain radiotherapy by incorporating hippocampal avoidance when feasible, which can help spare memory and other cognitive functions, as well as the use of memantine for similar purposes.
Dr. Schiff noted that because the recommendations are based on already published clinical trials, they aren’t necessarily practice-changing, although they are certainly practice-relevant.4-8
“What these recommendations do is bring together in one place a comprehensive, carefully vetted set of guidelines that physicians from all the disciplines involved in treating patients with solid tumors can rely upon to chart a treatment path for an individual patient with this type of cancer,” he said.
Coming to a Consensus
Although the broader joint guideline and the detailed ASTRO guideline were developed somewhat in tandem and by several of the same individuals, there was not total agreement between the respective guideline committees.
For instance, it is currently unknown whether it is more advantageous to give adjuvant radiosurgery before or after a planned surgery for brain metastases, with some data suggesting preoperative radiosurgery may decrease the risk of nodular meningeal and local failure.9 The ASCO/SNO/ASTRO panel believed current data could not sufficiently address this issue, whereas the new ASTRO guideline offered conditional support for preoperative surgical resection as a potential alternative to postoperative resection. However, forthcoming data from a phase III clinical trial from NRG Oncology, which should be open by the end of the year, will be prospectively asking this question and should provide a more definitive response for guidelines in the future.
Despite such areas of slight divergence, the joint guideline and the ASTRO guideline are largely consistent and complementary.
“We thought ASTRO’s data analyses were well performed and that the conclusions and interpretations were reasonable. And we think these two guidelines will be very useful to practitioners,” Dr. Vogelbaum said. “For the ASCO audience specifically, this guideline is a reminder that radiation remains a highly active and useful modality for patients with brain metastases, particularly with respect to use of focused or conformal modalities, such as radiosurgery.”
1. Schiff D, Messersmith H, Brastiano PK, et al: Radiation therapy for brain metastases: ASCO guideline endorsement of ASTRO guideline. J Clin Oncol 40:2271-2276, 2022.
2. Gondi V, Bauman G, Bradfield L, et al: Radiation therapy for brain metastases: An ASTRO clinical practice guideline. Pract Radiat Oncol 12:265-282, 2022.
3. Vogelbaum MA, Brown PD, Messersmith H, et al: Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J Clin Oncol 40:492-516, 2022.
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 29:134-141, 2011.
5. 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 10:1037-1044, 2009.
6. Brown PD, Jaeckle K, Ballman KV, et al: Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases a randomized clinical trial. JAMA 316:401-409, 2016.
7. 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 295:2483-2491, 2006.
8. Hong AM, Fogarty GB, Dolven-Jacobsen K, et al: Adjuvant whole-brain radiation therapy compared with observation after local treatment of melanoma brain metastases: A multicenter, randomized phase III trial. J Clin Oncol 37:3132-3141, 2019.
9. Prabhu RS, Dhakal R, Vaslow ZK, et al: Preoperative radiosurgery for resected brain metastases: The PROPS-BM multicenter cohort study. Int J Radiat Oncol Biol Phys 111:764-772, 2021.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, May 19, 2022. All rights reserved.