Benefits of Stereotactic Brain Radiosurgery Demonstrated in Phase III Trial

stereotactic brain radiosurgery: stereotactic brain radiosurgeryBOSTON—Metastatic brain cancer patients respond more favorably to radiosurgery of the brain cavity than to whole-brain radiation therapy (WBRT) without forfeiting longer survival, according to findings from a multi-institutional phase III clinical trial (Radiat Oncol 2016;96;2 Supplement:S2). Fewer cognitive symptoms and better patient-reported quality of life were among the trial's findings, presented at the 58th Annual Meeting of the American Society for Radiation Oncology. More selective radiosurgery was just as effective as whole-brain radiation in killing residual cancer cells, investigators found. Conducted at cancer centers across the U.S. and Canada, 194 patients were involved with an average age of 61 years, each with 1-4 brain metastases. They were randomized to receive either stereotactic radiosurgery (SRS) or WBRT after surgical resection of one lesion. Among the patients, 77 percent had a single brain metastasis, with lung tumors the primary site in 59 percent. Both arms of the study were balanced for baseline patient and tumor characteristics. Primary outcomes included overall survival (OS) and cognitive deterioration free survival (CDFS), defined as a decline greater than one standard deviation from baseline in any of six cognitive tests. Major secondary endpoints included local control of the surgical bed, time to intracranial failure, and quality of life (QOL). Researchers computed Hazard Ratios to compare outcomes between treatment arms. Study Results At a median of up of 15.6 months, there was no statistically significant difference in OS rates between treatment groups, with a median OS of 11.5 months following SRS and 11.8 months following WBRT. SRS patients experienced significantly longer survival without cognitive decline, with a median CDFS of 3.2 months for SRS and 2.8 months for WBRT. The cognitive impact of WBRT persisted at 6 months following treatment; the rate at 6 months was 85.7 percent after WBRT versus 53.8 percent after SRS. A greater percentage of WBRT patients experienced worse immediate recall, memory, and attention compared to SRS-treated patients. Moreover, WBRT did provide higher overall intracranial tumor control. Rates at 6 and 12 months were 90.0 percent and 78.6 percent with WBRT versus 74.0 percent and 54.7 percent with SRS. There was also no clinically meaningful difference in median surgical bed relapse-free survival between treatment arms, although long term follow-up showed better control with WBRT (7.7 months vs. 7.5 months). Patients treated with SRS experienced better quality of life than those who received WBRT. At 3 months following treatment, declines in QOL and physical well-being were significantly smaller after SRS than WBRT (mean QOL change from baseline: -1.5 versus -7.0; mean well-being change from baseline -6.4 versus -20.2). At 6 months, physical well-being (decline of 3.2 vs. 15.1) remained significantly better for SRS patients. “This trial confirms radiosurgery to the surgical cavity is a viable treatment and should be one of the standards of care after resection of brain metastases,” said lead author Paul Brown, MD, a radiation oncologist at Mayo Clinic in Rochester, Minn. “We found no difference in survival whether a patient receives postoperative radiosurgery or whole-brain radiotherapy; however, radiosurgery avoids the cognitive damage caused by whole-brain radiotherapy and other unpleasant side effects, such as hair loss, fatigue, and skin redness.” Recovery after radiosurgery is typically shorter than with WBRT, so patients can restart systemic therapies such as chemotherapy sooner, he added. Although postoperative WBRT significantly reduces tumor recurrence in the brain and is the current standard of care for patients following resection, the treatment can negatively impact a patient's cognitive function and quality of life. SRS targets escalated doses of radiation to the tumor with extreme precision; the advanced technique can eliminate cancerous cells in a single or very small number of sessions while limiting the impact on surrounding tissue. “Stereotactic radiosurgery to the surgical cavity is widely used, despite the lack of clinical trials to substantiate its effectiveness,” said Brown. “Our results confirm that radiosurgery to the surgical cavity is a viable treatment option to improve local control with less impact on cognitive function and quality of life compared to WBRT,” he continued. “There is no significant difference in survival whether a patient receives postoperative radiosurgery or WBRT, and radiosurgery avoids the well-known toxicities of WBRT. Furthermore, due to less time commitment and a quicker recovery after SRS, patients can restart systemic therapies more rapidly. Radiosurgery to the surgical cavity after resection of brain metastases should be considered a standard of care and a less toxic alternative than the historic standard of care WBRT.” Implications for Practice Arjun Sahgal, BSc, MD, FRCPC, Associate Professor and Chief of Radiation Oncology and Surgery at the University of Toronto Sunnybrook Health Sciences Centre, said the data are persuasive. “This highly important trial provides level 1 evidence that SRS alone results in better outcomes for patients with respect to neurocognition and quality of life, and these benefits persist even at 6 months. Importantly, this is despite worse overall brain control with SRS alone,” he told Oncology Times. “The data are consistent with what has been found in multiple randomized trials in patients with intact metastases treated with SRS alone or SRS, with WBRT and, therefore, this shows that the results in the trial can be considered robust.” Quality of life and neurocognition are highly important outcomes for patients with brain metastases although survival is generally short, he emphasized. “The patients are palliative, and we should provide a treatment option that maximizes the ability for patients to function best in their daily activities in both the short and longer term,” Sahgal explained. “Should relapse occur there are always options for salvage that include WBRT, further surgery, SRS, and now systemic agents that cross the blood-brain barrier and can yield control of brain metastases. “In the modern era of managing brain metastases with increasing therapeutic options, we should consider SRS for postoperative surgical cavities as a treatment option offered to our patients,” he added. “There is need to better understand the relapse patterns observed in this study with a breakdown of local control, distant brain control, and leptomeningeal failure rates.” The latter is a major point as leptomeningeal dissemination is a significant development that compromises survival, he noted. “Whether or not WBRT influences this pattern of relapse as a complication of surgery, as has been observed in 10 percent to 20 percent of patients depending on the series, is a major source of controversy and we need to learn more about this aspect from the trial results,” Sahgal concluded. “With what we have learned from the trial, we should offer patients the option of SRS alone. However we await publication of the trial results before firm conclusions can be drawn with respect to standard of care.” Kurt Samson is a contributing writer.

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