By Will Boggs MD
NEW YORK (Reuters Health) - Postoperative stereotactic radiosurgery (SRS) reduces local recurrences with fewer adverse effects on cognitive function, according to results from two phase 3 trials.
“We believe that post-operative SRS should be standard of care after surgical resection of metastases to maximize local control,” Dr. Ganesh Rao from The University of Texas MD Anderson Cancer Center, Houston, Texas told Reuters Health by email.
Dr. Rao’s team compared postoperative SRS versus observation in 132 patients who underwent complete resection of brain metastases.
In the final analysis of 128 patients followed a median 11.1 months, the local recurrence rate was twice as high with observation alone (48%) as with SRS (24%), according to the July 4th Lancet Oncology online report.
At 12-months, freedom from local recurrence was significantly higher in the SRS group (72%) than in the observation group (43%), but the two groups did not differ in overall survival, time to distant brain recurrence, or subsequent treatment with whole brain radiation therapy (WBRT).
“Stereotactic radiation is effective in maximizing local control after surgical resection of metastasis,” Dr. Rao concluded. “There may be an opportunity for other local radiation techniques (hypofractionated radiation) to achieve a similar result.”
In a second study, Dr. Paul D. Brown from Mayo Clinic, Rochester, Minnesota and colleagues from 48 institutions in the United States and Canada compared postoperative SRS with WBRT in 194 patients with a resected brain metastasis and a resection cavity less than 5.0 cm in maximal extent.
Overall survival did not differ between the treatment groups, but local control and distant brain control were worse in the SRS group than in the WBRT group.
At six months, cognitive deterioration was significantly less frequent in the SRS group (52%) than in the WBRT group (85%).
Patients in the SRS group were more likely to show clinically significant improvements in quality of life at six months, and their functional independence at three months was significantly higher, compared with patients in the WBRT group.
Among 54 long-term survivors who had a cognitive evaluation 12 or more months after randomization, cognitive deterioration was significantly less frequent after SRS than after WBRT.
Other adverse events were nominally less frequent in the SRS group than in the WBRT group.
“Based on earlier trials, the negative cognitive impact of WBRT was not unexpected,” Dr. Brown told Reuters Health. “However, we were surprised to find that the WBRT also had a negative impact on physical well-being, overall quality of life, and functional independence months after the treatment was completed.”
“Despite MRI-confirmed, gross total resection of a brain metastasis, more than half of patients will suffer recurrence in the surgical bed,” he explained. “Therefore, radiosurgery to the surgical cavity should be strongly considered for the vast majority of patients after resection of a brain metastasis to improve local control of the surgical bed. Even for small lesions (e.g., <2.5 cm), which have lower rates of recurrence, post-operative radiosurgery still results in a meaningful improvement in surgical bed control.”
“This is a practice-changing trial as to date most patients have been treated with whole brain radiotherapy after resection of brain metastases,” Dr. Brown said in an email. “Because of the results of this trial, many patients will be spared the toxicities of whole brain radiotherapy. In addition, since radiosurgery can be delivered in a single day, patients can resume systemic therapies for their cancers much quicker.”
Dr. Simon S. Lo from University of Washington School of Medicine in Seattle, Dr. Eric Chang from Keck School of Medicine, University of Southern California, Los Angeles, and Dr. Arjun Sahgal from University of Toronto, who coauthored an editorial related to these reports, told Reuters Health in a joint email, “When discussing with patients about treatment options, the patients will need to understand the pros and cons of each treatment option, and this is basically a balance between preservation of neurocognitive function/quality of life and improved intracranial tumor control.”
“Surgery alone is not enough, and surgery + WBRT is probably too much given the toxicities,” they said. “SRS is a viable adjuvant therapy for resected brain metastases and a good compromise between surgery alone and surgery + WBRT for cavities.”
Dr. Marike L. Broekman from University Medical Center Utrecht, The Netherlands, who recently compared SRS versus WBRT in a systematic review and meta-analysis but who was not involved in either of these studies, told Reuters Health by email, "These data indicate that brain metastases patients are at risk of cognitive deterioration. But also that after SRS, cognitive deterioration was less frequent compared to WBRT. In addition, the duration of stable or better functional independence was longer after SRS than after WBRT. As the choice of post-surgical treatment - WBRT or SRS - does not seem to impact survival, SRS should be considered.”
“I think this is a very important - carefully executed - study that might impact the way we treat brain metastases patients - not only focusing on radiological results (tumor control), but also on such functional outcomes as cognitive function and functional independence,” she said.
SOURCE: http://bit.ly/2txqOdR, http://bit.ly/2t8vAPw, and http://bit.ly/2u10zjg
Lancet Oncol 2017.
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