Practice Changing? SRS Alone for Brain Mets Improves Overall Survival

Nick Mulcahy

October 04, 2013

ATLANTA — Stereotactic radiosurgery (SRS) alone should be the favored first-line radiation therapy option for cancer patients younger than 50 years of age who have a minimal number of brain metastases, according to a potentially practice-changing meta-analysis.

The study shows, for the first time, that SRS alone can provide superior survival in the treatment of brain metastases in select patients.

Historically, patients with any number of brain metastases have been treated with whole-brain radiotherapy (WBRT), explained lead author Arjun Sahgal, MD, from the University of Toronto.

More recently, with the development of SRS, many patients with minimal metastases have been treated with a combination of the 2 therapies, he explained during a press briefing here at the American Society for Radiation Oncology 55th Annual Meeting.

The theory has been that combination treatment provides a dual benefit — the precision of SRS for treating specific metastases and the wider treatment coverage of WBRT for treating possibly hidden micromets, he explained.

The "dogma" about SRS alone has been that it is considered risky because it does not treat such metastases, Dr. Sahgal added.

However, in their new analysis, Dr. Sahgal and his colleagues found evidence that SRS alone provides superior outcomes in some patients.

The team combined data from 3 published randomized controlled trials comparing SRS alone with SRS plus WBRT in cancer patients with newly diagnosed minimal (4 or fewer) brain metastases.

They found that average survival in patients 50 years and younger was significantly better with SRS alone than with SRS plus WBRT (10.0 vs 8.2 months), and these patients were at no greater risk for new brain metastases.

Table. Estimated Hazard Ratios for Patients Treated With SRS Alone

Patient Age Hazard Ratio 95% Confidence Interval
≤35 years 0.46 0.24–0.90
≤40 years 0.52 0.29–0.92
≤45 years 0.58 0.35–0.95
≤50 years 0.64 0.42–0.99

 

"For the first time, we have shown that there may be a survival difference," said Dr. Sahgal.

"These survival results have the potential to change our practice as our field moves away from whole-brain radiation," said press-briefing moderator Daphne Haas-Kogan, MD, from the University of California, San Francisco, who was not involved in the study.

The older age groups in the study did not have a survival benefit from SRS alone, compared with the combination therapy, noted Dr. Sahgal. In short, the benefits of SRS alone in patients with minimal metastases are not uniform across all age groups.

 
These survival results have the potential to change our practice.
 

"The bottom line is that we really don't understand why this age cut-off was evident," said Dr. Haas-Kogan.

But Dr. Sahgal offered a hypothesis: WBRT did not improve survival in younger patients and might have impaired it because of diminished quality of life. In other studies, WBRT has been proven to be detrimental to short-term memory and to have a negative impact on quality of life, he explained.

The investigators found that despite not being treated with WBRT, patients 50 years and younger treated with SRS alone had no additional risk for new brain metastases.

Multivariable analysis revealed that in patients treated with SRS alone, significant increases in distant brain failures (or new metastases) occurred only in patients older than 50 years; they did not occur in younger patients.

Dr. Haas-Kogan cautioned that the study's conclusions should only be applied to select patients. One of the "strengths of the study" is that it involved a cohort of patients who were "not at high risk" for new metastases. Patients with more than 4 metastases are still candidates to receive WBRT, she said.

Improved Local Control Overall With WBRT

The individual patient data meta-analysis conducted by Dr. Sahgal and colleagues involved 364 patients from 3 randomized controlled trials. All had a recursive partitioning analysis score of 1 or 2 and a Karnofsky performance score of 70 or higher.

These are "optimal" patients for receiving radiotherapy, Dr. Sahgal noted.

About half the cohort had been treated with SRS alone and about half with SRS plus WBRT (51% vs 49%); 19% of the cohort was 50 years and younger. In addition, 21% had local brain failure (progression of previously treated brain metastases) and 44% had distant brain failure (new metastases).

Many (86%) of the patients died during follow-up. Most had an original diagnosis of lung cancer.

WBRT did provide better local control, Dr. Sahgal acknowledged.

Overall, local brain failure occurred earlier with SRS alone than with SRS plus WBRT (median, 6.6 vs 7.4 months posttreatment). Distant brain failure also occurred earlier, overall, with SRS alone than with SRS plus WBRT (4.5 vs 6.5 months posttreatment).

However, as noted, the risk for distant brain failure was not higher in younger patients treated with SRS alone.

Dr. Sahgal and Dr. Haas-Kogan have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 55th Annual Meeting: Abstract LBA3. Presented September 22, 2013.

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