WBRT OVER SRS ALONE BENEFITS SOME NSCLC PATIENTS

NEW YORK (Reuters Health) - For patients with brain metastases from non-small-cell lung cancer (NSCLC) who otherwise have a favorable prognosis, the addition of whole-brain radiotherapy (WBRT) could extend their overall survival by six months compared with stereotactic radiosurgery (SRS) alone, researchers from Japan report.

"The current study indicated that improved intracranial control could translate to improved survival for patients with favorable prognosis," said Dr. Hidefumi Aoyama from Niigata University Graduate School of Medical and Dental Sciences in Niigata.

"WBRT is one of the most powerful tools for controlling brain metastases; therefore, we need to discuss the use of up-front WBRT for each case when brain metastases are diagnosed before treating them simply by using SRS or chemotherapy only," Dr. Aoyama told Reuters Health by email.

WBRT has fallen out of favor with the publication of several trials that showed no adverse impact on overall survival with its omission in patients with a limited number of brain metastases.

Dr. Aoyama and colleagues in the Japanese Radiation Oncology Study Group (JROSG) 99-1 randomized clinical trial, in a secondary analysis of that trial, investigated the impact of WBRT on overall survival in 88 patients with NSCLC who had one to four brain metastases and who also received SRS.

The cohort was fairly evenly divided between those having a favorable prognosis (n=47) and those with an unfavorable prognosis (n=41), based on diagnosis-specific Graded Prognostic Assessment scores of 2.5-4.0 or 0.5-2.0, respectively.

For patients with favorable prognosis, median overall survival was 16.7 months with WBRT+SRS, compared to 10.6 months with SRS alone (p=0.04), the researchers report in JAMA Oncology, online May 14.

There was no survival benefit of adding WBRT for patients with unfavorable prognosis.

Brain tumor recurrence rates were increased at both the initial and distant sites in the brain with the omission of WBRT, and the effect was most prominent in the favorable prognosis group.

Using the Japanese version of the Mini-Mental State Examination, there were no significant differences in neurocognitive function at last follow-up between the WBRT+SRS and SRS-only groups, regardless of prognosis.

"To the best of my knowledge, this is the first study in which a subset of patients that may derive a survival benefit by the addition of WBRT to SRS was identified," Dr. Aoyama concluded. "It was simply surprising."

Dr. Jay Steven Loeffler from Massachusetts General Hospital, Harvard Medical School, in Boston, who coauthored an editorial related to the report, urged caution.

"Post hoc analyses should be interpreted with caution, because it is plausible that statistical significance is found by chance alone," he told Reuters Health by email. "Only 47 of the original 132 participants met the criteria of NSCLC and favorable prognosis. The findings of the JROSG 99-1 secondary analysis are provoking, but not necessarily conclusive."

"Even if a survival advantage to WBRT exists for this select population, in nearly all cases of brain metastases, patients are faced with deciding between quality and length of life," Dr. Loeffler said. "The vast majority of our patients facing a terminal illness will choose quality. This preference argues against WBRT and for the judicious use of SRS or systemic therapies."

"The role of WBRT in securing 'total intracranial control' is facing fierce competition by more effective systemic agents in melanoma, renal cell carcinoma, NSCLC, breast cancer, and other malignancies," Dr. Loeffler added. "At the same time, the side effect profile of WBRT has been improved by use of technology and agents that are protective against late neurocognitive toxicities."

Dr. Michael Brada, a radiation oncologist from University of Liverpool in the UK who was not involved in the new work, echoed the cautious note.

"While the result can be hypothesis generating it cannot be used as evidence to guide practice as it is open to considerable bias," he told Reuters Health by email. "My view of the publication itself is therefore that it is not adequate to affect practice as it suffers from potential bias -- too few patients, retrospective stratification (and barely significant result especially with the two caveats)."

"The other issue is that a larger European study of WBRT after stereotactic radiosurgery &/or surgery failed to show any survival, functional, or quality of life benefit," Dr. Brada explained. "Detailed quality of life studies actually demonstrated a disadvantage for WBRT."

Dr. John Thompson, executive director of Melanoma Institute Australia in Sydney, told Reuters Health by email that the findings support "our contention that it is premature to abandon adjuvant WBRT following either surgical resection of brain metastases or treatment of brain metastases with stereotactic radio surgery. The results do not surprise us and they are important because there have been very few randomized clinical trials assessing the value of WBRT."

"We are approaching complete patient accrual to a randomized trial of adjuvant WBRT following resection or SRS for melanoma brain metastases, and expect that results of this trial will assist in answering the question definitively," Dr. Thompson said.

"There is now quite good evidence that WBRT with hippocampal sparing greatly diminishes the risk of cognitive impairment, which is the main argument used by those who recommend not using WBRT," Dr. Thompson added. "The value of hippocampal sparing will be documented when the results of the currently accruing ANZMTG/TROG trial are available."

SOURCE: http://bit.ly/1Gpri9A and http://bit.ly/1JA9ysY

JAMA Oncol 2015.