WBRT Supported For Brain Metastases In Favourable Prognosis NSCLC Patients

Non-small-cell lung cancer patients with a favourable prognosis may derive survival benefit from the addition of whole brain radiotherapy to stereotactic radiosurgery for brain metastases control

medwireNews: Whole-brain radiotherapy (WBRT) may significantly improve overall survival (OS) for select non-small-cell lung cancer (NSCLC) patients with no more than four brain metastases, suggests research published in JAMA Oncology.

“Despite the current trend of using SRS [stereotactic radiosurgery] alone, the important role of WBRT for patients with [brain metastases] from NSCLC with a favorable prognosis should be considered”, write the Japanese Radiation Oncology Study Group (JROSG) 99-1 investigators.

The phase III trial compared SRS alone or alongside 30 Gy of WBRT, given in 10 fractions, in 88 NSCLC patients who were followed up for a median of 8.05 months, explain Hidefumi Aoyama, from Niigata University Graduate School of Medical and Dental Sciences in Japan, and co-authors.

In all, 47 of the patients had a favourable prognosis, defined as a diagnosis-specific Graded Prognostic Assessment (DS-GPA) score of 2.5 to 4.0, while 41 had an unfavourable outlook with a DS-GPA of 0.5 to 2.0.

Among the favourable prognosis patients, OS was significantly higher in the 21 patients given combined radiotherapy than the 26 given SRS alone, at a median of 16.7 versus 10.6 months and a hazard ratio (HR) of 1.92.

But no significant benefit was found for WBRT in the patients with an unfavourable prognosis, with comparable OS between the combined and SRS only groups, at 4.75 versus 6.50 months.

The researchers believe that superior prevention of brain tumour recurrence with WBRT plus SRS in favourable prognosis patients may explain this discrepancy.

Patients with a favourable prognosis given WBRT plus SRS had a significantly longer time to recurrence, of 37.5 months versus 6.2 months for the SRS only group (HR=8.31).

By contrast, combined radiotherapy showed only a trend towards longer time to brain tumour recurrence in the unfavourable prognosis patients, at 10.6 months versus 5.3 months for SRS alone.

Recommending validation of their results in prospective studies of NSCLC patients and those with other malignancies, the team concludes: [F]urther investigations targeting WBRT methods that result in less cognitive impairment with a reliable and durable neurocognitive end point after treatment are warranted.”

Kevin Oh and Jay Loeffler, from Massachusetts General Hospital in Boston, USA, observe in an invited commentary that the “landscape of managing multiple brain metastases is complex and rapidly changing.”

Noting that multiple molecular targeted therapies for NSCLC and melanoma are thought to have intracranial penetration and efficacy against brain metastases, they suggest that use of WBRT should not be a “binary decision” but instead be considered for patients whose disease progression is a greater threat than the risk of WBRT-associated neurocognitive deficits.

“In cases of wild-type EGFR and ALK NSCLC, there are few effective systemic options, and therefore WBRT may have a more prominent role”, say the commentators. “When WBRT is used, there is encouraging evidence of strategies to mitigate late neurocognitive toxic effects.”


Aoyama H, Tago M, Shirato H,et al. Stereotactic radiosurgery with or without whole-brain radiotherapy for brain metastases. Secondary analysis of the JROSG 99-1 randomized clinical trial. JAMA Oncol 2015; Advance online publication 14 May. doi:10.1001/jamaoncol.2015.1145

Oh KS, Loeffler JS. The changing landscape of whole-brain radiation therapy. JAMA Oncol 2015; Advance online publication 14 May. doi:10.1001/jamaoncol.2015.1144

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