Cranial irradiation doesn't boost survival in locally advanced lung cancer

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - 26/3/2019

Prophylactic cranial irradiation (PCI) doesn't appear to increase overall survival (OS) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), long-term data from a phase 3 trial suggest.

"PCI decreased the 5- and 10-year rate of brain metastases and improved 5- and 10-year disease-free survival, but did not improve overall survival compared with observation alone," Dr. Alexander Sun of the University of Toronto, Canada, and colleagues write in JAMA Oncology, online March 14.

The research team randomized 340 patients with LA-NSCLC (mean age, 61) to receive either PCI or observation in the NRG

Oncology/RTOG 0214 study at 291 sites worldwide. Participants were stratified by stage (IIIA vs. IIIB), histologic characteristics (nonsquamous vs. squamous), and therapy (surgery vs. no surgery).

Overall, 163 received PCI and 177 were assigned to observation. Those receiving PCI were treated with 2 Gy/fraction, five days each week, up to 30 Gy.

Patients were followed up every six months for two years, then each year. They underwent magnetic resonance imaging (MRI) or computed tomography (CT) at six and 12 months, then yearly. The median follow-up for all patients was 2.1 years and for living patients was 9.2 years.

The OS for PCI was not significantly longer than for observation (hazard ratio, 0.82; P=0.12; five- and 10-year rates, 24.7% and 17.6% vs. 26.0% and 13.3%, respectively).

However, PCI significantly boosted disease-free survival (HR, 0.76; P=0.03; five- and 10-year rates, 19.0% and 12.6% vs. 16.1% and 7.5%) and lowered the number of brain metastases (HR, 0.43; P=0.003; five- and 10-year rates, which were identical in both groups, at 16.7% vs. 28.3%, respectively).

Participants in the PCI group were 57% less likely to develop brain metastases than those being observed. Patients under 60 years of age and those with nonsquamous disease developed more brain metastases.

On multivariable analysis, PCI was linked with fewer brain metastases and longer disease-free survival, but not with longer OS.

Dr. Megan E. Daly, an associate professor of radiation oncology at the UC Davis Comprehensive Cancer Center in Sacramento, told Reuters Health by email, "Brain metastases are very common in lung cancer patients, particularly those with locally advanced disease, and are a common cause of cancer death. In small-cell lung cancer, PCI has improved survival in some studies, and it was hypothesized that it might improve survival in non-small-cell lung cancer patients as well, by reducing rates of brain metastases."

The new study "unfortunately closed early due to slow accrual (enrolling 340 eligible patients instead of the planned 1,058 patients)," noted Dr. Daly, who was not involved in the work. "The results strongly suggest that additional studies are needed to evaluate PCI in LA- NSCLC in high-risk patient sub-groups."

Dr. Dheerendra Prasad, medical director of the department of radiation medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York, told Reuters Health by email, "The most important point often overlooked is that we do not leave brain metastases untreated, and using stereotactic radiosurgery in managing these patients as needed has no adverse effect on their overall survival and has improved progression-free survival. It, however, offers significant improvement in the cognitive function of these patients long term. This is the primary reason the study accrued slowly."

"This fascination for the use of whole-brain radiation is out of touch with current clinical practice. Improved patient survival in the world of targeted therapy will only amplify the cognitive disadvantage of this approach," added Dr. Prasad, who also was not involved in the study. "It is unlikely that the findings of this study will alter the management of patients with NSCLC in the current climate of normal tissue protection."

Dr. Sun did not respond to requests for comment.


JAMA Oncol 2019.

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