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Prophylactic cranial irradiation fails to improve overall survival in NSCLC

Dr. Joseph Delano Fule Robles
08 Oct 2018
Dr Alex Sun

An updated 10-year analysis of the RTOG 0214 trial showed that the use of prophylactic cranial irradiation (PCI) improved disease-free survival (DFS) and reduced brain metastases, but failed to improve overall survival (OS) in patients with locally advanced non-small-cell lung carcinoma (LA-NSCLC).

The results of the 10-year follow-up of this phase III study, done from September 2001 to August 2007 in 356 patients with stage III A/B LA-NSCLC (median age, 60), showed that PCI did not improve OS rate vs observation alone (17.6 percent vs 13.3 percent; hazard ratio [HR], 1.23; 95 percent confidence interval [CI], 0.95 to 1.59; p=0.124)  [Sun A, et al, WCLC 2018 abstract OA01.01]

Patients who underwent PCI, however, experienced better DFS (12.6 percent vs 7.5 percent; HR, 1.32; 95 percent CI, 1.03 to 1.69; p=0.0298) and less central nervous system (CNS) metastasis (16.7 percent vs 28.3 percent; HR, 2.33; 95 percent CI, 1.31 to 4.15; p=0.0298) vs those who were just observed.

“There was only 45 percent power to detect the hypothesized difference [HR=1.25], and if we were able to accrue the targeted number, there may have been a benefit in OS,” said study investigator Dr Alex Sun from the University of Toronto, Toronto, Ontario, Canada.

“As compared with previous trials, PCI employing delivery of 30 Gy in 15 fractions as used in the RTOG 0214 study might also be too low a dose to exert its desirable effects,” commented discussant Dr John Armstrong of St Luke's Radiation Oncology Network, Dublin, Ireland. [Radiat Oncol 2016;11:67]

“However, a subgroup analysis among 225 patients who did not have surgery as primary treatment showed that patients who underwent PCI had better OS [p=0.026] and DFS [p=0.014] and a lower incidence of brain metastases [p=0.003],” said Sun.

Most patients in the study experienced grade 1 (14.6 percent) or grade 2 (35 percent) acute toxicities or grade 1 (12.7 percent) or grade 2 (8.7 percent) late toxicities, with neurocognitive-associated toxicities being the most commonly reported.

“The most probable reason why we do not do much PCI is due to concerns about its reported toxicities such as somnolence, cognitive disturbances, neuropathy, memory impairment and dizziness. It is difficult to convince patients to undergo a procedure which will unlikely alter their survival,” said Armstrong. [J Clin Oncol 2018;36:2366-2377]

A previous study in 113 cancer patients with brain metastases showed that hippocampus-sparing intensity-modulated radiation therapy (IMRT) is associated with a significantly lower decline in Hopkins Verbal Learning Test-Revised Delayed Recall scores vs historical controls (p<0.001). [J Clin Oncol 2014;32:3810-3816]

In the future, PCI in NSCLC is foreseen to involve identification of ultra-high-risk individuals and performance of research which can be used for profiling patients who will experience brain metastases. For these patients, aggressive surveillance with volumetric MRI and early intervention with stereotactic surgery should be performed.

 

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