Use of Prophylactic Cranial Irradiation in Patients with Limited Stage SCLC

Researchers found that using prophylactic cranial irradiation after thoracic radiation in patients with limited-stage small cell lung cancer undergoing contemporary head imaging is not associated with a decrease in risk of developing new brain metastasis.

In a study published in JAMA Network Open, researchers found that the use of prophylactic cranial irradiation (PCI) after thoracic radiation in patients with limited-stage small cell lung cancer (LS-SCLC) undergoing contemporary head imaging was not associated with a decrease in the risk of developing new brain metastasis.

Additionally, the use of PCI was not found to be associated with an overall survival (OS) benefit in this patient population.

“Synthesizing the available modern data would suggest that in regard to central nervous system radiation therapy recommendations, SCLC and non-SCLC should not be treated as distinctly as historically thought,” the study authors wrote. “Growing evidence from multiple retrospective studies suggests that MRI surveillance and stereotactic radiosurgery may be considered as a first-line option for selected patients with SCLC, and in the era of increasingly aggressive salvage stereotactic radiosurgery and new immunotherapeutic options for extensive-stage SCLC, this is now the focus of multiple prospective clinical trials.”

In this study, researchers included 297 patients with LS-SCLC from a large US academic cancer center. Participants were treated with thoracic radiation, and 205 members of the cohort also underwent PCI while the other 92 did not. All of the patients underwent at least baseline MRI, with restaging brain MRI and/or computed tomography, though they did not have disease progression after thoracic radiation treatment. 

A propensity score-matching analysis was also completed in an attempt to adjust for potential bias. Of the 297 patients who met the study criteria, the propensity score was calculated for 295, using patient, tumor, and treatment characteristics. 

Of the total cohort, the 3-year cumulative incidence rate of brain metastases was found to be higher in the non-PCI group versus the PCI group, when including death as a competing risk, however the difference was not statistically significant (20.40% [95% CI, 12.45%-29.67%] vs 11.20% [95% CI, 5.40%-19.20%]; P = 0.10). The use of PCI was also not associated with a difference in overall survival between the patient groups (hazard ratio [HR], 0.844; 95% CI, 0.604-1.180; P = 0.32). 

“Although the neurotoxicity associated with whole-brain radiation therapy and/or PCI is difficult to quantify, in some studies, PCI has been associated with substantial neurotoxicity compared with observation, as well as worse quality of life, particularly in older patients,” the authors wrote. “It is because of this neurotoxicity that stereotactic radiosurgery is now the standard of care in favor of whole-brain radiation therapy for selected patients with a limited number of (brain metastasis), and randomized trials have been completed to use medications and/or conformal radiation techniques to avoid the hippocampus, both with the objective to minimize neurocognitive decline.”

Overall though, the researchers indicated that the clinical decision is complex, and the toxic effects that have been associated with PCI must be weighed against the possible decline in the incidence of new brain metastasis, which has the potential to be associated with neurological symptoms and quality-of-life detriment.

“The use of PCI for patients with LS-SCLC is complex and is a personalized decision that should include discussion regarding the context of the survival benefit seen in the historical data, the consequence of the potential intracranial control benefit, patient understanding, the availability of various radiation salvage options, and the associated neurotoxic effects of whole-brain radiation therapy,” the authors wrote. “Prospective studies are warranted.”



Pezzi TA, Fang P, Gjyshi O, Feng L, Liu S, Komaki R, Lin SH. Rates of Overall Survival and Intracranial Control in the Magnetic Resonance Imaging Era for Patients With Limited-Stage Small Cell Lung Cancer With and Without Prophylactic Cranial Irradiation. JAMA Network Open. doi:10.1001/jamanetworkopen.2020.1929.