Brain MRI Surveillance without Prophylactic Cranial Irradiation Improves Cognitive Outcomes in SCLC

In the SWOG S1827 MAVERICK phase III randomized trial, patients with small-cell lung cancer (SCLC) who underwent regular brain MRI surveillance without prophylactic cranial irradiation (PCI) had significantly better cognitive failure–free survival (the primary endpoint of the trial), without an apparent difference in overall survival, according to results presented at the Presidential Symposium of the IASLC 2026 World Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer, in Seoul, Republic of Korea.

“In the Maverick trial, MRI surveillance alone resulted in improved cognitive failure–free survival compared to a strategy of MRI surveillance plus PCI, with similar benefits observed in patients with both limited- and extensive-stage disease,” said Chad Rusthoven, MD, of the University of Colorado, the principal investigator of the S1827 trial. “These results support MRI surveillance as the standard of care for patients with SCLC.”

SCLC frequently spreads to the brain, and PCI was developed as a strategy to reduce the incidence of brain metastases. Older studies from the pre-MRI era demonstrated improved overall survival (OS) with PCI, which led to PCI becoming a standard therapy. However, PCI may be associated with neurocognitive toxicity, and its use has become increasingly controversial in the era of routine brain MRIs. Regular MRI surveillance allows for earlier identification of and therapy for brain metastases, potentially eliminating the OS advantage previously observed with PCI.

The international SWOG S1827 Maverick trial enrolled 304 patients with limited-stage or extensive-stage SCLC who had completed initial therapy and had no brain metastases on MRI. Patients were randomly assigned to MRI surveillance alone or MRI surveillance plus PCI. Brain MRI was performed every three months during the first year and every six months during the second year, with standardized cognitive testing at the same time points. Sixty-eight percent of patients had limited-stage disease.

After a median follow-up of 22 months among living patients, cognitive failure–free survival was significantly better with MRI surveillance alone (hazard ratio, 0.60; 90% CI, 0.46–0.78; P=0.0005). Cognitive failure was defined as a decline in scores on any one of a battery of six standard cognitive tests given to patients. Cognitive failure–free survival was defined as the time from randomization to either cognitive failure or death. The benefit was consistent across patients with limited-stage SCLC and those with extensive-stage SCLC and was not significantly affected by receipt of immunotherapy.

Preliminary analysis of OS after 128 deaths showed no apparent difference between the groups (hazard ratio for MRI surveillance alone, 0.90; 90% CI, 0.67–1.20). The final OS analysis will be performed after 190 deaths. Progression-free survival also did not differ significantly between the treatment groups.

The investigators conclude that these results support MRI surveillance alone for patients with SCLC, while noting that final overall survival analyses are pending.

The S1827 trial is supported by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), led by SWOG Cancer Research Network, and conducted by the NIH-funded NCI National Clinical Trials Network (NCTN). The trial is funded by the NIH/NCI through grants U10CA180888, U10CA180819, and UG1CA189974.

In addition to Dr. Rusthoven, authors on the presented work include Mary W. Redman, Fred Hutch Cancer Center; Paul D. Brown, Mayo Clinic; Jeffrey S. Wefel, MD Anderson Cancer Center; Jieling Miao, SWOG Statistics & Data Management Center; Ming-Huia Hsieh, Fred Hutch Cancer Center; Justin Honce, University of Colorado School of Medicine; Joseph M. Unger, Fred Hutch Cancer Center; N. Lynn Henry, University of Michigan; Abhijit A. Patel, Yale School of Medicine; Daphna Y. Gelblum, Memorial Sloan Kettering Cancer Center; Jonathan Greenland, Memorial University of Newfoundland; Drew Moghanaki, University of California – Los Angeles; Tithi Biswas, University of Florida College of Medicine; Laura Alder, Duke University Medical Center; Neal Sean McCall, University of Pittsburgh Medical Center Hillman Cancer Center; Jhanelle Gray, Moffitt Cancer Center; and Karen Kelly, International Association for the Study of Lung Cancer.

Reference: “SWOG S1827 MAVERICK: Phase III Trial of Brain MRI Surveillance +/- Prophylactic Cranial Irradiation for Small-Cell Lung Cancer,” Rusthoven CG, Redman MW, Brown PD, et al. IASLC 2026 World Conference on Lung Cancer, Sept 12-15, 2026. https://cattendee.abstractsonline.com/meeting/21487/Session/47