Brain MRI Surveillance Alone Helps Preserve Cognition in Small Cell Lung Cancer

Brain MRI surveillance without prophylactic cranial irradiation (PCI) led to improved cognitive failure-free survival (CFFS) in patients with small cell lung cancer (SCLC), the phase III MAVERICK trial showed.

Patients randomized to MRI surveillance alone were more likely to be alive and free from cognitive decline compared with those randomized to MRI surveillance plus PCI, with estimated 6-month CFFS rates of 38% versus 17% (HR 0.60, 90% CI 0.46-0.78, P=0.0005), reported Chad Rusthoven, MD, of the University of Colorado Cancer Center in Aurora, at the World Conference on Lung Cancer in Seoul, South Korea.

There was no significant difference in the benefit of MRI alone by either disease stage (limited vs extensive) or receipt of immunotherapy.

A preliminary overall survival (OS) analysis conducted after 128 deaths showed no difference between strategies (HR 0.90, 90% CI 0.67-1.20).

“These results support MRI surveillance as the preferred management approach for patients with small cell lung cancer,” Rusthoven said.

Invited discussant Hideyuki Harada, MD, PhD, of the Shizuoka Cancer Center in Nagaizumi, Japan, said that “for extensive-stage small cell lung cancer, based on the results from MAVERICK and previous phase III trials, MRI surveillance can be considered the standard of care in the MRI era.”

However, he noted that limited-stage SCLC is potentially curable and that the decision to omit PCI should be based on a comprehensive evaluation of the final OS results in MAVERICK, as well as results from the PRIMALung trial, which is evaluating whether brain MRI surveillance alone is noninferior for OS compared with PCI plus MRI surveillance in SCLC.

“Until then, in my opinion, MRI surveillance remains a valid option in limited-stage small cell lung cancer,” he added.

In explaining the rationale behind the MAVERICK trial, Rusthoven said that, relative to other tumors, SCLC has high rates of brain metastases.

PCI, which involves radiation to the whole brain in the absence of detectable brain metastases, reduces the rate of subsequent intracranial progression by approximately 50%, he explained. “However, there have long been concerns that PCI may cause toxicity to cognition and quality of life.”

While PCI became standard of care when studies from the pre-MRI era demonstrated improved OS with PCI versus observation, Rusthoven noted it has become “increasingly controversial in the era of routine brain MRI staging and surveillance.”

“Brain MRI surveillance may allow for earlier detection of brain metastases and more effective salvage therapy, and thus potentially eliminate the overall survival benefit previously observed with PCI,” he pointed out.

For this study, Rusthoven and team enrolled 304 patients with both limited- and extensive-stage SCLC between January 2020 and December 2025. Median age was 67 years in the PCI/MRI arm and 66 years in the MRI-alone arm, slightly more than half were women, and about two-thirds had limited-stage SCLC. All patients had completed upfront therapy and had no evidence of brain metastases on MRI prior to enrollment.

In both groups, brain MRIs were performed every 3 months during the first year and every 6 months during the second year, with cognitive testing conducted at the same intervals. Cognitive function assessments included the Hopkins Verbal Learning Test-Revised, the Controlled Oral Word Association, and the Trail Making Test.

Rusthoven explained that due to the observed accrual rate, the trial was amended to make CFFS — previously a key secondary endpoint, defined as time to cognitive failure or death — the primary endpoint of the trial.

“As expected,” the incidence of brain metastases was higher with MRI surveillance alone compared with MRI plus PCI (subdistribution HR 2.19, 95% CI 1.31-3.64), with 6-month cumulative incidence rates of 21% and 7%, and 12-month incidence rates of 30% and 15%, Rusthoven reported.

“However, there were no significant differences in progression-free survival between the arms,” he said, although PCI did alter the patterns of initial failure. For patients in the MRI-alone group, there were higher rates of central nervous system progression (18% vs 5% in the PCI/MRI arm), while rates of extracranial-only progression were higher in the PCI/MRI arm (45% vs 31%).

He also reported that brain metastasis-free survival numerically favored the PCI/MRI arm, but the difference between arms was not statistically significant (HR 1.25, 90% CI 0.95-1.66).

Grade ≥3 adverse events occurred in just 0.8% of patients receiving MRI surveillance alone compared with 7.9% of those receiving MRI plus PCI. There was one treatment-related grade 5 encephalopathy event in the latter group.