Clinical Summary: 

• Design/Population: This international phase 3 trial randomized patients with limited- or extensive-stage small cell lung cancer without brain metastases following initial therapy to MRI surveillance alone or MRI surveillance plus prophylactic cranial irradiation. The primary end point was cognitive failure-free survival, with overall survival (OS) noninferiority evaluated as a key secondary end point.
• Key Outcomes: MRI surveillance alone significantly improved cognitive failure-free survival, compared with prophylactic cranial irradiation plus MRI surveillance, with consistent benefit across disease stage and prior immunotherapy use. Preliminary OS results showed no apparent difference between strategies, while brain metastasis-free survival was also not significantly different. Severe treatment-related adverse events were less frequent with MRI surveillance alone.
• Clinical Relevance: These findings challenge the routine use of prophylactic cranial irradiation in the modern MRI surveillance era and support MRI-based surveillance as a potential strategy for preserving cognitive outcomes in both limited- and extensive-stage SCLC. Final OS results remain necessary to establish noninferiority.

Results from the phase 3 SWOG S1827 MAVERICK trial demonstrated that MRI surveillance alone significantly improved cognitive failure-free survival compared with MRI surveillance plus prophylactic cranial irradiation among patients with limited- or extensive-stage small cell lung cancer (SCLC) without brain metastases following initial treatment.

These results were presented in a plenary session at the World Conference on Lung Cancer by Chad Rusthoven, MD, University of Colorado, Aurora, Colorado. 

In this study, 304 patients with limited-or extensive-stage SCLC who had completed initial therapy and had no evidence of brain metastases on MRI before enrollment were randomized to undergo either MRI surveillance alone or MRI surveillance plus prophylactic cranial irradiation administered at 25 Gy in 10 fractions.

In both treatment groups, brain MRI was performed every 3 months during the first year and every 6 months during the second year. Cognitive assessments were conducted at the same time points using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association, and Trail Making Test.

The primary end point was cognitive failure-free survival, defined as the time to first cognitive failure on any of the prespecified cognitive tests or death. The key secondary objective was to determine whether OS with MRI surveillance alone was noninferior to MRI surveillance plus prophylactic cranial irradiation. Additional secondary end points included brain metastasis-free survival and safety.

At a median follow-up of 22 months, MRI surveillance alone significantly improved cognitive failure-free survival compared with MRI surveillance plus prophylactic cranial irradiation, corresponding to a 40% reduction of cognitive failure or death (hazard ratio [HR], 0.60; 90% confidence interval [CI], 0.46 to 0.78; P = .001).

The cognitive failure-free survival benefit with MRI surveillance alone was consistent regardless of disease stage, with no significant interaction between limited- and extensive-stage SCLC (P = .92). Similarly, receipt of immunotherapy did not significantly modify the cognitive failure-free survival benefit (P = .25).

At the preliminary OS analysis, which included 128 deaths, no apparent survival difference was observed between MRI surveillance alone and MRI surveillance plus prophylactic cranial irradiation. However, the prespecified final OS analysis is planned after 190 deaths, and noninferiority cannot yet be considered established. Brain metastasis-free survival was also not significantly different between treatment strategies.

Treatment-related grade ≥ 3 adverse events occurred in 0.8% of patients undergoing MRI surveillance alone compared with 7.9% of patients receiving MRI surveillance plus prophylactic cranial irradiation (P = .004). One treatment-related death occurred among patients receiving prophylactic cranial irradiation due to encephalopathy. 

The findings directly address the role of prophylactic cranial irradiation in an era in which routine brain MRI can identify intracranial disease earlier than was possible in the historical trials that established prophylactic cranial irradiation. Importantly, the cognitive benefit associated with MRI surveillance alone was observed in both limited- and extensive-stage disease.

Although the investigators concluded that the results support MRI surveillance alone as a standard-of-care strategy, the OS analysis remains preliminary. The final analysis will be important for determining whether MRI surveillance alone satisfies the study's prespecified OS noninferiority criterion.

Source: 

Rusthoven CG, Redman MW, Brown PD, et al. SWOG S1827 MAVERICK: Phase III trial of brain MRI surveillance +/- prophylactic cranial irradiation for small-cell lung cancer. Presented at the World Conference on Lung Cancer; September 12-15, 2026. Seoul, South Korea. Abstract PL02.01.