Regular brain MRI surveillance significantly improved cognitive failure–free survival compared with prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), according to findings from the phase III SWOG S1827/MAVERICK trial.

The results suggest that routine PCI may not be necessary for patients with SCLC who have no evidence of brain metastases following initial therapy, provided that regular MRI surveillance is available.

Patients managed with MRI surveillance alone had significantly better cognitive failure-free survival, defined as the time to cognitive decline or death, than those who received MRI surveillance plus PCI (HR, 0.60; 90% CI, 0.46–0.78; p=0.0005).

The benefit was observed in both limited-stage and extensive-stage SCLC and did not significantly differ according to whether patients received immunotherapy.

SCLC has a high incidence of brain metastases. PCI, which involves radiation to the whole brain in the absence of detectable brain metastases, reduces the subsequent incidence of brain metastases by approximately 50%. However, there have long been concerns that PCI may adversely affect cognitive function.

PCI became standard of care based largely on studies conducted in the pre-MRI era that demonstrated an overall survival (OS) benefit (Aupérin et al., New England Journal of Medicine, 1999; Slotman et al., New England Journal of Medicine, 2007). Its role has become increasingly controversial with the widespread use of brain MRI for staging and surveillance. Regular MRI surveillance may allow earlier detection of brain metastases and more effective salvage treatment, potentially eliminating the survival benefit previously observed with PCI.

A phase III trial in Japan randomized patients with extensive-stage SCLC to MRI surveillance with or without PCI and reported no significant difference in OS (Takahashi et al., Lancet Oncology, 2017). However, randomized data had been lacking for patients with limited-stage SCLC, and PCI had remained a standard option for patients with both limited-stage and extensive-stage disease because of conflicting results from prior studies.

MAVERICK was designed to address this question and is the first randomised phase III trial to compare MRI surveillance alone with MRI surveillance plus PCI in patients with both limited-stage and extensive-stage SCLC.

Patients underwent brain MRI every three months during the first year and every six months during the second year. Cognitive function was assessed at the same time points using standardised tests, including the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association and Trail Making Test.

As expected, PCI reduced the incidence of brain metastases. At 12 months, brain metastases occurred in 15% of patients receiving MRI surveillance alone compared with 30% of those receiving PCI (sHR, 2.19; 95% CI, 1.31–3.64).

However, this reduction did not translate into a progression-free survival benefit, with no significant difference between the groups (HR, 0.96; 90% CI, 0.75–1.23).

Preliminary overall survival data, based on 128 deaths, also showed no significant difference between MRI surveillance alone and MRI surveillance plus PCI (HR, 0.90; 90% CI, 0.67–1.20). Final overall survival analysis will be conducted after 190 deaths.

Patients receiving PCI also experienced more treatment-related toxicity. Grade 3–5 treatment-related adverse events occurred in 7.9% of patients in the PCI group compared with 0.8% in the MRI surveillance group (p=0.004). Fatigue, alopecia, nausea and poor appetite were among the most common adverse events associated with PCI.

The findings indicate that MRI surveillance can provide a strategy for monitoring patients closely for brain metastases while avoiding routine whole-brain radiation and its associated toxicity. Dr Rusthoven states that these results support MRI surveillance alone as the preferred approach for patients with SCLC who have no brain metastases on MRI after initial therapy.