2694 - Evaluating Neurocognitive Improvement Following Stereotactic Radiosurgery and Whole Brain Radiation Therapy: A Pooled Analysis of Two Phase III Trials

08:00am - 09:00am PT

Hall F

Screen: 11

POSTER

Presenter(s)

Reza Zarinshenas, MD - University of Maryland Radiation Oncology, Baltimore, MD

R. Zarinshenas¹, H. R. R. Cherng¹, K. Sun², S. M. Bentzen³, P. D. Brown⁴, T. S. Armstrong⁵, J. D. Palmer⁶, V. Gondi⁷, M. P. Mehta⁸, and M. V. Mishra⁹; ¹Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, ²Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, ³Department of Epidemiology and Public Health, Biostatistics and Bioinformatics Division, University of Maryland School of Medicine, Baltimore, MD, ⁴Mayo Clinic Cancer Center, Rochester, MN, ⁵NCI Center for Cancer Research, Bethesda, MD, ⁶Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, ⁷Northwestern Medicine Cancer Center Warrenville and Proton Center, Warrenville, IL, ⁸Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, ⁹Maryland Proton Treatment Center, Baltimore, MD

Purpose/Objective(s):

While neurocognitive decline following radiation therapy (RT) has been extensively studied in multiple randomized controlled trials, it remains unclear whether some patients experience neurocognitive improvement (NCI) relative to baseline. We hypothesize that a subset of patients may demonstrate NCI following RT. Additionally, we propose that treatment with stereotactic radiosurgery (SRS), rather than whole brain radiation therapy (WBRT), may be associated with higher rates of NCI.

Materials/Methods:

A pooled analysis of two phase III randomized clinical trials: NCCTG N107C/CEC.3 (postoperative SRS vs. WBRT) and NCCTG N0574 (SRS vs. SRS+WBRT) using the NCTN data archive was conducted. NCI was defined as an increase of at least one standard deviation from baseline on one or more of six cognitive tests at a given time point, with no other tests showing a decline of greater than one standard deviation at the same time. Patients with baseline testing and at least one follow-up visit testing were selected for final analysis (N107c, n= 129; N0574, n=117). To evaluate NCI over time, we estimated the cumulative incidence function and performed a time-to-event analysis with a competing risk of death. A metanalysis with random effects model of the two trials was performed to pool NCI outcomes between patients receiving SRS alone and those receiving WBRT, with or without SRS.

Results:

At six months, an overall cumulative incidence of 33.5% [95% CI 25.4%-41.8%] (N107c) and 25.1% [95% CI 17.4%-33.5%] (N0574) of patients experienced NCI relative to baseline. In the N107C trial, cumulative incidence of NCI was significantly higher in patients treated with postoperative SRS compared to WBRT (p < .0001), with a 6-month cumulative incidence 54.9% vs. 11.2%, respectively. In the N0574 trial, the cumulative incidence of NCI was increased in patients receiving SRS compared to SRS + WBRT (p = 0.11); the six-month NCI rate was 31.0% for patients treated with SRS compared to 17.2% for those receiving SRS + WBRT. A meta-analysis pooling participants from both trials demonstrated that the chance of NCI was significantly greater in patients treated with SRS compared to those who received WBRT (HR 2.66, p = 0.04). However, significant heterogeneity was observed between the two trials (I² = 78%, t² = 0.34, ?² = 4.54, p = 0.03), suggesting that the effect sizes varied across studies.

Conclusion:

Our findings suggest that a meaningful subset of patients experience NCI relative to baseline following treatment for brain metastases, with this improvement being more common in those receiving SRS compared to a WBRT regimen. These data can help guide patient counseling by providing a more comprehensive understanding of both the benefits and risks of RT for brain metastases. Future clinical trials of treatment for brain metastases should consider reporting neurocognitive improvement in addition to neurocognitive deterioration to ensure a more complete assessment of treatment outcomes.