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In JCO precision oncology

PURPOSE : Brain metastasis is common in lung cancer, and treatment of brain metastasis can lead to significant morbidity. Although early detection of brain metastasis may improve outcomes, there are no prediction models to identify high-risk patients for brain magnetic resonance imaging (MRI) surveillance. Our goal is to develop a machine learning-based clinicogenomic prediction model to estimate patient-level brain metastasis risk.

METHODS : A penalized regression competing risk model was developed using 330 patients diagnosed with lung cancer between January 2014 and June 2019 and followed through June 2021 at Stanford HealthCare. The main outcome was time from the diagnosis of distant metastatic disease to the development of brain metastasis, death, or censoring.

RESULTS : Among the 330 patients, 84 (25%) developed brain metastasis over 627 person-years, with a 1-year cumulative brain metastasis incidence of 10.2% (95% CI, 6.8 to 13.6). Features selected for model inclusion were histology, cancer stage, age at diagnosis, primary site, and RB1 and ALK alterations. The prediction model yielded high discrimination (area under the curve 0.75). When the cohort was stratified by risk using a 1-year risk threshold of > 14.2% (85th percentile), the high-risk group had increased 1-year cumulative incidence of brain metastasis versus the low-risk group (30.8% v 6.1%, P < .01). Of 48 high-risk patients, 24 developed brain metastasis, and of these, 12 patients had brain metastasis detected more than 7 months after last brain MRI. Patients who missed this 7-month window had larger brain metastases (58% v 33% largest diameter > 10 mm; odds ratio, 2.80, CI, 0.51 to 13) versus those who had MRIs more frequently.

CONCLUSION : The proposed model can identify high-risk patients, who may benefit from more intensive brain MRI surveillance to reduce morbidity of subsequent treatment through early detection.

Wu Julie, Ding Victoria, Luo Sophia, Choi Eunji, Hellyer Jessica, Myall Nathaniel, Henry Solomon, Wood Douglas, Stehr Henning, Ji Hanlee, Nagpal Seema, Hayden Gephart Melanie, Wakelee Heather, Neal Joel, Han Summer S