Stereotactic radiosurgery in the management of non–small cell lung cancer brain metastases: a prospective study using the NeuroPoint Alliance Stereotactic Radiosurgery Registry

Giorgos D. Michalopoulos Neuro-Informatics Laboratory, and
Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota;

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Konstantinos Katsos Neuro-Informatics Laboratory, and
Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota;

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Inga S. Grills Department of Neurological Surgery, Beaumont Health System, Royal Oak, Michigan;

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Ronald E. Warnick Department of Neurosurgery, The Jewish Hospital, Cincinnati, Ohio;

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James McInerney Department of Neurosurgery, Penn State Health, Hershey, Pennsylvania;

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Albert Attia Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee;

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Robert Timmerman Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, Texas;

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Eric Chang Department of Radiation Oncology, Keck School of Medicine, University of Southern California, Los Angeles, California;

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David W. Andrews Department of Neurosurgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania;

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Anthony L. D’Ambrosio The Valley Hospital, Paramus, New Jersey;

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William S. Cobb The Valley Hospital, Paramus, New Jersey;

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Nader Pouratian Department of Neurological Surgery, UT Southwestern Medical Center, Dallas, Texas;

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Aaron C. Spalding Norton Cancer Institute, Norton Healthcare, Louisville, Kentucky;

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Kevin Walter Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York;

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Randy L. Jensen Department of Neurosurgery, University of Utah, Salt Lake City, Utah;

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Mohamad Bydon Neuro-Informatics Laboratory, and
Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota;

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Anthony L. Asher Neuroscience Institute, Carolinas Healthcare System and Carolina Neurosurgery & Spine Associates, Charlotte, North Carolina; and

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Jason P. Sheehan Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia

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OBJECTIVE

The literature on non–small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry.

METHODS

The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions.

RESULTS

Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80–100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3–4 lesions, HR 2.2; 5–14 lesions, HR 2.5).

CONCLUSIONS

In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

ABBREVIATIONS

BM = brain metastasis; CITV = cumulative intracranial tumor volume; HR = hazard ratio; KPS = Karnofsky Performance Status; NPA = NeuroPoint Alliance; NSCLC = non–small cell lung cancer; OS = overall survival; PFS = progression-free survival; QALY = quality-adjusted life year; RCT = randomized controlled trial; RTOG = Radiation Therapy Oncology Group; SMD = standardized mean difference; SRS = stereotactic radiosurgery; WBRT = whole-brain radiotherapy.
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Illustration from Srinivasan et al. (pp 1335–1343). © Sandeep Kandregula, published with permission.
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