Internal dose escalation associated with increased local control for melanoma brain metastases treated with stereotactic radiosurgery

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  • 1 Departments of Radiation Oncology and
  • 4 Neurosurgery, Washington University School of Medicine, St. Louis, Missouri;
  • 2 Department of Biomedical Statistics and Informatics, Mayo Clinic, Scottsdale, Arizona; and
  • 3 Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
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OBJECTIVE

The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non–small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM.

METHODS

The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC.

RESULTS

Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31–86 years). The median follow-up was 7.6 months (range 0.5–81.6 months), and the median survival was 9.3 months (range 1.3–81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30.

CONCLUSIONS

For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

ABBREVIATIONS BM = brain metastasis; DVH = dose-volume histogram; IT = immunotherapy; LC = local control; MBM = melanoma BM; MVA = multivariable analysis; NSCLC = non–small cell lung cancer; OS = overall survival; RN = radiation necrosis; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery; TT = targeted therapy; UVA = univariable analysis; Vxx = metastasis volume percentages receiving at least xx Gy; WBRT = whole-brain radiation therapy.

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Contributor Notes

Correspondence Christopher D. Abraham: Washington University School of Medicine, St. Louis, MO. cabraham@wustl.edu.

INCLUDE WHEN CITING Published online December 11, 2020; DOI: 10.3171/2020.7.JNS192210

Disclosures Dr. Kim has received support of non–study-related clinical or research effort overseen by the author from Monteris and Stryker. Dr. Leuthardt is a consultant for Monteris and has ownership in Neurolotions, Inner Cosmos, Immunovalent, Osteovantage, and Sora Imaging Solutions. Dr. Dunn has ownership of Immunovalent. Dr. Tsien is a member of the speakers bureau for Varian. Dr. Robinson is a consultant for Radialogica, Varian, AstraZeneca, EMD Serona; has direct stock ownership in Radialogica; and has received clinical or research support from Varian, Merck, Elekta, and AstraZeneca for the study described.

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