DOI: 10.1227/neu.0000000000004138 ISSN: 0148-396X

Dose De-escalation in Stereotactic Radiosurgery for Melanoma Brain Metastases in Patients on Concurrent Immunotherapy or Targeted Therapy: A Multicenter Experience

Salem M. Tos, Bardia Hajikarimloo, Georgios Mantziaris, Nicholas D. Cassimatis, Stylianos Pikis, Mariam Ishaque, Carson Brantley, L. Dade Lunsford, Ajay Niranjan, Zhishuo Wei, Vanshika Lohia, Yoshua Esquenazi, Angel I. Blanco, Christian Amezquita-Contreras, Andrea Becerril-Gaitan, Piero Picozzi, Andrea Franzini, Luca Raspagliesi, David Bailey, Brad E. Zacharia, Carolina Gesteira Benjamin, Ronan Siqueira Costa, Gustavo Passos, Cheng-chia Lee, Huai-che Yang, Matthew J. Shepard, Rodney E. Wegner, Trent Kite, Selcuk Peker, Yavuz Samanci, Takuma Sumi, Hideyuki Kano, David Mathieu, Jocelyn Blanchard, Nuria Martinez Moreno, Roberto Martinez Álvarez, Ronald E. Warnick, Molly L. Egnot, Chloe Dumot, Maria Protopappa, Yuki Shinya, Jason P. Sheehan
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BACKGROUND AND OBJECTIVES:

The American Society for Radiation Oncology guidelines for stereotactic radiosurgery dose suggestions for brain metastases provide excellent local control but at the expense of higher adverse radiation effects (ARE). This study provides evidence that lower single-fraction prescription doses for patients with melanoma metastases who are concurrently receiving immunotherapy or targeted therapy are equally effective and safe.

METHODS:

This retrospective, multicenter study included 335 patients with melanoma brain metastases who underwent stereotactic radiosurgery between 2009 and 2024. After covariate balancing, 137 patients with 590 metastases were included in the high dose (HD) group and 59 patients with 590 metastases in the reduced dose (RD) group. The RD limits were set at <20 Gy for <2 cm lesions and <18 Gy for ≥2 to <3 cm lesions.

RESULTS:

After matching, the median diameter (6 vs 5.8 mm, P = .5) and imaging follow-up (6 vs 6 months, P = .13) were comparable. Cumulative incidence of progressing metastases was significantly higher in the HD group compared with the RD group ( P < .001) overall, but lower prescription doses resulted in higher progression rates for metastases >2 cm ( P = .023). Higher prescription volumes and HD-group prescription doses were linked with local progression in multivariable analysis. Radiographic AREs were significantly more common in the HD group compared with the RD group overall ( P < .001) but similar for metastases >2 cm ( P = .7). Higher prescription volumes, HD-group prescription doses, and concurrent BRAF or other tyrosine kinase inhibitors were linked with an increased risk of radiographic ARE, whereas concurrent immunotherapy was associated with lower rates of radiographic ARE.

CONCLUSION:

This study provides evidence that treatment with prescription doses under the currently the American Society for Radiation Oncology-suggested doses for brain melanoma metastases <2 cm is safe, having at least equal local control rate and lower radiographic AREs. Reducing prescription dose for lesions between 2 and 3 cm does not seem to convey reduced ARE rates and could potentially increase local failure.

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