Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases

Erin S Murphy; Kailin Yang; John H Suh; Jennifer S Yu; Glen Stevens; Lilyana Angelov; Michael A Vogelbaum; Gene H Barnett; Manmeet S Ahluwalia; Gennady Neyman; Alireza M Mohammadi; Samuel T Chao

doi:10.1093/neuonc/noae076

Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases

Neuro Oncol. 2024 Apr 24:noae076. doi: 10.1093/neuonc/noae076. Online ahead of print.

Authors

Erin S Murphy^{1

2

3}, Kailin Yang¹, John H Suh^{1

2

3}, Jennifer S Yu^{1

2

3}, Glen Stevens^{1

2

3}, Lilyana Angelov^{4

2

3}, Michael A Vogelbaum⁵, Gene H Barnett^{4

2

3}, Manmeet S Ahluwalia⁶, Gennady Neyman^{2

3}, Alireza M Mohammadi^{4

2

3}, Samuel T Chao^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, Taussig Cancer Center, Cleveland Clinic , Cleveland, Ohio.
² Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic , Cleveland, Ohio.
³ Cleveland Clinic Lerner College of Medicine of Case Western Reserve University , Cleveland, Ohio.
⁴ Department of Neurological Surgery, Neurological Institute, Cleveland Clinic , Cleveland, Ohio.
⁵ Department of Neuro-Oncology, Moffitt Cancer Center , Tampa, Florida.
⁶ Department of Medical Oncology, Miami Cancer Institute, Baptist Health South Florida , Miami, Florida.

PMID: 38656347
DOI: 10.1093/neuonc/noae076

Abstract

Background: Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses.

Methods: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity.

Results: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%.

Conclusion: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

Keywords: Brain metastases; Dose escalation; Neoadjuvant; Preoperative; Stereotactic radiosurgery.

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