Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial

Wei X Huff, Namita Agrawal, Scott Shapiro, James Miller, Charles Kulwin, Mitesh Shah, Jesse J Savage, Troy Payner, Alexander Vortmeyer, Gordon Watson, Mahua Dey, Wei X Huff, Namita Agrawal, Scott Shapiro, James Miller, Charles Kulwin, Mitesh Shah, Jesse J Savage, Troy Payner, Alexander Vortmeyer, Gordon Watson, Mahua Dey

Abstract

Background: Stereotactic radiosurgery (SRS) has emerged as a common adjuvant modality used with surgery for resectable brain metastases (BMs). However, the optimal sequence of the multi-modality therapy has not been established. The goal of the study is to evaluate 6-month local control utilizing pre-operative SRS followed by surgical resection for patients with 1-4 brain metastases.

Methods: This prospective, single arm, phase II trial will recruit patients with up to 4 brain metastases and at least one resectable lesion. All lesions will be treated with SRS and symptomatic lesions will be resected within 1-4 days after SRS. Patients will be monitored for 6-month local control, in-brain progression free survival, distant in-brain failure, rate of leptomeningeal spread, radiation necrosis and overall survival. Additionally, we will also perform correlative radiobiological molecular studies to assess the effect of radiation dosing on the tumor tissue and clinical outcomes. We expect that pre-operative SRS to the gross tumor prior to surgical resection will improve local control and decrease leptomeningeal failure.

Discussion: Our study is the second prospective trial to investigate the efficacy of pre-operative SRS in the treatment of multiple BMs. In addition, the correlative molecular studies will be the first to investigate early response of BMs at a cellular and genetic level in response to radiation doses and potentially provide molecular prognostic markers for local control and overall survival.

Trial registration: Clinicaltrials.gov identifier: NCT03398694 (registration date: January 12, 2018).

Keywords: Brain metastases; Immune profiling; Metastases surgery; Molecular profiling; Stereotactic radiosurgery.

Conflict of interest statement

Ethics approval and consent to participate

This study will be conducted in compliance with international Conference on Harmonization-Good Clinical Practice (Food and Drug Administration guideline) and with all applicable federal (including 21 CFR parts 56 & 50), state and local laws. The Institutional Review Board (IRB) has approved the protocol and the informed consent form, for this study. Informed consent and HIPAA authorization will be obtained prior to patients’ enrollment in the study and registration in the OnCore® database.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart describing the clinical trial study design

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