A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases (NASRS)

A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Stereotactic Radiosurgery

Detailed Description

Recently, a novel treatment strategy for large brain metastases was described whereby lesions appropriate for resection were treated with a single fraction of SRS pre-operatively. In a retrospective analysis, of 51 lesions with a median tumor size of 3 cm, 1-year LC was 86%. This neoadjuvant approach resulted in lower rates of leptomeningeal failure (3 vs. 17%) and symptomatic radiation toxicity (1.5 vs. 14.6 %) compared to a comparative cohort of lesions treated with post-operative cavity boost SRS (POCBS).

Based on promising results, we believe that a prospective trial to establish the value of neoadjuvant SRS (NaSRS) for the treatment of BM appropriate for resection is warranted.

This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, L4W4C2
      • University Health Network
• Germany
  • Berlin, Germany, 13353
    • Charité Universitätsmedizin Berlin, Campus Virchow Klinikum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Lymphoma, small cell carcinoma, and seminoma are excluded
• A lesion appropriate for resection, not previously treated with SRS. Lesions should be > 2 cm and < 4 cm in largest dimension, and require resection ( e.g. due to mass effect or to obtain a tissue diagnosis). Index lesions will be treated with SRS and surgery, as outlined in the treatment section of the protocol.
• Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate NaSRS, e.g., the ability to lie flat in a stereotactic head frame.
• Any unresected lesions or lesions for which there is no planned immediate resection (non index lesions) must measure < 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. Unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. .
• ECOG ≤ 2
• MRI confirmed 1-6 lesions, one of which is the index lesion. Each non-index lesion (up to 5) must measure ≤ 3.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection.

Note: The pre-registration MRI may be obtained ≤ 35 days prior to enrolment.

Exclusion Criteria:

• Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
• pregnancy
• Prior cranial radiotherapy targeting the index lesion, or any prior WBRT.
• Inability to complete a MRI with contrast of the head, or a known allergy to gadolinium.
• Cytotoxic Chemotherapy within 7 days prior to SRS (molecularly targeted therapies , including immune-modulatory drugs, can be given within seven days of SRS at the discretion of the treating physician)
• Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor

• Imaging Findings:

  • Widespread definitive leptomeningeal metastasis.
  • A brain metastasis that is located ≤ 2 mm of the optic chiasm
  • Evidence of midline shift
  • Fourth ventricular narrowing, concerning for hydrocephalus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm 1; Neoadjuvant SRS	Radiation: Stereotactic Radiosurgery; Stereotactic Radiosurgery before surgical resection of brain mets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiation toxicity	The rate at 1 year of symptomatic (≥grade 2) radiation toxicity	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival		2 years
progression-free survival		2 years
local control	1-year local control (PR+CR) of the index lesion resulting from NaSRS	1 year
leptomeningeal disease	1-year rates of leptomeningeal disease	1 year
Survival	Median survival	5 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: David Shultz, MD, University Health Network, Toronto

Publications and helpful links

General Publications

• Higazy R, Li D, Lau R, Millar BA, Laperriere N, Berlin A, Conrad T, Gutierrez-Valencia E, Zadeh G, Bernstein M, Kalyvas A, Spears J, Zips D, Vajkoczy P, Senger C, Acker G, Kongkham P, Shultz DB. Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: An International, Multicenter, Single-Arm Phase II Trial. Neurosurgery. 2025 Apr 14;97(4):793-800. doi: 10.1227/neu.0000000000003451.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2018
• Primary Completion (Actual): October 10, 2025
• Study Completion (Actual): October 10, 2025

Study Registration Dates

• First Submitted: December 4, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Surgery; Radiation; Stereotactic Radiosurgery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 17-5689

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No