Preoperative vs Postoperative Hypofractionated Radiosurgery for Patients With Large Brain Metastases

Trial Title: Preoperative vs Postoperative Hypofractionated Radiosurgery for Patients With Large Brain Metastases

NCT ID: NCT05545007

Condition: Brain Metastases, Adult

Conditions: Official terms:
Neoplasm Metastasis
Brain Neoplasms

Conditions: Keywords:
pre-operative hypofractionated radiosurgery
surgical resection
large brain metastases
post-operative hypofractionated radiosurgery

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Radiation
Intervention name: Hypofractionated Radiosurgery (HSRS)
Description: HSRS converges multiple radiation beams to deliver a single, large dose of radiation to a discrete tumor target with high precision, thereby minimizing radiation dose to the surrounding normal tissue.
Arm group label: HSRS post-operative
Arm group label: HSRS pre-operative

Intervention type: Procedure
Intervention name: Brain metastases surgical resection
Description: Complete surgical resection of brain lesions with adeguate margins.
Arm group label: HSRS post-operative
Arm group label: HSRS pre-operative

Summary: This is a phase III randomized trial with the aim to compare preoperative HSRS to postoperative HSRS in patients with large at least one BMs from solid tumors suitable for surgical resection.

Detailed description: The occurrence of BMs is a huge and challenging issue affecting about 20-40% of patients with solid primary tumors. Among these, about 25% of patients harbored large BMs, defined as ≥ 2.1 cm. Single dose SRS, using the dose guidelines suggested by the Radiation Therapy Oncology Group (RTOG) 90-05 study, obtains an unsatisfactory local control (LC) rate ranging from 45-49%. In this subset of patients other treatment pathways have been investigated. In the 1990s, Patchell and colleagues determined that patients with good functional status, and solitary intracranial metastases should undergo surgical resection. Unfortunately, surgery alone is able to control tumor in only 50% of patients, and an adjuvant radiation therapy (RT) is required. For several years, adjuvant whole brain radiation therapy (WBRT) has been considered the standard of cure, but a high risk of impairment in neurological functions was recorded, without an actual benefit on survival. Different RT approaches have been inquired with the aim to reduce neurological toxicity preserving the same brain tumor control. Recent randomized trials showed that single dose SRS on the tumor bed might be a valid, and less toxic alternative to WBRT, although an increased risk of radio necrosis (RN) was noticed when large surgical cavities are treated. In the last years hypofractionated stereotactic radiosurgery (HSRS) has gained interest. Its goal is to reduce the risk of RN compared to single dose SRS, while providing similar, or perhaps, improved LC, probably in relation to the need of reducing the dose prescribed in cases of larger lesions using SRS. However, there has been increasing evidence that patients treated with postoperative SRS have an increased rates of leptomeningeal disease (LMD) occurrence than what was observed when postoperative WBRT was used as the standard. Several retrospective studies have demonstrated a LMD rates up to 31% in the postoperative SRS setting. The proposed mechanism of this increased risk is iatrogenic tumor dissemination into the cerebrospinal fluid (CSF) at the time of surgical resection, which was not as apparent when the entire intracranial CSF space was treated with routine postoperative WBRT, but has become more apparent with increasing use of postoperative SRS only. It is important to note that a standardized definition of radiographic LMD does not exist and ascertainment bias as to what constitutes radiographic LMD (vs local or distant meningeal failure as an example) is an unresolved issue. Due to the perceived drawbacks of postoperative SRS, namely the need for cavity margin expansion due to target delineation uncertainty, the variable postoperative clinical course and potential delay in administering postoperative SRS, and the theoretical risk of tumor spillage into CSF at the time of surgery, investigators began to study the use of preoperative SRS as an alternative paradigm to maximize local control of the resection cavity and minimize neurocognitive detriment associated with WBRT. Preoperative SRS has several potential advantages compared to postoperative SRS consisting in : - a better target delineation to an intact lesion - the reduction of normal brain irradiated considering the useless of additional margins - the potential prevention of any cells spilled during resection - a greater oxygenation ratio of the intact region - a sterilization effect - the resection of the majority of irradiated tissues Based on this background we designed this phase III randomized trial comparing preoperative HSRS to postoperative HSRS in patients with large at least one BMs from solid tumors suitable for surgical resection.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Age >18 years - Histological or cytological confirmation of solid tumor malignancy - Clinical indication for surgical resection of one brain metastasis - Karnosky performance status (KPS) ≥70 - Controlled or responsive extra cranial metastatic lesions - Limited brain metastases (1-4 BMs) - Single metastatic lesion ≥ 2.1 cm in maximum diameter (4 cm3) - Lesions ≤2 cm conditioning mass effect or neurological deficits or massive edema unresponsive to steroids - Written informed consent form Exclusion Criteria: - Prior WBRT - KPS < 70 - Diagnosis of small cell lung cancer (SCLC), germinal cell tumour or Lymphoproliferative disease - Pregnant women - Prior open neurosurgery for malignancy - More than 4 brain metastases - Patients with incompatibility to perform MRI

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: IRCCS Istituto Clinico Humanitas

Address:
City: Rozzano
Zip: 20089
Country: Italy

Status: Recruiting

Contact:
Last name: Pierina Navarria, MD

Phone: 0282247458
Email: pierina.navarria@humanitas.it

Start date: January 31, 2023

Completion date: January 1, 2026

Lead sponsor:
Agency: Istituto Clinico Humanitas
Agency class: Other

Collaborator:
Agency: Brainlab AG
Agency class: Industry

Source: Istituto Clinico Humanitas

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05545007