Overview
This phase I trial finds out the possible benefits and/or side effects of radiosurgery before surgery (preoperative) in treating patients with high grade glioma. Radiosurgery uses special equipment to position the patient and precisely give a single large dose of radiation to the tumor. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving pre-operative radiosurgery may improve the odds of brain tumor control and reduce treatment-related side effects.
Description
PRIMARY OBJECTIVE:
I. To evaluate the feasibility, safety and maximum tolerated dose (MTD) of preoperative radiosurgery in the treatment of patients with biopsy-proven high-grade glioma prior to conventional therapy.
SECONDARY OBJECTIVES:
I. Acute clinical toxicity profile using Common Terminology Criteria for Adverse Events (CTCAE) version 5 (defined as within 4 weeks of completion of postoperative radiotherapy.
II. Radiographic tumor control at 12 months following surgery (per Response Assessment in Neuro-Oncology [RANO] criteria).
III. Rate of pseudoprogression at first post radiation scan (RANO criteria). IV. Overall survival at 12 months following surgery.
CORRELATIVE RESEARCH OBJECTIVE:
I. Evaluation of the tumor repair pathways triggered by radiation, tumor vascular changes, tumor microenvironment immune profiling, cell cultures, and the creation of orthotopic xenograft models for future study.
OUTLINE: This is a dose-escalation study.
Patients undergo magnetic resonance imaging (MRI)-guided stereotactic biopsy. Within 14 days of registration, patients undergo either standard of care surgery or radiosurgery in 1 fraction. Within 14 days, patients who underwent radiosurgery then undergo surgery. Within 4-6 weeks, all patients then receive standard of care radiation therapy over 30 fraction and temozolomide daily with or without tumor treating fields (TTF) at the discretion of the treating neuro-oncologist. Additionally, patients undergo MRI and blood sample collection and optional biopsy throughout the study.
After completion of study treatment, patients are followed up every 2-3 months for 12 months and then every 3 months for up to 3 years after registration.
Eligibility
Inclusion Criteria:
- Age >= 18 years
- Clear clinical and radiographic evidence of primary high grade glioma (HGG) as judged by the Mayo multidisciplinary neuro-oncology team (World Health Organization [WHO] grade III-IV, including glioblastoma) regardless of IDH and MGMT status
- Patients who underwent a previous biopsy confirming high grade glioma are eligible for enrollment
- Planned neurosurgical resection of tumor
- Judged to not be at risk of significant clinical risk (i.e. herniation) with radiation-induced edema prior to resection
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only. Patients over 50 years of age who decline pregnancy testing are still eligible without a pregnancy test.
- Ability to complete questionnaire(s) by themselves or with assistance
- Provide written informed consent
- Willing to receive adjuvant radiotherapy at enrolling institution at the time of registration
- Willing to provide tissue and/or blood samples for correlative research purposes
Exclusion Criteria:
- Any of the following:
- Pregnant women
- Nursing women who are unwilling to cease during therapy
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Prior history of cranial radiotherapy
- Unwillingness to participate in study
- Investigator discretion that enrollment on the study would pose undo harm or risk to the patient
- Non-MRI compatible implanted medical device
- Use of systemic anti-cancer therapy within the previous 3 months
- Medical contraindication to craniotomy and tumor resection
- Pathologic confirmation of grade I-II glioma, brain metastasis, or other brain tumor
- Note: Patients with a history of grade I-II glioma are eligible if they have only received surgery as treatment and now there is concern for transformation to grade III-IV tumor
- Primary spinal cord glioma or primary brainstem glioma
- Residual tumor of excessive volume or eloquent location per investigator discretion
- Patients who are unwilling or unable to comply with study procedures