Stereotactic Radiosurgery or Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases That Have Been Removed By Surgery

Official Title

A Phase III Trial of Post-Surgical Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiation Therapy (WBRT) for Resected Metastatic Brain Disease

Summary:

RATIONALE: Stereotactic radiosurgery may be able to send x-rays directly to the tumour and cause less damage to normal tissue. Radiation therapy uses high-energy x rays to kill tumour cells. It is not yet known whether stereotactic radiosurgery is more effective than whole-brain radiation therapy in treating patients with brain metastases that have been removed by surgery. PURPOSE: This randomized phase III trial studies how well stereotactic radiosurgery works compared to whole-brain radiation therapy in treating patients with brain metastases that have been removed by surgery.

Trial Description

Primary Outcome:

• Neurocognitive progression at 6 months post-radiation in patients who received SRS compared to patients who received WBRT
• Overall survival

Secondary Outcome:

• Local control of the surgical bed
• Time to CNS failure in these patients
• Quality-of-life at 6 months of these patients

OBJECTIVES:
Primary

• To ascertain in patients with one to four brain metastases whether there is improved overall survival in patients who receive stereotactic radiosurgery (SRS) to the surgical bed compared to patients who receive whole-brain radiation therapy (WBRT).
• To ascertain in patients with one to four brain metastases whether there is less neurocognitive progression at 6 months post-radiation in patients who receive SRS to the surgical bed compared to patients who receive WBRT. Secondary
• To ascertain in patients with resected brain metastases whether there is improved quality-of-life (QOL) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To ascertain in patients with one to four brain metastases whether there is equal longer time to central nervous system (CNS) failure (brain) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To ascertain in patients with one to four brain metastases whether there is longer duration of functional independence in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To ascertain in patients with one to four brain metastases whether there is better long-term neurocognitive status in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
• To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.
• To evaluate local tumour bed recurrence at 6 months with post-surgical SRS to the surgical bed in comparison to WBRT.
• To evaluate time to local recurrence with post-surgical SRS to the surgical bed in comparison to WBRT.
• To evaluate if there is any difference in CNS failure patterns (local, distant, leptomeningeal) in patients who receive SRS to the surgical bed compared to patients who receive WBRT. Exploratory
• To evaluate radiation changes in the limbic system that may correlate with neurotoxicity using brain MRI scans.
• To determine whether Apo E (i.e., Apo E2, Apo E3, and Apo E4) genotyping may prove to be a predictor of radiation-induced neurocognitive decline (or neuroprotection).
• To determine whether inflammatory markers (i.e., IL-1, IL-6, and TNF-α) may prove to be predictors of radiation-induced neurocognitive decline.
• To determine whether oxidative stress biomarkers (i.e., protein carbonyl content, lipid hydroperoxides, and isoprostane levels) may prove to be predictors of radiation-induced neurocognitive decline.
• To determine whether hormone and growth factors [i.e., glucocorticoids (e.g., cortisol), gonadal steroids (e.g., estradiol, testosterone, progesterone), growth hormone, human chorionic gonadotropin (hCG), insulin-like growth factor-1 (IGF-1), and neuronal growth factor (NGF)] may prove to be a predictor of radiation-induced neurocognitive decline.

OUTLINE:
This is a multicentre study. Patients are stratified according to age in years (< 60 vs ≥ 60), extracranial disease controlled (≤ 3 months vs > 3 months), number of pre-operative brain metastases (1 vs 2-4), histology (lung vs radioresistant [brain metastases from a sarcoma, melanoma, or renal cell carcinoma histology] vs other), and resection cavity maximal diameter (≤ 3 cm vs > 3 cm). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo whole-brain radiation therapy (WBRT) once a day, 5 days a week, for approximately 3 weeks.
• Arm II: Patients undergo stereotactic radiosurgery (SRS) using a gamma knife or a linear accelerator procedure. Serum, whole blood, and urine samples are collected at baseline and periodically during study for genetic markers, inflammatory markers, oxidative stress biomarkers, and hormone and growth factor studies by ELISA and other assays. Patients complete the Functional Assessment of Cancer Therapy-Brain (FACT-BR), the activities of daily living (ADLs), the Fatigue/Uniscale Assessment, and the Linear Analog Self Assessment (LASA) quality-of-life questionnaires at baseline and periodically during study. Neurocognitive functions, such as memory, verbal fluency, visual attention, executive function, and delayed memory, are also assessed. After completion of study therapy, patients are followed up periodically for 5 years.

View this trial on ClinicalTrials.gov