Single Fraction Stereotactic Radiosurgery or Three to Five Fraction Stereotactic Radiosurgery in Treating Patients with Brain Metastasis That Has Been Removed By Surgery

Summary

Objectives

PRIMARY OBJECTIVE:
I. To ascertain if time to surgical bed failure is increased with fractionated stereotactic radiosurgery (FSRS) compared to single-fraction stereotactic radiosurgery (SSRS) in patients with resected brain metastasis.

SECONDARY OBJECTIVES:
I. To ascertain if there is better emotional well-being at 9 months as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-BR) in patients with resected brain metastasis undergoing FSRS compared to SSRS (Primary quality of life [QOL] objective).
II. To ascertain whether there is improved overall survival in patients with resected brain metastases who undergo FSRS compared to patients who receive SSRS.
III. To ascertain in patients with resected brain metastases whether there is improved overall QOL as assessed by the FACT-BR and Linear Analog Self-Assessment (LASA) in patients who receive FSRS compared to patients who receive SSRS (Secondary QOL objective).
IV. To compare the functional independence in patients who receive FSRS to patients who receive SSRS.
V. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions, including the potential impact of immunotherapy and targeted therapy.
VI. To compare rates of radiation necrosis at 12 months in patients who receive FSRS to patients who receive SSRS.
VII. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local, distant brain failure, local leptomeningeal disease, widespread leptomeningeal disease) in patients who receive FSRS compared to patients who receive SSRS after resection of brain metastasis.
VIII. To ascertain in patients with resected brain metastases whether there is increased time to whole-brain radiotherapy (WBRT) in patients who receive FSRS compared to patients who receive SSRS.
IX. To determine in long-term survivors (patients who are alive more than 12 months from time of randomization) whether there is better emotional well-being and overall QOL as assessed by the FACT-BR and LASA in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Secondary QOL objective).
X. To assess for differences in CNS failure patterns (surgical, local, distant brain failure, leptomeningeal disease) as well as radiation necrosis rates as assessed by central review in patients who receive FSRS compared to patients who receive SSRS after resection of a brain metastasis.
XI. To ascertain in patients with resected brain metastases whether there is improved QOL as assessed by all other total and individual FACT-BR and LASA items and subscale values in patients who receive FSRS compared to patients who receive SSRS (Exploratory QOL objective).
XII. To determine in patients with resected brain metastases whether there is less cognitive progression in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Exploratory cognitive objective).

CORRELATIVE SCIENCE OBJECTIVES:
I. To collect and bank blood and tissue for future correlative studies.
II. To ascertain if there are differences in local site versus centrally reviewed scan-reads; specifically differences in dates of progression or patterns of failure.
III. To differentiate tumor recurrence and radiation necrosis using an image-based biomechanically-coupled tumor growth model to estimate patient-specific model parameters and model-derived measures.
IV. To correlate patterns of recurrence (surgical bed recurrence, marginal brain recurrence, marginal pachymeningeal recurrence, distant brain recurrence, distant pachymeningeal recurrence [nodular leptomeningeal disease], classical leptomeningeal recurrence, recurrence in concurrently treated intact brain metastases) and necrosis to the radiotherapeutic target, dosimetric measures, and Radiation Therapy Quality Assurance grading.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo SSRS over 1 session.

ARM II: Patients undergo FSRS over 3 or 5 daily sessions.

Patients undergo magnetic resonance imaging (MRI) throughout the study and may optionally undergo collection of blood samples on study and during follow up.

After completion of study, patients are followed up at 30 days, at 3, 6, 9, 12, 16, and 24 months, then every 6 months until 5 years from randomization.