A Phase III Trial of Post-Surgical Stereotactic Radiosurgery (SRS) Compared With Whole Brain Radiotherapy (WBRT) for Resected Metastatic Brain Disease
- 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 radiotherapy (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.
- 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
- To evaluate local tumor 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.
- 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
- 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
OUTLINE: This is a multicenter 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
- Arm I: Patients undergo whole-brain radiotherapy (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.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Neurocognitive progression at 6 months post-radiation in patients who received SRS compared to patients who received WBRT
Paul D. Brown, MD
M.D. Anderson Cancer Center
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - Mount Sinai Medical Center||Miami Beach, Florida 33140|
|Swedish Medical Center||Englewood, Colorado 80110|
|St. Mary - Corwin Regional Medical Center||Pueblo, Colorado 81004|
|West Michigan Cancer Center||Kalamazoo, Michigan 49007-3731|
|United Hospital||St. Paul, Minnesota 55102|
|Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Natalie Warren Bryant Cancer Center at St. Francis Hospital||Tulsa, Oklahoma 74136|
|Marshfield Clinic - Marshfield Center||Marshfield, Wisconsin 54449|
|Rapid City Regional Hospital||Rapid City, South Dakota 57709|
|Memorial Hospital of South Bend||South Bend, Indiana 46601|
|Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill||Chapel Hill, North Carolina 27599-7570|
|Cleveland Clinic Taussig Cancer Center||Cleveland, Ohio 44195|
|USC/Norris Comprehensive Cancer Center and Hospital||Los Angeles, California 90033-0804|
|Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center||Milwaukee, Wisconsin 53201-2901|
|Thompson Cancer Survival Center||Knoxville, Tennessee 37916|
|Advocate Christ Medical Center||Oak Lawn, Illinois 60453|
|SUNY Upstate Medical University Hospital||Syracuse, New York 13210|
|Presbyterian Cancer Center at Presbyterian Hospital||Charlotte, North Carolina 28233-3549|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|Hollings Cancer Center at Medical University of South Carolina||Charleston, South Carolina 29425|
|St. Vincent Hospital Regional Cancer Center||Green Bay, Wisconsin 54307-3508|
|M.D. Anderson Cancer Center at Orlando||Orlando, Florida 32806|
|Geisinger Cancer Institute at Geisinger Health||Danville, Pennsylvania 17822-0001|
|Huntsman Cancer Institute at University of Utah||Salt Lake City, Utah 84112|
|Rosenfeld Cancer Center at Abington Memorial Hospital||Abington, Pennsylvania 19001|
|Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest||Allentown, Pennsylvania 18105|
|Mercy Regional Cancer Center at Mercy Medical Center||Cedar Rapids, Iowa 52403|
|CentraCare Clinic - River Campus||St. Cloud, Minnesota 56303|
|Billings Clinic - Downtown||Billings, Montana 59107-7000|
|Summa Center for Cancer Care at Akron City Hospital||Akron, Ohio 44309-2090|
|Mount Carmel St. Ann's Cancer Center||Westerville, Ohio 43081|
|Legacy Good Samaritan Hospital & Comprehensive Cancer Center||Portland, Oregon 97210|
|Salem Hospital Regional Cancer Care Services||Salem, Oregon 97309-5014|
|Saint Joseph's Hospital||Marshfield, Wisconsin 54449|
|Mid Dakota Clinic, PC||Bismarck, North Dakota 58501|
|Louisville Oncology at Norton Cancer Institute - Louisville||Louisville, Kentucky 40202|
|Medcenter One Hospital Cancer Care Center||Bismarck, North Dakota 58501|
|Cancer Institute of Cape Girardeau, LLC||Cape Girardeau, Missouri 63703|
|Frankford Hospital Cancer Center - Torresdale Campus||Philadelphia, Pennsylvania 19114|
|Tufts Medical Center Cancer Center||Boston, Massachusetts 02111|
|Seacoast Cancer Center at Wentworth - Douglass Hospital||Dover, New Hampshire 03820|