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Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction

Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy Genu-sparing whole brain radiation therapy (GS-WBRT) 30 Gy in 3 Gy per fraction

whole brain radiation therapy

Kristin Redmond, MD

Victoria Croog, MD

Tracy Vannorsdall, PhD

Haris Sair, MD

Russell Hales, MD

Lawrence Kleinberg, MD

Brandi Page, MD

Deborah Frassica, MD

Fariba Asrari, MD

Kristin Janson

This is a trial that evaluates the preservation of cognition and neuropsychiatric function following genu-sparing whole brain radiation in patients with brain metastases.

Efforts at treating radiation-induced cognitive and neuropsychiatric declines with medications have shown only minimal preliminary cognitive benefit and do not affect quality of life (QOL). Given the structural and functional brain alterations associated with WBRT, preventing rather than treating these radiation-induced changes may produce more favorable outcomes. Innovative radiotherapy techniques can limit the dose of radiation applied to specific brain structures without compromising tumor coverage. In this light, Radiation Therapy Oncology Group (RTOG) recently published a study evaluating the hippocampal avoidance whole brain radiation therapy (WBRT) in patients with brain metastases. They suggest potential preservation of cognitive function with this approach with no perceived detriment in survival. This concept is currently undergoing investigation in a definitive randomized controlled study (NRG-CC003) in patients receiving prophylactic cranial irradiation for small cell lung cancer. However, no other studies to date have prospectively evaluated avoidance of other particularly sensitive brain regions.

One brain region that has received little attention in the radiotherapy literature is the corpus callosum. The genu of the corpus callosum contains thin, densely packed neural fibers that primarily connect the prefrontal association areas and the anterior inferior parietal regions of the brain. Damage or thinning of the genu is associated with reduced functioning on tests of executive functioning, attention, working memory, processing speed, verbal fluency and memory in a variety of healthy and patient groups including aging, cerebral small vessel disease, traumatic brain injury, multiple sclerosis , human immunodeficiency virus, mild cognitive impairment secondary to Parkinson's disease, and euthymic bipolar disorder. The limited existing data in adults receiving WBRT for brain metastases suggest that they also perceive progressive declines in motivation following treatment. Given its apparent involvement in a wide range of cognitive processes, the genu of the corpus callosum is an excellent candidate for sparing in WBRT. This relatively small area has the potential to preserve cognitive functioning across several domains if guarded from the damaging effects of radiation. In this study patients will receive the standard whole brain radiation dose of 3000 centigray (cGy) in 10 fractions, but intensity modulated radiation therapy will be utilized to limit radiation dose to the genu of the corpus callosum. Patients will undergo cognitive testing at baseline and at 4-, 6- and 12-months following completion of brain radiation to evaluate the study hypothesis.

Patients will be treated to a total dose of 30 Gy with a once daily fractionation schedule of 3 Gy per fraction, administered five days per week.

Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases

Preservation of Cognition and Neuropsychiatric Functioning With Corpus Callosum Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases: A Pilot Study

Evaluate changes in cognition from baseline to 4 months following genu-sparing whole brain radiation therapy (GS-WBRT)

Evaluate change in white matter microstructure following GS-WBRT utilizing diffusion tensor imaging

Evaluate changes in cognition from baseline to 4, 6 and 12 months following GS-WBRT

Document development of brain metastases in the spared genu of the corpus callosum

Document changes in QOL, neuropsychiatric symptoms, and functioning in patients receiving GS-WBRT from pre-treatment to 4, 6 and 12 months following GS-WBRT

Document the stability of other frontally-mediated cognitive functions in those receiving GS-WBRT from pre-treatment to 4, 6 and 12 months following GS-WBRT.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases	NCT03223922	Brain Metastase...	whole brain rad...	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases	NCT03223922	Brain Metastase...	whole brain rad...	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Neurocognitive Functioning With Genu-Sparing Whole Brain Radiation Therapy for Brain Metastases	NCT03223922	Brain Metastase...	whole brain rad...	18 Years - 100 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for genu of corpus callosum