Neurocognitive Outcome of Conformal WBRT w/wo Hippocampal Avoidance for Brain Metastases
- Conditions
- Metastatic Malignant Neoplasm to Brain
- Interventions
- Radiation: Hippocampal avoidance WBRTRadiation: Conformal WBRT
- Registration Number
- NCT02393131
- Lead Sponsor
- National Taiwan University Hospital
- Brief Summary
Brain metastases are the most common brain tumors in adults. It is estimated that around 10-30% of cancer patients would develop brain metastases during the course of their illness.
Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. WBRT yields high radiologic response rate (27\~56%) and is effective in rapid palliation of neurologic symptoms as well as prolongs time to neurocognitive function decline caused by intracranial lesions. By using conventional fractionation, 33% of patients developed late neurocognitive toxicity while memory impairment was the most common symptom. The incidence is even higher when a formal and sensitive neurocognitive assessment was prospectively evaluated. With more long-term survivors nowadays, it has become increasingly important to minimize neurocognitive function decline and maintain quality of life in patients with brain metastasis.
The function of hippocampus is cooperation in learning, consolidation and retrieval of information and essential for formation of new memories. Bilateral and unilateral radiation injury of the hippocampus is known to alter learning and memory formation. Several preclinical studies support the hypothesis of hippocampus-mediated cognitive dysfunction by ionizing radiation. Clinical studies show increase in radiation dose to hippocampus is associated with subsequent neurocognitive function impairment in adult and pediatric patients. Furthermore, the preliminary result of Radiation Therapy Oncology Group (RTOG) 0933 suggested hippocampal avoidance significant reduce the mean relative decline at 4 months from 30% in historical cohort with WBRT to 7% in experimental cohort.
Previous studies showed brain structures other than hippocampus are also associated with radiation-induced decline in neurocognitive function. There is presence of placebo effect for interventions seeking improvement in neurocognitive function. In present study, a single blind randomized phase II trial is designed to investigate the effectiveness of neurocognitive function preservation using conformal WBRT with or without hippocampal avoidance.
- Detailed Description
This is a single institutional, randomized phase II study to assess the neurocognitive outcome of conformal WBRT with or without hippocampal avoidance in patients with multiple brain metastases.
Patients will be randomly assigned 1:1 to receive conformal WBRT with or without hippocampal avoidance using permuted blocks within strata that are defined by Graded Prognostic Assessment (GPA) score and baseline neurocognitive status. All patients and co-investigators except the principal investigator and attending radiation oncologists will be blinded for treatment groups.
The whole brain planning target volume (PTV) will receive 30 Gy in 10 fractions. Treatment will be delivered once daily, 5 fractions per week, over 2 to 2.5 weeks. Breaks in treatment should be minimized.
Hippocampal Avoidance WBRT:
The dose is prescribed such as 90% of cranial content PTV is covered by the prescription dose.
Maximum dose to 2% of the PTV (D2%) is 37.5 Gy, and minimum dose to 98% of the PTV (D98%) is 25 Gy. Minimum dose to 100% of the hippocampal avoidance regions is 10 Gy, and dose to any point within the hippocampal avoidance regions cannot exceed 17 Gy.
Conformal WBRT:
The dose is prescribed such as 95% of cranial content PTV is covered by the prescription dose.
Maximum dose to 1% of the PTV (D1%) is 36 Gy, and minimum dose to 99% of the PTV (D99%) is 27 Gy.
Follow-up \& Assessment
Side effect evaluation:
* Acute (≤ 90 days from WBRT start) toxicities (CTCAE ver.4)
* Late (\> 90 days from WBRT start) toxicities (CTCAE ver.4)
Functional evaluation: at baseline, 2-, 4- ,and 6-month, every 3 months for 12 months until intracranial disease progression or death after WBRT
* Neurocognitive function
* Self-reported cognitive functioning (two items from EORTC Quality of Life Questionnaire-C30 Taiwan)
* Health-related quality of life specific for brain neoplasms (EORTC Quality of Life Questionnaire-Brain Neoplasm Taiwan)
Efficacy evaluation:
* Follow-up brain MRI at 4-, 9- ,and 12-month until intracranial disease progression, or death.
* Overall survival
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Hippocampal avoidance WBRT Hippocampal avoidance WBRT Conformal whole brain radiotherapy with hippocampal avoidance Conformal WBRT Conformal WBRT Conformal whole brain radiotherapy without hippocampal avoidance
- Primary Outcome Measures
Name Time Method Hopkins Verbal Learning Test-Revised (HVTL-R) delayed recall score At 4 months after radiotherapy Decline in Hopkins Verbal Learning Test-Revised (HVTL-R) delayed recall score from baseline to 4 months after the start of conformal whole brain radiotherapy with or without hippocampal avoidance for brain metastases
- Secondary Outcome Measures
Name Time Method Patient reported outcome (Quality of Life questionnaire) at 1, 2, 4, 6, 9, 12 months after radiotherapy, and then every 3 months until date of death from any cause, assessed up to 24 months EORTC Quality of Life-Core 30 questionnaire module and Quality of Life questionnaire -brain
Acute toxicity (Common Toxicity Criteria for Adverse Events version 4) From date of radiotherapy until 90 days after radiotherapy starts Common Toxicity Criteria for Adverse Events version 4
Intracranial progression (Number of participant with intracranial progression on MRI of brain) From date of enrolment until the date of first documented intracranial progression or date of death from any cause, whichever came first, assessed up to 60 months Number of participant with intracranial progression on MRI of brain
Overall survival From date of enrollment until the date of death from any cause, assessed up to 60 months Number of patients died
Neurocognitive function by a standardized neurocognitive battery at 1, 2, 4, 6, 9, 12 months after radiotherapy, and then every 3 months until date of death from any cause, assessed up to 24 months Evaluate neurocognitive function by a standardized neurocognitive battery (HVTL-R, Trail Making Test Part A \& B, forward \& backward Digit Span).
Late toxicity (Common Toxicity Criteria for Adverse Events version 4) From 90 days after radiotherapy starts until the date of death from any cause, up to 60 months Common Toxicity Criteria for Adverse Events version 4
Trial Locations
- Locations (1)
National Taiwan University Hospital
🇨🇳Taipei, Taiwan