An interventional study of Hippocampal avoidance WBRT and Conformal WBRT in Metastatic Malignant Neoplasm to Brain, sponsored by National Taiwan University Hospital. Status unknown at 1 site in Taiwan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2019-07-19.
Sponsored by National Taiwan University Hospital · Not applicable, Interventional, and Treatment
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.
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:
Functional evaluation: at baseline, 2-, 4- ,and 6-month, every 3 months for 12 months until intracranial disease progression or death after WBRT
Efficacy evaluation:
3,517 studies on the registry are indexed under Neoplasm Metastasis; 885 are open to participants now.
This study's enrollment of 70 is above the median of 54 across 2,767 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →National Taiwan University Hospital is the lead sponsor of 2,563 studies on the registry; 569 are open to participants now.
Of its 11 completed or terminated interventional studies of FDA-regulated products, 2 (18%) have results posted.
Counted across the registry records on this site, refreshed daily.
To be eligible for inclusion, patients must fulfill the following criteria:
Exclusion criteria:
Patients fulfill any of the following criteria will be excluded from this trial
Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
Conformal whole brain radiotherapy with hippocampal avoidance
Radiation: Hippocampal avoidance WBRT
Conformal whole brain radiotherapy without hippocampal avoidance
Radiation: Conformal WBRT
Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy
Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy
Hopkins Verbal Learning Test-Revised (HVTL-R) delayed recall score
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
Time frame: At 4 months after radiotherapy
Neurocognitive function by a standardized neurocognitive battery
Evaluate neurocognitive function by a standardized neurocognitive battery (HVTL-R, Trail Making Test Part A \& B, forward \& backward Digit Span).
Time frame: 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
Patient reported outcome (Quality of Life questionnaire)
EORTC Quality of Life-Core 30 questionnaire module and Quality of Life questionnaire -brain
Time frame: 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
Acute toxicity (Common Toxicity Criteria for Adverse Events version 4)
Common Toxicity Criteria for Adverse Events version 4
Time frame: From date of radiotherapy until 90 days after radiotherapy starts
Late toxicity (Common Toxicity Criteria for Adverse Events version 4)
Common Toxicity Criteria for Adverse Events version 4
Time frame: From 90 days after radiotherapy starts until the date of death from any cause, up to 60 months
Intracranial progression (Number of participant with intracranial progression on MRI of brain)
Number of participant with intracranial progression on MRI of brain
Time frame: 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
Overall survival
Number of patients died
Time frame: From date of enrollment until the date of death from any cause, assessed up to 60 months
Genomic risk of neurocognitive decline after WBRT
Number of participants with Genomic risk of neurocognitive impairment after WBRT
Time frame: At 4 months after radiotherapy
Plan to share: No
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National Taiwan University Hospital