Recently, the evidence supports hippocampal avoidance with whole brain radiotherapy (HA-WBRT) as the recommended treatment option in patients with good prognosis and multiple brain metastases as it gives better neurocognitive preservation compared to historical whole brain radiotherapy controls. There is however often poor tumour control with this technique due to the low doses given. Stereotactic Radiosurgery (SRS), a form of focused radiotherapy which is given to patients who have a limited number of brain metastases, gives a higher radiation dose to the metastases resulting in better target lesion control. With improvements in radiation technology, advanced dose-painting techniques now allow a simultaneous integrate boost (SIB) dose to lesions whilst minimising doses to the hippocampus to potentially improve brain tumour control and preserve cognitive outcomes (HA-SIB-WBRT). The Investigators believe that the SIB in HA-SIB-WBRT (experimental) will result in better functional and survival outcomes compared to HA-WBRT (control). Patients who are fit, have multiple brain metastases (5-25 lesions) and reasonable life expectancy (\>6 months) will be recruited from NCCS over 2 years. Patients will be followed up the over the following year with imaging, toxicity data, quality of life, activities of daily living and cognitive measurements at set time points. The results will be compared across the 2 arms. Patients with brain metastases are living longer. Maintaining functional independence and brain metastases control is thus increasingly important. Improved radiotherapy treatment techniques could provide better control and survival outcomes whilst maintain QoL and functional capacity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
The accepted standard HA-WBRT doses in the control arm are 30Gy in 10 fractions.
The doses selected for experimental HA-SIB-WBRT arm are 30Gy in 10 fractions to the whole brain with 40 to 45Gy in 10 fraction SIB doses to tumours.
National Cancer Center Singapore
Singapore, Singapore
Target lesion progression
Time frame: From time of randomisation to target lesion progression, up to 6 months after last day of radiotherapy.
Time to symptomatic brain metastases
Time frame: From time of randomisation to symptomatic brain progression, up to 12 months after last day of radiotherapy.
Incidences of treatment-emergent adverse events (AE)
Identified and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria.
Time frame: From time of randomisation to 12 months after last day of radiotherapy.
Overall Survival
Time frame: From time of randomisation to death from any cause, up to 12 months after last day of radiotherapy.
Progression Free Survival
Time frame: From time of randomisation to overall progression, up to 12 months after last day of radiotherapy.
Cognitive function
Assessed using Hopkins Verbal Learning Test
Time frame: From time of randomisation to 12 months after last day of radiotherapy.
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