Neoplasm Metastasis
Conditions
Brief summary
Recently stereotactic radiosurgery (SRS) in 5 up to 10 brain metastases showed to have equal survival as in 2 up to 4 brain metastases. Whole brain radiotherapy (WBRT) is currently the gold standard for patients with more than 3 brain metastases, but has significant side effects. In this prospective randomized phase III trial WBRT is compared to SRS for patients with 4 up to 10 BM.
Detailed description
Dutch guideline advices stereotactic radiosurgery (SRS) for patients with 1 up to 3 brain metastases (BM) and whole brain radiotherapy (WBRT) for patients with 4 or more BM. The interim analysis from the QUARTZ study showed that WBRT did not provide benefit in quality of life nor survival over best supportive care. WBRT has significant side effects, such as hair loss, fatigue, and cognitive dysfunction which may impair quality of life. A recently published study showed that SRS in patients with 5 up to 10 BM had a comparable survival to patients treated with 2 up to 4 BM. Many systemic therapies do not have a satisfactory intracranial response, because of the blood-brain barrier. The potential advantages of SRS i.e, limiting radiation doses to the uninvolved brain and a high rate of local tumour control by just a single treatment. Next logic step would be to compare WBRT with SRS alone in patients with 4-10 BM and evaluate whether SRS is superior to WBRT with regard to QOL.
Interventions
RADIATIONStereotactic Radiosurgery
Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases
RADIATIONWhole Brain Radiotherapy
Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases
Sponsors
Maastricht Radiation Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Minimal 4 up to a maximum of 10 BM on diagnostic MRI scan * Max diameter of single GTV 2.5cm * Max cumulative GTV of 30cm3 * Karnofsky performance status ≥ 70 * Any solid primary tumour. Small cell lung carcinoma, germinoma, and lymphoma are excluded * Ability to provide written informed consent
Exclusion criteria
* Contra-indication for MRI * Prior treatment for BM (i.e. surgery, SRS or WBRT) * Concurrent use of systemic therapy * Maximum cumulative GTV of more than 30cm3 on planning-MRI * More than 10 BM on planning-MRI * A brainstem metastasis with a PTV of more than 20 cm3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life in patients with 4 - 10 brain metastases comparing WBRT and SRS | Change in quality of life measured from baseline to 3 months after radiotherapy | Quality of life is measured by the EQ-5D-5L, a descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival steroid use (mg), toxicity including hair loss and fatigue. | 1 year | Overall survival |
| Time that patient is functioning independently (Karnofsky ≥ 70) | Change in Karnofsky index from baseline to 3 months after radiotherapy | Time that patient is functioning independently (Karnofsky ≥ 70) |
| Steroid use | Change in steroid use from baseline to 3 months after radiotherapy | Steroid use in mg over time |
| Toxicity measured by hair loss and fatigue | Change in toxicity from baseline to 3 months after radiotherapy | Toxicity measured by hair loss and fatigue using CTCAE version 4.0 |
| Degree of independence | Change in independence from baseline to 3 months after radiotherapy | Degree of independence of patients using the Barthel index |
Other
| Measure | Time frame | Description |
|---|---|---|
| Verbal learning | Change in verbal recall and verbal recognition from baseline to 3 months after radiotherapy | Verbal recall and verbal regognition is measured using the Hopkins Verbal Learning Test - Revised |
| Quality of life of cancer patients | Change in Quality of life from baseline to 3 months after radiotherapy | QoL will be measured using the EORTC QLQ-C30 |
| Quality of life of cancer patients with brain neoplasms | Change in Quality of life from baseline to 3 months after radiotherapy | QoL will be measured using the EORTC QLQ-BN20 |
| Quality of life of cancer patients measuring cancer-related fatigue | Change in Quality of life from baseline to 3 months after radiotherapy | QoL will be measured using the EORTC QLQ-FA13 |
| Brain salvage during follow-up | 1 year | Brain salvage during follow-up, type of salvage, and time to salvage after randomisation |
Countries
Netherlands
Outcome results
None listed