Whole Brain Radiotherapy (WBRT) Versus Stereotactic Radiosurgery (SRS) for 4 Upto 10 Brain Metastases

Not Applicable

Terminated

• Conditions: Neoplasm Metastasis
• Interventions: Radiation: Stereotactic Radiosurgery; Radiation: Whole Brain Radiotherapy

• Registration Number: NCT02353000
• Lead Sponsor: Maastricht Radiation Oncology

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.

Study Timeline

• Study First Submitted: 2015-01-16
• Study First Submitted QC: 2015-01-28
• Study First Posted: 2015-02-02
• Study Start: 2016-07
• Primary Completion: 2019-04
• Study Completion: 2019-12
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-29
• Last Update Posted: 2020-06-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Stereotactic Radiosurgery	Stereotactic Radiosurgery	Stereotactic Radiosurgery for patients with 4 up to 10 brain metastases:
Whole Brain Radiotherapy	Whole Brain Radiotherapy	Whole Brain Radiotherapy for patients with 4 up to 10 brain metastases:

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Overall survival steroid use (mg), toxicity including hair loss and fatigue.	1 year	Overall survival
Degree of independence	Change in independence from baseline to 3 months after radiotherapy	Degree of independence of patients using the Barthel index
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

Trial Locations

Locations (7)

VUmc; 🇳🇱 Amsterdam, Netherlands

Haaglanden MC; 🇳🇱 Den Haag, Netherlands

Instituut Verbeeten; 🇳🇱 Tilburg, Netherlands

Maastricht Radiation Oncology (MAASTRO clinic); 🇳🇱 Maastricht, Netherlands

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

ZRTI; 🇳🇱 Vlissingen, Netherlands

AMC; 🇳🇱 Amsterdam, Netherlands