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

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

Whole Brain Radiotherapy vs. Stereotactic Radiosurgery for 4 - 10 Brain Metastases:a Phase III Randomized Multicenter Trial

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.

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.

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)

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

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