A Randomised Trial of Surgery Plus Whole Brain Radiotherapy (WBRT) Versus Radiosurgery Plus WBRT for Solitary Brain Metastases
Primary objectives - to evaluate for solitary brain metastases whether both overall survival
and health related quality of life (HQoL) in patients treated with radiosurgery (RS) plus
whole brain radiotherapy (WBRT) are non-inferior to those of patients treated with surgery
(S) plus WBRT.
Secondary objectives - to compare between the two treatment arms time to local and distant
brain recurrence, failure free survival, acute and late toxicity.
Hypothesis - Patients treated with RS + WBRT have neither worse survival nor worse quality
of life than those treated with S + WBRT.
- Trial design - Single-centre prospective randomised Phase III controlled two arm
non-inferiority study with the "gold standard" of surgery (plus WBRT) as the control
arm. Blinding to trial arm will not be feasible. Stratification is by Radiation
Therapy Oncology Group Recursive Partitioning Analysis (RPA) prognostic Class 1 vs 2 vs
- Main eligibility criteria - single presumed metastasis on MRI brain; systemic cancer
diagnosed within the last 5 years; considered suitable for both S and RS; written
- Main exclusion criteria - surgery indicated for life-threatening raised intra-cranial
pressure or tissue diagnosis; surgery contra-indicated by site or medical
co-morbidities; leptomeningeal disease; primary is small cell lung cancer, germ cell
tumour, lymphoma, leukaemia or myeloma.
- Radiation - WBRT dose is 30 Gy in 10 fractions over 2 weeks. RS dose is based on lesion
size up to 4 cm (15-20 Gy).
- Surgery - Aim is complete excision.
- Treatment sequence and patient assessments - Any sequencing of S/RS and WBRT is
allowable, as long as the brain treatment is commenced within 2 weeks after, and
completed within 6½ weeks after the diagnostic MRI brain. Assessments at baseline,
during brain treatment, at 2 and 3 months after commencement, then 3 monthly, with MRI
brain at 3 and 6 months, and/or as clinically indicated. Acute toxicity monitored by
NCI Common Toxicity Criteria, late toxicity by RTOG/EORTC Late Radiation Morbidity
Scheme. HQoL assessed by EORTC QLQ-C30 and QLQ-BN20.
- Sample size - 30-40 patients over 5 years.
Outcomes and Significance:
The trial will enable Level I evidence to be applied to this common clinical problem.
Patients will be able to make an informed choice based upon valid survival, quality of life
and toxicity comparisons.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival and Quality of life
Until death or study completion
Daniel Roos, MD, FRANZCR
Royal Adelaide Hospital
Australia: Human Research Ethics Committee