After resecting a brain metastasis, fractionation looks like a choice rather than a decision

Design

Systematic review and meta-analysis of seven retrospective comparative studies, ROBINS-I risk of bias

Population

589 adults with 649 resected brain metastasis cavities; single fraction 15-20 Gy versus 3-6 fractions totalling 14-32.5 Gy

Primary outcome

Local control at 6 and 12 months, and 12-month overall survival

Effect

6-month local control RR 1.05 (95% CI 1.01-1.09, p=0.006) favouring single fraction; 12-month 1.06 (0.99-1.14, p=0.08); 12-month survival 1.08 (0.82-1.41, p=0.59)

Postoperative cavity-directed stereotactic radiotherapy is standard after resection of limited brain metastases, and how to fractionate it is not settled. Single-fraction radiosurgery is one visit. Hypofractionated radiotherapy over three to six fractions is used where the cavity is large or awkwardly placed, on the argument that it spares normal tissue. This meta-analysis pooled the seven retrospective comparative studies that exist: 589 patients, 649 cavities, most commonly from non-small-cell lung cancer, then melanoma and breast.

At six months local control marginally favoured single fraction (RR 1.05, 95% CI 1.01-1.09, p=0.006). At twelve months the difference was not significant (1.06, 0.99-1.14, p=0.08), and twelve-month overall survival showed nothing between them (1.08, 0.82-1.41, p=0.59).

The authors do the honest thing with their own positive result: they attribute the six-month difference to confounding by indication. Hypofractionation was chosen precisely for larger and deeper cavities, which have worse local control whatever you do to them, and no retrospective adjustment fixes a treatment allocation made on prognosis.

So the usable conclusion is that neither regimen has been shown superior, and the choice can be made on the grounds it is actually made on: cavity size, proximity to eloquent or critical structures, and how many visits the patient can manage. In Indian practice, where travel and machine time are real constraints, single fraction is often the option that gets completed - and this evidence gives no reason to argue against it for a cavity of suitable size. A randomised trial remains outstanding.

• Choose fractionation on cavity size and location, not on a claimed local control advantage
• Single fraction is reasonable for small, accessible cavities and reduces the treatment burden
• Prefer hypofractionation for large cavities or those adjacent to critical structures
• Do not quote the six-month local control difference to patients - it is confounded by indication
• Record cavity volume; it is the variable that drove treatment choice in every one of these studies

The statistics, in plain English

A risk ratio of 1.05 for six-month local control is a 5% relative difference with an interval only just excluding 1.0 - statistically significant, clinically trivial, and, as the authors say, most likely produced by which patients got which treatment. Confounding by indication is the central problem in all seven studies: the sicker cavity systematically received hypofractionation, so the comparison is not between treatments but between patient groups. The twelve-month survival interval (0.82-1.41) is wide enough to include a meaningful benefit either way, because only three studies contributed.

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