To characterize the cosmetic outcomes and local recurrence (LR) rates of various hypofractionated radiation therapy (RT) regimens for skin basal and squamous cell cancers (BCCs/SCCs).

A PICOS/PRISMA/MOOSE selection protocol was performed to identify 344 articles published between 1985-2016 evaluating patients with T1-2 N0 SCCs/BCCs treated with definitive RT. Biologically equivalent doses with α/β=3 (BEDs) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED and cosmetic outcomes.

A total of 21 studies were identified detailing the treatment of 9729 skin BCC/SCC patients, across seven countries, with external beam RT (n=9255) or brachytherapy (n=474). Median follow-up was 36months (range: 12-77). Median dose was 45Gy/11 fractions (interquartile range: 37.5Gy/6-55Gy/18) at 4Gy/fraction (interquartile range: 2.5-6Gy); most hypofractionated 18.75Gy/1. There was a trend to decreased "good" cosmesis with higher total dose: -3.4% "good" cosmesis/10Gy BED, p=0.01. Similarly, there was a trend to increased "fair" cosmesis with higher dose: +3.8% "fair" cosmesis/10Gy BEDp=0.006. At a BED of 100Gy, the expected rate of "good" cosmesis is 79% (95% confidence interval: 70%, 88%). Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED. Fewer than 8% of patients experienced "poor" cosmesis, independent of dose or fractionation regimen.

Hypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED of ∼100Gy: 50Gy/15 fractions, 36.75Gy/7 fractions, or 35Gy/5 fractions, as they result in "good" cosmesis in 80% of patients.