Hypofractionated radiation therapy for basal and squamous cell skin cancer: A meta-analysis

Abstract

Purpose: 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).

Methods: 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 (BED₃s) were calculated. The primary endpoint was post-treatment cosmesis. Mixed effects regression models were used to estimate weighted linear relationships between BED₃ and cosmetic outcomes.

Results: 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 BED₃, p=0.01. Similarly, there was a trend to increased "fair" cosmesis with higher dose: +3.8% "fair" cosmesis/10Gy BED_3,p=0.006. At a BED₃ 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 BED₃. Fewer than 8% of patients experienced "poor" cosmesis, independent of dose or fractionation regimen.

Conclusion: Hypofractionated RT has favorable cosmesis for patients with skin BCCs/SCCs. We recommend clinicians consider these commonly-used regimens, which all have BED₃ of ∼100Gy: 50Gy/15 fractions, 36.75Gy/7 fractions, or 35Gy/5 fractions, as they result in "good" cosmesis in 80% of patients.

Keywords: Cosmesis; Elderly; Meta-analysis; Radiation therapy; Skin neoplasms; Systematic review.

Figure 1.. Cosmesis as a function of BED

(A-C) The rates of “good,” fair,” and “poor” cosmesis are plotted vs. BED₃ using mixed effects regression models (upper left, upper right, lower left plots), with the 95% confidence interval (shaded region) representing the area of the anticipated average cosmetic outcome at a particular dose, and a p-value < 0.05 representing an association between cosmetic outcome and BED₃. To help compare fractionation regimens, the BED₃s of several fractionation regimens are labeled in the upper left plot. Hypofractionated schedules produced similar cosmesis to conventionally fractionated schedules, at the same BED₃; further, no regimens to produce “poor” toxicity were identified. (A) There was a trend to decreased “good” cosmesis with higher total dose: −3.4 % “good” cosmesis / 10 Gy BED₃, p = 0.01. (B) Similarly, there was a trend to increased “fair” cosmesis with higher dose: + 3.8% “fair” cosmesis / 10 Gy BED_3, p = 0.006. (C) Fewer than 8% of patients experienced “poor” cosmesis, independent of dose or fractionation regimen. (D) The rates of cosmesis are also co-plotted as a function of BED₃ in the lower right plot. Taken together with the low LR rates, the results suggest that hypofractionated regimens are safe and efficacious for elderly patients with BCCs and SCCs of the skin.

Figure 2.. An illustration of recommended RT fractionation options for indolent skin cancers.

UPPER PANEL: The two principal fractionation options are conventional fractionation (2 Gy daily fractions, up to a total dose of ~64 Gy) and hypofractionation (>2 Gy fractions). Based on the current meta-analysis, we recommend clinicians consider these commonly-used regimens: 50 Gy in 15 fractions, 36.75 Gy / 7 fractions, 35 Gy / 5 fractions. The fractionation options listed here have similar BED₃s and result in LR rates of < 15% and “good” cosmesis in 80% of patients. LOWER PANEL: The spectrum of patient factors influencing RT fractionation. Several factors may preclude surgical extirpation (and promote use of RT instead), including tumor location in a region that would engender substantial morbidity (e.g. nose, orbit), subsequent presence of a large uncorrectable surgical defect, patient comorbidities, use of anticoagulants (blue box on bottom). In general, more hypofractionated options are preferred in those with comorbidities, advanced age, poor performance status, and restrictions in travel (increasing blue triangular area).