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

  • Author Footnotes
    1 The authors contributed equally to this work.
    Nicholas G. Zaorsky
    Corresponding authors at: Department of Radiation Oncology, Penn State Cancer Institute, 500 University Drive, Hershey, PA 17033, USA (N.G. Zaorsky). Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA (T.J. Galloway).
    [email protected] @NicholasZaorsky
    1 The authors contributed equally to this work.
    Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, USA

    Department of Radiation Oncology, Penn State Cancer Institute, Hershey, USA
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  • Author Footnotes
    1 The authors contributed equally to this work.
    Charles T. Lee
    1 The authors contributed equally to this work.
    Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, USA
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  • Eddie Zhang
    Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, USA
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  • Scott W. Keith
    Department of Pharmacology and Experimental Therapeutics, Division of Biostatistics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, USA
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  • Thomas J. Galloway
    Corresponding authors at: Department of Radiation Oncology, Penn State Cancer Institute, 500 University Drive, Hershey, PA 17033, USA (N.G. Zaorsky). Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA (T.J. Galloway).
    Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, USA
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  • Author Footnotes
    1 The authors contributed equally to this work.



      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 (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.


      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 36 months (range: 12–77). Median dose was 45 Gy/11 fractions (interquartile range: 37.5 Gy/6–55 Gy/18) at 4 Gy/fraction (interquartile range: 2.5–6 Gy); most hypofractionated 18.75 Gy/1. There was a trend to decreased “good” cosmesis with higher total dose: −3.4% “good” cosmesis/10 Gy BED3, p = 0.01. Similarly, there was a trend to increased “fair” cosmesis with higher dose: +3.8% “fair” cosmesis/10 Gy BED3, p = 0.006. At a BED3 of 100 Gy, 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.


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


      BCC (basal cell carcinoma), BED (biologically equivalent dose), CI (confidence interval), EBRT (external beam radiation therapy), HDR-BT (high dose rate brachytherapy), IQR (interquartile range), PICOS (Population, Intervention, Control, Outcome, Study Design), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), RT (radiation therapy), RTOG (Radiation Therapy Oncology Group), SCC (squamous cell carcinoma)


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