8.5 Radiotherapy for actinic keratosis and cutaneous squamous cell carcinoma in situ

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Clinical practice guidelines for keratinocyte cancer > 8.5 Radiotherapy for actinic keratosis and cutaneous squamous cell carcinoma in situ

Unless stated otherwise, tumour stage is according to the American Joint Committee on Cancer (AJCC) cancer staging manual 8th edition[1] and Union for International Cancer Control (UICC) TNM classification of malignant tumours 8th edition.[2]

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Actinic keratoses (AKs) can be symptomatic and may be a precursor to invasive disease. A minority (less than 5%) become invasive, although genital lesions such as squamous cell carcinoma in situ of the penis (erythroplasia of Queyrat, Bowen’s diseasecSCC in situ (also known as intra-epidermal SCC)) may have higher rates of invasion (10–30%).[3]

Actinic keratoses can involve large areas (skin field cancerisation).[4]

Several authors recommend early treatment rather than waiting for invasive disease to arise[5][6][7] and recommend that the entire field should be treated.[8]

Actinic keratoses are routinely cleared with cryotherapy, 5-fluorouracil cream or surgery. Surgery has been considered the gold standard, but its superiority has not been definitively demonstrated in a properly conducted randomised controlled trial.[9]

Adequate surgical margins are important to achieve control,[10] but this involves more tissue loss.

All these modalities can cause significant side effects and may not achieve long-term control.[11]

Occasionally, longstanding cutaneous squamous cell carcinoma (cSCC) in situ can grow to a large diameter and become extended skin field cancerisation, which can be difficult to treat with the usual modalities. Field cancerisation can also occur in cosmetically sensitive areas such as the nose, where current treatments may not be possible or effective. Radiotherapy (RT) can be used to treat widespread and resistant AK.

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Overview of evidence (non-systematic literature review)

Historically, the role of RT in the treatment of AK has been considered to be limited to salvage treatment for smaller areas after a number of failed previous therapies in a minority of patients.[12]

A 2012 Cochrane review of interventions for AK[11] and a 2013 Cochrane review Cochrane review of interventions for cSCC in situ[13] did not include any studies assessing RT.

Squamous cell carcinoma in situ of the scalp has traditionally been treated with brachytherapy moulds.[14] Newer, improved external beam RT (EBRT) techniques provide better treatment options,[15][4][16] especially for convex areas of extensive skin field cancerisation, which comprise most ultraviolet (UV)-induced AK fields.

Techniques for RT in the treatment of AK have not been well defined. A review found that doses from 25–70 Gy were effective.[17] Fractions sizes over 4 Gy were associated with long-term poor cosmetic outcome.[17]

RT has been used in AK in the salvage setting and therefore most evidence is anecdotal and consists of small series and case studies. All have shown prolonged duration of control in heavily pre-treated patients. One case study using modern techniques (VMAT) shows enduring control.[18]

An Australian review[3] reported that a dose fractionation schedule of 40–50 Gy in 10–20 fractions using superficial (110–150 kVp) energy photons will achieve a local control rate of 95–100%.

Radiotherapy has been reported to be effective as a definitive treatment for periungual SCC in situ.[19][20]

Large convex surfaces of extensive skin field cancerisation are common and include the scalp, forehead, cheeks, forearms, legs, chest, upper back, and shoulders. Volumetric modulated arc therapy (VMAT) can now be used to treat these skin surfaces with definitive VMAT photon RT (see: Recent advances in the radiotherapy of skin cancer).[4]
Key point(s)

For patients with persistent or recurrent actinic keratosis, consider referral to a radiation oncologist for assessment.

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  1. Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, et al. (Eds.). AJCC Cancer Staging Manual (8th edition). Springer International Publishing: American Joint Commission on Cancer; 2017 [cited 2016 Dec 28].
  2. Brierley JD, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours, 8th Edition. Wiley-Blackwell; 2017.
  3. 3.03.1 Veness MJ. The important role of radiotherapy in patients with non-melanoma skin cancer and other cutaneous entities. J Med Imaging Radiat Oncol 2008 Jun;52(3):278-86 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18477123.
  4. Fogarty GB, Christie D, Spelman LJ, Supranowicz MJ, Sinclair RS.. Can Modern Radiotherapy be used for Extensive Skin Field Cancerisation: An Update on Current Treatment Options. Biomed J Sci &Tech Res 2018;4(1).
  5. Arenberger P, Arenbergerova M. New and current preventive treatment options in actinic keratosis. J Eur Acad Dermatol Venereol 2017 Sep;31 Suppl 5:13-17 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28805940.
  6. Cohen JL. Actinic keratosis treatment as a key component of preventive strategies for nonmelanoma skin cancer. J Clin Aesthet Dermatol 2010 Jun;3(6):39-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20725550.
  7. Rigel DS, Stein Gold LF. The importance of early diagnosis and treatment of actinic keratosis. J Am Acad Dermatol 2013 Jan;68(1 Suppl 1):S20-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23228303.
  8. Stockfleth E. The importance of treating the field in actinic keratosis. J Eur Acad Dermatol Venereol 2017 Mar;31 Suppl 2:8-11 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/28263021.
  9. Övermark M, Koskenmies S, Pitkänen S. A Retrospective Study of Treatment of Squamous Cell Carcinoma In situ. Acta Derm Venereol 2016 Jan;96(1):64-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26073523.
  10. Westers-Attema A, van den Heijkant F, Lohman BG, Nelemans PJ, Winnepenninckx V, Kelleners-Smeets NW, et al. Bowen's disease: A six-year retrospective study of treatment with emphasis on resection margins. Acta Derm Venereol 2014 Jul;94(4):431-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24337161.
  11. 11.011.1 Gupta AK, Paquet M, Villanueva E, Brintnell W. Interventions for actinic keratoses. Cochrane Database Syst Rev 2012 Dec 12;12:CD004415 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23235610.
  12. Dinehart SM, Graham M, Maners A. Radiation therapy for widespread actinic keratoses. J Clin Aesthet Dermatol 2011 Jul;4(7):47-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21779420.
  13. Bath-Hextall F, Ozolins M, Armstrong SJ, Colver GB, Perkins W, Miller PS, et al. Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial. Lancet Oncol 2014 Jan;15(1):96-105 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24332516.
  14. Gandhi AK, Laviraj MA, Kashyap L, Purkait S, Sharma DN, Julka PK, et al. Recurrent Bowen's disease of scalp treated with high dose rate surface mold brachytherapy: a case report and review of the literature. J Contemp Brachytherapy 2015 Jan;6(4):389-94 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25834584.
  15. Martin TE, Moutrie Z, Tighe D, Fallah H, Fogarty GB. Volumetric modulated arc therapy (VMAT) for skin field cancerisation of the nose - A technique and case report. Journal of International Radiology & Radiation Therapy 2018;5(3) Abstract available at https://medcraveonline.com/IJRRT/IJRRT-05-00152.
  16. Fogarty GB, Christie DH, Kaminski A,Potter AE. A radiation oncology approach for using definitive radiotherapy with volumetric modulated arc therapy (VMAT) for skin field cancerisation (SFC). Journal of International Radiology & Radiation Therapy 2018;5(4).
  17. 17.017.1 Anna Z, John K, Maria T, George K, Ivelina B, Ioanna K, et al. The potential role of radiation therapy in Bowen's disease: a review of the current literature. Rev Recent Clin Trials 2012 Feb;7(1):42-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21864250.
  18. De Martin T, Moutrie Z, Tighe D, Fallah H, Fogarty GB. Volumetric modulated arc therapy (VMAT) for skin field cancerisation of the nose - A technique and case report. Int J Radiol Rad Ther 2018 May 14 [cited 2019 Sep 5] Abstract available at https://medcraveonline.com/IJRRT/IJRRT-05-00152.pdf.
  19. Hunt WT, Cameron A, Craig P, de Berker DA. Multiple-digit periungual Bowen's disease: a novel treatment approach with radiotherapy. Clin Exp Dermatol 2013 Dec;38(8):857-61 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23937119.
  20. Herman JM, Pierce LJ, Sandler HM, Griffith KA, Jabbari S, Hiniker SM, et al. Radiotherapy using a water bath in the treatment of Bowen's disease of the digit. Radiother Oncol 2008 Sep;88(3):398-402 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18571754.

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