Advertisement

Skin Cancer pp 409-417 | Cite as

Photodynamic Therapy

  • Raffaella Sala
  • Maria Teresa Rossi
  • Piergiacomo Calzavara-Pinton
Chapter
Part of the Current Clinical Pathology book series (CCPATH)

Abstract

Photodynamic therapy (PDT) is a two-step therapeutic technique in which topical or systemic delivery of photosensitising drugs is followed by irradiation with visible light with an adequate emission spectrum and irradiance. Activated photosensitisers transfer energy to molecular oxygen generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators.

The low light dosages can trigger only photochemical reactions without ablative photothermal effects.

All the photosensitisers are selective, i.e. they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while relatively avoiding the surrounding healthy tissue.

A strong interest for PDT in dermatology was raised only in the 1990s by the availability of a simple and effective technique: the topical application of aminolevulinic acid (ALA) and its methyl ester (methyl aminolevulinate, MAL) followed by the irradiation of broadband red light. These drugs do not induce strong generalised cutaneous photosensitisation like the systemically applied porphyrins or their derivatives. For dermatological purposes incoherent lamps or LED arrays can be used for light activation.

PDT is used for the prevention and treatment of non-melanoma skin cancer. Clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and, since 2006, Bowen disease. Treating superficial oncologic lesions, cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedures often with better cosmetic results.

Keywords

Basal Cell Carcinoma Complete Response Rate Actinic Keratosis Excellent Cosmetic Result Placebo Cream 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Glossary

ALA

Aminolevulinic acid

CO

Cosmetic outcome

CR

Complete response

LEDs

Light-emitting diodes

MAL

Methyl aminolevulinate

PDT

Photodynamic therapy

PpIX

Protoporphyrin IX

References

  1. 1.
    Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol. 1992;55:145–57.PubMedCrossRefGoogle Scholar
  2. 2.
    Gaullier JM, Berg K, Peng Q, et al. Use of 5-aminolevulinic acid esters to improve photodynamic therapy on cells in culture. Cancer Res. 1997;57:1481–6.PubMedGoogle Scholar
  3. 3.
    Barr H, Kendall C, Reyes Goddard J, et al. Clinical aspects of photodynamic therapy. Sci Prog. 2002;85:131–50.PubMedCrossRefGoogle Scholar
  4. 4.
    Datta SN, Loh CS, MacRobert AJ, et al. Quantitative studies of the kinetics of 5-aminolaevulinic acid induced fluorescence in bladder transitional cell carcinoma. Br J Cancer. 1998;78:1113–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Fritsch C, Homey B, Stahl W, et al. Preferential relative porphyrin enrichment in solar keratoses upon topical application of 5-aminolevulinic acid methyl ester. Photochem Photobiol. 2000;71:640–7.CrossRefGoogle Scholar
  6. 6.
    Kennedy JC, Pottier RH, Pross DC. Photodynamic therapy with endogenous protoporphyrin IX: basic principles and present clinical experience. J Photochem Photobiol B. 1990;6:143–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Szeimies RM, Karrer S, Radakovic-Fijan S, et al. Photodynamic therapy using topical methyl 5- aminolevulinate compared with cryotherapy for actinic keratosis: a prospective, randomized study. J Am Acad Dermatol. 2002;47:258–62.PubMedCrossRefGoogle Scholar
  8. 8.
    Morton CA. Methyl aminolevulinate (Metvix) photodynamic therapy – practical pearls. J Dermatolog Treat. 2003;14 Suppl 3:23–6.PubMedGoogle Scholar
  9. 9.
    Touma D, Yaar M, Whitehead S, et al. A trial of short incubation, broad-area photodynamic therapy for facial actinic keratoses and diffuse photodamage. Arch Dermatol. 2004;140:33–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Peng Q, Soler AM, Warloe T, et al. Selective distribution of porphyrins in skin thick basal cell carcinoma after topical application of methyl 5-aminolevulinate. J Photochem Photobiol B. 2001;62:140–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Freeman M, Vinciullo C, Francis D, et al. A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomised study. J Dermatolog Treat. 2003;14:99–106.PubMedCrossRefGoogle Scholar
  12. 12.
    Pariser DM, Lowe NJ, Stewart DM, et al. Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis: results of a prospective randomised multicenter trial. J Am Acad Dermatol. 2003;48:227–32.PubMedCrossRefGoogle Scholar
  13. 13.
    Tarstedt M, Rosdahl I, Berne B, et al. A randomized multicenter study to compare two treatment regimens of topical methyl aminolevulinate (Metvix)-PDT in actinic keratosis of the face and scalp. Acta Derm Venereol. 2005;85:424–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Morton C, Campbell S, Gupta G, et al. Intraindividual, right-left comparison of topical methyl aminolevulinate-photodynamic therapy and cryotherapy in subjects with actinic keratosis: a multicentre, randomized controlled study. Br J Dermatol. 2006;155:1029–36.PubMedCrossRefGoogle Scholar
  15. 15.
    Dragieva G, Prinz BM, Hafner J, et al. A randomized controlled clinical trial of topical photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratoses in transplant patients. Br J Dermatol. 2004;151:196–200.PubMedCrossRefGoogle Scholar
  16. 16.
    Dragieva G, Hafner J, Dummer R, et al. Topical photodynamic therapy in the treatment of actinic keratoses and Bowen’s disease in transplant recipients. Transplantation. 2004;77:115–21.PubMedCrossRefGoogle Scholar
  17. 17.
    Soler AM, Warloe T, Berner A, et al. A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolevulinate-based photodynamic therapy alone and with prior curettage. Br J Dermatol. 2001;145:467–71.PubMedCrossRefGoogle Scholar
  18. 18.
    Basset-Seguin N, Ibbotson SH, Emtestam L, et al. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Eur J Dermatol. 2008;18(5):547–53.PubMedGoogle Scholar
  19. 19.
    Foley P. Clinical efficacy of methyl aminolevulinate (Metvix) photodynamic therapy. J Dermatolog Treat. 2003;14 Suppl 3:15–22.PubMedGoogle Scholar
  20. 20.
    Rhodes LE, de Rie MA, Leifsdottir R, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol. 2007;143(9):1131–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Szeimies RM, Ibbotson S, Murrell DF, et al. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20 mm), with a 12-month follow-up. J Eur Acad Dermatol Venereol. 2008;22(11):1302–11.PubMedCrossRefGoogle Scholar
  22. 22.
    Vinciullo C, Elliott T, Francis D, et al. Photodynamic therapy with topical methyl aminolaevulinate for ‘difficult-to-treat’ basal cell carcinoma. Br J Dermatol. 2005;152:765–72.PubMedCrossRefGoogle Scholar
  23. 23.
    Horn M, Wolf P, Wulf HC, et al. Topical methyl aminolevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment. Br J Dermatol. 2003;149:1242–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Kao GF. Carcinoma arising in Bowen’s disease. Arch Dermatol. 1986;122:1124–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Stables GI, Stringer MR, Robinson DJ, et al. Large patches of Bowen’s disease treated by topical aminolaevulinic acid photodynamic therapy. Br J Dermatol. 1997;136:957–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Morton CA, Whitehurst C, Moore JV, et al. Comparison of red and green light in the treatment of Bowen’s disease by photodynamic therapy. Br J Dermatol. 2000;143:767–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Britton JE, Goulden V, Stables G, et al. Investigation of the use of the pulsed dye laser in the treatment of Bowen’s disease using 5-aminolaevulinic acid phototherapy. Br J Dermatol. 2005;153:780–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Svanberg K, Andersson T, Killander D, et al. Photodynamic therapy of non-melanoma malignant tumours of the skin using topical delta-amino levulinic acid sensitization and laser irradiation. Br J Dermatol. 1994;130:743–51.PubMedCrossRefGoogle Scholar
  29. 29.
    Fijan S, Honigsmann H, Ortel B. Photodynamic therapy of epithelial skin tumours using delta-aminolaevulinic acid and desferrioxamine. Br J Dermatol. 1995;133:282–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Morton C, Horn M, Leman J, et al. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or fluorouracil for treatment of squamous cell carcinoma in situ: results of a multicenter randomized trial. Arch Dermatol. 2006;142:729–35.PubMedCrossRefGoogle Scholar
  31. 31.
    Calzavara-Pinton PG, Venturini M, Sala R, et al. Methylaminolaevulinate-based photodynamic therapy of Bowen’s disease and squamous cell carcinoma. Br J Dermatol. 2008;159:137–44.PubMedCrossRefGoogle Scholar
  32. 32.
    Grapengiesser S, Ercson M, Gudmundsson F, et al. Pain caused by photodynamic therapy of skin cancer. Clin Exp Dermatol. 2002;27:493–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Fuchs J, Weber S, Kaufmann R. Genotoxic potential of porphyrin type photosensitizers with particular emphasis on 5-aminolevulinic acid: implications for clinical photodynamic therapy. Free Radic Biol Med. 2000;28:537–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Wolf P, Fink- Puches R, Reimann- Weber A, et al. Development of malignant melanoma after repeated topical photodynamic therapy with 5- aminolevulinic acid at the exposed site. Dermatology. 1997;194:53–4.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Raffaella Sala
    • 1
  • Maria Teresa Rossi
    • 1
  • Piergiacomo Calzavara-Pinton
    • 1
  1. 1.Department of DermatologyUniversity of BresciaBresciaItaly

Personalised recommendations