市橋正光：【高齢者の皮膚疾患 考え方と対応】皮膚の老化 光老化．皮膚科の臨床 2001;43:1305-1312.
D P SLAUGHTER, H W SOUTHWICK, W SMEJKAL
Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin.
Cancer. 1953 Sep;6(5):963-8.
Abstract/Text
Boudewijn J M Braakhuis, Maarten P Tabor, J Alain Kummer, C René Leemans, Ruud H Brakenhoff
A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications.
Cancer Res. 2003 Apr 15;63(8):1727-30.
Abstract/Text
The concept of "field cancerization" was first introduced by Slaughter et al. [D. P, Slaughter et al., Cancer (Phila.), 6: 963-968, 1953] in 1953 when studying the presence of histologically abnormal tissue surrounding oral squamous cell carcinoma. It was proposed to explain the development of multiple primary tumors and locally recurrent cancer. Organ systems in which field cancerization has been described since then are: head and neck (oral cavity, oropharynx, and larynx), lung, vulva, esophagus, cervix, breast, skin, colon, and bladder. Recent molecular findings support the carcinogenesis model in which the development of a field with genetically altered cells plays a central role. In the initial phase, a stem cell acquires genetic alterations and forms a "patch," a clonal unit of altered daughter cells. These patches can be recognized on the basis of mutations in TP53, and have been reported for head and neck, lung, skin, and breast cancer. The conversion of a patch into an expanding field is the next logical and critical step in epithelial carcinogenesis. Additional genetic alterations are required for this step, and by virtue of its growth advantage, a proliferating field gradually displaces the normal mucosa. In the mucosa of the head and neck, as well as the esophagus, such fields have been detected with dimensions of >7 cm in diameter, whereas they are usually not detected by routine diagnostic techniques. Ultimately, clonal divergence leads to the development of one or more tumors within a contiguous field of preneoplastic cells. An important clinical implication is that fields often remain after surgery of the primary tumor and may lead to new cancers, designated presently by clinicians as "a second primary tumor" or "local recurrence," depending on the exact site and time interval. In conclusion, the development of an expanding preneoplastic field appears to be a critical step in epithelial carcinogenesis with important clinical consequences. Diagnosis and treatment of epithelial cancers should not only be focused on the tumor but also on the field from which it developed.
J A Deltondo, K F Helm
Actinic keratosis: precancer, squamous cell carcinoma, or marker of field cancerization?
G Ital Dermatol Venereol. 2009 Aug;144(4):441-4.
Abstract/Text
The early detection, recognition, and progression of the actinic keratosis (AK) and its relationship with squamous cell carcinoma have long been an area of debate. Recent advancements in medicine have examined the role of field cancerization in a variety of tumors. The role of AK as a marker for field cancerization will be here discussed.
I Zalaudek, J Giacomel, G Argenziano, R Hofmann-Wellenhof, T Micantonio, A Di Stefani, M Oliviero, H Rabinovitz, H P Soyer, K Peris
Dermoscopy of facial nonpigmented actinic keratosis.
Br J Dermatol. 2006 Nov;155(5):951-6. doi: 10.1111/j.1365-2133.2006.07426.x.
Abstract/Text
BACKGROUND: The accuracy of clinical diagnosis of nonpigmented, facial actinic keratosis (AK) is often suboptimal, even for experienced clinicians.
OBJECTIVES: To investigate the dermoscopic features of nonpigmented AK located on the head/neck that may assist the clinical diagnosis.
METHODS: Forty-one nonpigmented AKs on facial sites were examined by dermoscopy for any consistent underlying features. Lesions were gathered from skin cancer centres in Australia, Austria, Italy and the U.S.A. All cases were diagnosed histopathologically.
RESULTS: Four essential dermoscopic features were observed in facial AK: (i) erythema, revealing a marked pink-to-red 'pseudonetwork' surrounding the hair follicles (95%); (ii) white-to-yellow surface scale (85%); (iii) fine, linear-wavy vessels surrounding the hair follicles (81%); and (vi) hair follicle openings filled with yellowish keratotic plugs (66%) and/or surrounded by a white halo (100%). These features combined, in 95% of cases, to produce a peculiar 'strawberry' appearance.
CONCLUSIONS: A dermoscopic model of 'strawberry' pattern is presented, which may prove helpful in the in vivo diagnosis of nonpigmented, facial AK. A limitation of this study is the lack of testing of the specificity of the described dermoscopic criteria in differentiating nonpigmented AKs from other nonpigmented skin lesions at this site.
安齋眞一ほか: 皮膚悪性腫瘍ガイドライン第3版 有棘細胞癌診療ガイドライン2020. 日皮会誌2020; 130: 2501-2533.
J A Siegel, K Korgavkar, M A Weinstock
Current perspective on actinic keratosis: a review.
Br J Dermatol. 2017 Aug;177(2):350-358. doi: 10.1111/bjd.14852. Epub 2016 Aug 8.
Abstract/Text
Actinic keratoses (AKs) are common, with prevalence in the U.S.A. estimated at almost 40 million in 2004 and annual costs of > $1 billion (U.S.D.). However, there is no universally accepted definition of AK and thus it is difficult to identify reliably. AKs are lesions of epidermal keratinocytic dysplasia that result from chronic sun exposure and have the ability to progress to invasive squamous cell carcinoma (SCC), but clinicians disagree about whether AKs are premalignant lesions, superficial SCCin situ or epiphenomena of chronically sun-damaged skin. Yearly AK to SCC progression rates of 0·6% were reported in an elderly population with multiple prior keratinocyte carcinomas (KCs); and rates of spontaneous AK regression have been reported to be > 50%, but regressed lesions often reappear. As AKs have both cosmetic consequences and potential for malignant transformation, there are multiple reasons for treatment. There is no current agreement on the most efficacious treatment, but 5-fluorouracil has been shown to both prevent and treat AKs, and imiquimod and photodynamic therapy may have the best cosmetic outcomes. AKs may be treated to improve appearance and relieve symptoms, but the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, may be what actually threatens patient health. Thus, treatments should aim to decrease the risk of KC or facilitate KC diagnosis by reducing the potential for misidentification created when a KC appears in a field of AKs. Improved agreement among clinicians on AK definition may improve management.
Published [2016]. This article is a U.S. Government work and is in the public domain in the USA.
Vincent D Criscione, Martin A Weinstock, Mark F Naylor, Claudia Luque, Melody J Eide, Stephen F Bingham, Department of Veteran Affairs Topical Tretinoin Chemoprevention Trial Group
Actinic keratoses: Natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial.
Cancer. 2009 Jun 1;115(11):2523-30. doi: 10.1002/cncr.24284.
Abstract/Text
BACKGROUND: Actinic keratoses (AKs) are established as direct precursors of squamous cell carcinoma (SCC), but there is significant controversy regarding the rate at which AKs progress to SCC. The authors of this report studied a high-risk population to estimate the risk of progression of AK to SCC and to basal cell carcinoma (BCC) and the risk of spontaneous regression of untreated AKs.
METHODS: Data were obtained from participants in the Department of Veterans Affairs Topical Tretinoin Chemoprevention Trial. Participants were examined every 6 months for up to 6 years. At each examination, the locations on the face and ears of clinically diagnosed AKs and lesions scheduled for biopsy were marked, and high-resolution digital photographs were taken. These photographs were used later to map and track the presence, absence, or biopsy of each AK across visits.
RESULTS: In total, 7784 AKs were identified on the face and ears of 169 participants. The risk of progression of AK to primary SCC (invasive or in situ) was 0.60% at 1 year and 2.57% at 4 years. Approximately 65% of all primary SCCs and 36% of all primary BCCs diagnosed in the study cohort arose in lesions that previously were diagnosed clinically as AKs. The majority of AKs (55%) that were followed clinically were not present at the 1-year follow-up, and the majority (70%) were not present at the 5-year follow-up.
CONCLUSIONS: In the current study, the authors quantified the malignant potential of clinically diagnosed AKs for both SCC and BCC, although many did not persist, and the results suggested that AKs may play a greater role in the overall burden of keratinocyte carcinomas than previously documented.
R Marks, G Rennie, T S Selwood
Malignant transformation of solar keratoses to squamous cell carcinoma.
Lancet. 1988 Apr 9;1(8589):795-7. doi: 10.1016/s0140-6736(88)91658-3.
Abstract/Text
1689 people aged 40 years and over were examined over a 5-year period to determine the incidence of malignant transformation of solar keratoses. They were seen on 2 consecutive years on 4267 occasions; a total of 21,905 solar keratoses were present on the first visit. A squamous cell carcinoma (SCC) developed within 12 months on 28 of the 4267 occasions. Where accurate mapping of both SCCs and pre-existing solar keratoses was available, it was found that 10/17 (60%) SCCs arose from a lesion diagnosed clinically as a solar keratosis in the previous year and the other 7 (40%) SCCs on what had been clinically normal skin 12 months previously. The risk of malignant transformation of a solar keratosis to SCC within 1 year was less than 1/1000. The cost-effectiveness of treating all solar keratoses to prevent the development of SCC is questionable.
S C Thompson, D Jolley, R Marks
Reduction of solar keratoses by regular sunscreen use.
N Engl J Med. 1993 Oct 14;329(16):1147-51. doi: 10.1056/NEJM199310143291602.
Abstract/Text
BACKGROUND: The incidence of and mortality from skin cancer are increasing in many countries. In view of the added concern about ozone depletion, many organizations are promoting the regular use of sunscreens to prevent skin cancer, despite the absence of evidence that these products have this effect. Solar (actinic) keratosis is a precursor of squamous-cell carcinoma of the skin.
METHODS: We conducted a randomized, controlled trial of the effect on solar keratoses of daily use of a broad-spectrum sunscreen cream with a sun-protection factor of 17 in 588 people 40 years of age or older in Australia during one summer (September 1991 to March 1992). The subjects applied either a sunscreen cream or the base cream minus the active ingredients of the sunscreen to the head, neck, forearms, and hands.
RESULTS: The mean number of solar keratoses increased by 1.0 per subject in the base-cream group and decreased by 0.6 in the sunscreen group (difference, 1.53; 95 percent confidence interval, 0.81 to 2.25). The sunscreen group had fewer new lesions (rate ratio, 0.62; 95 percent confidence interval, 0.54 to 0.71) and more remissions (odds ratio, 1.53; 95 percent confidence interval, 1.29 to 1.80) than the base-cream group. There was a dose-response relation: the amount of sunscreen cream used was related to both the development of new lesions and the remission of existing ones.
CONCLUSIONS: Regular use of sunscreens prevents the development of solar keratoses and, by implication, possibly reduces the risk of skin cancer in the long-term.
Steven Darlington, Gail Williams, Rachel Neale, Christine Frost, Adèle Green
A randomized controlled trial to assess sunscreen application and beta carotene supplementation in the prevention of solar keratoses.
Arch Dermatol. 2003 Apr;139(4):451-5. doi: 10.1001/archderm.139.4.451.
Abstract/Text
BACKGROUND: Solar keratoses (SKs) are among the strongest determinants of skin cancer, but little is known about the success of measures to control these common skin tumors.
OBJECTIVE: To determine whether daily sunscreen application and/or beta carotene supplementation retards the rate of occurrence of SKs in adults in the medium term.
DESIGN: Randomized controlled trial conducted between February 1992 and August 1996.
SETTING: General community of the subtropical township of Nambour, Australia (latitude, 26 degrees south).
PARTICIPANTS: A total of 1621 adults aged 25 to 74 years. Interventions Participants were randomized to daily use of sunscreen (application of a high-protection sunscreen to their head, neck, arms, and hands every morning) or application of sunscreen at their usual discretionary rate. They were also randomly assigned to take either one 30-mg tablet of beta carotene or one placebo tablet each day.
MAIN OUTCOME MEASURE: Change in the prevalent number of SKs in the intervention group relative to change in the control group.
RESULTS: The ratio of SK counts in 1994 relative to 1992 was lower in people randomized to daily sunscreen use (1.20; 95% confidence interval, 1.04-1.39) than in those randomized to discretionary sunscreen use (1.57; 95% confidence interval, 1.35-1.84). This 24% reduction is equivalent to the prevention of an average of 1 additional SK per person over that time. A reduction in the rate of change of SK prevalence was also seen in the sunscreen intervention group relative to the discretionary sunscreen group between 1994 and 1996, but it was not significant. No effect on the rate of change of prevalent SK counts was seen among those taking beta carotene supplements relative to those taking placebo tablets.
CONCLUSIONS: Daily application of sunscreen retarded the rate of SK acquisition among adults in a subtropical environment, while a beta carotene supplementation of 30 mg/d had no influence on the occurrence of SKs.
D de Berker, J M McGregor, M F Mohd Mustapa, L S Exton, B R Hughes
British Association of Dermatologists' guidelines for the care of patients with actinic keratosis 2017.
Br J Dermatol. 2017 Jan;176(1):20-43. doi: 10.1111/bjd.15107.
Abstract/Text
Daniel B Eisen, Maryam M Asgari, Daniel D Bennett, Suzanne M Connolly, Robert P Dellavalle, Esther E Freeman, Gary Goldenberg, David J Leffell, Sue Peschin, James E Sligh, Peggy A Wu, Lindsy Frazer-Green, Sameer Malik, Todd E Schlesinger
Guidelines of care for the management of actinic keratosis.
J Am Acad Dermatol. 2021 Oct;85(4):e209-e233. doi: 10.1016/j.jaad.2021.02.082. Epub 2021 Apr 2.
Abstract/Text
BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma.
OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed.
METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus.
RESULTS: Analysis of the evidence resulted in 18 recommendations.
LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data.
CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Markus V Heppt, Ulrike Leiter, Theresa Steeb, Teresa Amaral, Andrea Bauer, Jürgen C Becker, Eckhard Breitbart, Helmut Breuninger, Thomas Diepgen, Thomas Dirschka, Thomas Eigentler, Michael Flaig, Markus Follmann, Klaus Fritz, Rüdiger Greinert, Ralf Gutzmer, Uwe Hillen, Stephan Ihrler, Swen Malte John, Oliver Kölbl, Klaus Kraywinkel, Christoph Löser, Dorothée Nashan, Seema Noor, Monika Nothacker, Christina Pfannenberg, Carmen Salavastru, Lutz Schmitz, Eggert Stockfleth, Rolf-Markus Szeimies, Claas Ulrich, Julia Welzel, Kai Wermker, Carola Berking, Claus Garbe
S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma - short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators.
J Dtsch Dermatol Ges. 2020 Mar;18(3):275-294. doi: 10.1111/ddg.14048.
Abstract/Text
Actinic keratoses (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was developed using the highest level of methodology (S3) according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF). The guideline is aimed at dermatologists, general practitioners, ENT specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings as well as other medical specialties involved in the diagnosis and treatment of patients with AK and cSCC. The guideline is also aimed at affected patients, their relatives, policy makers and insurance funds. In the first part, we will address aspects relating to diagnosis, interventions for AK, care structures and quality-of-care indicators.
© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.
Colin Morton, Michael Horn, Joyce Leman, Brigitte Tack, Christophe Bedane, Milan Tjioe, Sally Ibbotson, Abdallah Khemis, Peter Wolf
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 Jun;142(6):729-35. doi: 10.1001/archderm.142.6.729.
Abstract/Text
OBJECTIVE: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ.
DESIGN: Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment.
SETTING: Forty outpatient dermatology centers in 11 European countries.
PATIENTS: Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression.
INTERVENTIONS: Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated.
MAIN OUTCOME MEASURES: Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale).
RESULTS: At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months.
CONCLUSION: Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis.
Joanna L Walker, Julia A Siegel, Moniyka Sachar, Hyemin Pomerantz, Suephy C Chen, Susan M Swetter, Robert P Dellavalle, George P Stricklin, Abrar A Qureshi, John J DiGiovanna, Martin A Weinstock
5-Fluorouracil for Actinic Keratosis Treatment and Chemoprevention: A Randomized Controlled Trial.
J Invest Dermatol. 2017 Jun;137(6):1367-1370. doi: 10.1016/j.jid.2016.12.029.
Abstract/Text
Trevor J Cunningham, Mary Tabacchi, Jean-Pierre Eliane, Sara Moradi Tuchayi, Sindhu Manivasagam, Hengameh Mirzaalian, Ahu Turkoz, Raphael Kopan, Andras Schaffer, Arturo P Saavedra, Michael Wallendorf, Lynn A Cornelius, Shadmehr Demehri
Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy.
J Clin Invest. 2017 Jan 3;127(1):106-116. doi: 10.1172/JCI89820. Epub 2016 Nov 21.
Abstract/Text
BACKGROUND: Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis.
METHODS: The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed.
RESULTS: Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4+ T cell infiltration, which peaked on days 10-11 after treatment, without pain, crusting, or ulceration.
CONCLUSION: Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell-mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02019355.
FUNDING: Not applicable (investigator-initiated clinical trial).
M Freeman, C Vinciullo, D Francis, L Spelman, R Nguyen, P Fergin, K-E Thai, D Murrell, W Weightman, C Anderson, C Reid, A Watson, P Foley
A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study.
J Dermatolog Treat. 2003 Jun;14(2):99-106. doi: 10.1080/09546630310012118.
Abstract/Text
BACKGROUND: Actinic keratosis (AK) is a very common condition, which has the potential of progressing to squamous cell carcinoma. The present study is a prospective, randomized study comparing the lesion response, cosmetic outcome, patient satisfaction and tolerability of a new treatment modality, photodynamic therapy (PDT), using topical methyl aminolevulinate (Metvix), with the most commonly used standard therapy for AK, cryotherapy.
METHODS: A total of 204 patients with clinically diagnosed AK were randomized to either cryotherapy or PDT. The PDT patients were further assigned to an active or placebo group in a random, double-blind manner. Cryotherapy was performed using liquid nitrogen spray in a single freeze-thaw cycle. PDT was performed using 160 mg/g methyl aminolevulinate cream or placebo, a 3-hour application time, red light (570-670 nm) and a total light dose of 75 J/cm(2). PDT was repeated after 7 days. Two sessions of PDT were undertaken, as a previous study had shown a single session had similar efficacy to cryotherapy. Lesion response was assessed clinically after 3 months (complete response or non-complete response).
RESULTS: The lesion response rate was 91% in the methyl aminolevulinate PDT group, 68% in the cryotherapy group and 30% in the placebo PDT group. Methyl aminolevulinate PDT was statistically significantly better than both cryotherapy and placebo PDT in terms of response rates and cosmetic outcome. Most patients preferred PDT to other treatments.
CONCLUSIONS: PDT with methyl aminolevulinate is an excellent treatment option, particularly for patients with widespread damage or AK lesions in cosmetically sensitive areas.
R M Szeimies, S Karrer, S Radakovic-Fijan, A Tanew, P G Calzavara-Pinton, C Zane, A Sidoroff, M Hempel, J Ulrich, T Proebstle, H Meffert, M Mulder, D Salomon, H C Dittmar, J W Bauer, K Kernland, L Braathen
Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study.
J Am Acad Dermatol. 2002 Aug;47(2):258-62.
Abstract/Text
BACKGROUND: Actinic keratoses (AKs) are the most common premalignant tumors. Without treatment, a significant number of patients with AK will experience squamous cell carcinoma. Photodynamic therapy (PDT) using the new highly selective photosensitizer methyl 5-aminolevulinate is a promising new treatment modality for AK.
OBJECTIVE: We investigated the complete response rates, cosmetic outcome, and patient satisfaction after photodynamic therapy (PDT) using methyl 5-aminolevulinate (Metvix) versus cryotherapy in the treatment of AKs.
METHODS: Patients were randomized to receive either cryotherapy with liquid nitrogen spray or PDT using methyl 5-aminolevulinate cream 160 mg/g, 3 hours application time, and red light (75 J/cm(2)).
RESULTS: Efficacy results from 193 patients with 699 lesions (92% face/scalp and 93% thin/moderately thick) were analyzed. Overall complete response rates after 3 months were 69% for PDT and 75% for cryotherapy. Both treatments gave higher response rates in thin lesions (PDT 75%, cryotherapy 80%). PDT gave better cosmetic results and higher patient satisfaction than cryotherapy.
CONCLUSION: PDT using methyl 5-aminolevulinate is an attractive treatment option for patients with AK, with a response rate similar to that of cryotherapy, but with superior cosmetic results and high patient satisfaction.
C Zane, E Facchinetti, M T Rossi, C Specchia, B Ortel, P Calzavara-Pinton
Cryotherapy is preferable to ablative CO2 laser for the treatment of isolated actinic keratoses of the face and scalp: a randomized clinical trial.
Br J Dermatol. 2014 May;170(5):1114-21. doi: 10.1111/bjd.12847.
Abstract/Text
BACKGROUND: Actinic keratosis (AK) may progress to squamous cell carcinoma. In the case of normal or mildly photodamaged skin, lesion-directed treatments are considered valuable options despite poor published evidence of their therapeutic activity.
OBJECTIVES: The aim of this single-centre, open-label, prospective, nonsponsored, randomized, controlled clinical trial was to compare CO2 laser ablation with cryotherapy in the treatment of isolated AKs of the face and scalp.
PATIENTS AND METHODS: Patients with isolated (≤ 4) AKs of the face and scalp were randomized to receive CO2 laser ablation or cryotherapy. After 90 days, the overall complete remission (CR) rates of patients and lesions were assessed and correlated with thickness grade.
RESULTS: Two hundred patients with a total number of 543 AKs were enrolled. The CR rates of lesions after 3 months were 78·2% with cryotherapy and 72·4% with CO2 laser ablation. Thicker lesions were significantly more responsive to cryotherapy (P = 0·034). Seventy-three patients (71·6%) had CR of all lesions 3 months after cryotherapy and 64 (65·3%) after laser ablation. At 12 months after treatment the number of patients with CR was reduced to 53 with cryotherapy and 14 with laser ablation.
CONCLUSIONS: The rate of patients and lesions with CR is similar after 3 months, but more patients remain in stable remission for 12 months after cryotherapy. Cryotherapy is more effective for thick lesions. The cosmetic outcome was good or excellent in almost all patients.
© 2014 British Association of Dermatologists.
N Krawtchenko, J Roewert-Huber, M Ulrich, I Mann, W Sterry, E Stockfleth
A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up.
Br J Dermatol. 2007 Dec;157 Suppl 2:34-40. doi: 10.1111/j.1365-2133.2007.08271.x.
Abstract/Text
BACKGROUND: Actinic keratoses (AK) frequently occur on sun-exposed skin and are considered as in situ squamous cell carcinoma. To date, no treatment algorithm exists for first or second line therapies due to the lack of comparative studies.
OBJECTIVE: This study compared the initial and 12-month clinical clearance, histological clearance, and cosmetic outcomes of topically applied 5% imiquimod (IMIQ) cream, 5% 5-fluorouracil (5-FU) ointment and cryosurgery for the treatment of AK.
PATIENTS/METHODS: Patients were randomised to one of the following three treatment groups: one or two courses of cryosurgery (20-40 s per lesion), topical 5-FU (twice daily for 4 weeks), or one or two courses of topical imquimod (three times per week for 4 weeks each).
RESULTS: Sixty-eight per cent (17/25) of patients treated with cryosurgery, 96% (23/24) of patients treated with 5-FU, and 85% (22/26) of patients treated with IMIQ achieved initial clinical clearance, p = 0.03. The histological clearance rate for cryosurgery was 32% (8/25), 67% (16/24) for 5-FU, and 73% (19/26) in the IMIQ group, p = 0.03. The 12-month follow-up showed a high rate of recurrent and new lesions in the 5-FU and cryosurgery arms. The sustained clearance rate of initially cleared individual lesions was 28% (7/25) for cryosurgery, 54% (13/24) for 5-FU and 73% (19/26) for IMIQ (p < 0.01). Sustained clearance of the total treatment field was 4% (1/25), 33% (8/24), and 73% (19/26) of patients after cryosurgery, 5-FU, and IMIQ, respectively (p < 0.01). The patients in the IMIQ group were judged to have the best cosmetic outcomes (p = 0.0001).
CONCLUSION: Imiquimod treatment of AK resulted in superior sustained clearance and cosmetic outcomes compared with cryosurgery and 5-FU. It should be considered as a first line therapy for sustained treatment of AK.
Basil M Hantash, Daniel B Stewart, Zachary A Cooper, Wingfield E Rehmus, R James Koch, Susan M Swetter
Facial resurfacing for nonmelanoma skin cancer prophylaxis.
Arch Dermatol. 2006 Aug;142(8):976-82. doi: 10.1001/archderm.142.8.976.
Abstract/Text
OBJECTIVE: To determine the effect of facial skin resurfacing for treatment of actinic keratoses (AKs) and prophylaxis against new primary basal and squamous cell carcinomas in individuals with previous nonmelanoma skin cancer (NMSC) or severe photodamage.
DESIGN: Randomized, prospective 5-year trial.
SETTING: Dermatology and otolaryngology clinics of a Veterans Affairs hospital.
PATIENTS: Thirty-four patients with a history of facial or scalp AKs or basal or squamous cell carcinoma were enrolled. Five of 7 eligible patients who declined study-related treatment were used as controls. Twenty-seven patients were randomized to 3 treatment arms; 3 patients were discontinued from the study.
INTERVENTIONS: Carbon dioxide laser resurfacing, 30% trichloroacetic acid peel, or 5% fluorouracil cream applied twice daily for 3 weeks.
MAIN OUTCOME MEASURES: Reduction in the number of AKs was measured 3 months after treatment. The incidence of new NMSC in treated areas was assessed between January 1, 2001, and June 30, 2005. Times from baseline to diagnosis of first skin cancer were compared between the treatment and control groups.
RESULTS: Treatment with fluorouracil, trichloroacetic acid, or carbon dioxide laser resulted in an 83% to 92% reduction in AKs (P< or =.03), a lower incidence of NMSC compared with the control group (P<.001), and a trend toward longer time to development of new skin cancer compared with the control group (P=.07). However, no significant differences were noted among the treatment groups.
CONCLUSION: All 3 modalities demonstrated benefit for AK reduction and skin cancer prophylaxis compared with controls and warrant further study in a larger trial.
E Sotiriou, Z Apalla, F Maliamani, N Zaparas, D Panagiotidou, D Ioannides
Intraindividual, right-left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities.
J Eur Acad Dermatol Venereol. 2009 Sep;23(9):1061-5. doi: 10.1111/j.1468-3083.2009.03259.x. Epub 2009 Apr 8.
Abstract/Text
BACKGROUND: Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is important. Objective To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms.
METHODS: Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients' preference 6 months after treatment. Efficacy end point included the individual AK lesion clearance rate.
RESULTS: Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ). Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT.
CONCLUSIONS: Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper extremities AKs with comparable efficacy and cosmetic outcomes.
