A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies

Sinclair, Rodney; Baker, Christopher; Spelman, Lynda; Supranowicz, Madeleine; MacMahon, Beth

doi:10.1111/ajd.13447

Cited by 19 publications

(24 citation statements)

References 57 publications

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“…The high rate of complete clearance at 12 months seen in this case series, compares very favourably with other treatments, including topical 5-fluorouracil, imiquimod, and photodynamic therapy [1, 3, 4]. Our case series also suggests that radiotherapy is potentially a durable salvage option following previous treatment failure.…”

Section: Discussionsupporting

confidence: 58%

“…Extensive Skin Field Cancerization (ESFC) describes areas of solar damage involving multiple actinic keratoses, the clinical signs of photoaging, and variable numbers and types of keratinocyte skin cancers [ 1 ]. These areas are prone to new malignancies, including melanoma and non-melanoma skin cancer [ 1 ]. Significant morbidity is associated with the condition including discomfort, pruritus, and scaling, along with a poor cosmetic appearance.…”

Section: Introductionmentioning

confidence: 99%

“…Patients may also decline surgery because of the fear of poor functional or cosmetic outcomes, or simply from a surgical weariness associated with high tumour loads. Furthermore, current topical field therapies that are generally used as a first-line treatment approach for ESFC, have demonstrated limited durability outcomes with both frequent recurrence and short-term cancer prophylaxis [ 1 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy, Utilizing Volumetric Modulated Arc Therapy, for Extensive Skin Field Cancerization: A Retrospective Case Series Assessing Efficacy, Safety, and Cosmetic Outcomes at 12 Months After Treatment

Spelman

Christie

Kaminski³

et al. 2022

Case Rep Dermatol

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Extensive Skin Field Cancerization (ESFC) describes multiple actinic keratoses, with and without keratinocyte skin cancers. These areas are characterised by dysplastic keratoses, are prone to new malignancies, involve significant morbidity, have a poor cosmetic appearance, and impact negatively on quality of life. Available topical field therapies have limited durability of efficacy. Volumetric modulated arc therapy (VMAT) is an advanced form of intensity-modulated radiotherapy which achieves highly modulated and conformal dosimetry, delivering a homogeneous dose, particularly over curved surfaces, for example, scalps and limbs. This series describes the 12-month follow-up analysis of 41 VMAT treated fields from 32 (21 M, 11 F) patients. Consent was obtained after VMAT treatment to allow access to outcomes data. Conditions treated include ESFC, Bowen’s disease/SCC in situ, cutaneous squamous cell carcinoma, and basal cell carcinoma (BCC). Efficacy was measured by the percentage reduction of visible pathology within the treatment field. The primary endpoint for this review was the assessment of treatment success, defined as >90% clearance of the treatment field. As part of this definition, the appearance of isolated keratoses at 12 months was considered not significant if the field overall was clear. The development of new or recurrent cancers within the 12-month follow-up period was recorded. Thirty-six fields (87%) achieved a clinical clearance >90%. Of those, 33 (80%) fields achieved complete clearance >99% of visible actinic keratosis or keratinocyte cancers. Three fields (7%) demonstrated 91–99% clinical clearance, and no treatment failures were recorded. Two newly occurring lesions (1 BCC and 1 SCC in situ) were identified within a treated field at 12 months. The reported toxicities at 12-month post-treatment were grade 1 or 2 only, with no cases of persistent radiation dermatitis. Toxicities reported in more than 5% of cases included: alopecia (n = 4); dryness (n= 3); erythema (n = 2); and telangiectasia ulceration (n = 4). The high rate of complete clearance at 12 months seen in this case series compares very favourably with other treatments, including topical 5-fluorouracil, imiquimod, and photodynamic therapy. Toxicities reported in our patient population demonstrated that VMAT was well tolerated at 12-month post-treatment. VMAT treatment may play a growing role in future therapy for ESFC with and without keratinocyte cancers.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Radiotherapy, Utilizing Volumetric Modulated Arc Therapy, for Extensive Skin Field Cancerization: A Retrospective Case Series Assessing Efficacy, Safety, and Cosmetic Outcomes at 12 Months After Treatment

Spelman

Christie

Kaminski³

et al. 2022

Case Rep Dermatol

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“…1 AKs are premalignant proliferations of atypical keratinocytes that develop secondary to ultraviolet light exposure on chronically sun-exposed skin resulting in subsequent skin field cancerization. 2 Rates of progression from AK to squamous cell carcinoma (SCC) are unclear, however progression rates of 0 to 0.075% per lesion year or 0.53% per lesion have been reported. 3…”

Section: Introductionmentioning

confidence: 99%

Ingenol Mebutate Is Associated With Increased Reporting Odds for Squamous Cell Carcinoma in Actinic Keratosis Patients, a Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

Jedlowski

2022

J Cutan Med Surg

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Background Recently the production and marketing of ingenol mebutate in the European Union (EU) and Canada was halted due to a possible increased risk of squamous cell carcinoma (SCC) in patients with actinic keratosis (AK). Objective To investigate the relationship between SCC and topical AK medications including ingenol mebutate in the FDA Adverse Event Reporting System (FAERS). Methods Case/non-case analyses were performed in FAERS using data from 2012 to 2020 to examine the reporting odds ratio (ROR) signal for SCC for ingenol mebutate and all classes of topical AK medications under multiple conditions: i. comparison to all other drugs in FAERs, ii. comparison to other topical AK medications, iii. comparison to all other topical AK medications where only a single agent was implicated, iv. comparison of ingenol mebutate vs. imiquimod. Results A statistically significant ROR for SCC was found for ingenol mebutate under all conditions (i. 31.57 (25.45, 39.16), ii. 50.35 (32.21, 78.82), iii 61.09 (35.36, 105.56), iv. 2.53 (1.27, 5.05). A significant but substantially smaller signal was observed for imiquimod (i. 12.38 (6.42, 32.84), ii. 5.18 (2.61, 10.26), iii 5.42 (2.49, 11.78), but not for fluorouracil or diclofenac. When compared to imiquimod directly, ingenol mebutate had a statistically significant ROR for SCC (2.53 (1.27, 5.05). Conclusion Our findings support an association between SCC and ingenol mebutate. This association is maintained under controls to limit bias and falsely elevated signal including controlling for disease state and cases with multiple drug exposures and when compared to imiquimod as in Phase IV studies of ingenol mebutate.

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“…A range of 'field-directed' treatments are available for the management of ESFC. 13 These include topical treatments such as 5-fluorouracil, imiquimod, diclofenac gel, cryotherapy, 14 photodynamic therapy, laser therapy and widefield radiation therapy (e.g. intensitymodulated radiotherapy, volumetric-modulated arc therapy).…”

Section: Introductionmentioning

confidence: 99%

Method of Assessing Skin Cancerization and KeratosesTM (MASCK™): development and photographic validation in multiple anatomical sites of a novel assessment tool intended for clinical evaluation of patients with extensive skin field cancerization

Baker

James

Supranowicz

et al. 2022

Clinical and Experimental Dermatology

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Summary Background A range of ‘field‐directed’ treatments is available for the management of extensive skin field cancerization (ESFC), but to date, the only validated objective quantitative tools are limited to assessment of actinic keratoses (AKs) affecting the head. Aims To develop a versatile quantitative instrument for objective clinical assessment of ESFC and perform initial internal validation across multiple anatomical zones. Methods The study comprised instrument development, pilot testing and instrument refinement and two rounds of reliability and inter‐rater validation testing. The study was noninterventional and used a convenience sample of de‐identified patient photographs selected based on preset criteria. An expert panel developed the instrument and scoring system via a modified Delphi voting process. A sample of 16 healthcare professionals from multiple specialties undertook the pilot testing, and a panel of seven dermatologists were involved in validation testing. Validation was determined by assessment of overall inter‐rater agreement using Gwet chance‐corrected agreement coefficients (ACs). Results The instrument produced, called the Method for Assessing Skin Cancer and Keratoses™ (MASCK™), comprises the Skin Field Cancerization Index (SFCIndex), derived from area of skin involvement and AKs (number and thickness), a global assessment score and a cancer‐in‐zone score, and uses Likert scales for quantitative scoring. The SFCIndex is a composite score comprising the number and thickness of AKs multiplied by area of skin involvement. ACs for the SFCIndex components, the overall SFCIndex score and the global assessment score were > 0.80 (rated ‘almost perfect’) while the AC for the cancer‐in‐zone metric was lower (0.33, rated ‘fair’). Internal consistency was demonstrated via positive correlation between the overall SFCIndex score and the global assessment score. Conclusions Our study found near‐perfect agreement in inter‐rater reliability when using MASCK to assess the severity of ESFC in multiple anatomical sites. Further validation of this novel instrument is planned to specifically assess its reliability, utility and feasibility in clinical practice.

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A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies

Cited by 19 publications

References 57 publications

Radiotherapy, Utilizing Volumetric Modulated Arc Therapy, for Extensive Skin Field Cancerization: A Retrospective Case Series Assessing Efficacy, Safety, and Cosmetic Outcomes at 12 Months After Treatment

Radiotherapy, Utilizing Volumetric Modulated Arc Therapy, for Extensive Skin Field Cancerization: A Retrospective Case Series Assessing Efficacy, Safety, and Cosmetic Outcomes at 12 Months After Treatment

Ingenol Mebutate Is Associated With Increased Reporting Odds for Squamous Cell Carcinoma in Actinic Keratosis Patients, a Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

Method of Assessing Skin Cancerization and KeratosesTM (MASCK™): development and photographic validation in multiple anatomical sites of a novel assessment tool intended for clinical evaluation of patients with extensive skin field cancerization

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