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Deutsches Arzteblatt International Sep 2019Cutaneous squamous cell carcinoma (cSCC) and its precursors, actinic keratoses (AK), are common. Physicians of multiple specialties are confronted with their treatment. (Review)
Review
BACKGROUND
Cutaneous squamous cell carcinoma (cSCC) and its precursors, actinic keratoses (AK), are common. Physicians of multiple specialties are confronted with their treatment.
METHODS
This review is based on publications retrieved by a selective search in PubMed, as well as on the German guidelines on AK and cSCC, skin cancer prevention, and surgery with histologic guidance.
RESULTS
Local treatments for AK include lesional cryotherapy, curettage, and laser ablation as well as field-directed treatments with topical agents, e.g., diclofenac plus hyaluronic acid, imiquimod, 5-fluorouracil, ingenol mebutate, and photodynamic therapy. These treatments can be administered in various sequences or combinations, depending on individual factors and the stage of the disease. The gold standard of treatment for cSCC is histologically confirmed complete resection; radiotherapy is an alternative. Locally uncontrollable or metastatic disease is treated with systemic drugs. The use of various chemotherapeutic agents, EGFR-directed therapies, and the PD-I inhibitor cemiplimab, either singly or in combination, has been described in uncontrolled trials and case series. Cemiplimab has a reported response rate of 47% and was recently approved for the treatment of advanced cSCC.
CONCLUSION
There are many options for the treatment of AK and cSCC that must be considered in the interdisciplinary care of these entities.
Topics: Carcinoma, Squamous Cell; Humans; Keratosis, Actinic; Skin Neoplasms
PubMed: 32048593
DOI: 10.3238/arztebl.2019.0616 -
Anais Brasileiros de Dermatologia 2019Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or... (Review)
Review
Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder.
Topics: Albinism; Brazil; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Keratosis, Actinic; Male; Melanins; Prevalence; Risk Factors; Skin Neoplasms; Ultraviolet Rays
PubMed: 31777350
DOI: 10.1016/j.abd.2019.09.023 -
International Journal of Molecular... Mar 2023Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic... (Review)
Review
Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.
Topics: Humans; Keratosis, Actinic; Aminolevulinic Acid; Diclofenac; Imiquimod; Photochemotherapy; Fluorouracil; Photosensitizing Agents; Treatment Outcome
PubMed: 36902419
DOI: 10.3390/ijms24054989 -
Anais Brasileiros de Dermatologia 2019Actinic keratoses are dysplastic proliferations of keratinocytes with potential for malignant transformation. Clinically, actinic keratoses present as macules, papules,... (Review)
Review
Actinic keratoses are dysplastic proliferations of keratinocytes with potential for malignant transformation. Clinically, actinic keratoses present as macules, papules, or hyperkeratotic plaques with an erythematous background that occur on photoexposed areas. At initial stages, they may be better identified by palpation rather than by visual inspection. They may also be pigmented and show variable degrees of infiltration; when multiple they then constitute the so-called field cancerization. Their prevalence ranges from 11% to 60% in Caucasian individuals above 40 years. Ultraviolet radiation is the main factor involved in pathogenesis, but individual factors also play a role in the predisposing to lesions appearance. Diagnosis of lesions is based on clinical and dermoscopic examination, but in some situations histopathological analysis may be necessary. The risk of transformation into squamous cell carcinoma is the major concern regarding actinic keratoses. Therapeutic modalities for actinic keratoses include topical medications, and ablative and surgical methods; the best treatment option should always be individualized according to the patient.
Topics: Carcinoma, Squamous Cell; Dermoscopy; Humans; Keratosis, Actinic; Risk Factors; Severity of Illness Index; Skin Neoplasms
PubMed: 31789244
DOI: 10.1016/j.abd.2019.10.004 -
The Journal of Dermatological Treatment Aug 2017Actinic keratosis (AK) is a chronic skin disease in which multiple clinical and subclinical lesions co-exist across large areas of sun-exposed skin, resulting in field... (Review)
Review
Actinic keratosis (AK) is a chronic skin disease in which multiple clinical and subclinical lesions co-exist across large areas of sun-exposed skin, resulting in field cancerisation. Lesions require treatment because of their potential to transform into invasive squamous cell carcinoma. This article aims to provide office-based dermatologists and general practitioners with simple guidance on AK treatment in daily clinical practice to supplement existing evidence-based guidelines. Novel aspects of the proposed treatment algorithm include differentiating patients according to whether they have isolated scattered lesions, lesions clustered in small areas or large affected fields without reference to specific absolute numbers of lesions. Recognising that complete lesion clearance is rarely achieved in real-life practice and that AK is a chronic disease, the suggested treatment goals are to reduce the number of lesions, to achieve long-term disease control and to prevent disease progression to invasive squamous cell carcinoma. In the clinical setting, physicians should select AK treatments based on local availability, and the presentation and needs of their patients. The proposed AK treatment algorithm is easy-to-use and has high practical relevance for real-life, office-based dermatology.
Topics: Algorithms; Aminoquinolines; Antineoplastic Agents; Combined Modality Therapy; Cryotherapy; Disease Progression; Humans; Imiquimod; Keratosis, Actinic; Laser Therapy
PubMed: 27796187
DOI: 10.1080/09546634.2016.1254328 -
Current Treatment Options in Oncology Sep 2018Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used... (Review)
Review
Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used routinely for all pigmented and non-pigmented cutaneous neoplasms. It is especially useful for the early stage of melanoma when melanoma-specific criteria are invisible to the unaided eye. Preselection by the unaided eye is therefore not recommended. The increased availability of polarized dermatoscopes, and the extended use of dermatoscopy in non-pigmented lesions led to the discovery of new criteria, and we recommend that lesions should be examined with polarized and non-polarized dermatoscopy. The "chaos and clues algorithm" is a good starting point for beginners because it is easy to use, accurate, and it works for all types of pigmented lesions not only for those melanocytic. Physicians, who use dermatoscopy routinely, should be aware of new clues for acral melanomas, nail matrix melanomas, melanoma in situ, and nodular melanoma. Dermatoscopy should also be used to distinguish between different subtypes of basal cell carcinoma and to discriminate highly from poorly differentiated squamous cell carcinomas to optimize therapy and management of non-melanoma skin cancer. One of the most exciting areas of research is the use of dermatoscopic images for machine learning and automated diagnosis. Convolutional neural networks trained with dermatoscopic images are able to diagnose pigmented lesions with the same accuracy as human experts. We humans should not be afraid of this new and exciting development because it will most likely lead to a peaceful and fruitful coexistence of human experts and decision support systems.
Topics: Adult; Aged; Algorithms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermoscopy; Female; Humans; Keratosis, Actinic; Male; Melanoma; Sensitivity and Specificity; Skin; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 30238167
DOI: 10.1007/s11864-018-0573-6 -
The Journal of Clinical Investigation Jan 2017Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic... (Randomized Controlled Trial)
Randomized Controlled Trial
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).
Topics: Administration, Topical; Aged; Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols; CD4-Positive T-Lymphocytes; Calcitriol; Carcinoma, Squamous Cell; Cytokines; Female; Fluorouracil; Humans; Immunity, Cellular; Keratosis, Actinic; Male; Mice; Mice, Transgenic; Middle Aged; Precancerous Conditions; Skin Neoplasms; Thymic Stromal Lymphopoietin
PubMed: 27869649
DOI: 10.1172/JCI89820 -
The New England Journal of Medicine Oct 2015Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.
METHODS
In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide.
RESULTS
At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued.
CONCLUSIONS
Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials Registry number, ACTRN12612000625875.).
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Double-Blind Method; Female; Humans; Keratosis, Actinic; Male; Middle Aged; Niacinamide; Secondary Prevention; Skin Neoplasms; Vitamin B Complex
PubMed: 26488693
DOI: 10.1056/NEJMoa1506197 -
Journal of Cutaneous Medicine and... 2022Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC).
OBJECTIVE
To evaluate the effect of nicotinamide in prevention of skin cancers.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of nicotinamide. We used Medline, EMBASE, CENTRAL, and Web of Science databases from their inception to October 2020 to search the following concepts: "nicotinamide"; "randomized controlled trial" (validated filters). Two independent reviewers screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. To be eligible, ≥1 outcome had to be covered. We used a standardized collection grid to complete data extraction in duplicate. The primary outcome was skin cancers (all types). Secondary outcomes were basal cell carcinomas (BCCs); cSCCs; actinic keratoses; melanomas; digestive, cutaneous, and biochemical adverse effects (AEs). Subgroup analyses were planned .
RESULTS
We screened 4730 citations and found 29 trials (3039 patients) meeting inclusion criteria. Nicotinamide was associated with a significant reduction in skin cancers compared to control (rate ratio 0.50 (95% CI, 0.29-0.85; = 64%; 552 patients; 5 trials); moderate strength of the evidence). Heterogeneity was explained by risk of bias. Nicotinamide was associated with a significant reduction in BCCs and cSCCs, and increased risk of digestive AEs.
CONCLUSION
Oral nicotinamide should be considered in healthy patients or organ transplant recipients with history of skin cancer (GRADE: weak recommendation; moderate-quality evidence), in particular of BCC and cSCC.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemoprevention; Drug-Related Side Effects and Adverse Reactions; Humans; Keratosis, Actinic; Niacinamide; Skin Neoplasms
PubMed: 35134311
DOI: 10.1177/12034754221078201 -
Nature Communications Sep 2023Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It may progress from actinic keratosis...
Cutaneous squamous cell carcinoma (cSCC) is a serious public health problem due to its high incidence and metastatic potential. It may progress from actinic keratosis (AK), a precancerous lesion, or the in situ carcinoma, Bowen's disease (BD). During this progression, malignant keratinocytes activate dermal fibroblasts into tumor promoting cancer-associated fibroblasts (CAFs), whose origin and emergence remain largely unknown. Here, we generate and analyze >115,000 single-cell transcriptomes from healthy skin, BD and cSCC of male donors. Our results reveal immunoregulatory and matrix-remodeling CAF subtypes that may derive from pro-inflammatory and mesenchymal fibroblasts, respectively. These CAF subtypes are largely absent in AK and interact with different cell types to establish a pro-tumorigenic microenvironment. These findings are cSCC-specific and could not be recapitulated in basal cell carcinomas. Our study provides important insights into the potential origin and functionalities of dermal CAFs that will be highly beneficial for the specific targeting of the cSCC microenvironment.
Topics: Male; Humans; Carcinoma, Squamous Cell; Cancer-Associated Fibroblasts; Skin Neoplasms; Carcinoma, Basal Cell; Carcinoma in Situ; Keratosis, Actinic; Tumor Microenvironment
PubMed: 37669956
DOI: 10.1038/s41467-023-41141-9