Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: A retrospective analysis.

BACKGROUND: Cemiplimab, a programmed cell death-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy. OBJECTIVE: This retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution. METHODS: A retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-free survival (PFS) and overall survival were evaluated alongside clinical-pathologic characteristics. RESULTS: Forty-five patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and overall survival were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (P values: .043 and .046, respectively). LIMITATIONS: Limitations include its retrospective nature, the low number of patients analyzed, and the potential for inherent biases. CONCLUSIONS: The study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.

Incidence of Nonmelanoma Skin Cancers in Alberta, Canada, From 2007 to 2018.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common malignancy affecting Caucasian populations and has been seeing steady increases in incidence globally for decades. Our previous study (from Alberta, Canada) had shown a plateau in the incidence rates for NMSC. This contrasts with data from other regions within Canada and throughout the world that indicated a continued increase in incidence rates of NMSCs. OBJECTIVES: The objective of this study was to provide an update on the trends in incidence of NMSC in Alberta, Canada, from 2007 to 2018. METHODS: A retrospective analysis of patients from Alberta diagnosed with NMSC from 2007 to 2018 inclusive was conducted with data retrieved from Alberta Cancer Registry. Sex-, age-, anatomical location-, NMSC subtype-, stage-specific incidence rates and trends were examined. RESULTS: From 2007 to 2018, overall incidence rates of NMSC increased by 36%. Invasive squamous cell carcinoma (SCC) and in situ SCC demonstrated the most significant increase, invasive SCC [annual percentage change (APC) 3.48, P = .014] and in situ SCC (APC 5.61, P = .0001). In addition, we were able to determine that females had the most significant increases in NMSC incidence rates from 2007 to 2018 particularly invasive SCC (APC 3.03, P = <.0001) and in situ SCC (APC 5.08, P = <.0001). CONCLUSIONS: After initial levelling of NMSC incidence in Alberta in the early part of 21st century, the incidence of NMSC continues to increase over the past decade. The reasons for this change are not clear and likely multifactorial.

Fragile hands: targeting nonmelanoma skin cancer on older hands using 595 nm pulsed dye laser.

PURPOSE: The mainstay of treatment for nonmelanoma skin cancer (NMSC) on thin skin remains surgical, but procedures on older hands may be complicated by skin fragility and dermal atrophy. Used without cooling, 595 nm (nm) pulsed dye laser (PDL) has the capability of destroying NMSC through nonspecific thermal necrosis. The purpose of this study was to understand recurrence of NMSC on dorsal hands of older patients after one or two treatments using 595 nm PDL. METHODS: A retrospective chart review identified 147 cases of NMSC located on the dorsal hands treated with 595 nm PDL. Cases of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were included. All patients received one to two treatments with PDL. The primary outcome was the recurrence of carcinoma. RESULTS: Among NMSC cases treated with PDL, recurrence occurred in 12 patients (8.2%). No cases of BCC recurred during the study period. Recurrence of SCC was 4.7% for SCC in situ and 10.4% recurrence for invasive SCC (p = 0.34). Among 71 patients treated once, recurrence occurred in 10 patients (14.1%), and among 76 cases treated twice, recurrence occurred in 2 patients (2.6%, p = 0.01). CONCLUSION: Two treatments of PDL for NMSC on the dorsal hands of older patients was well tolerated, had low recurrence, and seemed more effective than one treatment.

Clinicopathological Pattern of Nonmelanoma Skin Cancer in Kuwait: A Retrospective Study.

OBJECTIVE: One in every three diagnosed malignancies is skin cancer, making it the most prevalent type of cancer in the world. As skin cancer is not commonly reported in Kuwait, this study was conducted to analyze the clinicopathological characteristics of nonmelanoma skin cancers (NMSC), primarily basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), during the last 13 years in a tertiary dermatology center in Kuwait. MATERIALS AND METHODS: Data were searched for patients with NMSC, primarily BCC and SCC, from 2010 to 2022. A retrospective review was conducted and descriptive data analysis was performed. RESULTS: Of 7,645 cases, a total of 146 patients had NMSC. The patient's average age was 64.9 years. 123 cases (84.2%) had BCC, whereas 23 (15.8%) had SCC. Most of the tumors were seen on the face (35.6%), scalp (20.8%), and nose (17.8%), followed by the back (6.2%), trunk (5.5%), and ear (5.5%). Well-differentiated Cutaneous SCCs were detected in 82.6% of cases. Ulceration was observed in (21.9%) of tumors. The nodular BCC subtype was observed in 50.4% of patients. CONCLUSION: BCC is the most common type of NMSC detected in Kuwait, with the scalp and face being the most common sites of involvement. Any suspicious lesions should be biopsied to rule out skin malignancy.

Review: PD-L1 as an emerging target in the treatment and prevention of keratinocytic skin cancer.

Recent advances in the understanding and targeting of immune checkpoints have led to great progress in immune therapies against many forms of cancer. While many types of immune checkpoints are currently targeted in the clinic, this review will focus on recent research implicating the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis as an emerging focus for the treatment of keratinocytic tumors. PD-L1 is of particular interest in nonmelanoma skin cancer (NMSC), as it is not only upregulated in these tumors but is stimulated by environmental ultraviolet exposure. This response may also make PD-L1 an excellent target for photochemoprevention using topically applied small molecule inhibitors. Here, we summarize recent investigations on PD-L1 expression and clinically relevant immune checkpoint inhibitor treatment in cutaneous squamous cell carcinoma, basal cell carcinoma, and head and neck squamous cell carcinoma, as well as small molecule agents targeting PD-L1 that may be useful for clinical development aiming at treatment or prevention of NMSC.

Appearance-related psychosocial distress after facial non-melanoma skin cancer surgery: A 1-year prospective study.

OBJECTIVE: Patients undergoing Mohs Micrographic Surgery (MMS) for facial non-melanoma skin cancer (NMSC) experience appearance-related psychosocial distress due to its post-surgical esthetic changes. However, little is known about its development over a longer follow-up period. This study prospectively assessed appearance-related psychosocial distress in patients undergoing MMS for facial NMSC over a 1-year follow up period. METHODS: Patients who had MMS for facial NMSC between September 2020 and October 2021 were invited to answer the FACE-Q Skin Cancer - appearance-related psychosocial distress scale preoperatively, 2 weeks, 6 months, and 1 year after surgery. RESULTS: A total of 217 patients completed the questionnaire at baseline. In addition, 158 (72.8%), 139 (64.1%), and 120 (55.3%) questionnaires were successfully answered 2 weeks, 6 months, and 1 year after surgery, respectively. Patients with a peripheral lesion presented higher appearance-related psychosocial distress scores at baseline than patients with a central lesion (p = 0.02). There was a decreasing trend in appearance-related psychosocial distress over time, but without a significant result (baseline-2-week; p = 0.73, 2-week-6-month; p = 0.80, 6-month-1-year; p = 0.17, baseline-1-year; p = 0.23). Patients with secondary intention healing and graft reconstruction methods experienced more appearance-related psychosocial distress over time than patients with primary wound closures (p = 0.03). CONCLUSIONS: Patients still experience appearance-related psychosocial distress 1 year after MMS. These patients may benefit from targeted counseling. Additionally, predictors of more appearance-related psychosocial distress, such as secondary intention healing and graft reconstruction methods, may benefit from additional psychological care.

Malignancy rates through 5 years of follow-up in patients with moderate-to-severe psoriasis treated with guselkumab: Pooled results from the VOYAGE 1 and VOYAGE 2 trials.

BACKGROUND: Malignancy risk surveillance among patients receiving long-term immunomodulatory psoriasis treatments remains an important safety objective. OBJECTIVE: To report malignancy rates in patients with moderate-to-severe psoriasis treated with guselkumab for up to 5 years versus general and psoriasis patient populations. METHODS: Cumulative rates of malignancies/100 patient-years (PY) were evaluated in 1721 guselkumab-treated patients from VOYAGE 1 and 2. Malignancy rates (excluding nonmelanoma skin cancer [NMSC]) were compared with rates in the Psoriasis Longitudinal Assessment and Registry. Standardized incidence ratios comparing malignancy rates (excluding NMSC and cervical cancer in situ) between guselkumab-treated patients and the general US population using Surveillance, Epidemiology, and End Results data were calculated, adjusting for age, sex, and race. RESULTS: Of 1721 guselkumab-treated patients (>7100 PY), 24 had NMSC (0.34/100PY; basal:squamous cell carcinoma ratio, 2.2:1), and 32 had malignancies excluding NMSC (0.45/100PY). For comparison, the malignancy rate excluding NMSC was 0.68/100PY in the Psoriasis Longitudinal Assessment and Registry. Malignancy rates (excluding NMSC/cervical cancer in situ) in guselkumab-treated patients were consistent with those expected in the general US population (standardized incidence ratio = 0.93). LIMITATIONS: Inherent imprecision in determining malignancy rates. CONCLUSIONS: In patients treated with guselkumab for up to 5 years, malignancy rates were low and generally consistent with rates in general and psoriasis patient populations.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part I: Calcineurin inhibitors, thiopurines, IMDH inhibitors, mTOR inhibitors, and corticosteroids.

Immunosuppression is a well-documented risk factor for skin cancer, as exemplified by the 65- to 250-fold higher squamous cell carcinoma risk, 10-fold higher basal cell carcinoma risk, and 0 to 8-fold higher melanoma risk in solid organ transplant recipients (SOTRs) receiving potent, prolonged courses of immunosuppressive therapies. Numerous immune system components have been shown to either suppress or promote tumor growth, and immunosuppressive drugs may have additional effects on proliferative pathways independent of the immune system. Thus, evaluation of the specific regimen by the dermatologist is key for assessing skin cancer risk in each patient. In the present manuscript, the immune-mediated mechanisms of skin cancer development and regression are first reviewed. Next, a synthesis of the evidence shows the differing effects of immunosuppressive agents commonly used in SOTRs on melanoma and nonmelanoma skin cancer risk. These include systemic calcineurin inhibitors, thiopurines, IMDH (inosine monophosphate dehydrogenase) inhibitors, mTOR (mammalian target of rapamycin) inhibitors, and systemic corticosteroids. Finally, recommendations for skin cancer screening in SOTRs are discussed. We further offer recommendations for select nontransplant patients who may benefit from routine skin cancer screening due to risks associated with specific immunosuppressant exposure, and we propose evidence-based strategies for minimizing high-risk immunosuppressant use in clinical practice.

Mohs micrographic surgery and dermatopathology concordance: An analysis of 1421 Mohs cases over 17 years.

BACKGROUND: The success of Mohs micrographic surgery depends on the surgeon's ability to correctly interpret intraoperative frozen sections. OBJECTIVE: This retrospective study analyzed the rate of concordance between Mohs surgeons and dermatopathologists in reading slides from Mohs surgery cases. METHODS: A dermatopathologist reviewed all the frozen sections and the corresponding Mohs map for every 30th Mohs case at a practice employing 6 different Mohs surgeons during 2001-2017. Cases in which the dermatopathologist and the Mohs surgeon disagreed on the interpretation were noted. RESULTS: The concordance rate between Mohs surgeons and dermatopathologists was 99.79%. The 3 discordant cases included a case of squamous cell carcinoma, a case of superficial basal cell carcinoma, and a case of hypertrophic squamous cell carcinoma in situ. LIMITATIONS: This analysis is limited to fellowship-trained Mohs surgeons and, therefore, might not be applicable to all physicians who perform Mohs. CONCLUSION: Fellowship-trained Mohs surgeons show high concordance with board-certified dermatopathologists in the accurate and precise interpretation of histology slides in the setting of Mohs micrographic surgery.

Ultraviolet B phototherapy does not increase the risk of skin cancer among patients with atopic dermatitis: A population-based retrospective cohort study.

BACKGROUND: UV-B phototherapy is a common treatment modality for patients with atopic dermatitis (AD), but its long-term safety in terms of cutaneous carcinogenic risk has not been studied. OBJECTIVE: To investigate the risk of skin cancer among patients with AD receiving UV-B phototherapy. METHODS: We conducted a nationwide population-based cohort study from 2001 to 2018 to estimate the risk of UV-B phototherapy for skin cancer, nonmelanoma skin cancer, and cutaneous melanoma in patients with AD. RESULTS: Among 6205 patients with AD, the risks of skin cancer (adjusted hazard ratio [HR], 0.91; 95% CI, 0.35-2.35), nonmelanoma skin cancer (adjusted HR, 0.80; 95% CI, 0.29-2.26), and cutaneous melanoma (adjusted HR, 0.80; 95% CI, 0.08-7.64) did not increase among patients with AD treated with UV-B phototherapy, compared with those who did not receive UV-B phototherapy. Additionally, the number of UV-B phototherapy sessions was not associated with an increased risk of skin cancer (adjusted HR, 0.99; 95% CI, 0.96-1.02), nonmelanoma skin cancer (adjusted HR, 0.99; 95% CI, 0.96-1.03), or cutaneous melanoma (adjusted HR, 0.94; 95% CI, 0.77-1.15). LIMITATIONS: Retrospective study. CONCLUSION: Neither UV-B phototherapy nor the number of UV-B phototherapy sessions was associated with an increased risk of skin cancers among patients with AD.

Host and primary tumor factors for the development of multiple cutaneous squamous cell carcinomas among a retrospective cohort in Rhode Island.

INTRODUCTION: Risk factors for a primary cutaneous squamous cell carcinoma (CSCC) are well-established; however, the host and primary tumor risk factors for subsequent CSCC have not been fully explored. METHODS: We performed a retrospective chart review of patients diagnosed with CSCC in an academic dermatology clinic in Rhode Island from 2016-2019. Logistic regression was used to evaluate the associations between host factors and multiple CSCC and between primary tumor characteristics and the risk of subsequent CSCC. Adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: A total of 1312 patients with CSCC diagnoses were included. Host risk factors significantly associated with multiple CSCCs included: aged >80 years (aOR, 2.18; 95% CI, 1.46-3.31); history of: solid organ transplant (aOR, 2.41; 95% CI, 1.20-4.80); skin cancer (aOR, 1.96; 95% CI, 1.52-2.54); other cancer (aOR, 1.49; 95% CI, 1.11-2.00); family history of skin cancer (aOR, 1.36; 95% CI, 1.03-1.78); and actinic keratosis (aOR, 1.52; 95% CI, 1.18-1.95). Tumor location, diameter, histologic differentiation, and treatment were not significant predictors of subsequent CSCCs. LIMITATIONS: Study patients were predominantly White and from a single institution, limiting the generalizability of results. CONCLUSIONS: Certain host characteristics were associated with the development of subsequent CSCC, which may inform clinical guidelines for follow-up.

Risk of melanoma and nonmelanoma skin cancer with immunosuppressants, part II: Methotrexate, alkylating agents, biologics, and small molecule inhibitors.

In solid organ transplant recipients, skin cancer risk associated with posttransplant immunosuppression has been well-described, and screening practices generally reflect these risks. In addition to agents used posttransplant, other classes of immunosuppressants also have the potential to raise the risk of nonmelanoma skin cancer (NMSC) or melanoma. In the present manuscript, the evidence for melanoma and NMSC risk associated with methotrexate, cyclophosphamide, biologic cytokine inhibitors including TNF (tumor necrosis factor)-alpha and interleukin inhibitors, costimulation blockers such as abatacept, integrin inhibitors such as natalizumab, targeted B-cell, and T-cell inhibitors including CD20 (cluster of differentiate 20), CD52, and BTK (Bruton's tyrosine kinase) inhibitors, and JAK (Janus kinase) inhibitors is reviewed. Based on the available data, we recommend regular skin cancer screening for select nontransplant patients receiving immunosuppressive regimens that are shown to raise the risk of NMSC or melanoma. We also offer suggestions for conscientious use of these therapies in high-risk patients. Finally, a comprehensive summary of the relative risk associated with each immunosuppressant class and associated recommendations is presented.

Factors associated with suspected nonmelanoma skin cancers, dysplastic nevus, and cutaneous melanoma among first-time SpotMe screening program participants during 2009-2010.

BACKGROUND: There have been no studies of the American Academy of Dermatology's SpotMe skin cancer screening program to collectively analyze and determine the factors associated with suspected basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dysplastic nevus (DN), and cutaneous melanoma (CM) diagnoses. OBJECTIVE: Describe the demographics, risk factors, and access to care profiles associated with suspected diagnoses of BCC, SCC, DN, and CM among first-time SpotMe screenees during 2009-2010. METHODS: We conducted a cross-sectional analysis of data from the SpotMe skin cancer screenings conducted in 2009 and 2010. We performed multivariable logistic regression analysis for each diagnosis, incorporating standard demographic, access to care, and risk factor variables in the models. RESULTS: Men, those without a regular dermatologist, persons reporting recently changing moles, and those with a personal history of melanoma were at increased risk for each of the suspected diagnoses analyzed. Uninsured persons were at increased risk for suspected malignancies (BCC, SCC, and CM). LIMITATIONS: Lack of histologic confirmation for diagnoses and cross-sectional design. CONCLUSION: Among first-time SpotMe participants, suspected diagnoses of BCC, SCC, DN, and CM shared several associated factors, which may be considered when planning outreach and screening for populations at risk for skin cancer.

Predictors of patient satisfaction with Mohs micrographic surgery at time of surgery and 3 months postsurgery: A prospective cohort study.

BACKGROUND: Despite the importance of patient satisfaction in ensuring high-quality care, studies investigating patient satisfaction in Mohs micrographic surgery (MMS) are limited. OBJECTIVE: We investigated the factors associated with patient satisfaction in MMS for nonmelanoma skin cancer and how patient satisfaction changes in the postoperative period. METHODS: In this prospective cohort study including 100 patients, patient satisfaction surveys were administered at the time of surgery and at 3 months postsurgery. Sociodemographic characteristics, medical history, and surgical parameters were collected by chart review. Univariate linear and logistic regression models were created to examine these relationships. RESULTS: Decreased satisfaction was observed in patients requiring 3 or more MMS stages both at the time of surgery (P = .047) and at 3 months post-surgery (P = .0244). Patients with morning procedures ending after 1:00 pm had decreased satisfaction at the time of surgery (P = .019). A decrease in patient satisfaction between the time of surgery and 3 months postsurgery was observed in patients with surgical sites on the extremities (P = .036), larger preoperative lesion sizes (P = .012), and larger defect sizes (P = .033). LIMITATIONS: Single-institution data, self-selection bias, and recall bias. CONCLUSION: Patient satisfaction with MMS is impacted by numerous factors and remains dynamic over time.

Therapeutic Cancer Vaccines for Nonmelanoma Skin Cancer.

OPINION STATEMENT: The development of immunotherapies for nonmelanoma skin cancer (NMSC) has lagged far behind that for melanoma in the past few decades, given that the majority of cases are surgically curable. Nevertheless, given the steady growth in the incidence rate of NMSC and attendant increase in patients with unresectable or advanced-stage tumors, the demand for systemic therapy is noticeably increasing. To date, the most widely used immunotherapeutic strategies, including immune checkpoint inhibitors and T-cell therapy, have obtained satisfactory results in some patients but not others. Even with an objective response in a fraction of patients, some accompanying adverse events may lead to intolerance and noncompliance. The expanding understanding of immune surveillance and tumor escape has provided us with novel perspectives in the field of immunotherapy. One emerging approach, the therapeutic cancer vaccine, encompasses the potential to newly "prime" T cells by activating antigen presentation in regional lymph nodes and the tumor microenvironment. Immune cells are therefore preconditioned and awakened to be ready to attack tumors. In NMSCs, multiple clinical trials of cancer vaccines are underway. The vaccine targets include tumor-associated antigens, tumor-specific antigens, oncolytic viruses, and toll-like receptors. Although clinical benefits have been shown in specific case reports and trials, various challenges remain to be resolved to guarantee applicability in the general patient population. Standing on the shoulders of pioneers expedites the pace of advances in therapeutic cancer vaccines, making them the rising star in the field of immunotherapy.

Cross-cultural adaptation of the Skin Cancer Index into Brazilian Portuguese for patients with cervicofacial nonmelanoma skin cancer.

PURPOSE: This study aimed to translate the Skin Cancer Index (SCI) into Portuguese, adapt it for Brazilian culture, and clinically validate it. METHODS: A five-stage cross-cultural adaptation model was followed, with subsequent clinical validation. Inter-rater agreement was assessed using the content validity index (CVI). The hypothesis of the non-inferiority of the CVI at 80% probability level was evaluated using an exact binomial test. We used Spearman's rank-order and Pearson's product-moment correlation analysis, internal consistency using McDonald's ω and Cronbach's α metric, and construct validity using confirmatory factor analysis. The factorial model was validated using the chi-squared test, root mean square error of approximation (RMSEA), comparative fit index (CFI), and standardized root mean square residual (SRMR). RESULTS: The first stage yielded two independent translations. After synthesis, back-translation, and review, the prefinal version was tested on 40 patients. Inter-rater agreement indices on content validity were significantly higher than 80% (p < 0.05). The SCI remained stable, and the Spearman's rank-order (rs), Pearson product-moment (r), and intraclass correlation coefficients were > 0.9, indicating excellent reliability. The reliability of McDonald's ω was considered ideal (> 0.8) in all subdimensions and scale. Cronbach's α was considered ideal in the "Emotional" and "Social" subdimensions and scale. Construct validity was observed in all subdimensions and scale through the criteria (χ2) p value > 0.05, RMSEA < 0.08, CFI ≥ 0.9, and SRMR ≤ 0.08. CONCLUSION: The cross-cultural adaptation of the SCI to Portuguese for Brazilian culture showed content validity and reliability, contributing to quality of life assessment in patients with NMSC.

Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness.

BACKGROUND: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHIs) changed the treatment landscape for this complex patient population. OBJECTIVES: The aims of the present study are to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC and to investigate effectiveness and safety of HHI. METHODS: A multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 - October 15, 2022. Patients aged ≥18 years and diagnosed with aBCC (locally advanced [laBCC] and metastatic BCC [mBCC]) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (complete response [CR]: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with nonresponse to HHI therapy ([OR: 2.61; 95% CI: 1.09-6.05; p: 0.03] and [OR: 2.74; 95% CI: 1.03-7.9; p: 0.04]), respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity. CONCLUSIONS: Our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting.

Skin Cancer Development Is Strongly Associated with Actinic Keratosis in Solid Organ Transplant Recipients: A Danish Cohort Study.

BACKGROUND AND OBJECTIVES: Solid organ transplant recipients (SOTRs) are at increased risk of skin cancer and suffer from greater disease-specific morbidity and mortality. To risk stratify the expanding SOTR population for more targeted skin cancer screening, a detailed understanding of risk factors is needed. Using combined clinical and pathological data to capture prevalence of actinic keratosis (AK) and skin cancer, this study aimed to identify risk factors of skin cancer development in a Danish SOTR cohort. METHODS: The trial comprised a retrospective cohort study of patients attending organ transplant clinics at the dermatological departments of Bispebjerg and Gentofte Hospitals in Copenhagen, Denmark, between 2009 and 2021. In addition to pathology records, AK prevalence was determined by review of electronic medical records (EMRs) of SOTR visits which specifically included descriptions of clinical AK. Prevalence of skin cancer, here defined as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) (invasive or in situ), or melanoma (invasive or in situ), was determined by EMR and pathology code review. Additional data extracted from EMRs included age, sex, Fitzpatrick skin type, transplantation date and type, and immunosuppressive therapy. The effect of risk factors on skin cancer was calculated by Cox proportional hazards regression. RESULTS: A total of 822 SOTRs were included with a mean follow-up duration of 10.8 years (SD 2.4 years). A skin dysplasia diagnosis was identified in 30% (n = 250) of the population, consisting of either AK (22%; n = 177), skin cancer (23%; n = 186) or both (14%; n = 113). An AK diagnosis predicted both SCC (odds ratio [OR]: 31.5 [95% CI: 9.8-100.6], p < 0.0001) and BCC development (OR: 2.3 [95% CI: 1.6-3.3], p < 0.0001), with AKs diagnosed an average 3.1 years before the first SCC (p < 0.0001). Correspondingly, while the risk of SCC in SOTRs without AK was 1.4% 25 years after transplantation, SOTRs with AKs had a 23% SCC risk only 10 years posttransplant. Other identified risk factors included Fitzpatrick skin type I (BCC: OR: 2.4 [95% CI: 1.2-5.0], p = 0.018; SCC: 3.2 [95% CI: 1.2-8.2], p = 0.016) and transplantation duration >15 years (BCC: OR: 1.8 [95% CI: 1.2-2.7], p = 0.007). No significant association between skin cancer development and sex or immunosuppressive regimen was shown. CONCLUSION: Keratinocyte carcinoma is strongly associated with an AK diagnosis in SOTRS and should prompt intensified skin cancer screening in affected individuals.

Ultrasound Assessment of Skin Tumors Local Recurrence.

Skin cancer may recur at or around the surgical site despite wide excisions. Prompt clinical and sonographic detection of local recurrence is important since subjects with relapsing melanomas or nonmelanoma malignancies can be managed efficaciously, with a relevant impact on morbidity and survival. Ultrasound is being employed with increasing frequency in the assessment of skin tumors, but most of the published articles relate to initial pretherapeutic diagnosis and staging. This review aims to offer an illustrated guide to the sonographic evaluation of locally recurring skin cancer. We introduce the topic, then we provide some sonographic tips for patient follow-up, then we describe the ultrasound findings in case of local recurrence, illustrating the main mimickers, and finally, we mention the role of ultrasound in guiding diagnostic and therapeutic percutaneous procedures.

Risk of subsequent keratinocyte carcinomas after a first diagnosis in Tasmania, Australia.

BACKGROUND/OBJECTIVE: A history of keratinocyte carcinoma (KC) is a risk factor for further KCs, but population-based studies quantifying the risk are lacking in Australia. We aimed to describe the risk of subsequent KCs after first KCs in the Australian state of Tasmania. METHODS: Tasmanian residents identified in the Tasmanian Cancer Registry with a first histologically confirmed basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or synchronous BCC and SCC (within 3 months) between January 1985 and December 2013 were followed up for at least 5 years for the development of a subsequent KC. Cumulative risk, incidence rates and standardised incidence ratios (SIRs) were calculated. RESULTS: Those first diagnosed with BCC-only, SCC-only or synchronous BCC and SCC had (i) 5-year cumulative risks of subsequent KCs of 32%, 29% and 51%, (ii) annualised 5-year incidence rates of 8100/100,000 person-years at risk (PYR), 7747/100,000 PYR and 16,634/100,000 PYR and (iii) SIRs of 10.6 (95% CI: 10.5-10.6), 12.5 (95% CI: 12.4-12.6) and 313.0 (95% CI: 305.2-321.1), respectively. Risk estimates increased substantially when multiple (two or more) lesions of any type were diagnosed synchronously. CONCLUSIONS: In the first Australian population-based study to describe the risk of subsequent KCs according to histological types, around one in three Tasmanians diagnosed with first KCs were diagnosed with subsequent KCs within 5 years. The risk of subsequent KCs was higher among those with a history of multiple synchronous lesions, especially if they included both BCC and SCC lesions.