Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study

Background: Basal cell carcinoma (BCC) is the most prevalent cancer. A minority of BCCs have an aggressive behaviour (laBCC) and may require hedgehog pathway inhibitors such as sonidegib as its treatment. Objective: To describe the use of sonidegib in a large number of patients and provide more data on its real-life efficacy and safety profile.Methods: We conducted a retrospective and multicentric study that included patients treated with sonidegib. Epidemiological, effectiveness and safety data were collected.Results: A total of 82 patients with a mean age of 73.9 years were included. Ten patients had Gorlin syndrome. Median treatment duration was 6 months. Median follow-up duration was 34.2 months. Globally, 81.7% of the patients showed clinical improvement (52.4% partial response and 29.3% complete response), 12.2% clinical stability and 6.1% disease progression. There was no statistically significant difference in clinical improvement between the 24 h and 48 h sonidegib posology. After 6 months of treatment, 48.8% of the patients discontinued sonidegib. Prior vismodegib treatment and recurrent primary BCC were associated with a poorer response to sonidegib. At 6 months of treatment, 68.3% of the patients experienced at least one adverse effect. Conclusion: Sonidegib shows good effectiveness and acceptable safety profile in usual clinical practice.& COPY; 2023 AEDV. Published by Elsevier Espan & SIM;a, S.L.U.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model

Antecedentes y objetivos La pandemia del coronavirus SARS-CoV-2 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las enfermedades oncológicas. El objetivo de este estudio es estimar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para los carcinomas de células escamosas (CCE) como de los melanomas. Material y método Estudio observacional retrospectivo de cohorte multicéntrico. Se desarrolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. Resultados Se incluyeron un total de 200 pacientes con CCE localizados en la cabeza y el cuello y 1.000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 meses tras el diagnóstico. En la muestra, los CCE mayores de 4 cm o > 6 mm de grosor (definidos como T3) pasaron de 83 (41,5%) en el grupo de estudio real a una estimación del 58,5, 70,5 y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado, respectivamente. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2, 8,2 y 5,2% a los 2, 5 y 10 años, respectivamente, tras 3 meses de retraso. Para los melanomas ultragruesos (> 6 mm de Breslow) pasaron del 6,9% en el grupo de estudio al 21,9, 30,2 y 30,2% tras 1, 2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. Conclusiones En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes.Background and objectives Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. Material and methods Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. Results Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter >4cm or thickness >6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (>6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. Conclusions In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays

External Validation of the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) in a Large European Solid Organ Transplant Recipient Cohort

Key PointsQuestionIs the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool valid for guiding skin cancer screening in solid organ transplant recipients (SOTRs)? FindingsThis prognostic study found good prognostic discrimination in a European cohort of 3421 SOTRs. The observed skin cancer incidences were similar to those predicted from the US SOTR population for each risk group. MeaningThese findings suggest that the SUNTRAC tool can be transported to different populations to stratify SOTRs into distinct skin cancer risk groups and identify those at a very high risk, opening the door to efficient and effective preventive measures.This prognostic study assesses the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool to validate it in different populations of solid organ transplant recipients.ImportanceThe Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool has been developed in the US to facilitate the identification of solid organ transplant recipients (SOTRs) at a higher risk of developing skin cancer. However, it has not yet been validated in populations other than the one used for its creation. ObjectiveTo provide an external validation of the SUNTRAC tool in different SOTR populations. Design, Setting, and ParticipantsThis retrospective external validation prognostic study used data from a prospectively collected cohort of European SOTRs from transplant centers at teaching hospitals in the Netherlands (1995-2016) and Spain (2011-2021). Participants were screened and followed up at dermatology departments. Data were analyzed from September to October 2021. Main Outcomes and MeasuresThe discrimination ability of the SUNTRAC tool was assessed via a competing risk survival analysis, cumulative incidence plots, and Wolbers concordance index. Calibration of the SUNTRAC tool was assessed through comparison of projected skin cancer incidences. Skin cancer diagnoses included squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. ResultsA total of 3421 SOTRs (median age at transplant, 53 [quartile 1: 42; quartile 3: 62] years; 2132 [62.3%] men) were assessed, including 72 Asian patients (2.1%), 137 Black patients (4.0%), 275 Latinx patients (8.0%), 109 Middle Eastern and North African patients (3.2%), and 2828 White patients (82.7%). With a total of 23213 years of follow-up time, 603 patients developed skin cancer. The SUNTRAC tool classified patients into 4 groups with significantly different risks of developing skin cancer during follow-up. Overall, the relative rate for developing skin cancer estimated using subdistribution hazard ratios (SHRs) and using the low-risk group as the reference group, increased according to the proposed risk group (medium-risk group: SHR, 6.8 [95% CI, 3.8-12.1]; P<.001; high-risk group: SHR, 15.9 [95% CI, 8.9-28.4]; P<.001; very-high-risk group: SHR, 54.8 [95% CI, 29.1-102.9]; P<.001), with a concordance index of 0.72. Actual skin cancer incidences were similar to those predicted by the SUNTRAC tool (5-year skin cancer cumulative incidence for medium-risk group: predicted, 6.2%; observed, 7.0%). Conclusions and RelevanceThe findings of this external validation prognostic study support the use of the SUNTRAC tool in European populations for stratifying SOTRs based on their skin cancer risk and also detecting patients at a high risk of developing skin cancer. This can be helpful in prioritizing and providing better screening and surveillance for these patients

Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study

none25siBackground The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. Objective To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. Methods Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. Results A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P &lt; 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. Limitations Retrospective design and heterogeneity of SOTR cohort. Conclusions MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.Ferrándiz-Pulido, C; Gómez-Tomás, A; Llombart, B; Mendoza, D; Marcoval, J; Piaserico, S; Baykal, C; Bouwes-Bavinck, J N; Rácz, E; Kanitakis, J; Harwood, C A; Cetkovská, P; Geusau, A; Del Marmol, V; Masferrer, E; Orte Cano, C; Ricar, J; de Oliveira, W R; Salido-Vallejo, R; Ducroux, E; Gkini, M A; López-Guerrero, J A; Kutzner, H; Kempf, W; Seçkin, DFerrándiz-Pulido, C; Gómez-Tomás, A; Llombart, B; Mendoza, D; Marcoval, J; Piaserico, S; Baykal, C; Bouwes-Bavinck, J N; Rácz, E; Kanitakis, J; Harwood, C A; Cetkovská, P; Geusau, A; Del Marmol, V; Masferrer, E; Orte Cano, C; Ricar, J; de Oliveira, W R; Salido-Vallejo, R; Ducroux, E; Gkini, M A; López-Guerrero, J A; Kutzner, H; Kempf, W; Seçkin,