Longitudinal Study of Different Progression Patterns in High-Risk Cutaneous Squamous Cell Carcinoma. / Estudio longitudinal de los diferentes patrones de progresión en el carcinoma cutáneo de células escamosas de alto riesgo.

BACKGROUND AND OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. MATERIAL AND METHOD: We conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. RESULTS: A total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. CONCLUSIONS: The mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.

Sonidegib as a Locally Advanced Basal Cell Carcinoma Therapy in Real-life Clinical Setting: A National Multicentre Study. / [Artículo traducido] Sonidegib para el tratamiento del carcinoma basocelular avanzado en práctica clínica real: estudio nacional multicéntrico.

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.

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 24h and 48h 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.

Phototherapy for Prurigo Nodularis: Our Experience and a Review of the Literature. / Fototerapia en el prurigo nodular. Experiencia propia y revisión de la literatura.

BACKGROUND AND OBJECTIVE: Prurigo nodularis is a chronic inflammatory skin disease characterized by highly pruritic nodular lesions that cause constant itching and scratching and significant quality-of-life impairment. It has been described in a range of conditions, including skin diseases (mainly atopic dermatitis) and metabolic, neurological, and psychiatric disorders. The pathophysiological mechanisms are largely unknown. Various modalities of phototherapy have been described as appropriate and safe treatments for achieving clinical control and alleviating symptoms. In this article, we describe our experience with phototherapy in patients with prurigo nodularis. MATERIAL AND METHODS: Retrospective observational study of patients who received their first cycle of phototherapy to treat prurigo nodularis between March 2011 and October 2019. Information was collected on epidemiological and clinical characteristics, concomitant treatments, type and duration of phototherapy, maximum dose reached, and response to treatment. RESULTS: We studied 44 patients (30 women and 14 men) with a median age of 65.5years. The most common form of phototherapy used was narrowband UV-B phototherapy (34 cycles, 77.27%) followed by a combination of UV-B and UV-A phototherapy (8 cycles). Response to treatment was considered satisfactory (clearance rate of ≥75%) in 24 patients (55.4%). CONCLUSIONS: Phototherapy is a suitable treatment for prurigo nodularis in a considerable proportion of patients. It can be used as monotherapy or combined with other treatments.

Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: Modelo basado en un crecimiento exponencial / Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: AnExponential Growth Model

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 > 4 cm 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 tosee 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

ANTECEDENTES Y OBJETIVOS: La pandemia del coronavirus COVID-19 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las patologías comunes. 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 cohortes 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 CCEs localizados en la cabeza y el cuello y 1000 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 mes 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 de 58,5%, 70,5% y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado. 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 tres meses de retraso. Para los melanomas, los melanomas ultragruesos (> 6 mm) 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. Palabras clave: melanoma, pronóstico, diagnóstico precoz, carcinoma de células escamosas cutáneo, COVID-19, confinamiento

Reconstruction of Extreme Rainfall Event on September 19-20, 2017, Using a Weather Radar in Bengkulu of Sumatra Island.

Extreme rainfall accompanied by strong winds hit the province of Bengkulu in the western coastal area of Sumatera Island during September 19-20, 2017, causing floods and landslides in Seluma and Central Bengkulu district. This extreme rainfall was recorded by Bengkulu Meteorological Station about 257.0 mm day-1 using rain-gauge observation. The spatial distribution of extreme rainfall cannot be seen if only using a rain-gauge observation in this location. The spatial distribution of extreme rainfall is needed to identify the impact of rainfall on landslides in large areas. The study aims to (1) develop the reconstruction of the spatial distribution of extreme rainfall using weather radar and (2) investigate the trigger that caused extreme rainfall by analyzing the synoptic-scale tropical waves. Each weather radar datum is saved in a Constant Altitude Plan Position Indicator (CAPPI). To get rainfall information, the CAPPI must be derived from Quantitative Precipitation Estimation (QPE) values. In this paper, we derived CAPPI using a Marshall-Palmer reflectivity-rain rate relationship. The result shows that rainfall formed on September 20, 2017, 21.00 UTC with total daily rainfall ranged between 176 and 247 mm in both districts and the mean of total daily rainfall has exceeded the average of monthly rainfall. The analysis of tropical waves suggests that only Kelvin waves were active and served as a possible trigger factor while the Madden-Julian Oscillation (MJO) and Equatorial Rossby (ER) waves were inactive during this extreme rainfall.

[Estimated Effect of COVID-19 Lockdown on Skin Tumor Size and Survival: An Exponential Growth Model]. / Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: modelo basado en un crecimiento exponencial.

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.

Social-media and newspaper reports reveal large-scale meteorological drivers of floods on Sumatra.

Floods are a major contributor to natural disasters in Sumatra. However, atmospheric conditions leading to floods are not well understood due, among other factors, to the lack of a complete record of floods. Here, the 5 year flood record for Sumatra derived from governmental reports, as well as from crowd-sourcing data, based on Twitter messages and local newspapers' reports, is created and used to analyze atmospheric phenomena responsible for floods. It is shown, that for the majority of analyzed floods, convectively coupled Kelvin waves, large scale precipitation systems propagating at ∼12 m/s along the equator, play the critical role. While seasonal and intraseasonal variability can also create conditions favorable for flooding, the enhanced precipitation related to Kelvin waves was found in over 90% of flood events. In 30% of these events precipitation anomalies were attributed to Kelvin waves only. These results indicate the potential for increased predictability of flood risk.

Postoperative radiotherapy provides better local control and long-term outcome in selective cases of cutaneous squamous cell carcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is a feature of poor prognosis in cutaneous squamous cell carcinoma (CSCC). The benefit of postoperative radiotherapy (PORT) in the management of CSCC with PNI is still not well established. OBJECTIVES: We aimed to evaluate the usefulness of PORT in the treatment of CSCC with PNI so as to determine which patients would best benefit from this type of treatment. METHODS: A retrospective multicenter cohort of 110 CSCCs with PNI was evaluated. Eighteen recurrent cases were excluded for subsequent analysis. We searched for the types of PNI associated with poor outcome and analysed the effectiveness of PORT on different groups of CSCC with PNI. We also assessed for the usefulness of PORT depending on the surgical margin status (either clear or positive). RESULTS: Postoperative radiotherapy showed clear benefit over observation in CSCC with PNI and positive margins after surgery, where the management by observation increased the risk of poor outcome events 2.43 times (P = 0.025), and especially in those with positive margins and PNI ≥0.1 mm, where the risk of poor prognosis is eight times greater following a management by observation (P = 0.0065). Multivariate competing risk analysis preserved statistical significance. CONCLUSIONS: The use of PORT on patients with CSCC with PNI and positive margins after surgery, especially in PNI ≥0.1 mm, significantly improves long-term outcome. The benefit of PORT in cases with clear margins is not as evident, especially in those with PNI of small-calibre nerves. Clinical trials are imperative.

Utilidad de la radioterapia en adyuvancia en el carcinoma epidermoide cutáneo / The Value of Adjuvant Radiotherapy in Cutaneous Squamous Cell Carcinoma: A Review

El carcinoma epidermoide cutáneo (CEC) es el segundo tumor más frecuente en humanos y tiene una incidencia creciente. Aunque la cirugía representa el tratamiento de elección del CEC, la radioterapia adyuvante postoperatoria tiene un papel relevante en el control local y locorregional de la enfermedad. En esta revisión analizamos la utilidad de la radioterapia postoperatoria en el manejo del CEC de alto riesgo (especialmente con infiltración perineural), en el control del CEC con márgenes positivos tras la cirugía y en el CEC localmente avanzado (con metástasis parotídeas o ganglionares)

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans and its incidence is rising. Although surgery is the treatment of choice for cSCC, postoperative adjuvant radiotherapy has an important role in local and locorregional disease control. In this review, we analyze the value of postoperative radiotherapy in the management of high-risk cSCC (in particular, cases with perineural invasion), cSCC with positive surgical margins, and locally advanced cSCC (with parotid gland and/or lymph node metastasis)

The Value of Adjuvant Radiotherapy in Cutaneous Squamous Cell Carcinoma: A Review. / Utilidad de la radioterapia en adyuvancia en el carcinoma epidermoide cutáneo.

Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans and its incidence is rising. Although surgery is the treatment of choice for cSCC, postoperative adjuvant radiotherapy has an important role in local and locorregional disease control. In this review, we analyze the value of postoperative radiotherapy in the management of high-risk cSCC (in particular, cases with perineural invasion), cSCC with positive surgical margins, and locally advanced cSCC (with parotid gland and/or lymph node metastasis).

Factores predictores de respuesta y revisión de la toxicidad cutánea de cetuximab y panitumumab en 116 pacientes / Predictors of Tumor Response to Cetuximab and Panitumumab in 116 Patients and a Review of Approaches to Managing Skin Toxicity

INTRODUCCIÓN Y OBJETIVOS: Cetuximab y panitumumab son anticuerpos anti-factor de crecimiento epidérmico (anti-EGFR) usados para el cáncer colorrectal metastásico. La mayoría de los pacientes desarrollan una erupción papulopustulosa que podría predecir la respuesta tumoral. Además, producen otros efectos adversos cutáneos, por lo que hemos estudiado si estos también podrían ser predictores clínicos de respuesta. Así mismo, hemos realizado una revisión del tratamiento de la erupción papulopustulosa, ya que no existen directrices basadas en la evidencia. MATERIAL Y MÉTODOS: Estudio retrospectivo de 116 pacientes. Se incluyeron pacientes afectos de cáncer colorrectal metastásico en tratamiento con los anticuerpos anti-EGFR, cetuximab o panitumumab, en el Hospital Universitario Donostia. RESULTADOS: El 81,9% de los pacientes desarrolló la erupción papulopustulosa, siendo el riesgo mayor y de mayor intensidad cuantos más ciclos de anti-EGFR se administraban (p = 0,03). Todos los pacientes que obtuvieron una respuesta tumoral completa desarrollaron la erupción. Cuanto peor era la respuesta tumoral, menor era la frecuencia de la erupción (p = 0,03). También se encontró una asociación entre la xerosis y la respuesta tumoral (el 53,4% de los que obtuvieron respuesta tumoral desarrollaron xerosis, p = 0,002). El manejo de la erupción papulopustulosa se llevó a cabo mediante un algoritmo desarrollado por nuestro servicio. CONCLUSIONES: En la práctica clínica la erupción papulopustulosa grave y la xerosis pueden ser predictores clínicos de buena respuesta al tratamiento anti-EGFR. Los pacientes con esta erupción deben tratarse precozmente, ya que el tratamiento subóptimo de estos efectos secundarios puede conllevar un retraso en la dosis o su interrupción

INTRODUCTION AND OBJECTIVES: Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most patients develop a papulopustular rash, which may predict tumor response. We studied whether the other adverse cutaneous effects associated with these monoclonal antibodies are also clinical predictors of response. We also reviewed publications describing approaches to treating the papulopustular rash since no evidence-based guidelines have yet been published. MATERIAL AND METHODS: We performed a retrospective study of 116 patients with metastatic colorectal cancer receiving anti-EGRF therapy with cetuximab or panitumumab at Hospital Universitario Donostia. RESULTS: In total, 81.9% of the patients developed a papulopustular rash. Patients who received the most cycles of treatment with the EGFR inhibitor were at the highest risk of developing the rash, and these patients also had the most severe rash reactions (P = .03). All of the patients who exhibited a complete tumor response had the rash, and the incidence of rash was lower in patients with poor tumor response (P = .03). We also observed an association between tumor response and xerosis (53.4% of the patients who developed xerosis also exhibited tumor response, P = .002). The papulopustular rash was managed according to an algorithm developed by our department. CONCLUSIONS: Severe papulopustular rash and xerosis may be clinical predictors of good response to anti-EGFR therapy. Patients who develop a papulopustular rash should be treated promptly because suboptimal treatment of this and other adverse effects can lead to delays in taking the prescribed anti-EGFR dose or to interruption of therapy

Predictors of Tumor Response to Cetuximab and Panitumumab in 116 Patients and a Review of Approaches to Managing Skin Toxicity.

INTRODUCTION AND OBJECTIVES: Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most patients develop a papulopustular rash, which may predict tumor response. We studied whether the other adverse cutaneous effects associated with these monoclonal antibodies are also clinical predictors of response. We also reviewed publications describing approaches to treating the papulopustular rash since no evidence-based guidelines have yet been published. MATERIAL AND METHODS: We performed a retrospective study of 116 patients with metastatic colorectal cancer receiving anti-EGRF therapy with cetuximab or panitumumab at Hospital Universitario Donostia. RESULTS: In total, 81.9% of the patients developed a papulopustular rash. Patients who received the most cycles of treatment with the EGFR inhibitor were at the highest risk of developing the rash, and these patients also had the most severe rash reactions (P=.03). All of the patients who exhibited a complete tumor response had the rash, and the incidence of rash was lower in patients with poor tumor response (P=.03). We also observed an association between tumor response and xerosis (53.4% of the patients who developed xerosis also exhibited tumor response, P=.002). The papulopustular rash was managed according to an algorithm developed by our department. CONCLUSIONS: Severe papulopustular rash and xerosis may be clinical predictors of good response to anti-EGFR therapy. Patients who develop a papulopustular rash should be treated promptly because suboptimal treatment of this and other adverse effects can lead to delays in taking the prescribed anti-EGFR dose or to interruption of therapy.