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.

Risk of a Second Skin Cancer in a Cohort of Patients With Nonmelanoma Skin Cancer -Basal Cell Carcinoma or Squamous Cell Carcinoma-Treated With Mohs Micrographic Surgery: A National Prospective Cohort Study. / Riesgo de aparición de segundas neoplasias cutáneas en una cohorte de pacientes diagnosticados de carcinoma queratinocítico (carcinoma basocelular y carcinoma epidermoide) tratados con cirugía de Mohs. Estudio de cohortes prospectivo nacional.

OBJECTIVE: Patients with nonmelanoma skin cancer (NMSC)-ie, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC)-have an increased risk of developing a second skin cancer. The aim of this study was to describe the frequency, incidence per 1000 person-years, and predictors of a second skin cancer in a cohort of patients with NMSC treated with Mohs micrographic surgery (MMS). MATERIAL AND METHODS: Prospective study of a national cohort of patients with NMSC who underwent MMS at 22 Spanish hospitals between July 2013 and February 2020; case data were recorded in the REGESMOHS registry. The study variables included demographic characteristics, frequency and incidence per 1000 person-years of second skin cancers diagnosed during the study period, and risk factors identified using mixed-effects logistic regression. RESULTS: We analyzed data for 4768 patients who underwent MMS; 4397 (92%) had BCC and 371 (8%) had SCC. Mean follow-up was 2.4 years. Overall, 1201 patients (25%) developed a second skin cancer during follow-up; 1013 of the tumors were BCCs (21%), 154 were SCCs (3%), and 20 were melanomas (0.4%). The incidence was 107 per 1000 person-years (95% CI, 101-113) for any cancer, 90 per 1000 person-years (95% CI, 85-96) for BCC, 14 (95% CI, 12-16) per 1000 person-years for SCC, and 2 (95% CI, 1-3) per 1000 person-years for melanoma. More men than women developed a subsequent skin cancer (738 [61%] vs 463 [39%]). The main risk factors were a history of multiple tumors before diagnosis (relative risk [RR], 4.6; 95% CI, 2.9-7.1), immunosuppression (RR, 2.1; 95% CI, 1.4-3.1), and male sex (RR, 1.6; 95% CI, 1.4-1.9). CONCLUSION: Patients have an increased risk of developing a second tumor after MMS treatment of NMSC. Risk factors are a history of multiple tumors at diagnosis, immunosuppression, and male sex.

Description of patients excluded for Mohs surgery after pre-surgical evaluation: data from the Regesmohs Spanish registry. / Descripción de pacientes no aptos para ser sometidos a cirugía de Mohs tras valoración prequirúrgica: datos del registro español Regesmohs.

BACKGROUND: Regesmohs registry is a nationwide registry including patients evaluated for Mohs surgery in 17 Spanish centres since July 2013. Given that Mohs surgery is the therapy with best results for high risk basal cell carcinoma (BCC) and other skin tumours, we wanted to describe the reasons that lead to some patients being excluded from this therapy and the alternative treatments that they received. These data may be useful to avoid excluding patients for Mohs surgery use, to estimate the healthcare demand of these patients and the demand for Hedgehog inhibitors therapy in this group. OBJECTIVE: To describe patients excluded for Mohs surgery after pre-surgical assessment, and the treatments that they received. METHODS: Regesmohs includes all consecutive patients assessed for Mohs surgery in the participating centres, collecting data on patient characteristics, intervention, and short and long-term results. Patients excluded for Mohs surgery after pre-surgical evaluation were described. RESULTS: 3011 patients were included in Regesmohs from July 2013 to October 2016. In 85, Mohs surgery was not performed as they were considered inadequate candidates. 67 had BCC. Reasons for exclusion were: medical contraindication (27.1%, n=23) low-risk tumour in (18.8%, n=16) and giant tumour and bone invasion (15.3%, n=13). Only 1 patient (1.2%) showed lymph node involvement and no patients had visceral metastases. Of the 85 excluded patients, 29 (34.1%) were treated with conventional surgery, 24 (28.3%) with radiotherapy, 4 (4.7%) with inhibitors of the Hedgehog pathway (only indicated for BCC), and 2 (2.4%) received palliative care. We had no follow-up data on 14 patients (16.5%). CONCLUSION: Medical comorbidities were the most common reason for withholding Mohs surgery. Withholding therapy on the basis of distant extension is uncommon. Most excluded patients received simpler therapies: conventional surgery or radiotherapy, with hedgehog inhibitors being a new option.

Mohs micrographic surgery in the elderly: comparison of tumours, surgery and first-year follow-up in patients younger and older than 80 years old in REGESMOHS.

BACKGROUND: The elderly population is increasing and more patients in this group undergo Mohs micrographic surgery (MMS). The few publications investigating MMS in elderly people conclude that it is a safe procedure; however, these are single-centre studies without a comparison group. OBJECTIVE: To compare the characteristics of patients, tumours, MMS and 1-year follow-up in patients younger than 80 years, with patients older than 80 years at the time of surgery. METHODS: Data was analysed from REGESMOHS, a prospective cohort study of patients treated with MMS. The participating centres were 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patient, tumour and surgery were recorded. Follow-up data were collected from two visits; the first within 1 month postsurgery and the second within the first year. RESULTS: From July 2013 to October 2016, 2575 patients that underwent MMS were included in the registry. Of them, 1942 (75.4%) were aged <80 years and 633 (24.6%) were ≥80 years old. In the elderly, the tumour size was significantly higher with a higher proportion of squamous cell carcinoma. Regarding surgery, elderly more commonly had tumours with deeper invasion and required a higher number of Mohs surgery stages, leaving larger defects and requiring more time in the operating room. Despite this, the incidence of postoperative complications was the same in both groups (7%) and there were no significant differences in proportion of relapses in the first-year follow-up. CONCLUSION: The risk of short-term complications and relapses were similar in elderly and younger groups. MMS is a safe procedure in the elderly.

Characterization of Surgical Procedures in the Spanish Mohs Surgery Registry (REGESMOHS) for 2013-2015. / Descripción de las intervenciones quirúrgicas recogidas en el registro español de cirugía de Mohs (REGESMOHS) (2013-2015).

INTRODUCTION: The Spanish Mohs Surgery Registry is used to collect data on the use and outcomes of Mohs micrographic surgery (MMS) in Spain. The aim of this study was to describe perioperative and intraoperative data recorded for MMS procedures performed between July 2013 (when the registry started) and January 2016. MATERIAL AND METHODS: Prospective cohort study of data from 18 hospitals. The data collected included type of anesthesia, surgical technique, hospital admission, number of Mohs stages, management of preoperative risk factors, additional treatments, previous treatments, type of tumor, operating time, and complications. RESULTS: Data were available for 1796 operations. The most common tumor treated by MMS was basal cell carcinoma (85.96%), followed by squamous cell carcinoma (6.18%), lentigo maligna (2.81%), and dermatofibrosarcoma protuberans (1.97%). Primary tumors accounted for 66.9% of all tumors operated on; 19.2% of tumors were recurrent and 13.9% were persistent. The most common previous treatment was surgical. MMS was mostly performed under local anesthesia (86.7% of cases) and as an outpatient procedure (71.8%). The frozen section technique was used in 89.5% of cases. One stage was needed to achieve tumor-free margins in 56.45% of patients; 2 stages were required in 32.1% of patients, 3 in 7.1%%, 4 in 2.7%, and 5 or more in 1.8%. The defect was reconstructed by the dermatologist in 98% of patients and the most common technique was flap closure (47.2%). Intraoperative complications were recorded for just 1.62% of patients and the median (interquartile range) duration of surgery was 75 (60-100) minutes. CONCLUSION: The characteristics of the patients and tumors treated by MMS are similar to those reported for similar studies in other geographic areas. Lentigo maligna and dermatofibrosarcoma protuberans accounted for a higher proportion of cases in our series, and repair of the surgical defect by a dermatologist was also more common. Operating times in MMS are not much longer than those reported for other procedures and the rate of intraoperative complications is very low.

Description of Patients Undergoing Mohs Surgery in Spain: Initial Report on Data From the Spanish Registry of Mohs Surgery (REGESMOHS).

INTRODUCTION: The Spanish registry of Mohs micrographic surgery started collecting data in July 2013. The aim of the registry is to report on the use of this technique in Spain and the outcomes achieved. In the present article, we describe the characteristics of patients and the tumors treated. MATERIAL AND METHODS: This is a prospective cohort study of patients treated with Mohs micrographic surgery. The participating centers are hospitals where at least one intervention of this type is performed each week. All patients considered for Mohs micrographic surgery in participating centers are included in the registry except those who have been declared legally incompetent. RESULTS: Between July 2013 and October 2014, data from 655 patients were included in the registry. The most common tumor involved was basal cell carcinoma, and the most common histological subtype was infiltrative basal cell carcinoma. Most of the tumors treated were located on the face or scalp, and the most common site was the nose. Almost 40% of the tumors treated were recurrent or persistent, and preoperative tumor size was similar to that reported in other European studies and in Australia. In total, 45.5% of patients had received previous surgical treatment. CONCLUSION: The findings are similar to those reported in other studies, and the data collected are useful for assessing whether the results of studies carried out elsewhere are applicable in Spain.

Vismodegib: a review.

In January 2012, vismodegib (Erivedge, manufactured by Genentech) became the first selective inhibitor of the Hedgehog signaling pathway to be approved by the US Food and Drug Administration for the treatment of locally advanced and metastatic basal cell carcinoma. The drug selectively binds to Smoothened, a 7-helix transmembrane receptor, thereby inhibiting activation of transcription factors of the glioma-associated oncogene family and suppressing tumor proliferation and growth. Studies published to date have assessed the efficacy of vismodegib according to clinical and radiologic outcomes but little information is available on the molecular mechanisms underpinning the proven clinical efficacy of the drug. This review will cover recent data on the Hedgehog signaling pathway and data from clinical trials with vismodegib in the treatment of basal cell carcinoma, and will consider its use in other types of tumor.

Ustekinumab in clinical practice: response depends on dose and previous treatment.

OBJECTIVES: To evaluate the efficacy of ustekinumab in a series of patients with moderate to severe psoriasis treated according to the European Medicines Agency (EMA) label and to identify factors such as dose, baseline PASI or previous treatment potentially related to therapeutic outcome. METHODS: Retrospective review of the clinical records from 36 consecutive patients treated with ustekinumab during at least 36 weeks at a single referral center. Candidates for treatment had a PASI≥10 or a BSA≥10 and either failure to respond to, or a contraindication to, or intolerance to some systemic or another biologic treatment. The main outcome measures were PASI improvement with respect to baseline at weeks 12 and 24 (prior to the third injection of ustekinumab). RESULTS: Overall 75%, 69%, and 86% patients achieved PASI75 response rates at weeks 12, 24 and 36, respectively. Patients weighing≤100 kg and treated with 45 mg doses had better PASI 50, PASI75 and PASI90 response rates than heavier patients (treated with 90 mg) at every point in time, and the differences were statistically significant at week 24. PASI75 response rates at week 24 were significantly better in patients with no prior exposure to TNFα blocking agents (85% vs. 50%, P=0.0235). CONCLUSIONS: In clinical practice, ustekinumab is effective both in biologic-naÿve patients and as salvage therapy when other biological treatments have failed. The response rates prior to the third injection in our series were better in patients weighing≤100 kg and in those without previous exposure to biologics.

[Our experience in high-flow priapism due to uni-or bilateral arterio-lacunar fistula]. / Nuestra experiencia en el priapismo de alto flujo por fístula arterio-lacunar uni y bilateral.

OBJECTIVE: To present our experience in both uni-and bilateral priapism, highlighting good results obtained with supraselective embolisation. MATERIAL AND METHODS: We present 5 cases of high-flow priapism secondary to perineal trauma, with a mean age of 31 years (24-43 years). The mean time to presentation from the moment of the trauma was 18, 6 days (1-60 days). Diagnosis was confirmed through gasometry of the corpora cavernosa, penile Doppler ultrasound (2 cases) and selective arteriography of the pudendal artery. In all cases treatment was by supralective embolisation with gelatin sponge. In the two bilateral cases, embolisation was performed in the same act. RESULTS: In the short-term was a recovery of flaccidity and in the long-term (3-4 months) a recovery of erection with no fibrotic sequelae of the corpora cavernosa. CONCLUSIONS: Embolisation of the lacerated artery, in a single procedure in cases of bilateral lacerations, provides excellent results.