Publications by authors named "Ketty Peris"

275 Publications

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study.

Dermatol Ther 2021 Oct 21:e15166. Epub 2021 Oct 21.

A.O.U. Città della Salute e della Scienza PO Molinette, Torino, Italy.

CANOVA study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 months and 24 weeks before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/dth.15166DOI Listing
October 2021

Pediatric Hidradenitis Suppurativa: A Cross-Sectional Study on Clinical Features and Treatment Approaches.

J Cutan Med Surg 2021 Oct 6:12034754211039993. Epub 2021 Oct 6.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Dermatologia, Rome, Italy.

Background: Hidradenitis suppurativa is uncommon in patients of pediatric age, and differentiation with adult-onset disease is controversial. Treatment of pediatric hidradenitis suppurativa is scarcely standardized, and specific guidelines are lacking.

Objective: We report the clinical features, relevant risk-factors, comorbidity profile, and treatment patterns of a hospital-based cohort of pediatric hidradenitis suppurativa.

Methods: In a cross-sectional study data on patients' demographics, disease-specific characteristics, early/pre-pubertal onset of disease, comorbidities, and treatment management were retrieved. Reference population data and clinical data from the national hidradenitis suppurativa disease registry were used for comparison.

Results: From a database of 870 patients with hidradenitis, 71 (15 males and 56 females) patients aged <18 years (mean age: 15.3 years; range 8-17 years), with mild (Hurley I, 45.1%) and moderate-severe disease (Hurley II-III, 54.9%), were retrieved. Smoking (23.9%) and overweight/obese frequencies (59.2%) were higher than reference population standards. Patient's older age at baseline (OR 1.43, 95% CI: 1.01 to 2.02) and higher BMI (OR 1.26, 95% CI: 1.07-1.48) were the only factors associated with moderate-severe disease. Family history and early/pre-pubertal onset of disease were not associated with severity or extent of disease. Sebaceous-follicular comorbid conditions were associated with cigarette smoking ( = .002). Among 81 treatment courses, clindamycin-based and zinc-sulphate-based combination regimens were most frequently used (59.3%). Female preponderance, family history of disease and extensive involvement were significantly different from the general hidradenitis suppurativa population.

Conclusions: Pediatric hidradenitis suppurativa presents a clinical spectrum comparable to adult-onset disease. Increased preventive measures should target obesity and smoking in this population.
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http://dx.doi.org/10.1177/12034754211039993DOI Listing
October 2021

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study.

Clin Drug Investig 2021 Oct 18;41(10):917-925. Epub 2021 Sep 18.

Istituto di Dermatologia, Università Cattolica del Sacro Cuore, L.go F. Vito 1, 00135, Rome, Italy.

Background: The efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including  body mass index (BMI).

Objective: This study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m).

Methods: A multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006-December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12- and 24-month drug survival as a measure of long-term efficacy, performing multivariate analyses to assess the impact of different variables.

Results: Five hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m compared with those with a BMI ≥ 30 kg/m [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan-Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI.

Conclusions: Obesity (BMI ≥ 30 kg/m) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs.
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http://dx.doi.org/10.1007/s40261-021-01080-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481196PMC
October 2021

Real world data of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma.

Eur J Cancer 2021 Sep 15;157:250-258. Epub 2021 Sep 15.

University of Brescia, Department of Medical-Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology, ASST-Spedali Civili, Brescia, Lombardia, Italy. Electronic address:

Background: Cutaneous squamous cell carcinoma (cSCC) has an overall favourable outcome, except for patients with an advanced stage disease. The programmed death protein-1 (PD-1) inhibitor cemiplimab has been approved for use in advanced cSCC. We report clinical outcomes from the named patient programme-compassionate use of cemiplimab for patients with advanced cSCC in Italy.

Methods: This is a retrospective, observational, multicentre study. We analysed medical records of patients with advanced cSCC treated with cemiplimab between May 2019 and February 2020 in 17 referral Italian centres. We assessed the safety profile according to the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v 5.0), the clinical activity in terms of response rate, clinical benefit and duration of response and baseline clinical-pathologic characteristics associated with response.

Results: 131 patients were included, with a median age of 79 years. Of them, 9.2% had a concurrent chronic lymphoproliferative disease and 8.5% a concomitant autoimmune disease. Some 42.7% of the total patients had at least one treatment-related adverse events (AEs); out of above, 9.2% had grade 3-4 adverse events, and there were two fatal adverse events. The overall response rate (ORR) was 58%, and the disease control rate (DCR) was 71.7%. Cutaneous squamous cell carcinomas (cSCCs) arising on the head and neck area (p = 0.007) and haemoglobin values in normal range (p = 0.034) were significantly associated with a better response, while cSCCs on the genitalia (p = 0.041), treatment with any systemic antibiotic within 1 month of cemiplimab initiation (p = 0.012), performance status ≥1 (p = 0.012), chronic corticosteroids therapy (p = 0.038), previous radiation therapy to lymph nodes (p = 0.052) and previous chemotherapy (p = 0.0020) were significantly associated with a worse response.

Conclusions: Our real-world study showed safety and effectiveness results comparable to those obtained in clinical trials. We identified some clinical and biochemical factors potentially associated with response to cemiplimab.
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http://dx.doi.org/10.1016/j.ejca.2021.08.018DOI Listing
September 2021

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BMC Health Serv Res 2021 Sep 6;21(1):924. Epub 2021 Sep 6.

A.O.U. Città della Salute e della Scienza PO Molinette, Turin, Italy.

Background: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy.

Methods: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%).

Results: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time.

Conclusion: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.
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http://dx.doi.org/10.1186/s12913-021-06866-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422702PMC
September 2021

Sonidegib after vismodegib discontinuation in a patient with Gorlin-Goltz syndrome and multiple basal cell carcinomas.

Dermatol Ther 2021 Sep 19;34(5):e15095. Epub 2021 Aug 19.

Institute of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.1111/dth.15095DOI Listing
September 2021

Cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia: a systematic review of the literature.

Int J Dermatol 2021 Aug 5. Epub 2021 Aug 5.

Centro Oncologico ad Alta Tecnologia Diagnostica, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy.

The continuous improvement of life expectancy of patients with chronic lymphocytic leukemia (CLL) has resulted in increased risk of second primary malignancy that potentially may affect survival and quality of life of CLL patients. We performed a systematic review to assess the risk and the clinical-pathological features and prognosis of cutaneous squamous cell carcinoma (cSCC) in patients with CLL. We searched PubMed, Embase, and Cochrane Central Register of Control Trials databases for articles published from database inception to December 31, 2019. English-language studies reporting original data on patients with a specific diagnosis of CLL and cSCC were included. Data were extracted using a standardized extraction form, and any discordance was resolved by consensus. Descriptive data were generated by pooling patients from eligible studies. Of the 4588 non-duplicate records identified, 55 articles met our inclusion criteria. These studies reported that CLL patients have a 3.2% prevalence of cSCC, with an 11.5% cSCC-related lethality and an overall risk of metastasis of 5.7% (7.3% for regional lymph node involvement and 3.8% for distant metastasis). The quality of evidence was limited by the high heterogeneity in the design, populations, and objectives of the included studies. This systematic review suggests that cSCC in CLL patients tends to behave less aggressively compared with the solid organ transplant recipients but has a higher morbidity and mortality than in the general population. Future prospective studies are needed to increase the quality of evidence and to determine the best treatment modalities and screening intervals for these patients.
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http://dx.doi.org/10.1111/ijd.15813DOI Listing
August 2021

Patient satisfaction with calcipotriol/betamethasone dipropionate cutaneous foam for the treatment of plaque psoriasis: The LION real-life multicenter prospective observational cohort study.

Dermatol Ther 2021 Sep 9;34(5):e15077. Epub 2021 Aug 9.

UOC di Dermatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real-life Italian dermatological clinical practice. A multicenter, 4-week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.
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http://dx.doi.org/10.1111/dth.15077DOI Listing
September 2021

Treatment adherence with diclofenac 3% gel among patients with multiple actinic keratoses: an integrated low-intensity intervention program versus standard-of-care.

Ital J Dermatol Venerol 2021 Jul 20. Epub 2021 Jul 20.

Dermatologia, Università Cattolica del Sacro Cuore, Rome, Italy -

Background: Diclofenac 3% gel is a widely used topical treatment with proven efficacy in reducing the burden of Actinic Keratosis (AK), however clinical benefit might not fully translate in clinical practice as non-adherence is substantial for prolonged treatment regimens. We evaluated the efficacy of an integrated low-intensity intervention program versus standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3%.

Methods: We designed an open label, randomized, parallel group, interventional, multicenter, longitudinal cohort study including patients with multiple, grade I/II AKs. Visits were scheduled for end of treatment (T4), follow-up 1 (T5) and follow-up 2 (T6) at 90, 180 and 365 days from baseline, respectively. Patients in the intervention group received additional visits at 30 and 60 days from baseline, a brief health education intervention, an enhanced patient-physician communication, a weekly SMS reminder to medication prescriptions.

Results: Patients were equally allocated between intervention (intervention group [IG], N=86) and control group (CG, N=86); at baseline, both groups had similar socio-demographic and clinical characteristics. Change scores from baseline showed a slight increment in quality of life related to AK in both groups (CG: ΔT4 - T1=-0.079; IG: ΔT4 - T1=-0.006; p=0.39) and in quality of physicianpatient interaction reported by IG (ΔT3 - T2=0.18; p<.0001). Adherence rate was not statistically different between IG and CG (28.4% vs 40.7%; p=0.11). Patients reported similar satisfaction for effectiveness, convenience and side effects of treatment. Clinical conditions improved over time and results did not differ between groups; complete clearance rate at 1 year was 18% and 29% for CG and IG, respectively.

Conclusions: Our findings showed no difference in adherence rate between the two groups, suggesting that enhanced follow-up interventions and health care education may not be sufficient drivers to promote adherence among this clinical population. Further studies are needed to explore barriers to adherence with treatments for AKs.
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http://dx.doi.org/10.23736/S2784-8671.21.07111-5DOI Listing
July 2021

Predictive factors of lack of response to adalimumab among bio-naive patients suffering from moderate-to severe psoriasis: analysis of a multicenter data collection in Italy.

Expert Opin Biol Ther 2021 Sep 18;21(9):1291-1298. Epub 2021 Jul 18.

Department of Dermatology, Università Cattolica Del Sacro Cuore, Rome, Italy.

Introduction: Efficacy of anti-TNF-a agents seems inferior to IL-17 and IL-23 inhibitors. Nevertheless, after biosimilars approval, anti TNF-a agents are recommended as first-line for psoriatic patients, for economic reasons.

Methods: Predictive factors of response or non-response to adalimumab in bionaive patients who started adalimumab (originator or biosimilar) over 12 years in 9 dermatologic centers in Italy. Effectiveness was assessed with Psoriasis Area and Severity Index (PASI75 and PASI90) at weeks 12, 24 and 48. Multiple logistic regressions were used for variables predicting clinical response; Kaplan-Meier survival curves and Cox regression for drug survival.

Results: The drug survival analysis showed reduced hazard ratio of overall discontinuation with male gender and scalp localization. In contrast, baseline PASI and genital psoriasis were significantly associated with increased risk of overall discontinuation. Predictive factors of non-response seemed elevated in patients with baseline PASI, older age groups, previously treated patients with phototherapy, females or patients with palmo-plantar while scalp psoriasis, previous cyclosporine and acitretin appeared as a positive predictive factor.

Conclusions: This real-life analysis might be useful for clinicians in case of bio-naive patients with moderate-to-severe psoriasis and various comorbidities.
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http://dx.doi.org/10.1080/14712598.2021.1948530DOI Listing
September 2021

Management of the kidney transplant patient with Cancer: Report from a Multidisciplinary Consensus Conference.

Transplant Rev (Orlando) 2021 07 24;35(3):100636. Epub 2021 Jun 24.

Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy; Dipartimento di Scienze Mediche e Chirurgiche, U.O.C. Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

Introduction: Cancer is the second most common cause of mortality and morbidity in Kidney Transplant Recipients (KTRs). Immunosuppression can influence the efficacy of cancer treatment and modification of the immunosuppressive regimen may restore anti-neoplastic immune responses improving oncologic prognosis. However, patients and transplant physicians are usually reluctant to modify immunosuppression, fearing rejection and potential graft loss. Due to the lack of extensive and recognised data supporting how to manage the immunosuppressive therapy in KTRs, in the context of immunotherapy, chemotherapy, radiotherapy and loco-regional treatments, a Consensus Conference was organised under the auspices of the European Society of Organ Transplantation and the Italian Society of Organ Transplantation. The conference involved a multidisciplinary group of transplant experts in the field across Europe.

Methods: The overall process included a) the formulation of 12 specific questions based on the PICO methodology, b) systematic literature review and summary for experts for each question, c) a two-day conference celebration and the collection of experts' agreements. The conference was articulated in three sessions: "Immunosuppressive therapy and immunotherapy", "Systemic therapy", "Integrated Therapy", while the final experts' agreement was collected with a televoting procedure and defined according to the majority criterion.

Results: Twenty-six European experts attended the conference and expressed their vote. A total of 14 statements were finally elaborated and voted. Strong agreement was found for ten statements, moderate agreement for two, moderate disagreement for one and uncertainty for the last one.

Conclusions: The consensus statements provide guidance to transplant physicians caring for kidney transplant recipients with cancer and indicate key aspects that need to be addressed by future clinical research.
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http://dx.doi.org/10.1016/j.trre.2021.100636DOI Listing
July 2021

Novel MAPK/AKT-impairing germline NRAS variant identified in a melanoma-prone family.

Fam Cancer 2021 Jul 3. Epub 2021 Jul 3.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, EPS 7106, Bethesda, MD, 20892, USA.

While several high-penetrance melanoma risk genes are known, variation in these genes fail to explain melanoma susceptibility in a large proportion of high-risk families. As part of a melanoma family sequencing study, including 435 families from Mediterranean populations we identified a novel NRAS variant (c.170A > C, p.D57A) in an Italian melanoma-prone family. This variant is absent in exomes in gnomAD, ESP, UKBiobank, and the 1000 Genomes Project, as well as in 11,273 Mediterranean individuals and 109 melanoma-prone families from the US and Australia. This variant occurs in the GTP-binding pocket of NRAS. Differently from other RAS activating alterations, NRAS D57A expression is unable to activate MAPK-pathway both constitutively and after stimulation but enhances EGF-induced PI3K-pathway signaling in serum starved conditions in vitro. Consistent with in vitro data demonstrating that NRAS D57A does not enrich GTP binding, molecular modeling suggests that the D57A substitution would be expected to impair Mg2 + binding and decrease nucleotide-binding and GTPase activity of NRAS. While we cannot firmly establish NRAS c.170A > C (p.D57A) as a melanoma susceptibility variant, further investigation of NRAS as a familial melanoma gene is warranted.
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http://dx.doi.org/10.1007/s10689-021-00267-9DOI Listing
July 2021

Non-melanoma Skin Cancer Treated by Contact High-dose-rate Radiotherapy (Brachytherapy): A Mono-institutional Series and Literature Review.

In Vivo 2021 Jul-Aug;35(4):2313-2319

U.O.C. Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Background/aim: Non-melanoma skin cancers (NMSC) are the most common neoplasms worldwide and their incidence has been proven to increase in recent years and their treatment should aim at cancer cure as well as cosmetic and functional results. The aim of the study was to report the results of our mono-institutional series of high-dose-rate radiotherapy (cHDR-RT) in NMSC, based on a homogenous technique and two different treatment schedules.

Patients And Methods: All patients affected by NMSC who were consecutively evaluated and treated at our Interventional Oncology Center from October 2018 to August 2020, were included. Patients underwent cHDR-RT using flap applicators and remotely afterloaded Ir-192 sources.

Results: Overall, 51 patients were treated for a total of 67 lesions. Local control (LC) and disease-specific survival (DSS) were 94.0% and 100%, respectively. Grade 1, grade 2, grade 3 and grade 4 acute toxicity rates were 24.6%, 3.5%, 3.5%, and 0.0%, respectively. The cosmetic results were graded as excellent/good, fair, and poor in 73.7%, 19.3%, and 7.0%.

Conclusion: cHDR-RT of NMSC is an effective alternative to surgery due to excellent outcomes both in terms of local control and aesthetic results especially in the face.
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http://dx.doi.org/10.21873/invivo.12505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286496PMC
June 2021

Molecular alterations in basal cell carcinoma subtypes.

Sci Rep 2021 06 24;11(1):13206. Epub 2021 Jun 24.

Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy.

A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour. We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p = 0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p = 0.018) and NOTCH1 (p = 0.020) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p = 0.046) and the occurrence of single lesions (p = 0.021), while NOTCH1 mutations were more frequent in BCCs located on the trunk compared to the head/neck and extremities (p = 0.001). In conclusion, we provide further insights into the molecular alterations underlying the tumorigenic mechanism of superficial and nodular BCCs with a view towards novel rationale-based therapeutic strategies.
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http://dx.doi.org/10.1038/s41598-021-92592-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225846PMC
June 2021

Flares as dynamic predictive factor of response to adalimumab in hidradenitis suppurativa, real-life data.

Ital J Dermatol Venerol 2021 Jun 23. Epub 2021 Jun 23.

Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Hidradenitis suppurativa (HS) is characterized by periodic worsening of both clinical manifestations and symptoms. The aim was to investigate the role of flare outbreak as a possible predictive factor of response to Adalimumab.

Methods: 115 HS patients in treatment with adalimumab, with moderate-severe HS, ≥3 abscesses and inflammatory-nodules (ANs) from 5 Italian centers were included in this retrospective analysis. The information about gender, ages at onset/baseline, therapeutic delay, family history, body mass index, smoking, comorbidities, phenotypes, body areas, severity indexes at baseline was collected. Baseline characteristics, total number and timeline of flares were analysed by regression and survival analysis with Hidradenitis Suppurativa Clinical Response (HiSCR).

Results: During the observational period, 80.9% of patients developed flares, detecting 252 flares. Univariate model identified five factors associated with the absence of response: age (p-value=0.020), comorbidities (p-value=0.030), genital-perineal involvement (pvalue= 0.004), no response at week-12 (p-value=0.027), and flares outbreak (p-value=0.010). Joint analysis of recurrent and terminal events showed a positive correlation between flare recurrence and no-response (p-value<0.001). Among the identified variables associated with poor response to the therapy: occurrence of a flare before week-12 was the one with the highest risk of no response (p-value<0.001). The limitations are: study's retrospective design, limited number of patients, absence either of a consensus about flare definition, placebo control group or standard therapy of flares during adalimumab therapy.

Conclusions: The analysis of a "dynamic" variable, as flares evaluation together with an appropriate clinical baseline assessment can be a useful approach to predict the middle-long-term response to adalimumab.
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http://dx.doi.org/10.23736/S2784-8671.21.07049-3DOI Listing
June 2021

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

Allergy 2021 06 9;76(6):1813-1824. Epub 2021 Mar 9.

Dermatology Unit, Department of MedicalSpecialties, Arcispedale Santa Maria Nuova-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

Background: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic.

Methods: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity.

Results: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred.

Conclusions: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.
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http://dx.doi.org/10.1111/all.14767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014537PMC
June 2021

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial.

Lancet Oncol 2021 06 14;22(6):848-857. Epub 2021 May 14.

Skin Cancer Center, Department of Dermatology, Harz Clinics, Quedlinburg, Germany.

Background: Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy.

Methods: We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years and with an Eastern Cooperative Oncology Group performance status of 0 or 1) with a histologically confirmed diagnosis of metastatic basal cell carcinoma (group 1) or locally advanced basal cell carcinoma (group 2) who had progressed on or were intolerant to previous HHI therapy were enrolled. Patients were not candidates for further HHI therapy due to progression of disease on or intolerance to previous HHI therapy or having no better than stable disease after 9 months on HHI therapy. Patients received cemiplimab 350 mg intravenously every 3 weeks for up to 93 weeks or until progression or unacceptable toxicity. The primary endpoint was objective response by independent central review. Analyses were done as per the intention-to-treat principle. The safety analysis comprised all patients who received at least one dose of cemiplimab. The primary analysis is reported only for group 2; group 1 data have not reached maturity and will be reported when the timepoint, according to the statistical analysis plan, has been reached. This study is registered with ClinicalTrials.gov, NCT03132636, and is no longer recruiting new participants.

Findings: Between Nov 16, 2017, and Jan 7, 2019, 84 patients were enrolled and treated with cemiplimab. At data cutoff on Feb 17, 2020, median duration of follow-up was 15 months (IQR 8-18). An objective response per independent central review was observed in 26 (31%; 95% CI 21-42) of 84 patients, including two partial responses that emerged at tumour assessments before the data cutoff and were confirmed by tumour assessments done subsequent to the data cutoff. The best overall response was five (6%) patients with a complete response and 21 (25%) with a partial response. Grade 3-4 treatment-emergent adverse events occurred in 40 (48%) of 84 patients; the most common were hypertension (four [5%] of 84 patients) and colitis (four [5%]). Serious treatment-emergent adverse events occurred in 29 (35%) of 84 patients. There were no treatment-related deaths.

Interpretation: Cemiplimab exhibited clinically meaningful antitumour activity and an acceptable safety profile in patients with locally advanced basal cell carcinoma after HHI therapy.

Funding: Regeneron Pharmaceuticals and Sanofi.
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http://dx.doi.org/10.1016/S1470-2045(21)00126-1DOI Listing
June 2021

Severe and resistant palmar psoriasis successfully treated with risankizumab.

Ital J Dermatol Venerol 2021 May 13. Epub 2021 May 13.

Institute of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.23736/S2784-8671.21.06972-8DOI Listing
May 2021

Factors related to the onset and recurrence of flares in hidradenitis suppurativa patients treated with adalimumab.

Ital J Dermatol Venerol 2021 May 13. Epub 2021 May 13.

Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Hidradenitis suppurativa (HS) is characterized by periodic worsening of symptoms. However, clinical parameters associated with flare are still to be established. The aim was too investigate factors associated with flare outbreak in HS patients in treatment with adalimumab.

Methods: Moderate-severe HS patients were included in this retrospective analysis. In total, 115 HS patients treated with adalimumab from 5 Italian centers were reviewed. Gender, ages at onset/baseline, therapeutic delay, family history, body mass index, smoking, comorbidities, phenotypes, body areas involved, Hurley stage, International Hidradenitis Suppurativa Severity Score System (IHS4), Dermatology Life Quality Index (DLQI) and Visual Analogue Scale for pain (pain-VAS) were collected at baseline. Flares were modelled with baseline features using univariate and multivariate Coxregression. The factors significantly correlated with flares in the univariate model were analyzed using a recurrent event survival analysis (Andersen-Gill model) to assess the relation between them and flares recurrence.

Results: During the observation period 80.9% of patients developed flares, detecting 252 flares, overall. A univariate model identified five risk factors associated with the outbreak of flares: age, therapeutic delay, groin involvement, Hurley III, higher IHS4, whereas, from multivariate model, only IHS4 resulted to be significantly correlated. Additionally, flares were positively associated with higher DLQI and pain-VAS. Finally, the Andersen-Gill model showed four factors correlated with flares recurrence: age, therapeutic delay, Hurley III and higher IHS4. The limitations are: study's retrospective design, absence of a consensus about flare definition.

Conclusions: An early treatment of HS may prevent both the disease progression and reduce the recurrence of flares.
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http://dx.doi.org/10.23736/S2784-8671.21.06966-8DOI Listing
May 2021

SARS-CoV-2 vaccines and biological treatments: dermatological perspectives.

Ital J Dermatol Venerol 2021 Apr;156(2):118-120

Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy.

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http://dx.doi.org/10.23736/S2784-8671.21.07055-9DOI Listing
April 2021

Secukinumab Exhibits Sustained and Stable Response in Patients with Moderate-to-Severe Psoriasis: Results from the SUPREME Study.

Acta Derm Venereol 2021 Oct 21;101(10):adv00576. Epub 2021 Oct 21.

Dermatology Unit, Department of Biomedical Sciences, Humanitas University, IRCCS Istituto Clinico Humanitas, Via Alessandro Manzoni 113, IT-20089, Rozzano-Milan, Italy.

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.
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http://dx.doi.org/10.2340/00015555-3816DOI Listing
October 2021

Violett-rote Papeln während der Anti-PD1-Immuntherapie bei metastasiertem Melanom.

J Dtsch Dermatol Ges 2021 Apr;19(4):628-630

Institute of Dermatology, Università Cattolica del Sacro Cuore, Rome, Italy.

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http://dx.doi.org/10.1111/ddg.14324_gDOI Listing
April 2021

Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review.

Hum Vaccin Immunother 2021 Apr 13:1-8. Epub 2021 Apr 13.

UOC Radioterapia Oncologica, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy.

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment. Combining radiotherapy with immunotherapy provides an opportunity to increase immunostimulatory potential of radiation. We therefore provide the latest clinical evidence about radiobiological rationale, radiotherapy techniques, timing, and role both in advanced and systemic disease (with a special focus on ocular melanoma and brain, liver, and bone metastases) with a particular attention also in geriatric patients. The combination of immunotherapy and radiotherapy seems to be a safe therapeutic option, supported by a clear biological rationale, even though the available data confirm that radiotherapy is employed more for metastatic than for non-metastatic disease. Such a combination shows promising results in terms of survival outcomes; however, further studies, hopefully prospective, are needed to confirm such evidence.
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http://dx.doi.org/10.1080/21645515.2021.1903827DOI Listing
April 2021

Pruritus as a Distinctive Feature of Type 2 Inflammation.

Vaccines (Basel) 2021 Mar 23;9(3). Epub 2021 Mar 23.

Section of Dermatology and Venereology, Department of Medicine, University of Verona, 37126 Verona, Italy.

Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients' quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.
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http://dx.doi.org/10.3390/vaccines9030303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005108PMC
March 2021

"Skin rashes" and immunotherapy in melanoma: distinct dermatologic adverse events and implications for therapeutic management.

Hum Vaccin Immunother 2021 Mar 24:1-8. Epub 2021 Mar 24.

Dermatologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Immune checkpoint inhibitors have shown efficacy in the treatment of different cancers by stimulating the antitumoral activity of the patient's immune system, representing a major breakthrough in the field of cancer therapy. Monoclonal antibodies including anti-cytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1 and its ligand inhibitors have been approved for advanced melanoma among other solid cancers. Although immunotherapy demonstrated a good safety profile, a new spectrum of multisystemic immune-related adverse events has been recently reported due to their use. Cutaneous reactions represent one of the leading adverse events, often reported in literature as "skin rash", and rarely further characterized in distinct dermatologic entities. Herein we describe the distinctive cutaneous rashes occurring during immunotherapies for advanced melanoma, discussing implications in the treatment management.
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http://dx.doi.org/10.1080/21645515.2021.1889449DOI Listing
March 2021

Effectiveness and Safety of Long-Term Dupilumab Treatment in Elderly Patients with Atopic Dermatitis: A Multicenter Real-Life Observational Study.

Am J Clin Dermatol 2021 Jul;22(4):581-586

Department of Medicine and Health Sciences Vincenzo Tiberio, University of Molise, Via Francesco De Santis, snc., 86100, Campobasso, Italy.

Objective: The objective of this study was to assess the effectiveness and safety of dupilumab in treating elderly patients with atopic dermatitis from baseline to 52 weeks.

Methods: A retrospective observational real-life study was conducted in a group of elderly patients with severe atopic dermatitis treated with dupilumab for 52 weeks. Inclusion criteria were: age ≥ 65 years; diagnosis of atopic dermatitis made by an expert dermatologist; Eczema Area and Severity Index ≥ 24; and a contraindication, side effects, or failure to respond to cyclosporine. The primary outcome was the mean percentage reduction in the Eczema Area and Severity Index score from baseline to week 52. Secondary measures included the mean percentage reduction in the Pruritus and Sleep Numerical Rating Scales and the Dermatology Life Quality Index, and the types and rates of adverse events from baseline to week 52.

Results: One hundred and five patients were eligible for the study. Flexural dermatitis was the most frequent clinical phenotype (63.8%). The coexistence of more than one clinical phenotype was found in 70/105 (66.6%) patients. We observed a reduction in all disease severity scores from baseline to week 52 (p < 0.001). Adverse events were recorded in 30/105 (28.6%) patients, with conjunctivitis and injection-site reaction the most frequent.

Conclusions: In this study, dupilumab is an effective and safe treatment for the long-term management of atopic dermatitis in patients aged over 65 years.
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http://dx.doi.org/10.1007/s40257-021-00597-5DOI Listing
July 2021

Satisfaction and attitudes toward systemic treatments for psoriasis: A cross-sectional study.

Dermatol Ther 2021 05 25;34(3):e14949. Epub 2021 Mar 25.

Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, Italy.

In psoriasis patients, satisfaction and patients' attitude toward treatment are heterogeneous depending on several factors and remain poorly investigated, although the availability of several new targeted therapeutic options. A multicentre cross-sectional investigation was conducted to estimate treatment satisfaction and attitudes (awareness, trust, and therapeutic alliance) in a large population of adult psoriasis patients undergoing a systemic biologic or non-biologic agent for moderate-to-severe plaque-type psoriasis. Patients' satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication II questionnaire and patients' attitudes toward treatment were evaluated using a Lickert scale. Results were related to patients' and treatment characteristics and therapeutic outcomes. The study included 899 psoriasis patients and demonstrated high-treatment satisfaction and positive attitudes toward systemic treatments, with greater influence of the perceived efficacy and the type of treatment. Biologic treatments and, in particular anti-IL17 agents showed higher results. More efforts in developing tools facilitating communication and exploring important aspects of patients' view are needed.
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http://dx.doi.org/10.1111/dth.14949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243966PMC
May 2021
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