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

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

Real-Life Experience with Sonidegib for Locally Advanced Basosquamous Carcinoma: A Case Series.

Introduction: Basosquamous carcinoma is an uncommon subtype of basal cell carcinoma (BCC), characterized by aggressive local growth and metastatic potential, that mainly develops on the nose, perinasal area, and ears, representing 1.2-2.7% of all head-neck keratinocyte carcinomas. Although systemic therapy with hedgehog inhibitors (HHIs) represents the first-line medical treatment in advanced BCC, to date, no standard therapy for advanced basosquamous carcinoma has been established. Herein, we reported a case series of patients affected by locally advanced basosquamous carcinomas, who were treated with HHIs. Case Presentation: Data of 5 patients receiving HHIs for locally advanced basosquamous carcinomas were retrieved (2 women and 3 males, age range: 63-89 years, average age of 77 years). Skin lesions were located on the head-neck area; in particular, 4 tumors involved orbital and periorbital area and 1 tumor developed in the retro-auricular region. A clinical response was obtained in 3 out of 5 patients (2 partial responses and 1 complete response), while disease progression was observed in the remaining 2 patients. Hence, therapy was interrupted, switching to surgery or immunotherapy. Conclusion: Increasing evidence suggests considering HHIs for large skin tumors developing in functionally and cosmetically sensitive areas, in patients with multiple comorbidities, although their use for basosquamous carcinoma require more exploration, large cohort populations, and long follow-up assessment.

Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor.

In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.