Dynamic optical coherence tomography evaluation in locally advanced basal cell carcinoma during sonidegib treatment.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the Caucasian population. It has a multifactorial pathogenesis, in which constitutive activation of the Sonic Hedgehog signalling (SHH) pathway (via mutations in PTCH1 or SMO genes) represents by far the most common genetic aberration. The introduction of vismodegib and sonidegib, two SHH pathway inhibitors, changed the therapeutic approach of locally advanced and metastatic BCCs. EADO's (European Association of Dermato-Oncology) new staging system refers to these as 'difficult-to-treat' BCCs. OBJECTIVE: The aim was to evaluate sonidegib's effectiveness in patients affected by difficult-to-treat BCCs by using non-invasive diagnostic techniques. METHODS: We retrospectively evaluated 14 patients (4 females, 10 males; mean age 77 ± 11 years) affected by difficult-to-treat BCCs treated with oral sonidegib 200 mg/day that were followed with total body videodermoscopy (V-Track, Vidix 4.0) and dynamic optical coherence tomography (D-OCT, VivoSight Dx) since May 2022. Considering the risk of rhabdomyolysis routine blood tests, especially for creatine kinase concentrations, were performed. All treated patients were inserted in the BasoCare database, which aims to offer support to patients taking sonidegib. Complete and partial responses were evaluated by the overall reduction of the number of lesions and their individual sizes. Safety was evaluated by assessing the occurrence and severity of adverse reactions. RESULTS: Eighty per cent achieved complete clearance and 75% reduction of diameter. D-OCT scans performed at every follow-up showed concordance with clinical appearance and demonstrated reduction of hyporeflective structures, that is, islets of tumour cells and overall improvement of morphology. CONCLUSION: Sonidegib can be considered an effective treatment option in cases where surgery or radiotherapy would be unfeasible or has previously failed, although pigmented lesions did not show complete clearance, suggesting that there are factors other than the SHH pathway involved in tumour growth. Videodermoscopy and D-OCT were useful in the quick and seamless follow-up of lesions and added valuable information in assessing efficacy.

Modelling peak exposure of pesticides in terrestrial and aquatic ecosystems: importance of dissolved organic carbon and vertical particle movement in soil.

In the present work, an existing vegetation/air/litter/soil model (SoilPlusVeg) was modified to improve organic chemical fate description in terrestrial/aquatic ecosystems accounting for horizontal and vertical particulate organic carbon (POC) transport in soil. The model was applied to simulate the fate of three pesticides (terbuthylazine, chlorpyrifos and etofenprox), characterized by increasing hydrophobicity (log KOW from about 3 to 7), in the soil compartment and more specifically, their movement towards surface and groundwater through infiltration and runoff processes. The aim was to evaluate the role of dissolved organic carbon (DOC) and POC in the soil in influencing the peak exposure of pesticides in terrestrial/aquatic ecosystems. Simulation results showed that while terbuthylazine and chlorpyrifos dominated the free water phase (CW-FREE) of soil, etofenprox was mainly present in soil porewater as POC associated chemical. This resulted in an increase of this highly hydrophobic chemical movement towards groundwater and surface water, up to a factor of 40. The present work highlighted the importance of DOC and POC as an enhancer of mobility in the water of poor or very little mobile chemicals. Further studies are necessary to evaluate the bioavailability change with time and parameterize this process in multimedia fate models.