Search

Background: Basal cell carcinoma is the most prevalent skin cancer, most characterized by local aggressiveness but with low metastatic potential, and bone metastasis is quite heterogeneous, thus the incidence profile is variable size from 0.0028% to 0.5%. We have this patient with an unusual example of basal cell carcinoma with bone metastases to add to the scarce report on this matter. Case description: Here we document a 48-year-old Persian man with a background of being exposed to the sun for a long time. He was diagnosed with an ulcer on the cheek, which was clinically characterized and further confirmed by biopsy as morpheaform basal cell carcinoma. Following the first round of excision, multiple relapses eventually metastasized to the bone. The latter was found on follow-up radiologic scans. This case is characterized by the aggressive nature of the disease and the heterogeneity of basal cell carcinoma growth, thus challenging the conventional view of basal cell carcinoma behavior. Treatment included surgical excision of the primary lesion, which was treated with radiotherapy afterward. However, the skeleton improved slowly during follow-up, and palliative care was eventually pursued to control symptoms and improve quality of life. Conclusions: This was a rare case of basal cell carcinoma metastasis to non-bone organs, which reminded us to consider basal cell carcinoma metastasis, especially in the case of atypical basal cell carcinoma. Therefore, risk-aware patient management is essential. Moreover, these findings highlight the role of further research into the mechanisms of basal cell carcinoma metastasis, leading to improved therapeutic strategies that may lead to potential improvements in patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The BOLT study for sonidegib, a Hedgehog pathway inhibitor (HHI) approved for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy, used modified Response Evaluation Criteria in Solid Tumors (mRECIST) for laBCC tumor evaluation. The ERIVANCE study for vismodegib, another HHI, used a composite RECIST endpoint of ≥30% reduction in externally visible tumor or radiographic dimension, or complete ulceration resolution. This preplanned sensitivity BOLT analysis evaluated efficacy outcomes using ERIVANCE-like criteria in patients with laBCC who received sonidegib 200 mg once daily.Methods: This phase 2, double-blind study randomized patients 1:2 to sonidegib 200:800 mg daily, respectively. Key endpoints included objective response rate (ORR), duration of response (DOR), complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). laBCC tumors were assessed by both mRECIST and ERIVANCE-like criteria. Per mRECIST, an overall response of CR was based on negative histology; photographic assessment of CR, PR (scar/fibrosis only), SD (scar/fibrosis only), or not available (NA); and a magnetic resonance imaging response of CR or NA. An overall response of CR was primarily based on negative histology using ERIVANCE-like criteria.Results: Per mRECIST criteria, ORR (95% confidence interval [CI]) by central and investigator review for patients with laBCC (n = 66) was 56.1% (43.3-68.3%) and 71.2% (58.7-81.7%), respectively. CR per central review was achieved in 3 (4.5%) patients and PR, SD, and PD occurred in 34 (51.5%), 23 (34.8%), and 1 (1.5%) patient, respectively. Median (95% CI) DOR was 26.1 months (not estimable [NE]). Using ERIVANCE-like criteria, efficacy outcomes per central and investigator review were higher, with an ORR (95% CI) of 60.6% (47.8-72.4%) and 74.2% (62.0-84.2%), respectively. CR per central review was reached in 14 (21.2%) patients and PR, SD, and PD occurred in 26 (39.4%), 20 (30.3%), and 1 (1.5%) patient, respectively. DOR was unchanged with a median (95% CI) of 26.1 months (NE).Conclusions: Overall, applying ERIVANCE-like criteria to patients with laBCC receiving sonidegib 200 mg daily yielded higher response rates vs mRECIST criteria.Trial Registration: BOLT registration: ClinicalTrials.gov ( NCT01327053 ) on March 30, 2011. [ABSTRACT FROM AUTHOR]

Background: The smoothened (SMO) receptor is an essential component of the Sonic hedgehog (SHH) signalling, which is associated with the development of skin basal cell carcinoma (BCC). SMO inhibitors are indicated for BCC patients when surgical treatment or radiation therapy are not possible. Unfortunately, SMO inhibitors are not always well tolerated due to severe side effects, and their therapeutical success is limited by resistance mutations.Methods: We investigated how common are resistance-causing mutations in two genomic databases which are not linked to BCC or other cancers, namely 1000 Genomes and ExAC. To examine the potential for combination therapy or other treatments, we further performed knowledge-based simulations of SHH signalling, in the presence or absence of SMO and PI3K/Akt inhibitors.Results: The database analysis revealed that of 18 known mutations associated with Vismodegib-resistance, three were identified in the databases. Treatment of individuals carrying such mutations is thus liable to fail a priori. Analysis of the simulations suggested that a combined inhibition of SMO and the PI3K/Akt signalling pathway may provide an effective reduction in tumour proliferation. However, the inhibition dosage of SMO and PI3K/Akt depended on the activity of phosphodiesterases (PDEs). Under high PDEs activities, SMO became the most important control node of the network. By applying PDEs inhibition, the control potential of SMO decreased and PI3K appeared as a significant factor in controlling tumour proliferation.Conclusions: Our systems biology approach employs knowledge-based computer simulations to help interpret the large amount of data available in public databases, and provides application-oriented solutions for improved cancer resistance treatments. [ABSTRACT FROM AUTHOR]