[Show abstract][Hide abstract] ABSTRACT: Purpose of review:
We summarize the concept of a locally advanced basal cell carcinoma (laBCC) and present the current consensus definition. We also review the key pieces of primary research undertaken in the past year and how these affect the use of smoothened inhibitors in a clinical setting.
Medium term follow-up (30 months) of patients treated with vismodegib shows an improvement in response rates for patients with laBCC. The safety profile of vismodegib demonstrated in the original ERIVANCE study has been replicated in a larger patient cohort in a repeat study. Sonidegib is a new smoothened inhibitor currently under investigation for treatment of laBCC, which demonstrates a comparable safety profile to vismodegib. The side-effects of smoothened inhibitors appear related to both dose and duration of treatment. The durability of response to vismodegib is uncertain, but has been observed to last for over a year following discontinuation of treatment.
The understanding of the efficacy and safety of vismodegib has improved since its introduction in 2012. A broadening evidence base supports its use as a valid treatment for laBCC. However, questions remain as to how to integrate its use into existing pathways for treating laBCC and its long-term efficacy.
No preview · Article · Jan 2016 · Current Opinion in Oncology
[Show abstract][Hide abstract] ABSTRACT: This is the protocol for a review and there is no abstract. The objectives are as follows:
To determine the diagnostic accuracy of diagnostic tests for the diagnosis of the keratinocyte skin cancers BCC and cSCC in adults.
Accuracy will be estimated separately according to the target condition and prior testing undergone by study participants, i.e., primary presentation and referred populations.
To estimate and compare the accuracy of diagnostic tests for the detection of any skin cancer.
Investigation of sources of heterogeneity
We will consider a range of potential sources of heterogeneity for investigation in each individual test review. These may vary between reviews but may include the following.
i. Population characteristics
general versus higher risk populations
ii. Index test characteristics
type of test or algorithm used for test interpretation within each 'group' of tests
expert versus generalist practitioner
diagnosis in person versus image-based diagnosis
the nature of and definition of criteria for test positivity
approaches to lesion preparation (e.g., use of keratolytics before exfoliative cytology or of oil for dermoscopy)
iii. Reference standard characteristics
reference standard used
whether histology-reporting meets pathology-reporting guidelines
use of excisional versus diagnostic biopsy
whether two independent dermatopathologists reviewed histological diagnosis
iv. Study quality
consecutive or random sample of participants recruited
index test interpreted blinded to the reference standard result
index test interpreted blinded to the result of any other index test
presence of partial or differential verification bias (whereby only a sample of those subject to the index test are verified by the reference test or by the same reference test with selection dependent on the index test result)
use of an adequate reference standard
overall risk of bias
We will examine the quality and quantity of research evidence available on the effectiveness of each index test and make recommendations regarding where further research might be required.
Full-text · Article · Oct 2015 · Cochrane database of systematic reviews (Online)
[Show abstract][Hide abstract] ABSTRACT: Background:
Ingenol mebutate (IngMeb) is a novel patient-applied topical field therapy for actinic keratosis.
To demonstrate the efficacy and safety of follow-up IngMeb field treatment of actinic keratoses (AKs) present at 8 weeks after initial treatment or emerging in a previously cleared field.
In this phase III, randomised, double-blind study in patients with 4-8 clinically visible AKs within a contiguous 25 cm(2) treatment area on the face or scalp, all patients were treated initially with IngMeb 0.015% gel for 3 consecutive days. If lesions were present in the field at 8 weeks, or emerged at week 26 or 44, patients were randomised (2:1) to follow-up IngMeb or vehicle gel for 3 consecutive days. Main outcome was complete clearance rates of AKs 8 weeks after randomisation.
Of 450 patients who received initial treatment with IngMeb, 61.6% demonstrated complete clearance at 8 weeks. Patients with AKs present at 8 weeks or emerging at 26 or 44 weeks were randomised to IngMeb (n = 134) or vehicle (n = 69). IngMeb achieved a higher complete clearance rate than vehicle 8 weeks after randomisation in AKs present at 8 weeks (46.7% vs. 18.4%, P = 0.001) and in emergent AKs (59.5% vs. 25.0%, P = 0.013). Based on those who completed 12 months follow-up (n = 340), the overall 12-month clearance rate was estimated at 50.0%. Follow-up IngMeb treatment was well tolerated.
This study demonstrated long-term benefit of IngMeb 0.015% gel for initial and follow-up therapy. This article is protected by copyright. All rights reserved.
Full-text · Article · Oct 2015 · British Journal of Dermatology
[Show abstract][Hide abstract] ABSTRACT: We read with interest the timely and important article by Nissen and colleagues (1) reporting a significant age-related decline in protoporphyrin IX (PpIX) formation following photodynamic therapy (PDT). As our society ages, studies such as this which aim to explore the relationship of age to the efficacy of various treatments and the underlying molecular mechanisms are increasingly of clinical and economic importance. We feel the age-related reduction in PpIX formation reported may not necessarily translate into clinical relevance. The suggestion of inferior PDT efficacy for treatment of basal cell carcinoma (BCC) in older patients is at odds with our own findings in a larger cohort of BCCs. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
No preview · Article · Aug 2015 · British Journal of Dermatology
[Show abstract][Hide abstract] ABSTRACT: While actinic keratoses (AKs) have a known association with cutaneous squamous cell carcinoma (SCC), the relation of actinic field change to SCC has not been quantified. This study investigated the presence of field change and AKs in renal transplant recipients (RTRs) and estimated SCC risk. May 2010 to October 2011, a dermatologist examined 452 white RTRs (mean age 53 years) at two hospitals in Manchester, UK, counting AKs and recording field change presence by body site and SCCs arising during the study period. Of the participants 130 (29%) had AKs at examination. In 60 (13%) RTR patients with AKs but no field change, 4 (7%) developed SCCs, compared with 15 (21%) of the 70 (15%) with AKs and field change. SCCs developed directly within field change areas in 11/15 (73%) RTRs. This study confirms that RTRs with widespread confluent actinic skin damage are at very high risk of SCC and should be monitored closely.
Preview · Article · Mar 2015 · Acta Dermato-Venereologica
[Show abstract][Hide abstract] ABSTRACT: Basal cell carcinoma (BCC) is a common malignancy with a good prognosis in the majority of cases. However, some BCC patients develop a more advanced disease that poses significant management challenges. Such cases include locally advanced, recurrent or metastatic BCC, or tumours that occur in anatomical sites where surgical treatment would result in significant deformity. Until recently, treatment options for these patients have been limited, but increased understanding of the molecular basis of BCC has enabled potential therapies, such as hedgehog signalling pathway inhibitors, to be developed. A clear definition of advanced BCC as a distinct disease entity and formal management guidelines have not previously been published, presumably because of the rarity, heterogeneity and lack of treatment options available for the disease. Here we provide a UK perspective from a multidisciplinary group of experts involved in the treatment of complex cases of BCC, addressing the key challenges associated with the perceived definition and management of the disease. With new treatments on the horizon, we further propose a definition for advanced BCC that may be used as a guide for healthcare professionals involved in disease diagnosis and management.British Journal of Cancer advance online publication, 11 September 2014; doi:10.1038/bjc.2014.270 www.bjcancer.com.
Full-text · Article · Sep 2014 · British Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan-Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20-34) compared with 34 years (95% CI: 30-40) for wild-type individuals (hazard ratio (HR)=1.64, 95% CI: 1.04-2.58, P=0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28-37) compared with 41 years (95% CI: 32-48, HR=1.44, 95% CI: 1.08-1.93, P=0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28-34) compared with 44 years of age (95% CI: 38-53) in wild-type individuals (HR=2.48, 95% CI: 1.47-4.17, P=0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.European Journal of Human Genetics advance online publication, 27 August 2014; doi:10.1038/ejhg.2014.167.
Full-text · Article · Aug 2014 · European journal of human genetics: EJHG