Summary
Background
Even though progress has been made, the detection of melanoma still poses a challenge. In light of this situation, the Nevisense electrical impedance spectroscopy (EIS) system ...(SciBase AB, Stockholm, Sweden) was designed and shown to have the potential to be used as an adjunct diagnostic tool for melanoma detection.
Objectives
To assess the effectiveness and safety of the Nevisense system in the distinction of benign lesions of the skin from melanoma with electrical impedance spectroscopy.
Methods
This multicentre, prospective, and blinded clinical study was conducted at five American and 17 European investigational sites. All eligible skin lesions in the study were examined with the EIS‐based Nevisense system, photographed, removed by excisional biopsy and subjected to histopathological evaluation. A postprocedure clinical follow‐up was conducted at 7 ± 3 days from the initial measurement. A total of 1951 patients with 2416 lesions were enrolled into the study; 1943 lesions were eligible and evaluable for the primary efficacy end point, including 265 melanomas – 112 in situ and 153 invasive melanomas with a median Breslow thickness of 0·57 mm 48 basal cell carcinomas (BCCs) and seven squamous cell carcinomas (SCCs).
Results
The observed sensitivity of Nevisense was 96·6% (256 of 265 melanomas) with an exact one‐sided 95% lower confidence bound estimated at 94·2% and an observed specificity of 34·4%, and an exact two‐sided 95% confidence bound estimated at 32·0–36·9%. The positive and negative predictive values of Nevisense were 21·1% and 98·2%, respectively. The observed sensitivity for nonmelanoma skin cancer was 100% (55 of 48 BCCs and seven SCCs) with an exact two‐sided 95% confidence bound estimated at 93·5–100·0%.
Conclusions
Nevisense is an accurate and safe device to support clinicians in the detection of cutaneous melanoma.
What's already known about this topic?
Although progress has been made in the detection of melanoma it still poses a challenge.
Electrical impedance spectroscopy (EIS) may potentially be used as a diagnostic aid for the detection of melanoma.
What does this study add?
In the largest international prospective study of its kind in melanoma detection, the EIS system Nevisense was shown to be both accurate and safe in the lesion cohort studied.
In the absence of a perfect gold standard, the accuracy of a device should be compared with the consensus diagnosis from multiple experts.
Summary
Background
Actinic keratoses (AKs) are early in situ carcinomas of the skin caused by cumulative sun exposure. Cryosurgery is an easy and practicable lesion‐directed approach for treatment of ...isolated lesions.
Objectives
To investigate whether an upfront combination of cryosurgery with a topical intervention is superior to cryosurgery alone for treatment of AK.
Methods
We performed a systematic literature search in MEDLINE, Embase and CENTRAL and hand searched pertinent trial registers for eligible randomized controlled trials until 17 July 2018. Results from individual studies were pooled using a random effects model. The risk of bias was estimated with the Cochrane Risk of Bias Tool and the quality of evidence of the outcomes with the GRADE approach.
Results
Out of 1758 records initially identified, nine studies with a total sample size of 1644 patients were included. Cryosurgery in combination with a topical approach showed significantly higher participant complete clearance rates than monotherapy risk ratio (RR) 1·74, 95% confidence interval (CI) 1·25–2·43, I2 = 73%, eight studies. The participant partial clearance rate was not statistically different (RR 1·64, 95% CI 0·88–3·03, I2 = 77%, three studies). The number of patients who completed the study protocol and did not withdraw due to adverse events was equal in both groups (RR 0·98, 95% CI 0·95–1·01, I2 = 75%, seven studies). The studies were estimated to have high risk for selective reporting bias.
Conclusions
Our results suggest the superiority of a combination regimen for AK clearance, with equal tolerability. This study highlights the importance of a field‐directed approach in patients with multiple AKs or field cancerization.
What's already known about this topic?
Cryosurgery is a fast and easy approach for treatment of isolated actinic keratoses.
A variety of effective field‐directed topical interventions are available, but they may lose efficacy in thicker lesions.
Combining cryosurgery with a topical intervention offers the benefits of a lesion‐ and field‐directed approach.
What does this study add?
This meta‐analysis suggests the superiority of a combination of cryosurgery and topical interventions for participant complete clearance, without a difference in tolerability, in comparison with cryosurgery alone.
Cryosurgery in combination with a topical intervention is an attractive and effective option for patients with multiple actinic keratoses or field cancerization.
Our results highlight the importance of treating the entire actinic field in patients with multiple actinic keratoses.
Linked Comment: Dirschka and Gupta. Br J Dermatol 2019; 180:701.
Summary
Background
The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains ...unknown.
Objectives
To investigate the diagnostic value of OCT for BCC in a typical clinical setting. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions.
Methods
This was an observational, prospective, multicentre study in which consecutive patients with nonpigmented pink lesions suspicious for BCC underwent clinical assessment, dermoscopy and OCT, with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the histological results were disclosed. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions in 155 patients for analysis.
Results
Sixty per cent of lesions (141 of 235) were identified as BCC by histology. A slight increase of sensitivity was noted following OCT, which did not reach statistical significance. The specificity increased significantly from 28·6% by clinical assessment to 54·3% using dermoscopy and to 75·3% with the addition of OCT (P < 0·001). The positive predictive value for the diagnosis of BCC using OCT was 85·2% 95% confidence interval (CI) 78·6–90·4, and the negative predictive value was 92·1% (95% CI 83·6–97·0). The accuracy of diagnosis for all lesions increased from 65·8% with clinical evaluation to 76·2% following additional dermoscopy and to 87·4% with the addition of OCT.
Conclusions
OCT significantly improved the diagnostic specificity for BCC compared with clinical assessment and dermoscopy alone.
What's already known about this topic?
The diagnostic criteria of basal cell carcinoma (BCC) by optical coherence tomography (OCT) have previously been defined.
Recent studies have also described the OCT criteria of actinic keratoses.
What does this study add?
The results of this study support the additional diagnostic value of OCT for the diagnosis of pink patches.
The diagnostic specificity for BCC may be increased by the use of OCT.
The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without ...prior KIT inhibitor treatment.
Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400 mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors.
ORR was 26.2% (n = 11/42; 95% CI, 13.9%–42.0%), sufficient to reject the null hypothesis (ORR ≤10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib.
Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.
ClinicalTrials.gov, NCT01028222.
Recent evidence suggests that ionizing radiation may be associated with unexpected side-effects in melanoma patients treated with concomitant BRAF inhibitors. A large multicenter analysis was carried ...out to generate reliable safety data and elucidate the mechanism.
A total of 161 melanoma patients from 11 European skin cancer centers were evaluated for acute and late toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with concomitant BRAF inhibitor therapy. To further characterize and quantify a possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma patients were used for individual radiosensitivity testing by fluorescence in situ hybridization of chromosomal breaks after ex vivo irradiation.
With radiotherapy and concomitant BRAF inhibitor therapy the rate of acute radiodermatitis ≥2° was 36% and follicular cystic proliferation was seen in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%) and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis ≥2° were 44% and 8% (P < 0.001) for patients with and without BRAF inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced acute radiodermatitis ≥2° more frequently than treatment with dabrafenib (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal breaks ex vivo indicated significantly increased radiosensitivity for patients under vemurafenib (P = 0.004) and for patients switched from vemurafenib to dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities were reported after stereotactic treatment.
Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.
Background
Photodynamic therapy (PDT) is a highly effective treatment option for patients with actinic keratoses (AK). However, efficacy can be reduced by insufficient illumination or hyperkeratotic ...nature of lesions.
Objectives
To investigate if PDT combined with a topical intervention is superior to monotherapy in terms of efficacy and tolerability.
Methods
A systematic literature research was conducted in Medline, Embase and CENTRAL. Pertinent trial registers were hand‐searched for eligible randomized controlled trials (RCTs) until 20 August 2018. Results were pooled using a random effects model to calculate relative risks (RR) or mean differences. The risk of bias was assessed with the Cochrane Risk of Bias Tool. The quality of evidence was estimated for each outcome of interest according to GRADE.
Results
Out of 1800 references initially identified, 10 RCTs with a total sample size of n = 277 were included. Four studies investigated a combination of PDT with imiquimod cream, three with 5‐fluorouracil cream and one each with ingenol mebutate gel, tazarotene gel and calcipotriol ointment, respectively. Patients treated with a combination showed higher participant complete (RR 1.63; 95% CI 1.15‐2.33; P = 0.007) and partial clearance rates (RR 1.19; 95% CI 0.84–1.67; P = 0.33). Similarly, the lesion‐specific clearance was higher for PDT plus topical intervention compared to monotherapy (RR 1.48; 95% CI 1.04–2.11; P = 0.03). A subgroup analysis was performed for PDT combined with imiquimod, revealing an increased participant complete clearance rate compared to monotherapy (RR 1.57, 95% CI 1.09–2.25, P = 0.02). PDT‐induced pain and local skin reactions after treatment were poorly reported. The studies were estimated at high risk for performance and detection bias.
Conclusion
The combination of PDT with another topical drug intervention does improve AK clearance rates compared to either monotherapy alone. This study highlights that the sequential application of two field‐directed treatments represents an efficient approach in patients with multiple AK and field cancerization.
Background
Lately, various smartphone applications have been introduced as diagnostic self‐monitoring tools in the evaluation of pigmented moles, but most of these techniques have not been evaluated ...systematically.
Objectives
The purpose of this study was to evaluate prospectively the sensitivity and specificity of a recently developed smartphone application using fractal image analysis for the risk evaluation algorithm in the diagnosis of malignant melanoma compared to clinical diagnosis and histopathological result.
Methods
Consecutive patients with melanocytic lesions were recruited and clinical and dermoscopical diagnosis was documented by two dermatologists independently. Imaging and analysis with the smartphone application was performed prior to excision of lesions. The findings were compared to the histological results as gold standard.
Results
Of 195 included lesions histopathological analysis revealed 40 melanomas, 42 dysplastic nevi and 113 benign nevi. The sensitivity of the diagnosis melanoma by fractal image analysis using smartphone images was 73%, the specificity was 83% compared to a sensitivity of 88% and specificity of 97% regarding the clinical diagnosis by the dermatologists.
Conclusion
The smartphone application using fractal analysis might be a promising tool in the pre‐evaluation of pigmented moles by laypersons, while it is to date inferior to the diagnostic evaluation by a dermatologist.
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