Accuracy of SIAscopy for pigmented skin lesions encountered in primary care: development and validation of a new diagnostic algorithm.

BACKGROUND: Diagnosing pigmented skin lesions in general practice is challenging. SIAscopy has been shown to increase diagnostic accuracy for melanoma in referred populations. We aimed to develop and validate a scoring system for SIAscopic diagnosis of pigmented lesions in primary care. METHODS: This study was conducted in two consecutive settings in the UK and Australia, and occurred in three stages: 1) Development of the primary care scoring algorithm (PCSA) on a sub-set of lesions from the UK sample; 2) Validation of the PCSA on a different sub-set of lesions from the same UK sample; 3) Validation of the PCSA on a new set of lesions from an Australian primary care population. Patients presenting with a pigmented lesion were recruited from 6 general practices in the UK and 2 primary care skin cancer clinics in Australia. The following data were obtained for each lesion: clinical history; SIAscan; digital photograph; and digital dermoscopy. SIAscans were interpreted by an expert and validated against histopathology where possible, or expert clinical review of all available data for each lesion. RESULTS: A total of 858 patients with 1,211 lesions were recruited. Most lesions were benign naevi (64.8%) or seborrhoeic keratoses (22.1%); 1.2% were melanoma. The original SIAscopic diagnostic algorithm did not perform well because of the higher prevalence of seborrhoeic keratoses and haemangiomas seen in primary care. A primary care scoring algorithm (PCSA) was developed to account for this. In the UK sample the PCSA had the following characteristics for the diagnosis of 'suspicious': sensitivity 0.50 (0.18-0.81); specificity 0.84 (0.78-0.88); PPV 0.09 (0.03-0.22); NPV 0.98 (0.95-0.99). In the Australian sample the PCSA had the following characteristics for the diagnosis of 'suspicious': sensitivity 0.44 (0.32-0.58); specificity 0.95 (0.93-0.97); PPV 0.52 (0.38-0.66); NPV 0.95 (0.92-0.96). In an analysis of lesions for which histological diagnosis was available (n = 111), the PCSA had a significantly greater Area Under the Curve than the 7-point checklist for the diagnosis of melanoma (0.83; 95% CI 0.71-0.95 versus 0.61; 95% CI 0.44-0.78; p = 0.02 for difference). CONCLUSIONS: The PCSA could have a useful role in improving primary care management of pigmented skin lesions. Further work is needed to develop and validate the PCSA in other primary care populations and to evaluate the cost-effectiveness of GP management of pigmented lesions using SIAscopy.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Survival outcomes and interval between lymphoscintigraphy and SLNB in cutaneous melanoma- findings of a large prospective cohort study

Introduction: Sentinel lymph node biopsy (SLNB) in cutaneous melanoma (CM) is performed to identify patient at risk of regional and distant relapse. We hypothesized that timing of lymphoscintigraphy may influence the accuracy of SLNB and patient outcomes. Methods: We reviewed prospective data on patients undergoing SLNB for CM at a large university cancer-center between 2008-2015, examining patient and tumor demographics and time between lymphoscintigraphy (LS) and SLNB. Kaplan-Meier survival analysis assessed disease-specific (DSS) and overall-survival (OS), stratified by timing of LS. Cox multivariate regression analysis assessed independent risk factors for survival. Results: We identified 1015 patients. Median follow-up was 45 months (IQR 26-68 months). Univariate analysis showed a 6.8% absolute DSS (HR 1.6 [1.03-2.48], p= 0.04) benefit and a 10.7% absolute OS (HR 1.64 [1.13-2.38], p=0.01) benefit for patients whose SLNB was performed 12 hours (n=652). Multivariate analysis identified timing of LS as an independent predictor of OS (p=0.007) and DSS (p=0.016) when competing with age, sex, Breslow thickness (BT) and SLN status. No difference in nodal relapse rates (5.2% v 4.6%; p=0.67) was seen. Both groups were matched for age, sex, BT and SLN status. Conclusion: These data have significant implications for SLNB services, suggesting delaying SLNB >12 hours after LS using a Tc99-labelled nanocolloid has a significant negative survival impact for patients and should be avoided. We hypothesise that temporal tracer migration is the underlying cause and advocate further trials investigating alternative, 'stable' tracer-agents

A feasibility study of indocyanine green fluorescence mapping for sentinel lymph node detection in cutaneous melanoma

Objectives: Sentinel lymph node biopsy (SLNB) is standard of care for staging regional LN in AJCC stage IB-IIC melanoma; using dual localization with radiolabelled colloid and blue dye. Combining these gives optimal accuracy; drawbacks include cumulative radiation exposure for healthcare workers, coordination between disciplines and anaphylaxis. An alternative tracer agent is indocyanine green (ICG); an optical enhancer that fluoresces in the near infrared range. This prospective cohort study assesses the feasibility of using ICG as a tracer agent to detect SLN in cutaneous melanoma. Methods: Primary melanoma patients diagnosed with pT1b-pT4b tumours undergoing SLNB were recruited over a 6-month period at a tertiary referral centre. All underwent standard preoperative lymphoscintigraphy (LSG) using 20-40MBq of Tc99radiolabelled nanocolloid plus intraoperative Patent Blue dye (PBD). ICG was administered as a third tracer agent intraoperatively. Results: 62 patients (33M/29F) were recruited; median age was 61 years. Median melanoma Breslow thickness was 1.6mm. 144 specimens containing 135 SLN were excised. Concordance rate for all 3 tracer agents was 88.1%(119/135 LN); that for radioisotope/PBD was 88.2%(95%CI:82.2,93.7). There were no discordance pairs between radioisotope/PBD compared to radioisotope/PBD/ICG. Radioisotope/ICG significantly increased the sensitivity of detecting SLN to 98.5%(95%CI:94.8,99.8); p<0.00001 compared to radioisotope/PBD. Concordance rate of intraoperative ICG drainage pattern with LSG was 22.6%. Conclusion: ICG utilization showed comparable sensitivity with gold standard. Technical challenges e.g. ICG leakage into biopsy field, poor concordance with LSG limits its efficacy in melanoma SLNB. We therefore do not recommend replacing current practice with ICG alone or by using a combination with TC99

1 Versus 2-cm Excision Margins for pT2-pT4 Primary Cutaneous Melanoma (MelMarT): A Feasibility Study

Abstract Background There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma &gt; 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma &gt; 1 mm in BT. Methods This phase III, multicentre trial [NCT02385214] administered by the Australia &amp; New Zealand Medical Trials Group (ANZMTG 03.12) randomised patients with a primary cutaneous melanoma &gt; 1 mm in BT to a 1 versus 2-cm wide excision margin to be performed with sentinel lymph node biopsy. Surgical closure technique was at the discretion of the treating surgeon. Patients’ QoL was measured (FACT-M questionnaire) at baseline, 3, 6, and 12 months after randomisation. Results Between January 2015 and June 2016, 400 patients were randomised from 17 centres in 5 countries. A total of 377 patients were available for analysis. Primary melanomas were located on the trunk (56.9%), extremities (35.6%), and head and neck (7.4%). More patients in the 2-cm margin group required reconstruction (34.9 vs. 13.6%; p &lt; 0.0001). There was an increased wound necrosis rate in the 2-cm arm (0.5 vs. 3.6%; p = 0.036). After 12 months’ follow-up, no differences were noted in QoL between groups. Discussion This pilot study demonstrates the feasibility of a large international RCT to provide a definitive answer to the optimal excision margin for patients with intermediate- to high-risk primary cutaneous melanoma. </jats:sec

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Predictive indicators for revisional surgery in nasal reconstruction after Mohs surgery

Background: Reconstruction of nasal lesions is complex due to the topography, mobile free margins and borders of anatomical subunits. Reconstructive challenges can lead to multiple revisional surgeries to achieve the final aesthetic result. This study aimed to evaluate risk factors and predictors of revisional surgery in patients undergoing reconstruction after Mohs micrographic surgery for nasal tumours. Methods: This was a prospective cohort study from April 2, 2008 to February 26, 2019. The study population included all consecutive patients who underwent Mohs micrographic surgery for nasal skin cancer. Resection and reconstruction of nasal skin cancer was performed by the Mohs team. Results: A total of 988 cases met our study inclusion criteria with 64 (6.5%) cases requiring unplanned surgical revision. Revision rates were highest in the ala (9.0%, p < 0.05) and complex anatomical subunits (16.7%, p < 0.0001). In contrast, revision rates for dorsum lesions were lowest (1.8%, p < 0.001). In terms of reconstructive modalities, local flaps resulted in significantly higher rates of revision when compared to grafts (relative risk, 2.37; 95% CI, 1.15–5.0; p < 0.01). In terms of histological diagnosis, squamous cell carcinoma had significantly higher revision rates when compared to basal cell carcinoma (p < 0.05). Conclusions: To our knowledge, this is the first study to report the risk factors and predictors of revision surgery in patients undergoing MMS for nasal tumours. This study highlights that the reconstructive modality utilised affects the functional and cosmetic outcome of MMS. We note that ala complex subunit lesions, squamous cell carcinoma and flap reconstruction were associated with an increased risk of revision after Mohs reconstruction of nasal lesions. Level of evidence: Level III, risk/prognostic; therapeutic study. Trial registration number: (Ref: PLA-19-20_A03) 04/02/2020

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN