Adjuvant radiotherapy after salvage surgery for melanoma recurrence in a node field following a previous lymph node dissection

Background and Objectives: Adjuvant radiotherapy (RT) can be given to melanoma patients following salvage surgery for node field recurrence after a previous regional node dissection, but the value of this treatment strategy is poorly documented. This study evaluated long-term node field control and survival of patients treated in this way in an era before effective adjuvant systemic therapy became available. Methods: Data for 76 patients treated between 1990 and 2011 were extracted from an institutional database. Baseline patient characteristics, treatment details and oncological outcomes were analysed. Results: Adjuvant RT with conventional fractionation (median dose 48 Gy in 20 fractions) was given to 43 patients (57%) and hypofractionated RT (median dose 33 Gy in 6 fractions) to 33 patients (43%). The 5-year node field control rate was 70%, 5-year recurrence-free survival 17%, 5-year melanoma-specific survival 26% and 5-year overall survival 25%. Conclusions: Salvage surgery with adjuvant RT achieved node field control in 70% of melanoma patients with node field recurrence following a prior node dissection. However, disease progression at distant sites was common and survival outcomes were poor. Prospective data will be required to assess outcomes for contemporary combinations of surgery, adjuvant RT and systemic therapy.</p

Confirmation of Sentinel Lymph Node Identity by Analysis of Fine-Needle Biopsy Samples Using Inductively Coupled Plasma–Mass Spectrometry

Background: The sentinel lymph node (SLN) biopsy technique is a reliable means of determining the tumor-harboring status of regional lymph nodes in melanoma patients. When technetium 99 m-labeled antimony trisulfide colloid (99 mTc-Sb2S3) particles are used to perform preoperative lymphoscintigraphy for SLN identification, they are retained in the SLN but are absent or present in only tiny amounts in non-SLNs. The present study investigated the potential for a novel means of assessing the accuracy of surgical identification of SLNs. This involved the use of inductively coupled plasma-mass spectrometry (ICP-MS) to analyze antimony concentrations in fine-needle biopsy (FNB) samples from surgically procured lymph nodes. Methods: A total of 47 FNB samples from surgically excised lymph nodes (32 SLNs and 15 non-SLNs) were collected. The SLNs were localized by preoperative lymphoscintigraphy that used 99 mTc-Sb2S3, blue dye, and gamma probe techniques. The concentrations of antimony were measured in the FNB samples by ICP-MS. Results: The mean and median antimony concentrations (in parts per billion) were .898 and .451 in the SLNs, and .015 and .068 in the non-SLNs, the differences being highly statistically significant (P < .00005). Conclusions: Our results show that ICP-MS analysis of antimony concentrations in FNB specimens from lymph nodes can accurately confirm the identity of SLNs. Used in conjunction with techniques such as proton magnetic resonance spectroscopy for the nonsurgical evaluation of SLNs, ICP-MS analysis of antimony concentrations in FNB samples could potentially serve as a minimally invasive alternative to surgery and histopathologic evaluation to objectively classify a given node as sentinel or nonsentinel and determine its tumor-harboring status. © 2007 The Author(s)

Effect of Histopathological Explanations for Dermoscopic Criteria on Learning Curves in Skin Cancer Training: A Randomized Controlled Trial

Introduction: Case-based training improves novices pattern recognition and diagnostic accuracy in skin cancer diagnostics. However, it is unclear how pattern recognition is best taught in conjunction with the knowledge needed to justify a diagnosis. Objectives: The aim of this study was to examine whether an explanation of the underlying histopathological reason for dermoscopic criteria improves skill acquisition and retention during case-based training in skin cancer diagnostics. Methods: In this double-blinded randomized controlled trial, medical students underwent eight days of case-based training in skin cancer diagnostics, which included access to written diagnosis modules. The modules dermoscopic subsections differed between the study groups. All participants received a general description of the criteria, but the intervention group additionally received a histopathological explanation. Results: Most participants (78%) passed a reliable test in skin cancer diagnostics, following a mean training time of 217 minutes. Access to histopathological explanations did not affect participants' learning curves or skill retention. Conclusions: The histopathological explanation did not affect the students, but the overall educational approach was efficient and scalable

Ground reaction force, spinal kinematics and their relationship to lower back pain and injury in cricket fast bowling: A review

BACKGROUND: Fast bowlers display a high risk of lower back injury and pain. Studies report factors that may increase this risk, however exact mechanisms remain unclear. OBJECTIVE: To provide a contemporary analysis of literature, up to April 2016, regarding fast bowling, spinal kinematics, ground reaction force (GRF), lower back pain (LBP) and pathology. METHOD: Key terms including biomechanics, bowling, spine and injury were searched within MEDLINE, Google Scholar, SPORTDiscuss, Science Citation Index, OAIster, CINAHL, Academic Search Complete, Science Direct and Scopus. Following application of inclusion criteria, 56 studies (reduced from 140) were appraised for quality and pooled for further analysis. RESULTS: Twelve times greater risk of lumbar injury was reported in bowlers displaying excessive shoulder counter-rotation (SCR), however SCR is a surrogate measure which may not describe actual spinal movement. Little is known about LBP specifically. Weighted averages of 5.8 ± 1.3 times body weight (BW) vertically and 3.2 ± 1.1 BW horizontally were calculated for peak GRF during fast bowling. No quantitative synthesis of kinematic data was possible due to heterogeneity of reported results. CONCLUSIONS: Fast bowling is highly injurious especially with excessive SCR. Studies adopted similar methodologies, constrained to laboratory settings. Future studies should focus on methods to determine biomechanics during live play

Diagnostic Accuracy of Fine Needle Biopsy for Metastatic Melanoma and Its Implications for Patient Management

The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. A retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up. FNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results. FNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma

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

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

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

Whole-genome sequencing of acral melanoma reveals genomic complexity and diversity

To increase understanding of the genomic landscape of acral melanoma, a rare form of melanoma occurring on palms, soles or nail beds, whole genome sequencing of 87 tumors with matching transcriptome sequencing for 63 tumors was performed. Here we report that mutational signature analysis reveals a subset of tumors, mostly subungual, with an ultraviolet radiation signature. Significantly mutated genes are BRAF, NRAS, NF1, NOTCH2, PTEN and TYRP1. Mutations and amplification of KIT are also common. Structural rearrangement and copy number signatures show that whole genome duplication, aneuploidy and complex rearrangements are common. Complex rearrangements occur recurrently and are associated with amplification of TERT, CDK4, MDM2, CCND1, PAK1 and GAB2, indicating potential therapeutic options.This work was supported by a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1093017, G.J.M., R.A.S., N.H., G.V.L., J.F.T.), an NHMRC project grant (APP1123217) and NHMRC Fellowship grants (R.A.S., N.K.H. - APP1139071, G.VL.). G.V.L is supported by an NHMRC Practitioner Fellowship and the University of Sydney Medical Foundation. R.A.S is supported by an NHMRC Practitioner Fellowship. J.S.W. is supported by a NHMRC early career fellowship (1111678). N.W. is supported by an NHMRC Senior Research Fellowship (1139071). N.K.H. is supported by an NHMRC Senior Principal Research Fellowship (1117663). P.M.F. was supported by the Deborah and John McMurtrie MIA Pathology Fellowship. T.J.D. was supported by the Jani Haenke Melanoma Pathology Fellowship. Support from Melanoma Institute Australia, the Royal Prince Alfred Hospital and New South Wales Health Pathology is also gratefully acknowledged