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Lauren E Haydu, Richard A Scolyer, Serigne Lo, Michael J Quinn, Robyn P M Saw, Kerwin F Shannon, Andrew J Spillane, Jonathan R Stretch, William H McCarthy, John F Thompson
Purpose Standard cancer staging and prognostic estimates are determined at the time of the patient's initial disease presentation. Conditional survival is an alternative, dynamic assessment from follow-up time points after the initial disease diagnosis and is based on the condition of survivorship. Estimates of conditional survival can provide critical prognostic information for patients and clinicians, guide subsequent cancer follow-up schedules, and influence decisions regarding treatments. The current study presents conditional survival estimates developed from a cohort of 4,540 patients diagnosed with stage III melanoma treated at a single institution...
April 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
J H Lee, G V Long, S Boyd, S Lo, A M Menzies, V Tembe, A Guminski, V Jakrot, R A Scolyer, G J Mann, R F Kefford, M S Carlino, H Rizos
Background: Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information. Patients and methods: We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab. Results: ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Thomas R Crookes, Richard A Scolyer, Serigne Lo, Martin Drummond, Andrew J Spillane
BACKGROUND: Inconsistent data suggests extranodal spread (ENS) is an adverse prognostic factor in Stage III melanoma patients but it remains contentious. By rigorously matching cohorts, this study sought to clarify associations with recurrence and survival. METHODS: Melanoma patients with lymph node metastases (AJCC Stage III), with or without ENS, sub-classified on the basis of known (MKP) or unknown primary (MUP), were identified from a single institution prospective database...
January 27, 2017: Annals of Surgical Oncology
Jonathan J Lee, Ricardo E Vilain, Scott R Granter, Nina R Hu, Scott C Bresler, Shuyun Xu, Alexander H Frank, Martin C Mihm, Robyn P M Saw, Christopher D Fletcher, Richard A Scolyer, George F Murphy, Christine G Lian
BACKGROUND: 5-Hydroxymethylcytosine (5-hmC) is an epigenetic marker detectable through immunohistochemistry (IHC) that has been shown to distinguish benign nevi from melanoma with high sensitivity and specificity. The purpose of the study was to explore its diagnostic utility in a subset of histologically challenging, heavily pigmented cutaneous melanocytic neoplasms. METHODS: 5-hmC IHC was performed on 54 heavily pigmented melanocytic tumors. Semi-quantitative analysis of immunoreactivity was correlated with clinical, pathologic and follow-up data...
December 29, 2016: Journal of Cutaneous Pathology
Laveniya Satgunaseelan, Ruta Gupta, Jason Madore, Noel Chia, Trina Lum, Carsten E Palme, Michael Boyer, Richard A Scolyer, Jonathan R Clark
Phase 2 clinical trials utilising novel anti-PD1/PD-L1 antibodies are being conducted in oral cavity squamous cell carcinoma (OSCC) patients. However, data regarding PD-L1 expression in OSCC is limited. The aim of this study was to characterise the PD-L1 immunohistochemical expression in OSCC and its association with clinicopathological factors. Clinicopathological review of 217 patients with OSCC was performed, including quantifying tumour-infiltrating lymphocytes. Immunohistochemistry with PD-L1, CD4 and CD8 was performed...
October 2016: Pathology
P Guitera, S W Menzies, G Argenziano, C Longo, A Losi, M Drummond, R A Scolyer, G Pellacani
BACKGROUND: Amelanotic melanomas are often difficult to diagnose. OBJECTIVES: To find and test the best methods of diagnosis using dermoscopy and reflectance confocal microscopy (RCM) tools. METHODS: We selected consecutive, difficult-to-diagnose, light-coloured and amelanotic skin lesions from three centres (in Australia and Italy). Dermoscopy and RCM diagnostic utility were evaluated under blinded conditions utilizing 45 melanomas (16 in situ, 29 invasive), 68 naevi, 48 basal cell carcinomas (BCCs), 10 actinic keratoses, 10 squamous cell carcinomas (SCCs) and 13 other benign lesions...
December 2016: British Journal of Dermatology
H M Cheng, S Lo, R Scolyer, A Meekings, G Carlos, P Guitera
BACKGROUND: Superficial basal cell carcinoma (sBCC) can be safely treated topically. Potentially noninvasive imaging techniques, such as optical coherence tomography (OCT), may be useful to diagnose and manage patients with sBCC and obviate the need for biopsy. OBJECTIVES: To evaluate in OCT (i) the sensitivity and specificity for sBCC diagnosis, (ii) the accuracy in determining BCC depth and (iii) the role in management of sBCC mimickers. METHODS: A prospective, consecutive cohort of lesions for which sBCC was considered in the differential diagnosis...
December 2016: British Journal of Dermatology
Alyson L Mahar, Carolyn Compton, Susan Halabi, Kenneth R Hess, Jeffrey E Gershenwald, Richard A Scolyer, Patti A Groome
The 7th edition American Joint Committee on Cancer (AJCC) melanoma staging system classifies patients according to prognosis. Significant within-stage heterogeneity remains and the inclusion of additional clinicopathologic and other host- and tumor-based prognostic factors have been proposed. Clinical prognostic tools have been developed for use in clinical practice to refine survival estimates. Little is known about the comparative features of tools in melanoma. We performed a systematic search of the scientific published literature for clinical prognostic tools in melanoma and web-based resources...
September 2016: Annals of Surgical Oncology
Alastair D MacKenzie Ross, Lauren E Haydu, Michael J Quinn, Robyn P M Saw, Kerwin F Shannon, Andrew J Spillane, Jonathan R Stretch, Richard A Scolyer, John F Thompson
BACKGROUND: At presentation, most primary cutaneous melanomas are "thin" (Breslow thickness ≤1 mm, designated T1 in the American Joint Committee on Cancer staging system) and local recurrence (LR) is rare. Most current management guidelines recommend 1 cm surgical excision margins for T1 melanomas, but evidence to support this recommendation is sparse. We sought to identify clinical and pathologic factors associated with LR in patients with T1 melanomas that might guide primary tumor management...
April 2016: Annals of Surgical Oncology
Jennifer S Ko, Victor G Prieto, Paul J Elson, Ricardo E Vilain, Melissa P Pulitzer, Richard A Scolyer, Jordan P Reynolds, Melissa P Piliang, Marc S Ernstoff, Brian R Gastman, Steven D Billings
Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown...
February 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Elin S Gray, Helen Rizos, Anna L Reid, Suzanah C Boyd, Michelle R Pereira, Johnny Lo, Varsha Tembe, James Freeman, Jenny H J Lee, Richard A Scolyer, Kelvin Siew, Chris Lomma, Adam Cooper, Muhammad A Khattak, Tarek M Meniawy, Georgina V Long, Matteo S Carlino, Michael Millward, Melanie Ziman
Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab)...
December 8, 2015: Oncotarget
Lauren E Haydu, Joram T Stollman, Richard A Scolyer, Andrew J Spillane, Michael J Quinn, Robyn P M Saw, Kerwin F Shannon, Jonathan R Stretch, Johannes J Bonenkamp, John F Thompson
OBJECTIVE: This study was designed to determine the minimum safe pathologic excision margin for primary cutaneous melanomas 1.01-2.00-mm thick (T2) and to identify prognostic factors that influence survival in these patients. BACKGROUND: Several studies have shown previously that "narrow" clinical excision margins (1-2 cm in vivo) are as safe as "wide" excision margins (4-5 cm) for management of primary T2 melanomas. However, pathologic margins are likely to be a better predictor of recurrence than clinical margins...
April 2016: Annals of Surgical Oncology
Susan Seifried, Lauren E Haydu, Michael J Quinn, Richard A Scolyer, Jonathan R Stretch, John F Thompson
BACKGROUND: Primary melanomas of the vulva and vagina are rare. As a result, it has been difficult to develop evidence-based guidelines for their management. By analyzing a large series of patients with vulval and vaginal melanomas, this study sought to document the most common presenting features, identify clinical and pathologic predictors of outcome, and provide management guidelines. METHODS: A clinicopathologic analysis of 85 patients with primary melanomas of the vulva or vagina diagnosed and treated at Melanoma Institute Australia and associated units in Sydney, Australia, between 1960 and 2011 was performed...
2015: Annals of Surgical Oncology
Rachael M Anforth, Giuliana R M Carlos, Richard A Scolyer, Shaun Chou, Pablo Fernandez-Peñas
LGX818 is a new-generation BRAF inhibitor (BRAFi) that is currently undergoing phase 3 trials for the treatment of BRAF mutant metastatic melanoma patients (NCT01909453). Cutaneous toxicities associated with the administration of BRAF inhibitors are considered to be induced by the paradoxical activation of the mitogen-activated protein kinase pathway in wild-type BRAF cells. Changes in naevi, including new naevi, hyperpigmentation and fading of existing naevi, have also been reported. In addition, some patients receiving these therapies have developed second primary melanomas...
February 2015: Melanoma Research
Matteo S Carlino, Carina Fung, Hamideh Shahheydari, Jason R Todd, Suzanah C Boyd, Mal Irvine, Adnan M Nagrial, Richard A Scolyer, Richard F Kefford, Georgina V Long, Helen Rizos
BACKGROUND: MEK1 mutations in melanoma can confer resistance to BRAF inhibitors, although preexisting MEK1(P124) mutations do not preclude clinical responses. We sought to determine whether recurrent, preexisting MEK1(P124) mutations affected clinical outcome in BRAF inhibitor-treated patients with melanoma. METHODS: Data from four published datasets were analyzed to determine whether preexisting MEK1(P124) mutations affect radiologic response or progression-free survival (PFS) in patients with BRAF(V600)-mutant metastatic melanoma treated with vemurafenib or dabrafenib...
January 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Rebecca L Read, Lauren Haydu, Robyn P M Saw, Michael J Quinn, Kerwin Shannon, Andrew J Spillane, Jonathan R Stretch, Richard A Scolyer, John F Thompson
PURPOSE: To analyze a large, single-institution database to further understanding of melanoma in-transit metastases (ITM) with regard to incidence, prognosis, and the role of lymphadenectomy. METHODS: A total of 11,614 patients with single primary cutaneous melanomas were treated at Melanoma Institute Australia between January 1994 and December 2009. Of these, 505 developed ITM. Clinicopathologic characteristics, sentinel node (SN) status, patterns of disease progression, and outcomes were analyzed...
February 2015: Annals of Surgical Oncology
Lieke G E Lamboo, Lauren E Haydu, Richard A Scolyer, Michael J Quinn, Robyn P M Saw, Kerwin F Shannon, Andrew J Spillane, Jonathan R Stretch, Johannes J Bonenkamp, John F Thompson
OBJECTIVE: To determine the optimum excision margin and nodal management for patients with primary cutaneous melanomas 2.01- to 4.00-mm thick (T3 melanomas). BACKGROUND: Currently available evidence does not reliably define the minimum safe excision margin and best nodal management for patients with primary cutaneous T3 melanomas. METHODS: A retrospective study was conducted, analyzing data on 1587 patients with melanomas 2.01- to 4.00-mm thick treated at a single center...
December 2014: Annals of Surgery
M E Laing, E Coates, A Jopp-McKay, R A Scolyer, P Guitera
Naevus spilus (NS) is a naevoid disorder characterized by hyperpigmented macules or papules scattered over a café-au-lait macule. Such café-au-lait macules are often present at birth, and the darker pigmented speckles of NS slowly increase in number and size over a period of several years. NS can therefore be difficult to evaluate clinically for the development of melanoma. In vivo confocal microscopy (IVCM) is a novel method that allows examination at cellular resolution of cutaneous lesions in vivo. IVCM has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity...
July 2014: Clinical and Experimental Dermatology
M S Carlino, L E Haydu, H Kakavand, A M Menzies, A L Hamilton, B Yu, C C Ng, W A Cooper, J F Thompson, R F Kefford, S A O'Toole, R A Scolyer, G V Long
BACKGROUND: The prognostic significance of BRAF and NRAS mutations in metastatic melanoma patients remains uncertain, with several studies reporting conflicting results, often biased by the inclusion of patients treated with BRAF and MEK (MAPK) inhibitors. We therefore interrogated a historical cohort of patients free of the confounding influence of MAPK inhibitor therapy. METHODS: Patients with available archival tissue first diagnosed with metastatic melanoma between 2002 and 2006 were analysed...
July 15, 2014: British Journal of Cancer
Augustinus P T van der Ploeg, Lauren E Haydu, Andrew J Spillane, Richard A Scolyer, Michael J Quinn, Robyn P M Saw, Kerwin F Shannon, Jonathan R Stretch, John F Thompson
BACKGROUND: Several reports in the literature suggest a difference in outcome between melanoma patients with macroscopic (clinically palpable) nodal disease from an unknown primary (MUP) and a known primary (MKP). The purpose of this study was to compare the outcomes for MUP and MKP patients after therapeutic lymph node dissection (TLND) for macroscopic nodal disease. METHODS: From a large, prospective, single-institution database, the details of melanoma patients who first presented with macroscopic nodal disease and underwent TLND between 1971 and 2010 were extracted and analyzed...
September 2014: Annals of Surgical Oncology
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