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Melanoma: HELP
Articles by E. Marshall
Based on 6 articles published since 2010
(Why 6 articles?)

Between 2010 and 2020, E. Marshall wrote the following 6 articles about Melanoma.
+ Citations + Abstracts
1 Guideline Uveal Melanoma UK National Guidelines. 2015

Nathan, P / Cohen, V / Coupland, S / Curtis, K / Damato, B / Evans, J / Fenwick, S / Kirkpatrick, L / Li, O / Marshall, E / McGuirk, K / Ottensmeier, C / Pearce, N / Salvi, S / Stedman, B / Szlosarek, P / Turnbull, N / Anonymous4080839. ·Mount Vernon Cancer Centre, Northwood, Middlesex, UK. Electronic address: nathan.pd@gmail.com. · Ocular Oncology Service, St Bartholomew's and Moorfields Eye Hospital, London, UK. · Department Molecular and Clinical Cancer Medicine, University of Liverpool, UK. · OcuMel UK, UK. · Royal Liverpool University Hospital, Liverpool, UK. · University Hospital Aintree, Liverpool, UK. · Patient Representative, UK. · Moorfields Eye Hospital, London, UK. · The Clatterbridge Cancer Centre, NHS Foundation Trust, Liverpool, UK. · Southampton University Hospitals and University of Southampton, UK. · University Hospital Southampton, Southampton, UK. · Royal Hallamshire Hospital, Sheffield, UK. · Southampton University Hospitals, NHS Trust, Southampton, UK. · St Bartholomew's Hospital, UK; Barts Cancer Institute, Queen Mary University of London, London, UK. · Project Manager, London, UK. ·Eur J Cancer · Pubmed #26278648.

ABSTRACT: The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.

2 Clinical Trial Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial. 2019

Urbonas, V / Schadendorf, D / Zimmer, L / Danson, S / Marshall, E / Corrie, P / Wheater, M / Plummer, E / Mauch, C / Scudder, C / Goff, M / Love, S B / Mohammed, S B / Middleton, M R. ·Early Phase Clinical Trials Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; National Cancer Institute, Vilnius, Lithuania. · Department of Dermatology, University Hospital Essen, West German Cancer Centre, University Duisburg-Essen, Essen, Germany; The German Cancer Consortium, Essen, Germany. · Department of Oncology, Sheffield Experimental Cancer Medicine Centre, Weston Park Hospital, Sheffield, UK. · Department of Oncology, Clatterbridge Cancer Centre, Wirral, UK. · Department of Oncology, Addenbrookes Hospital, Cambridge, UK. · Department of Oncology, Southampton General Hospital, Southampton, UK. · Department of Oncology, Freeman Hospital, Newcastle upon Tyne, UK. · Köln Universitätsklinik, Köln, Germany. · Oncology Clinical Trials Office, University of Oxford, Oxford, UK. · Centre for Statistics in Medicine, University of Oxford, Oxford, UK. · Early Phase Clinical Trials Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Oncology, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. Electronic address: mark.middleton@oncology.ox.ac.uk. ·Ann Oncol · Pubmed #30428063.

ABSTRACT: BACKGROUND: Advanced melanoma treatments often rely on immunotherapy or targeting mutations, with few treatment options for wild-type BRAF (BRAF-wt) melanoma. However, the mitogen-activated protein kinase pathway is activated in most melanoma, including BRAF-wt. We assessed whether inhibiting this pathway by adding kinase inhibitors trametinib or pazopanib to paclitaxel chemotherapy improved outcomes in patients with advanced BRAF-wt melanoma in a phase II, randomised and open-label trial. PATIENTS AND METHODS: Patients were randomised (1 : 1 : 1) to paclitaxel alone or with trametinib or pazopanib. Paclitaxel was given for a maximum of six cycles, while 2 mg trametinib and 800 mg pazopanib were administered orally once daily until disease progression or unacceptable toxicity. Participants and investigators were unblinded. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and objective response rate (ORR). RESULTS: Participants were randomised to paclitaxel alone (n = 38), paclitaxel and trametinib (n = 36), or paclitaxel and pazopanib (n = 37). Adding trametinib significantly improved 6-month PFS [time ratio (TR), 1.47; 90% confidence interval (CI) 1.08-2.01, P = 0.04] and ORR (42% versus 13%; P = 0.01) but had no effect on OS (P = 0.25). Adding pazopanib did not benefit 6-month PFS; (TR 1.36; 90% CI 0.96-1.93; P = 0.14), ORR, or OS. Toxicity increased in both combination arms. CONCLUSION: In this phase II trial, adding trametinib to paclitaxel chemotherapy for BRAF-wt melanoma improved PFS and substantially increased ORR but did not impact OS.This study was registered with the EU Clinical Trials Register, EudraCT number 2011-002545-35, and with the ISRCTN registry, number 43327231.

3 Clinical Trial Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial. 2014

Leyvraz, S / Piperno-Neumann, S / Suciu, S / Baurain, J F / Zdzienicki, M / Testori, A / Marshall, E / Scheulen, M / Jouary, T / Negrier, S / Vermorken, J B / Kaempgen, E / Durando, X / Schadendorf, D / Gurunath, R Karra / Keilholz, U. ·Oncology Department, University Hospital, Lausanne, Switzerland. ·Ann Oncol · Pubmed #24510314.

ABSTRACT: BACKGROUND: In uveal melanoma (UM) with metastatic disease limited to the liver, the effect of an intrahepatic treatment on survival is unknown. We investigated prospectively the efficacy and toxicity of hepatic intra-arterial (HIA) versus systemic (IV) fotemustine in patients with liver metastases from UM. PATIENTS AND METHODS: Patients were randomly assigned to receive either IV or HIA fotemustine at 100 mg/m(2) on days 1, 8, 15 (and 22 in HIA arm only) as induction, and after a 5-week rest period every 3 weeks as maintenance. Primary end point was overall survival (OS). Response rate (RR), progression-free survival (PFS) and safety were secondary end points. RESULTS: Accrual was stopped after randomization of 171 patients based on the results of a futility OS analysis. A total of 155 patients died and 16 were still alive [median follow-up 1.6 years (range 0.25-6 years)]. HIA did not improve OS (median 14.6 months) when compared with the IV arm (median 13.8 months), hazard ratio (HR) 1.09; 95% confidence interval (CI) 0.79-1.50, log-rank P = 0.59. However, there was a significant benefit on PFS for HIA compared with IV with a median of 4.5 versus 3.5 months, respectively (HR 0.62; 95% CI 0.45-0.84, log-rank P = 0.002). The 1-year PFS rate was 24% in the HIA arm versus 8% in the IV arm. An improved RR was seen in the HIA (10.5%) compared with IV treatment (2.4%). In the IV arm, the most frequent grade ≥3 toxicity was thrombocytopenia (42.1%) and neutropenia (62.6%), compared with 21.2% and 28.7% in the HIA arm. The main grade ≥3 toxicity related to HIA was catheter complications (12%) and liver toxicity (4.5%) apart from two toxic deaths. CONCLUSION: HIA treatment with fotemustine did not translate into an improved OS compared with IV treatment, despite better RR and PFS. Intrahepatic treatment should still be considered as experimental. EUDRACT NUMBER AND CLINICALTRIALSGOV IDENTIFIER: 2004-002245-12 and NCT00110123.

4 Article Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study. 2019

Khoja, L / Atenafu, E G / Suciu, S / Leyvraz, S / Sato, T / Marshall, E / Keilholz, U / Zimmer, L / Patel, S P / Piperno-Neumann, S / Piulats, J / Kivelä, T T / Pfoehler, C / Bhatia, S / Huppert, P / Van Iersel, L B J / De Vries, I J M / Penel, N / Vogl, T / Cheng, T / Fiorentini, G / Mouriaux, F / Tarhini, A / Patel, P M / Carvajal, R / Joshua, A M. ·Department of Medical Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge. · AstraZeneca UK, Clinical Discovery Unit, Early Clinical Development, IMED Biotech Unit, Melbourn, UK. · Department of Biostatistics, University Health Network, Toronto, Canada. · EORTC Headquarters, Brussels, Belgium. · Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland. · Department of Medical Oncology, Thomas Jefferson University, Philadelphia, USA. · Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK. · Charité-Universitätsmedizin, Berlin. · Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. · Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Medical Oncology, Institut Curie, Paris, France. · Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), IDIBELL, Barcelona, Spain. · Ocular Oncology Service, Department of Ophthalmology, University of Helsinki, Helsinki University Hospital, Helsinki, Finland. · Department of Dermatology, Saarland University Medical School, Hamburg, Germany. · Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, USA. · Department of Diagnostic and Interventional Radiology, Darmstadt, Germany. · Department of Medical Oncology, Maastricht University Medical Centre, Maastricht. · Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands. · Centre Oscar Lambret, Lille, France. · Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Frankfurt, Germany. · Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Canada. · Oncology Unit, Azienda Ospedaliera 'Ospedali Riuniti Marche Nord', Pesaro, Italy. · University of Rennes, INSERM, Department of Ophthalmology, CHU Rennes, Rennes, France. · UPMC Hillman Cancer Center, University of Pittsburgh, UPMC Hillman Cancer Center, Pittsburgh, USA. · Academic Unit of Oncology, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK. · Division of Hematology/Oncology, Columbia University Medical Center, New York, USA. · Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. · Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney. · Melanoma Institute of Australia, Sydney, Australia. ·Ann Oncol · Pubmed #31150059.

ABSTRACT: BACKGROUND: Despite the completion of numerous phase II studies, a standard of care treatment has yet to be defined for metastatic uveal melanoma (mUM). To determine benchmarks of progression free survival (PFS) and overall survival (OS), we carried out a meta-analysis using individual patient level trial data. METHODS: Individual patient variables and survival outcomes were requested from 29 trials published from 2000 to 2016. Univariable and multivariable analysis were carried out for prognostic factors. The variability between trial arms and between therapeutic agents on PFS and OS was investigated. RESULTS: OS data were available for 912 patients. The median PFS was 3.3 months (95% CI 2.9-3.6) and 6-month PFS rate was 27% (95% CI 24-30). Univariable analysis showed male sex, elevated (i.e. > versus ≤ upper limit of normal) lactate dehydrogenase (LDH), elevated alkaline phosphatase (ALP) and diameter of the largest liver metastasis (≥3 cm versus <3 cm) to be substantially associated with shorter PFS. Multivariable analysis showed male sex, elevated LDH and elevated ALP were substantially associated with shorter PFS. The most substantial factors associated with 6-month PFS rate, on both univariable and multivariable analysis were elevated LDH and ALP. The median OS was 10.2 months (95% CI 9.5-11.0) and 1 year OS was 43% (95% CI 40-47). The most substantial prognostic factors for shorter OS by univariable and multivariable analysis were elevated LDH and elevated ALP. Patients treated with liver directed treatments had statistically significant longer PFS and OS. CONCLUSION: Benchmarks of 6-month PFS and 1-year OS rates were determined accounting for prognostic factors. These may be used to facilitate future trial design and stratification in mUM.

5 Article Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial. 2018

Corrie, P G / Marshall, A / Nathan, P D / Lorigan, P / Gore, M / Tahir, S / Faust, G / Kelly, C G / Marples, M / Danson, S J / Marshall, E / Houston, S J / Board, R E / Waterston, A M / Nobes, J P / Harries, M / Kumar, S / Goodman, A / Dalgleish, A / Martin-Clavijo, A / Westwell, S / Casasola, R / Chao, D / Maraveyas, A / Patel, P M / Ottensmeier, C H / Farrugia, D / Humphreys, A / Eccles, B / Young, G / Barker, E O / Harman, C / Weiss, M / Myers, K A / Chhabra, A / Rodwell, S H / Dunn, J A / Middleton, M R / Anonymous13471124. ·Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. · Warwick Clinical Trials Unit, University of Warwick, Coventry, UK. · Medical Oncology, Mount Vernon Hospital, Northwood, UK. · Department of Medical Oncology, Christie Hospital, Manchester, UK. · Royal Marsden Hospital NHS Trust, London, UK. · Oncology Research, Broomfield Hospital, Chelmsford, UK. · Oncology Department, Leicester Royal Infirmary, Leicester, UK. · Sir Bobby Robson Cancer Trials Research Centre, Freeman Hospital, Newcastle upon Tyne, UK. · Leeds Cancer Centre, St James's University Hospital, Leeds, UK. · Weston Park Hospital, Academic Unit of Clinical Oncology, Sheffield, UK. · Cancer & Palliative Care, St. Helen's Hospital, St. Helens, UK. · Oncology Department, Royal Surrey County Hospital, Guildford, UK. · Rosemere Cancer Centre, Royal Preston Hospital, Preston, UK. · Clinical Trials Unit, Beatson WOS Cancer Centre, Glasgow, UK. · Department of Clinical Oncology, Norfolk & Norwich University Hospital, Norwich, UK. · Guy's & St. Thomas' Hospital, Guy's Cancer Centre, London, UK. · Velindre Cancer Centre, Cardiff, UK. · Exeter Oncology Centre, Royal Devon and Exeter Hospital, Exeter, UK. · St George's Hospital, Cancer Centre, London, UK. · Cancer Centre, Queen Elizabeth Hospital, Birmingham, UK. · Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, UK. · Cancer Centre, Ninewells Hospital, Dundee, UK. · Royal Free Hospital, London, UK. · Castle Hill Hospital, Cottingham, UK. · Academic Unit of Clinical Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK. · CRUK and NIHR Southampton Experimental Cancer Medicine Centre, Southampton University Hospitals NHS Foundation Trust, Southampton, UK. · Oncology Centre, Cheltenham General Hospital, Cheltenham, UK. · Oncology Department, James Cook University Hospital, Middlesbrough, UK. · Oncology Department, Poole Hospital, Dorset, UK. · Department of Oncology, University of Oxford, Oxford, UK. · Experimental Cancer Medicine Centre, Oxford, UK. · Melanoma Focus, Cambridge, UK. · Oxford NIHR Biomedical Research Centre, Oxford, UK. ·Ann Oncol · Pubmed #30010756.

ABSTRACT: Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

6 Article The Liverpool uveal melanoma liver metastases pathway: outcome following liver resection. 2014

Gomez, D / Wetherill, C / Cheong, J / Jones, L / Marshall, E / Damato, B / Coupland, S E / Ghaneh, P / Poston, G J / Malik, H Z / Fenwick, S W. ·North Western Hepatobiliary Unit, Aintree University Hospital NHS Foundation Trust, Liverpool, UK. ·J Surg Oncol · Pubmed #24357463.

ABSTRACT: AIM: To determine the outcome of patients that underwent liver resection for metastases from uveal melanoma. METHODS: Over a 9-year period, patients referred with uveal melanoma metastases were included. Following treatment of primary uveal melanoma, high-risk patients were offered to be enrolled into a 6-monthly non-contrast liver magnetic resonance imaging (MRI) surveillance. Following detection of liver metastases, patients were staged with a contrast-enhanced (Primovist(®)) liver MRI, computer tomography (CT) of the thorax and staging laparoscopy. RESULTS: 155 patients were referred with uveal melanoma liver metastases, of which 17 (11.0%) patients had liver resection and one patient was treated with percutaneous radio-frequency ablation. The majority of patients undergoing liver resection were treated with multiple metastectomies (n = 8) and three patients had major liver resections. The overall median survival for patients treated with surgery/ablation was 27 (14-90) months, and this was significantly better compared to patients treated palliatively [median = 8(1-30) months, P < 0.001]. Following surgery, 11 patients had recurrent disease [median = 13(6-36) months]. Patients who had undergone a major liver resection had a significantly poorer disease-free survival (P = 0.037). CONCLUSIONS: Patients who can undergo surgical resection for metastatic uveal melanoma have a more favorable survival compared to those who do not.