Ocumel UK Patient Conference REPORT 22/9/ 2017

Ocumel UK Patient Conference 22nd September 2017 Reading, UK

Report by Joanne Finnegan for OcuMel IRL

Dr Paul Nathan, Medical Oncologist from Mount Vernon Cancer Centre, Northwood
Highlighted how immunotherapy does work well for cutaneous (40% and higher) but not so for uveal melanoma.

Current clinical trial operating in the UK

IMCGP 100 - Mount Vernon & Clatterbridge (Liverpool)

Chemosaturation - Southampton

Selumetinib

Paul Nathan advised “patient must be strategic” when choosing a clinical trial and when choosing treatments offered. Patients he said must be offered a strategy by their team to allow maximum choice. Melanoma is not the same condition across different anatomical sites. He explained that all of the centres have trials to offer and each one of them can refer to the other depending on what the patients needs are. UK centres communicate with each  other as a network

Prof Christian Ottensmeier, Consultant Medical Oncologiest University Hospitals Southampton

Immune system

• Talked about Til Therapy - 40% response rate (not for OM for another cancer)
• Stated that cutaneous melanoma and uveal melanoma are biologically very different 
• With Um there is a lower importance placed on ultra violet exposure. 
• Cutaneous has many many mutations – Uveal has only a small number of mutations
• Check point inhibitors – “relatively ineffective with uveal melanoma”.
• T cell therapy “shows potential”. 
• “We need to be smarter about how we use the immune system”. 
• Immune systems – “we all have different immune systems”

Dr Neil Steven, Consultant Oncologist University of Birmingham

Challenges in treating Uveal Melanoma.

Pointed out that there are specialist OM centres in the UK and that each centre forms a network. Every new patient is discussed at a network meeting. Not useful if all patients he says are sent directly to Southampton initially

Dr. Brian Stedman, Consultant Interventional radiologist, Southampton

Interventional Oncology and its role in liver metastatic disease

Tumor biology – Occular melanoma very different to cutaneous “Think of it as a separate disease”. When it spreads 80% of the time it will go to the liver

Screening/Surveillance

Dr. Stedman is in “no doubt that MRI is the better” method of imaging. Ultrasound technique – “depends on who is actually doing it and small disease can be missed” he says. He talked about mri with contrast and advises with new MRI machines it may no longer be required as there are techonologically so powerful. He feels there can be further discussion re same.

Liver directed therapies available are;

• TACE (small disease that is unresectable)
• Chemostauration/delcath
• SIRT (if delcath is not an option)
• Radioembolization

Liver directed treatment is he says is “buying time” for the patient. Unfortunately delcath/chemosaturation is not yet available on the NHS. Focus Trial is ongoing (6 treatments 6 weeks apart)

Professor Sarah Coupland, NWCR Centre University of Liverpool

Update on collaborative international research efforts in Uveal melaonoma

Dr Coupland firstly talked about the TCGA (The Cancer Genome Atlas) inter project established in 2005 by American president George Bush at a cost of 250 million. Set up to look at solid cancers and genetics of tumors. Its aim was to improve the diagnosis and treatment of cancers. In 2013 its first publication appeared. Uveal Melanoma “was an after thought as there was some monies left over”. Found that there are very few mutations in the tumor of Uveal melanoma.

Project – UM cure 2020 is an EU lead project

• 5 year project
• 12 partners
• Creating a biobank (12 centres)
• Liverpool have made their submission
• 77 ennucleations
• 3 local resections
• 20 had mets at the time of analysis

http://www.umcure2020.org/en/

Joanne asked why the cutaneous support group are on the board rather than an OM patient group and was told that ocumel Uk were approached but at that time they were not in a position to come on board. So MPNE were asked if they wanted to be involved and did so.

Of note

• BAP 1 is seen in 83% of UM
• 4 groups of tumors
• 3 plus PRAME
• Mutation s - again as stated above very few mutations in UM - ONLY 9 EXAMPLE - COLON CANCER HAS 100 MUATIONS

TCGA study of uveal melanoma reveals prognostic subtypes

In a comprehensive, multiplatform analysis of 80 primary uveal melanoma (UM) tumors, researchers of The Cancer Genome Atlas Research Network identified and characterized four distinct subtypes that have unique genomic aberrations, gene expression features, and patient outcomes. Cancers of the uvea, the pigmented middle layer of the eye, are relatively rare and have not been previously well-studied. Up to 50% of UM patients develop metastatic disease, for which there are no effective therapies. This study, published in Cancer Cell on August 14, 2017, suggests that the four subtypes uncovered, each with unique molecular pathway changes and associated clinical prognoses, may require different therapeutic strategies.

The researchers deployed a range of sequencing technologies and novel analytical approaches to characterize molecularly and clinically distinct subtypes of UM. Notably, using DNA-seq and RNA-seq reassembly, they identified multiple novel and complex alterations of the BAP1 gene that otherwise would not have been found. These BAP1 alterations, along with global DNA methylation profiling, can distinguish the previously known disomy 3 (D3-UM) and monosomy 3 (M3-UM) subtypes of UM, which carry more and less favorable prognoses, respectively. Within M3-UM, the investigators found that genomic aberrations, gene expression characteristics, and immune profiles further divide the group into distinct clinical outcomes. The researchers also refined the D3-UM subtype: they identified mutually exclusive EIF1AX- and SRSF2/SF3B1-mutant tumors with distinct somatic copy number alterations and DNA methylation profiles that may contribute to different prognoses. These subtypes may aid in stratifying patients based on the aggressiveness of their disease. Overall, this study expanded our basic understanding of a rare, deadly disease and revealed novel genomic characteristics that may guide the development and application of tailored clinical strategies for UM subtypes in the future. TCGA is a collaboration jointly supported and managed by the National Cancer Institute and the National Human Genome Research Institute, both parts of the National Institutes of Health.

Determined that uveal melanoma is molecularly distinct from cutaneous melanoma, with a lower somatic mutation density, no ultraviolet radiation mutational signature, and a discrete set of significantly mutated genes

See https://cancergenome.nih.gov/newsevents/newsannouncements/uveal-melanoma...

Genetic testing

Talked briefly of liquid biopsies

Joanne asked about genetic testing samples from Dublin to Liverpool. Sarah advised she is not understanding why the samples do not go to her lab. There is more testing done there and more frequent so better trained etc.

Joanne asked about Irish patients getting tested fr MRPA at 38:40 in the video. The presentation is rather a god one to watch.

Dr Heimann Consultant Ocular Oncologist, University of Liverpool

Damato developed the service

Centres are; Glasgow, Liverpool, Sheffield and London Biopsy is done after radiation. Fine needle biopsy not recommended – this is however done in America

Nevus - Watch wait or treat – discussion ensued

Monosomy 3 can be found in a small tumor

No guidelines for low risk OM

Recommends dilation for the population

ENDS