The Biennial International Society of Ocular Oncology meeting (ISOO) took place from 24–28 March at Sydney’s International Convention Centre, Darling Harbour. This is the first time the ISOO conference has been held in Australia and it occurred in conjunction with the Royal Australian and New Zealand College of Ophthalmologists NSW branch Annual Scientific Meeting (RANZCO-NSW ASM).
The focus of the ISOO is eye cancer, with full day sessions devoted to uveal melanoma, retinoblastoma and neoplasia of the lids, orbit and conjunctiva, at this meeting. Additionally around 49 E-posters were presented.
Other sessions over the four-day conference included ocular pathology courses and ‘The second eye cancer working day session’.
The speakers represented a very focussed group of academic and clinical global experts in the field. Content was pitched at a very high level yet presenters managed to convey the key points in digestible chunks for the general ophthalmologists, ocular oncologists and related oncology clinicians and researchers in attendance.
…monitoring and prompt referral to a specialist in the field is paramount
Uveal Melanoma (UM) remains one of the greatest threats. In some studies, patients died within six months, with many dying within ten years.
Fortunately, new techniques and drug therapies are providing improved outcomes, especially in people who were formerly regarded as beyond treatment. Lifespan and quality of life for sufferers of eye-related cancers are also improving.
As we know, it is critical to make an early diagnosis of melanoma and other neoplasms using the tools we have such as slit-lamp and dilated fundal examinations, regular and super wide-field retinal imaging as well as the use of ultrasound, OCT and of course MRI and CT scanning. Scintigraphy and gamma cameras have also proven beneficial.
Decision-making as to what consists a suspicious lesion, monitoring and prompt referral to a specialist in the field is paramount.
Early detection of, for example, eyelid and conjunctival tumours can mean earlier excision and dramatically improved functional and cosmetic outcomes.
As a number of speakers highlighted, we discover new things in the field of UM all the time, yet there are many things we still don’t know.
Dr. Emine Kilic of the Rotterdam Ocular Melanoma study group presented ‘Molecular classification of uveal melanoma subtypes using integrative mutational and whole-genome copy number analysis.’ She detailed low, intermediate and high-risk genetic mutations regarding UM, including UMs harbouring mutations in BAP1, SF3B1 or EIF1AX genes. These have distinct chromosomal aberration patterns. She highlighted the biological difference between UMs on a genetic level.
Dr. Vanessa Morales-Tirado, Assoc.Professor at the Hamilton Eye Institute, University of Tennessee Health Science Centre presented ‘Microenvironment regulation of inflammasomes in Uveal melanoma favours metastatic growth’. UM cells disseminate hematogenously to the liver. Despite multiple advances in medicine, there are no anti-metastasis drugs and current adjuvant therapies for liver metastasis. Recent work suggests the inflammasomes can act either in anti-cancer immunosurveillance or could promote tumour growth, based on microenvironmental signals.
Old Age and Ciliary Body Involvement
Natasha van Poppelen, a PhD student from the Erasmus Medical Centre of Rotterdam in The Netherlands, presented ‘The genetic background of iris melanoma’. She noted that around 2 to ten per cent of all UM arises in the iris. Iris melanomas are rare but account for 65 to 72 per cent of all primary iris tumours. The genetic changes of confirmed iris melanoma cases were analysed using next-generation sequencing (NGS).
A number of presenters showed that in general, older age is a significant risk factor, as is ciliary body involvement.
Prof. Richard Scolyer, Consultant Pathologist and Co-Director of Research, Melanoma Institute Australia presented ‘Molecular characterisations of cutaneous melanoma’. He stated that melanoma is one of the ‘top ten’ cancers, with a lifetime risk of 2 per cent and is the most common cause of cancer death in young adults.
Sun exposure is a cause. The risk is lower in other parts of the world at less than 1 per cent. The heavily mutated landscape of cutaneous melanoma involves both
the coding and non-coding regions of the genome and novel and known ultraviolet radiation signatures of mutagenesis have been identified.
In ‘Eyelid and conjunctival melanoma, crossing the grey line’, Prof. Bita Esmaeli of the Department of Plastic Surgery at The University of Texas M. D. Anderson Cancer Centre, explained that conjunctival and eyelid melanomas are rare but important causes of ocular morbidity with a real potential for recurrence and metastasis. She mentioned surgical and new immunotherapy options which have revolutionised treatment for complex ocular adnexal melanomas, which include promising results with immune checkpoint inhibitors such as PD1 and drugs such as vemurafenib and dabrafenib for treating BRAF-mutation related cancers. For eyelid melanoma, surgery with wide excision and 5-10mm margins, multiple excisions and delayed reconstruction were recommended and thus local recurrence was quite rare. Tumour thickness was very important in skin and conjunctival melanomas, with those greater than 2mm thick significantly affecting survival.
In one case a scalp neoplasm was found to be the source of metastatic cancer of the orbit from a cutaneous source.
As clinicians, it pays to be observant of more than just the eye and lids.
Prof. John Thompson AO, former Professor of Melanoma and Surgical Oncology at the University of Sydney, presented ‘Sentinel node biopsy in cutaneous melanoma’. The outcome for patients with many types of primary malignant tumours is predicted with considerable accuracy by the presence or absence of metastatic disease in regional lymph nodes. Simply put, lymphatic drainage from any site in the body passes first to a ‘sentinel’ lymph node. Sentinal Nodes (SNs) can be identified by lymphoscintigraphy. If SNs are tumour-free, the remaining nodes in the draining node field very rarely contain tumours. Knowledge of the regional node status allows rational treatment planning based on accurate staging.
Dr. Bertil Damato, Director of the Ocular Oncology Service at the University of California San Francisco put a human face on the proceedings with his talk ‘Patient-reported outcomes after treatment of choroidal melanoma: a comparison of enucleation vs. radiotherapy in 1,596 patients’. Contrary to previous studies, patients reported better quality of life after radiotherapy than enucleation. Special measures should be taken to predict, detect and treat psychological morbidity in patients with uveal melanoma. We must encourage close relatives and friends to support patients (and those at risk), in their fight against the disease. Support from psychologists was essential to manage anxiety and stress in such patients.
Optical Coherence Tomography-A
Speakers also covered the use of Optical Coherence Tomography-A (OCT-A) for a variety of diagnostic and monitoring benefits. Assoc. Prof Alison Skalet, an ocular oncologist of the Casey Eye Institute at Oregon Health and Science University discussed ‘Optical coherence tomography angiography characteristics of iris melanocytic tumours’. She showed the benefits of OCT-A for evaluating tumour vasculature in malignant iris melanomas and benign iris lesions. A normal iris has radially-oriented vessels while iris melanomas demonstrated tortuous and disorganised intratumoral vasculature. Tumour regression after radiation therapy for melanomas was associated with decreased vessel density. OCT-A may provide a dye-free, cost-effective method for monitoring a variety of tumours, including iris melanocytic lesions. This could be helpful in evaluating tumours for malignant transformation and response to treatment.
Running concurrently with the Saturday afternoon uveal melanoma free paper and short-case sessions was a RANZCO film session where surgeons described their techniques and cases, while showing short videos of their surgery. It’s always amazing to see the fantastic results that surgeons at the top of their game can achieve. Superb surgical techniques provide remarkable functional and cosmetic results in patients who have quite large parts of their lids, orbit and adnexae excised. Their surgical and reconstructive skills are notable.
Space and time constraints meant we could only cover a small fraction of presentations and provide a short synopsis of a few selected papers. Abstracts, results and conclusions for most of the hundreds of presentations at the ISOO and RANZCO – NSW ASM conference can be accessed at: app.core-apps.com/invisage_isoo2017. Another useful resource can be found at oculonco.com