Two melanoma patients, Sean Guinness and Imogen Cheese, came to Julia Newton-Bishop and said they wanted to make a difference to the lives of all patients with melanoma: what could we do together? We three talked with colleagues and Professor Mark Middleton from Oxford agreed to work with us.
This proposal, to build the world’s largest patient-lead melanoma research cohort, is a result of that discussion. In building this cohort we want to promote a different mindset in the melanoma research community, one that genuinely has the patient at its heart and mobilises their experiences for the benefit of future generations.
Fatal cases of melanoma as reported by IARC for 2018 show that the majority of these deaths occur in the US and in Europe, although significant numbers of deaths occur worldwide (Figure 1).
To date, most drug treatment aimed at saving lives takes place after the melanoma has already relapsed, but in recent years adjuvant therapies have been introduced. These are drugs intended for use in people when they first attend the melanoma treatment service if there is evidence that they are likely to relapse. Adjuvant therapies are therefore intended to reduce the risk of relapse in patients with a poor prognosis. The issue is that although the AJCC staging system is a pretty good predictor of relapse it is far from perfect. It explains a little more than 60% of the variance ie that in 4 out of 10 patients the prognosis is inaccurate. The need therefore is to find tests that better predict relapse at the time the patient presents with primary melanoma so that they may consider treatment then to "ward off" relapse.
There is evolving evidence that the chance of relapse is modified by lifestyle: smoking, vitamin D deficiency and poor general health all being associated with a greater probability of relapse. When we better understand this then we will be able to advise patients with primary melanoma how to modify their lifestyles in order to prevent that relapse.
In discussions between Sean and Imogen, key UK melanoma researchers, Keith Flaherty (Harvard), Paul Chapman (Memorial Sloan Kettering), we agreed therefore that the international community needs to focus on primary melanoma research now, in order to address the crucial “unknowns” for melanoma patients.
For patients starting drug treatment, we can say currently that around 50% of people benefit but yet these are quite toxic therapies. There is a great need for predictive biomarkers so that the patients can make a better choice around taking such drugs either in the adjuvant or therapeutic settings. The identiciation of biomakers in general terms has been disappointing. We argue that the disappointing progress has resulted at least in part that the studies have been greatly underpowered statistically to find biomarkers. Moreover that it is unlikely that any one test will serve as a clinical useful predictive biomarker. MyMelanoma will explore the hypothesis that measure of variation in the tumour AND in the host response to the tumour will be necessary.
Finally, MyMelanoma will actually start by addressing a different question. We will collaborate internationally to establish the risk of any cancer in individuals carrying mutations in high penetrance melanoma susceptibility genes eg POT1. Measures of cancer risk in mutation carriers unbiased by ascertainment can only be estimated in prospective studies: identifying and then following up mutation carriers for many years. As the mutations are in themselves rare this is only possible if groups collaborate internationally and long term follow up is possible. Digital recruitment internationally seems like the only way of addressing this question which is very important for melanoma families and clinical genetics teams trying to advise them about screening.
To sign up to be part of MyMelanoma visit http://mymelanomastudy.org but if you have any further questions related to fund raising for us then please fill out the form. One of our team will be in touch as soon as possible.