Melanoma Institute Australia Co-Medical Directors, Professor Richard Scolyer AO and Professor Georgina Long AO, are global leaders in the fight against melanoma.

Devastatingly, Richard recently received an incurable brain cancer diagnosis.

Together, in a world first, they began applying their melanoma expertise to try to save Richard’s life and accelerate brain cancer research. Early results are in. The world is watching in earnest.

They shared their story with the National Press Club on Wednesday. An edited version of their speech is reproduced below with their permission.

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It is a privilege to be here today, addressing the National Press Club of Australia 12 months to the day from our inaugural address.

Last year, we stood here side by side, and put melanoma prevention in the national spotlight.

We called for more to be done to promote sun safety amongst our children and in sport, and we pleaded with social media and advertisers to stop the glamourisation of tanning.

The response was instant and impactful.

Social media giant TikTok was spurred into action, launching its aptly named ‘Tanning. That’s Cooked’ campaign – a first for a social media powerhouse.

Government and policy makers began working closely with us on several initiatives, including to improve sun safety in sport, which will be launched later this year at the Australian Institute of Sport.

Whilst our focus firmly remains on melanoma research, treatment and education- today we have a much broader agenda.

It is one pushed to the forefront by a devastating personal diagnosis, one which has the power to transform how we treat all cancers, globally.

Today we will detail world first treatments and scientific breakthroughs in relation to the worst subtype of glioblastoma, a type of brain cancer.

We are melanoma experts and therefore cancer experts. We have applied the learnings from our pioneering melanoma research to glioblastoma. We have generated in 10 weeks discoveries that would normally take many years.

Inspired by progress we have made in recent months we will today also call on the global cancer field to think big and be courageous:

1) Firstly, challenge the paradigm, look beyond the confines of one cancer, particularly for the subset of cancer patients who are dying on “standard treatments”.

2) Secondly, design better clinical trials and ensure greater access to patients

3) And lastly, we must  embed research into clinical care to generate scientific data faster

This must be the pathway to transform the outcome for cancer patients.

And that is what we are here to do today.

It is important first to understand the leading role that melanoma has taken on the world research stage.

Little more than 10 years ago, advanced melanoma was an almost certain death sentence within months, the ‘incurable’ cancer.

Australia has the highest melanoma rates in the world, and together, we saw the challenge of melanoma as a tremendous opportunity to make a difference to many.

Key to shifting the dial has been Melanoma Institute Australia’s model of embedding research into clinical care. So this is how it works:

1)       Questions arise in our clinics.

2)       These questions then inform research priorities, which underpin new research programs and clinical trials.

3)       We apply these results back in our clinics to benefit future patients.

This is the ‘bedside to bench and back to bedside’ or otherwise known as the ‘translational research ‘model.

We take a multi-disciplinary approach – all working towards our goal of ‘Zero deaths from melanoma’ by contributing to ground breaking clinical and research outcomes.

You may all have heard about immunotherapy in cancer. Immunotherapy drugs work by unleashing the body’s immune system to specifically fight the cancer cells.  Immunotherapy has been a transformative revolution in cancer management.

But what you may not realise is that immunotherapy was pioneered in melanoma first, and other cancers followed, for example lung cancer. And Melanoma Institute Australia remains at the forefront of global immunotherapy clinical trials. Now, more than 50% of advanced melanoma patients are cured – a term the cancer field doesn’t use lightly.

We are now using immunotherapy for earlier stage melanoma patients, so before disease has spread around the body.  We’ve begun giving immunotherapy before their initial definitive surgery.

This is called neoadjuvant immunotherapy.

It is a simple concept – the immune system is better able to see the enemy, and be trained against it, and thus mop up any cancer cells that we cannot see.

Immunotherapy is like sniffer dogs being trained through exposure to illicit drugs, so when they get to work, they know what they are searching for.

And the results have been  stunning – recurrence rates have dropped substantially and survival rates escalated even further.

And now, melanoma science is fuelling world-first breakthroughs in brain cancer – the impetus for which – Richard’s own diagnosis – no one could have predicted.

Professor Richard Scolyer

I stand here today as a doctor, pathologist, a researcher and a clinical leader who has dedicated my career to saving lives from melanoma.

I also stand here as a devoted husband to Katie, and the proud dad of 3 amazing teenagers – Emily, Matthew and Lucy.

And devastatingly, as of 5 June this year, I also stand here as a terminal brain cancer patient, with Grade 4 IDH wildtype glioblastoma – the worst subtype of brain cancer. A brain cancer for which standard treatment and survival rates haven’t changed in nearly 20 years.

It is essentially incurable. No one survives it. And no-one saw it coming, least of all me.

I was fit, having represented Australia at the World Aquathon Championships in Ibiza in early May alongside my eldest daughter Emily and Georgina.

A few weeks later, I was in Poland doing a presentation on melanoma pathology. This was one of the rare occasions when Katie, who is also a doctor, had travelled with me.

The day after the conference, we went up the mountains to a beautiful town called Zakopane (Zakopanuh). We hiked through some incredible scenery.

I woke the next morning, not feeling quite right.

I had a brief phone chat with my mum back in Tasmania. I don’t remember much after that.

I know now that I had a seizure. An initial CT scan in the local hospital cleared me of a brain bleed.

Later that evening, I was taken by ambulance, under lights and siren, to the larger University Hospital in Krakow, 90 min away, for further investigations.

Katie called Georgina, who is also our close family friend, and also the world’s top melanoma and immunotherapy expert.

Georgina asked Katie to text her a video of my MRI scan.

Back in Sydney, Georgina sent it to our colleagues, neurosurgeon Assoc Prof Brindha Shivalingam and radiologist Dr Rony Kapoor. They immediately thought glioblastoma was a strong possibility.

This early expert opinion, whilst I was still in hospital in Poland, enabled the Melanoma Institute team led by Georgina to mobilise.

It was a bleak outlook – standard treatment has remained unchanged for nearly two decades. And for my cancer, survival rates are zero.

There were no clinical trials that I was eligible for. Accepting that status quo was never going to be an option.

By the time Katie and I arrived back in Sydney, 5 days after my seizure, Georgina had started developing a novel treatment plan for my brain cancer.

It is an interesting phenomenon having a terminal diagnosis as a cancer researcher and clinician. Knowledge is power – but can this make it difficult to maintain hope?

I’ve been a pathologist for 30 years – I can interpret my pathology slides and radiology reports, and understand what they mean.

That initial biopsy confirmed that I have the worst of the worst – Grade 4 glioblastoma, IDH wildtype, unmethylated, with a wide range of other poor prognostic molecular features.

With standard treatment – surgery to remove as much tumour as possible without causing deficits, followed by an intense course of daily radiotherapy, then chemotherapy – I had 6 to 9 months at best.

My type of brain cancer always comes back.

There is no sugar coating it. I knew I was facing a terminal diagnosis.

That is tough – I’ve cried, we’ve cried as a family, we still do. I just don’t want to miss what lies ahead for my kids, my wife, my friends and my colleagues.

I am only 56. I love my life, and have so much more to do, and to contribute.

I watched my RPA friend and colleague, Chris O’Brien, go through his own brain cancer battle. The loss of such a brilliant, and kind man, still stings.

Maybe I’m too much of an optimist, but my deep scientific understanding has allowed me to view my own diagnosis through a different lens.

Rather than just a devastating challenge, I also see my diagnosis as a unique opportunity to progress research and treatment for, another ‘incurable’ cancer.

So here we are today, 4 months after my diagnosis.

With incredible guidance from Georgina supported by the Melanoma Institute team, and unwavering support from my family, for which I can never thank them enough, we have embarked on a never-before-trodden path of applying melanoma science to treatment for my glioblastoma.

What we have done is experimental in brain cancer. But it is underpinned by science.

I can only do this because I am a cancer researcher and clinician, and so inherently understand the risks – this treatment may extend, or shorten my life.

It hasn’t been a simple path. There was initial resistance from some in the oncology community. Understandable. But Katie and I spent many hours writing long letters detailing what I wanted to do, and why. In effect I was signing away any recourse should my 6-9 months become far less.

The potential benefits are immense:

• I may survive, and beat the unbeatable, and in doing so, we will massively impact the whole brain cancer field.
• At worst, I will leave a legacy of increased scientific knowledge to benefit future brain cancer patients.

So, what have we done?

I have not had the standard treatment protocol for brain cancer, and instead stand here today as patient zero in what may become the new frontier of brain cancer treatment.

Less than 3 weeks after my seizure, I became the first brain cancer patient in the world to have combination neoadjuvant immunotherapy, so before surgery to remove my brain tumour. This was my frontline treatment.

Georgina warned me of the potential side effects of immunotherapy. I’d had a combination dose, which can be more toxic than single agent.

My side effects were manageable. I had some nausea and vomiting, fevers with trouble sleeping, and at times uncontrollable shivers.

Surgery to resect my tumour was planned for 12 days later to give the drugs time to work and to activate my immune system against the cancer cells.

Early in the morning on 21st June, I was wheeled in for neurosurgery with Brindha SHIVALINGAM at the Royal Prince Alfred Hospital – my workplace for nearly 25 years, and where we are today.

Brindha has been a colleague of ours at RPA and Melanoma Institute for many years, and there was no one I trusted more for my surgery.  She was going to remove as much tumour as she could, without impairing my brain function.

The challenge with my type of brain cancer is that you simply can’t cut it all out. Surgeons are limited by needing to maintain function and quality of life.

Glioblastoma also has tentacles, much like tree roots. It’s those tumour cells you can’t see, spreading silently within your brain, that eventually re-appear and ultimately prove fatal. To remove my cancer, you would need to remove a large part of my brain, which is probably not compatible with life.

By utilising combination immunotherapy pre-surgery, first line treatment, we were hoping my immune system would destroy the cancer cells which had undoubtedly already begun spreading deep into my brain.

It was a 6 hour surgery. I awoke not feeling too bad considering. I could still talk, I recognised my family and colleagues.

I vividly recall Georgina excitedly saying to Brindha at my bedside, ‘you didn’t take the Richard out of Richard.’

The surgery was a success, although some tumour was left behind intentionally to maintain my functional capacity and quality of life.

Then came the anxious wait for laboratory analysis of my tumour.

As a leader of the International Neoadjuvant Melanoma Consortium, I’ve closely analysed thousands of tumours from melanoma patients treated with neoadjuvant immunotherapy for signs of response

The hope was that my tumour would show similar signs.

After recovering from surgery, I returned to work including at our , melanoma translational research lab at the University of Sydney.

I am also back exercising, running as well as stationary cycling.

I have had three more infusions of immunotherapy and. 6 weeks of daily radiotherapy.

And I am proud to announce, that only days ago, I had another world first treatment for my brain cancer.

I stand here today as the first brain cancer patient to have a personalised cancer vaccine with combination immunotherapy, instead of standard treatment.

The vaccine is based on my specific tumour DNA and RNA. It was administered at Melanoma Institute, in the same clinic where melanoma patients receive their personalised vaccines on a clinical trial Georgina is overseeing.

I understand the risks I am taking – we do not know if these treatments will work, I may do worse.

Although this is my personal journey, I am not alone. A terminal cancer diagnosis is one that many have travelled before, and sadly, many will travel after me.

Early on, I decided to publicly document my journey. I have been blown away by the overwhelming response from people across Australia and around the world.

A common question is “why am I doing this – why be so open, and a human guinea pig?”

It’s a ‘no brainer’, I like to quip.

Faced with certain death, there was no other decision to make. I have spent my life diagnosing and researching cancer, so why would I stop now?

In addition to the novel treatments I’m having, I’ve also chosen to have additional tests and procedures, purely to progress research. This includes a riskier open biopsy, delayed resection of my tumour, many lumbar punctures, multiple scans and blood tests and various other cognitive tests.

Science has a long history of being pushed forward by scientists using themselves as subjects.

What I am doing may not be as extreme as the likes of Marie and Pierre Curie, who routinely exposed themselves to radiation and suffered the consequences for the rest of their lives.

But hopefully the scientific learnings we will generate will be just as profound.

Of course I hope for my life to be saved. But I am also proud of the global advances in brain cancer we have already generated.

I am indebted to my friend and colleague, Georgina, and the wider Melanoma Institute team, for their, expertise and vision in developing this novel treatment path, and for travelling this journey with me.

The world is watching, and as Georgina will now detail, the scientific discoveries already made are immense.

Professor Georgina Long

Thanks Richard, your strength, courage and passion are truly inspiring.

I have known Richard for more than 25 years. As Co-Medical Directors of Melanoma Institute Australia, we lead a team dedicated to changing the face of melanoma treatment globally.

We’ve faced many challenges during that time – but nothing prepared me for that phone call from Katie from Poland.

Richard is my closest colleague and one my best friends. His glioblastoma diagnosis devastated me.

When I got the call I felt a physical pain like nothing I’ve ever experienced before. It was grief for what Richard and his family were about to go through, and for the thought of losing my dear friend and colleague.

The struggle I had at that time was to process the grief and move forward and develop a plan as there was no time to lose.

Our collective knowledge is immense, and Richard’s glioblastoma was an opportunity to apply our knowledge to an entirely different cancer.

Richard’s subtype of glioblastoma is a death sentence, and treatment has not changed in 20 years. Given this unique situation, in my view it would be morally and ethically inappropriate to not apply our knowledge.

I have put thousands of patients on immunotherapy. I have managed their side effects, I have monitored their progress, and I have designed, written and led multiple immunotherapy clinical trials, including in melanoma that has spread to the brain.

I knew that if anything was going to have an impact on the tumour and save Richard, it could be immunotherapy.

Those early days after Richard’s seizure were spent researching glioblastoma – I spent hours with international glioblastoma experts, who generously gave me their time, and pharmaceutical companies – from small biotechs to large corporations.

It was the week leading up to the world’s premier annual cancer conference in the US – the American Society of Clinical Oncology. I never miss it.

I almost cancelled – but then decided to go and utilise every available moment trying to understand the drug landscape in glioblastoma.

I attended every glioma session possible, and met with experts from across the globe.

I trawled through scientific and medical journals searching for latest papers and treatment options.

It was a barren landscape. You could count the number of immunotherapy clinical trials for glioblastoma on one hand.

After all that work, and despite the presence of a small and passionate group of clinician researchers and scientists in the glioma field, there was little interest in drug development in glioblastoma from the pharmaceutical industry, particularly for Richard’s subtype.

In an absolute travesty, there was not one single clinical trial available for Richard, that is, upfront, first line. Not one. And by extension, that meant not one single clinical trial for other patients like him.

Perhaps we were naïve in our expectation. In melanoma, every patient, particularly those with the most difficult to treat subtypes, are considered for clinical trials, and we have many trials open at any one time.

It seemed so unjust for Richard, whose expertise has been critical in some of the most innovative clinical trials in melanoma, to not have access to a clinical trial himself.

All that was on offer was the standard treatment which hasn’t changed since the early 2000’s.

I was astounded, disappointed, but above all, frustrated.

As scientists and researchers, it is incumbent upon us all to push the medical field forward.

Melanoma had broken new ground and many thousands of lives saved as a result. Could any of these learnings be applied to the most difficult to treat cancers, such as glioblastoma?

Our colleague, Professor Helen Rizos, an incredible scientist and chair of the Melanoma Institute’s research committee, shared my vision that we had an opportunity, actually an obligation, to try something ground breaking.

We wanted to try to save Richard, or at the least extend his life, but we also wanted to push the field forward.

Helen and I gathered the Melanoma Institute’s translational research teams, and we began strategising, along with the neuropathology team and others from around Australia.

We are not brain cancer specialists. This was a new field for us. But we know how melanoma works, we know how cancer works, and we know how immunotherapy works.

There was pushback. There were no clinical trials, no protocols for using immunotherapy this way in this type of brain cancer. This cancer is in the most precious and critical organ, the brain – and that organ is contained in a closed box, the skull. Any swelling could be exacerbated by immunotherapy, with dire consequences.  And with that came a lot of fear.  Because you cannot live without a brain.

But the upside of immunotherapy is that it may deal with this problem; by stimulating immune cells to selectively kill cancer cells, and preserve normal brain cells.

It’s just like those sniffer dogs at the airport, darting around luggage searching for illicit substances, but ignoring everything and everybody else.

Brain swelling was only a relative risk, and likely low from our experience in melanoma that had spread to brain.

Other barriers put forward included;

1)       that brain cancer is immunosuppressive, so it would not respond to immunotherapy, and

2)       brain cancer is heterogenous, meaning full of different cancer cells, so impossible to target all of them effectively.

But these weren’t barriers for us. We’d navigated all of these supposed barriers in melanoma, including using immunotherapy to treat tumours which had spread to the brain.

We were comfortable as cancer researchers to not have fear.

Combination immunotherapy, in a true neoadjuvant setting, has never before been used in brain cancer. By this, we mean frontline, first up treatment –  before surgery, before radiotherapy, before chemotherapy.

In melanoma we have proven that it is much more effective to give immunotherapy, just like this, before definitive surgery, so that the immune system is more activated to fight the cancer.

There have only been a very small number of international clinical trials using immunotherapy in brain cancer, but none using combination immunotherapy as frontline treatment.

So Richard’s treatment: combination neoadjuvant immunotherapy, upfront, first line, before surgery – has broken new ground.

Yes, Richard is a patient of one, but early scientific results are nothing short of phenomenal and I am delighted to share these with you now

Laboratory tests on Richard’s tumour, removed 12 days after he received combination neoadjuvant immunotherapy, showed:

1. Firstly, there was a 10 fold increase in the immune cells within the tumour.
2. Secondly, these immune cells were activated against an enemy
3. Thirdly, the immune cells within the tumour were bound to drug, proving something we had already shown in melanoma – that there is no blood brain barrier as historically conceptualised, preventing the drugs from reaching the tumour.

We couldn’t have hoped for better results. The neoadjuvant combination immunotherapy was doing what we had seen it do in melanoma, but this time it was doing it in Richard’s brain cancer.

As Richard also revealed, he is the first person in the world to have a personalised brain cancer vaccine with combination checkpoint inhibitors, instead of standard treatment.

Melanoma Institute and the melanoma-field has led the world in the development of personalised cancer vaccines. So using that expertise, we took Richard’s tumour, analysed the whole genome of his tumour, and of him, to identify what is unique to Richard’s tumour that has high potential for the immune system to recognise as an enemy. Using this scientific data, a personalised vaccine was developed to further boost the immune reaction against his cancer cells. We are now looking at laboratory data to determine the effectiveness of the vaccine.

But we have a backup plan. We were able to isolate so many activated immune cells from Richard’s tumour after the neoadjuvant immunotherapy, we have a substantial supply of Richard’s immune cells to infuse into him should the need arise.

We are looking forward to publishing all our data in a high-impact peer-reviewed journal, and presenting at a scientific conference in a few weeks.

Whilst this early scientific evidence is promising, it is too early to tell if this will translate to clinical benefit for Richard. Only follow up scans, as the weeks and months go by, will determine that.

Importantly, the global glioblastoma field is already taking action, as they see our data.

Based purely on our scientific findings, some forward thinking biopharmaceutical companies are investigating starting programs for glioblastoma, including support of truly neoadjuvant clinical trials.

Such trials are how new treatments are tested in a clinical context and if effective, save lives.

As a scientist it is ingrained in me to treat these results with caution. But as Richard’s long term close friend and colleague, for the first time since Katie’s call from Poland, I feel some optimism.

Conclusion – both

Turning now to what needs to be done. We know we are not curing as many cancers as we could.  Today we call on the cancer research field to collectively re-think its approach to tackling cancer. Think big and be courageous.

As we mentioned at the start, there are three important messages.

Firstly, challenge the paradigm.

Our brain cancer advances, based on one single patient and one single tumour, are the tip of the iceberg of what can be achieved when cancer researchers and clinicians, underpinned by science, are brave and prepared to challenge the status quo.

Secondly, clinical trial participation needs to be bolstered – it is key to developing lifesaving treatments and pushing cancer research forward.

In Australia last year, <6% of cancer patients were on a clinical trial, leaving the remaining 94% reliant on standard treatment or the status quo. That’s a bleak outlook for patients with the most difficult to treat cancers, like Richard’s, which is incurable.

To bolster participation in clinical trials, the trial design for drug therapies needs to integrate scientific knowledge generated across all cancers, and be performed in the right patient population.

For example, immunotherapies after radiotherapy and chemotherapy, and in patients receiving immune suppressing drugs for brain swelling are unlikely to be effective.  That’s why Richard received immunotherapy upfront, first-line.

Also, pharmaceutical companies need to invest and open clever clinical trials that include all cancers, even rare cancers.

Glioblastoma gets knocked back for drug trials because it’s a small market, with such a poor prognosis, and for Richard’s tumour, standard treatment hasn’t changed in 20 years.

Drug companies should consider the 50,000 people dying from cancer in Australia, not just consider for example the 1,300 dying from glioblastoma. Then they can generate monumental change.

Doing research into these difficult to treat and rarer cancers is similar to  the Matilda’s recipe for success – any player, on field or coming off the bench,  can kick the winning goal, just like research into any cancer, rare or common, can transform  the field globally.

And now to our third and final message, we must  embed research into clinical care to generate scientific data faster.  This provides insights in to the biology of cancer, and is critical to informing clinical trial development for drug therapies.

What we are advocating here today is to embed research into all clinical care, it is a philosophy:

1)       use observations in clinic to generate research questions

2)       address these questions in the laboratory and  via clinical trials

3)       Feed the results back int the clinic to impact future patient care and outcomes

And the cycle continues, this is translational research at its best and its most impactful, ‘bedside to bench, and back to bedside.

In summary, overhauling the global cancer research paradigm is long overdue.

Cancer patients are dying every minute of every day across the world. There is so much we should, and can be doing, collectively. And if not now, then when?

There is hope, and there is progress.

Look at what we at Melanoma Institute have achieved in a short period of time working with one single tumour, Richards. Collectively, the global cancer community needs to be brave and it needs to be bold.

We hope for nothing more than both of us being able to stand here again this time next year, as proof that the breakthroughs we’ve outlined today, and our calls for change, have saved lives.

I would like to end by publicly thanking you, Georgina, and a special thanks to Katie and my wonderful family and thank you all for your incredible ongoing support.