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X OCTO- MONTH library at www . ausdoc . com . au / therapy-update

2022

BER

Paul Smith

It is a story of deep tragedy — nobody survives the diagnosis — but also one of hope .

Professor Scolyer believes the immunotherapy that has transformed outcomes for melanoma over the past 20 years can successfully treat the worst form of brain cancer and save his own life .

The media excitement has been significant — after all , Professor Scolyer is co-medical director of Melanoma Institute Australia ( MIA ).

The diagnosis

Speaking at the National Press

Club in Canberra , Professor Scolyer and his colleagues at the institute acknowledged there was resistance from the oncology community because he and his colleagues were not brain cancer specialists and there were no clinical trials or protocols for immunotherapy to treat his brain cancer .

“ What we have done is experimental in brain cancer , but it ’ s underpinned by science ,” he said .

“ I can only do this because I ’ m a cancer researcher and clinician and so inherently understand the risks .”

His diagnosis was made just over three months ago while overseas in Poland with his wife , Kate , for a conference when he had woken up not feeling quite right .

He said he had a brief chat with his mum in Tasmania and then , shortly after that , experienced a seizure , about which he remembers little .

An initial CT scan in the local hospital cleared him of a brain bleed .

But later that evening , he was taken by ambulance under lights and sirens to a larger university hospital in Krakow .

Following more investigations and conversations with his medical colleagues back in Sydney , glioblastoma seemed the likely diagnosis .

“ There is no sugar coating it ; I knew I was facing a terminal diagnosis ,” he said .

“ It has been tough . I have cried . We have cried as a family . We still do . I don ’ t want to miss what lies ahead for my kids , my wife , my friends , my colleagues . “ I am only 56 . I love my life .” He went on to describe the “ interesting phenomenon ” of having a terminal diagnosis as a cancer researcher and a clinician .

“ Knowledge is power , but does this make it difficult to maintain hope ?”

“ I have been a pathologist for

30 years . I can interpret my own pathology slides , radiology reports ; I understand what they mean , and the initial biopsy confirmed I had the worst of the worst brain cancer . “ I had 6-9 months at best .” His close friend Professor Georgina Long — co-director at the institute and an expert in immuno-oncology in melanoma — said she was devastated when she heard news of the diagnosis .

“ When I got that call , I felt a physical pain like nothing I have experienced , and it was grief for what Richard and his family were about to go through ,” she told the press club audience .

Pushing the field forward

She said , in the days after his seizure

, she reached out to experts in glioblastoma from around the world , but having trawled through scientific and medical journals for treatment options , she discovered a “ barren landscape ”.

But despite a scarcity of clinical trials of immunotherapy in the treatment of brain cancer — something that shocked her given the therapeutic revolution in her own field — she believed it was an option .

“ I have put thousands of patients on immunotherapy ,” she said .

“ 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 had 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 .”

She said senior colleagues at their institute were enthusiastic to

be involved , wanting to help Professor Scolyer but also hoping to “ push the medical field forward ”.

“ We are not brain cancer specialists ,” she said . “ 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 in this way , in this type of brain cancer .”

They decided to administer combination neoadjuvant immunotherapy for Professor Scolyer ’ s tumour — apparently , a world first .

From the initial course , he experienced nausea and vomiting and , at

times , uncontrollable shivers .

Twelve days later , he underwent

neurosurgery at the Royal Prince Alfred Hospital under Sydney neurosurgeon Dr Brindha Shivalingam .

“ Glioblastoma has tentacles like tree roots ,” Professor Scolyer told the press club .

“ It ’ s those tumour cells you can ’ t see spreading silently within your brain that eventually reappear and ultimately prove fatal .

“ To remove my cancer , you ’ ll need to remove a large part of my brain , which is probably not compatible with life .”

But using combination immunotherapy pre-surgery as the firstline treatment , they hoped his

immune system would be activated to destroy the cancer cells that had “ undoubtedly already begun spreading deep into my brain ”, he said .

The surgery took six hours , with Professor Scoyler feeling afterwards “ not 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 Richard out of Richard !’”

He said the other novel element of his treatment was the administration of a personalised cancer vaccine based on his tumour ’ s DNA and RNA — again , it was an approach that had been used with

‘ We are not brain cancer specialists , but we know how immunotherapy works .’

— Professor Georgina Long

the melanoma patients treated at the institute .

Professor Long said they knew there was a risk that the immunotherapy could cause brain swelling , but based on their experience with patients with melanoma that had spread to the brain , they considered it low .

“ Other barriers were put forward , and these included that brain cancer is immunosuppressive , so it would not respond to immunotherapy , and that brain cancer [ involved many ] different cancer cells , so it would be impossible to target all of them effectively ,” she added .

“ But these were not barriers for us . We had navigated all of these

Professor Richard Scolyer and Professor

Georgina Long .

supposed barriers in melanoma itself , including using immunotherapy to treat tumours which had spread to the brain . We were comfortable as cancer researchers to not have fear .”

‘ A patient of only one ’

It is important to stress that none

of the results of this experimental treatment have been published .

Professor Long acknowledged that her colleague was “ a patient of only one ”.

But she said the early scientific results were “ nothing short of phenomenal ”.

Laboratory tests on the tumour removed 12 days after Professor Scolyer had received the combination neoadjuvant immunotherapy showed a 10-fold increase in the immune cells , she said .

She also said the immune cells within the tumour were “ bound to the drug ”.

“ This proved something we had already shown in melanoma : that there is no blood – brain barrier , as historically conceptualised , preventing the drugs from reaching the tumour .”

In terms of the vaccine , she said they were still looking at the laboratory data to find out if it had been effective .

“ But we have a backup plan ,” she added .

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

“ We are looking forward to publishing our data in PAGE 10