Pancreatic cancer cells - image courtesy of the London Research Institute EM Unit
Mr Tilly had a tough start in life. Abandoned and unwanted, he was down on his luck. But the tide turned when he was adopted by the owners of a Scottish tea shop. Now Mr Tilly has a new life and a new mission – to help others.
Mr Tilly, the helpful pug dog, is the protagonist in children’s books written by Scottish actress Noreen Boswell.
While Noreen is busy creating adventures for Mr Tilly, many miles away in Liverpool a scientist called John is planning his next big research project. More formally known as Professor John Neoptolemos, he’s a world-leading pancreatic cancer expert.
John and Noreen don’t know each other, although their lives are more closely linked than they realise. But to understand how and why we need to go back to the 1980s – when John was about to rock the world of pancreatic cancer research, and Noreen was a happy newlywed.
“Imagination is more important than knowledge”-Einstein
1989 was a year of change. Chinese students were taking a stand at Tiananmen Square and the Berlin wall came tumbling down. Noreen had been married for a year and was thinking about starting a family. And a group of young scientists had an idea that would change the way we think about pancreatic cancer forever.
Back then, overall cancer survival rates were much lower than they are today: around a third of patients could expect to survive for 10 years or more, compared to half today.
But for pancreatic cancer, survival rates were trailing well behind the average – only one in 10 made it past the first year after being diagnosed.
For some pancreatic cancer patients, surgery was the best form of treatment, but success rates were very low. Little research was being undertaken and there was a general sense of futility about improving the outlook for these patients.
An injection of hope was desperately needed, and that’s where John came in. He rallied together scientists from across Europe to tackle the problem head on.
As he explains: “The situation needed some ‘young bloods’ who had nothing to lose. We knew something needed to change and we believed we could do it”.
John had an idea to test whether extra treatment after surgery could help improve survival for people with pancreatic cancer.
But turning this idea into reality wasn’t easy. “At first I was told I was wasting my time,” he says. “Survival from surgery wasn’t good and nobody believed patients would be able to tolerate chemotherapy, let alone benefit from it.”
But he wouldn’t give up, and after some initial tests he convinced Cancer Research UK to fund a groundbreaking clinical trial called ESPAC-1.
“You must be the change you wish to see in the world” –Mahatma Gandhi
ESPAC-1 was the biggest trial ever carried out in pancreatic cancer at the time, involving 594 patients over six years. Patients were given either:
- Surgery alone
- Surgery plus chemotherapy
- Surgery plus chemoradiotherapy (a combination of a short course of chemotherapy given at the same time as, and immediately after, radiotherapy)
- Surgery plus chemoradiotherapy followed by a full course of chemotherapy.
John and his colleagues thought that chemotherapy and chemoradiotherapy might improve survival individually, but that together they might have an even bigger effect.
However, as John says: “The first shock was when we started to see the results from the chemoradiotherapy. It was actually having a detrimental effect on survival. This was the first time we realised we couldn’t use chemoradiation on these patients.”
This was clearly vital information, and that part of the trial stopped as soon as the evidence was clear. But perhaps the biggest finding was yet to come. John and his colleagues found that patients receiving a full course of chemotherapy after surgery had a 15 per cent higher chance of surviving five years or more than those who did not receive it. Not only that, but they had a much better quality of life. Although modest in absolute terms, such a significant improvement in survival had never been seen before in pancreatic cancer.
“Ideas shape the course of history” John Maynard Keyes
John says: “From that point on, everything changed. People suddenly thought it was worth researching and treating pancreatic cancer. People realised ‘Wow, we can actually do something about this problem.’”
This change in mindset was widespread. Researchers started thinking about pancreatic cancer, pharmaceutical companies got interested and health services were reorganised to improve pancreatic cancer care.
Things were changing for Noreen too. After the breakdown of her marriage, she was a single mum working two part-time jobs and taking the first tentative steps to rebuilding every aspect of her life.
By 2011 she was walking several miles to one of her jobs each day, and on her walk one morning was surprised by a nauseous feeling that persisted over the next few days. She felt grey and exhausted and, alarmed by the green and greasy look of her stools, decided to go to the doctor. Blood tests revealed that all was not well.
A GP friend suggested that she should go straight to hospital for further tests.
“When the curtain went around my bed and I heard the word ‘cancer’ I was in state of total disbelief,” says Noreen. “I thought they had made a mistake.”
Things moved very quickly from there and after revealing that she had a tumour in her pancreas, Noreen underwent an operation to remove it.
Here is where our two stories collide.
“In the middle of difficulty lies opportunity”- Einstein
Following her surgery, Noreen was asked by her oncologist if she’d be willing to take part in a clinical trial.
“I agreed – if I could in any way enable more enlightened treatment for those yet to be diagnosed with this cancer it would be worthwhile.”
Noreen was enrolled on the ESPAC-4 trial, also led by John and funded by us, which was testing whether combinations of different drugs during chemotherapy could improve patient survival.
These weren’t easy treatments for Noreen. “I was very sick at first and sorely tempted not to continue” she says. “But I heeded the words of a friend who had already been through chemotherapy after breast cancer.”
Taking her friend’s advice, Noreen ticked off every chemo session on her calendar with a coloured marker pen, and gradually saw the light at the end of the tunnel.
“In time I stopped feeling sick and recognised this was my second chance and I had to make the most of it, not just for myself but for those who loved me.”
And so we bring our story right up to the present. ESPAC-4 has just finished, and John and his colleagues are now carefully analysing the data collected from Noreen and hundreds of other patients.
“A journey of a thousand miles begins with a single step” –Lao-Tzu Chinese philosopher
It’s been three years since her diagnosis and Noreen is doing well. She has an important message, one that we are heeding in the future direction of our research.
“I would urge that more funds be made available for research like this, to bring pancreatic cancer out of the shade,” she says.
We couldn’t agree more – which is why we’re particularly focusing on pancreatic cancer as part of our new research strategy. And although pancreatic cancer remains an extremely tough-to-treat disease we now know much more about its weak points.
For those eligible for surgery we know that chemotherapy can increase survival and quality of life. Work since ESPAC-1 has helped us narrow down exactly which drugs work best and how to give them for maximum effect.
“My life is transformed,” says Noreen, “All that has happened to me is beginning to make sense. I live in the moment of every day.”
Writing has been an important way for Noreen to capture this new way of seeing the world, including her stories about Mr Tilly the helpful pug. With four books published and more on the way, Noreen sees this as her legacy for her grandchildren.
And while she knows that her future is uncertain, she’s taking each day as it comes. “I’m taking huge delight in my two small grandchildren, Eilidh and Bobbie. The past has been turbulent and the future is uncertain, but the present is very good. I’m embracing every day with gratitude – Mr Tilly’s stories encapsulate some of my hope and positivity. But scientists like John are my true life heroes.”
John is also looking to the future – a future in which we are able to do large trials, like the ESPAC studies, much more efficiently and quickly, ultimately buying more time for patients who desperately need it.
Another Cancer Research UK trial, ESPAC-5, has just started. It will test whether we can increase survival by giving chemotherapy before surgery, in the hope of shrinking pancreatic tumours. This could make surgery an option for those people who wouldn’t otherwise be able to have it.
But we are acutely aware there is still so much to do. For patients with inoperable pancreatic cancer there are still very few options, and survival from the disease still trails well behind many other cancers.
Even with the positive results from the ESPAC studies, progress is coming in achingly small steps. But that’s because it’s starting from so far behind. In relative terms, though, short-term survival has increased by around 60 per cent since the late 1980s – one in five patients now survives the disease for a year or more. But only one in every 100 patients will survive the disease for 10 years or more – a tiny number that hasn’t changed since the 90s.
With short term survival increasing we’ve made small but important steps in the right direction, but it’s not good enough. That’s why we’re pledging to do more.
We know that great successes are born out of many steps in the right direction, and as the pace gathers in the global research community, we hope that progress will accelerate. Thanks to the ESPAC trials, and dedicated work by our scientists and others around the world, we are now shining a light on pancreatic cancer research.
Our story doesn’t have an end because our journey is not yet complete. We want many more people like Noreen to look forward to a future with their families. And although the road is long and hard, there are no short cuts. We must all walk it together, and one day we will get there.
Hayley Frend (Science Communications Manager) and Flora Malein (Press Officer)
With special thanks to Noreen for sharing her story with us, and we look forward to Mr Tilly’s next adventure.