Exercising during chemotherapy and before surgery may help the body send more immune cells into cancerous tumours, according to a first-of-its-kind pilot study from the University of Surrey and Royal Surrey NHS Foundation Trust. Researchers are now looking to invite more patients to take part in a larger clinical trial called OPTIMUS, led by Consultant General Surgeon and scientist Professor Adam Frampton, to understand how these early results could help improve cancer treatment on a wider scale.

In a study published in the Journal of Sport and Health Sciences, the research team conducted a randomised controlled trial with 22 people diagnosed with oesophageal adenocarcinoma – a type of oesophageal cancer. These patients were recruited from Royal Surrey NHS Foundation Trust, home to one of the country’s leading cancer centres. Eleven participants took part in a 16-week structured exercise programme (known as “prehabilitation”), while the other eleven did not. The programme included two supervised exercise sessions per week during the chemotherapy period (for about eight weeks), followed by a second phase of exercise leading up to surgery.

After surgery, the research team analysed each patients’ tumour samples to measure immune cells using multispectral immunohistochemistry. They also studied gene activity using a platform called NanoString. Finally, they assessed each patients’ aerobic fitness through tests carried out before, during and after chemotherapy.

Dr Nicola Annels, co-senior author of the study from the University of Surrey, said:

“To the best of our knowledge, we believe that our study is the first randomised controlled trial in humans to show that prehabilitation – structured exercise during chemotherapy – can change the tumour environment in a meaningful way. We found that tumours from people who exercised had more cancer-fighting immune cells, especially CD8+ T cells and natural killer cells, compared to those who didn’t.

"These early results are promising, but we need to understand them better, and that’s why we’re encouraging more patients to take part in the ongoing clinical trial.”

There have been a number of animal-based studies showing that exercise can improve immune responses and reduce cancer growth. However, previous studies in humans – mainly focused on prostate or colorectal cancer – have not shown a clear increase in tumour-infiltrating immune cells after exercise, even after multiple sessions.

Dr David Bartlett, co-first author of the study from the University of Surrey, added:

“We found that the fitter a person became, the stronger their immune response inside the tumour. In fact, the more a patient improved their aerobic fitness, the more immune cells we found as well as signs of mature ‘tertiary lymphoid structures’, which are immune hubs linked to better responses. It’s hard not to be excited by these results, but we need to confirm them in a larger clinical trial.”

OPTIMUS aims to recruit 50 patients who are scheduled for surgery after neoadjuvant chemotherapy for oesophageal adenocarcinoma.

Patients will be randomised into one of two groups: either an exercise group similar to the published study that improved the immune response to the tumour, or a higher intensity exercise group that may increase the immune response further.

Mr Charles Rayner, co-first author of the study and Fellow in oesophago-surgery from Royal Surrey NHS Foundation Trust, said:

“So far, seven patients have completed OPTIMUS, and in some cases, the tumour was undetectable during surgery, which is only found in around 6% of patients. While these are early results, they are quite remarkable.

“Importantly, patients are fitter for surgery and are dealing with the stress of surgery and recovery much better.”

Mr Nima Abbassi-Ghadi, Senior author of the study and Consultant oesophago-gastric surgeon at Royal Surrey NHS Foundation Trust, said:

“These are exciting findings which support the importance of preoperative exercise training for patients undergoing cancer surgery at Royal Surrey. The feedback from our patients has been overwhelmingly positive with some patients who would otherwise not have been able to undergo this life saving surgery, improving their fitness to such a degree that they have now had successful procedures.”

One of the OPTIMUS participants said:

"When you first get a cancer diagnosis one tends to clutch at anything which might make a difference, so when I was asked if I wanted to take part in the OPTIMUS study I jumped at the chance.

“I did this as an already active person but had no idea how large a part the OPTIMUS trial would play during my chemo and in preparation for my recovery from surgery.

“Cancer and its treatment take away many things which give us normality; our jobs, our health, our appearance, quality time with family, whilst introducing myriad appointments, chemo side effects, stress over incomes, difficult questions and conversations with children and the very obvious chance of early death. As a cancer patient, one has little or no agency over any of these factors.

“What the OPTIMUS trial gave me was one thing over which I had control.

It is an enthusiastic environment, staffed by dedicated young people, all simultaneously trying to help us and to also push scientific understanding of the effect of exercise on cancer outcomes.

“Like most things in life, it is the people running the day-to-day that make this trial special.

“They both help you to achieve the best outcome for you (age spread ~57-84), pushing you where appropriate, but they also have the emotional intelligence to know when you need a tissue and an arm round the shoulder, as cancer is an emotional roller coaster.

“Although I am a reasonably determined person anyway, I can categorically say that, along with the oncologists and surgeons that saved my life, the Optimus team made the biggest qualitative difference to my cancer journey and recovery."

People can join the study if they are being treated at the Royal Surrey Cancer Centre and should ask their oncology or surgical teams about the study. Alternatively, they can email Dr Bartlett and Dr Annels directly at d.bartlett@surrey.ac.uk or n.annels@surrey.ac.uk.

Funding for the research [IIG_FULL_2023_029] was obtained from the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme.