Exercise may boost impact of pre-surgical chemo in patients with oesophageal cancer, says study
A research team that offered rehab exercise regimes to patients with oesophageal cancer before they received chemotherapy to shrink their tumours believes the results were promising, according to a paper that was published online in the British Journal of Sports Medicine earlier this month.
The paper’s lead author, Janine Zylstra, works in gastrointestinal medicine and surgery at Guy's and St Thomas' Hospitals NHS Trust in London and at the school of sport and exercise science at Liverpool John Moores University. She is one of 19 specialists who contributed to the paper, one of whom – Gemma Tham* – is a clinical specialist physiotherapist.
The comparative trial data show that there was more tumour shrinkage among patients consigned to an exercise group than their counterparts who didn’t exercise. If the findings are confirmed in further larger studies, they should strengthen the argument that ‘prehab’ exercise should become standard for all patients about to start treatment for cancer – and not just those who need surgery – say the researchers. They wanted to find out if prehab might boost the impact of pre-surgical, or neoadjuvant, chemotherapy among patients with oesophageal cancer.
Neoadjuvant chemotherapy (NAC) can improve survival in patients with this type of cancer, by shrinking the tumour and helping to stop it spreading elsewhere, an effect known as ‘downstaging’. But pre-surgical chemo can take a physical toll, effectively reducing physical fitness, and hastening the loss of skeletal muscle mass and function (sarcopenia), which may limit subsequent treatment options, and potentially survival, say the researchers.
Instruction on physical activity during NAC was provided by a specialist physiotherapist to all patients attending a regular surgical-oncology clinic at St Thomas’ Hospital, the paper states. In addition, a structured 'medium intensity' exercise training programme was given to the intervention group by a specialist exercise physiologist at the Centre for Health and Human Performance in London.
Patients with operable oesophageal cancer either received a structured programme of moderate exercise incorporating aerobic and strength training (‘prehab’) plus pre-surgical chemo or conventional best practice (lifestyle advice) plus pre-surgical chemo.
Five-month exercise programme
The exercise programme was designed to last until the day before surgery – a period lasting about five months, on average – and comprised 150 weekly minutes of moderate intensity activity plus two strength-based sessions. Each patient received four cycles of chemo before their surgery.
To assess the impact of the exercise programme during chemo, blood samples were taken before starting treatment, within a week of finishing, and then again, one, three, and six days after surgery to check on levels of inflammation and other key biochemical indicators of immunity.
Each patient was also scanned to assess changes in skeletal muscle mass and visceral fat and tumour size before and after chemo.
In all, 21 patients were assigned to prehab and 19 to conventional best practice with no additional structured exercise. An analysis of the clinical data showed that after pre-surgical chemo the prehab group had higher rates of tumour shrinkage than patients treated conventionally: 15/20 (75 per cent) compared with 7/19 (37 per cent). Based on tissue samples and the number of affected lymph nodes, more patients in the prehab group had their cancer ‘downstaged’: nine (43 per cent) vs. three (16 per cent).
These patients also had greater skeletal muscle mass and less visceral fat, but without any weight loss, as well as a stronger immune response and lower levels of inflammatory chemicals in their blood.
A relatively small number of patients were included in this clinical trial and they weren’t randomly allocated to try and eliminate the influence of unknown factors, so further larger studies are needed to confirm the findings, caution the researchers. But they point out: ‘Tumour downstaging and response to chemotherapy are arguably the most important prognostic factors in oesophageal cancer.'
That structured exercise programmes might contribute to improved cancer regression, possibly through enhanced immunological and/or inflammatory modulation, is potentially clinically significant [Janine Zylstra et al.]
Dr Zylstra and the team note: ‘That structured exercise programmes might contribute to improved cancer regression, possibly through enhanced immunological and/or inflammatory modulation, is potentially clinically significant.'
And they conclude:‘The results from this analysis, showing improvements in pathological regression in the primary tumour and clinical downstaging are hypothesis generating and the first to be demonstrated in a clinical trial in oesophageal cancer.
‘While the limitations in patient numbers and non-randomised design mandate caution, the impact for patients is potentially significant. Further work to confirm or refute these findings is urgently required, including whether or not improvements in chemotherapy response may translate into a survival advantage. Pending this, the present results further strengthen the rationale for exercise to be prescribed as standard care in patients undergoing treatment for cancer.'
What is the aim of ‘prehab’ or prehabilitation exercise?
it can help to boost patients' strength, stability, balance and mobility in preparation for surgery or other medical intervention
while the benefits of exercise among patients with cancer is becoming widely accepted, animal studies have indicated it may also help shrink tumours after chemotherapy
To see the full version of the paper, titled Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non randomised trial, visit: https://bjsm.bmj.com/lookup/doi/10.1136/bjsports-2021-104243
*A video featuring Gemma Tham and colleagues discussing an enhanced recovery programme for patients at Guy's and St Thomas' is available at: https://www.guysandstthomas.nhs.uk/our-services/gi-surgery/specialties/upper-gi/overview.aspx
Author: Ian A McMillan