Multidisciplinary rehabilitation in oesophago-gastric cancer patients

The incidence of oesophago-gastric cancer is increasing steadily in Western countries in line with increasing overweight and obesity levels.¹ Traditionally, the prognosis associated with this aggressive disease was poor due to the high numbers presenting with locally-advanced or metastatic disease. Mortality rates are however slowly improving² leading to the emergence of a new group of post-treatment oesophageal and gastric cancer survivors. 

The transition from active treatment to becoming a cancer survivor and coping with the ‘new normal’ is particularly challenging for this cohort who endure aggressive medical and surgical cancer treatment leading to decreased health-related quality of life in survivorship.³ There is a need for greater understanding of the rehabilitative needs of this unique group in order to optimise patient function, reduce the impact of disease and treatment-related side-effects and reduce the risk of secondary morbidity. 

Patients with oesophago-gastric cancer experience a negative functional impact of the disease from pre-diagnosis. Data from our institute has reported that 74% of patients were actively losing weight at diagnosis, with 34% experiencing clinically severe weight loss.⁴ Weight loss of ≥ 5% body weight defines a state of cachexia, a multifactorial condition characterised by loss of skeletal muscle and adipose tissue, a dysregulated metabolic state and resistance to nutritional intervention.^5,6 Up to 80% of upper gastrointestinal patients are cachectic at diagnosis and cancer cachexia correlates with poor physical performance, decreased quality of life, and increased mortality.⁷ Furthermore, cachexia is oesophago-gastric canceriated with a pro-inflammatory, dysmetabolic environment which is thought to further drive morbidity and secondary complications.^5,7

Current treatment for loco-regional or locally advanced oesophago-gastric cancer generally involves a multimodal approach which may include neo-adjuvant chemoradiotherapy, surgical resection (oesophagectomy or gastrectomy) and adjuvant chemotherapy for node-positive patients.⁸ The risks and subsequent morbidity associated with oesophagectomy and gastrectomy greatly exceed that of other surgical procedures and long-term complications including dysphagia, diarrhoea, fatigue, swallow dysfunction, and malabsorption are well reported.^3,9,10,11 Furthermore, a dramatic and long-term decrease in health-related quality of life is observed following upper gastrointestinal resection.¹² 

The side-effects of the severe treatment protocols are associated with continued nutritional and functional decline, leading to decreased health-related quality of life, decreased functional status and increased morbidity post treatment.^3,5,12 Cachectic patients in particular experience more frequent and severe dose-limiting toxicity from chemotherapy,¹³ thus identifying the need to optimise body composition and nutritional status during treatment. 

Little is known about the physical presentation and functional status of post-treatment oesophago-gastric cancer survivors. Pilot data from our institute has investigated the status of a number of physical performance outcomes in survivors from six months to two years post treatment completion (n = 28).^14,15 Results demonstrate suboptimal levels of hand-grip strength and aerobic fitness levels rated as ‘poor’ or ‘very poor’ compared to age- and gender-matched normative data. In addition, habitual physical activity levels, measured by accelerometry, indicate that a staggering 57.8% of waking hours are spent engaging in sedentary behaviour, with only 13% (n = 2) of participants achieving recommended physical activity levels for cancer survivors.¹⁵ Many oesophago-gastric cancer survivors begin to lose weight from the onset of the disease and some find it difficult to maintain weight in the post-treatment period due to persistent nutritional insufficiency.¹⁶ Recent research in our institute demonstrates persistent weight loss, muscle wasting, altered gut hormone secretion and malabsorption in oesophago-gastric cancer survivors.^10,11

There is increasing evidence that rehabilitation following treatment for cancers such as breast or colon cancer will optimise patient outcomes. It is acknowledged however that there is a need to research the role of rehabilitation in lesser studied cancers.¹⁷  Oesophago-gastric cancer patients endure numerous disease and treatment-associated side-effects which increase morbidity in survivorship. There is an absence of research examining how best to intervene to optimise patient recovery and function following curative oesophago-gastric cancer treatment. 

Critically, in order to prescribe an effective rehabilitation programme to optimise recovery following oesophago-gastric cancer, there is a need to increase our understanding of potential drivers of functional decline during treatment and to quantify the extent of function deterioration. The mechanisms driving the decline in measures of physical performance during oesophago-gastric cancer treatment are poorly investigated, however it is hypothesised that persistent weight loss, sarcopenia and nutritional deficiency are significant contributors. Due to the complex, multi-dimensional nature of cancer cachexia, a multi-factor profile approach, incorporating potential biological mechanisms has been shown to be most predictive of subjective and objective functional deficits.⁷ In our programme of research, we plan to complete a multi-factorial investigation of potential drivers of functional decline from oesophago-gastric cancer diagnosis to treatment completion. Results will identify rehabilitative needs in this group which will be addressed in a multi-disciplinary rehabilitation programme, completed in early survivorship. 

The Rehabilitation Strategies Following Oesophago-gastric Cancer (ReStORe) trial is a Health Research Board funded three-year project that commenced in October 2014. It is a multidisciplinary programme, incorporating expertise in dietetics, physiotherapy, surgery, medicine and molecular oncology aimed at optimising outcomes in oesophago-gastric cancer survivors. The project has two specific aims. The first aim is to investigate if progressive cachexia and associated inflammatory and metabolic dysfunction during treatment for oesophago-gastric cancer contributes to functional deficits and secondary morbidity in survivorship. The second aim of this work is to examine if multidisciplinary rehabilitation in early survivorship may improve functional status of oesophago-gastric cancer survivors.

This research programme is being conducted in two phases. Phase one consists of a longitudinal analysis, tracking the progression of cachexia and associated dysmetabolic state throughout treatment for oesophago-gastric cancer and examining the impact of this decline on measures of function. A total of 88 newly-diagnosed oesophago-gastric cancer patients will be recruited for phase one, with assessments carried out at diagnosis, during neoadjuvant treatment, pre-operatively, at discharge and at one and six months post discharge. 

In phase two, participants from phase one, who have completed their cancer treatment, will be re-assessed and, if deemed suitable, will be enrolled onto a multidisciplinary team rehabilitation programme aimed at improving functional status. This rehabilitation programme takes the form of a 12-week randomised controlled trial. Participants in the intervention group will engage in supervised and home-based exercise, receive one-to-one dietary education and attend group education sessions delivered by members of MDT, eg. psychological oncology services and also cancer support groups. Exercise is prescribed by percentage heart rate reserve (HRR), commencing at 30-45% HRR working up to 60% HRR (monitored using polar heart rate monitor). Duration and frequency of exercise increases as the programme progresses, reaching up to 150 mins of moderate intensity exercise per week.¹⁸ The number of supervised and one-to-one sessions with the dietitian and physiotherapist decrease as the programme progresses to encourage independence. Participants in the control group continue to receive standard medical follow-up. Assessments are completed at baseline, post intervention and three months post intervention. 

The primary outcome across both phase one and phase two is functional capacity. Secondary outcomes including inflammatory status, energy metabolism and nutritional status will be measured at designated timepoints during the study (see Table).

The ReStOre Trial will provide novel information on rehabilitation for survivors by identifying drivers of functional decline during treatment for oesophago-gastric cancer, quantifying the degree of functional deterioration during treatment, and examining the feasibility and efficacy of multidisciplinary programme in early oesophago-gastric cancer survivorship. 

Suzanne L Doyle, School of Biological Sciences; Emer M Guinan, Linda O’Neill and Juliette Hussy, Dublin Institute of Technology; John V Reynolds, Department of Surgery, Trinity Centre for Health Sciences, St James’s Hospital, Dublin

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