Nutrition in Oncology: Overcoming Challenges to Optimize the Patient Journey from Prehabilitation to Rehabilitation

Abstract

Patients with cancer are likely to be more malnourished than patients treated in other specialties, with many remaining at high nutritional risk prior to surgery or medical treatment. Malnutrition in patients with cancer can result in suboptimal clinical outcomes, and is linked to post-operative complications and reduced mortality, along with increased dose-limiting and treatment side effects. In addition, many medical treatments have gastrointestinal side effects which can further compromise the nutritional status of the patient. However, early patient assessment and proactive management of malnutrition using medical nutrition can have a positive impact on a patient’s physiological parameters and functional status, while helping to support their metabolic and dietary needs during their cancer journey. A European Masterclass for Nutrition in Oncology which brought together 50 practitioners, took place on 10–11 October 2024 in Prague, Czech Republic, and aimed to provide an overview of nutrition as the cornerstone of cancer treatment, the use of nutritional prehabilitation in surgery and medical oncology, and optimization of the patient journey with nutrition, including rehabilitation. This paper provides a summary of the content presented, along with insights gained from attendees during four interactive workshop sessions.

Plain Language Summary

Many patients with cancer are in a poor functional state, and their diets may not contain sufficient nutrients or their disease may reduce absorption and utilization of food, which can lead to an increased risk of malnutrition. If a cancer patient has malnutrition or is at risk of developing malnutrition, this can make it more difficult for them to withstand the stress of surgery, if required, and lead to a higher chance of post-surgical complications and a shorter than expected survival. In addition, those patients with cancer and malnutrition or at a high risk of malnutrition also find it more difficult to tolerate medical treatments, which often have gut-related side effects, which can lead to the need for the use of less effective reduced treatment doses. Early assessment of patients with cancer and a proactive approach to managing malnutrition, when identified, can help to improve their functional status and nutritional needs during their cancer journey. A meeting of 50 European practitioners, which took place on 10–11 October 2024, in Prague, Czech Republic, explored nutrition as an essential part of cancer treatment. The use of nutritional prehabilitation (dietary support prior to surgery and prior to/during medical treatment) and rehabilitation (dietary support after surgery or medical treatment) were discussed. This paper provides a summary of the content presented during the meeting, along with insights gained from attending practitioners during four interactive workshop sessions.

Key Summary Points

Proactive early and systematic assessment, management, and regular monitoring of malnutrition is an important, yet overlooked, step in the overall treatment plan for all patients with cancer and throughout the cancer journey.

The use of screening and a comprehensive evaluation of the cancer patient enables an individualized nutritional plan to be developed and implemented for those patients identified to have malnutrition or be at a high nutritional risk.

A multimodal, multiphasic, multidisciplinary team-coordinated patient-centric approach to the use of medical nutrition is an important part of the cancer patient journey, and it is important to include a specialist in nutrition (dietitian, nutritionist, specialized nurse).

Prehabilitation with medical nutrition is an important component of the nutritional care pathway for patients with cancer, with the aim of optimizing their functional state to help them withstand the stresses of cancer surgery, optimize post-surgical outcomes, and continue medical treatment with a reduced requirement for dose delays or adjustments.

Rehabilitation also remains an important part of the continuum of care for patients following surgery or treatment for gastrointestinal cancer, particularly where they remain at high nutritional risk and/or may be expected to require additional treatment.

Introduction

Cancers are among the leading causes of morbidity and mortality worldwide, with the number of new cases expected to rise significantly over the coming decades [1]. While cancer treatments, such as surgery, radiation therapy, and pharmacological therapies, have become more able to target specific molecular characteristics of individual cancers through improved sophistication and precision, their use can be limited by malnutrition and metabolic derangements in patients [2]; both can be induced by the patient’s tumour and/or by the therapeutic approach itself. In addition, patients with cancer typically have reduced food intake, often related to a suppressed appetite, physical limitations to food consumption, disease-related symptoms, and/or treatment side effects [2].

The prevalence of malnutrition in oncology remains an important health issue across Europe [3–7]. European Society for Medical Oncology (ESMO) guidelines have highlighted that approximately half of all patients with advanced cancer experience malnutrition, which may be an early indicator of a malignancy prior to diagnosis [8]. Gyan et al. (2018) have previously reported that malnutrition may be perceived differently by patients, relatives, and physicians [3]. While the French multicentric NutriCancer 2012 study showed the prevalence of malnutrition to be 39%, this was often underestimated by patients and relatives, while physicians often overlooked its symptoms. A post hoc analysis from the same study also suggested that older people with cancer were more likely to experience weight loss than younger patients, with physicians overestimating food intake [6]. A sub-analysis of the Prevalence of Hospital Malnutrition and Associated Costs in Spain study demonstrated that one third of patients with cancer were at nutritional risk at admission, although a similar number remained malnourished at discharge [4]; the mean duration of hospitalization (and associated healthcare costs) were greater in patients at nutritional risk at discharge than in well-nourished patients and only one third of patients at risk of malnutrition at discharge had received any form of nutritional support during their hospitalization. The Belgian ONCOCARE study reported that more than half of all recruited patients with cancer about to receive neoadjuvant therapy or first-, second-, or third-line anticancer therapy for metastatic disease had malnutrition at their baseline visit [7]; this malnutrition was underestimated by physician assessment and only 10% of patients subsequently received a nutritional care plan. All these findings highlight the need for early integration of nutritional counselling and medical nutrition in patients with cancer, particularly older individuals.

A prospective, multicentre study of patients with gastrointestinal cancer undergoing elective surgery in Spain has highlighted the urgent need to improve nutritional risk screening both pre- and post-surgery, along with improving nutritional interventions during hospitalization [9]. While elevated levels of malnutrition risk were reported in patients prior to surgery (around 40%) and around 50% of patients received nutritional support as part of their in-patient care, levels of malnutrition were only marginally reduced prior to discharge, and 14% of patients continued to be at high nutritional risk when leaving hospital. Such findings underline the unmet need of malnutrition in gastrointestinal surgical oncological patients.

The consequences of malnutrition in patients with cancer include treatment toxicity, complications such as post-surgical infections, reduced physical functioning, and decreased survival [2, 10, 11]. In addition, malnutrition in patients with cancer can increase the burden on available healthcare resources [12] and the estimated total additional annual cost of managing adult patients with disease-related malnutrition is €17 billion in the European Union alone [13, 14]. Thus, the implementation of appropriate and consistent nutritional care in patients with cancer has the potential to improve health outcomes, decrease the need for treatment modification (dose reduction, dose delay, or treatment discontinuation), and support improved response to anticancer therapy, while reducing overall healthcare costs. In addition, the early use of additional supportive care has previously been shown to improve survival in patients with cancer compared with the use of chemotherapy alone [15]. Therefore, early nutritional care should be an integral part of a patient’s cancer journey. A European Masterclass for Nutrition in Oncology took place on 10–11 October 2024 in Prague, Czech Republic, and was attended by 50 healthcare professionals (oncologists, surgeons, dietitians, and nutritionists) from 10 European countries (Austria, Czech Republic, France, Germany, Italy, Poland, Slovakia, Spain, Switzerland, UK). The aim of this Masterclass was to provide an overview of nutrition as the cornerstone of cancer treatment, the use of nutritional prehabilitation in surgery and medical oncology, and optimizing the patient journey with nutrition, including rehabilitation. The objectives of this paper were to provide an overview of the content presented, along with insights gained from attendees during four interactive workshop sessions, for use as an educational tool for physicians and other members of the multidisciplinary team (MDT).

Ethical Approval

All content is based on previously conducted studies and does not contain any new studies with human participants or animals performed by the authors.

Nutrition as a Cornerstone of Cancer Treatment

Patients with cancer are likely to be more malnourished than patients treated in other specialties [2], and various pathophysiological patterns of malnutrition have been identified among patients with cancer [2, 16]. European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines define patients with cancer and malnutrition as having weight loss ≤ 5%, anorexia and metabolic change or weight loss > 5% or body mass index (BMI) < 20 kg/m² and weight loss > 2% or sarcopenia and weight loss > 2%, often reduced food intake/systemic inflammation) [2]; harmful changes are driven by proinflammatory cytokines and tumour-derived factors.

Malnutrition and a loss of muscle mass in patients with cancer has a negative effect on clinical outcome [2, 17]. However, reduced energy intake, inflammation, and fatigue with low levels of physical activity provide targets for therapeutic interventions, such as medical nutrition, including the use of immunonutrition [2].

Multiple factors contribute to an unfavourable energy balance in patients with cancer, and these can be nutritional, inflammatory, or metabolic in nature [18, 19]. Nutritional factors can include lipolysis and acute-phase protein synthesis, along with reduced energy intake, while inflammatory factors include deregulation of systemic inflammatory pathways leading to anorexia and impaired gastrointestinal function due to treatment toxicities [18]. Metabolic factors include increased muscle catabolism and impaired gastrointestinal function due to tumour involvement. Half of all patients with cancer present with hypermetabolism (measured as a resting energy expenditure [REE] > 110% of predicted REE), which is caused by cellular reprogramming and subsequent adjustment of energy metabolism in order to fuel cell growth and division [20]. Such hypermetabolism has been associated with the clinical and biological features of cachexia in patients with cancer [21, 22]. However, it should be noted that recent evidence suggests brown adipose tissue may reduce weight loss and risk of cancer cachexia [23, 24].

Whole-body skeletal mass is dependent on rates of muscle protein turnover, with muscle mass being maintained or increased when muscle protein synthesis (MPS) is equivalent to or greater than muscle protein breakdown [25]. However, the homeostatic state of muscle protein turnover is disrupted in patients with cancer, with the upregulation of ubiquitin proteasome/autophagy pathways and a decline in MPS leading to increased degradation of intracellular proteins and subsequent loss of muscle mass. Reduced protein intake, adverse effects of cancer therapy, and reduced levels of physical activity can also negatively affect muscle mass. It is important to remember, though, that muscle anabolism is possible in patients with cancer [26, 27]. For example. Ford et al. (2024) demonstrated that increased protein consumption of 2.0 g/kg/day and 1.0 g/kg/day helped patients with colorectal cancer (stage II–IV) to either maintain or gain muscle mass in 59% and 44% of cases, respectively, over a 12-week period [27]. Thus, physicians need to be aware that when judging energy and nutrient intake, patients with cancer require more protein than healthy individuals, with specific requirements typically differing from average recommended values [17, 25].

Key components of a nutritional care plan for patients with cancer at risk of malnutrition are energy, nutrient, and fluid requirements, measurable immediate and long-term nutrition goals, instructions for implementing a specified form of medical nutrition along with selection of the most appropriate route of administration, the anticipated duration of medical nutrition, monitoring and assessment parameters, and discharge planning and training at home, as appropriate [28]. Of note, data from the EFFORT study have shown costs associated with the provision of medical nutrition (versus standard hospital food) to be insignificant compared with the overall cost of hospitalization and/or cost of other medical treatments [29].

Nutritional intervention, including dietary counselling, evaluation by specialists (nutritionist, dietitian, nurse specialist), and medical nutrition therapy with different types of nutritional support, is an important step to cover the additional dietary needs of patients with cancer [28]. Medical nutrition includes oral nutritional supplements (ONS; typically provided as ‘ready-to-drink’ liquids or powders), enteral nutrition (EN; administered via a tube or stoma into the intestinal tract distal to the oral cavity), and parenteral nutrition (PN; administered intravenously either centrally or peripherally) [28]. Components of ONS, EN, and PN vary [28], offering a flexible approach to filling the caloric and protein gaps of patients with cancer, while offering the possibility of inflammation modulation via the inclusion of omega-3 polyunsaturated fatty acids (PUFA), as recommended in the ESPEN guidelines for those receiving chemotherapy [2]. Neither ESPEN [2, 10, 11] nor ESMO guidelines [8] currently distinguish between male and female patients with cancer with regard to nutritional requirements and the use of medical nutrition.

Nutritional care (i.e. screening, diagnosis, assessment, delivery of a medical nutrition therapy plan, and ongoing monitoring) is multifactorial with consideration given to cancer stage and the potential benefit of early use, the need for regular and systematic reassessment to enable medical nutrition to be adapted to a specific clinical situation (for example, the severity of malnutrition), and patient expectations [2, 8, 10]. Thus, as a continuum of care, comprehensive treatment of the cancer patient (disease staging, first-line therapy, follow-up, and periodical re-evaluation, second-line therapy, etc.) should run in parallel and in close collaboration with a nutritional pathway (nutritional screening/assessment within 4 weeks of diagnosis, nutritional/metabolic interventions tailored to patient needs/treatment, follow-up and periodical re-evaluation, and ‘upper-level’ nutritional/metabolic strategies). Medical nutrition therapy should also be considered to be an important component in multiphasic and multimodal prehabilitation [30]; this conceptual health-optimizing strategy aims to encompass the variability of cancer treatment experiences and guide further investigation of the viability and impact of repeated, pre-treatment interventions that target improved health outcomes throughout the entire cancer continuum.

A global, yet personalized, approach to medical nutrition is needed for each individual cancer patient wherein all clinical, biological, physical, and psychological dimensions of the patient are considered as part of the continuum of care [2, 8, 10, 19]. An MDT approach to medical nutrition therefore remains an important part of the cancer patient journey [2, 8]. The MDT should comprise physicians, dietitians, nurses, pharmacists, and others, to provide medical nutrition with the aim of providing a coordinated therapeutic approach, shared decision-making, and comprehensive care of patients with cancer. A coordinated MDT approach also enables the development and consistent use of agreed evidence-based protocols and referral pathways. An effective MDT should aim to identify nutritional disturbances at an early stage and aim to achieve a stable nutritional state in a cancer patient as per current guidelines [8, 10], particularly given that available data suggest that only half of all patients with cancer are screened for nutritional status [31, 32]. Given that patients are often experts in their own conditions, the MDT should also consider their perspectives and preferences, along with those of their carers [28, 33]. Personalized medical nutrition interventions which acknowledge strong relationships between diet and the social-cultural environment, ideally in conjunction with nutritional counselling, can also support the development of a trusting relationship between the patient and their nutritionist/dietitian and adherence to medical nutrition regimens [33]. A meta-synthesis of qualitative studies in the nutritional management of patients with oesophageal cancer has previously demonstrated that an MDT approach maximized the effectiveness of nutritional therapy, promoted early patient recovery, and was a patient expectation [34]. Kang et al. [35] also reported early supportive care via an MDT to be an important predictor of improved overall health status and quality of life in patients with advanced cancer.

It is important to recognize that multiple barriers to the effective use of medical nutrition therapy in patients with cancer remain, which need to be addressed and overcome [36, 37]. These barriers can be related to the patient, physician, or hospital/medical institution [36, 37]; lack of reimbursement may also be an issue [38]. Patient-related barriers may include preference, high expectations, low motivation, and a lack of family support, while physician-related barriers may include lack of training, experience, and knowledge regarding the benefit(s) of nutritional intervention(s), lack of clinical time, and their belief and perception of nutritional care. Hospital/institution-related barriers can include a lack of guidance or protocol for the implementation of nutritional intervention(s), along with a lack of resources/nutritional team, and budget constraints. Such barriers need to be identified and acknowledged at the earliest possible stage, with the most effective ways of overcoming these barriers shared between clinical teams to optimize best practice.

Nutritional Prehabilitation for Surgery in Oncology

Tumours release inflammatory cytokines that affect the brain, muscle, liver, and fat function, with a subsequent ‘spillover’ increasing systemic inflammation and leading to a disrupted metabolism of carbohydrates, fats, and proteins throughout the body [39]. Surgery represents significant trauma and stress which results in an additional metabolic and physiological response in the cancer patient [2, 40–43]; the release of stress hormones and inflammatory mediators during surgery results in the catabolism of glycogen, protein, and lipid to facilitate healing.

As with other patients with cancer, individuals undergoing gastrointestinal cancer surgery are at risk of malnutrition [44–46]. For example, weight loss and malnutrition have been reported in 54–67% and 17–20% of patients prior to gastrointestinal surgery, respectively. In addition, available data have shown that metabolic and nutritional alterations can impede post-surgical recovery and survival of patients with cancer. Both Thomas et al. and Hanad et al. [47, 48] reported malnutrition in patients undergoing abdominal surgery to be predictive of post-operative complications and longer length of hospital stay at 1 week. Advanced age, weight loss, and low serum albumin have also been identified as independent risk factors for the onset of post-operative complications following major abdominal surgery for gastrointestinal cancer [49]. Severe malnutrition is also a risk factor for 30-day mortality following elective surgery for colorectal or gastric cancer [50].

Malnutrition in patients with gastrointestinal cancer can also increase the risk of post-operative complications [51, 52]. A small study by Nishiyama et al. [51] reported malnutrition to an independent predictive factor for severe post-operative complications in surgical patients with colorectal cancer, while a meta-analysis by Simonsen et al. [52] demonstrated that patients with gastrointestinal cancer and preoperative sarcopenia (sarcopenia range of 12–78%) had a significantly increased risk of post-surgical complications. A meta-analysis by Zhao et al. [53] also reported that a preoperative underweight status (defined as a BMI < 18.5 kg/m²) increased the risk of post-surgical complications following gastric resection in patients with cancer. Post-surgical loss of muscle strength and mass also has the potential to cause sarcopenic obesity [54].

ESPEN guidelines recommend three key steps to address nutrition therapy in patients with cancer [2]. Firstly, all patients with cancer should be screened for nutritional risk at the earliest possible opportunity, regardless of BMI and weight history. Secondly, nutrition-related assessment practices should be expanded to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function. As a third step, multimodal nutritional interventions should be used which incorporate individualized plans which focus on increasing nutritional intake and physical activity, while lessening inflammation and hypermetabolic stress. For the management of cancer cachexia, ESMO guidelines also underline the need for nutritional screening and nutritional support [8]. For patients with cancer who require surgery, ESPEN guidelines recommend preoperatively assessing the nutritional status of all patients by using the Nutrition Risk Score-2002 with the four principles of assessment including current condition, stability (recent involuntary weight loss), negative influence of disease (stress metabolism associated with severe disease), and potential for worsening (via reduced food intake) [11]. Severe metabolic risk is defined by ESPEN as weight loss > 10–15% within 6 months, a BMI < 18.5 kg/m², Subjective Global Assessment C or Nutritional Risk Screening ≥ 5, and levels of preoperative serum albumin < 30 g/L (with no evidence of hepatic or renal dysfunction) [55]. The use of Global Leadership Initiative on Malnutrition criteria for the diagnosis of malnutrition, which include phenotypical (weight loss, low BMI, reduced muscle mass) and aetiological criteria (reduced food intake/assimilation, inflammation, or disease burden) [56], are also recommended [11].

Enhanced Recovery After Surgery (ERAS) is a multimodal, multidisciplinary, and evidence-based approach to surgical patient care, with elements for consideration at pre-, intra-, and post-operative stages [42]. ESPEN guidelines are aligned with ERAS from a metabolic and nutritional point of view, with a focus on the integration of nutrition and nutritional status in overall patient management, along with initiation of medical nutrition as soon as any nutritional risk becomes apparent [11].

From a surgical perspective, prehabilitation complements ERAS care to support optimal patient outcomes given that recovery is not a passive process and begins preoperatively [43]. Here, prehabilitation is defined as a process from diagnosis to surgery, which consists of ≥ 1 preoperative interventions of nutrition, exercise, psychological strategies (a ‘trimodal’ approach), and/or respiratory training [57–59]; the goal of prehabilitation is to optimize physiological reserves (via prevention of further weight loss as a minimum requirement) and address modifiable risk factors prior to surgery across a suitable timeframe to optimally improve post-operative outcomes [57–59]. Prehabilitation is an important part of the cancer patient journey given that enhanced functional capacity and physiological reserves enable patients to withstand surgical stressors, improve their post-operative outcomes, and facilitate recovery. For example, prehabilitation can modify surgical outcomes via mediation of the surgical stress response [43].

Medical nutrition in prehabilitation can include ONS, EN, or PN types [28]. For patients with cancer who require surgery, ESPEN guidelines recommend the initial preoperative use of ONS, followed by EN when oral nutrition is inadequate, and then PN where EN is insufficient or not feasible [11]. Available data show that the use of prehabilitation nutrition can have a positive impact on post-surgical outcomes in patients with gastrointestinal cancer. Preoperative nutritional support significantly decreased the incidence of post-operative surgical-site infections (SSI) in patients who were malnourished with gastric cancer compared with those individuals who received no medical nutrition or had inadequate calorie intake [60]. Specifically, preoperative nutritional support for ≥ 10 days with adequate caloric support (≥ 25 kcal/kg ideal body weight per day) resulted in significantly fewer post-operative SSIs. Preoperative PN combined with EN significantly improved recovery following surgery in Chinese patients with gastric cancer and early gastric outlet obstruction, including a faster time to first post-operative bowel sounds, flatus, and bowel movement [61]. Given that omega-3 PUFAs have known anti-inflammatory, immunomodulatory, and antioxidative properties, there is some evidence to suggest that their inclusion in PN may reduce post-surgical hyperinflammation and immunosuppression [62]. The use of exercise (where possible) prior to surgery also appears to be an effective modulator of the metabolic consequences of gastrointestinal tumours, and should therefore warrant inclusion in any prehabilitation plan [42]; exercise can help to increase protein synthesis and reduce systemic inflammation, insulin resistance, and the formation of reactive oxygen species.

From a practical clinical perspective, prehabilitation is a critical component of the nutritional care pathway in patients requiring gastrointestinal surgery [11, 58]. ESPEN guidelines highlight that importance of preoperatively screening for malnutrition and assessment of nutritional status, with the extended use of prehabilitation for at least 4–6 weeks and ONS for a period of 5–7 days prior to the patient becoming an inpatient [11]; prolonged periods of nil by mouth should be avoided. When the patient is in hospital, early oral feeding and mobilization adapted to tolerance should be implemented, with clinical use of medical nutrition via ONS, EN, or PN when calorie/protein intake is inadequate; the placement of feeding jejunostomy in patients undergoing upper gastrointestinal surgery should also be considered.

A workshop during the meeting enabled attendees to discuss the prehabilitation pathway for gastrointestinal surgery in oncology with their peers. Key considerations from this group discussion are shown in Fig. 1.

Fig. 1.

Prehabilitation for gastrointestinal surgery in oncology: key considerations (workshop output). GI, gastrointestinal; MDT, multidisciplinary team

Nutritional Prehabilitation in Medical Oncology

Nutritional prehabilitation in medical oncology should be used before the patient starts treatment but can also be used during treatment, as part of a multimodal therapeutic approach to improve nutritional status and support optimization of treatment outcomes [17, 30].

When considering the role of nutritional prehabilitation in patients with cancer undergoing radiotherapy or chemotherapy, it is important to recognize the negative impact of these treatments on nutritional status. Radiotherapy causes damage to the gut epithelium, microstructure, and intestinal nervous system with chronic consequences [63, 64]; poor nutrient absorption and abnormal transport of intestinal contents related to increased intestinal inflammation and subsequent fibrosis and sclerosis of blood vessels located in the intestinal wall are common side effects of radiotherapy. The gut microbiome is also negatively impacted by radiotherapy with a subsequent reshaping of the tumour microenvironment via an imbalance of anti-inflammatory and pro-inflammatory cells and their corresponding cytokines [65].

The gastrointestinal mucosa is also sensitive to chemotherapy cytotoxicity, with subsequent mucositis leading to malnutrition and nutritional deficiencies via the disruption of the gastrointestinal architecture and decreased mucosal area available for nutrient absorption, along with impairment of the immune response [66]. Most chemotherapies have gastrointestinal side effects which could negatively affect a patient’s nutritional status [67]. For example, Sánchez-Lara et al. [67] reported a weight loss of ≥ 5% to be significantly associated with nausea, vomiting, and anorexia—all side effects of chemotherapy—highlighting the need to assess and manage gastrointestinal symptoms from an early stage during treatment. Poor nutritional status and sarcopenia are both significant predictors of chemotherapy toxicity and tolerability, with patients with sarcopenia experiencing increased toxicity from chemotherapy, leading to treatment modification (dose reduction, dose delay, or treatment discontinuation) [68]. Chemotherapy and sarcopenia also form a vicious cycle given that sarcopenia is a both a cause and consequence of chemotherapy toxicity [68, 69]; while the rate of muscle loss in normal aging is around 1% per year, muscle loss can be 24-fold more rapid in patients receiving chemotherapy for metastatic colorectal cancer [69]. Sarcopenia has also been identified as an unfavourable prognostic factor for survival in patients with solid tumours treated with chemotherapy, with a low skeletal muscle index being associated with significantly reduced overall and cancer-specific survival [70].

The use of medical nutrition during prehabilitation may vary according to the proposed treatment strategy [19], although both ESPEN and ESMO guidelines highlight the need for nutritional support in medical oncology patients both before and during anticancer treatment, including radiotherapy and/or chemotherapy [8, 10]. A meta-analysis has highlighted that the use of medical nutrition during prehabilitation, particularly high-protein omega-3 PUFA-enriched types, can have a positive effect on the body weight and BMI of patients with cancer during chemo(radio)therapy regimens [71]; this finding highlights the potential benefits of targeting metabolic alterations. Similarly, a meta-analysis by Wang et al. (2023) reported significant increases in body weight and BMI with omega-3 PUFA-enriched ONS when used alongside chemo(radio)therapy, along with significant reductions in the levels of plasma-based inflammatory mediators, such as C-reactive protein, interleukin-6, and tumour necrosis factor-alpha [72]; patients receiving omega-3 PUFA-enriched also had a significant reduction in the incidence of adverse events. A meta-analysis by Mocellin et al. [73] also reported that use of omega-3 PUFA-enriched medical nutrition in parallel with chemotherapy could reduce inflammation in patients with colorectal cancer. However, it is important to remember that these meta-analyses included a limited number of studies, which were also heterogeneous, and were inadequately powered to show any potential effects on treatment toxicity or survival.

New and promising personalized treatments for gastrointestinal cancers, such as immunotherapy and targeted agents, are now available, with differing adverse event and toxicity profiles, and the potential for cumulative toxicity when combined with chemotherapeutic agents. Thus, these new treatments provide a potentially different patient journey in parallel with the need to carefully assess the individual nutritional requirements of patients along the way. Immune checkpoint inhibitors have several potential therapeutic targets, such as cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein-1 (PD-1), and programmed cell death protein ligand-1 [74]. A multicentre retrospective cohort analysis of patients with gastrointestinal cancer has suggested that patients experiencing immune-related adverse events on anti-PD-1 immunotherapy have significant improvements in progression-free and overall survival [75]. However, immune-related adverse events with immunotherapy, which appear to increase when using a combination of these agents, can negatively affect nutritional status [76]. Importantly, immune-related adverse events with immunotherapy can have a delayed onset and prolonged duration, in contrast with more typically short-lived adverse events after ending chemotherapy, with potential for a prolonged negative impact on a patient’s nutritional status [76–78]. Clinicians therefore need to remain vigilant for the diverse clinical presentations of immune-related side effects given that they may present at a later stage or even years after treatment ends, thus impacting on patient rehabilitation.

Side effects of targeted therapy can negatively affect the nutritional status of the patient [79]. For example, bevacizumab is associated with rectal bleeding and proteinuria, cetuximab with diarrhoea, nausea, vomiting, dehydration, electrolyte disturbances, weight loss, and weakness, and panitumumab with diarrhoea, nausea, vomiting, hypokalaemia, hypomagnesemia, weight loss, and weakness; all these side effects have the potential to negatively impact upon the nutritional status of the patient. The additional combined use of targeted therapies, such as epidermal growth factor receptor tyrosine kinase inhibitors, has also been shown to significantly increase the risk of gastrointestinal-related adverse events, such as diarrhoea and mucositis, which could further affect nutritional status [80]. However, a retrospective Taiwanese national registry multicentre study has demonstrated that the use of supplemental PN can improve oncological outcomes in patients with RAS wild-type metastatic colorectal cancer receiving first-line chemotherapy in combination with the targeted agent cetuximab [81]; nutritional status was improved, enabling patients to receive treatment for longer and therefore increase the possibility of positive therapeutic outcomes, such as longer duration of response and survival.

Abnormal basal energy metabolism/hypermetabolism appears to be a sensitive parameter for predicting the occurrence of early limiting toxicity (ELT) in patients treated with either cytotoxic chemotherapy or targeted therapy [20, 82]. Thus, baseline resting energy expenditure measurement has the potential to improve ELT risk assessment and the treatment decision-making process [82].

An interactive workshop during the meeting discussed the characteristics of patients with gastrointestinal cancer who would be deemed ideal candidates for early nutritional prehabilitation in medical oncology. Key considerations are shown in Fig. 2. Another workshop discussed the use of medical nutrition to prevent and manage gastrointestinal toxicities in medical oncology, with key considerations shown in Fig. 3.

Fig. 2.

Prehabilitation in medical oncology: Which patients are the ideal candidates for early nutritional intervention? (workshop output). BMI, body mass index; GI, gastrointestinal

Fig. 3.

Nutritional intervention in medical oncology: Prevention and management of GI toxicities (workshop output). BMI, body mass index; CRC, colorectal cancer; GI, gastrointestinal

Optimizing the Patient Journey with Nutrition

Prehabilitation and rehabilitation for patients with cancer are complementary and provide a continuum of care, with the latter referring to the process of helping them to maximize their physical, social, and psychological well-being after surgery or treatment [30]; while prehabilitation requires careful assessment of the patient and planning from an early stage, rehabilitation has historically often been initiated in response to post-surgical or treatment sequelae rather than a proactive process. The use of medical nutrition in rehabilitation is now recognized as part of the continuum of care following cancer surgery [11], but there are limited published data regarding the use of this approach in medical oncology. Garth et al. [45] previously reported the increased risk of complications following a prolonged post-operative ‘nil-by-mouth’ period in patients with gastrointestinal cancer. In contrast, early enteral feeding (≤ 24 h) following gastrointestinal surgery led to a reduced hospital length of stay [83], improved mortality [84], and reduced risk of infection [85]. ESPEN guidelines recommend the use of early EN (≤ 24 h) for those patients unable to receive early oral nutrition and would then be expected to have inadequate oral intake (defined as < 50% normal intake) for a period of at least 1 week [11]; such patients include those deemed to have malnutrition at the time or surgery, and those who require major gastrointestinal or head and neck surgery. In addition, regular reassessment of nutritional status during a patient’s hospital stay and continuation of nutritional support following discharge are warranted, particularly in those patients at high nutritional risk prior to surgery and those who may not have achieved a required level of oral self-feeding post-operatively. A similar rehabilitation process should be considered for medical oncology patients who have completed treatment, particularly where they may be expected to require additional treatment (wherein supportive rehabilitation following treatment and prehabilitation before the next treatment phase would have similar clinical targets) [30].

The final workshop held during the meeting discussed the use of rehabilitation nutrition following surgery or medical treatment in oncology. Key considerations are shown in Fig. 4.

Fig. 4.

Rehabilitation following surgery or medical treatment in oncology: Which patients benefit most from nutritional intervention? (workshop output). BMI, body mass index; EN, enteral nutrition; GI, gastrointestinal; MDT, multidisciplinary team; ONS, oral nutritional supplement; PN, parenteral nutrition. *Immediately after surgery/medical treatment. ^†Particularly if additional treatment is required

Conclusions

The proactive early and systematic assessment, management, and regular monitoring of malnutrition is an important, yet sometimes overlooked, step in the overall treatment plan for all patients with cancer and throughout the cancer journey. The use of screening and a comprehensive evaluation of the patient enables an individualized nutritional plan to be developed and implemented for those patients identified to have malnutrition or be at a high nutritional risk. A multimodal, multiphasic, MDT-coordinated patient-centric approach to the use of medical nutrition is an important part of the cancer patient journey, and it is important that a specialist in nutrition (dietitian, nutritionist, specialized nurse) is always included as part of the team. Prehabilitation with medical nutrition is an important component of the nutritional care pathway for patients with cancer, with the aim of optimizing the functional status of the patient, enabling them to receive necessary treatments essential for cancer-specific survival. For patients with gastrointestinal cancer requiring surgery, the use of prehabilitation can help patients at nutritional risk withstand the stresses of cancer surgery and optimize post-surgical outcomes. For medical oncology patients, the use of medical nutrition both prior to and during therapy may allow patients with cancer to continue medical treatment with a reduced requirement for dose delays or adjustments and a reduced incidence of treatment-related side effects, thus helping to support optimal therapeutic outcomes. A brief summary of where medical nutrition can be used in patients with cancer is shown in Fig. 5. While available data for the use of medical nutrition in patients with cancer have previously focused on post-surgical outcomes, it follows that this approach in medical oncology patients can also help to support optimal therapeutic outcomes when used prior to and during treatment; the sharing of best clinical practice between physicians and MDTs will help to improve clinical knowledge and understand the most effective use of medical nutrition in these patients, although additional supportive evidence still needs to be generated in medical oncology. Rehabilitation also remains an important part of the continuum of care for patients following surgery or treatment for gastrointestinal cancer, particularly where they remain at high nutritional risk and/or may be expected to require additional treatment. Finally, a practical approach is needed to overcome the current knowledge gaps and challenges in the nutritional management of patients with cancer. Thus, there is a call to action for increased awareness and knowledge of the nutritional management of patients with cancer to improve MDT nutritional practices.

Fig. 5.

Summary of when to use medical nutrition in patients with cancer

Author Contribution

Stanislaw Klek, Alessandro Laviano, Hervé Chrostek, and Diana Cardenas were involved in the development, writing, and review of this manuscript. Stanislaw Klek, Alessandro Laviano, Hervé Chrostek, and Diana Cardenas read and approved the final manuscript.

Funding

This manuscript and the European Masterclass for Nutrition in Oncology, upon which the content of this manuscript is based, were funded by Fresenius-Kabi, along with the Rapid Service Fee.

Declarations

Conflict of Interest

Stanislaw Klek has received speaker honoraria from Baxter, B. Braun, Fresenius-Kabi, Nutricia, and Nestlé. Alessandro Laviano has received honoraria from medical nutrition companies for invited lectures at scientific and educational events, along with consulting fees. He is also a member of the board of directors at the Danone Nutricia Campus. Hervé Chrostek is an employee of Fresenius-Kabi Region Europe. Diana Cardenas has received speaker honoraria from Fresenius-Kabi, Nutricia, B. Braun, and Nestlé.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by the authors.