Nutritional treatment as an essential element of oncological therapy

Introduction

Malnutrition in cancer patients is one of the most serious problems facing contemporary oncology. Recent studies indicate that this problem affects 40–80% of cancer patients, and its incidence depends on the type of cancer, stage, and treatment administered [1, 2]. Patients with gastrointestinal cancers (up to 87%), as well as head, neck, and lung cancers, are at particularly high risk [3, 4]. According to the European Society for Clinical Nutrition and Metabolism (ESPEN) definition, malnutrition is a condition resulting from a lack of absorption or consumption of nutrients, leading to changes in body composition, impaired physical and mental function, and negatively impacting treatment outcomes for the underlying disease [5, 6]. The causes of malnutrition in oncology are complex and multifaceted. These include direct effects of cancer on metabolism (increased energy demand, production of proinflammatory cytokines), local tumour effects (such as obstruction, dysphagia, malabsorption) and side effects of anticancer treatment (nausea, vomiting, mucositis, taste disturbances) [7, 8].
Malnutrition in oncology leads to higher mortality (over 20% of cancer patients die from malnutrition), longer hospitalisation, higher risk of postoperative complications, poorer tolerance of chemotherapy and radiotherapy, and reduced quality of life [9]. Therefore, early diagnosis and effective treatment of nutritional disorders are key elements of comprehensive oncology care.
In clinical practice, the most commonly used screening tools are the NRS-2002 (Nutrition Risk Screening 2002) and subjective global assessment (SGA) scales [10]. In Poland, the use of these scales is mandatory in accordance with the Regulation of the Minister of Health of 22 November 2013 on guaranteed services in the scope of hospital treatment (current consolidated text: Journal of Laws of 2023, item 870, as amended), § 6 of which contains detailed regulations on this issue. § 6 sec. 1 of the Regulation stipulates that a healthcare provider providing services in the form of hospitalisation and planned hospitalisation shall subject all beneficiaries admitted for treatment, excluding the hospital emergency department, to a screening assessment of nutritional status (SGA or NRS 2002 – in adults, on growth charts in children and adolescents), in accordance with the principles set out in the Standards of parenteral nutrition and enteral nutrition of the Polish Society of Parenteral and Enteral Nutrition or, in the case of children, in accordance with the principles set out by the Polish Society of Clinical Nutrition of Children [11].
However, comparative studies have demonstrated limitations of the NRS-2002 in the oncology population. Chen et al., in a study of 2645 oncology patients, demonstrated that the patient-generated subjective global assessment (PG-SGA) identified the risk of malnutrition in 66.6% of patients, whereas the NRS-2002 identified it in only 9.1% of patients [12]. These significant differences indicate a higher sensitivity of the PG-SGA in identifying nutritional disorders in oncology patients.

GLIM criteria – a new diagnostic standard

In 2018, the Global Leadership Initiative on Malnutrition (GLIM) introduced new, standardised diagnostic criteria for malnutrition [13, 14]. The Global Leadership Initiative on Malnutrition criteria require the presence of at least one phenotypic criterion (unintentional weight loss, low body mass index – BMI, reduced muscle mass) and one etiological criterion (reduced food intake, inflammation). Validation studies in the oncology population have confirmed the usefulness of the GLIM criteria. In a meta-analysis of 14 studies involving 14,196 oncology patients, Zhang et al. demonstrated that the GLIM criteria have a sensitivity of 69% and a specificity of 84% compared to PG-SGA. Additionally, the use of GLIM criteria allows for the prediction of mortality and complications in oncology patients [15].

PG-SGA assessment as the gold standard in oncology

The subjective assessment of the nutritional status of cancer patients, known as PG-SGA, is considered the gold standard in this field [16, 17]. This tool was developed for cancer patients and takes into account specific symptoms that may affect their nutritional status. The patient-generated subjective global assessment consists of 2 parts: the first is completed by the patient (including weight history, dietary intake, and symptoms) and the second by a specialist (including a physical examination, assessment of the underlying disease, and metabolic requirements). Based on the obtained results, patients are classified into 3 categories (A – well-nourished, B – moderately malnourished, C – severely malnourished), which allows the urgency of nutritional intervention to be determined. Bauer et al. demonstrated that the PG-SGA has a sensitivity of 98% and a specificity of 82% in identifying malnutrition in cancer patients [18].
Additionally, the PG-SGA result correlates with biochemical and anthropometric parameters and clinical prognosis [19].

Nutritional treatment methods

Oral supplementation and its clinical effectiveness

Oral supplementation is a key method in the nutritional treatment of cancer patients with preserved gastrointestinal function. According to the ESPEN guidelines, oral nutritional supplementation (ONS) is recommended for patients who are unable to consume sufficient amounts of food orally (< 60% of their needs) for periods longer than 7–10 days, or for those who already suffer from malnutrition [20].
Randomised trials have found that the use of ONS in cancer patients undergoing chemotherapy leads to a significant increase in body weight (mean difference 1.31 kg, 95% CI: 0.42–2.20) and improved PG-SGA scores and quality of life. These bene fits were particularly evident in older patients, those with low body weight at baseline, women, and non-Asian patients. A multicentre study demonstrated that ONS containing whey protein, leucine, and zinc was safe and well-tolerated in cancer patients. Protein intake increased from 66.75 ±31.57 γ to 88.57 ±35.11 γ per day (p < 0.01) and calorie intake from 1549 ±596 to 1756 ±614 kcal per day (p = 0.02).
Oral nutritional supplementation preparations can be divided into standard ones, which contain essential macro- and micronutrients, and those enriched with immunomodulatory ingredients. Ozorio et al. found that protein-based preparations (40%) and standard ones (37.8%) were the most commonly used, while preparations with additional immunomodulatory ingredients accounted for only 4.44% of all ONS [2]. A systematic review of 28 studies showed that most ONS preparations contained one or more functional ingredients in addition to essential nutrients. The effectiveness of these preparations was observed in approximately 40% of studies examining nutritional status and quality of life, as well as in 65% of studies assessing markers of immune function and inflammatory response.

Enteral nutrition – indications and treatment efficacy

Enteral nutrition (EN) is recommended for cancer patients who are unable to meet more than 60–85% of their nutritional requirements through oral intake (including ONS) for periods longer than 7–14 days. Enteral nutrition is the preferred method when the gastrointestinal tract is still functioning normally. According to the ASPEN guidelines, the main indications for EN in oncology include the following [21]:

• solid tumours with moderate/severe malnutrition and inability to meet > 60–85% of nutritional requirements orally,
• planned inability to provide oral nutrition for > 7–14 days in previously well-nourished patients,
• patients with pre-cachexia/cachexia with insufficient food intake.

Special indications also exist in patients after haematopoietic cell transplantation and during head and neck radiotherapy [22, 23]. The choice of access route depends on the expected duration of nutrition. In patients requiring nutrition for < 30 days, access via nasogastric or nasojejunal tubes is used. For long-term nutrition (> 30 days), percutaneous endoscopic gastrostomy (PEG) or jejunostomy is performed. Percutaneous endoscopic gastrostomy is particularly indicated in patients with head and neck cancers during radiotherapy due to the risk of severe mucositis of the mouth and oesophagus [24]. Studies have shown that prophylactic PEG insertion in high-risk patients (lower laryngeal cancer, female gender, stage T4, chemoradiation) leads to a lower incidence of malnutrition and a better quality of life [25].
ESPEN guidelines indicate high efficacy of EN in oncology patients. In patients with head and neck cancer receiving radiotherapy, intensive nutritional counselling and ONS prevent weight loss and radiotherapy discontinuation (level A recommendation). Enteral nutrition has been shown to be safe and feasible in glioma patients receiving chemoradiotherapy, leading to a reduction in serum glucose levels [26].

Parenteral nutrition – indications and effectiveness of treatment

Parenteral nutrition (TPN), on the other hand, is a backup method, used when EN is not possible or sufficient. The main indications include gastrointestinal dysfunction, severe mucositis, intestinal obstruction, and severe malabsorption. According to the German guidelines, TPN in oncology is indicated as follows:

• when oral and enteral intake < 500 kcal/day for > 5 days (or 3–5 days in patients with severe malnutrition),
• when oral and enteral intake < 60% of requirements for 10–14 days,
• in paediatric patients with severe malnutrition or high risk of malnutrition.

Parenteral nutrition has been shown to provide clinical benefits in severely malnourished cancer patients in the preoperative period and in patients after bone marrow transplantation. However, the negative impact on quality of life, the adverse event profile, and the cost demand cautious use [27]. Studies indicate that TPN can stabilise nutritional status and prevent progressive weight loss. In patients with advanced cancer and chronic small bowel defects, the median survival time is 50–150 days, with possible stabilisation of body weight and quality of life parameters. The incidence of infectious complications associated with TPN is 0.34–2.68 per 1000 catheter days. Proper patient selection and close monitoring of therapy are crucial.

Home nutrition – eligibility and outcomes

Home nutrition (HAN) allows for the continuation of nutritional therapy in an outpatient setting, which is particularly important for patients with head and neck and gastrointestinal cancers requiring long-term nutritional support. ESPEN recommends HAN for patients with a survival prognosis of at least one month. Key eligibility criteria include the following:

• stable clinical condition,
• life outcomes > 6 weeks (assessed by the palliative prognostic score),
• Karnofsky performance status ≥ 40,
• presence of malnutrition or progressive weight loss.

A study of 1063 patients from the HAN program showed that 736 patients (who survived > 6 weeks) achieved a positive energy balance, leading to improved body weight and Karnofsky performance index after one month of therapy.
Folwarski indicates that the effectiveness of HEN depends on several factors: dietary tolerance, management of EN complications, appropriate pain management, mental health support, and rehabilitation [28]. Specialised nutritional teams reduce the number of hospitalisations, the incidence of infectious complications, and treatment costs.

Immunonutrition in oncology

Immunonutrition utilises nutrients with immunomodulatory properties to improve the immune response, reduce inflammation, and accelerate healing in cancer patients [29, 30]. For example, arginine plays a key role in wound healing, collagen synthesis, and immune system function. Studies have shown that arginine improves the body’s immunity and reduces the incidence of infections .
In a meta-analysis of 16 studies (n = 1387), preoperative administration of immunonutrition (omega-3 fatty acids, arginine, nucleotides) in patients undergoing surgery for gastrointestinal cancers reduced the incidence of infectious complications and shortened hospital stay. Studies have shown that the use of enteral immunotherapy (arginine, omega-3 fatty acids, nucleotides) in the preoperative period in patients with oesophageal cancer improves nutritional status parameters and reduces the incidence of infections. Omega-3 fatty acids, especially eicosapentaenoic acid (EPA), also exhibit potent anti-inflammatory properties by inhibiting NF-B activity and reducing the production of proinflammatory cytokines [31].
In a randomised study of patients after head and neck cancer surgery, a formula enriched with omega-3 fatty acids led to an increase in fat mass (15.4 ±6.6 vs. 18.1 ±8.4 kg; p < 0.05) and total body weight compared to an arginine-enriched formula [32, 33]. Omega-3 fatty acids at a dose of 600 mg – 2.2 γ of EPA per day are recommended for the treatment of cancer anorexia. There are also reports of the effectiveness of a combination of EPA and docosahexaenoic acid at a ratio of 1.5 : 2.0 at a dose of 1–3 γ per day. Glutamine also plays a key role in immune function. It maintains the integrity of the gastrointestinal mucosa and improves immune function.
Glutamine supplementation reduces the incidence of acute esophagitis grade 2 and 3 and improves the quality of life in patients with gastric cancer. However, ESPEN guidelines do not recommend the routine use of glutamine in EN during haematopoietic cell transplantation due to inconclusive data. Nucleotides supporting the regeneration of intestinal villi and their importance for the functioning of rapidly dividing cells of the immune system should also be considered. Probiotics also play multiple roles, mainly inhibiting carcinogenesis, reducing the incidence of diarrhoea, and modifying the gut microbiome. Some studies suggest that the use of probiotics for 3–8 days in the preoperative period in patients with colorectal cancer may reduce infectious complications and improve intestinal permeability.

Adjunctive pharmacotherapy

According to ASCO and ESPEN recommendations, appetite-enhancing medications, including glucocorticosteroids and progestogens, are helpful in the treatment of malnutrition and cachexia [34]. Progestogens (medroxyprogesterone acetate) are currently the only approved medications in Europe for the treatment of cancer cachexia.
They are effective in increasing appetite and modulating metabolic disorders, but the risk of thromboembolic complications should be considered. Mirtazapine at a dose of 15–45 mg/day or olanzapine 5 mg/day are effective in the treatment of anorexia. Despite evidence of the effectiveness of megestrol acetate and corticosteroids, they are not considered first-line treatments due to side effects. Anamorelin, a selective ghrelin receptor agonist, has been shown to be effective in increasing body weight and improving appetite. Myostatin inhibitors protect muscles and promote their growth by suppressing myostatin.
Ponsegromab, a GDF-15 inhibitor, significantly and directly increases muscle mass, appetite, and quality of life with a good safety profile. Selective androgen receptor modulators (enobosarm) have shown promising results in clinical trials [35, 36]. Modern anti-inflammatory drugs such as momelotinib or tocilizumab reduce proinflammatory cytokine levels and improve quality of life but carry the risk of immunosuppression. Pentoxifylline reduces inflammation and chemotherapy toxicity, improves body weight, and improves survival. Celecoxib (a COX-2 inhibitor) at a dose of 200–300 mg/day led to significant improvements in lean body mass and grip strength. TNF- inhibitors such as pentoxifylline and infliximab have not shown significant improvements in appetite and body weight in clinical trials.

Nutritional therapy in specific phases of therapy

Preoperative period

In surgical patients at high risk of malnutrition (weight loss of 10–15% within 6 months, BMI < 18.5, SGA grade C, or albumin < 30 g/l), ESPEN recommends initiating nutritional therapy for 10–14 days prior to surgery, even if this involves delaying the procedure [37].
Preoperative EN with immunomodulatory substances (arginine, omega-3 fatty acids, nucleotides) for 5–7 days is recommended for all patients undergoing major abdominal surgery, regardless of nutritional status (recommendation level A).
Meta-analyses indicate that preoperative nutrition with immunonutrients may reduce postoperative complications in malnourished, but not in adequately nourished patients.

During chemotherapy

Routine EN during chemotherapy does not affect treatment response or chemotherapy-related side effects and is therefore not considered useful. Recommendations focus on early recognition of nutritional problems and dietary intervention supported by ONS.
Studies have shown that ONS during chemotherapy may increase body weight but does not affect the effectiveness of anticancer treatment. The quality of these studies is limited by the heterogeneity of the patient groups and the inclusion of individuals without malnutrition [38, 39].

During radiotherapy

In patients receiving radiotherapy to the head and neck and gastrointestinal regions, intensive dietary counselling and ONS prevent weight loss and radiotherapy discontinuation (level A recommendation).
A study in patients with head and neck cancer receiving radiotherapy demonstrated that the addition of ONS led to better weight maintenance, increased protein and calorie intake, improved quality of life, and better tolerability of anticancer treatment [40].
In patients with obstructive head and neck or oesophageal cancers that interfere with swallowing, tube feeding is recommended. Due to radiotherapy-induced mucositis, PEG may be preferred.

Palliative care

In palliative care, EN should be used to minimise weight loss as long as the patient consents and the dying phase has not begun.
When the end of life is very near, most patients require only minimal amounts of food and small amounts of water to reduce thirst and hunger. Small amounts of fluids can also help avoid confusion due to dehydration.
Subcutaneous intravenous fluids in the hospital or at home can be helpful and provide a route for medication administration. ESPEN recommends artificial nutrition for terminally ill patients with weight loss and reduced nutrient intake for at least 6– 12 months [41].

Challenges and perspectives

Personalisation of nutritional therapy

The future of nutritional therapy in oncology involves personalising therapy based on the patient’s genetic, metabolic, and microbiome characteristics. Studies indicate gender differences in response to caloric restriction during radiotherapy, suggesting the need to consider the composition of the gut microbiome as a potential factor influencing treatment efficacy.
Valdemarin et al. demonstrated that fasting-mimicking diets (FMDs) are safe and feasible in cancer patients, leading to significant reductions in c-peptide, IGF1, IGFBP3, and leptin levels, which may enhance the efficacy of chemotherapy and PI3K-mTOR pathway-targeted therapies.

New research directions

Current research focuses on the role of the ketogenic diet, intermittent fasting, and caloric restriction in cancer treatment. Preclinical studies and early clinical trials suggest that these dietary interventions may reduce the toxicity and potentially enhance the efficacy of chemotherapy and radiotherapy. Short-term caloric restriction in patients with diffuse large B-cell lymphoma receiving R-CHOP has been shown to be safe and lead to increased phase angle and stable prealbumin levels.

Economic aspects

Properly managed HAN can significantly reduce healthcare costs. Specialised nutrition teams reduce hospitalisations, the incidence of infectious complications, and overall treatment costs [42]. However, the availability and reimbursement of ONS preparations remain a problem – 48.89% of patients consider the cost of ONS unacceptable.

Conclusions

Nutritional therapy is an essential element of comprehensive oncological therapy, directly impacting the effectiveness of anticancer treatment, quality of life, and patient survival. The contemporary approach to nutritional therapy in oncology is based on following key principles.
Early identification of nutritional disorders using standard screening tools, with preference given to the GLIM criteria and the PG-SGA scale in cancer patients.
A hierarchical approach to nutritional methods: oral supplementation (ONS) as a first-line treatment, EN for oral intake dysfunction, and TPN as a backup treatment for gastrointestinal dysfunction.
Personalisation of therapy tailored to the cancer type, stage, phase of oncological treatment, and individual patient needs.
The use of immunonutrition in selected patient groups, particularly in the preoperative period in patients undergoing major abdominal surgery.
A multidisciplinary approach involving collaboration between oncologists, dietitians, pharmacists, and palliative care specialists.
Recent research confirms the effectiveness of various nutritional treatment methods: ONS leads to improved body weight, reduced treatment toxicity, and improved quality of life, EN enables long-term nutritional support while maintaining gastrointestinal function, and TPN is a lifesaving nutritional method in the most complex cases. The future of nutritional treatment in oncology involves further personalisation of therapy, the use of new biomarkers of nutritional status, the development of home nutrition, and the integration of nutritional interventions with modern cancer treatment methods. Improving the availability and reimbursement of specialised nutritional preparations and educating medical staff on contemporary clinical nutrition standards is also crucial.

Disclosures

1. Institutional review board statement: Not applicable.
2. Assistance with the article: None.
3. Financial support and sponsorship: None.
4. Conflicts of interest: None.

References