Cancer patients are at high risk for involuntary body weight loss and protein-energy malnutrition because of the underlying catabolic disease, the metabolic and inflammatory underlying changes associated with cancer, and the negative effects of the anticancer treatments on the nutritional status [1▪▪,2]. Cancer-related nutritional risk is often under-estimated by physicians and patients are largely under-treated for malnutrition [3▪▪].
It has been strongly supported that reduced food intake and negative energy balance play crucial roles in the pathogenesis of weight loss and cancer cachexia [4▪▪,5].
Cancer profoundly modifies the normal homeostatic control of energy balance. Body weight is stable when there is a balance between total energy expenditure by the body and the energy intakes consisting in calories provided by oral, enteral or parenteral routes. Cancer metabolism and inflammation may increase total energy expenditure and, at the same time, decrease appetite (determining low food intake), moving towards a negative energy balance .
Also, cancer therapies negatively influence energy balance. Energy intake may be reduced more than 50% of requirement (approximately 1.200 kcal per day) during chemotherapy and radiotherapy, contributing to the negative energy balance in cancer-associated weight loss [1▪▪]. Reduced food intake is an important and often predominant aspect of cancer-associated weight loss [1▪▪].
Reduced synthesis of muscle proteins has also been documented in cancer patients presenting weight loss, highlighting the importance of reduced dietary intake in the pathogenesis of cancer-associated sarcopenia and cachexia, and indicating the crucial role of generating an anabolic response by the supplementation of nutrients able to reactivate protein synthesis [1▪▪,7,8].
The pathogenesis of this condition includes multiple factors, and its treatment should be based on different and multimodal targets. In the recent years, the improved understanding of the mechanisms underlying weight loss in cancer, cachexia and sarcopenia led to consider clinical parameters, that is, BMI, body weight change and food intake, and their modification overtime (a low BMI and the amount of weight loss) predicting independently the overall survival . It appears important the impact of high versus low initial BMI in the risk assessment of patients with weight loss. It has been seen that for individuals with the higher BMI (i.e. larger energy reserves) the risk of mortality associated with any degree of weight loss is less than for individuals with lower initial BMI . A BMI-adjusted weight loss grading system has been proposed as a useful clinical prognostic tool to predict survival, combining together BMI and percentage of weight loss to provide a risk of shortened survival and to early identify patient subgroups with the greatest long-term nutritional risk .
On the basis of these evidences, we believe that nutritional aspects should be carefully considered when managing cancer patients, in particular during treatments. Also, nutritional issues negatively impact on patents’ quality of life in every stage of cancer journey.
The present article aims at focusing on the recent advances and directions on nutrition support to treat cancer-associated body weight loss.
NUTRITIONAL AND METABOLIC SUPPORT IN CANCER: UPDATED EVIDENCES
Cancer-associated weight loss results from a strict combination of anorexia, which very frequently leads to low food intake, and metabolic derangements inducing body weight loss, reducing the potential recovery by nutrients supplementation and negatively impacting on patients’ nutritional status [4▪▪,9].
The lack of awareness by many physicians regarding nutritional status of cancer patients frequently results in progressive and underestimated weight loss until it becomes severe and scarcely treatable [3▪▪]. A nutritional and metabolic approach in cancer has been proposed, the ‘parallel pathway,’ involving a multidisciplinary team and multimodal approach aimed at prevention, early recognition and treatment of the metabolic and nutritional derangements occurring in any phase of the disease [3▪▪,10]. Reduction in food intake should be early recognized and managed, and oral energy intake should be assessed at least qualitatively and, if possible, quantitatively [3▪▪,9].
In line with the definition of cancer precachexia and cachexia , a recent clinical study has highlighted the interest in clinical parameters such as weight loss and BMI. Loss of ability to maintain body weight, even approximately around 2% of weight loss, is significantly related to decreased survival, in particular, if associated with metabolic derangements . This condition should indicate to start nutritional and metabolic support, rather than delaying any intervention for weight loss levels arbitrarily defined [2,3▪▪].
Aims of the nutritional support in cancer are to maintain or restore nutritional status, improve tolerance to aggressive anticancer therapies, and ameliorate the functional capacity, including physical performance and quality of life. Therefore, nutritional treatment should be preceded by an assessment of treatable issues that impact on food intake (i.e. xerostomia, nausea, vomiting, changes in smell and taste, mucositis, constipation, diarrhea, malabsorption, therapies’ side-effects, acute and chronic pain and psychological distress) [9,12].
According to the latest guidelines, nutritional support should be initiated preferably when patients are not yet severely malnourished and to patients who are expected to develop anorexia and weight loss .
First-line approaches include oral nutritional supplements, semi-solids or powders, that provide macronutrients and micronutrients for individuals who are unable to meet their nutritional requirements through oral diet and consultation with nutritional healthcare professionals to increase the quantity and quality of the patient's food .
For example, head and neck cancer patients are a group of patients who more frequently experience unintentional weight loss and malnutrition since diagnosis and/or during chemo-radiotherapy and after the end of therapies because of impairment of food intake . Recently, it has been documented that energy requirements in these patients may be at least 35 kcal/kg/day during and after anticancer therapies to maintain a stability of body weight and body composition parameters measured by bioelectrical impedance vector analysis . However, these interventions, although carried out at an early phase, have been reported to be only partially effective in controlling weight loss and body composition , strengthening the view that cancer-associated weight loss is not only determined by insufficient nutrient intake, but is the result of active catabolic processes and negative nutrient balance .
Studies have shown that the efficacy of nutrition support is dependent on a strict monitoring of the patient and the timely increase of calorie and protein supplementation as soon as the food intake ability decreases [2,14].
As previously shown, weight loss can be induced by several side-effects of the anticancer treatments, that is, anorexia, reduced hedonic intake and gastrointestinal symptoms , and/or by physical inactivity resulting from fatigue and psychosocial and physical distress [17▪], which may lead to further loss of lean body mass and muscle mass and to malnutrition.
A recent meta-analysis, carried out on data obtained in cancer patients on the effects of oral nutritional support on clinical outcomes during chemotherapy and radiotherapy, has shown positive results on the stability of body weight during therapies, specifically after oral supplementation with high-protein omega-3 polyunsaturated fatty acid (PUFA)-enriched formula, indicating the benefit of targeting specific metabolic alterations, such as inflammation [17▪]. Evidences remain limited regarding the effects of oral nutrition support in improving clinically relevant outcomes including quality of life, treatment-related toxicity and survival [17▪].
Although parenteral nutrition is not routinely indicated in oncology , supplemental home parenteral nutrition (sHPN) has been recently shown to be of some benefit in advanced gastrointestinal cancer patients. In a single-center open-label randomized controlled trial, sHPN was shown to significantly increase fat-free mass and to improve quality of life, but not survival, when compared with best practice nutritional care and dietetic counselling . Conversely, the potentials of supplemental parenteral nutrition during active anticancer treatments, for example, neoadjuvant therapy, remains to be fully explored .
In line with the concept of the ‘parallel pathway,’ a pilot study has been conducted on naïve cancer patients presenting cachexia, treated with interventional protocol consisting in personalized dietary counseling (nutrition therapy group), and compared with regular dietary counseling (control group) before and during cancer therapies . The study showed that the nutrition therapy based on patient's specific biophysical parameters resulted in maintaining body weight stable and improving nutritional balance in cachectic cancer patients, as well as in lower hospital stay and improved survival . Although these were preliminary results, the authors documented that cancer cachexia can be effectively counteracted by a tailored nutritional approach under tight supervision of a dedicated multidisciplinary team .
According to the ESPEN (European Society for Clinical Nutrition and Metabolism) guidelines, nutritional interventions should be conducted in a stepwise manner, starting with dietary counseling and oral nutritional support since the time of cancer diagnosis .
If nutrient intake results inadequate, supplemental or complete nutritional support by the oral, enteral or parenteral route may be indicated, depending on the level of function of the gastrointestinal tract . Parenteral nutritional support is indicated when clinical conditions such as mucositis, radiation enteritis or intestinal failure are present.
A European hospital study has shown that only one-third of cancer patients, presenting body weight loss and at risk of malnutrition, received nutritional support . Recently, a prospective, observational study  was conducted in more than 20 Italian medical oncology centers aimed at investigating the prevalence of malnutrition in cancer patients at their first medical oncology visit (PreMio study). In particular, appetite was assessed to detect the presence of anorexia and recent body weight changes were recorded to investigate the presence of malnutrition and precachexia and cachexia . Results showed that 65% of the enrolled patients (53% nonmetastatic) reported unintentional weight loss during the previous 6 months when they entered the study, and more than 50% had nutritional impairment, highlighting the importance of increased awareness of malnutrition risk in cancer patients, even in those with nonmetastatic disease, and the relevance of conducting early assessment of nutritional status and early nutritional support as part of routine supportive cancer treatments .
Moreover, three global surveys conducted across Europe and North America have investigated the awareness, knowledge and treatment clinical practices among healthcare professionals involved in the management of cancer-associated cachexia [3▪▪]. Interestingly, the 69% of healthcare professionals participating the surveys identified as primary factor for a nutritional support in cancer patients a weight loss more than 5%. Moreover, 50% of the participants would consider a drug treatment if the patient were not responsive to anticancer treatment or developed a weight loss more than 2% with a BMI less than 20 kg/m2, and 35% of participants reported that they would wait until weight loss was 15–20%, and over 10% of participants would wait until weight loss was more than 25% [3▪▪]. The conclusions from the three global surveys have recognized that, although increasing body weight is the ideal outcome, stabilizing or maintaining this parameter is a more realistic goal for many healthcare professionals, and that an increased awareness on cancer cachexia and its management is needed for an early nutritional counseling and intervention to obtain advantages in terms of treatment tolerance and clinical outcomes [3▪▪].
In the last years, several studies have documented existing evidence on cancer-associated weight loss from perspectives of healthcare professionals and also with a specific focus on the psychosocial impact of weight loss and on quality of life [3▪▪,22,23]. The results revealed the multidimensional nature of cachexia, loss of appetite and weight loss experienced by patients and caregivers, which was not recognized and adequately managed by healthcare professionals. It underscores the need for increased awareness among physicians on this condition and its management [3▪▪,22,23].
According to ESPEN recommendations on action against cancer-related malnutrition , three key points to update nutritional care for cancer patients have to be highlighted: to screen all cancer patients for nutritional risk early in the course of their management, with specific attention to BMI and body weight change in the previous months, to include in the clinical practice at least the assessment of anorexia, body composition, physical function, to use multimodal nutritional support in a stepwise manner with individualized plans, including care aimed at improving nutritional intake and physical activity .
Efforts should focus on identifying barriers and knowledge gaps of healthcare professionals, and providing effective and clinically relevant nutritional guidelines.
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Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
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