Expert Consensus on Nutritional Therapy for Malignancies
Successful nutrition therapy relies first on an accurate assessment of the nutritional status of each cancer patient, identification of those eligible for the therapy by screening, and timely delivery of care. For objective evaluation of the therapeutic efficacy, follow-up evaluation will be needed during the treatment course for timely adjustment of the treatment plan.
The following concepts should be clarified for the purpose of assessing the nutritional status of patients with malignant cancer. First, malnutrition consists of both undernutrition and obesity (overweight), where undernutrition is determined by a body mass index (BMI) of <18.5 kg/m in combination with indicative clinical manifestations. Second, a nutritional risk describes the probability of an adverse effect on the clinical outcomes (such as infection-related complications, costs, and length of stay) of a patient due to his/her disease, surgery and nutritional factors, rather than the risk of occurrence of malnutrition (undernutrition). The nutritional risk can be interpreted in two ways: (I) patients with a higher risk are prone to adverse clinical outcomes; and (II) high-risk patients may benefit more from nutritional treatment.
Nutritional status assessment is completed in two steps: a preliminary screening, and then a comprehensive assessment. While the second step is a continuation of the former, they may not be confused with each other. The main purpose of the first step is to identify patients with existing malnutrition (undernutrition) or corresponding risks, particularly high-risk individuals who have not yet developed undernutrition, which should be completed at visit or upon admission to facilitate the formulation of nutrition treatment plans as clinically indicated. On the other hand, the second step, with a wider range of goals, is a comprehensive analysis of various nutritional parameters performed at any time when necessary to identify complications due to malnutrition (undernutrition), estimate nutritional requirements, develop nutrition treatment plans, and evaluate the therapeutic effect.
Screening approaches are developed to be simple and efficient with high sensitivity. Commonly used screening tools include: Subjective Globe Assessment (SGA), Mini Nutritional Assessment (MNA), Malnutrition Universal Screening Tools (MUST), Nutritional Risk Screening 2002 (NRS2002) (Table 2), and Patient-Generated Subjective Global Assessment (PG-SGA) (Table 3). SGA, an ASPEN-recommended tool for clinical nutritional status assessment published in 1987, incorporates a detailed medical history and physical assessment parameters that can be used to predict the incidence of complications. However, it is not capable of identifying mild undernutrition or reflecting the changes of acute nutritional status, and the correlation with clinical outcomes is not well supported by evidence. Therefore, this tool is more suitable for use by trained professionals, rather than serving as a routine nutrition screening tool in large hospitals. PG-SGA is a modified version of SGA that has been widely used for rough screening, the preferred method of nutritional screening in cancer patients recommended by the American Dietetic Association. MNA is a fast, simple and easy-to-use tool published in 1999, which includes both nutrition screening and nutrition assessment, making it suitable for both patients with nutritional risks and undernourished hospitalized patients. The tool is useful for patients at the age of 65 or above and community populations. MUST, published by the Multidisciplinary Advisory Group on Malnutrition of the British Society for Parenteral and Enteral Nutrition in 2000, is mainly designed for screening protein-energy malnutrition and its risk, and is thus a useful tool for nutritional risk screening in different medical institutions, particularly communities.
Published in 2003 by the Danish Association of Parenteral and Enteral Nutrition (detailed inTable 2), NRS2002 is an ESPEN-recommended tool for inpatient nutrition risk screening, which includes three main components: (I) Score of impaired nutritional status (0 to 3); (II) Score of disease severity (0 to 3); and (III) Age score, where one extra point will be assigned to this category for patients aged 70 years or older. The total score is 0 to 7 points. The analysis of 128 randomized clinical trials (RCT) on nutrition therapy versus clinical outcomes has suggested that, when the NRS score is three or above, effective therapy (significantly improved clinical outcomes) is demonstrated in most studies; when the NRS score is lower than three, the therapy is ineffective for most of them. The cut-off point for nutritional risks is thus set at three, meaning that a nutritional risk is present when the NRS score reaches three points or above and warrants individualized nutritional intervention plan based on the specific clinical conditions. Although patients with a NRS score lower than three are free of nutritional risks, a weekly screening is still needed during hospitalization.
Supported by the 128 RCTs, NRS2002 is an evidence-based, simple and easy-to-use tool that objectively reflects the nutritional risks of patients based on comprehensive analysis of the nutritional status, disease severity and age-related compounding factors to minimize subjective disturbance. Accordingly, the Parenteral and Enteral Nutrition Society of Chinese Medical Association has chosen and recommended NRS2002 as the screening tool to identify patients in need of nutritional intervention because it: (I) is oriented towards hospitalized patients; (II) is evidence-based; and (III) simple, easy-to-use. As verified by Liang et al., the adaptability of NRS2002 was 94.0% and 99.5%, respectively, for patients in a teaching hospital in China and the other in the United States. A study conducted by Yu et al. also demonstrated that NRS2002 could be used as the preferred tool for nutrition risk screening. Chen et al. conducted a feasibility study on NRS2002 for inpatient nutrition risk screening in China; as confirmed by their results, it is feasible to use NRS2002 for nutrition risk screening of Chinese hospitalized patients to identify those in need of nutritional intervention, based on the BMI values of the Chinese population.
However, NRS2002 is still associated with certain drawbacks. For example, body weight measurement is not possible for patients lying in bed, or will be inaccurate when edema or ascites is present. Unconscious patients who are unable to answer the questions are also ineligible for being assessed with this tool. Although serum albumin measurement may provide supplementary information, it can only be used in patient without significant liver and kidney dysfunction. In addition, NRS2002 may have limitations when applied to the special group of patients with malignant tumors. First, all subjects observed in the 128 RCTs were hospitalized patients, whereas the outpatient day treatment model has been gradually popular in clinical practice for cancer patients receiving radiotherapy and chemotherapy, making the use of this tool controversial. Second, the RCTs were conducted in almost exclusively general hospitals, mostly from the 1970s to 1990s, when the principles for malignant cancer treatment were considerably different from today' s standardized multidisciplinary model, and the observation of specific clinical outcomes related to malignant cancer was not as accurate as it was supposed to be. Third, the classification of tumors into "tumors" and "hematological malignancies" in the disease severity section of NRS2002 remains controversial. With the two categories being assigned with one and two points, respectively, gastrointestinal tumors or head and neck cancer associated with a higher incidence of cachexia were not distinguished from breast cancer and other tumors that had a relatively better nutritional status. Meanwhile, standardized nomenclature of major abdominal surgeries has yet to be introduced in this tool.
Nevertheless, NRS2002 remains the most evidence-based tool for nutrition risk screening compared with its counterparts. In 2004, the Parenteral and Enteral Nutrition Society of Chinese Medical Association hosted the first inpatient nutrition risk screening with NRS2002 in tertiary Class A hospitals in large cities. According to the results of 15,098 hospitalized patients, NRS2002 is applicable for 99% or more Chinese hospitalized patients based on the normal BMI values of the Chinese people. They then conducted a prospective study of patients with malignant tumors admitted in large, medium and small hospitals in the eastern, central and western part of China from March 2005 to October 2008, finding that 40–41% of the subjects had nutrition risks that warranted a nutritional treatment plan based on their specific conditions. However, only 46% of those high-risk patients had received nutritional intervention. Malnutrition (undernutrition) and nutritional risks both increase along with age, indicating the need to emphasize nutrition therapy for elderly cancer patients. As the foregoing prospective study was carried out in the general wards of general hospitals, and did not involve specialized cancer centers or dedicated wards, or end-stage patients, it was unable to reflect the actual condition of nutrition risk screening for Chinese patients with malignant cancer. Therefore, in 2010, the Experts Committee on Nutritional Therapy for Cancer Patients of CSCO conducted a large-scale prospective observational study in cancer centers and specialized wards across the country, aiming to provide more evidence for the applicability of NRS2002 in malignant patients.
After screening, patients with nutritious risks have to undergo the process of assessment before they are considered in need of medical nutrition therapy, which is conducted in combination with medical history review, physical examination, laboratory tests, anthropometry and a number of other indicators.
The efficacy of nutritional therapy should eventually be reflected in improved quality of life and higher tolerance of anti-tumor therapy. In terms of the former, efficacy monitoring can be used in a clinical study with focus on the impact of hospital stay, complications, adverse reactions, nutritional status, immune function, and organ function on the quality of life; for the latter, a rigorously designed, randomized, controlled trial or retrospective cohort study can be performed to observe the overall survival for comparing the long-term efficacy with nutritional therapy of different approaches, time and formulas, identifying the need of combined nutrition support in anti-tumor therapy, and determining the impact of combined therapy on the long-term survival, with the aim to establish the most scientific nutrition therapy model.
2. Nutrition Risk Screening and Assessment for Tumor Patients Other Section
Successful nutrition therapy relies first on an accurate assessment of the nutritional status of each cancer patient, identification of those eligible for the therapy by screening, and timely delivery of care. For objective evaluation of the therapeutic efficacy, follow-up evaluation will be needed during the treatment course for timely adjustment of the treatment plan.
The following concepts should be clarified for the purpose of assessing the nutritional status of patients with malignant cancer. First, malnutrition consists of both undernutrition and obesity (overweight), where undernutrition is determined by a body mass index (BMI) of <18.5 kg/m in combination with indicative clinical manifestations. Second, a nutritional risk describes the probability of an adverse effect on the clinical outcomes (such as infection-related complications, costs, and length of stay) of a patient due to his/her disease, surgery and nutritional factors, rather than the risk of occurrence of malnutrition (undernutrition). The nutritional risk can be interpreted in two ways: (I) patients with a higher risk are prone to adverse clinical outcomes; and (II) high-risk patients may benefit more from nutritional treatment.
Nutritional status assessment is completed in two steps: a preliminary screening, and then a comprehensive assessment. While the second step is a continuation of the former, they may not be confused with each other. The main purpose of the first step is to identify patients with existing malnutrition (undernutrition) or corresponding risks, particularly high-risk individuals who have not yet developed undernutrition, which should be completed at visit or upon admission to facilitate the formulation of nutrition treatment plans as clinically indicated. On the other hand, the second step, with a wider range of goals, is a comprehensive analysis of various nutritional parameters performed at any time when necessary to identify complications due to malnutrition (undernutrition), estimate nutritional requirements, develop nutrition treatment plans, and evaluate the therapeutic effect.
2.1 Nutrition Risk Screening
Screening approaches are developed to be simple and efficient with high sensitivity. Commonly used screening tools include: Subjective Globe Assessment (SGA), Mini Nutritional Assessment (MNA), Malnutrition Universal Screening Tools (MUST), Nutritional Risk Screening 2002 (NRS2002) (Table 2), and Patient-Generated Subjective Global Assessment (PG-SGA) (Table 3). SGA, an ASPEN-recommended tool for clinical nutritional status assessment published in 1987, incorporates a detailed medical history and physical assessment parameters that can be used to predict the incidence of complications. However, it is not capable of identifying mild undernutrition or reflecting the changes of acute nutritional status, and the correlation with clinical outcomes is not well supported by evidence. Therefore, this tool is more suitable for use by trained professionals, rather than serving as a routine nutrition screening tool in large hospitals. PG-SGA is a modified version of SGA that has been widely used for rough screening, the preferred method of nutritional screening in cancer patients recommended by the American Dietetic Association. MNA is a fast, simple and easy-to-use tool published in 1999, which includes both nutrition screening and nutrition assessment, making it suitable for both patients with nutritional risks and undernourished hospitalized patients. The tool is useful for patients at the age of 65 or above and community populations. MUST, published by the Multidisciplinary Advisory Group on Malnutrition of the British Society for Parenteral and Enteral Nutrition in 2000, is mainly designed for screening protein-energy malnutrition and its risk, and is thus a useful tool for nutritional risk screening in different medical institutions, particularly communities.
Published in 2003 by the Danish Association of Parenteral and Enteral Nutrition (detailed inTable 2), NRS2002 is an ESPEN-recommended tool for inpatient nutrition risk screening, which includes three main components: (I) Score of impaired nutritional status (0 to 3); (II) Score of disease severity (0 to 3); and (III) Age score, where one extra point will be assigned to this category for patients aged 70 years or older. The total score is 0 to 7 points. The analysis of 128 randomized clinical trials (RCT) on nutrition therapy versus clinical outcomes has suggested that, when the NRS score is three or above, effective therapy (significantly improved clinical outcomes) is demonstrated in most studies; when the NRS score is lower than three, the therapy is ineffective for most of them. The cut-off point for nutritional risks is thus set at three, meaning that a nutritional risk is present when the NRS score reaches three points or above and warrants individualized nutritional intervention plan based on the specific clinical conditions. Although patients with a NRS score lower than three are free of nutritional risks, a weekly screening is still needed during hospitalization.
Supported by the 128 RCTs, NRS2002 is an evidence-based, simple and easy-to-use tool that objectively reflects the nutritional risks of patients based on comprehensive analysis of the nutritional status, disease severity and age-related compounding factors to minimize subjective disturbance. Accordingly, the Parenteral and Enteral Nutrition Society of Chinese Medical Association has chosen and recommended NRS2002 as the screening tool to identify patients in need of nutritional intervention because it: (I) is oriented towards hospitalized patients; (II) is evidence-based; and (III) simple, easy-to-use. As verified by Liang et al., the adaptability of NRS2002 was 94.0% and 99.5%, respectively, for patients in a teaching hospital in China and the other in the United States. A study conducted by Yu et al. also demonstrated that NRS2002 could be used as the preferred tool for nutrition risk screening. Chen et al. conducted a feasibility study on NRS2002 for inpatient nutrition risk screening in China; as confirmed by their results, it is feasible to use NRS2002 for nutrition risk screening of Chinese hospitalized patients to identify those in need of nutritional intervention, based on the BMI values of the Chinese population.
However, NRS2002 is still associated with certain drawbacks. For example, body weight measurement is not possible for patients lying in bed, or will be inaccurate when edema or ascites is present. Unconscious patients who are unable to answer the questions are also ineligible for being assessed with this tool. Although serum albumin measurement may provide supplementary information, it can only be used in patient without significant liver and kidney dysfunction. In addition, NRS2002 may have limitations when applied to the special group of patients with malignant tumors. First, all subjects observed in the 128 RCTs were hospitalized patients, whereas the outpatient day treatment model has been gradually popular in clinical practice for cancer patients receiving radiotherapy and chemotherapy, making the use of this tool controversial. Second, the RCTs were conducted in almost exclusively general hospitals, mostly from the 1970s to 1990s, when the principles for malignant cancer treatment were considerably different from today' s standardized multidisciplinary model, and the observation of specific clinical outcomes related to malignant cancer was not as accurate as it was supposed to be. Third, the classification of tumors into "tumors" and "hematological malignancies" in the disease severity section of NRS2002 remains controversial. With the two categories being assigned with one and two points, respectively, gastrointestinal tumors or head and neck cancer associated with a higher incidence of cachexia were not distinguished from breast cancer and other tumors that had a relatively better nutritional status. Meanwhile, standardized nomenclature of major abdominal surgeries has yet to be introduced in this tool.
Nevertheless, NRS2002 remains the most evidence-based tool for nutrition risk screening compared with its counterparts. In 2004, the Parenteral and Enteral Nutrition Society of Chinese Medical Association hosted the first inpatient nutrition risk screening with NRS2002 in tertiary Class A hospitals in large cities. According to the results of 15,098 hospitalized patients, NRS2002 is applicable for 99% or more Chinese hospitalized patients based on the normal BMI values of the Chinese people. They then conducted a prospective study of patients with malignant tumors admitted in large, medium and small hospitals in the eastern, central and western part of China from March 2005 to October 2008, finding that 40–41% of the subjects had nutrition risks that warranted a nutritional treatment plan based on their specific conditions. However, only 46% of those high-risk patients had received nutritional intervention. Malnutrition (undernutrition) and nutritional risks both increase along with age, indicating the need to emphasize nutrition therapy for elderly cancer patients. As the foregoing prospective study was carried out in the general wards of general hospitals, and did not involve specialized cancer centers or dedicated wards, or end-stage patients, it was unable to reflect the actual condition of nutrition risk screening for Chinese patients with malignant cancer. Therefore, in 2010, the Experts Committee on Nutritional Therapy for Cancer Patients of CSCO conducted a large-scale prospective observational study in cancer centers and specialized wards across the country, aiming to provide more evidence for the applicability of NRS2002 in malignant patients.
2.2 Further Comprehensive Nutrition Assessment
After screening, patients with nutritious risks have to undergo the process of assessment before they are considered in need of medical nutrition therapy, which is conducted in combination with medical history review, physical examination, laboratory tests, anthropometry and a number of other indicators.
Medical history: a patient's acceptance of nutrition therapy is affected by previous tumors, past medical history, dietary surveys, drug history, social habits, lifestyle, health insurance, religious and cultural background, as well as economic situation;
Physical examination: the depletion of adipose tissues and muscle tissues, presence of edema and ascites, and appearance of hair and nails, skin and oral mucosa are investigated to help evaluate the severity of energy and protein deficiency. Weight loss is not the only manifestation of malnutrition (undernutrition), as overnutrition and undernutrition can be simultaneously present in many patients, obscuring the differential diagnosis of malnutrition (undernutrition). The condition is often overlooked in obese patients;
Laboratory tests: organ functions are investigated as an essential part in cancer treatment. Plasma proteins, blood urea, creatinine, plasma C-reactive protein (CRP), and immune function can be used as non-specific reference indicators;
Body measurements: Dynamic weight monitoring is the most convenient and direct clinical indicator, but it is vulnerable to interference, such as fluid retention, coma, paralysis, edema, and huge tumor. In addition, the specific time and accurate result of the last weighing are often hard to trace for many patients. Other indicators include upper arm circumference (AC), triceps skinfold thickness (TSF), arm muscle circumference (AMC), reaction fat, and skeletal muscle reserve.
CT or MRI assessment of muscle mass was first introduced in the Definition and Classification of Cancer Cachexia: an International Consensus in 2010, as an extremely important component of the assessment system. It is not only one of the criteria for diagnosis, but also one of the goals of treatment, because the reduction of muscle mass is more critical than that of fat during weight loss, and low muscle mass is an independent predictor of mortality for patients with advanced tumors;
Determination of body function and composition: changes in body function and composition can provide certain information for nutritional assessment. Nutrition therapy is an important link in the comprehensive treatment of malignant tumors, and the assessment of nutritional status should be conducted simultaneously with the assessment of the tumor, therapeutic effect, physical state and quality of life.
The efficacy of nutritional therapy should eventually be reflected in improved quality of life and higher tolerance of anti-tumor therapy. In terms of the former, efficacy monitoring can be used in a clinical study with focus on the impact of hospital stay, complications, adverse reactions, nutritional status, immune function, and organ function on the quality of life; for the latter, a rigorously designed, randomized, controlled trial or retrospective cohort study can be performed to observe the overall survival for comparing the long-term efficacy with nutritional therapy of different approaches, time and formulas, identifying the need of combined nutrition support in anti-tumor therapy, and determining the impact of combined therapy on the long-term survival, with the aim to establish the most scientific nutrition therapy model.
2.3 Recommendation
Upon a definite diagnosis, patients with malignant tumors should be subject to nutritional risk screening immediately (Level 1).
At present, PG-SGA and NRS2002 are the most widely used tools for nutrition risk screening of patients with malignancies (Level 1).
A nutritional risk is determined when the NRS score reaches three or above, where an individualized nutrition plan should be developed according to the patient's clinical conditions and nutritional intervention be administered (Level 2A).
Although patients with a NRS score lower than three are free of nutritional risks, a weekly screening is still needed during hospitalization (Level 2A).
Medical history, physical examination and laboratory tests are helpful in understanding the cause and severity of malnutrition in patients with malignant tumors, facilitating a comprehensive nutrition assessment (Level 2A).
Nutrition risk screening and comprehensive nutrition assessment should be conducted simultaneously in combination with imaging evaluation of anti-tumor efficacy to provide an all-round assessment of the benefits from anti-cancer therapy(Level 2A).
SHARE
![Pediatric Supportive Care (PDQ®): Supportive care - Patient Information [NCI]-Overview](https://cdnus.oss-us-west-1.aliyuncs.com/libs/images/NewsJpg/cate_6/072_215x160.jpg)
