Version May 2024
INTRODUCTION — Weight loss is common among cancer patients, and can be attributed to many causes, including mucositis, inability to ingest or absorb adequate calories because of a problem with the alimentary tract, loss of appetite, and metabolic aberrations. Unintentional weight loss may be associated with decreased quality of life (QOL) and a poorer prognosis. Furthermore, for patients who are already in a catabolic state, the increased metabolic demands associated with anticancer treatment (particularly surgery) further worsen the problem. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)
Intuitively, it would seem that caloric repletion, by either the enteral or parenteral route, would be the optimal approach to the treatment of cancer-associated weight loss. However, the routine use of enteral or parenteral nutritional support in patients with incurable cancer is not recommended [1]. The routine use of nutritional support in patients with advanced incurable cancer is associated with a higher risk of treatment-related complications [2,3], and no evidence of a survival benefit. Nevertheless, nutritional support is frequently prescribed for patients with cancer. In fact, malignant disease is the most frequent indication for home total parenteral nutrition, accounting for approximately one-half of all cases in one large series [4].
An overview of the general use of both parenteral and enteral/oral nutritional supplementation in cancer patients and detailed discussions of nutritional support related to the perioperative setting, hematopoietic cell transplantation, head and neck cancer, esophageal cancer, and in patients with advanced incurable cancers are discussed here. The use of nutritional support in surgical patients and the intensive care unit setting, and the basic principles of enteral and parenteral nutrition are discussed elsewhere. (See "Overview of perioperative nutrition support" and "Nutrition support in intubated critically ill adult patients: Initial evaluation and prescription".)
NUTRITIONAL STATUS AND CANCER OUTCOMES — According to the Malnutrition Advisory Action Group of the British Association for Parenteral and Enteral Nutrition, malnutrition is defined as a deficiency in energy, protein, or other nutrients causes measurable adverse effects on tissues or body form, function, or clinical outcomes. Malnutrition occurs in 40 to 80 percent of cancer patients and is a major cause of morbidity and mortality in patients with advanced disease [5,6]. It is particularly frequent in patients with digestive and upper aerodigestive tract tumors. Malnutrition may be related to an inability to ingest or absorb nutrients because of a problem with the alimentary tract related to the primary disease process (ie, obstructing esophageal tumor) or cancer treatment (ie, combined modality therapy for head and neck cancer, which may cause severe oral mucositis), or the cancer-associated anorexia/cachexia syndrome. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)
Regardless of the cause, malnutrition in cancer patients is associated with poorer overall survival in various malignancies [7-9], as well as reduced benefit from surgical [10,11] and medical therapies [12,13], a poorer tumor response to chemotherapy [7,8,13], increased chemotherapy-related toxicity [12,14,15], and poorer quality of life [8,16-18]. It is important to point out that although several investigators refer to "malnutrition" in cancer patients, the provision of calories is often not the most appropriate response to this situation, as caloric supplementation can lead to complications and no reversal of the clinical picture. Thus, some might argue that the term "malnutrition" is a misnomer.
Screening for nutritional status — Multiple scores are available for nutritional status evaluation of cancer patients. One simple to use and objective tool is the Nutritional Risk Index (NRI), which has been validated in various clinical settings, including gastrointestinal cancers [19-21]. The NRI can be calculated as (= 1.519 x serum albumin level [g/L] + 0.417 X current weight/usual weight X 100) [19]. Based on the NRI, patients can be classified as having no malnutrition (NRI >97.5), moderate malnutrition (97.5 ≥ NRI ≥ 83.5), or severe malnutrition (NRI <83.5).
Additional issues related to screening for nutritional status are addressed in detail elsewhere. (See "Geriatric nutrition: Nutritional issues in older adults", section on 'Screening for nutritional status'.)
INDICATIONS AND BENEFITS OF NUTRITIONAL SUPPORT IN CANCER PATIENTS — Nutritional support may improve outcomes in selected cancer patients. However, due to the paucity of evidence demonstrating benefit, the indiscriminate use of enteral or parenteral nutrition in well-nourished or mildly malnourished patients with cancer is not recommended. Oral nutritional interventions might improve some aspects of quality of life in cancer patients who are malnourished or at risk for malnutrition, but they do not appear to improve survival. (See 'Evidence to support benefit' below.)
Parenteral or enteral nutritional supplementation may be an appropriate option for cancer patients who meet both of the following criteria:
●They are either notably malnourished or at risk of becoming so during cancer treatment.
●They have a potentially curable disease or look forward to the promise of a long disease-free period after cancer treatment.
There are no widely accepted guidelines for when to initiate nutritional support in cancer patients. While decisions about nutrition support are relatively easy for malnourished patients who have a potentially curable cancer but are unable to meet their nutrient needs for prolonged periods (eg, because of esophageal obstruction or intestinal failure), these decisions are more difficult when nutritional intake is closer to meeting needs, when the likely period of inadequate intake is uncertain, or in situations where the malignancy is treatable but incurable and the patient is unable to take in sufficient nutrients. In these settings, decision-making is more complex, especially given that providing nutrition support is not without risk.
Guidance from expert groups — This lack of consensus as to specific indications for nutritional support in patients with cancer is reflected in the vagueness of available guidelines from expert groups:
●International guidelines on the nutritional management of patients with cancer from the European Society for Clinical Nutrition and Metabolism (ESPEN), the American Dietetic Association, the American Society for Parenteral and Enteral Nutrition, and the Dietitians Association of Australia recommend that nutritional intervention be started in malnourished patients or those in whom difficulties with eating are anticipated [22-25].
In addition, ESPEN has published a 2020 update on indications and contraindications for home enteral nutrition, and its implementation and monitoring [26].
●In the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) recommends that health care professionals consider oral nutritional support to improve nutritional intake for people who can swallow safely and who are malnourished or at risk of malnutrition (NICE guidelines for nutritional support for adults).
●Guidelines from the National Comprehensive Cancer Network (NCCN) [27] suggest consideration of nutritional support, as appropriate, in patients who have an estimated life expectancy of months to years, but not those with a life expectancy measured in weeks to months.
●Guidelines for managing cancer-associated cachexia from the American Society for Clinical Oncology support that it is reasonable for clinicians to refer patients with cancer and loss of appetite and/or body weight to a registered dietician for assessment and counseling with the goals of providing practical and safe advice for feeding; education regarding high-protein, high-calorie, nutrient-dense foods; and advice against fad, unproven, or other extreme diets [1]. Outside of the context of a clinical trial, clinicians should not routinely offer enteral tube feeding or parenteral nutrition to manage cachexia in advanced cancer. A short-term trial of parenteral nutrition may be offered to a very select group of patients, such as those who have reversible bowel obstruction, short-bowel syndrome, or other issues contributing to malabsorption, but otherwise are reasonably fit. Discontinuation of previously initiated enteral or parenteral nutrition near the end of life is appropriate. (See 'Patients with cancer at the end of life' below.)
●In 2020, the European Society of Medical Oncology endorsed comfort-directed care as the primary nutritional goal for patients with only a few estimated (three to six) weeks of life, less invasive nutritional interventions for patients with less than three to six months of estimated life, and that regular screening and nutritional interventions should be considered in patients with more than three to six months of estimated life expectancy [28].
●The Multinational Association of Supportive Care in Cancer (MASCC) has developed evidence-based recommendations for clinically assisted nutrition in patients with cancer, but they do not address specific indications for nutritional support beyond a recommendation not to pursue any form of clinically assisted nutrition for treatment of cancer cachexia [29].
Evidence to support benefit — The evidence to support benefit from either parenteral or enteral nutritional intervention in patients with cancer is limited:
●A systematic review of the literature by the American Gastroenterological Association (AGA) identified 26 randomized trials of parenteral nutritional support in cancer patients, including 19 in those receiving chemotherapy, three in patients being treated with radiation therapy (RT), and four in those undergoing stem cell transplantation [3].
Key observations included the following:
•In 19 trials with 1050 patients, the use of parenteral nutrition did not significantly decrease mortality.
•In eight trials that included 333 patients where information was available regarding overall complications, there was a statistically significant 40 percent increase in the total complication rate in the treated group. The incidence of infectious complications was significantly increased, by 16 percent.
•In 15 assessable trials that included 910 patients where tumor response data were provided, the tumor response rate was significantly lower (by an absolute value of 7 percent) in patients receiving parenteral nutrition.
●At least four systematic reviews have addressed the role of enteral/oral nutritional support in cancer patients; none demonstrates a survival benefit [2,30-32]. The most recent and largest of these included 13 randomized trials of oral nutritional intervention (dietary advice, oral nutritional supplements, or both) totaling 1414 participants with a variety of cancer types [30]. Trials were included if they were undertaken in adults who were clearly malnourished (although the definitions of malnourished differed according to trial) or were judged to be at risk for malnutrition on the basis of their clinical condition, and were receiving active anticancer treatment or palliative care; the included trials compared oral nutritional intervention with usual care.
Key observations included the following:
•All trials were judged to be of low to moderate quality and at risk for bias.
•There was considerable clinical (cancer site and stage, length and type of dietetic intervention, baseline nutritional status) and statistical heterogeneity among the trials. Only four defined baseline nutritional status as an inclusion criterion; six included both well-nourished and malnourished patients.
•Nutritional intervention was associated with statistically significant improvements in weight (mean difference 1.8 kg) and energy intake (mean difference 432 kcal) compared with routine care; however, these differences were no longer apparent when the data from trials that contributed the most to statistical heterogeneity were removed from the analysis.
•Nutritional intervention provided significant benefit for some aspects of quality of life (emotional functioning, dyspnea, loss of appetite, global quality of life) but had no impact on mortality (relative risk for death in the intervention group 1.06, 95% CI 0.92-1.22).
These data suggest that oral nutritional interventions might improve some aspects of quality of life in cancer patients who are malnourished or at risk for malnutrition, but they do not appear to improve cancer outcomes.
The best patients for consideration of nutritional intervention have a potentially curable disease or look forward to the promise of a long disease-free period after cancer treatment. The following sections will describe the use of and evidence for the benefit of nutritional support in specific clinical scenarios.
Specific clinical scenarios in which nutritional support may be considered
The perioperative setting — Preoperative malnutrition is associated with poor postoperative outcomes in patients undergoing surgery for cancer [33-36]. Although multiple studies have failed to demonstrate a survival benefit from perioperative nutrition support in patients undergoing major cancer surgery [37-40], others have documented fewer operative complications and a shorter length of hospital stay in malnourished patients who receive nutritional support [19,41-43]. In general:
●Patients undergoing major surgery for cancer who have severe malnutrition may derive benefit from nutritional support and, if feasible and safe, delaying surgery to be fed.
●Patients clearly benefit more from enteral feeding, whenever possible, rather than total parenteral nutrition (TPN), as TPN is associated with an increased risk for infectious complications. However, TPN may be justified in a malnourished patient undergoing cancer surgery when enteral nutrition is not a viable option and where there is a strong possibility that a patient may be cured of his or her malignancy or attain a substantial improvement in survival as a result of cancer therapy. Even under these circumstances, the benefits of parenteral nutrition must be counterbalanced by the risks associated with its use.
●The role for immunonutrition (ie, enteral formulas that are supplemented with L-arginine, RNA nucleotides, and omega-3 fatty acids) is unclear. Thus far, there is insufficient high-quality evidence to suggest any specific amino acid or other supplementation for surgical patients with cancer. This subject is discussed in detail elsewhere. (See "Overview of perioperative nutrition support".)
Hematopoietic cell transplantation — The majority of patients who undergo allogeneic hematopoietic cell transplantation (HCT) develop significant mucositis and have difficulty maintaining adequate caloric intake. The degree of mucositis is related to the particular cytotoxic regimen. Oral intake may be further compromised by the development of acute graft-versus-host disease (GVHD) affecting the alimentary tract. Parenteral nutritional support is commonly administered prophylactically to such patients until they are able to maintain adequate oral nutritional intake, which usually does not occur until the bone marrow recovers. (See "Oral toxicity associated with systemic anticancer therapy" and "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease".)
Total parenteral nutrition — Initial support for the routine use of TPN during HCT was provided by an older study that randomly assigned 137 previously well-nourished patients undergoing HCT for a variety of different malignancies (predominantly acute leukemia) to either prophylactic TPN or intravenous maintenance fluids (5 percent dextrose, electrolytes, minerals, trace elements, and vitamins) [44]. Treatment was initiated during cytoreductive chemotherapy, and continued for four weeks following transplantation. Compared with controls, patients receiving TPN had significantly better overall and disease-free survival, and a longer time to relapse. This difference occurred despite the fact that 61 percent of control patients eventually started TPN because of a decline in nutritional status.
In part because this study was performed a number of years ago, many questions regarding nutritional support in the setting of HCT remain unanswered. The care of patients undergoing HCT has undergone marked change over the last 20 years. Hospital stays are shorter, and with other improvements in supportive care (eg, better antiemetics, use of recombinant hematopoietic growth factors, better prophylaxis against GVHD), and the increasing use of autologous transplantation, the appropriate use of TPN in transplant patients is deserving of future trials.
These additional studies have not provided firm support for the routine use of TPN in patients undergoing HCT:
●In one trial, 57 patients undergoing HCT were randomly assigned to prophylactic TPN or to an enteral feeding program [45]. TPN was associated with significantly more days of diuretic use, more frequent hyperglycemic episodes, and more catheter-related complications. This study was smaller than the trial referenced above, but nonetheless suggests that the role of TPN in patients undergoing HCT deserves further investigation.
●In a second trial, 258 patients who were discharged following marrow infusion were randomly assigned to either TPN or intravenous hydration [46]. TPN did not influence the rate of hospital readmission, relapse rate or overall survival [46]. In fact, patients undergoing TPN had a longer median time to resume >85 percent of their caloric requirement (16 versus 10 days), suggesting that the administration of TPN suppressed the return of normal appetite. Furthermore, nutrition-related costs were 2.3-fold greater in the TPN group. Although this study did not examine the issue of whether prophylactic TPN is indicated in patients who receive HCT, it does suggest that after hospital discharge, TPN does not appear to be necessary in all patients.
One study attempted to define specific subgroups of patients who had hematologic malignancies, who were undergoing intensive cytotoxic chemotherapy with or without HCT, and who were likely to require TPN [47]. The following criteria were used to define the need for TPN:
●Severe malnutrition at admission
●A prolonged period (7 to 10 days) of minimal oral intake
●Clinical weight loss during treatment exceeding 10 percent of body weight
Using these definitions, TPN was judged to be necessary in only 55 percent of patients undergoing HCT, ranging from 37 percent of autologous recipients, to 92 percent of those receiving an HLA mismatched allograft (the latter being associated with a higher rate of GVHD). (See "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease" and "Donor selection for hematopoietic cell transplantation".)
Further studies will be required to determine whether TPN should be used based on need, or prophylactically in all patients regardless of nutritional status. Until then, it seems prudent to administer TPN to patients who are undergoing HCT and who have severe mucositis or gastrointestinal manifestations of GVHD, when a long period of insufficient oral intake is anticipated.
Glutamine supplementation — Glutamine is an important precursor for nucleotide synthesis, and an important fuel source for rapidly dividing cells, such as the lining epithelia of the GI tract. Furthermore, glutamine is postulated to facilitate healing of the GI mucosa following damage by either radiation therapy (RT) or chemotherapy [48]. Although considered a nonessential amino acid, glutamine is a conditionally essential amino acid during periods of stress [49]. It is not usually included in TPN formulations due to stability issues.
Animals sustained on TPN develop atrophy of the gut, an effect that may be ameliorated by glutamine supplementation [50,51]. These data have led to the study of glutamine supplementation, both parenterally and enterally, in patients undergoing hematopoietic cell transplantation.
Parenteral supplementation — It cannot be definitively concluded based on the limited available data that there is benefit for parenteral glutamine supplementation in patients undergoing HCT.
Two small trials have evaluated the role of parenteral glutamine supplementation in patients undergoing HCT [52,53]:
●In one study, 45 patients undergoing allogeneic HCT for hematologic malignancies were randomly assigned to parenteral TPN with glutamine supplementation (0.57 g/kg per day) or an isocaloric, isonitrogenous glutamine-free TPN formula [52]. The glutamine-supplemented group had significantly lower infection (13 versus 43 percent) and colonization rates, better nitrogen balance, a decreased incidence of infection, and a shorter length of stay (29 versus 36 days).
●In a second report, 29 patients with both hematologic and solid malignancies undergoing either allogeneic or autologous HCT were randomly assigned to supplemental parenteral glutamine or placebo [53]. Despite finding a similar six day shorter length of hospital stay in the glutamine group, there were no significant differences in the incidence of positive bacterial cultures, clinical infections, or mortality.
Enteral supplementation — At least two trials of oral glutamine supplementation have failed to confirm any benefit in patients undergoing HCT:
●In the first, 193 patients undergoing autologous or allogeneic HCT were randomly assigned to oral glutamine (1 gm/m2 four times daily) or supplemental glycine (placebo) from days 1 through 28 [54]. The glutamine-supplemented group undergoing autologous HCT had significantly less mouth pain and opiate use than controls, but no difference was seen in the allogeneic patients. The authors postulated an interaction with the individual chemotherapy regimens to explain this difference.
●In a similarly designed second study, 66 patients with either hematologic or solid tumors undergoing allogeneic or autologous HCT were randomly assigned to oral glutamine (30 gm per day) or a glycine placebo [55]. There were no significant differences between the groups in length of hospital stay, number of TPN days, neutrophil recovery time, incidence of positive blood cultures, sepsis, mucositis, or diarrhea. There was only a suggestion of improved long-term survival with glutamine, and a possible reduction in the need for TPN.
Thus, the impact of oral glutamine supplementation to prevent gut atrophy and decrease mucositis and infectious complications in patients undergoing HCT remains controversial.
Head and neck cancer — Head and neck cancer (HNC) is commonly diagnosed at an advanced stage. In addition to the alterations in chewing and swallowing that can accompany specific tumors or their surgical treatment, aggressive chemotherapy and RT can lead to dysphagia, odynophagia, and dehydration, all of which may result in malnutrition, treatment interruption, and morbidity [56]. (See "Management and prevention of complications during initial treatment of head and neck cancer" and "Management of late complications of head and neck cancer and its treatment" and "Health-related quality of life in head and neck cancer" and "Overview of treatment for head and neck cancer".)
Nutritional support during RT and combined modality therapy — Many patients with HNC undergo radiation therapy (RT) rather than surgery for local control. Concurrent or sequential chemotherapy and RT represents a promising approach for patients with advanced HNC, particularly for preservation of organ function. However, combined therapy is associated with enhanced mucosal toxicity; loss of 8 to 10 percent of body weight is common, even with early nutritional support [57,58]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)
Research has focused primarily on three areas: nutritional support versus no support, prophylactic versus "as needed" support, and the optimal way to deliver enteral nutrition (gastrostomy versus nasogastric tube [NGT] feeding).
Support versus no support — Retrospective series suggest that patients with HNC who receive nutritional support have less weight loss and fewer hospitalizations for treatment-related complications. As an example, in an observational series of 88 patients with locally advanced HNC treated with accelerated twice-daily RT (n = 59) or concurrent chemoradiotherapy (n = 29), 36 had undergone gastrostomy tube placement prior to starting therapy [59]. Enterally supplemented patients had significantly less average weight loss during therapy (3.1 versus 7.0 kg), required significantly fewer hospitalizations for dehydration and malnutrition, and had fewer interruptions in their cancer treatment (0 versus 18 percent). (See "Management and prevention of complications during initial treatment of head and neck cancer" and "Gastrostomy tubes: Uses, patient selection, and efficacy in adults".)
On the other hand, whether the benefits of enteral nutritional support translate into better outcomes from cancer therapy is unclear. In a randomized trial, 40 patients with inoperable squamous cell carcinoma of the nasopharynx and oropharynx were randomly assigned to oral nutrition or intensive nasogastric tube feedings during RT [60]. Despite the significantly higher caloric intake of the NG-supplemented group, and less weight loss during treatment in this group, radiation response rates and overall survival were similar. Slightly more patients who received tube feedings returned to their regular activities after six months of follow-up, compared with controls (62 versus 45 percent). This trial had limited power to find significant differences with its small sample size.
Prophylactic versus as needed support — Although the comparative evidence is not robust, retrospective and prospective studies comparing prophylactic with "as needed" feeding tube placement in patients receiving chemoradiotherapy for HNC have come to the following conclusions [61]:
●One trial showed a modest improvement in malnutrition with prophylactic therapy [62], but among lower quality studies, there were no differences in body mass index (BMI) at six months posttreatment or in the amount of weight loss during treatment [63-69].
●Only one [64] of five studies [63-67] found that prophylactic feeding tubes prevented unplanned treatment interruptions.
●No study reported better disease-free survival with prophylactic nutritional support [62,65-69].
Feeding tubes can adversely affect quality of life (QOL) by interfering with family life, intimacy, and social activities [70]. However, two prospective randomized trials found that, after an initial decline, HNC patients who were receiving chemoradiotherapy and were randomized to receive feeding tubes had improved QOL at six months post completion of treatment [62,66]. Given the limited available data, the end decision regarding the preventative use of feeding tubes needs to be made on a case-by-case basis, taking into account the clinical status of each individual patient and their values, concerns, and preferences.
Gastrostomy versus nasogastric tube versus oral support — The optimal method of nutritional support for HNC is not established. In the absence of well-conducted, robust clinical data, it is impossible to provide definitive conclusions on whether gastrostomy feedings or NGT feedings are preferable. In our own anecdotal experience, however, the NGT seems less preferable to gastrostomy placement in the eyes of health care providers because of discomfort, negative cosmetic effects, fears of erosion of the tubing into surrounding structures as it sits in the nostril and descends beyond the oropharynx, less secure positioning, and even hypothetical concerns for tumor seeding with initial insertion. However, decisions need to be undertaken on a case-by-case basis with input from the patient and other members of the health care team.
In uncontrolled studies of patients undergoing combined modality therapy for HNC, prophylactic nutritional support has been associated with increase in body weight, preservation of pretreatment nutritional status, improved QOL, fewer toxicity-related treatment interruptions, and shorter duration of hospitalization [71-75]. However, as with RT alone, it is unclear whether the enteral nutritional support improves overall outcomes from therapy, especially survival; prospective investigations have not been conducted.
There is insufficient evidence to determine the optimal method of enteral feeding in HNC patients who are receiving multimodality therapy [76]. A single randomized trial comparing gastrostomy with NGT approaches in patients undergoing chemoradiotherapy for HNC (which closed early for slow accrual with only 33 patients eligible for analysis) concluded that there were no significant differences in complication rates or patient assessment of QOL; gastrostomy feedings were 10 times more costly than NGT feedings, and the duration of gastrostomy tube use was significantly longer (139 versus 66 days) [77].
Additional data are available from two retrospective comparative studies. In one, gastrostomy feeding was associated with better cosmesis, mobility and QOL [72], while the other suggests that nutritional support delivered through a gastrostomy was associated with a longer duration of support (28 versus 8 weeks) and more dysphagia after completion of treatment [73]. Approximately 8 to 20 percent of long-term survivors become gastrostomy tube-dependent. Preexisting swallowing difficulties and advanced T-stage were associated with an increased risk of prolonged gastrostomy tube dependence.
Long-term QOL may be affected by the prolonged presence of gastrostomy tubes following primary surgery for oral and oropharyngeal cancers [78]. Follow-up of 243 patients who had surgery for oropharyngeal cancer noted that those patients with gastrostomy tubes still in place (median 34 months) had a poorer QOL than patients who had their gastrostomy tubes removed (median seven months) [70]. The major gastrostomy tube-related problems were not leakage, blockage, or discomfort, but interference with family life, intimate relationships, social activities, and hobbies. It should be noted that these data do not prove that poorer QOL in long-term gastrostomy tube patients is necessarily due to the gastrostomy tubes that are present, which could be influenced by the fact that patients with more severe disease (cancer and/or complications of cancer treatment) need to have the gastrostomy tubes in place for a longer time.
For patients who are able to swallow, aggressive oral nutritional support may provide similar benefit to gastrostomy feedings, as illustrated by the following two trials:
●In one small trial, patients undergoing RT for HNC were randomly assigned to aggressive oral feeding with nutritional supplements or no additional nutritional support [79]. Treatment-related toxicity necessitated interruption of RT in significantly more patients not receiving nutritional support (5 of 12 compared with 0 of 11). However, radiation outcomes were not reported.
●A benefit for dietary counseling was suggested in a trial in which 75 patients with HNC undergoing RT were randomly assigned to dietary counseling with regular foods (n = 25), usual diet plus supplements (n = 25), or usual diet only [80]. At three months, patients who received dietary counseling improved their oral intake, while those in the other two groups returned to, or below, baseline. The dietary counseling group also had the greatest improvement in anorexia, xerostomia, and dysgeusia at three months. QOL outcomes also favored dietary counseling.
Immunonutrition versus standard nutrition — Immunonutrition refers to enteral formulas that are supplemented with L-arginine, RNA nucleotides, and omega-3 fatty acids. Benefit of immune-enhanced nutritional support in the perioperative setting is unclear and is addressed elsewhere and below. (See "Overview of perioperative nutrition support", section on 'Immune-enhancing nutritional supplements' and 'Perioperative nutritional support' below.)
The benefit of immunonutrition versus standard nutrition for patients undergoing chemoradiotherapy was addressed in a systematic review and meta-analysis; of the 27 included trials, six were conducted entirely in head and neck cancer [81]. The trials were generally small (ranging from 17 to 70 patients). Among this subgroup, the risk of oral mucositis was not significantly improved by the use of immunonutrition (risk ratio 0.97, 95% CI 0.92-1.02).
Perioperative nutritional support — Malnourished patients who are undergoing resection for HNC may benefit from perioperative nutritional support. In one report, factors associated with the need for long-term nutritional support included heavy alcohol use, tongue base surgery or pharyngectomy, myocutaneous flap reconstruction, or the need for postoperative RT [82].
The benefit of immunonutrition in this setting is controversial as indicated by the following data:
●In one double-blind trial, 136 patients undergoing resection for HNC were randomly assigned to perioperative nutritional supplementation with arginine, omega-3 fatty acids and RNA, or a standard enteral nutritional formula [83]. Patients receiving the supplemented formula had significantly fewer postoperative infectious complications and a higher serum albumin concentration when compared with standard formula.
●Contrasting results were noted in a second small trial of 49 patients who had HNC and a preoperative weight loss >10 percent of body weight and who were randomly assigned to standard postoperative tube feeding, preoperative plus postoperative tube feeding, or arginine-supplemented preoperative and postoperative tube feeding [84]. Compared with only postoperative feeding, preoperative enteral nutrition with or without arginine supplementation did not significantly improve nutritional status, decrease the incidence of major postoperative complications, or alter survival.
Perioperative immunonutrition is addressed in detail elsewhere. (See "Overview of perioperative nutrition support", section on 'Immune-enhancing nutritional supplements'.)
Esophageal cancer — Nutritional issues are important for patients with localized esophageal cancer. Many of these patients present in a nutritionally depleted state from progressive dysphagia. Some degree of malnutrition is present in up to 80 percent of patients at presentation [85,86]. (See "Clinical manifestations, diagnosis, and staging of esophageal cancer", section on 'Clinical manifestations'.)
Patients who undergo multimodality therapy for esophageal or esophagogastric junction (EGJ) cancer often have significantly worse nutritional parameters than do those who only undergo resection [87]. The side effects of chemotherapy include nausea, vomiting, and diarrhea; the use of concurrent radiation therapy frequently causes odynophagia that further aggravates preexisting dysphagia [88,89]. Malnutrition itself reduces the rate of patient tolerance of a complete chemoradiotherapy regimen [90], and it becomes an even more important issue among patients who are candidates for esophagectomy following chemoradiotherapy [87,91,92]. (See "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus" and "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas".)
Many patients who are able to eat upon initial presentation will require some form of supplementation during the course of therapy [90,93]. Because of this, some centers advocate routine placement of a feeding tube in all patients undergoing multimodality treatment [94,95], although this is not a universal practice.
Early evaluation and intervention by a dietitian can identify patients who have nutritional risk factors [96], and who may benefit from close nutritional monitoring and potentially from nutritional interventions [95,97]. Dietary measures alone (oral nutritional supplements, frequent small meals during treatment with avoidance of abrasive, spicy, or acidic foods) may allow some patients to maintain nutrition through the course of therapy [85]. While the use of oral nutritional supplementation does not dramatically alter surgical outcomes [98-101], it improves perioperative weight gain [102,103].
Patients who fail conservative measures may need additional nutritional supplementation. While the evidence base to support the benefit of supplemental feeding is weak, retrospective series suggest that nutritional support may improve the higher mortality associated with preoperative nutritional depletion in patients undergoing neoadjuvant chemoradiotherapy, and prevent further nutritional deterioration [104-106]. In a retrospective review of 30 patients who were unable to maintain an oral diet and who received total parenteral nutrition (TPN) during neoadjuvant therapy for esophageal cancer, the patients receiving TPN tolerated higher doses of chemotherapy than did those who did not, and their surgical outcomes were similar to that of patients who were able to maintain an oral diet [99]. Whether the benefit had anything to do with TPN, or was simply a reflection of patient selection bias is unclear.
Although randomized trials have failed to demonstrate either improved treatment tolerance, or a survival benefit from nutritional support, they were not restricted to malnourished patients [98-101]. Benefit has been shown when this intervention is restricted to malnourished patients undergoing major cancer surgery. (See 'The perioperative setting' above.)
Timing of the nutritional support may also be a relevant factor. Many studies have provided only postoperative nutritional support. Others have noted a trend toward a decrease in major postoperative complications in esophageal cancer patients who were malnourished and who received TPN prior to surgery when compared with those who did not receive TPN or received it only after surgery [107].
Special issues related to enteral feeding support — For patients who need adjunctive nutritional support, enteral nutritional support is generally seen as superior to parenteral nutrition in a patient with a functioning gut. In the postoperative setting, it is associated with fewer complications and more efficacious reversal of malnutrition. (See 'The perioperative setting' above.)
There are some special considerations for enteral feeding support in patients who are being treated for esophageal cancer:
●Most of the experience with tube feeding in cancer patients comes from the use of gastrostomy tubes. However, gastrostomy tubes are sometimes avoided in operable patients with esophagus cancer because of the risk of injuring the gastroepiploic artery, thus rendering the stomach unusable as a replacement conduit for the esophagus. However, others have shown that gastrostomy placement is safe in the setting of esophageal cancer, and that it does not compromise the stomach or esophagogastric anastomosis [95].
Gastrostomy tube placement using a pull-through technique may risk tumor seeding from the tumor site to the gastrostomy tract by mechanical transfer [108]. Although the magnitude of this risk and the clinical consequences are not entirely clear, alternative means of gastrostomy tube placement (eg, direct insertion) may be better for such patients. (See "Gastrostomy tubes: Complications and their management", section on 'PEG tract tumor seeding'.)
●Placement of a jejunostomy (J) tube avoids potential injury to the stomach. J tubes can be placed using either an open or a laparoscopic technique. J tubes can also be placed via a percutaneous endoscopic technique, but compared with gastrostomy tubes, rates of moderate to severe complications are higher (2 to 10 percent), and success rates are lower (approximately 70 percent). (See "Enteral feeding: Gastric versus post-pyloric".)
Patients with cancer at the end of life — For most patients with advanced cancer who are terminally ill and who have an estimated life span that is measured in weeks to a few months, we suggest against the use of enteral or total parenteral nutrition support.
The great majority of patients in the terminal phase of an advanced illness, such as cancer, reduce their oral intake before death, either voluntarily or because they are unable to take in sufficient nutrients and fluids for a variety of reasons, such as appetite loss, nausea, vomiting, dysphagia, generalized weakness, gastrointestinal tract obstruction, or impaired cognition. While nutrient supplementation might appear ideal to control or reverse malnutrition, the routine use of nutritional support in patients with advanced incurable cancer is associated with a higher risk of treatment-related complications, and no evidence of a survival benefit, although the quality of the evidence is low [2,3,109-113]. Several groups such as the Working Group for Developing Guidelines for Parenteral Nutrition of the German Association for Nutritional Medicine, the NCCN [27], and the American Society of Parenteral Nutrition (ASPEN), specifically recommend against routine administration of parenteral nutrition in patients with advanced cancer [22,114,115]. (See "Stopping nutrition and hydration at the end of life", section on 'Use of artificial nutrition'.)
However, in highly selected patients (eg, high-grade bowel obstruction or malabsorption from advanced cancer) who might otherwise have a prognosis that is measured in several months or years, home parenteral nutritional support may be considered after extensive deliberation among the health care staff, the patient, and caregivers [116,117]. Even under such circumstances, however, the use of parenteral nutrition is the exception rather than the rule. Central venous access device selection, which is based in part on anticipated duration of use, is discussed in detail elsewhere. (See "Central venous access: Device and site selection in adults", section on 'Factors influencing catheter selection'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Nutrition support (parenteral and enteral nutrition) in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Managing loss of appetite and weight loss with cancer (The Basics)" and "Patient education: Malnutrition (The Basics)" and "Patient education: Malnutrition – Discharge instructions (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Nutritional status and cancer outcomes
•Malnutrition occurs in 40 to 80 percent of cancer patients (especially upper aerodigestive tract tumors) and is a major cause of morbidity and mortality in those with advanced disease. Malnutrition is associated with poorer overall survival, reduced benefit from cancer therapy, increased chemotherapy-related toxicity, and poorer quality of life. (See 'Nutritional status and cancer outcomes' above.)
•In some cases, malnutrition may be related to an inability to ingest or absorb nutrients because of the primary disease process or its treatment, but in most cases, it is attributable to cancer-associated anorexia/cachexia syndrome. (See "Pathogenesis, clinical features, and assessment of cancer cachexia".)
Use of the term "malnutrition" does not indicate that the provision of nutrition is the answer to this set of circumstances.
•Multiple scores are available for assessing nutritional status of cancer patients. One simple to use and objective tool is the Nutritional Risk Index. (See 'Screening for nutritional status' above.)
●Indications and benefits of nutritional support
•Nutritional support may improve outcomes in selected cancer patients. However, due to the paucity of evidence demonstrating benefit, the indiscriminate use of enteral or parenteral nutrition in well-nourished or mildly malnourished patients with cancer is not recommended. (See 'Indications and benefits of nutritional support in cancer patients' above.)
•Oral nutritional interventions might improve some aspects of quality of life in cancer patients who are malnourished or at risk for malnutrition, but they do not appear to improve survival.
•Parenteral or enteral nutritional supplementation may be an appropriate option for cancer patients who meet both of the following criteria:
-They are either notably malnourished or at risk of becoming so during cancer treatment.
-They have a potentially curable disease or look forward to the promise of a long disease-free period after cancer treatment.
•Among patients with advanced incurable cancers, total parenteral nutrition appears to be justified only if the patient has trouble with oral or enteral nutrition because of intestinal failure (eg, short bowel syndrome or unresectable obstruction) and if they otherwise have a prognosis that would likely be measured in terms of many months or years. Even under these circumstances, the benefits of parenteral nutrition must be counterbalanced by the risks associated with its use. (See "Overview of perioperative nutrition support".)
●Specific clinical scenarios in which nutritional support may be considered
•Given the results of available randomized trials, we recommend that adjunctive nutritional therapy for cancer patients be limited to the following circumstances (Grade 1B):
-Malnourished patients who are undergoing major abdominal surgery. (See 'The perioperative setting' above.)
-During hematopoietic cell transplantation for patients who have severe mucositis or gastrointestinal manifestations of graft-versus-host disease, when a long period of insufficient oral intake is anticipated. (See 'Hematopoietic cell transplantation' above.)
-During combined modality therapy for head and neck cancer. (See 'Head and neck cancer' above.)
•A role of nutritional support in patients with localized esophageal cancer who are undergoing concurrent chemotherapy and radiation therapy followed by surgery is less clear. Although some centers advocate routine placement of a feeding tube in all patients undergoing multimodality treatment, this is not a universal practice. The use of nutritional support in these patients should be decided on a case-by-case basis. (See 'Esophageal cancer' above.)
●Patients with cancer at the end of life – For most patients with advanced cancer who are terminally ill and who have an estimated life span that is measured in weeks to a few months, we suggest against the use of enteral or total parenteral nutrition support (Grade 2C). (See 'Patients with cancer at the end of life' above.)
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