Malnutrition ‘almost epidemic’ among patients with advanced cancer

Malnutrition is one of the most common — and most serious — side effects of cancer and its treatment.

The condition affects up to 80% of patients depending on tumor type and stage, according to NCI, and is responsible for nearly one in five cancer-related deaths.

“Malnutrition is very widespread — almost epidemic,” David Jennings II, MSN, RN, AGPCNP-BC, oncology nurse practitioner at Levine Cancer Institute at Carolinas HealthCare System and a HemOnc Today Editorial Board member, told HemOnc Today. “Almost everyone I see is either malnourished or at very high risk for being malnourished. We in the oncology community should be more proactive in identifying and managing at-risk patients.”

Despite its prevalence, malnutrition remains one of the least researched and most undertreated cancer-associated adverse events.

As little as a 5% drop in weight can predict shorter survival. When physicians ask dieticians to intervene on behalf of patients with severe weight loss — often used as a diagnostic criterion for malnutrition — often little can be done to reverse the condition’s course.

“Nutritionists and oncologists need to be locked in the same room and collaborate to provide a treatment plan that will benefit patients who have very high risk for poor cancer outcomes because they are malnourished,” Vickie Baracos, PhD, professor of palliative care medicine and a lead researcher in oncology and metabolism at University of Alberta in Canada, told HemOnc Today. “These providers’ fundamental approaches to dealing with someone at nutritional risk are completely different.”

Photo by Ross Neitz, courtesy of University of Alberta.

HemOnc Today spoke with oncology care providers about the importance of monitoring for malnutrition in patients diagnosed with cancer; best practices for prevention, assessment and management; how patients’ nutritional needs evolve during treatment and in the survivorship phase; and the impact diet and nutrition may have on cancer outcomes.

‘Part of the cancer experience’

Depending upon tumor type, up to 80% of patients with cancer experience significant involuntary weight loss, defined as at least 10% of total body weight lost within 6 months. This often is associated with treatment interruption, infections, hospital readmission and early mortality, according to a study published in Journal of Oral and Maxillofacial Pathology.

Many oncologists overlook weight loss as an early indicator for malnutrition, which occurs when individuals do not get enough calories or consume the appropriate amount of key nutrients.

“There is a certain level of tolerance,” Declan Walsh, MD, MSc, chair of the department of supportive oncology at Levine Cancer Institute, told HemOnc Today. “Clinicians will say, ‘Well, of course you’re not eating properly, you have cancer.’ In other words, it is just accepted as being part of the cancer experience.”

Patients’ weight at diagnosis also may lead clinicians to overlook malnutrition, Walsh said. NIH data show 69% of American adults are overweight or obese.

“Because of the obesity epidemic, somebody could present to a physician having lost 15% of their pre-illness body weight and are at serious nutritional risk,” Walsh said. “But they look OK because they were so overweight before they got cancer and they do not have the traditional cachexic appearance.”

Monitoring involuntary weight loss in combination with BMI has been standard to determine malnutrition among patients with cancer.

Clinicians also should monitor patients’ muscle mass to detect sarcopenia — or low muscle mass — and cancer-related malnutrition.

“If you stand at the front door of a cancer center anywhere in North America — even in an advanced-disease, metastatic setting — you’d be hard-pressed to find even 1% or 2% of patients who are visibly malnourished,” Baracos said. “This lends itself to the conclusion by most oncologists that they have other things more important to worry about. Although they may recognize their patients are losing weight, they may not see that as being an imminent challenge to their well-being, even though the weight-losing cancer patient has a terrible prognosis.”

Weight loss and BMI can independently predict cancer survival.

A study by Martin and colleagues — published in 2015 in Journal of Clinical Oncology — showed that weight-stable patients with a BMI at or above 28 survived nearly five times longer (20.5 months; 95% CI, 17.9-23.9) than those who lost 15% or more of their body weight and recorded a BMI of 22 or less (4.3 months; 95% CI, 4.1-4.6).

“That paper shows that — regardless of whether your starting body weight is large, medium or small — weight loss is still highly associated with mortality,” Baracos said.

This issue is “the elephant in the room in cancer care,” Walsh said.

“We know that being cachexic leads to worse outcomes from surgery, more side effects from chemotherapy or radiation therapy, and a serious impairment in life expectancy,” he said. “Lack of attention to this is a significant issue.”

Several factors contribute to weight loss among patients with cancer. These include tumor location, surgery, chemotherapy, radiation and stress. Treatment side effects — such as nausea, vomiting, diarrhea, anorexia, mouth sores, difficulty swallowing, taste changes and poor appetite — also play a role.

“Malnourished patients are often unable to withstand the rigorous and aggressive treatments that best treat the cancer, and that may mean they have to reduce doses or take breaks from treatment,” Rachael Lopez, MPH, RD, clinical research dietician for surgical oncology and cancer immunotherapy at the NIH Clinical Center, told HemOnc Today. “This ultimately leads to a suboptimal treatment plan, which translates to poor cancer outcomes.”

Patients with head and neck cancers who undergo surgery around their esophagus, mouth or nasal cavity can have difficulty eating and swallowing. Those with solid tumors who require radiation can experience painful symptoms such as mucositis and esophagitis.

“Radiation therapy can destroy taste buds and salivary glands, which changes the pH of your mouth,” Jennings said. “Patients with lung cancer who undergo radiation are at similar risk. Depending on the size and location of the radiation field, their gastrointestinal health can be at risk, and pain and reflux symptoms can occur. These are all factors that discourage patients from eating.”

Chemotherapeutic agents such as carboplatin and cisplatin are platinum based, often producing a metallic taste in a patient’s mouth. For that reason, Jennings said he encourages those patients not to eat with metal forks and spoons.

Improved monitoring

Adults routinely lose muscle at a rate of 0.3% per year as part of the normal aging process. However, patients with cancer may lose 3.3% of muscle each year.

Sarcopenia can occur 10 to 25 times faster among patients who receive chemotherapy or radiation, Baracos said. Patients who require bone marrow transplants can experience even greater losses of muscle mass.

“It’s like aging 10 years in 1,” Baracos said. “One of the big issues is that no action is being taken until the malnutrition gets very bad. Leaving it until then is completely missing the opportunity for effective intervention.”

Despite the consequences of late action, muscle loss and other effects of malnutrition often go unaddressed.

“Oftentimes when people are referred to a dietician, it is already late in the game,” Walsh said. “By the time malnutrition is obvious, it may already be too late to do something about it.”

However, measuring muscle loss can be one piece of the puzzle in identifying risk for malnutrition early on.

Before 2007, clinicians often determined malnutrition by a patient’s weight in relation to his or her height. Over the past decade, cancer centers have identified additional markers, such as caloric intake, body fat, muscle mass, fluid accumulation and grip strength.

At NIH, it is standard for a registered dietitian to screen each inpatient for nutrition risk and to follow-up with a nutrition assessment and plan for each patient found to be at risk. In outpatient centers, tools such as the Nutrition Risk Screening 2002 (NRS 2002) survey, a validated five-question survey, can be used at diagnosis and during each outpatient visit to assess for nutrition risk.

“NRS 2002 is one screening tool to catch people before they’ve lost 20% of their body weight, or before they’ve lost so much lean body mass that they are unable to perform their activities of daily living,” Lopez said.

Clinicians at Levine Cancer Institute assess patients with a validated malnutrition screening tool. The electronic survey alerts the nutrition department if a patient is at risk.

“It puts the patient on the nutritionists’ radar,” Jennings said. “They can contact the physician and be proactive about it instead of waiting until malnutrition becomes problematic during treatment.”

Many cancer centers have adopted the use of CT to measure muscle loss in patients with cancer.

“All you’re really doing is putting body weight under a different lens and quantifying the muscle and fat tissues,” Baracos said. “It is a paradigm change. [Previously], all we ever asked was how much patients weighed and how tall they were. Using diagnostic imaging to reveal the exact composition of a person’s body is regarded as a gold standard.”

Toxicity vs. nutrition

Metabolic changes also may drive cancer-associated malnutrition, meaning it can only be partially reversed by conventional nutritional support.

Negative energy balance and skeletal muscle loss due to metabolic derangements — such as insulin resistance and systemic inflammation — can lead to malnutrition, according to European Society for Parenteral and Enteral Nutrition guidelines issued last year.

“Having those patients eat more and more calories does not work because they have such bad metabolic dysfunction,” Colin Champ, MD, radiation oncologist at UPMC Cancer Center and co-author of several studies on malnutrition in patients with cancer, told HemOnc Today. “Those are the cases that are extremely difficult and, frankly, we have no solution.”

Oncologists and nutritionists often debate the toxicity of treatments and their impact on patients already at risk for malnutrition. Chemotherapy dosing is frequently based on overall body weight, not lean tissue. Although researchers in France are comparing dosing in patients with varying body compositions, there are many unknowns.

“Theoretically, if the amount of chemotherapy is scaled to body weight, a very heavy person will get a large dose,” Baracos said. “If, however, that dose effectively partitions and is metabolized in the nonfat part of the body, very big people with very bad muscle wasting may be overdosed.”

If a malnourished patient is at risk for severe treatment toxicity, dose reduction could be considered, Baracos said.

However, to help a patient stay nourished and avoid scaling back on treatment, many nutritionists will attempt “every other intervention possible,” Lopez said.

“That might be medical management to improve appetite, control symptoms, or add nutritional supplements like fortified drinks that provide nutrition when people are unable to eat regular meals or tolerate solid foods,” Lopez said.

Patients who undergo stem cell transplants who are at risk for graft-versus-host disease, or those with gastric or esophageal cancer, sometimes require additional interventions.

Nutritionists may recommend enteral feeding tubes — which deliver nutrition through a tube into the gut — or parenteral feedings through IVs, Lopez said. These help prevent dose reductions and breaks from treatment.

Weighing the risks and rewards of enteral and parenteral feedings is a source of ongoing debate, Jennings told HemOnc Today.

“In our head and neck cancer population, the utilization of feeding tubes is somewhat controversial,” Jennings said. “Is it worth putting the patient at risk of complication and infection with an additional surgery? Some patients easily tolerate 7 weeks of radiation therapy with concurrent chemotherapy and never use a feeding tube, and others rely heavily on it.”

It is important for clinicians to understand that patients with cancer may continue to lose weight despite the fact they have a good diet or are on nutritional support, Walsh said.

Individualized diets

Dietary recommendations and studies often provide inconsistent and conflicting guidance about how to stay nourished during cancer treatments and into survivorship.

“It’s the most common question patients ask: ‘What should I eat?’” Champ said. “We should have an answer, but it is an epidemiologic minefield. The recommendations are all over the place.”

Champ and colleagues surveyed 21 National Comprehensive Cancer Network institutions. The results — published in 2013 in Nutrition and Cancer — showed only four of them provided dietary recommendations for patients with cancer on their websites. Of those four, two recommended diets that contained food rich in carbohydrates, protein and fat, and two recommended diets that primarily consisted of carbohydrate-rich foods.

“There is so much misinformation out there,” Lopez said. “A simple internet search of ‘diet and cancer’ will bring you pages and pages of fad diets that claim to cure cancer or diets recommending expensive supplements that have not been tested. For people searching for their cure [who] want to do everything they possibly can, it is really heartbreaking to see them spend their money on these unresearched supplements or to follow these very restrictive diets that end up making them malnourished.”

Some patients are “woefully malnourished” because they refuse to eat foods with carbohydrates, Lopez said.

“We have had patients unable to go through treatments because they are on so many supplements it is interfering with their liver function and it is not safe to start chemotherapy,” she added. “They are actually setting themselves back.”

A Women’s Intervention Nutrition Study showed an association between low-fat diet and reduced recurrence among certain women with breast cancer.

Long-term follow-up from that trial — presented in 2014 at San Antonio Breast Cancer Symposium — showed median survival was 11.7 years in the control arm, 13.6 years among women with ER–negative disease who received the dietary intervention (HR = 0.64; P = .045) and 14 years among women with ER/PR–negative tumors who received the intervention (HR = 0.46; P = .006).

However, low-fat, “cardiac prudent” diets may not be best for all patients with cancer, Champ said.

“A diet that includes healthy fats is prudent for everyone,” Champ said. “A lot of calorically dense foods that are traditionally shunned are nutrient-dense with minerals and vitamins, things cancer patients need.”

Champ encourages his patients to eat healthy sources of fats like eggs from free-range chickens from local farms.

“We know eggs from those chickens have higher amounts of nutrients and vitamins,” he said. “I don’t tell them to not eat meat. I tell them to eat better-sourced types of meat — beef from grass-fed cows, which has higher amounts of conjugated linoleic acid and omega-3 [fatty acids], which help fight breast cancer.”

American Cancer Society guidelines suggest a lower fiber diet for patients who experience diarrhea or cramping, and those who have trouble digesting food (see Table). Clinicians also may recommend this diet after certain types of cancer surgery.

Green, leafy vegetables offset toxins, can stimulate the immune system and are good for patients with cancer who are not on blood thinners, Champ said. Protein powders and medium chain triglycerides from coconut oil also are recommended to help spare muscle in patients with sarcopenia, he added.

Addressing the dietary needs of patients with cancer requires an individualized approach, said Champ, who spends up to 90 minutes discussing food options with his patients.

“I don’t just tell people to eat ‘low carb’ or ‘high carb’ or ‘low fat’ or ‘high fat,’” he said. “I go through the types of food they like and try to get them to eat the healthiest sources of those foods. It takes quite a bit of time, and I’m not sure everyone is up for that challenge.”

Stimulating appetite

The definition of healthy eating changes throughout a patient’s treatment course. It can be affected by their tolerance of treatments and other chronic conditions, such as high blood pressure, high cholesterol or diabetes.

“It can be very challenging to have two-thirds of your plate filled with fruits, vegetables, whole grains and lean proteins if you are having profuse diarrhea and should be limiting those types of foods because of treatments,” Lopez said.

Patients whose appetite is suppressed because of chemotherapy or radiation may benefit from megestrol acetate or dronabinol (Marinol, AbbVie), as well as corticosteroids such as dexamethasone or prednisone, or antidepressants such as mirtazapine (Remeron, Organon USA). However, megestrol acetate can increase the risk for blood clots or strokes, and dronabinol can increase fatigue.

“Because our patients are often experiencing treatment-related fatigue, we might not want to add a medication that would compound that problem,” Jennings said.

Simply increasing a patient’s appetite does not necessarily translate to better nutritional status, Walsh said.

“Early satiety is a very unrecognized symptom, where somebody is hungry and they have a spoonful or two of food and they think they are full and cannot eat anymore,” Walsh said. “If that is the case, maybe they are better off having six meals a day instead of three.”

Other, more practical strategies can enhance a patient’s appetite during treatment, Lopez said. She suggested patients avoid their favorite foods when their taste buds are compromised.

“When people lose their love for their favorite food because it tastes like cardboard, it can be very depressing,” Lopez said. “Once they are able to tolerate food without nausea and taste changes, I encourage patients who can leave their hospital beds to sit down at a table that’s nicely set for a home-cooked meal with loved ones.”

Oncologists, nutritionists and dieticians agree on the need for earlier intervention by nutritionists, as well as the need for increased research funding to study the nutritional needs of patients with cancer.

“We know that patients who have better nutrition tolerate chemotherapy more easily, which leads to improved outcomes,” Jennings said. “That’s why we frequently collaborate with our dieticians and nutritionists. The first remedy for malnutrition is prevention, and it is too great a task to tackle on our own. It takes a multidisciplinary approach.”

Baracos is on a research team studying more than 17,000 cases from 17 cancer centers to produce definitive criteria for diagnosing malnutrition in patients with cancer.

More research is needed in that area, as well as more comprehensive dietary recommendations for patients with specific cancers, Champ said.

“There are no good randomized studies and there absolutely should be,” Champ said. “We should know more about how diet impacts survival. We do not have the answers, but if we are not pushing research in that direction, how are we supposed to get closer to providing answers? If we want to give doctors the right things to say to patients, we have to come up with those answers.” – by Chuck Gormley

Click here to read the , “Do the benefits of a feeding tube outweigh the risks for a malnourished patient with cancer treated with curative intent?”

References:

Arends J, et al. Clinical Nutrition. 2016;doi:10.1016/j.clnu.2016.07.015.

Champ CE, at al. Nutr Cancer. 2013;doi:10.1080/01635581.2013.757629.

Chlebowski RT and Blackburn GL. Abstract S5-08. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-13, 2014; San Antonio.

de Melo Silva FR, et al. Nutr J. 2015;doi:10.1186/s12937-015.0113-1.

Dhanapal R, et al. J Oral Maxillofacial Path. 2011;doi:10.4103/0973-029X.86670.

Martin L, et al. J Clin Oncol. 2015;doi:10.1200/jco.2014.56.1894.

NCI. Basic principles of nutrition in patients with cancer. Available at: www.cancer.gov/about-cancer/treatment/side-effects/appetite-loss/nutrition-hp-pdq. Accessed on May 29, 2017.

For more information:

Vickie Baracos, PhD, can be reached at vbaracos@ualberta.ca.

Colin Champ, MD, can be reached at champce@upmc.edu.

David Jennings II, MSN, RN, AGPCNP-BC, can be reached at david.jennings@carolinashealthcare.org.

Rachael Lopez, MPH, RD, CSO, CDR, can be reached at rachael.lopez@nih.gov.

Declan Walsh, MD, MSc, can be reached at declan.walsh@carolinashealthcare.org.

Disclosure: Baracos, Champ, Jennings, Lopez and Walsh report no relevant financial disclosures.