How an epidemic of untreated malnutrition is worsening cancer

Abstract

Physicians have long observed that patients who have cancer and are also malnourished are more likely to die. Beyond making treatments less effective and more toxic, malnutrition can reduce a patient’s functional abilities and quality of life while increasing the risk of complications. For many decades, however, the surprisingly common and largely unresolved phenomenon of malnutrition in patients with cancer was seen as an inevitability.

Jann Arends, MD, a gastroenterologist, hematologist, and medical oncologist at the University of Freiburg in Germany, says that weight loss and emaciation were once taken for granted as a standard feature of intractable cancers. “Most cancers would not respond to even aggressive anticancer treatments, and weight loss was seen as a harbinger of death and not as a condition requiring supportive care,” Dr Arends says.

That mindset further solidified, he says, when clinical trials testing routine artificial nutrition (delivered via feeding tubes or intravenous lines) yielded no discernable benefits for patients but higher complication rates than oral feeding. In response, the American Society for Parenteral and Enteral Nutrition recommended not using artificial nutrition to treat patients with cancer and thus furthered what Dr Arends calls “nutritional nihilism in an age of only rare oncological success.”

As cancer treatment successes have multiplied during the past 15 years, however, more research has helped to change recommendations, refine the benefits and limitations of nutritional care in patients, and provide better estimates of just how common malnutrition can be.

One eye-opening 2014 study of approximately 1900 patients with cancer in 154 hospitals throughout France found that 39% were malnourished, including more than 60% of patients diagnosed with pancreatic, esophageal, or stomach cancer.¹

Although malnutrition rates tend to be higher in hospitalized patients, the condition also is common even in newly diagnosed patients. In 2017, the Prevalence of Malnutrition in Oncology study in Italy sought to get a better view of the nutritional status of adult patients at their first visit to a medical oncology center after being diagnosed with a solid tumor.² Conducted at 22 centers across the country, the observational study enrolled nearly 2000 patients. Oncologists used several scales, including the Mini Nutritional Assessment, to assess the patients for signs of nutritional impairment.

Collectively, they found that 51% of the patients had a nutritional impairment, 9% were overtly malnourished, and 43% were at risk for malnutrition. More than 40% had anorexia, or an abnormal loss of appetite, while 64% had lost weight during the previous 6 months. The results, the authors asserted, supported a “call to action” for oncologists to be more aware of the significant risk of malnutrition, even in patients with nonmetastatic cancer, and to make early screening and aggressive treatment a routine part of supportive cancer care.

As the French study suggested, some cancers are associated with malnutrition more than others. In a 2021 review, in fact, a separate group of Italian researchers concluded that the tumor subsite is one of the biggest determinants.³ From a decade’s worth of studies, they found, in agreement with the French study, that pancreatic, esophageal, and other gastroenteric cancers; head and neck cancers; and lung cancers are associated with the highest prevalence. Unsurprisingly, they also linked advanced stages of cancer to a higher risk of malnutrition as an expression of the combined effects of tumor burden, inflammatory status, reduced caloric intake, and malabsorption.

The nutritional deficiencies, in turn, can interfere with cancer treatments ranging from chemotherapy to surgery. Focusing on the latter, an international, multicenter study enrolled more than 5700 patients from 381 hospitals in 75 countries. As the researchers found, “severe malnutrition is common in patients undergoing surgery for gastrointestinal cancers and is a risk factor for 30-day mortality following elective surgery for colorectal or gastric cancer.”⁴ The results led the authors to conclude that “there is an urgent need to examine whether perioperative nutritional interventions can improve early outcomes following gastrointestinal cancer surgery worldwide.”

Cancer treatment likewise can increase the risk of nutritional deficiencies and form a kind of negative feedback loop in which escalating malnutrition can interfere with the treatment, further weaken the patient, and worsen outcomes. To counter that decline, experts such as Dr Arends now are calling for a more personalized nutritional and metabolic approach to providing targeted care, including muscle training and psychological support.

Malnutrition is further complicated by the varied forms that it can take. For example, inadequate food intake in an otherwise healthy person can initiate starvation metabolism, including ketosis, in which the body burns fat so that it can use the breakdown compounds—ketones—as fuel. The body’s primary goal during this lack of available or adequate food, as Dr Arends explains, is to spare proteins from being used as fuels and help to maintain critical body functions.

By contrast, systemic inflammation-associated malnutrition, or cachexia, can result from disease-associated inflammation, either acute or chronic, and the body’s basic reaction to serious injury. “Inflammation induces fatigue, anorexia, and catabolism, all colluding to induce weight loss and loss of cell and muscle mass,” Dr Arends says.

So far, no universal screening tool is able to assess a patient’s nutritional status, although recent studies and reviews have compared the relative advantages and predictive power of multiple screens and the benefits of several nutritional support systems. Multiple groups also have issued clinical practice guidelines for identifying and treating cancer-related cachexia.^{5, 6}

“To switch from an age of overlooking malnutrition, we urge the implementation of routine screening for malnutrition in all oncological treatment settings and institutions,” Dr Arends says. “We also urge to more broadly include high-quality nutritional education in medical schools.”

The condition still is confounding researchers. Dr Arends says that he has been particularly surprised at how hard it was to demonstrate the benefit of nutritional treatments in patients with cancer and how long it took researchers to acknowledge the metabolic basis of cachexia, which is at the root of the need for its multitargeted treatment. So far, no pharmacological drugs have been approved for targeting the metabolic basis of cancer-related cachexia, although Dr Arends notes that some promising candidates are being tested.

For both patients and health care systems, though, studies have repeatedly shown that early identification and nutritional support are paramount. In one study of 400 oncology patients in Spain, researchers found that the percentage of those at nutritional risk actually increased during their hospitalization, from 34% to more than 36%.⁷ “Only a third of the patients at risk of malnutrition at discharge had received any kind of nutritional support,” they found. Tellingly, the condition was associated with both longer hospital stays and higher health care costs.

Despite the remaining unknowns, Dr Arends says that the accumulating research has yielded some key take-home messages. First, cancer providers should perform routine and repeated screening for malnutrition in all patients with cancer. Next, they should perform a nutritional and metabolic assessment of all patients whose screening results suggest a nutritional pathology. That assessment can help to diagnose the causes of malnutrition in each patient as well as the extent of the nutritional and metabolic deficiencies and subsequently aid the design of personalized nutritional and metabolic care.