Attributable Risk of Nutrition in Cancer
In 1981, Doll and Peto published a widely quoted estimate that 35% of all cancer deaths may be avoided by changes
in diet (7
). Willett updated this estimate, narrowing the confidence interval but still concluding that about 32% of all cancer in the United States may be avoided by dietary modifications (range, 20% to 42%) (8
). Given insights concerning the relationship between obesity and cancer risk, an updated estimate likely would be higher (9
). Especially strong associations are observed between diet and cancer risk for colorectal cancer, breast cancer, prostate cancer, pancreas cancer, endometrial cancer, and gall bladder cancer (8
). These data are of even greater significance in light of improved trends in cancer survival. More patients are surviving cancer and are therefore at risk for developing second primary cancers. These cancer survivors are an accessible and receptive group for education about dietary cancer prevention and secondary interventions.
Prevalence and Significance: Undernutrition
Anorexia and weight loss are frequent findings in patients with cancer. As many as 40% of patients with cancer present with weight loss, and the prevalence of the cancer cachexia syndrome (CCS; see elsewhere in this volume) is as high as 80% in those with advanced malignancies (10
). The extent of weight loss at the time of diagnosis is of prognostic significance. For any given tumor type, survival is shorter in patients with significant pretreatment weight loss (more than 10% of usual body weight) (Table 88.1
). A weight loss of greater than 2.75% per month has been linked to decreased survival (12
). Additionally, weight loss is a significant contributor to symptom distress in patients with cancer. Changes in body image and associated fatigue can contribute to depression and social withdrawal. Observation of these changes in a loved one also may have profound effects on family and friends (13
). Early recognition of these consequences of weight loss may afford the best opportunity to prevent the debilitating consequences. These issues may be especially problematic in children and the elderly (16
). In the therapeutic armamentarium, surgery is the modality most frequently used to actually cure cancer. Numerous studies dating back at least 75 years demonstrate the increased morbidity and mortality of major operations in malnourished patients (17
). A study estimated a fivefold increase in mortality in underweight patients (body mass index [BMI] <18.5 kg/m2
) undergoing major intra-abdominal cancer surgery (21
). In fact, some patients may not be candidates for potentially curative cancer surgery because of the overwhelming risk of life-threatening complications as a result of malnutrition.
TABLE 88.1 THE RELATIONSHIP BETWEEN WEIGHT LOSS AND PROGNOSIS IN PATIENTS WITH CANCERa
MEDIAN SURVIVAL (WEEKS)
SITE OF CANCER
NO WEIGHT LOSS
Acute nonlymphocytic leukemia
Lung (non-small cell)
Lung (small cell)
Non-Hodgkin lymphoma (favorable)
Non-Hodgkin lymphoma (unfavorable)
aResults described as weight loss of any amount.
b p < .01.
c p < .05.
Prevalence and Significance: Overnutrition
Overnutrition also is being seen more frequently in patients with cancer as a result of the rising incidence of overweight and obesity in the United States and the link between obesity and cancer risk. Its impact on patients with cancer is only just being elucidated. Cancer is usually thought of as a wasting disease. Weight loss and cachexia are hallmarks of cancer, in much the same sense that tuberculosis was referred to as “consumption” because of the gradual but relentless undernutrition that developed during the course of the disease and marked its progression toward lethality. Although this remains true for some cancers on presentation or as advanced, incurable disease develops, overnutrition also is becoming a significant problem in patients with cancer. Obesity is associated with higher risk of death from a variety of cancers, including cancers traditionally associated with wasting such as liver, pancreas, gastric, and esophageal cancer. Especially strong associations are seen in women for uterine cancer (6.25 relative risk [RR]), cervix cancer (3.20 RR), and breast cancer (2.12 RR). It is estimated that excess weight contributes to 14% of all cancer deaths in men and 20% in women (22
). The causes of this are unclear, but many hypotheses seem plausible (23
). Strong animal evidence and some human data exist that caloric restriction increases longevity and prevents cancer (24
). Obesity may interfere with cancer detection, because physical exam findings can be masked. It is difficult to properly dose chemotherapy and plan radiation therapy in overweight and obese patients (25
). Surgical morbidity is higher in obese patients, and obesity may make it technically more difficult to perform precise surgery to assure adequate margins and lymph node harvest (21
). Weight gain and physical activity are associated with decreased survival in a number of site-specific cancers, including breast and colorectal cancer, possibly as a result of the effect of adipose tissue on hormonal mediators such as estrogens, insulin, insulinlike growth factor-I (IGF-1), and adipokines, and the overall host inflammatory milieu (27
Causes of Malnutrition in Patients with Cancer
Multiple metabolic and cytokine-induced changes, and clinical factors contribute to the development of malnutrition in patients with cancer (Table 88.2
). They are detailed in the discussion of CCS. However, the interplay of these factors varies from patient to patient. Anorexia is a prominent contributor to weight loss in many patients with cancer. Its causes are complex and likely relate to an altered metabolic milieu resulting from cytokine and metabolic derangements (28
). Anorexia is not usually the primary cause of weight loss; it is a secondary effect that contributes to the downward cycle often observed in patients with cancer who lose weight. A number of lines of evidence support this contention. Parenteral nutrition (PN) support may be used to adequately deliver required energy and nutrients to undernourished patients with cancer, but this usually does not reverse the weight loss or the metabolic stigmata of CCS (30
). The clinical and metabolic features of starvation and cachexia in humans differ markedly, suggesting decreased intake is not the underlying cause of cancer-associated weight loss. Additionally, cancer weight loss may precede changes in appetite (31
). Finally, in some situations, the perceived anorexia is actually an adaptive decrease of food intake in response to weight loss (32
). Therefore, merely telling patients to eat more and better is unlikely to reverse the presence of CCS.
Other factors that contribute to weight loss in patients with cancer include mechanical factors, the side effects of cancer therapy, and psychosocial factors. The psychological factors associated with cancer that may alter food intake include pain, anxiety, depression, and social isolation. Mechanical causes may be a direct effect of tumor, or may relate to complications of therapy. Tumors may cause obstruction of the gastrointestinal (GI) tract; they may involve or compress hollow viscus, altering gastric and small bowel compliance. Cancer and cancer surgery may be complicated by the development of GI fistulas, with resultant effects on nutrition status, nutrient absorption, and fluid and electrolyte balance. Symptoms that relate to these mechanical issues include alterations in taste, early satiety, pain, cramps, vomiting, diarrhea, and constipation, all of which may exacerbate anorexia. Cancer treatments may induce anorexia and weight loss. The postoperative state is invariably accompanied by a temporary catabolic state and decreased nutrient intake, which can be prolonged if surgical complications occur. Chemotherapy often induces transient nausea and vomiting or injury to GI mucosa with resultant stomatitis, mucositis, diarrhea, and/or typhlitis. These may be particularly severe in profoundly neutropenic patients, such as those receiving chemotherapy for leukemias and lymphomas and those undergoing high-dose chemotherapy with either autologous or allogeneic bone marrow reconstitution. Radiation therapy can cause acute GI injury. It also may cause chronic radiation enteritis with malabsorption and stricture formation. These side effects of treatment may cause many of the symptoms noted in relation to mechanical factors.
TABLE 88.2 CAUSES OF MALNUTRITION IN PATIENTS WITH CANCER
Pain and other symptom distress
Alterations in taste
Gastrointestinal disruption, obstruction, dysmotility, and malabsorption
Depression and other psychosocial factors
Side effects of cancer therapies
Conditioned food aversion
Cytokine-, peptide-, and hormone-induced metabolic changes