The Patient with Colon Carcinoma (Nutritional Needs)

Key Supporting Information

Proper nutrition, including a diet rich in fruits and vegetables, is correlated with a lower risk and/or improved treatment outcomes of many common cancer types.1,2 Unfortunately, many patients with cancer, especially those with cancer of the stomach, colon, or rectum, are malnourished due to altered metabolism and/or medication-induced side effects such as nausea and vomiting; this may negatively impact their treatment outcomes.3-6 At the molecular level, studies have pointed to the role of vitamins in mediating cellular processes that are often hijacked by cancerous cells. For instance, vitamin D has been shown to inhibit cell proliferation and angiogenesis, and patients with metastatic colorectal cancer who have high levels of vitamin D have demonstrated improved survival in recent studies; similar trends were observed in patients with breast cancer.2,7,8 Despite the proven impact of proper nutrition on optimizing outcomes for patients with cancer, physicians receive inadequate nutritional training and many do not feel prepared to provide nutritional counseling to their patients.9-11 Compounding this, the scientific evidence and recommendations for nutritional guidelines and treatment options for specific cancer types are evolving, further challenging physician competence and confidence in making dietary recommendations to their patients.

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Nutrition and Cancer

For decades, studies have investigated the impact of nutrition on the prevention and treatment of patients with cancer. For instance, limiting the intake of dairy products has been associated with a lower risk of prostate cancer, avoiding red meat may reduce the risk of developing colorectal cancer, increased consumption of soy products in adolescence is associated with decreased risk of developing breast cancer, etc.1,2 Additionally, several studies have investigated the impact of various nutrients on treatment outcomes for patients with various types of cancer. However, these studies are often more difficult to conduct and interpret, challenging clinicians.12,14

Given the importance of nutrition in the prevention and treatment of patients with cancer, The National Comprehensive Cancer Network (NCCN) and American Cancer Society (ACS) include nutritional recommendations as a part of their cancer prevention and treatment guidelines.15,16 However, with the minimal focus on nutrition as part of medical training, physicians are not adequately knowledgeable regarding the importance of nutrition in cancer prevention.3-5 Specifically, a recent study found that over the course of 4 years of medical school, only 20 hours of instruction were devoted to nutritional education; and, given the impact of nutrition on numerous disease states, it is likely that only a small percentage of these hours were devoted to cancer-specific topics.4,5 Unfortunately, despite the knowledge gained about the link between nutrition and health, very little has changed regarding the lack of nutrition education for physicians.17

Nutritional Intervention

Despite the proven importance of proper nutrition on improving outcomes for patients with cancer, many patients, especially those with cancer of the colon, rectum, and stomach, are malnourished and struggle to maintain a healthy weight due to the common side effects of cancer therapy, including nausea, vomiting, and fatigue.3,6 Moreover, in the diseased state, energy requirements may be higher, though the body may not process nutrients properly due to impaired metabolism. Unfortunately, malnutrition not only affects treatment outcomes, but also can cause unique symptoms, compounding the impact of disease.4 Indeed, a recent study showed that 89% of medical oncology patients suffered malnutrition-related symptoms, including decreased treatment tolerance, weight loss, and impaired quality of life.5

To circumvent this issue of malnutrition in patients with cancer, nutritional intervention, including oral nutritional supplementation and nutritional counseling, can improve quality of life, increase energy, and enhance performance scores.18 As studies have shown that weight loss impairs survival in patients receiving cancer chemotherapy, nutritional supplementation can be a critical component in improving patient outcomes and has been shown to improve quality of life and promote weight gain in patients with colorectal cancer, head and neck cancer, as well as other cancer types.18-21

To ensure adequate nutritional status of patients undergoing cancer chemotherapy, organizations such as the National Comprehensive Cancer Network (NCCN) and the American Society for Parenteral and Enteral Nutrition (ASPEN) issue guidelines for the monitoring and nutritional supplementation of patients.15,22 Such guidelines highlight the importance of routine assessment of weight, diet, food and nutrient intake, and lab work, as well as nutritional supplementation and counseling as necessary in patients with or at risk of developing malnutrion.15,22 Despite the clinical importance of adequate nutritional assessment and counseling, the majority of physicians in a recent survey reported being inadequately prepared, and possess a lack of substantive nutrition knowledge to administer effective nutritional counseling.3,5,17

Although general nutritional guidelines for the prevention of various cancer types have been established, the effect of specific nutrients, such as vitamins, essential fatty acids, and antioxidants, on treatment outcomes for patients with specific cancer types is not as clear, and often there is conflicting evidence. Moreover, sometimes what is protective for one cancer type may be detrimental for another.

Vitamin D, obtained from sunlight and/or dietary sources, is one nutrient that has been the focus of a number of studies investigating the impact of nutritional status on cancer treatment outcomes.2 Vitamin D is postulated to exert its anticancer activity by preventing tumor proliferation, though alternative mechanisms are proposed.2 A recent meta-analysis of 5 relevant studies was conducted to determine the effect of serum 25-hydroxyvitamin D [25(OH)D] levels at the time of diagnosis of breast cancer on survival of these patients.8 Statistical analysis demonstrated a strong linear, inverse dose-response relationship between serum 25(OH)D levels and breast cancer fatality rates. Those patients with breast cancer that had the highest levels of vitamin D demonstrated the highest survival rates. Because this study supports the protective role of vitamin D in cancer prevention and treatment, clinicians may find monitoring levels of serum 25(OH)D at the time of breast cancer diagnosis beneficial, though they should approach clinical interpretation with caution until further studies are completed.8

In another study, serum levels of 25(OH)D have correlated with improved survival in patients with metastatic colorectal cancer, the third most common type of cancer in the United States (US).23 Specifically, in a phase 3 study, serum 25(OH)D levels were measured in patients receiving chemotherapy plus the biologics bevacizumab, cetuximab, or both. Patients in the highest quintile of the 25(OH)D group demonstrated significantly improved overall and progression-free survival relative to those in the lowest quintile.7,15 Thus, as was observed in patients with breast cancer, high levels of vitamin D may be beneficial to patients undergoing therapy for metastatic colorectal cancer. As such, clinicians should be instructed on how to clinically interpret these findings and apply them to their practice.5,7

Other nutrients that have been the focus of several ongoing studies are the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both essential polyunsaturated fatty acids that impact cell membrane structure and intracellular signaling.24 EPA and DHA are suspected to exert their anticancer activity by impacting cell membrane structure and altering cell signaling that influences inflammation and/or cell proliferation. In clinical studies, higher levels of EPA and DHA from dietary intake have been associated with a 25% reduction in breast cancer recurrence and improved overall survival.25 In another study of patients receiving chemotherapy for breast cancer management, those with the highest levels of DHA demonstrated the highest overall survival rates.26 Given these findings, the use of EPA and DHA to improve outcomes for patients with breast cancer is a topic of ongoing research.27

Omega-3 fatty acids may also influence treatment outcomes for patients with colorectal cancer. One recent study investigated how oral administration of EPA in its free fatty-acid form impacted cell proliferation and vascularity, as well as overall and disease-free survival. Although EPA levels appeared to have no effect on measures of proliferation, there were trends towards reduced vascularity and improvements in survival with higher EPA levels. Phase 3 studies should be done to further elucidate the impact of EPA on outcomes for patients with metastatic colorectal cancer.

A controversial issue is the role of organic fruits and vegetables in preventing cancer. Organic and non-organic foods are equal in nutritional value. However, organic fruits and vegetables have not been exposed to pesticides and chemicals, which some consumers believe may be harmful to their health.28 The consensus among major peer-reviewed studies is that consuming non-organic fruits and vegetables is not harmful to your health. However, this is debated by organic food advocates, and some people refuse to believe that these foods are safe to consume. The American Cancer Society recommends a diet full of fresh fruits and vegetables to help reduce cancer risk. At this time, no research exists to demonstrate whether organic foods are more effective in reducing cancer risk than similar foods produced by other farming methods.29

The historical treatment for metastatic colorectal cancer was 5-flurouracil, though newer therapies, including oxaliplatin, irinotecan, bevacizumab, cetuximab, panitumumab, aflibercept, and regorafenib are improving patient outcomes.30 In patients without KRAS mutations, bevacizumab, cetuximab, or panitumumab are preferred therapies. Regorafenib has been recommended in patients with disease progression with standard therapy; and aflibercept with FOLFIRI (infusional 5-FU, leucovorin, oxaliplatin, irinotecan) is recommended in patients who are FOLFIRI-naïve.31 Additionally, several agents such as sunitinib, vatalanib, semaxanib, brivanib, and cediranib are currently under investigation.32 The treatment decisions for metastatic colon-rectal cancer (mCRC) need to be individualized based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, as well as patient preference.31

Although the advent of the new agents has led to improved survival rates, several patients do not have access to these therapies. This in part may be explained by the fact that the best way to use these therapies in terms of patient selection, drug combinations, and regimen sequences is not well understood.30 A recent report has demonstrated gaps in knowledge among oncologists that hindered their ability to individualize treatment in mCRC patients.13 The most recent guidelines also recommend physician clinical judgment and inclusion of patients in a clinical trial over standard or accepted therapy.31

Proper nutrition is an important factor in the prevention and treatment of cancer.1,2 However, physicians receive inadequate nutritional training and frequently report insufficient confidence in providing proper nutritional monitoring and counseling for their patients with cancer.3-5 In an era of evolving clinical evidence regarding the impact of specific nutrients on influencing cancer prevention and treatment outcomes, clinicians are challenged to best interpret clinical evidence and translate these findings effectively into practice.5,12 Physicians need to apply these clinical findings into the current therapeutic landscape.