Other Nutrition Issues
Nutrition in Advanced Cancer
Advanced cancer is often associated with cachexia.[1-4] Individuals diagnosed with cancer may develop new, or worsening, nutrition-related side effects as cancer becomes more advanced. The most prevalent symptoms in this population are the following:[1-3]
- Weight loss.
- Early satiety.
- Taste changes.
As defined by the World Health Organization, palliative care is an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial, and spiritual. The goal of palliative care is to give relief of symptoms that are bothersome to the patient. Although some of the symptoms listed above can be effectively treated, anorexia, though common, is a symptom that is often not noted as problematic for most terminally ill patients but is distressing to most family members; this distress may vary according to cultural factors. Several studies have demonstrated that terminally ill patients lack hunger, and of those who did experience hunger, the symptom was relieved with small amounts of oral intake.
Decreased intake, especially of solid foods, is common as death becomes imminent. Individuals usually prefer and tolerate soft-moist foods and refreshing liquids (full and clear liquids). Those who have increased difficulty swallowing have less incidence of aspiration with thick liquids than with thin liquids.
Dietary restriction is not usually necessary, as intake of prohibited foods (e.g., sweets in the diabetic patient) is insufficient to be of concern. As always, food should continue to be treated and viewed as a source of enjoyment and pleasure. Eating should not just be about calories, protein, and other macronutrient and micronutrient needs.
Diet restrictions are sometimes appropriate, however.[6,7] For example, people with pancreatic cancer, gynecologic cancer, abdominal carcinomatosis, pelvic masses, or retroperitoneal lymph node masses may have bowel obstruction less frequently when adhering to a prophylactic soft diet (i.e., no raw fruits and vegetables, no nuts, no skins, no seeds). Any restriction should be considered in terms of quality of life and the patient’s wishes.
Decisions regarding nutritional support should be made with the following considerations:
- Will quality of life be improved?
- Do the potential benefits outweigh the risks/costs?
- Is there an advance directive?
- What are the wishes and needs of the family?
The benefit of home parenteral nutrition in patients with advanced cancer is often debated, and evidence-based data regarding its use are lacking. For patients who still have good quality of life but also have mechanical or physiologic barriers to achieving adequate nourishment and hydration orally (e.g., head and neck cancer), prolonged survival may be achieved with the use of enteral or parenteral nutrition. In a qualitative study, 13 patients and 11 family members perceived some benefits with home parenteral nutrition. The most salient positive feature of home parenteral nutrition was a sense of relief and security that nutritional needs were met. In this study, patients were also able to take oral nutrition, and the administration of total parenteral nutrition was often described as a complement to the patients' oral intake. This contradicts the traditional indication for TPN, i.e., that its use be reserved for times when nourishment via the gastrointestinal tract is not possible. Patients in this study also had regular visits by home health care providers, which could have had a positive impact on their physical, social, and psychological well-being.
Although most patients with advanced cancer will not benefit from artificial nutrition, for someone who still has good quality of life but also has mechanical or physiologic barriers to achieving adequate nourishment and hydration orally (e.g., head and neck cancer), prolonged survival can be achieved with the use of enteral or parenteral nutrition.
All people with cancer and their caregivers have the right to make informed decisions. The healthcare team, with guidance from the registered dietitian, should inform patients and their caregivers about the pros and cons of using nutritional support in advanced disease. Despite the lack of proven benefit, artificial nutrition at the end of life will remain a sensitive topic for some patients and families. In most cases, the cons outweigh the pros. The following is a list of the pros and cons of using nutritional support in advanced disease:[6,7,9]
Pros and Cons of Enteral Nutritional Support
- May improve alertness.
- May provide comfort to the family.
- May decrease nausea.
- May decrease hopelessness and fears of abandonment.
- May increase secretions.
- May increase nausea.
- Surgery with gastrostomy or jejunostomy.
- Risk of aspiration or pneumonia.
- Risk of infection.
- Greater burden on caregiver.
Individuals being treated for cancer may require the use of a series of curative or supportive drugs throughout their care; they may also receive advice on the use of dietary supplements, or they may self-diagnose and self-prescribe the use of dietary supplements. Drug-nutrient interactions or dietary supplement-drug-nutrient interactions can occur and can compromise the safety and efficacy of the anticancer treatment plan. A review of antineoplastic drugs listed in various references revealed the interactions listed in Table 2.
|Trade Name||Generic Name||Food Interactions|
|MAOI = monoamine oxidase inhibitor.|
|Targretin||bexarotene||Grapefruit juice may increase drug concentration and toxicities.|
|Folex||methotrexate||Alcohol may increase hepatotoxicity.|
|Mithracin||plicamycin||Supplements containing calcium and vitamin D may decrease effect.|
|Matulane||procarbazine||This chemotherapy is a mild MAOI; a low-tyramine diet should be followed.|
|Temodar||temozolomide||Food may decrease drug rate and absorption.|
Nutrition and Survivorship
Survivors of cancer represent a population at risk for many nutrition-related morbidities, suggesting that programs aimed at lifestyle modification could be clinically applicable and beneficial. Research among survivors has focused on stages of and barriers to behavioral change and has included multidisciplinary lifestyle interventions. Lifestyle behaviors that are part of a multidisciplinary approach that includes dietary guidance, exercise, and stress management are more likely to result in success over the long term.
Lifestyle behaviors in adult and pediatric survivors of cancer
A number of surveys evaluating lifestyle practices among survivors of adult and childhood cancer have been published. One of the first studies explored lifestyle habits among 978 individuals who had been diagnosed with breast or prostate cancer. Forty-seven percent of breast cancer survivors and 35% of prostate cancer survivors reported consuming the recommended daily number of servings of fruits and vegetables. Whites were more inclined to eat the recommended number of fruits and vegetables than were African Americans (P = .006). Sixty-nine percent of participants followed a low-fat diet.
In a second prospective cohort study, variations in dietary patterns among 1,901 women with early-stage breast cancer were evaluated for effect on breast cancer recurrence and survival. Women aged 18 to 79 years who were diagnosed with breast cancer within the previous 11 to 39 months were surveyed. Dietary intake was assessed by using the Fred Hutchinson Cancer Research Center Food Questionnaire and by inquiring about dietary intake over the previous year. Healthy dietary patterns were defined by intake of foods typical of a cancer prevention diet and included assessing consumption of cruciferous vegetables, fruits, legumes, onions, and lean meats.
A statistically significant relationship was observed in women who were more physically active (P < .0001) and who gained less weight 1 year before diagnosis (P = .04). Unhealthier dietary patterns that included consumption of red meat, processed meat, creamy soups, butter, refined grains, and sweets were more likely followed by women who:
- Had a higher body mass index (BMI) at enrollment (P < .0001).
- Had a history of smoking (P = .04).
- Gained more weight the year before diagnosis (P = .0002).
Decreased risk of overall death (P trend = .05) and death from noncancer causes (P trend = .02) was observed among women who followed healthier dietary habits. No relationship between dietary patterns and death from breast cancer or recurrence of breast cancer was observed.
Finally, a smaller study explored the effects of dietary habits and exercise patterns on cancer-related late effects, social support, and stressful events in long-term survivors of breast cancer. Of the 227 women surveyed:
- 58% reported making healthy lifestyle changes after their diagnosis of cancer.
- 32% reported increased exercise.
- 44% reported decreasing fat intake.
- 42% reported increasing fiber intake.
- 43% reported increasing their intake of fruits and vegetables.
Survivors who adopted an exercise regimen reported decreased fatigue (P = .03). Women who increased their fruit and vegetable intake also reported decreased fatigue (P = .08). No significant effect on symptoms of depression, anxiety about breast cancer, sexual satisfaction, or body satisfaction was reported. Survivors who had a social support system were more inclined to adopt an exercise regimen (P = .06).
Few studies have explored lifestyle habits among survivors of childhood cancer. One survey (N = 380) reported the following:
- 79% of survivors of childhood cancer did not meet the guidelines for fruit and vegetable consumption.
- 84% obtained more than 30% of their calories from fat.
- 48% were meeting exercise guidelines.
A subsequent survey of 144 survivors of childhood cancer explored barriers to consuming healthy foods. Barriers to adopting healthier lifestyle habits included the following:
- Being too tired (57%).
- Being too busy (53%).
- Not belonging to a gym (48%).
- The visual appeal of fattier foods (58%).
- The typical consumption of high-fat foods in social situations (50%).
- Lack of knowledge about choosing healthier options (a major barrier).
A survey conducted of 72 survivors of childhood cancer found similar results. In this survey, none of the participants reported adhering to cancer prevention guidelines.
The results of the surveys described above suggest that survivors of cancer are not adhering to cancer prevention guidelines and are engaging in lifestyle behaviors that may further increase their risk of late effects. Survivors who engage in at-risk lifestyle behaviors are likely to accelerate the progression of some late effects. Given the increased vulnerability to disease among survivors of cancer, this group uniquely represents a high-risk population for whom intervention strategies can be optimally applied and tested. Interventions that educate survivors about modifying risky lifestyle behaviors and that promote self-efficacy may be effective strategies for lowering the risk of late effects.
Intervention trials among survivors of cancer
The growing population of survivors has fueled awareness about the unique needs for effective lifestyle intervention programs specifically designed for survivors of cancer. As highlighted by the literature, most survivors of cancer are not following cancer prevention guidelines. A number of trials have aimed to modify lifestyle behaviors, with the goal of minimizing the risk of developing late effects or decreasing the odds of recurrence. A summary of select intervention studies is presented below.
The association between increased fat intake and increased breast cancer recurrence coupled with an increase in the survivor population among breast cancer patients led to the development of two National Cancer Institute–funded trials evaluating dietary patterns and the effects of dietary intake of fat on breast cancer recurrence.
The Women’s Intervention Nutrition Study (WINS) (N = 2,437) was the first large-scale trial that explored the effects of dietary intervention on survival, relapse, or recurrence in women with breast cancer. The primary outcome measure of this trial was the effect of a low-fat diet on relapse-free survival among women who were within 1 year of diagnosis with breast cancer. In this study, subjects were counseled to reduce fat intake to 15% of total energy intake while maintaining a nutritionally balanced diet. Exercise was not a component of the intervention.
WINS participants maintained a favorable response rate at year 1: 86% for the intervention group and 91% for the control group. However, at year 5 the response rate decreased to 39% for the intervention group and 44% for the control group. A significant reduction in weight loss was observed at months 12, 24, 36, 48, and 60, compared to baseline (P < .0001).
The study did not find that adoption of a low-fat diet had an effect on overall survival, relapse, or recurrence. An exploratory analysis revealed a beneficial effect among women with estrogen receptor–negative breast cancer. In this group, adherence to a low-fat diet increased relapse-free survival in the intervention group, compared with controls (P < .034). WINS was limited by its sole reliance on self-reported data and by most patients being white and having advanced degrees, thereby limiting the generalizability of the study.
The Women's Healthy Eating and Living (WHEL) Study (N = 3,088) explored the effect of a dietary intervention promoting daily consumption of five vegetable servings plus 16 oz of vegetable juice, three fruit servings, and 30 g of fiber, with fat comprising 15% to 20% of energy intake. The primary outcome measures were cancer recurrence or new primary breast cancer and death from any cause.
The intervention arm included a series of telephone counseling sessions combined with 12 cooking classes held during the first year of the study, along with monthly newsletters tailored to the individuals. The control arm received education about the “5-A-Day” diet, attended an average of one of four cooking classes in the first year, and received 24 newsletters tailored to them. Objective data were also collected in this study. Plasma concentration of nutrients was obtained at 12, 48, and 72 months. Participants were monitored for 7 years, with response rates at 77.9% in the intervention arm and 86.2% in the control arm at 72 months.
Participants in the intervention arm of the WHEL Study significantly increased their vegetable consumption, from 3.9 servings per day at baseline to 5.8 servings per day at 72 months. Fruit intake went from 3.5 to 3.4 servings per day. The control arm reported decreased intake of fruits, from 3.4 to 2.6 servings per day, and of vegetables, from 3.8 to 3.6 servings per day. No significant effect on dietary fat intake as a percentage of total calories or fiber was observed in the intervention group. In concordance with WINS, no effect on overall survival or cancer recurrence was observed. A nested case-control analysis revealed that women who were hot flash negative at recruitment experienced a significantly decreased risk of cancer recurrence (P = .002).
While both WINS and the WHEL Study found that nutrition education can produce sustained dietary change among survivors of cancer, neither trial found significant effects on primary study outcomes. It is important to recognize that these studies evaluated slightly different questions. WINS focused more on the effects of a low-fat diet based on data correlating breast cancer with fat and circulating estrogen levels, while the WHEL Study evaluated a comprehensive diet change that included fruits, vegetables, decreased fat, and increased fiber.
These studies demonstrate that distance medicine–based nutrition education is effective at instituting change. However, the clinical benefit of these studies remains to be seen. WINS and the WHEL Study differ slightly in the following ways:
- The WHEL Study recruited women from a wider age range (18 to 70 years vs. 48 to 79 years for WINS) and included more women with larger tumor burden and increased nodal activity.
- The WHEL Study excluded women with cancers that recurred within the first 2 years of diagnosis, whereas women recruited to WINS were undergoing conventional therapy while also adopting dietary changes.
- The WHEL Study recruited women within 4 years of diagnosis, whereas WINS recruited women within 1 year of diagnosis.
As highlighted by the author, the WHEL Study undersampled individuals who experienced recurrence within 4 years of diagnosis.
WINS and the WHEL Study are limited in their generalizability because most participants were white and had higher levels of formal education. It is unknown whether the nutrition education interventions would be effective in ethnically diverse populations, low-income households, or individuals with low levels of education.
Only one study has explored the effects of a diet-plus-spirituality education intervention in a nonwhite population of survivors of breast cancer. The investigators hypothesized that the addition of a spiritual component would provide further support to dietary change. Participants were obese (BMI 30–45) African American women aged 18 to 70 years who had been diagnosed with breast cancer in the 10 years before recruitment. Individualized dietary counseling was provided by a registered dietician for 18 months. Counseling sessions were provided in person at baseline, 6 months, and 12 months, with interim telephone counseling. Participants also received coupons for free attendance at Weight Watchers meetings between visits to the registered dietician.
Participant dietary and exercise goals included the following:
- Decrease fat to 20% to 25% of calories.
- Maintain protein at 20% of calories.
- Choose whole grains for at least half of their daily grain intake.
- Eat at least six to eight servings of fruits and vegetables daily.
- Exercise for at least 30 minutes per day, at least 5 days per week.
Spiritual counseling focused on issues relevant to weight loss and was conducted by telephone weekly for 3 months, biweekly for 3 months, and then monthly. Objective assessments were collected at baseline, 6 months, 12 months, and 18 months. Thirty-one subjects were recruited to the study; however, five subjects did not meet the 6-month benchmark. At month 6, 24 subjects were randomly assigned to receive dietician-led counseling with or without spiritual counseling. Of the 24 women, 11 subjects in each arm completed the study.
No significant differences in weight loss were observed between the two groups. The spirituality group reported a larger increase in fruit consumption (2.5 servings per day) than did the dietician-only group (1.1 servings per day) and improved quality of life.
One small study has investigated a lifestyle modification program that included nutrition and exercise education for 45 obese or overweight women with endometrial cancer. Participants were randomly assigned to a 6-month intervention or usual care. The intervention group met weekly for 6 weeks, biweekly for 1 month, and then monthly thereafter.
The study's primary endpoint was weight change. Secondary endpoints were leisure activity and nutrition analysis, as measured by 3-day food records. Overall attrition to the study was 16%: 10% in the usual care group, compared with 22% in the intervention group. At 12 months, the intervention group had lost 3.5 kg, compared with a 1.4-kg gain in the usual care group (P = .018). Leisure scores increased for the intervention group, compared with the control group (P = .002).
Although these results may be encouraging, this study is limited by the small sample and high drop-out rate in the intervention group. The high attrition rate in the intervention group calls into question the feasibility of this intervention in a larger setting.
Breast and prostate cancer
In another large study (N = 543), FRESH START explored the effects of nutrition education coupled with exercise intervention in individuals with prostate cancer or breast cancer. FRESH START recruited individuals who were within 9 months of the diagnosis of breast or prostate cancer. The 10-month intervention trial included tailored printed education materials targeting behaviors to:
- Consume five or more servings of fruits and vegetables per day.
- Reduce total fat intake to 30% of total caloric intake.
- Increase exercise to at least 150 minutes per week.
The primary outcome measure was the percentage of patients who achieved goal behavior in at least two of the three behavioral domains.
After 1 year, a significant difference between the two arms in goal behaviors was observed, with 34% of subjects adopting two or more behaviors in FRESH START (P < .001) and 18% of subjects in the attention-control arm adopting change. Improvement in diet and exercise resulted in a significant loss of weight. This study did not explore the effects of dietary change on cancer recurrence or overall mortality.
FRESH START was one of the first studies to document significant improvements in fruit and vegetable consumption through a distance medicine–based educational program. One of the strengths of FRESH START was that it was a tailored intervention program; such interventions may be particularly effective at reaching a geographically scattered population, as the rate of attrition in this study was quite low.
As seen in the other behavioral studies described in this section, FRESH START was limited in that most survivors were white and had more years of formal education. It is unknown whether these types of lifestyle interventions would be effective in other patient populations.
The Reach out to ENhancE Wellness (RENEW) trial was a distance medicine–based nutrition and exercise intervention program that consisted of a personally tailored workbook and a series of quarterly newsletters, along with a program of telephone counseling and automated prompts (15 sessions and 8 prompts over the 12-month period). Eligible participants were survivors of breast, prostate, or colorectal cancer for 5 years or longer, had BMIs between 25 and 39.9, and were at least 65 years old.
The primary outcome measure was change in functional status between baseline and 12 months. The goals of intervention included having subjects:
- Engage in 15 minutes of strength training every other day.
- Engage in 30 minutes of endurance exercises every day.
- Consume at least seven servings (for women) or nine servings (for men) of fruits and vegetables every day.
- Limit consumption of saturated fat to less than 10% of total energy intake.
- Attain a 10% weight loss during the 12-month period.
At 12 months, significant differences in the change scores between the intervention and control groups were observed for the following outcomes:
- Strength training (P < .001).
- Duration of endurance training (P = .003).
- Strength training frequency (P < .001).
- Daily number of servings of fruits and vegetables (P < .001).
- Daily intake of saturated fat (P < .001).
At 12 months, more participants in the intervention group met the recommendations for the following outcomes:
- Strength training (P < .001).
- Endurance exercise (P = .07).
- Fruit and vegetable servings (P < .001).
- Saturated fat guidelines (P = .001).
As with most of the studies described in this section, the RENEW trial was limited in its generalizability. The population was primarily white and had at least some college education. Significant differences were also observed in respondents compared with nonrespondents:
- Participants were younger.
- There were more women than men.
- There were fewer cases of colorectal cancer.
- Time at recruitment was closer to diagnosis.
As in WINS, all outcome assessments were based on self-report; no objective measures were collected in RENEW.
The only intervention aimed at survivors of childhood cancer has been a small pilot study of 13 children aged 4 to 10 years who were in the maintenance phase of therapy for acute lymphoblastic leukemia. This study explored the feasibility of a 12-month home-based nutrition and exercise intervention program. Children were randomly assigned to the intervention group or the control group. The primary objectives of the program were to increase physical activity and to improve dietary patterns.
A physical activity pyramid for youth and the U.S. Department of Agriculture (USDA) Food Guide Pyramid provided the foundation for exercise and nutrition recommendations. The control group received standard recommendations to eat a well-balanced diet and perform activity as tolerated (essentially, standard of care).
Three-day activity records and 2-day food records were completed on a monthly basis by parents. Objective measures of progress were obtained through fitness tests conducted at baseline and at 3, 6, 9, and 12 months. Anthropometric measures and BMIs were obtained at baseline and every 3 months.
No significant differences were observed at 3, 6, and 12 months in any of the nutrition-related parameters. Improvements in physical activity and cardiovascular fitness were observed in the intervention group, compared with controls. Activity levels were higher for the intervention group than for controls (P = .05); however, improvements in fitness assessments did not differ between groups at 6 or 12 months.
Special attention and research should be focused on nutrition and lifestyle behaviors among survivors of cancer, who are at increased risk of many nutrition-related and lifestyle-related late effects.
The studies described in this section provide clear evidence that distance medicine–based lifestyle education programs that include nutrition counseling with or without exercise counseling are effective at promoting behavioral change among survivors of cancer. On the basis of two large studies of survivors of breast cancer, it seems prudent to recommend a low-fat, healthy diet to survivors who have estrogen receptor–negative breast cancer or who are symptomatic at diagnosis.
On the basis of available evidence, the effect of a low-fat diet or healthy diet on recurrence of breast cancer among women diagnosed with other stages of breast cancer is not conclusive. However, although diet may not prevent breast cancer recurrence, the data do not refute the importance of a healthy diet for minimizing the development of nutrition-related late effects such as obesity, heart disease, and metabolic syndrome. When counseling survivors of breast cancer, nutrition educators should highlight the global benefits and importance of a healthy diet. As more survivors enter ongoing research protocols, future studies may reveal that dietary change may play a more prominent role in preventing late effects when compared with preventing recurrence or second malignancies.
Guidelines for Healthy Eating
Health agencies and disease prevention organizations have developed diet and lifestyle guidelines for the public. These recommendations have been created for healthy individuals and are not based on the unique needs of survivors of cancers. More information about these guidelines may be found at USDA's ChooseMyPlate and in the USDA and U.S. Department of Health and Human Services Dietary Guidelines for Americans, 2010.
Cancer Prevention Dietary Guidelines
The American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention, first published in 1996, provide more detailed dietary advice with a focus on cancer prevention. These guidelines, updated in 2010, are consistent in principle with those recommended by USDA and other organizations.
The ACS guidelines form the beginning of a report that contains the most up-to-date information available on nutrition issues linked to neoplastic diseases. Included are in-depth answers on how different foods, food preparation methods, portion sizes, variety, and overall calories can reduce or increase the risk of specific cancers. These guidelines provide sound advice regarding healthy eating for cancer prevention for all individuals, including cancer survivors.
The ACS guidelines include the following:
- Achieve and maintain a healthy weight throughout life.
- Adopt a physically active lifestyle.
- Consume a healthy diet, with an emphasis on plant foods.
- Limit consumption of alcoholic beverages, if you drink at all.
The American Institute for Cancer Research (AICR) published a report in 1997  that included an expert scientist panel review and evaluation of more than 4,500 studies on diet and cancer. The AICR Diet and Health Guidelines for Cancer Prevention were developed from these recommendations, which were updated in 2007. AICR also maintains a Web site that provides information on recipes with a focus on cancer prevention. The AICR and ACS guidelines are similar.
The AICR guidelines include the following:
- Choose a diet rich in a variety of plant-based foods.
- Eat plenty of vegetables and fruits.
- Maintain a healthy weight and be physically active.
- Drink alcohol in moderation, if at all.
- Select foods low in fat and salt.
- Prepare and store food safely.
- Do not use tobacco in any form.
The use of soy foods in breast cancer survivors has led to significant research in this area. Several studies suggest soy consumption may reduce breast cancer risk and improve survival; however, the estrogenic effects of isoflavones naturally found in soy products have led to controversy among health professionals over the use of soy by breast cancer patients, especially those with estrogen receptor–positive tumors.
Research on genistein and daidzein, the two main isoflavones in soy, has shown that these phytochemicals may bind to estrogen receptors and decrease the plasma estrogen levels in women, thus acting in a preventive manner. Animal studies, however, have found that genistein inhibited the efficacy of tamoxifen, a drug used to block the body’s circulating estrogen.
One study  reviewed the relevant literature and found no convincing data to support the claim that soy is protective against breast cancer or that soy is harmful for women with a history of, or at high risk for, breast cancer. A follow-up study using data collected from a large cohort of breast cancer patients as part of the Shanghai Breast Cancer Study also concluded that soy foods do not have an adverse effect on breast cancer survival.
Researchers from these studies concluded that soy foods, as part of a healthy diet and in moderate amounts, are safe to consume; however, there is not enough evidence to recommend that breast cancer patients begin to consume soy specifically to prevent the occurrence of a secondary tumor and enhance survival. Adding soy to the diet after a diagnosis of breast cancer has not been shown to be protective against recurrences. Likewise, the consumption of concentrated, isolated isoflavone supplements in the form of powders or pills has not shown effects consistent with breast cancer risk reduction and is not recommended.[35,37]
As more research is conducted on the biological mechanisms relating to soy isoflavone intake, scientists may clarify the optimal exposure, duration, and timing of intake. Recommendations for the inclusion of soy in the diets of breast cancer survivors should be based on all available (and the most current) evidence.
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