Although our observational study does not provide conclusive evidence for causality, these findings support the potential role of energy balance factors in colon cancer progression and may offer opportunities to further improve patient survival.
—The CALGB 89803 investigators
In the News focuses on media reports that your patients may have questions about at their next visit. This continuing column will provide summaries of articles in the popular press that may prompt such questions, as well as comments from colleagues in the field.
Patients who have received standard treatment for colon cancer can take positive actions to reduce their risk of recurrence by following a balanced diet with fewer starchy foods that raise total glycemic load, according to Jeffrey A. Meyerhardt, MD, MPH, Associate Professor of Medicine at Dana-Farber Cancer Institute in Boston. Dr. Meyerhardt is lead author of a prospective, observational study examining the influence of glycemic load, glycemic index, fructose, and carbohydrate intake among patients with stage III colon cancer.
The study was embedded in a clinical trial (Cancer and Leukemia Group B [CALGB] 89803) comparing chemotherapy regimens for patients who underwent complete surgical resection of the primary tumor, and had regional lymph node metastases but no evidence of distant metastases. Results of the dietary study were published in the Journal of the National Cancer Institute1 and reported in The New York Times2and by other media outlets.
“This is our second study that has looked at diet in this cohort,” Dr. Meyerhardt told The ASCO Post. “The first study3 was related to the Western pattern diet characterized by higher intake of red meats, processed meats, sugary desserts, refined grains.” Also involving patients with stage III colon cancer, that study found that those in the highest quintile of consumption of the Western pattern diet had a threefold increase in cancer recurrence and death compared to those in the lowest quintile.
The second study was undertaken to “further understand which component of a Western pattern diet is associated with poorer outcomes and define the impact of dietary glycemic measures on colon cancer survival,” according to the study report. Results showed that higher dietary glycemic load—a measure of the body’s plasma glucose response to foods—and total carbohydrate intake had a statistically significant association with an increased risk of recurrence and mortality.
“It’s not that you have to totally avoid carbohydrates or totally avoid red meat,” Dr. Meyerhardt said, “but a healthy balanced diet is probably reasonable.”
Dr. Meyerhardt noted that all patients in the study received what would be considered standard care for stage III colon cancer. “They all received surgery, and they all had adjuvant chemotherapy.” He stressed that while following a healthy balanced diet is reasonable, “it is not a substitute” for treatment.
Physiologic Response to Carbohydrates
“Both total carbohydrates and glycemic load—measures that reflect your body’s response to foods high in those components—lead to higher insulin levels. And we know that insulin and insulin-like growth factors are drivers of colon cancer cell growth,” Dr. Meyerhardt said.
“The physiological response to carbohydrates can be quantified by the glycemic index, a qualitative assessment of foods calculated as a percentage of the body’s plasma glucose response to specific foods compared with the response induced by the same amount of carbohydrate from a standard carbohydrate source, usually white bread or pure glucose,” the study report explained.
In the study, 1,011 patients completed food questionnaires during and after participating in the adjuvant chemotherapy trial. The questionnaires included 131 food items, vitamins, mineral supplements, and open-ended questions for other supplements and foods not listed. The investigators calculated glycemic index values and used them to calculate the mean dietary glycemic load “by multiplying the carbohydrate content for each food by its glycemic index value, multiplying that product by the servings of that food per day, and summing values for all food items reported.” Median follow-up after completion of the first questionnaire was 7.3 years.
“The primary endpoint of this analysis was disease-free survival. Higher dietary glycemic load was associated with statistically significant worse disease-free, recurrence-free, and overall survival,” the investigators reported. “Moreover, the deleterious association of dietary glycemic load and total carbohydrate intake on survival was principally observed in patients who were overweight or obese.”
Associations between glycemic load and survival differed according to body mass index. “Compared with patients with the lowest glycemic load quintile, those in the highest quintile experienced an adjusted hazard ratio for disease-free survival of 1.79,” the authors reported. But those with a body mass index ≥ 25 kg/m2 had an adjusted hazard ratio of 2.26.
“We looked at a subgroup analysis of people who had a [body mass index] of 25 or less, which is considered either underweight or normal weight, or people whose [body mass index] was greater than 25, which is overweight and obese, and the association seemed to be strongest in those who were overweight and obese, which again is biologically plausible,” Dr. Meyerhardt said.
Increasing evidence suggests that an energy imbalance between the calories consumed and expended impacts outcomes in colon cancer survival. “People who are physically inactive after diagnosis seem to have a higher risk of recurrence from their colon cancer,” according to published reports, Dr. Meyerhardt said. These reports consistently show “the importance of energy balance in colon cancer survivors and maintaining a healthy energy balance,” he added.
The CALGB 89803 investigators concluded, “Although our observational study does not provide conclusive evidence for causality, these findings support the potential role of energy balance factors in colon cancer progression and may offer opportunities to further improve patient survival.”
Other Disease Stages
Although the current study involved only stage III patients with regional lymph node metastases, Dr. Meyerhardt said, “we have looked at energy balance factors—for example, physical activity—in earlier stages of disease, either stage I or stage II, and we see a similar effect. We haven’t been able to study diet as much in stage I or stage II patients, but at least biologically, it would make sense. Patients with early disease develop a recurrence when they have micrometastases that are not detected at the time of diagnosis. Assuming that these energy balance factors lead to a biologic response, perhaps insulin or insulin-like growth factors that drive the micrometastases to grow, that would provide the rationale for a similar response in early-stage disease,” he said.
“Whether these factors impact people with metastatic disease is a different question, because those are people who already have visible disease, and you are trying to slow the progression,” he continued. “We actually have a very large study for metastatic disease, also embedded in one of the cooperative groups trials.”
That trial, CALGB/Southwestern Oncology Group (SWOG) 80405, is a phase III study comparing chemotherapy regimens for patients with untreated metastatic adenocarcinoma of the colon or rectum. Patients complete a single questionnaire early on, when their ability to maintain physical activity and follow a balanced diet is less likely to be impacted by disease progression.
“We have already collected over 1,400 questionnaires from patients on that trial and will be able to look at those questions on diet and other lifestyle factors,” Dr. Meyerhardt said. The study has completed accrual but has not yet reached the primary endpoint of overall survival. Results are expected later in 2013.
Questionnaires have also been embedded into another adjuvant chemotherapy trial, CALGB 80702, comparing duration of chemotherapy and celecoxib (Celebrex) vs placebo. “In that trial, we expanded some questions related to energy balance and added questions about other comorbidities,” Dr. Meyerhardt said.” ■
Disclosure: Dr. Meyerhardt reported no potential conflicts of interest.
1. Meyerhardt JA, Sato K, Niedzwiecki D, et al: Dietary glycemic load and cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803. J Natl Cancer Inst 104:1702-1711, 2012.
2. O’Connor A: Can foods affect colon cancer survival? New York Times. November 9, 2012.
3. Meyerhardt JA, Niedzwiecki D, Hollis D, et al: Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA 298:754-764, 2007.
A study finding that a diet high in total carbohydrates can increase the risk of cancer recurrence and mortality doesn’t mean that patients need to totally avoid carbohydrates, any more than previous findings about increased risk from a Western pattern diet means patients can’t eat any red meat....