‘Precision nutrition’ may be on the horizon, but large-scale, definitive trials lacking

Oncology is a precision medicine-driven field. We strive to choose the right treatment based on each patient and their tumor characteristics. We’ve made great strides with this approach in terms of drug therapies. Our lifestyle recommendations, however, including dietary recommendations, have remained fairly general and, at this point, apply to all cancer survivors regardless of cancer type or tumor characteristics. We obviously consider certain patient characteristics — such as body weight, comorbidities, food preferences and allergies — but as much as we want to achieve personalized nutrition on a broad scale, we’re not quite there.

Interesting preclinical studies are evaluating specific diets for specific cancers and tumor characteristics, such as the tumor mutational profile. Small pilot studies and mechanistic studies in humans are looking at different diets for different patients. Such studies suggest certain diets may be more helpful for certain cancers.

Lindsay L. Peterson, MD, MSCR
Lindsay L. Peterson

For example, in a study of cell lines and subsequently mice, Strekalova and colleagues found that depriving triple-negative breast cancer of methionine — an essential amino acid that can be regulated through diet — increases the sensitivity of breast cancer cells to specific targeted therapies. A low-methionine diet is being tested for patients with triple-negative breast cancer, with one study planning to enroll 25 patients and another just over 100.

Similarly, there is interest in the ketogenic diet given the dependence of certain cancers on glucose. Again, there are promising preclinical studies, and some published data from human trials regarding its feasibility, impact on quality of life and effect on intermediary biomarkers. But, with most clinical trials still enrolling and few with clinical endpoints, its translation to clinical practice remains limited.

Thus, large-scale, confirmatory trials that indicate certain diets improve clinical outcomes for individual patients or groups of patients are lacking. One reason is the large number of patients and long follow-up required to show significant improvements in clinical outcomes such as PFS and OS. Such trials are expensive and logistically challenging in terms of successfully changing dietary patterns for many individuals for long periods. This does not mean these trials should not be completed, but rather that they must be carefully designed, as we do not have the means to conduct such studies for every possible dietary intervention in every possible population. Instead, we need to rely on well-designed preclinical studies and human studies using alternative clinical endpoints, such as pathologic complete response, and other changes in tumor characteristics, such as proliferation rate, to give us preliminary data regarding which diets are promising enough in which patient populations to be tested in larger-scale trials with more robust clinical endpoints.

Ultimately, we want to be able to recommend a specific type of diet for a specific patient based on patient and tumor characteristics. For example, the diet for two similar patients with a HER2-positive cancer may be different based on their tumor mutational profiles. Currently, however, the data to make such recommendations are lacking.

Guidelines from the World Cancer Research Fund and American Institute for Cancer Research recommend that cancer survivors follow the same guidelines recommended for cancer prevention. Those guidelines include maintaining a healthy weight; eating lots of whole grains, fruits and vegetables; and limiting fast food, processed food, and foods high in fat and sugar. They recommend that survivors limit their red meat, processed meat and alcohol intake.

We convey those recommendations to our patients across all cancer types. We’d like to get to the point where we can say more about particular nutrients, diet content and strategies for each patient, but we don’t yet have the large-scale, definitive trials to do so.

References:

Chung HY and Park YK. J Cancer Prev. 2017;doi:10.15430/JCP.2017.22.3.127.

Lv M, et al. PloS One. 2014;doi:10.1371/journal.pone.0115147.

Morscher RJ, et al. PloS One. 2017;doi:10.1371/journal.pone.0129802.

Strekalova E, et al. Clin Cancer Res. 2015;doi:10.1158/1078-0432.CCR-14-2792.

Vergati M, et al. Curr Med Chem. 2017;doi:10.2174/0929867324666170116122915.

For more information:

Lindsay L. Peterson, MD, MSCR, is assistant professor of medicine in the division of medical oncology at Washington University School of Medicine. She also is a HemOnc Today Next Gen Innovator. She can be reached at 660 S. Euclid Ave., St. Louis, MO 63110; email: llpeterson@wustl.edu.

Disclosure: Peterson reports serving on the external editorial board of the American Cancer Society.

Oncology is a precision medicine-driven field. We strive to choose the right treatment based on each patient and their tumor characteristics. We’ve made great strides with this approach in terms of drug therapies. Our lifestyle recommendations, however, including dietary recommendations, have remained fairly general and, at this point, apply to all cancer survivors regardless of cancer type or tumor characteristics. We obviously consider certain patient characteristics — such as body weight, comorbidities, food preferences and allergies — but as much as we want to achieve personalized nutrition on a broad scale, we’re not quite there.

Interesting preclinical studies are evaluating specific diets for specific cancers and tumor characteristics, such as the tumor mutational profile. Small pilot studies and mechanistic studies in humans are looking at different diets for different patients. Such studies suggest certain diets may be more helpful for certain cancers.

Lindsay L. Peterson, MD, MSCR
Lindsay L. Peterson

For example, in a study of cell lines and subsequently mice, Strekalova and colleagues found that depriving triple-negative breast cancer of methionine — an essential amino acid that can be regulated through diet — increases the sensitivity of breast cancer cells to specific targeted therapies. A low-methionine diet is being tested for patients with triple-negative breast cancer, with one study planning to enroll 25 patients and another just over 100.

Similarly, there is interest in the ketogenic diet given the dependence of certain cancers on glucose. Again, there are promising preclinical studies, and some published data from human trials regarding its feasibility, impact on quality of life and effect on intermediary biomarkers. But, with most clinical trials still enrolling and few with clinical endpoints, its translation to clinical practice remains limited.

Thus, large-scale, confirmatory trials that indicate certain diets improve clinical outcomes for individual patients or groups of patients are lacking. One reason is the large number of patients and long follow-up required to show significant improvements in clinical outcomes such as PFS and OS. Such trials are expensive and logistically challenging in terms of successfully changing dietary patterns for many individuals for long periods. This does not mean these trials should not be completed, but rather that they must be carefully designed, as we do not have the means to conduct such studies for every possible dietary intervention in every possible population. Instead, we need to rely on well-designed preclinical studies and human studies using alternative clinical endpoints, such as pathologic complete response, and other changes in tumor characteristics, such as proliferation rate, to give us preliminary data regarding which diets are promising enough in which patient populations to be tested in larger-scale trials with more robust clinical endpoints.

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Ultimately, we want to be able to recommend a specific type of diet for a specific patient based on patient and tumor characteristics. For example, the diet for two similar patients with a HER2-positive cancer may be different based on their tumor mutational profiles. Currently, however, the data to make such recommendations are lacking.

Guidelines from the World Cancer Research Fund and American Institute for Cancer Research recommend that cancer survivors follow the same guidelines recommended for cancer prevention. Those guidelines include maintaining a healthy weight; eating lots of whole grains, fruits and vegetables; and limiting fast food, processed food, and foods high in fat and sugar. They recommend that survivors limit their red meat, processed meat and alcohol intake.

We convey those recommendations to our patients across all cancer types. We’d like to get to the point where we can say more about particular nutrients, diet content and strategies for each patient, but we don’t yet have the large-scale, definitive trials to do so.

References:

Chung HY and Park YK. J Cancer Prev. 2017;doi:10.15430/JCP.2017.22.3.127.

Lv M, et al. PloS One. 2014;doi:10.1371/journal.pone.0115147.

Morscher RJ, et al. PloS One. 2017;doi:10.1371/journal.pone.0129802.

Strekalova E, et al. Clin Cancer Res. 2015;doi:10.1158/1078-0432.CCR-14-2792.

Vergati M, et al. Curr Med Chem. 2017;doi:10.2174/0929867324666170116122915.

For more information:

Lindsay L. Peterson, MD, MSCR, is assistant professor of medicine in the division of medical oncology at Washington University School of Medicine. She also is a HemOnc Today Next Gen Innovator. She can be reached at 660 S. Euclid Ave., St. Louis, MO 63110; email: llpeterson@wustl.edu.

Disclosure: Peterson reports serving on the external editorial board of the American Cancer Society.