Accelerated Aging after Cancer Treatment, with Arti Hurria, MD, Lee Jones, PhD, and Hyman B. Muss, MD, FASCO

February 28, 2017
Download MP3 (3.74 MB/12:34)

In today’s podcast, Dr. Arti Hurria, Dr. Lee Jones, and Dr. Hyman Muss will discuss their article “Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions.” They discuss research on why aging-related problems—such as physical conditions or cognitive decline—occur more frequently in cancer survivors, and how these aging-related problems can be prevented or minimized.  

Transcript: 

ASCO:You’re listening to a podcast from Lineagotica (Cancer dot Net). This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

This podcast is part of a series featuring articles from the 2016 ASCO Educational Book. Published annually, the Educational Book is a collection of articles written by ASCO Annual Meeting speakers and oncology experts. Each volume highlights the most compelling research and developments across the multidisciplinary fields of oncology.

In today’s podcast, Dr. Arti Hurria, Dr. Lee Jones, and Dr. Hyman Muss will discuss their article “Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions.” They discuss research on why aging-related problems—such as physical conditions or cognitive decline—occur more frequently in cancer survivors, and how these aging-related problems can be prevented or minimized. 

Dr. Hurria is the Director of the Cancer and Aging Research Program at City of Hope. Dr. Jones is a medical researcher at Memorial Sloan Kettering Cancer Center. Dr. Muss is the Director of the Geriatric Oncology Program at the University of North Carolina Lineberger Comprehensive Cancer Center Program.

ASCO would like to thank Dr. Hurria, Dr. Jones, and Dr. Muss for discussing this topic.

Dr. Hurria: Hello. My name is Dr. Arti Hurria from City of Hope. I'm joined today by Dr. Lee Jones from Memorial Sloan Kettering Cancer Center and Dr. Hyman Muss from the University of North Carolina at Chapel Hill. We will be sharing some of the key points from our 2016 educational book article titled, Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions, and talking about the implications for patients. There is a growing body of evidence showing that cancer and cancer treatment is associated with the accelerated aging for patients. Presently there are 8 million cancer survivors aged 65 or older in the United States, and this number is anticipated to grow to 11 million by 2020. A key survivorship issue for older adults with cancer is the short and long term impact of cancer therapy on the aging process. Dr. Jones, what is meant by the term accelerated aging and what does it mean for cancer survivors?

Dr. Jones: Accelerated aging means that the signs of aging, like physical and cognitive decline, occur earlier or differently than expected. Aging-related problems are often found among adults who are 65 and older. However, cancer survivors are more likely to develop age-related and other chronic conditions, such as heart attacks or things like heart failure, at a different rate than older adults without a history of cancer. Cancer survivors are more likely to report poorer physical and mental health-related quality of life, and also these individuals are more likely to have limitations in performing normal activities of daily living. And they also have mobility limitations if you look at individuals of the same age who don't have a history of cancer.

Dr. Hurria: Thank you Dr. Jones. It is also true that the aging process is unique to the individual, and chronological age is a poor descriptor of an older adult. For example, two individuals who are chronologically aged 75 can have very different functional ages. At the extremes, one individual could be wheelchair bound in a nursing home, and another may be a marathon runner. Dr. Muss, can you tell us more about how doctors can detect accelerated aging?

Dr. Muss: Dr. Hurria, there are two main ways in which an oncologist can get a better sense of the functional age of an adult. The first is through performing a geriatric assessment, and the second, is by assessing frailty. A geriatric assessment identifies factors other than chronological age that can predict the risk of morbidity and mortality in older adults. These include the functional status, cognition, comorbidity, psychological state, social support, and nutritional status. In patients with cancer, this assessment can identify areas of vulnerability not otherwise detected in a routine history and physical examination, predict cancer treatments toxicity and survival, and serve as a platform for interventions to decrease toxicity risk. Another means of assessing the aging process, is measuring frailty. Frailty can be defined as a decrease in physiologic reserve that places an individual at increased risk for adverse events such as hospitalization, falls and poor overall survival. There are several tools available to assess frailty that could be helpful for clinicians. Geriatric assessment is the cornerstone for assessing function in patients with cancer prior to treatment. It can be helpful in predicting survival, treatment-related toxicity and other outcomes. And it trumps performance status in making treatment decisions.

Dr. Hurria: Thank you, Dr. Muss. How does cancer treatment make a patient more likely to experience accelerated aging? Dr. Jones, can you please tell us more?

Dr. Jones: Of course, there is little doubt that the treatment of cancer, especially things like radiation and some of the newer forms of cancer therapy, some of these molecular-targeted therapies, can accelerate the aging process. Specific conditions that have been linked to these types of cancer treatments include things like heart failure or cardiovascular disease among the patients that have received a particular type of chemotherapy called anthracycline-based therapies. They can also experience conditions like peripheral neuropathy among patients who are receiving a certain kind of chemotherapy called taxanes. And there's also declines in bone health in individuals that receive a particular type of endocrine therapy called aromatase inhibitors.

A study of patients between the ages of 60 to 70 who had had a history of early stage breast cancer showed that those who received chemotherapy were at higher risk of cognitive decline after receiving such treatments.  Indeed, survivors of childhood cancer survivors have a greatly increased risk of developing serious or life-threatening chronic conditions by the age of 45. Measures of frailty—and frailty is basically measures of things like low muscle mass, low energy expenditure, low walking speed, and general overall weakness. If you look at a measure of frailty in the individuals diagnosed with cancer, basically, at age 40, those individuals have the same frailty measures and scores as an individual without a history of cancer, who is age 65. So again, this is another example of accelerated aging.

Dr. Hurria: It is clear that accelerated aging is a serious concern for cancer survivors. Dr. Muss, what is being done to help cancer survivors avoid these negative effects of treatment?

Dr. Muss: We know modern cancer treatment, especially chemotherapy and radiation, accelerate aging from studies of childhood cancer survivors. Here, great achievements in cure rates have been associated with increased risk of cardiovascular disease and frailty at earlier ages than the general population. Scientists are trying to tackle this issue before treatment even starts starting with using biomarkers. Biomarker is a term that refers to a certain molecular identifier found in persons' urine, or blood. We now know of several aging biomarkers and can use these to help identify patients who are most vulnerable to cancer treatment. This will allow doctors to minimize the negative effect of their patient's cancer treatment. More specifically, the p16INK4a gene expression has major promise as a biomarker of chemotherapy toxicity. This gene expression increases approximately tenfold between ages 20 and 80, and this dynamic range provides for a more robust marker as a predictor of molecular aging. In one study of women receiving chemotherapy for early stage breast cancer, p16INK4a expression increased immediately after treatment, and remained elevated for at least 12 months after. Data suggests that these elevations did not improve. This change corresponds to an almost 15-year increase in chronologic age.

Current studies are underway exploring the potential role of p16 gene expression as a predictor of toxicity and subsequent comorbidity in patients receiving chemotherapy.

Dr. Hurria: There are also steps cancer survivors can take to minimize the effects of accelerated aging due to their cancer treatment. We've seen, among woman who were treated for early-stage breast cancer, that aerobic exercise is the most effective therapy to improve reserved capacity of all oxygen transport organs, which together leads to favorable improvements in physical function.

Dr. Jones: That's right, Dr. Hurria. Patients with cancer experience considerable impairments in exercise capacity during cancer therapy that appear to persist even years following the completion of primary treatment. Such negative effects are consistent with an accelerated cardiovascular aging and may, in part, contribute to increased risk of cardiovascular disease, frailty, and functional dependence in certain cancer survivor populations. Based on current data, supervised aerobic training appears to be a safe, tolerable, and efficacious intervention strategy to potentially offset as well as recover impaired exercise capacity in a broad range of patients with cancer. The optimal timing, type, and schedule of exercise training, as well as the long-term clinical implications of declines and/or improvements in exercise capacity are a high research priority in geriatric oncology.

Dr. Hurria: We're finding a lot of evidence to support the hypothesis that cancer and/or cancer treatment is associated with accelerated aging. However, several gaps in knowledge remain, and future research is needed to understand the implications of these findings as well as ways to decrease the risk. Scientists are working hard to fill the gaps in knowledge by expanding studies focusing on the survivorship issues facing older adults with cancer, the impact of cancer on the aging process, as well as interventions to decrease the risk. Inclusion of a geriatric assessment and biomarkers of aging and research studies will be needed to accomplish these goals. Interventions are needed to halt or modify the accelerated aging phenotype seen in survivors of cancer. The compelling data with regard to exercise can serve as a model for future studies in the years to come. Please view our article online, at asco.org/edbook for a more in-depth discussion of this topic. Thank you.

ASCO: Thank you Dr. Hurria, Dr. Jones, and Dr. Muss. Please visit asco.org/edbook to read the full article. And for more expert interviews and stories from people living with cancer, visit the Lineagotica Blog at lineagotica.info/blog.

Lineagotica is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high-quality cancer care. Thank you for listening to this Lineagotica Podcast.