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Weighing Cognitive Decline After Prostate Cancer Treatment

October 22, 2019
by Julie Parry

The October 17, 2019 Department of Internal Medicine’s inaugural The Second Century of Women at Yale: Emerging Leaders in Internal Medicine Medical Grand Rounds, “Cognitive Side Effects of Cancer Therapy,” was presented by Herta H. Chao, MD, PhD, associate professor of medicine (medical oncology).

Chao is director of the Cancer Clinical Trials Program, and deputy director of the Comprehensive Cancer Center at the VA Connecticut Healthcare System (VACHS). Through her work at VACHS, she has encountered patients who underwent successful cancer therapy, but complained about cognitive side effects after certain treatments.

Officially identified by the National Coalition for Cancer Survivorship, cognitive decline secondary to cancer therapy is a challenge that many survivors report. Citing the work of Tim Ahles, PhD, she acknowledged that experiencing this cognitive decline can have an effect on work or school performance. Research into cognitive side effects in the pediatric population have changed the way that children with cancer are treated.

“It is very important for informed decision making before a patient decides to undergo cancer treatment,” explained Chao.

The first studies into this phenomenon, known as ‘chemo brain or chemo fog’ were published in the 1990s. In much of the previous research, neuropsychological tests were used that were developed to assess major organic brain dysfunction, like dementia or traumatic brain injury. These tests are often subject to training effects and may not have sufficient sensitivity to detect less severe neurocognitive changes.

“Why does a medical oncologist who wants to cure cancer actually start to study cognitive side effects of treatment? Patients will change your mind,” said Chao.

Chao recalled a patient who said that the hormone shots he was receiving to treat his prostate cancer has ‘fried’ his brain. He was referring to androgen deprivation therapy (ADT). However, he scored well on commonly used neuropsychological tests. This patient’s experience made her realize that better tools might be needed to assess the cognitive impact of cancer treatment. She wondered if ADT led to clinically relevant cognitive impairment that is underrecognized by traditional neuropsychological tests. Additionally, she thought that brain imaging with a functional MRI (fMRI) could be a better way to detect these changes.

In a pilot study at VACHS, Chao combined fMRI with N-back task to assess working memory and Stop-signal task to assess inhibitory control to evaluate patients with non-metastatic prostate cancer receiving ADT for six months compared to control patients. In her study, no statistically significant differences in the working memory and the inhibitory control tasks were observed. She admitted disappointment but needed to wait for her colleagues to look at the fMRI imaging. The fMRI analysis showed that ADT for six months resulted in significant alteration in brain activations during cognitive control and disrupted resting state functional brain connectivity. Read “Effects of androgen deprivation on brain function in prostate cancer patients – a prospective observational cohort analysis,” in BMC Cancer.

Chao’s current study investigates neurocognitive changes from longer-term ADT prospectively over 24 months in more than 200 men with non-metastatic prostate cancer.

“I want to emphasize that we need leaders with vision. I really thank Roy [Herbst] for all his support. He understood the importance of my work and gave me bridge funding to continue my work until I was able to secure grants.” She also thanked her numerous mentors and supporters, including Ruth McCorkle, PhD, RN, FAAN, FAPOS, who passed away on August 17.

On October 17, The Second Century of Women at Yale: Emerging Leaders in Internal Medicine was the inaugural event for this annual speaking series. This event was created as a way to celebrate the gender diversity and female leaders within the Department of Internal Medicine.

Chao was nominated by Medical Oncology Section Chief, Roy S. Herbst, MD, PhD, Ensign Professor of Medicine. In his nomination letter, Herbst called Chao as “one of our key oncology leaders within the VACHS, functioning in three high‐level roles since 2012. She has elevated the standard of care and education at the VA and she has done so through her exemplary administrative and clinical service.” Currently the principal investigator (PI) on three federal grants and the site-PI, or co‐investigator on 15 clinical trials, Chao’s research focuses on novel treatments for cancers that have high incidence rates in veterans, such as prostate and lung cancer.

To learn more about Chao’s work and watch Medical Grand Rounds, watch the Grand Rounds video or review her bio.   

The Section of Medical Oncology is one of the 11 sections within the Department of Internal Medicine at Yale School of Medicine. For more information on their work, visit Medical Oncology.

Submitted by Julie Parry on October 22, 2019