Heijnen Named Chair of Symptom Research
Jacoba (Cobi) J. Heijnen, Ph.D., has been named Chair of the Symptom Research department effective April 1, 2018.
Heijnen joined our faculty as a Professor in 2012. For the 15 years prior, she served as Professor of Neuroimmunology and Chair of the Psychoneuroimmunology edpartment at the University Medical Center Utrecht in the Netherlands.
Heijnen is one of the founding scientists of the field of psychoneuroimmunology. Her research focuses on cellular and molecular mechanisms of neuronal damage, rodent cognition and motoric behavior and therapeutic targets as neuroprotectants. Her more recent work seeks to understand the mechanisms and treatment of cancer-related stress, pain, fatigue and chemotherapy-induced cognitive deficits. She and her team have demonstrated that nasal application of mesenchymal stem cells repairs brain damage and can reverse existing chemobrain. On the prevention front, she has demonstrated that mitochondrial protectants prevent chemobrain and that Pifithrin-u and metformin can help prevent chemotherapy-induced neuropathy.
The Symptom Research department thanks Annemieke Kavelaars, Ph.D., who has served with distinction as Chair ad interim since September 2016.
The Departments of Symptom Research and Investigational Therapeutics hosted a 1-day workshop on methods of attributing adverse events during a cancer clinical trial.
Attribution is a judgment about the cause of toxicities that occur during the conduct of a clinical trial, and the degree to which these toxicities are due to the treatment under study or to a change in disease status or a comorbidity.
The workshop was co-chaired by Charles Cleeland, PhD and David Hong, MD, from MD Anderson and co-hosted by the Friends of Cancer Research and the Health and Environmental Sciences Institute. Participants represented academic researchers, pharmaceutical industry clinical trial sponsors and investigators, the US Food and Drug Administration, European regulatory agencies, the National Cancer Institute, and contract research organizations.
There was consensus that the current practice in attribution has challenges that may lead to misjudgments about drug safety. Overestimation of drug toxicity may lead to termination of a drug during its development or a decision about the maximum tolerated dose that may be below the level of the drug’s potential benefit. Conversely, underestimation may mask toxicities that will only become apparent after drug approval.
The current practice of attribution was reviewed, and concerns were raised about the variability of attribution judgments, the need for early identification of toxicities from new agents, and the utility of attribution in the drug-approval process.
The recommendations of the workshop will appear in a white paper suggesting changes in the attribution process that included training of principal investigators, revising the categories of attribution, and enhanced sharing of toxicity concerns during multisite, early-phase studies.
Funding for the workshop was provided by the MD Anderson Development Fund, the C. Stratton Hill Foundation, the MD Anderson Department of Investigational Cancer Therapeutics, AstraZeneca, and Genentech.
Tolerability is a crucial aspect of cancer therapeutic development, as it affects the ability of the patient to continue treatment at the recommended dose. Although safety is assessed by the clinician, the patient’s voice could provide vital information about how tolerable the therapy is (or isn’t).
Given the growing variety of new therapeutic agents and their wide range of mechanisms of action, the issue of treatment tolerability in clinical trials is becoming more urgent and more complex. This and related topics were explored at an April 2017 workshop organized by the US Federal Drug Administration and the Critical Path Institute.
A number of important challenges exist for conceptual usage of patient-reported outcomes assessment tools. These include demonstrating a trajectory of adverse events, especially for low grade events in the longer term. Another issue is how and whether to assess overall symptomatic side effect burden, whether a summary score can give appropriate sensitivity to specific side effects. Different dimensions to symptom burden can also be considered, such as the interference items used in the MDASI assessment. Further study is needed in this area.
There is significant value, the workshop concluded, in better forms of communicating a drug’s side-effect profile to patients, clinicians, and regulators. This will help with effective assessments of tolerability and safety at all stages of drug development. There is sustained international effort to include PRO assessments of adverse events in these stages, from trial design to label claims.
At ASCO 2017, Ethan M. Basch, MD, MSc, FASCO, of The University of North Carolina at Chapel Hill, presented data on the use of a web-based system that allowed patients to report symptoms to their clinicians, prompting them to intervene earlier.
“Although symptom management is a cornerstone of high-quality cancer care, prior research has shown that doctors miss up to half of patients’ symptoms during cancer treatment,” explained Dr. Basch.
Patients in the self-reporting arm experienced quality-of-life benefits and a median overall survival of 5 months longer, compared with patients in the standard-of-care arm.
Dr. Basch proposed that proactive symptom monitoring prompted earlier intervention, it helped patients stay more functional, and it enhanced control of chemotherapy side effects, enabling longer and more intensive treatment where prescribed doses can be maintained.
New Standard of Care?
The significant impact of the study led to calls for symptom monitoring of this kind to become the new standard of care.
As a discussant highlighted, this model offered similar if not greater benefits than many of the latest approved drugs, and this is a cost-effective way to improve outcomes.
Online Tool Shows High Levels of Adherence
In the study, even among the elderly, patients self-reported 73% of the time when prompted to do so, and nurses acted upon 77% of the alerts they received; interventions included referrals to emergency services, dose modifications, and counseling.
A symptom is a sensation or perception of change related to health function experienced by an individual. Symptoms such as fatigue, pain, and nausea can be classified according to their severity and perceived impact on function.
Symptoms add to the burden of having a chronic disease, such as cancer, and they affect virtually all aspects of life. Symptoms interfere with a person's mood, level of activity, and ability to relate to others.
How Can We Assess Symptoms?
Symptoms are best understood through self-report from patients at specific stages of specific types of cancer. Such patient-reported outcomes (PROs) have been recognized by the US Food and Drug Administration as legitimate primary outcome variables for clinical trials.
The Department of Symptom Research designs and licenses fit-for-purpose PRO-based assessment tools to measure the symptoms experienced by cancer patients, to determine their severity and how they affect quality of life. Please visit our Symptom Assessment Tools page.
A cutpoint is a number on a numerical rating scale that divides a continuous measure into discrete categories, such as mild, moderate, and severe. This categorization aims to better inform treatment decision making for clinicians, facilitate the interpretation of study outcomes, and aid in the development of policy or clinical practice guidelines.
How Do We Determine a Cutpoint?
To determine cutpoints on the 0‒10 numerical rating scale, such as that used in the MD Anderson Symptom Inventory (MDASI), the Brief Pain Inventory (BPI), and the Brief Fatigue Inventory (BFI), Serlin et al. (1995) correlated pain intensity to the level of interference of the pain with the daily functioning of patients with cancer pain, by estimating how much of the variance in pain-related functional impairment could be explained by different possible pain intensity classifications. This approach was repeated for other measures in cancer patients, i.e., fatigue (Wang et al., 2012) and pain interference (Shi et al., 2017).
Serlin RC, Mendoza TR, Nakamura Y, Edwards KR, Cleeland CS. When is cancer pain mild, moderate or severe? Grading pain severity by its interference with function. Pain 61(2): 277-84, 1995.
Wang XS, Zhao F, Fisch MJ, O'Mara AM, Cella D, Mendoza TR, Cleeland CS. Prevalence and characteristics of moderate to severe fatigue: a multicenter study in cancer patients and survivors. Cancer 120(3): 425-32, 2014.
Shi Q, Mendoza TR, Dueck AC, Ma H, Zhang J, Qian Y, Bhowmik D, Cleeland CS. Determination of mild, moderate, and severe pain interference in patients with cancer. Pain 158(6):1108-12, 2017.
Published Book Recognized
Robert Dantzer, PhD, DVM
Principal Investigator, Symptom Research Neuroimmunology Lab
Our book "Inflammation-Associated Depression: Evidence, Mechanisms and Implications" was the most highly cited of the 7,000 volumes published by Springer Nature in 2017.
Robert Dantzer, DVM, Ph.D., was awarded a 2017 Distinguished Investigator Grant from the Brain & Behavior Research Foundation. These grants support innovative projects in diverse areas of neurobiological and behavioral research. Dr. Dantzer's project will focus on the relationship between elevated levels of inflammation in the body and depression. His proposal, entitled "Motivational Basis ofInflammation-Induced Depression," will aim to understand the underlying mechanisms in depression and could lead to effective treatment of major depressive disorder in patients with chronic low-grade inflammation.
- Cobi and Annemieke - PQ9 R01 award – “Mesenchymal Stem Cells to Repair Chemobrain” - $402,051 per year, 5 years
- Robert IRG – “Role of exosomes in tumor-host interactions”, $75,000 – 2 years
- Elizabeth – Cancer Survivorship on “Investigating mitochondrial functioning in relation to fatigue” - $50,000 over 2 years
- Robert – Gold Medal of the French Academy of Agricultural Sciences for career achievements
- Geoffroy – DoIM Cyrus Scholar Award for Outstanding Basic/Translational Research
- Annemieke – MDACC 2017 Chamberlain Mentor Award
- Charlie – DoIM Gagel Lifetime Achievement Award
- Robert – should we mention Ajinomoto?
- Hosted the PNIRS conference in Galveston