Peter Grace Named Chair Ad Interim of Symptom Research
Peter M. Grace, PhD, was named Chair Ad Interim of the Symptom Research department in March 2022.
Dr. Grace joined our faculty as an Assisatant Professor in 2016. Prior to joining MD Anderson, he held a position as a Research Assistant Professor, University of Colorado at Boulder.
The goal of his research laboratory is to understand the neuroimmune mechanisms of chronic pain and its control. His current work is investigating the adaptive immune mechanisms that initiate and maintain neuropathic pain after traumatic nerve injury. His team is also delineating the analgesic mechanisms and therapeutic potential of the ‘master regulator’ of the antioxidant response Nrf2. He has shown that the Nrf2 activator dimethyl fumarate relieves neuropathic pain, with ongoing work to advance this drug class for clinical treatment of chronic pain.
Cobi Heijnen Retirement - March 1, 2022
Cobi Heijnen is the former chair of the Symptom Research department. Dr. Heijnen joined our faculty as a Professor in 2012. Before joining MD Anderson, she served as Professor of Neuroimmunology and Chair of the Psychoneuroimmunology department at the University Medical Center Utrecht in the Netherlands.
Dr. 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. More recently, she has sought to understand the mechanisms and treatment of cancer-related stress, pain, fatigue and chemotherapy-induced cognitive deficits. She and her team have shown that nasal application of mesenchymal stem cells repairs brain damage and can reverse existing chemobrain. On the prevention front, she has shown that mitochondrial protectants prevent chemobrain and that pifithrin-µ and metformin can help prevent chemotherapy-induced neuropathy.
Dr. Heijnen remains a Professor at Rice University in Houston, Texas.
Annemieke Kavelaars Retirement - March 1, 2022
Annemieke Kavelaars has more than 25 years of experience as a researcher in the field of neuroimmunology resulting in a broad background in the field of brain, behavior and immunity. She joined MD Anderson in 2012, when she, Cobi Heijnen, and Robert Dantzer established the Neuroimmunology Laboratories as a new basic science lab within the Department of Symptom Research.
Dr. Kavelaars' research was dedicated to understanding the mechanisms underlying the development of chronic pain. Her studies in this area have focused on the role of the immune system in pain resolution. She has also investigated novel ways to prevent or treat pain caused by chemotherapy.
Updates: Symptom Assessment and Patient Report
"Fit-for-purpose" patient-reported outcome (PRO) measures are an invaluable resource for helping us to better understand how patients are actually being affected by new therapies.
This is especially important in the developmental pathway for new drugs, given that these PRO measures will enhance information about treatment tolerability and potential symptom-reduction benefit earlier in the drug-development process.
Read below about issues related to PROs in research and clinical practice.
Peter Grace - promoted to Associate Professor
Michael Lacagnina - promoted to Instructor
Andrew Shepherd - Pain Research Consortium Executive Committee Co-Chair
NCI R01 CA227064 , PQ12 Targeting HDAC6 for Chemotherapy-Induced Neuropathy and Chemobrain (Kavelaars and Heijnen)
Eli Lilly, Symptom Burden in Patient with Advanced/Metastatic Gastric, Gastroesophageal Junction, or Non-Squamous Esophageal Cancer (Cleeland, Wang, Williams)
NCI R21 NS104804, An Exploratory Proposal to Move Select Drosophila Nociception Screen Hits into Mouse Models (Kavelaars)
Concept domain validation and item generation for the Treatment-Induced Neuropathy Assessment Scale (TNAS). Support Care Cancer (Williams, Mendoza, Cleeland)
The high costs of low-grade inflammation: persistent fatigue as a consequence of reduced cellular-energy availability and non-adaptive energy expenditure. Front Behav Neurosci (Vichaya, Dantzer, Heijnen)
Modification of existing patient-reported outcome measures: qualitative development of the MD Anderson Symptom Inventory for malignant pleural mesothelioma (MDASI-MPM). Qual Life Res (Williams, Mendoza, Cleeland)
An effort expenditure perspective on cancer-related fatigue. Psychoneuroendocrinology (Lacourt, Vichaya, Heijnen, Dantzer)
Effect of an Enhanced Recovery After Surgery program on opioid use and patient-reported outcomes. Obstet Gynecol (Shi, Wang)
Low GRK2 underlies hyperalgesic priming by glial cell-derived neurotrophic factor, Front Pharmacol (Heijnen, Kavelaars)
Resolution of inflammation-induced depression requires T lymphocytes and endogenous brain interleukin-10 signaling. Neuropsychopharmacology (Laumet, Dantzer, Heijnen, Kavelaars)
Understanding the toxicity of cancer immunotherapies: use of patient-reported outcomes. J Immunother Precis Oncol (Mendoza)
Opportunities and challenges of incorporating clinical outcome assessments in brain tumor clinical trials. Neurooncol Pract, in press (Mendoza)
Patient-reported lung symptoms as an early signal of impending radiation pneumonitis in patients with non-small cell lung cancer treated with chemoradiation: an observational study. Qual Life Res (Shi, Cleeland, Wang)
MDASI Symptom Library Now Available
Individual and sets of symptom items from the MDASI Symptom Library may be added to the core MDASI or MDASI module to create an experimental MDASI that is tailored to your clinical research or practice. Items are added to the end of the original questionnaire to maintain the integrity of its psychometric validity.
All symptom items are available in English, as well as in other languages.
- Design of a customized MDASI that meets the needs of your study or practice;
- Available linguistically and psychometrically validated language translations of your selected items;
- Information about the sensitivity of particular items in specific populations.
Charges apply for consultation services and are based on the scope of the request.
ITEMS MAY NOT BE USED WITHOUT CONSULTATION.
Symptom Research Co-Hosts Attribution Workshop
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.
Can Patient-Reported Outcomes Assess Treatment Tolerability?
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.
Routine Symptom Monitoring: An Idea Whose Time Has Come?
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.
What is a Symptom?
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.
What is a Cutpoint?
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.