NIH funding opportunity – Mechanisms of Cancer and Treatment-related Symptoms and Toxicities (R21)

May 23, 2016 by School of Medicine Webmaster

This FOA is intended to stimulate research aimed at better understanding the complex interaction of biological, cognitive, behavioral, and sociocultural factors that contribute to cancer and treatment related symptoms and toxicities throughout the disease trajectory. Data from these preliminary studies would be used to validate and extend the findings in larger cohort studies and/or test novel, mechanistically-driven interventions via the R01 funding mechanism. Of particular interest is to gain new insights about these factors, either alone or in combination, in minority, underserved, the elderly, and pediatric and young adult populations. Specifically, the FOA aims to identify, describe, and quantify these factors associated with acute and chronic symptoms and toxicities.

Many advances have been made in the treatment of cancer with an increasing number of treatment options available to cancer patients, including multimodality and targeted therapies. As a result, many patients are living longer but at the same time they are experiencing an increase in symptom burden due to exposure to multiple lines of cancer therapy. Some toxicities are acute while others become chronic, lasting months to years after the therapy is completed. Often, the extent of the toxicity burden is unknown until the drug is administered to a large population of ‘real-world’ patients with comorbidities that were not included in a clinical trial, or until long-term follow-up uncovers late-onset toxicities. Commonly, patients experience multiple symptoms concurrently. Symptomatic toxicities may include neurotoxicites (peripheral neuropathy, neurocognitive changes), altered sleep, altered gastrointestinal function (nausea/vomiting, diarrhea, constipation, dysphagia, mucositis), fatigue and dermatological changes (rash, hand/foot syndrome). Patients may also experience symptoms related to cancer including pain, dyspnea, and altered bowel and bladder function.

The impact of cancer and treatment related symptoms and toxicities on health related quality of life is significant. Fatigue and neurotoxicities, for example, may affect the patient’s ability to work and do household chores such as finances, grocery shopping and care for young children. Furthermore, patients are affected psychologically, socially and spiritually, experiencing symptoms such anxiety, depression, and insomnia.

Despite the prevalence and significant impact of cancer and treatment related symptoms and toxicities, gaps remain in symptom science research. The natural trajectory, as well as the underlying mechanisms of many symptoms and toxicities, is not well understood. There are no clear predictors of who may experience these symptoms and toxicities and why they vary in severity and duration from one individual to another. With the introduction of newer treatment approaches, specifically in the field of radiation oncology, little is known about the differential rate and severity of side effects and toxicities. Also, it is unknown why some patients respond and others do not to the same symptom intervention despite having similar disease and treatment. Lastly, most symptoms, such as pain, fatigue, and nausea, rely exclusively on patient reporting and ongoing research is needed to understand how these data are utilized and analyzed. There is a growing recognition of the role of patient reported outcomes (PROs) in symptom research, but their potential use in customizing healthcare interventions remains largely unknown.

For most of the toxic effects caused by cancer treatment, no approved mitigating therapies or evidence-based management strategies are in place. Efforts to develop nontoxic cancer treatments or therapies to relieve treatment-related toxicities are hampered by a lack of mechanistic insight into these adverse events, difficulties in objectively measuring treatment-related toxic effects and insufficient studies validating pre-clinical biomarkers in the clinical setting.

Beyond the biology of symptoms, there are gaps in understanding how individual characteristics, attitudes, emotional states and the social environment influence patients’ perceptions of symptoms, their severity and self-management. Further, the role behavioral factors play in influencing the reporting of symptoms (what, how, and frequency of information reported) needs further research. In addition, there is a lack of research on the trajectories of symptoms in special populations, such as the elderly, adolescent and young adult (AYA) and racial and ethnic minorities. Populations such as the elderly and certain racial and ethnic groups have a higher incidence of co-morbidities and it is unknown how these will impact the biology of certain symptoms, such as fatigue, sleep. Cancer among racial and ethnic populations occurs at a younger age, presents more aggressively in advanced stages and results in poorer outcomes. However, little is known whether the duration and severity of toxicities vary in these populations.

Specific Research Objectives

Applications submitted to this FOA should examine the complex interaction of biological, cognitive, behavioral, and sociocultural factors that contribute to cancer and treatment related symptoms and toxicities throughout the disease trajectory. Applications should bring together transdisciplinary teams of investigators with expertise in symptom science, including behavior, biology, and other basic and clinical science disciplines relevant to the pathways being studied. The research may occur in a variety settings (academic, community), during the various stages of the disease trajectory (diagnosis, active treatment, post-treatment/survivorship, palliative care, hospice). Research areas may include, but not limited to:

Biologic mechanisms of symptoms and toxicities

  1. What biomarkers are ready to be validated in the clinical setting to elucidate the mechanisms of symptoms and treatment related toxicities?
  2. What are the biomarkers that determine individual susceptibilities to symptoms and toxicities, either alone or in combination?
  3. How do certain co-morbidities affect the development and severity of symptoms and toxicities?
  4. What is the natural trajectory of selected symptoms lacking information?
  5. Are there biological differences by race that would impart a different symptom experience?

Behavioral, psychological, and sociocultural factors contributing to the development of symptoms and toxicities

  1. How do factors such as gender, age, and race/ethnicity influence the development and severity of symptoms and toxicities?
  2. What are the clinical, genetic and behavioral profiles of patients, including racially and ethnically diverse populations, undergoing the same cancer treatment, who do and do not develop disease and treatment related symptoms and toxicities.
  3. Are there predictive models of who may or may not develop certain symptoms and toxicities? Can severity and duration (acute to chronic) be predicted?
  4. What are the influences of knowledge, attitudes and culture on the experience of symptoms and toxicities?
  5. What factors, including self-management strategies, influence reporting of symptoms and toxicities?

Patient reported outcomes (PROs) in symptom research

  1. What novel methods for the analysis of PROs, symptom and toxicity data can be developed beyond descriptive?
  2. How can PRO data be used to customize interventions to prevent or manage symptoms and toxicities?
  3. What PRO tools need validation in special populations or cultures?

Deadlines:  standard dates apply


Filed Under: Funding Opportunities