Hemotherapy-related cognitive impairment (CRCI) is a significant problem that develops in up to 75% of breast cancer patients, often persisting for many years and significantly impairing quality of life. The etiology of CRCI is not clearly understood, and there are no effective management approaches. Reduction of inflammation is a promising target to alleviate CRCI, and translational investigators well versed in clinical and behavioral research, immunology and neuroscience are needed to advance knowledge in this area. Dr. Michelle Janelsins, an Assistant Professor in the Department of Radiation Oncology at the University of Rochester Medical Center, is applying for a K07 mentored career development award to expand her clinical and behavioral research skills and to integrate new skills with her strong basic science abilities as an independent clinical and translational cancer control investigator with expertise in interventions for CRCI. This application provides Dr. Janelsins with new training and skills necessary to develop, implement, and assess interventions in a clinical setting and combine these new abilities with her established skills and knowledge in immunology and neuroscience to successfully conduct the first randomized, controlled, pilot study we are aware of investigating the influence of two novel interventions (exercise and ibuprofen) on CRCI and inflammation. Career Development Plan: Dr. Janelsins'previous training provides an outstanding initial foundation, but she needs new training in the conduct of Phase II-III clinical trials, cognitive assessment and related bio behavioral immune pathways, and exercise intervention development to become a successful independent clinical researcher with expertise in bio behavioral research focusing on understanding and alleviating CRCI. Her four career development training goals are: 1) to develop expertise in cancer control Phase II-III clinical trials, 2) to develop expertise in cognitive science and cognitive assessments and related bio behavioral immune pathways, 3) to develop expertise in exercise physiology, physical activity assessments and exercise interventions, and 4) to promote the development of an independent academic research career. Dr. Janelsins has an outstanding mentoring team: Dr. Gary Morrow, a leading cancer control researcher with NCI funding for over thirty years, is her senior mentor;Drs. Tim Ahles and Deborah Cory-Slechta provide expertise in neurocognitive testing as her co-mentors;Dr. Karen Mustian provides expertise in exercise interventions as a co-mentor;and advisors Drs. Jan Moynihan (immunology), Michelle Shayne (medical oncology), and Charles Heckler (biostatistics) provide specific expertise in key areas. Research Plan: The proposed Phase II RCT, based partially on Dr. Janelsins'preliminary data, is a three-arm study comparing the influence of ibuprofen + health education (Arm 1), placebo + exercise (Arm 2) and placebo + health education (control;Arm 3) on CRCI in 120 breast cancer patients undergoing chemotherapy experiencing CRCI. The exercise and ibuprofen arms will each be compared to the control (Arm 3) with the primary goal of assessing, analyzing, and interpreting the preliminary efficacy of each intervention in alleviating CRCI and the effects of each intervention on inflammation. This award will position Dr. Janelsins to become a leader in the cancer and cognition field who, over her career, will make meaningful contributions to patient care. Research findings will be used to design future definitive RCTs, ensure Dr. Janelsins'successful transition to an independent, R01- funded, clinical and translational investigator, and ultimately reduce the public health burden from CRCI.

Public Health Relevance

Up to 75% of cancer patients experience chemotherapy-related cognitive impairment (CRCI), often termed chemobrain, which can last for many years after treatment. These difficulties in cognitive functioning, such as problems with memory, can impair a patient's ability to carry out routine daily activities. There are no effective treatments for CRCI and the exact etiology is unknown. This project will provide information on two possible interventions for CRCI and explore mechanisms of intervention effects.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Academic/Teacher Award (ATA) (K07)
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Study Section
Subcommittee G - Education (NCI)
Program Officer
Perkins, Susan N
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University of Rochester
Schools of Dentistry
United States
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Janelsins, Michelle C; Heckler, Charles E; Peppone, Luke J et al. (2018) Longitudinal Trajectory and Characterization of Cancer-Related Cognitive Impairment in a Nationwide Cohort Study. J Clin Oncol :JCO2018786624
Williams, AnnaLynn M; Shah, Raven; Shayne, Michelle et al. (2018) Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. J Neuroimmunol 314:17-23
Peoples, Anita R; Roscoe, Joseph A; Block, Robert C et al. (2017) Nausea and disturbed sleep as predictors of cancer-related fatigue in breast cancer patients: a multicenter NCORP study. Support Care Cancer 25:1271-1278
Janelsins, Michelle C; Heckler, Charles E; Peppone, Luke J et al. (2017) Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study. J Clin Oncol 35:506-514
Williams, Annalynn M; Zent, Clive S; Janelsins, Michelle C (2016) What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. Br J Haematol 174:835-46
Janelsins, Michelle C; Peppone, Luke J; Heckler, Charles E et al. (2016) YOCAS©® Yoga Reduces Self-reported Memory Difficulty in Cancer Survivors in a Nationwide Randomized Clinical Trial: Investigating Relationships Between Memory and Sleep. Integr Cancer Ther 15:263-71
Magnuson, Allison; Mohile, Supriya; Janelsins, Michelle (2016) Cognition and Cognitive Impairment in Older Adults with Cancer. Curr Geriatr Rep 5:213-219
Janelsins, Michelle C; Heckler, Charles E; Thompson, Bryan D et al. (2016) A clinically relevant dose of cyclophosphamide chemotherapy impairs memory performance on the delayed spatial alternation task that is sustained over time as mice age. Neurotoxicology 56:287-293
Williams, A M; Janelsins, M C; van Wijngaarden, E (2016) Cognitive function in cancer survivors: analysis of the 1999-2002 National Health and Nutrition Examination Survey. Support Care Cancer 24:2155-2162
Conley, Claire C; Kamen, Charles S; Heckler, Charles E et al. (2016) Modafinil Moderates the Relationship Between Cancer-Related Fatigue and Depression in 541 Patients Receiving Chemotherapy. J Clin Psychopharmacol 36:82-5

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