Principal Investigator

Michelle C
Janelsins
Awardee Organization

University Of Rochester
United States

Fiscal Year
2014
Activity Code
DP2
Project End Date

Clinical and Translational Approaches to Cognitive Impairments in Cancer

While chemotherapy has helped to improve survival for cancer patients, the side effects lead to substantial detrimental effects on quality of life tht can be debilitating; these side effects, including cognitive impairments, have become a major focus of research. Chemotherapy-related cognitive impairment (CRCI) is characterized by difficulty in memory, attention, concentration and executive function. CRCI is most pronounced and severe during chemotherapy (in up to 80% of patients), however, it can last for years following treatment in up to 35% of survivors. With over 13 million cancer survivors in the US, it is estimated that up to 4 million survivors could be living with long-lasting effects of CRCI. CRCI
is particularly significant because long-term cognitive impairment can develop, CRCI negatively impacts quality of life, and CRCI can affect treatment adherence. I'm currently conducting a NCI K Award in patient-oriented research investigating interventions targeting inflammation to alleviate cognitive difficulties in breast cancer patients receiving chemotherapy; my laboratory focuses solely on CRCI research. One of the main hypotheses in our field is that inflammation may drive cognitive impairment in these patients. While this is becoming well-accepted in our field, there is a gap in understanding the nature of this inflammatory response as most clinical research studies have limited access to biological correlates of CRCI. There is also a lack of investigators that can carefully assess neuro-immune factors in basic science models as well as in people. I am proposing to use my knowledge in basic immunology, neuroimmunology, and neuroscience with my behavioral research training in cognitive science, neuropsychology and clinical cancer control to address these gaps in the field. While this research focuses on CRCI, it
has broad implications for many areas of cancer control and survivorship. Part I of this application involves careful assessment and understanding of the role of inflammation on brain function and neuroinflammation in chemotherapy animal models (using a breast cancer chemotherapy paradigm; Part IA) and following up with analyzing possible etiological factors in a breast cancer patient cohort that is being treated with the same chemotherapy regimen (Part IB). In Part II of this application, we will utilize animal models to develop and test intervention for cancer-related cognitive impairment (this is not commonly done in cancer control research) which will allow us to move forward with the most successful interventions for testing in clinical research. Overall, this proposal will allow us to better understand immunologic and neurotoxic effects of CRCI, develop interventions for CRCI, and improve the overall public health burden of this troublesome side effect.

Publications

  • Williams AM, van Wijngaarden E, Seplaki CL, Heckler CE, Weber MT, Barr PM, Zent CS, Janelsins MC. Cognitive function in patients with chronic lymphocytic leukemia: a cross-sectional study examining effects of disease and treatment. Leukemia & lymphoma. 2020 Jul;61(7):1627-1635. Epub 2020 Mar 9. PMID: 32148161
  • Mustian KM, Cole CL, Lin PJ, Asare M, Fung C, Janelsins MC, Kamen CS, Peppone LJ, Magnuson A. Exercise Recommendations for the Management of Symptoms Clusters Resulting From Cancer and Cancer Treatments. Seminars in oncology nursing. 2016 Nov;32(4):383-393. Epub 2016 Oct 21. PMID: 27776835
  • Williams AM, Zent CS, Janelsins MC. What is known and unknown about chemotherapy-related cognitive impairment in patients with haematological malignancies and areas of needed research. British journal of haematology. 2016 Sep;174(6):835-46. Epub 2016 Jul 8. PMID: 27391367
  • Janelsins MC, Heckler CE, Peppone LJ, Ahles TA, Mohile SG, Mustian KM, Palesh O, O'Mara AM, Minasian LM, Williams AM, Magnuson A, Geer J, Dakhil SR, Hopkins JO, Morrow GR. Longitudinal Trajectory and Characterization of Cancer-Related Cognitive Impairment in a Nationwide Cohort Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Sep 21;36(32):JCO2018786624. Epub 2018 Sep 21. PMID: 30240328
  • Williams AM, Khan CP, Heckler CE, Barton DL, Ontko M, Geer J, Kleckner AS, Dakhil S, Mitchell J, Mustian KM, Peppone LJ, Kipnis V, Kamen CS, O'Mara AM, Janelsins MC. Fatigue, anxiety, and quality of life in breast cancer patients compared to non-cancer controls: a nationwide longitudinal analysis. Breast cancer research and treatment. 2021 May;187(1):275-285. Epub 2021 Jan 4. PMID: 33392843
  • Inglis JE, Janelsins MC, Culakova E, Mustian KM, Lin PJ, Kleckner IR, Peppone LJ. Longitudinal assessment of the impact of higher body mass index on cancer-related fatigue in patients with breast cancer receiving chemotherapy. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020 Mar;28(3):1411-1418. Epub 2019 Jul 2. PMID: 31267279
  • Janelsins MC, Peppone LJ, Heckler CE, Kesler SR, Sprod LK, Atkins J, Melnik M, Kamen C, Giguere J, Messino MJ, Mohile SG, Mustian KM. YOCAS©® Yoga Reduces Self-reported Memory Difficulty in Cancer Survivors in a Nationwide Randomized Clinical Trial: Investigating Relationships Between Memory and Sleep. Integrative cancer therapies. 2016 Sep;15(3):263-71. Epub 2015 Nov 29. PMID: 26621521
  • Janelsins MC, Heckler CE, Thompson BD, Gross RA, Opanashuk LA, Cory-Slechta DA. 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. 2016 Sep;56:287-293. Epub 2016 Jun 28. PMID: 27371410
  • Kerns SL, Kundu S, Oh JH, Singhal SK, Janelsins M, Travis LB, Deasy JO, Janssens AC, Ostrer H, Parliament M, Usmani N, Rosenstein BS. The Prediction of Radiotherapy Toxicity Using Single Nucleotide Polymorphism-Based Models: A Step Toward Prevention. Seminars in radiation oncology. 2015 Oct;25(4):281-91. Epub 2015 May 15. PMID: 26384276
  • Campbell KL, Zadravec K, Bland KA, Chesley E, Wolf F, Janelsins MC. The Effect of Exercise on Cancer-Related Cognitive Impairment and Applications for Physical Therapy: Systematic Review of Randomized Controlled Trials. Physical therapy. 2020 Mar 10;100(3):523-542. PMID: 32065236
  • Guida JL, Agurs-Collins T, Ahles TA, Campisi J, Dale W, Demark-Wahnefried W, Dietrich J, Fuldner R, Gallicchio L, Green PA, Hurria A, Janelsins MC, Jhappan C, Kirkland JL, Kohanski R, Longo V, Meydani S, Mohile S, Niedernhofer LJ, Nelson C, Perna F, Schadler K, Scott JM, Schrack JA, Tracy RP, van Deursen J, Ness KK. Strategies to Prevent or Remediate Cancer and Treatment-Related Aging. Journal of the National Cancer Institute. 2021 Feb 1;113(2):112-122. PMID: 32348501
  • Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. International review of psychiatry (Abingdon, England). 2014 Feb;26(1):102-13. PMID: 24716504
  • Williams AM, Janelsins MC, van Wijngaarden E. Cognitive function in cancer survivors: analysis of the 1999-2002 National Health and Nutrition Examination Survey. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2016 May;24(5):2155-2162. Epub 2015 Nov 9. PMID: 26559193
  • Loh KP, Janelsins MC, Mohile SG, Holmes HM, Hsu T, Inouye SK, Karuturi MS, Kimmick GG, Lichtman SM, Magnuson A, Whitehead MI, Wong ML, Ahles TA. Chemotherapy-related cognitive impairment in older patients with cancer. Journal of geriatric oncology. 2016 Jul;7(4):270-80. Epub 2016 Jul 5. PMID: 27197918
  • Magnuson A, Lei L, Gilmore N, Kleckner AS, Lin FV, Ferguson R, Hurria A, Wittink MN, Esparaz BT, Giguere JK, Misleh J, Bautista J, Mohile SG, Janelsins MC. Longitudinal Relationship Between Frailty and Cognition in Patients 50 Years and Older with Breast Cancer. Journal of the American Geriatrics Society. 2019 May;67(5):928-936. PMID: 31034595
  • Peppone LJ, Inglis JE, Mustian KM, Heckler CE, Padula GDA, Mohile SG, Kamen CS, Culakova E, Lin PJ, Kerns SL, Cole S, Janelsins MC. Multicenter Randomized Controlled Trial of Omega-3 Fatty Acids Versus Omega-6 Fatty Acids for the Control of Cancer-Related Fatigue Among Breast Cancer Survivors. JNCI cancer spectrum. 2019 Jun;3(2):pkz005. Epub 2019 Feb 21. PMID: 31119206
  • Lin PJ, Peppone LJ, Janelsins MC, Mohile SG, Kamen CS, Kleckner IR, Fung C, Asare M, Cole CL, Culakova E, Mustian KM. Yoga for the Management of Cancer Treatment-Related Toxicities. Current oncology reports. 2018 Feb 1;20(1):5. PMID: 29388071
  • Yao S, Hu Q, Kerns S, Yan L, Onitilo AA, Misleh J, Young K, Lei L, Bautista J, Mohamed M, Mohile SG, Ambrosone CB, Liu S, Janelsins MC. Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study. Clinical epigenetics. 2019 Mar 12;11(1):45. PMID: 30867049
  • Gilmore N, Mohile S, Lei L, Culakova E, Mohamed M, Magnuson A, Loh KP, Maggiore R, Belcher E, Conlin A, Weiselberg L, Ontko M, Janelsins M. The longitudinal relationship between immune cell profiles and frailty in patients with breast cancer receiving chemotherapy. Breast cancer research : BCR. 2021 Feb 5;23(1):19. PMID: 33546731
  • Gilmore N, Kadambi S, Lei L, Loh KP, Mohamed M, Magnuson A, Cole S, Esparaz BT, Giguere JK, Mohile S, Janelsins M. Associations of inflammation with frailty in patients with breast cancer aged 50 and over receiving chemotherapy. Journal of geriatric oncology. 2020 Apr;11(3):423-430. Epub 2019 Apr 13. PMID: 30992181
  • Magnuson A, Mohile S, Janelsins M. Cognition and Cognitive Impairment in Older Adults with Cancer. Current geriatrics reports. 2016 Sep;5(3):213-219. Epub 2016 Jun 29. PMID: 27547701
  • Williams AM, Shah R, Shayne M, Huston AJ, Krebs M, Murray N, Thompson BD, Doyle K, Korotkin J, van Wijngaarden E, Hyland S, Moynihan JA, Cory-Slechta DA, Janelsins MC. Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. Journal of neuroimmunology. 2018 Jan 15;314:17-23. Epub 2017 Oct 18. PMID: 29128118
  • Janelsins MC, Heckler CE, Peppone LJ, Kamen C, Mustian KM, Mohile SG, Magnuson A, Kleckner IR, Guido JJ, Young KL, Conlin AK, Weiselberg LR, Mitchell JW, Ambrosone CA, Ahles TA, Morrow GR. Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Feb 10;35(5):506-514. Epub 2016 Dec 28. PMID: 28029304