Structural Neuroimaging Findings Related to Adult Non-CNS Cancer and Treatment: Review, Integration, and Implications for Treatment of Cognitive Dysfunction

Neurotherapeutics. 2021 Apr;18(2):792-810. doi: 10.1007/s13311-021-01096-5. Epub 2021 Aug 16.


Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.

Keywords: Brain structure; Chemotherapy; Cognition; Neuroimaging; Non-CNS cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Antineoplastic Agents / adverse effects
  • Brain / diagnostic imaging*
  • Brain / drug effects
  • Cognitive Dysfunction / chemically induced*
  • Cognitive Dysfunction / diagnostic imaging*
  • Cognitive Dysfunction / epidemiology
  • Hormone Antagonists / adverse effects
  • Humans
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology
  • Neuroimaging / methods*
  • Neuroimaging / trends
  • Treatment Outcome


  • Antineoplastic Agents
  • Hormone Antagonists