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23 August 2019

Why is it important to assess cognitive safety in oncology trials?

Following steady improvements in survival rates, there is a growing interest in establishing the long-term side effects of cancer treatments. This includes a need for a better understanding of the cognitive safety profile of these interventions, particularly in children and adolescents. In this article, we demonstrate that CANTAB computerised assessments offer a sensitive and practical solution for assessing cognitive function in oncology trials.

Do cancer treatments affect cognition?

Earlier detection and advances in treatment have led to considerable improvements in cancer survival rates. With patients now living longer, there is a greater focus on limiting potentially detrimental long-term side effects of cancer treatment on patient’s everyday functioning and quality of life.

An issue that has recently been recognised is the adverse effect that a number of existing treatments can have on patient’s cognitive function, over and above that caused by the cancer itself.1 These effects have been found following the treatment of both central nervous system (CNS) and non-CNS tumours, in adult and child populations, and can include persistent problems across a variety of cognitive processes, including attention, memory, processing speed and executive function.2 These deficits can have a significant impact on an individual’s ability to perform everyday activities and may be particularly detrimental for children, given a loss of cognitive function could affect their academic performance and achievement.

Chemotherapy, hormonal therapy, radiation therapy and surgical interventions, used either alone or in combination, have all been associated with post-treatment cognitive dysfunction in cancer patients, typically in a dose-response manner. This has led to calls for a better understanding and improved assessment of the cognitive safety profile of cancer treatments.

Find out more

 

Are assessment tools available to evaluate cognitive safety in clinical trials?

The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a collection of highly sensitive computerised assessments that can be used to accurately assess changes in cognitive performance in order to gauge the comparative safety of different therapeutic interventions.

Originally developed at the University of Cambridge, these cognitive tests have been used in over 2200+ peer-reviewed publications across a range of populations and study designs (accessible via our online bibliography). Importantly, task performance has been shown to correlate with brain structure and function, as well as real-world functional outcomes.

The CANTAB platform is also regulatory and HIPAA compliant for administering cognitive tests in clinical trials and has been included in regulatory submissions as both a primary and/or secondary endpoint by a number of major pharmaceutical companies. This has included major safety studies, such as the EBBINGHAUS trial,3 in which the absence of an impairing effect of a compound on CANTAB measures of cognitive performance has been approved by the FDA for inclusion as a label claim for the marketed drug.

 

Has CANTAB been used in oncology research?

A number of published studies have demonstrated that CANTAB computerised assessments are both practical and sensitive tools for assessing cognitive function in patients with CNS and non-CNS cancers.4-6

For example, Vardy and colleagues used CANTAB tasks in a large multinational study to compare cognitive performance among patients with early-stage colorectal cancer (n = 265), metastatic colorectal cancer (n = 66) and healthy controls (n = 71), matched for age and level of education. Patients with colorectal cancer exhibited significantly greater levels of impairment on CANTAB measures of verbal memory, reaction time, working memory and executive function relative to healthy controls.6

Studies have also demonstrated the sensitivity of CANTAB tasks to changes in cognition arising after cancer treatment.7,8 Importantly, CANTAB tasks have also been successfully used to assess cognitive performance in children and adolescents involved in a range of oncology studies, including those with brain tumours.9-12

 

What are the advantages of conducting computerised cognitive assessments?

Paper-and-pencil based cognitive assessments are typically time-consuming, requiring specialist resources and a trained rater to administer and interpret the results of the tests. In contrast, computerised CANTAB tasks offer a number of practical benefits:

  • Automated instructions (available in a range of languages) and practice trials standardise the administration process, allowing tasks to be largely self-administered by participants.
  • The touchscreen platform ensures accurate response scoring, enabling precise assessment of subtle measures (such as reaction times), and permitting the simultaneous assessment of multiple aspects of cognition using single tasks.
  • Abstract stimuli and multiple parallel forms limit learning effects, while many CANTAB tasks are also adaptive to individual performance to avoid floor and ceiling effects.
  • Importantly, these tasks have been shown to be very well tolerated by patients, even among very ill and elderly individuals.
  • Blinded data reports can be downloaded online at any time by nominated individuals in a range of formats.
  • Additional patient and clinician-reported outcome measures can also be integrated into the system in order to harmonise data collection.

 

What support is available for designing and analysing safety trials?

Our expert in-house scientists and statisticians can provide advice to help optimise your trial design and the selection of cognitive endpoints, as well as the analysis and interpretation of your CANTAB data.

 

Are you planning an oncology trial?

Speak to our experts for tailored advice on ensuring the cognitive safety of your compound.

Contact us

 

References

  1. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncology 2011;12(7):703-8.
  2. Hardy SJ, Krull KR, Wefel JS, Janelsins M. Cognitive changes in cancer survivors. American Society of Clinical Oncology Educational Book 2018;38:795-806.
  3. Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, et al. Cognitive function in a randomized trial of evolocumab. New England Journal of Medicine 2017;377(7):633-43.
  4. Dhillon HM, Tannock IF, Pond GR, Renton C, Rourke SB, Vardy JL. Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy. Journal of Cancer Survivorship 2018;12(2):178-85.
  5. Williams AM, Shah R, Shayne M, Huston AJ, Krebs M, Murray N, et al. Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. Journal of Neuroimmunology 2018;314:17-23.
  6. Vardy J, Dhillon HM, Pond GR, Rourke SB, Xu W, Dodd A, et al. Cognitive function and fatigue after diagnosis of colorectal cancer. Annals of Oncology 2014;25(12):2404-12.
  7. Bender CM, Merriman JD, Gentry AL, Ahrendt GM, Berga SL, Brufsky AM, et al. Patterns of change in cognitive function with anastrozole therapy. Cancer 2015;121(15):2627-36.
  8. Capuron L, Ravaud A, Dantzer R. Timing and specificity of the cognitive changes induced by interleukin-2 and interferon-alpha treatments in cancer patients. Psychosomatic Medicine 2001;63(3):376-86.
  9. Darling S, De Luca CR, Anderson V, McCarthy M, Hearps S, Seal M. Brain morphology and information processing at the completion of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia. Developmental Neurorehabilitation 2019;22(5):293-302.
  10. Darling SJ, De Luca C, Anderson V, McCarthy M, Hearps S, Seal ML. White matter microstructure and information processing at the completion of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia. Developmental Neuropsychology 2018;43(5):385-402.
  11. Özyurt J, Müller HL, Warmuth-Metz M, Thiel CM. Hypothalamic tumors impact gray and white matter volumes in fronto-limbic brain areas. Cortex 2017;89:98-110.
  12. Szulc-Lerch KU, Timmons BW, Bouffet E, Laughlin S, de Medeiros CB, Skocic J, et al. Repairing the brain with physical exercise: cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention. NeuroImage: Clinical 2018;18:972-85.

Tags : oncology | cancer | cognition