Are adolescent and young adult cancer patients affected by ‘chemobrain’?: a call for evidence

KEYWORDS:

• Cognitive impairment
• adolescent and young adult
• survivorship
• cancer
• quality of life
• chemobrain

An adolescent and young adult (AYA) cancer patient is defined as an individual of 15–39 years of age at the time of initial cancer diagnosis [1,2]. The number of AYA cancer survivors has dramatically increased over the past decades due to availability of novel therapeutics, with the 5-year overall survival rate among adolescents aged 15–19 years exceeds 80% for most cancers [3]. AYA cancer survivors, however, often experience a myriad of treatment-related chronic and late toxicities that can lead to functional impairment at great economic, emotional, and social cost [4]. As the cure rates of AYA cancers continue to improve and survivors live longer, post-treatment health issues in these survivors are becoming increasingly relevant, and more in-depth research is needed in this group of patients.

Among the undesirable toxicities experienced by AYA patients, cognitive toxicity remains under-studied. Cognitive toxicity encompasses a wide range of symptoms during and after treatment such as memory loss, inability to concentrate, difficulty in thinking, poor response speed, and executive functioning and other subtle cognitive changes that can have a detrimental effect on patients’ daily functioning and health-related quality of life [5,6]. Research has also suggested that the quality of life and activities of daily living are immensely affected by subtle neuropsychological changes [7]. The prevalence of cognitive impairment is well recognized ranging from 16% to 75% among all adult cancer survivors [5,6,8]. The majority of studies in the literature evaluated cognitive impairment in adult breast cancer adults, with a small handful of studies conducted in adults diagnosed with prostate cancer and colorectal cancer and adults undergoing hematopoietic stem cell transplantation.

Cognitive toxicity was once believed to be caused solely by chemotherapy (as a result, cognitive toxicity is often referred to as ‘chemobrain’ or ‘chemofog’). Structural changes to the white matter of the brain have indicated that this phenomenon could be partly caused by chemotherapy; however, many researchers have argued that chemotherapeutic agents are unlikely to cross the blood–brain barrier due to their large molecular size. Accumulating evidence suggests that other therapies such as endocrine therapies (in breast/prostate cancer patients) and radiotherapy may be associated with cognitive impairment. Fatigue, depression, and anxiety also negatively influence cognitive function. Other proposed clinical determinants include pharmacological considerations such as the types and dose intensity of chemotherapy regimens, menopausal status (for females), baseline intelligence, and even the provision of pre-existing knowledge of ‘chemobrain.’ In addition to these established factors, experimental studies suggest that biological factors such as the pro-inflammatory cytokines may be key mediators contributing to the development of cognitive toxicity. Collectively, these clinical, biological, and demographic factors may contribute to the occurrence of cognitive toxicity.

In the current literature, whether AYA patients are disturbed by cognitive toxicity, as well as the long-term effects of cognitive toxicity on long-term survivorship in AYA patients are poorly depicted. In the Adolescent and Young Adult Health Outcomes and Patient Experience study, over 40% and 53% of AYA cancer patients reported problems with ‘forgetting’ at 6–14 months and 15–35 months after cancer diagnosis, respectively. One-third of these patients also found it difficult to pay attention at work or school after a cancer diagnosis [9]. These patients did not have central nervous system (CNS) metastasis and were not receiving chemotherapeutic agents to prevent CNS relapses, thus excluding the likelihood that the occurrence of cognitive impairment was caused by direct insult of the CNS through either the disease or the use of anti-cancer treatment.

Cognitive toxicity may pose substantial challenges for AYA cancer survivors who wish to resume or maintain their usual life, including school, work, and other social aspects, after cancer treatment. Research has shown that significantly fewer AYA cancer survivors report being employed as compared with age-matched peers without cancer [10]. Another study suggested that AYA survivors incur substantially greater loss of productivity than older cancer survivors, possibly due to difficulty in returning to full functionality in school or work [11].

Undoubtedly, our understanding of cognitive issues in patients diagnosed with cancer as an AYA is far less comprehensive as that in patients diagnosed as an adult. Robust epidemiological studies that consist of appropriate longitudinal assessments of cognitive impairment is required to accurately characterize the onset, trajectory, severity, and effects (short- and long-term) of cognitive toxicity in AYA patients diagnosed with cancer. Neuroimaging (such as functional MRI studies) can also provide important insights into the exact etiology and neural mechanism underpinning cognitive complaints, in order to explain whether these cognitive symptoms are attributable to changes that occur in the brain or to changes that are driven by psychological distress and symptoms (such as anxiety or fatigue) that are commonly experienced by AYA patients. As the biologic mechanisms, demographic, and clinical characteristics among AYA patients with cancer are substantially different when compared to younger and older patients with cancer [12], we call for more research that will focus on gaining an in-depth understanding of the epidemiology of cognitive toxicity specifically within the AYA context, in order to inform relevant interventions for this unique group of patients.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.