This study aims to evaluate the prevalence, biological mechanism and survivorship impact of cognitive toxicity among adolescent and young adult (AYA) patients diagnosed with curable cancers. The hypothesis is that cognitive impairment is clinically significant among AYA cancer patients treated with chemotherapy and that there will be detectable structural and functional changes in the brain for this patient group.

A prospective longitudinal cohort study will be conducted at National Cancer Centre Singapore (NCCS) and KK Women's and Children's Hospital (KKH) from April 2018 to April 2021. Eligible cancer patients aged between 15-39 years old will be recruited and followed up for a period of 12 months. In addition, healthy individuals will also be recruited into the control arm of the study. The prevalence of cognitive impairment will be assessed via objective cognitive functional assessments in the form of the Cambridge Neuropsychological Test Automated Battery (Cantab) test scores and Functional Assessement of Cancer-Therapy Cognitive Function (FACT-Cog v3.0). The overall cognitive performance and post-treatment health issues measured by the assessment tools used would be compared between AYA cancer patients and healthy controls at baseline and 6 months after baseline.

Other post-treatment health issues will be assessed in relation to cognitive impairment with a series of questionnaires including Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for cancer-related fatigue, the Rotterdam Symptom Checklist (RSCL) for symptom burden, the Paediatrics Quality of Life Inventory (PedsQL 4.0) for psychosocial outcomes, InCharge questionnaire for perceived financial distress and a work/education questionnaire respectively.

To enhance the understanding of the biological mechanism behind cognitive impairment, levels of biomarkers and genetic determinants will also be correlated with overall cognitive impairment. Blood plasma samples drawn from patients will be assessed for Brain-derived neutrotrophic factor (BDNF) levels, hormone levels and pro-inflammatory cytokines such as IL-1β, IL-4, and IL-6 using multiplex immunoassay. MRI scans and relevant neuroimaging techniques will be used to assess structural changes and functional connectivities in brain. Lastly, wearable devices will be utilized to track activity and lifestyle data among AYA cancer patients to investigate on the extent of impact of cognitive impairment and to assess the feasibility of using these wearables devices to personalize symptom management.

Findings from this proposed study will enhance understanding of cognitive toxicity and post-treatment health issues faced by the AYA patient group, which will facilitate the development of effective interventions to better cope with their daily lives.

Inclusion Criteria:

• between 15-39 years of age
• newly diagnosed with breast cancer, lymphoma or germ cell tumor with treatment intent determined as curative by medical oncologist
• scheduled for chemotherapy with or without non-cranial radiotherapy
• no prior history of chemotherapy and/or radiotherapy
• able to read and understand English
• capable of giving informed consent (or obtaining parents' consent if required)

Exclusion Criteria:

• physically or mentally incapable of providing verbal/written consent
• diagnosed with primary or metastatic brain tumor(s) or relapsed disease
• treatment includes intrathecal or intraventricular chemotherapy
• evidence of psychosis or underlying neuropsychiatric illness that may impair cognitive abilities
• have immediate family member who is enrolled as in the healthy control arm
• any contraindication to MRI as stated in the study protocol including: pregnancy, metal fragments/implants in body, known claustrophobia, and non-removable metal orthodontic braces, metallic retainers and oral wires

The proposed study will be a multicenter, prospective, longitudinal, observational study conducted at the National Cancer Centre Singapore (NCCS) and KK Women's and Children's Hospital (KKH).