Cognition Assessment and REhabilitation in Virtual Reality for Patients With Cancer

In this prospective, assessor-blinded, randomized controlled study, a total of 64 participants with cancer-related cognitive impairment will be recruited from oncology inpatient wards and outpatient clinics at a tertiary cancer center. 32 participants will be randomized to the intervention arm (VR-based cognitive rehabilitation therapy \[VR-CRT\]) and 32 participants will be randomized to the control arm (standard care).

The study will consist of a screening period of up to 14 days. Participants who fulfill all inclusion criteria will be consented and recruited during this screening period, constituting Visit 1 (Recruitment). During this visit, the principal investigator (PI) or co-investigator (Co-I) obtaining consent will ensure that the patient meets the following criteria:

For patients where a caregiver may assist with VR setup or monitoring, the study team will ensure that they are the primary caregiver of the patient.

Patient must be comfortable and committed to following directions for VR device usage.

Patient must not have severe cognitive or sensory impairments that preclude safe VR engagement.

After confirmation of the above criteria, the patient will undergo a 1-hour hands-on training session at the cancer center by trained study team members.

A set of training slides titled "VR-CRT User Training Slides" that is adapted from the standard "VR-CRT Instruction Manual" will be utilized for the training session for the patient. After which, a checklist titled "VR Training Checklist" will be completed by both the trainer and patient. This checklist is aimed to ensure that all necessary components of training have been covered by the trainer and also for trainers to indicate confidence of the patient during the training before both trainer and patient sign as a form of training acknowledgement.

Post training, a copy of the standard "VR-CRT Instruction Manual" will be given to the patient. Study team will emphasize to the patient that they can contact the study team at any juncture where they need additional clarifications relating to the device.

Depending on the treatment status at time of screening, the patient will be seen in the inpatient ward or specialist outpatient clinic at day 14 which is considered as Visit 2 (Randomization with allowance + 3 days). Allowance of up to 3 days is given in the event day 14 falls on a weekend/long weekend. Following Visit 2 (Randomization with allowance + 3 days), up to 3 days of habituation for VR device use and tolerability will take place. Participants will be required to engage with the VR device at low levels of immersion to allow conditioning for the habituation period. Because of the nature of the intervention, it may cause some discomfort to the participants, such as mild cybersickness, hence conditioning will increase the tolerability of the treatment for the participants.

Intervention with VR-CRT will take place over 8 weeks either in the inpatient setting of the cancer center or in the home setting, while standard oncology supportive care sessions happening concurrently as per existing clinical treatment protocol. Treatment with VR-CRT will consist of a daily session of 30-45 minutes for 24 sessions over 8 weeks (3 sessions per week). Compliance will be checked by research assistant via telephone or video call interview at regular intervals. One group will be randomized to the standard care (Control) arm and one group will be randomized to the active VR-CRT intervention arm. The standard care (Control) arm will involve routine oncology follow-up and educational resources on cognitive symptom management but no active VR engagement, with assessments conducted in a comparable manner to maintain blinding.

Assessment will be done at the time of recruitment which constitutes as Visit 1 (Recruitment), and again at Visit 3 (Last day of intervention, Week 8 post-intervention with allowance of + 7 days) and Visit 4 (Final follow-up, Week 20 post-intervention with allowance of + 7 days).

Management of adverse events (AEs and SAEs):

At recruitment, patients will be informed to take note and save research coordinator's contact number stated in the informed consent form (ICF). Patients will be reminded to contact research coordinators if patients experience any AE/SAE stated on ICF section 6 from the day of recruitment up to randomization. At randomization it will again be emphasized to patients that they are to continue to monitor for AE/SAE. During the duration of habituation through to the 8-week intervention period, patients are additionally required to report to the study coordinators with regards to any discomfort or issues with the device before proceeding with intervention. During the habituation and the 8-week intervention period, study coordinator will be keeping close contact with the patient by means of messaging apps to ensure compliance to the treatment regime and for AE/SAE reporting.

Patients who are starting the intervention in the inpatient setting will be monitored by the study team for any adverse events.

• EQ5D-5L [Time frame: From enrollment to Day 90 post intervention (with allowance of + 7 days).]
• Virtual Reality Simulation Sickness Questionnaire (VRSQ) [Time frame: From enrollment to Day 90 post-intervention (with allowance of + 7 days).]
• User-friendliness and engagement [Time frame: From enrollment to Day 90 post-intervention (with allowance of + 7 days).]
• Treatment satisfaction by VAS [Time frame: From enrollment to Day 90 post-intervention (with allowance of + 7 days)]