Wearable-Triggered Digital Safety Net for Real-Time Monitoring & Intervention in Leptomeningeal Metastasis

LMM is a condition where cancer has spread to the fluid and membranes surrounding the brain and spinal cord. It is a common complication of cancer and affects about 5-15% of all cancer patients. It causes rapid neurological decline and survival is usually around 6-12 months. LMM is treated with chemotherapy radiation, but this does not improve neurological function or quality of life. Many of the current assessments for LMM are not good detecting progression and symptoms are often missed.

There will be two parts to this study. Smartwatches will be used to continuously capture data such as gait stability, heart rate variability (HRV), step count, and sleep, which are affected by LMM. The first part of this study is to learn whether this can help detect early signs of neurological decline. The second part of this study will test whether sending an automatic alert to the participant's doctor when a change is detected can help reduce the amount of times the participants are admitted to the hospital unexpectedly.

• Calibration Phase (Device): Apple Watch Series 6+ or Samsung Galaxy Watch 4+ worn 10+ hours/day for 4+ days/week for 6 months. Passive wearable data collection from in-house cross-platform app to find out patient-specific digital signal thresholds for neurological decline, symptom logging, daily sync reminders, and monthly EORTC-QLQ-C30 surveys.
• Stepped Wedge Intervention Phase (Device): Apple Watch Series 6+ or Samsung Galaxy Watch 4+ worn 10+ hours/day for 4+ days/week for 5 months. Active monitoring with alerts using the data collected from the in-house cross-platform app and sent to study neuro-oncologist.

Primary outcomes

• Predicting Karnofsky Performance Scale (KPS) decline [6 months]: Karnofsky Performance scale of 100-0. Sensitivity, specificity, Positive Predictive Value (PPV), and lead time of participant-specific thresholds. Assessed from calibration phase data if there is a greater than10-point KPS decline.
• Predicting neurological progression [6 months]: Sensitivity, specificity, PPV, and lead time of participant-specific thresholds. Assessed from calibration phase data.
• Days in hospital per participant-month during silent monitoring periods [5 months]: Taken from EMR by staff blinded to alert status. Defined as incidence rate ratios (IRRs) with 95% CIs using mixed-effects negative binomial regression.
• Days in hospital per participant-month during active alerting periods [5 months]: Taken from EMR by staff blinded to alert status. Defined as incidence rate ratios (IRRs) with 95% CIs using mixed-effects negative binomial regression.
• Participant completion [5 months]: 80% or more of participants completing 3 months or more of active monitoring with median wear of 10 or more hours on 4 or more days/week
• Recruitment rate [12 months]: number of participants enrolled within 9-12 months
• Dropout rate [12 months]: Number of participants who do not complete study, assessed at study completion
• Alert pathway feasibility [5 months]: Alert frequency per participant-month and proportion judged clinically relevant.

Secondary outcomes

• Number of unplanned hospitalizations and ED visits per participant-month [5 months]: Evaluate the efficacy of alert pathway in reducing unplanned hospitalization and ED visits. EMR review throughout Phase 2 during active vs. silent periods.
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 ( EORTC-QLQ-C30) total and subscale scores [6 months]: EORTC-QLQ-C30 is a 30 item validated questionnaire to determine the participant's quality of life. The questions are in a 4- point scale from 1 ("Not at all)" to 4 ("Very much"). A higher functional or global health score represents a higher quality of life, while a higher symptom score means a higher level of reported symptoms. Change in EORTC-QLQ-C30 will be measured from baseline at each time point.
• Progression-free survival (PFS) [12 months]: Time from enrollment to first radiographic or clinical progression; assessed throughout treatment period
• Overall survival (OS) [12 months]: Time from enrollment to death; assessed throughout treatment period and via medical record review
• Wearable data quantity across iOS and Android platforms [12 months]: Assessed at each treatment visit per participant per month (mean, variance)
• Time from alert trigger to clinician-documented neurological progression [5 months]: Evaluate the efficacy of alert pathway in reducing unplanned hospitalization and ED visits. EMR review throughout Phase 2 during active vs. silent periods.
• Wearable data quality across iOS and Android platforms [12 months]: Assessed at each treatment visit per participant per month (mean, variance)
• Participant symptoms [12 months]: Logged per type per participant per month. Assessed at each treatment visit
• Variance in accelerometry [12 months]: This device is used to track changes in physical activity and sleep patterns. Assessed at study completion
• Variance in heart rate variability (HRV) [12 months]: This device assess HRV, which is where the amount of time between heartbeats fluctuate slightly. The participant's heart data will be collected and used to see if there any changes from the participant's month 1 mean. Assessed at study completion
• Variance in gait metrics [12 months]: This device assesses the speed, step length and asymmetry to see if changes these can predict any clinical events by days to weeks.
• Reasons for dropout [12 months]: Collected via exit questionnaire at withdrawal or study completion
• Participant device wear [12 months]: Collected via exit survey and structured questionnaires at each visit for participant reported quality of life (QOL)
• Participant symptom logging [12 months]: Collected via exit survey and structured questionnaires at each visit for participant reported quality of life (QOL).
• Participant app usage [12 months]: Collected via exit survey and structured questionnaires at each visit for participant reported quality of life (QOL).

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Participants must have leptomeningeal metastasis (LMM) diagnosed per clinical, imaging, and/or CSF/cytology criteria (cytology, flow cytometry, or circulating tumor DNA), arising from any solid or hematologic tumor primary.
* Participants must be undergoing active anti-cancer therapy (systemic, intrathecal, and/or radiation) or active surveillance for LMM.
* Age ≥18 years at the time of study enrollment. Because no safety or dosing data are available for wearable monitoring studies in children with LMM, participants under 18 years of age are excluded.
* Karnofsky Performance Status (KPS) ≥50 at time of study enrollment \[See Appendix I\], to ensure feasibility of wearing the device for ≥10 hours/day.
* Participants must have access to a compatible smartphone:

  * iPhone running iOS 16 or higher and willingness to wear Apple Watch ≥10 hours/day; OR
  * Android smartphone compatible with the study application and willingness to wear Samsung Galaxy Watch ≥10 hours/day.
* Ability to provide informed consent (or a legally authorized representative \[LAR\] is available and willing to provide consent on the participant's behalf, if appropriate).

Exclusion Criteria:

* Anticipated life expectancy <4 weeks at time of screening, per the treating physician.
* Severe dermatologic or musculoskeletal conditions precluding smartwatch wear (e.g., significant skin conditions on the wrist or forearm where the device will be placed, including tattoos that may substantially interfere with optical sensor function).
* Inability to adhere to study procedures after training, as assessed by the study team at enrollment.
* No access to a compatible smartphone (participant or caregiver) to interface with the watch application for symptom documentation and data transfer.
* Inability to give informed consent due to severe aphasia, severe cognitive impairment, or other language barrier, unless a legally authorized representative is available and willing to participate.

• Andrew Dhawan, MD, DPhil, Principal investigator, Cleveland Clinic, Case Comprehensive Cancer Center