The radiotherapy completion rate is defined as the number of successful radiotherapy fractions divided by the total number of scheduled radiotherapy fractions. A radiotherapy fraction is considered successful if the child is cooperative and the entire procedure is completed as planned. Conversely, a fraction is considered unsuccessful if the child is uncooperative, leading to the inability to start or an interruption that prevents the continuation of the radiotherapy session. Each radiotherapy fraction will be recorded as either successful or unsuccessful based on predefined criteria. The specific reasons for an unsuccessful fraction will be documented, including details such as the child's behavior and any interruptions during the fraction. For data analysis, the completion rate will be assessed by calculating the proportion of successful fractions out of the total scheduled fractions. In cases where a fraction is unsuccessful, additional measures may be taken to reschedule the radiotherapy session to ensure the full course of treatment is completed. Any adjustments to the treatment schedule due to unsuccessful fractions will also be documented and analyzed to understand their impact on the overall treatment timeline and outcomes.
Radiotherapy efficiency will be evaluated through two methods: the percentage of fractions requiring repositioning and the time required for radiotherapy. The percentage of repositioning due to OSMS-detected shifts represents the ratio of radiotherapy fractions in which the patient required repositioning because the patient's shift exceeded the predefined threshold of 5 mm detected by the OSMS, to the total number of radiotherapy fractions in that group. Each repositioning event will be recorded in detail, including the specific displacement and the time required for repositioning. In-room time, defined as the time from when the patient enters the treatment room to when the patient leaves the room after therapy, will also be documented for each radiotherapy fraction.
Radiotherapy accuracy will be assessed by evaluating both interfraction and intrafraction errors. Interfraction errors, which refer to positional discrepancies between treatment fractions, will be determined by comparing pretreatment CBCT scans from each fraction. Intrafraction errors, which occur within a single treatment fraction, will be calculated by analyzing differences between pretreatment and posttreatment CBCT scans. Additionally, intrafraction errors will be monitored using the OSMS system, which continuously tracks the patient’s surface using three cameras to promptly detect any deviations from the reference surface. To minimize additional radiation exposure from CBCT scans that are not necessary for treatment verification, posttreatment CBCT scans will be conducted once daily only during the first week of radiotherapy for each patient. Thereafter, these scans will be performed once weekly for the remainder of the treatment period. Interfraction and intrafraction errors measured by CBCT will be calculated in three directions: lateral, longitudinal, and vertical. Intrafraction errors monitored under OSMS guidance will be assessed in the lateral, longitudinal, and vertical directions, as well as along the rotation, roll, and pitch axes. Deviations will be defined as the distance between the reference isocenter and the treatment isocenter on the reconstructed body surface.
The quality of life for the children will be assessed using the Pediatric Quality of Life Inventory - Cancer Module (PedsQL), with scores ranging from 0 to 100, where higher scores indicate a better quality of life. The PedsQL is a widely validated instrument designed to measure health-related quality of life in children and adolescents [13]. The Cancer Module specifically addresses the unique challenges faced by pediatric cancer patients. The PedsQL Cancer Module consists of several core scales that evaluate various dimensions: pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication. For children aged 0–4 years, the PedsQL is administered via a parent-proxy report, as young children may not be able to complete the questionnaire themselves. Parents or primary caregivers are asked to observe and report on their child's well-being and functioning based on their daily interactions and observations. The mean of the scores for related questions within each dimension was calculated, and the total PedsQL scores were determined by averaging all completed items. These evaluations will be conducted before and after radiotherapy, and three months post-radiotherapy to monitor changes over time.
As the assessment of immune function and GH levels, blood samples will be collected at three time points: pre-radiotherapy, post-radiotherapy, and three months post-radiotherapy. The samples will be analyzed for immune function indicators, including lymphocyte subpopulations via flow cytometry, immunoglobulin levels (IgG, IgA, IgM) via ELISA, and cytokine profiles via a multiplex cytokine assay. GH levels will be measured using a radioimmunoassay or immunochemiluminometric assay.
The safety of the WASPE sleep adjustment method compared to standard sedation using chloral hydrate will be meticulously evaluated by monitoring and recording adverse events (AEs) and serious adverse events (SAEs) throughout the course of the study. AEs will be graded using the Common Terminology Criteria for Adverse Events (CTCAE). Continuous monitoring of all study participants will be conducted throughout the intervention period and the follow-up phase. Parents or guardians will be instructed to report any AEs or SAEs to the study team immediately. Routine clinical assessments will be performed at each study visit to identify potential AEs, including physical examinations and comprehensive laboratory tests such as blood counts and liver and renal function tests.
Potential AEs associated with chloral hydrate:
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Respiratory depression
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Hypotension
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Irritability
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Gastrointestinal disturbances (such as nausea and vomiting)
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Allergic reactions (such as rash or urticaria)
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Hepatotoxicity
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Nephrotoxicity
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Prolonged drowsiness or sedation
Potential AEs associated with the WASPE method:
By monitoring these potential AEs closely, we aim to capture the full safety profiles of both the WASPE method and chloral hydrate in pediatric patients. The incidence, severity, and duration of AEs and SAEs will be summarized and compared between the WASPE and sedation groups. Patient assessment schedule is shown in Table 1.
Table 1
Patient assessment schedule
Assessment | Pre-studya | Prior to RT | Weekly during RT | End of RT | Follow-Up visitb |
Informed Consent | X | | | | |
Eligibility Screening | X | | | | |
Medical History | X | | | | |
Physical Exam | X | X | X | X | X |
Complete blood count | X | X | X | X | X |
Liver and renal function | X | X | | X | X |
Immune Function and GH testing | X | X | | X | X |
Pediatric Quality of Life Inventory (PedsQL) | | X | | X | X |
Radiotherapy Planning CT | | X | | | |
AE evaluation | | | X | X | X |
a. Pre-study should be completed within 2 weeks prior to study entry.
b. Follow-up at three months after radiotherapy.
Abbreviations: RT, radiotherapy; GH, growth hormone; CT, computed tomography; AE, adverse event.