In Vivo Test-retest Quantitative Characterization of Echo Planar Imaging Apparent Diffusion Coefficient Reproducibility for Head and Neck Cancers on a 1.5T MR-Linac Platform: Technical Validation using QIBA Metrology

Background and Purpose To detect changes in apparent diffusion coefficient (ADC) values during radiation therapy for biological image-guided adaptive radiation therapy, the variability in ADC must be characterized. We evaluated the reproducibility of ADC values in head and neck cancers on a 1.5T MR-linac.

39 head and neck cancer patients (36 primary tumors, 55 lymph nodes) were imaged with echo-planar imaging diffusion-weighted MRI on a 1.5T MR-linac at two time points before the start of radiation therapy. Mean and median ADC values and volume were measured for each lesion. Absolute and percent reproducibility coefficients (RC) were calculated. Linear regression analyses and F-tests were performed to determine whether lesion volume or time between scans impacted reproducibility.

For primary tumors & lymph nodes: mean ADC, median ADC, and volume were 1.27 ± 0.33 mm2/s & 1.17 ± 0.34 mm2/s, 1.25 ± 0.35 & 1.16 ± 0.37 mm2/s, and 8.8 ± 12.3 cm3 & 6.5 ± 7.2 cm3, respectively. RC values of mean ADC were 0.355 mm2/s & 0.355 mm2/s for tumors & nodes, and %RC values were 29.1% & 31.1%; values were very similar for median ADC. Reproducibility was not significantly correlated with either volume or scan interval, but a trend of poorer reproducibility in smaller volumes was observed.

Considering previous reports that the optimal %ΔADC threshold for response prediction in head and neck cancers is around 15-30%, this sequence on the MR-linac has acceptable reproducibility for detecting larger ADC changes but may still miss some clinically significant changes. Competing Interest Statement The authors have the following conflicts of interest: Dr. Brigid McDonald has received funding from Elekta AB to attend a scientific meeting. Dr. Clifton D. Fuller has received travel, speaker honoraria, and/or registration fee waivers unrelated to this project from Siemens Healthineers/Varian, Elekta AB, Philips Medical Systems, The American Association for Physicists in Medicine, The American Society for Clinical Oncology, The Royal Australian and New Zealand College of Radiologists, Australian & New Zealand Head and Neck Society, The American Society for Radiation Oncology, The Radiological Society of North America, and The European Society for Radiation Oncology. Dr. Alex Dresner has stock or stock options in Philips healthcare and receives salary from Philips Healthcare, which is a subcontractor on the Elekta Unity product. Dr. John Christodouleas has grants or contracts from Health Holland, stock or stock options in Elekta, Inc and is an employee at Elekta, Inc. Funding Statement Dr. Brigid A. McDonald received support for this project from an Image Guided Cancer Therapy (IGCT) T32 Training Program Fellowship (T32CA261856) and an ASTRO-AAPM Physics Resident/Post-Doctoral Fellow Seed Grant. Dr. Clifton D. Fuller received related support from the NCI MD Anderson Cancer Center Core Support Grant Image-Driven Biologically-informed Therapy (IDBT) Program (P30CA016672-47) and has also received industry research support from Elekta AB, both related and unrelated to the current project. Dr. Clifton D. Fuller reports additional grants from NIH/National Cancer Institute (R01CA218148, 1R01CA225190, 1R01CA214825, P30CA016672, P50CA097007-10), NIH/NIDCR (1R01DE025248/R56DE025248), NIH/National Institute of Biomedical Imaging and Bioengineering (R25EB025787), Patient-centered Outcomes Research Institute (PCS-1609-36195), Sister Institute Network Fund (The University of Texas MD Anderson Cancer Center), and National Science Foundation Division of Civil, Mechanical, and Manufacturing Innovation (CMMI 1933369). Dr. Abdallah S. R. Mohamed receives support from NIH/NCI 1P01CA285249-01A1 OPC SURVIVOR: Optimizing OroPharyngeal Cancer SURVivorship and NIH/NIDCR U01 DE032168 Quantative Imaging Biomarker Prospective Validation of Dynamic Contrast-Enhanced MRI as a Metric of Orodental Injury After Radiotherapy (QI-ProVE-MRI). Dr. John Christodouleas has grants or contracts from Health Holland. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval for this study was obtained through a retrospective data collection protocol with a waiver of informed consent (University of Texas MD Anderson Cancer Center Institutional Review Board protocol number RCR03-0800). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors