Seed Spots Analysis to Characterize Linear Energy Transfer (LET) Effect in the Adverse Event Regions of Head and Neck Cancer Patients Treated by Intensity Modulated Proton Therapy (IMPT)

Y. Yang, Samir H Patel, J. Bridhikitti, William W Wong, Michele Y Halyard, L. A. McGee, J. C. Rwigema, Steven Eric Schild, S. A. Vora, T. Liu, M. Bues, M. Fatyga, Robert Foote, W. Liu

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE/OBJECTIVE(S): High linear energy transfer (LET) radiotherapy may cause unexpected adverse events (AEs) in head and neck (H&N) cancer patients treated by intensity-modulated proton therapy (IMPT). In this exploratory study, we propose to investigate the effects of LET upon AEs in IMPT using dose-linear-energy-transfer volume histograms (DLVHs) and seed spots analysis. MATERIALS/METHODS: We included 14 H&N patients with unanticipated CTCAEv4.0 grade≥3 AEs for analysis. The AE regions were contoured and the corresponding DLVHs of the AE regions were generated. DLVH was constructed with physical dose (Gy) and LET (keV/µm) as independent variables. The normalized volume of the structure was contoured as iso-volume lines in the dose-LET plane. All voxels in the structure were mapped into the dose-LET plane as dots to see how the dots with similar dose and LET were clustered. For seed spot analysis, we selected voxels at the top edge of the DLVH plots as critical voxels. Individually clustered critical voxels that are geometrically apart were considered as independent seed spots. Median dose/LET from seed spots were extracted. Bivariate-linear-regression models were established for all AEs. The dose and LET product (xBD) volume constraint of osteoradionecrosis was obtained using the receiver operating characteristic curve of 4 osteoradionecrosis patients and 15 additional independent control patients. RESULTS: Dose played a dominant role for in-field AEs such as hemorrhage and ulceration, while LET played an important role in out-of-field AEs such as osteoradionecrosis and mucositis. Intercept-free linear models between the reciprocal of dose and LET were found for different AEs. The corresponding xBD threshold values were included in Table 1. The xBD volume constraint of osteoradionecrosis was derived V (xBD≥275.18 Gy•keV/μm) < 0.0612cc, with an area under curve of 0.85. CONCLUSION: Our observations suggested that dose and LET can contribute to AEs in a complicated fashion. Using the intercept-free bivariate linear regression model, we found a LET-enhancing effect for all 6 AEs included in the study, substantiated by the positive slopes of the empirical dose-LET models. The xBD volume constraint of osteoradionecrosis was derived and showed good performance. We believe that both DLVH and seed spot analysis could be powerful tools for patient outcome studies in IMPT.

Original languageEnglish (US)
Pages (from-to)e388
JournalInternational journal of radiation oncology, biology, physics
Volume111
Issue number3
DOIs
StatePublished - Nov 1 2021

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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