Abstract
Background and purpose To characterize patterns and outcomes of brain MR image changes after proton therapy (PT) for skull base head and neck cancer (HNC).
Material and methods 127 patients treated with PT for HNC who had received at least 40 Gy(RBE) to the brain and had ≥ 1 follow-up MRI > 6 months after PT were analyzed. MRIs were reviewed for radiation- associated image changes (RAIC). MRIs were rigidly registered to planning CTs, and RAIC were contoured on T1 (post-contrast) and T2 weighted sequences, and dose-volume parameters extracted. Probability of RAIC over time was calculated using multistate analysis. Univariate/multivariate analyses were performed using Cox Regression. Recursive partitioning analysis was used to investigate dose-volume correlates of RAIC development.
Results 17.3% developed RAIC. All RAIC events were asymptomatic and occurred in the temporal lobe (14), frontal lobe (6) and cerebellum (2). The median volume of the RAIC on post-contrast T1 was 0.5 cc at their maximum size. The RAIC spontaneously resolved in 27.3%, progressed in 27.3% and improved or were stable in 29.6% of patients. The 3-year actuarial rate of developing RAIC was 14.3%. Brain and RAIC lesion doses were generally higher for temporal lobe RAIC compared to frontal lobe RAIC. RAIC was observed in 63% of patients when V67 Gy(RBE) of the brain ≥ 0.17 cc.
Conclusion RAIC lesions after PT were asymptomatic and either resolved or regressed in the majority of the patients. The estimated dose–volume correlations confirm the importance of minimizing focal high doses to brain when achievable.
Competing Interest Statement
All authors have completed the ICMJE uniform disclosure form and declare: Engeseth is funded by Trond Mohn Foundation. Dr S Stieb is funded by the Swiss Cancer League (BIL KLS-4300-08-2017). Stokkevåg is funded by Kreftforeningen. Dr Fuller received funding and salary support related to this project from the National Institutes of Health (NIH), including: the National Institute for Dental and Craniofacial Research Establishing Outcome Measures Award (1R01DE025248/R56DE025248) and an Academic Industrial Partnership Grant (R01DE028290). Dr. Fuller received funding and salary support unrelated to this during the project from: National Science Foundation (NSF), Division of Mathematical Sciences, Joint NIH/NSF Initiative on Quantitative Approaches to Biomedical Big Data (QuBBD) Grant (NSF 1557679); a National Institute of Biomedical Imaging and Bioengineering (NIBIB) Research Education Programs for Residents and Clinical Fellows Grant (R25EB025787-01); the NIH Big Data to Knowledge (BD2K) Program of the National Cancer Institute (NCI) Early Stage Development of Technologies in Biomedical Computing, Informatics, and Big Data Science Award (1R01CA214825); NCI Early Phase Clinical Trials in Imaging and Image-Guided Interventions Program (1R01CA218148); an NIH/NCI Cancer Center Support Grant (CCSG) Pilot Research Program Award from the UT MD Anderson CCSG Radiation Oncology and Cancer Imaging Program (P30CA016672) and an NIH/NCI Head and Neck Specialized Programs of Research Excellence (SPORE) Developmental Research Program Award (P50 CA097007). Dr. Fuller has received direct industry grant support, honoraria, and travel funding from Elekta AB. S.J. Dr. Frank reports personal fees from Varian, grants and personal fees from C4 Imaging, grants from Eli Lilly, grants from Elekta, grants and personal fees from Hitachi, other from Breakthrough Chronic Care, personal fees from Boston Scientific, and personal fees from National Comprehensive Cancer Center (NCCN). Dr. Gunn reports philanthropic donation from the Family of Paul W. Beach.
Clinical Trial
NCT 00991094, NCT 01627093
Funding Statement
Engeseth is funded by Trond Mohn Foundation. Dr S Stieb is funded by the Swiss Cancer League (BIL KLS-4300-08-2017). Stokkevåg is funded by Kreftforeningen. Dr Fuller received funding and salary support related to this project from the National Institutes of Health (NIH), including: the National Institute for Dental and Craniofacial Research Establishing Outcome Measures Award (1R01DE025248/R56DE025248) and an Academic Industrial Partnership Grant (R01DE028290). Dr. Fuller received funding and salary support unrelated to this during the project from: National Science Foundation (NSF), Division of Mathematical Sciences, Joint NIH/NSF Initiative on Quantitative Approaches to Biomedical Big Data (QuBBD) Grant (NSF 1557679); a National Institute of Biomedical Imaging and Bioengineering (NIBIB) Research Education Programs for Residents and Clinical Fellows Grant (R25EB025787-01); the NIH Big Data to Knowledge (BD2K) Program of the National Cancer Institute (NCI) Early Stage Development of Technologies in Biomedical Computing, Informatics, and Big Data Science Award (1R01CA214825); NCI Early Phase Clinical Trials in Imaging and Image-Guided Interventions Program (1R01CA218148); an NIH/NCI Cancer Center Support Grant (CCSG) Pilot Research Program Award from the UT MD Anderson CCSG Radiation Oncology and Cancer Imaging Program (P30CA016672) and an NIH/NCI Head and Neck Specialized Programs of Research Excellence (SPORE) Developmental Research Program Award (P50 CA097007). Dr. Fuller has received direct industry grant support, honoraria, and travel funding from Elekta AB. S.J. Dr. Frank reports personal fees from Varian, grants and personal fees from C4 Imaging, grants from Eli Lilly, grants from Elekta, grants and personal fees from Hitachi, other from Breakthrough Chronic Care, personal fees from Boston Scientific, and personal fees from National Comprehensive Cancer Center (NCCN). Dr. Gunn reports philanthropic donation from the Family of Paul W. Beach.
Author Declarations
All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.
Yes
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.