Accounting for fractionation and heterogeneous dose distributions in the modelling of osteoradionecrosis in oropharyngeal carcinoma treatment

Gerda M Verduijn; Nienke D Sijtsema; Yvette van Norden; Wilma D Heemsbergen; Hetty Mast; Aniel Sewnaik; Denzel Chin; Sarah Baker; Marta E Capala; Aad van der Lugt; Esther van Meerten; Mischa S Hoogeman; Steven F Petit

doi:10.1016/j.radonc.2023.109889

Accounting for fractionation and heterogeneous dose distributions in the modelling of osteoradionecrosis in oropharyngeal carcinoma treatment

Radiother Oncol. 2023 Nov:188:109889. doi: 10.1016/j.radonc.2023.109889. Epub 2023 Sep 1.

Affiliations

¹ Departments of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands. Electronic address: g.verduijn@erasmusmc.nl.
² Departments of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands; Departments of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
³ Departments of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
⁴ Departments of Oral and Maxillofacial Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
⁵ Departments of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
⁶ Departments of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
⁷ Departments of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.

PMID: 37659662
DOI: 10.1016/j.radonc.2023.109889

Abstract

Background and purpose: Osteoradionecrosis (ORN) of the mandible is a severe complication following radiotherapy (RT). With a renewed interest in hypofractionation for head and neck radiotherapy, more information concerning ORN development after high fraction doses is important. The aim of this explorative study was to develop a model for ORN risk prediction applicable across different fractionation schemes using Equivalent Uniform Doses (EUD).

Material and methods: We performed a retrospective cohort study in 334 oropharyngeal squamous cell carcinoma (OPSCC) patients treated with either a hypofractionated Stereotactic Body Radiation Therapy (HF-SBRT) boost or conventional Intensity Modulated Radiation Therapy (IMRT). ORN was scored with the CTCAE v5.0. HF-SBRT and IMRT dose distributions were converted into equivalent dose in 2 Gy fractions (α/β = 0.85 Gy) and analyzed using EUD. The parameter a that led to an EUD that best discriminated patients with and without grade ≥ 2 ORN was selected. Patient and treatment-related risk factors of ORN were analyzed with uni- and multivariable regression analysis.

Results: A total of 32 patients (9.6%) developed ORN grade ≥ 2. An EUD(a = 8) best discriminated between ORN and non-ORN (AUC = 0.71). In multivariable regression, pre-RT extractions (SHR = 2.34; p = 0.012), mandibular volume (SHR = 1.04; p = 0.003), and the EUD(a = 8) (SHR = 1.14; p < 0.001) were significantly associated with ORN.

Conclusion: Risk models for ORN based on conventional DVH parameters cannot be directly applied to HF-SBRT fractionation schemes and dose distributions. However, after correcting for fractionation and non-uniform dose distributions using EUD, a single model can distinguish between ORN and non-ORN after conventionally fractionated radiotherapy and hypofractionated boost treatments.

Keywords: Equivalent uniform doses (EUD); Hypofractionation; Oropharyngeal squamous cell carcinoma (OPSCC); Osteoradionecrosis (ORN); Radiotherapy (RT).