Dosimetric and Clinical Risk Factors for the Development of Maxillary Osteoradionecrosis in Adenoid Cystic Carcinoma (ACC) Patients Treated With Carbon Ion Radiotherapy.

Barbara Vischioni,Rossana Ingargiola,Mario Ciocca,Ester Orlandi,Anna Maria Camarda,Lorenzo Preda,Martino Meuli,Maria Bonora,Silvia Molinelli,Sara Ronchi,Stefania Russo,Sara Imparato

doi:10.3389/fonc.2022.829502

Abstract

BackgroundThe present study aims to evaluate dosimetric and clinical risk factors for the development of maxillary osteoradionecrosis (ORN) in head and neck adenoid cystic carcinoma (ACC) patients treated with carbon ion radiotherapy (CIRT).MethodsClinical data and treatment plans of ACC patients, consecutively treated from January 2013 to September 2016 within the phase II clinical trial CNAO S9/2012/C, were retrospectively reviewed. ORN and other treatment-related toxicity were graded according to the Common Terminology Criteria for Adverse Events (CTACE), version 4.0. The maxillary bone was contoured on the planning CT, and only patients receiving more than 10% of the prescription dose at their maxilla were considered for the analysis (67 patients). The volumes of maxilla receiving doses from 10 Gy (RBE) to 60 Gy (RBE) (VD), with an increment of 10 Gy (RBE), and additional clinical factors were correlated to the incidence of ORN with univariate analysis (Chi-square test). The logistic regression model was subsequently applied for multivariate analysis. Treatment plans calculated with a local effect model (LEM)-based optimization were recalculated with the modified microdosimetric kinetic model (MKM), and compared with literature data from the Japanese experience.ResultsThe median time interval from the start of CIRT to ORN appearance was 24 months (range, 8–54 months). Maxillary ORN was observed in 11 patients (16.4%). Grade 1 ORN was observed in 2 patients (18.1%), G2 in 4 (36.3%), G3 in 4 (36.3%) and G4 in 1 (9.3%). From univariate analysis, the site of the tumor, the presence of teeth within the PTV and acute mucositis correlated with the development of maxillary ORN. VD were significantly higher for all the dose levels tested in patients with maxillary ORN than patients without necrosis, according to both radiobiological models. The multivariate analysis showed that V60 significantly correlated with ORN risk.ConclusionThe volume of maxilla irradiated with high dose values was relevant for ORN development in our cohort of ACC patients. These results are in line with previously published data obtained with a different radiobiological model. Our findings might be helpful to prevent the risk of ORN in patients receiving CIRT.

Highlights

Osteoradionecrosis (ORN) is described as a chronic wound that fails to heal with bone exposure
We analyzed for the first time the risk factors for ORN development in patients treated with LEM-based carbon ion RT (CIRT)
We had a small sample of patients and of ORN events, we have still shown in our series the relevance of dosimetric parameters in predicting ORN risk after CIRT, with both the biological models mostly used in CIRT facilities worldwide for treatment planning, the LEM and microdosimetric kinetic model (MKM) model

Summary

Introduction

Osteoradionecrosis (ORN) is described as a chronic wound that fails to heal with bone exposure It is a treatment related complication primarily reported in the head and neck population treated with radiotherapy (RT) frequently associated with a substantial morbidity causing pain and infection. The incidence of ORN of the mandible when irradiating parotid tumors and at the skull base when irradiating tumors localized at the nasopharynx, has decreased in recent years with the transition from 2 and 3D-RT to the modern intensity modulated-RT (IMRT), since the more localized deposition of the higher doses to the tumor target in respect to the surrounding normal tissues [4, 5] In this regard, carbon ion RT (CIRT) has shown its superiority in dosimetric studies in delivering tumoricidal dose while sparing the surrounding normal tissues, due to the sharp penumbra of the therapeutic beams. The present study aims to evaluate dosimetric and clinical risk factors for the development of maxillary osteoradionecrosis (ORN) in head and neck adenoid cystic carcinoma (ACC) patients treated with carbon ion radiotherapy (CIRT)

Objectives

Methods

Results

Conclusion