Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia

Castelli et al. Radiation Oncology Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia Joel Castelli 0 1 Antoine Simon 0 Guillaume Louvel 1 Olivier Henry 1 Enrique Chajon 1 Mohamed Nassef 0 Pascal Haigron 0 Guillaume Cazoulat 0 Juan David Ospina 0 Franck Jegoux Karen Benezery Renaud de Crevoisier 0 1 0 Rennes University 1, LTSI, Campus de Beaulieu , Rennes F-35000 , France 1 Department of Radiotherapy, Centre Eugene Marquis , Avenue de la bataille Flandre Dunkerque, F-35000 Rennes , France Background: Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a standard IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Material and methods: Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Results: Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p < 0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p < 0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p < 0.001). Conclusion: During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk. Head and neck cancer; Anatomical variation; Adaptive RT; Xerostomia - Introduction The treatment of unresectable Head & Neck Cancer (HNC) consists of a chemoradiotherapy [1,2]. One of the most common toxicity of this treatment is xerostomia, inducing difficulties in swallowing and speaking, loss of taste, and dental caries, with therefore a direct impact on patient quality of life. Xerostomia is mainly caused by radiation induced damage mainly to the parotid glands (PG), and to a lesser extend to the submandibular glands [3]. Intensity modulated radiotherapy (IMRT) permits to deliver highly conformal dose in complex anatomical structures, while sparing critical structures. Indeed, three randomized studies have demonstrated improving (PG) sparing by using IMRT compared to non-IMRT techniques, resulting in better salivary flow and decreased xerostomia risk [4-6]. However, large variations can be observed during the course of IMRT treatment, such as body weight loss [7,8], primary tumor shrinking [7], and PG volume reduction [9]. Due to these anatomical variations and to the tight IMRT dose gradient, the actual administered dose may therefore not correspond to the planned dose, with a risk of radiation overdose to the PGs (Figure 1) [10,11]. This dose difference clearly reduces the expected clinical benefits of IMRT, increasing the risk of xerostomia. Although bone-based image-guided radiation therapy (IGRT) allows for setup error correction, the actual delivered dose to the PGs remains higher than the planned dose [12], due to the fact that IGRT does not take shape/volume variations into account. By performing one or more new planning during the radiotherapy treatment, adaptive radiotherapy (ART) aims to correct such uncertainties. ART has been already shown to decrease the mean PG dose during locally advanced head and neck cancer IMRT [13], but no surrogate of the PG dose difference and of the dosimetric benefit of ART has yet been identified. In the context of IMRT for locally advanced HNC, this study sought to: estimate the difference between the planned dose and the actual delivered dose (without replanning) to the PGs, i.e., the PG overdose; estimate the PG dose difference with replanning and without replanning to spare the PGs while keeping the same planning target volume (PTV), i.e., the benefit of ART; identify anatomical markers correlated with these dose differences (PG overdose and ART benefit). Materials and methods Patients and tumors The study enrolled a total of 15 patients with a mean age of 65 years (ranging from 50 to 87 years). Patient, tumor, and treatment characteristics are provided on Table 1. All tumors were locally advanced (Stage III or IV, AJCC 7th ed). The mean PG volume was 25.3 cc (ranging from 16.6 cc to 52.1 cc, standard deviation (SD): 8.1 cc). Treatment and planning All patients underwent IMRT using a total dose of 70 Gy (2 Gy/fraction/day, 35 fractions), with a simultaneous integrated boost technique [14] and concomitant chemotherapy. Planning CTs (CT0) with intravenous contrast agents were acquired with 2 mm slice thickness from the vertex to the carina. A thermoplastic head and shoulder mask with five fixation points was used. PET-CT and MRI coregistration was used for tumor delineation. Three target volumes were generated. Gross tumor volume (GTV) corresponded to the primary tumor along with involved lymph nodes. Clinical target volume 70 Gy (CTV70) was Figure 1 Illustration of the anatomical variations on the dose distribution. IMRT dose distributions at different times for a given patient, showing the PG overdose without replanning (B) and the benefit of replanning (C). A: Planned dose on the pre-treatment CT (CT0). B: Actual delivered dose without replanning during the treatment (Week 3). C: Adaptive planned dose with replanning to spare the parotid glands (PG) at the same fraction (Week 3). PGs are shown by the red line. The full red represents the Clinical Target Volume (CTV70). The arrow show the head thickness. Figure 1B and 1C compared to 1A shows that the PGs and the CTV70 volumes and the neck thickness have decreased. These anatomical variations have led to dose hotspots in the neck, close to the internal part of the two PG (Figure 1B). Replanning (Figure 1C) allowed to spare the PG even better than on the planning (Figure 1A). Table 1 Patient, tumor, and treatment characteristics at the initial planning (CT0) M: male; F: female; CT0: in (...truncated)