A Nomogram to predict parotid gland overdose in head and neck IMRT

Castelli et al. Radiation Oncology (2016) 11:79 DOI 10.1186/s13014-016-0650-6 RESEARCH Open Access A Nomogram to predict parotid gland overdose in head and neck IMRT J. Castelli1,2,3*, A. Simon2,3, B. Rigaud2,3, C. Lafond1, E. Chajon1, J. D. Ospina2,3, P. Haigron2,3, B. Laguerre4, A. Ruffier Loubière5, K. Benezery6 and R. de Crevoisier1,2,3 Abstract Purposes: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). Material and methods: Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. Results: Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. Conclusion: Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning. Keywords: Nomogram, Adaptive radiotherapy, Head and neck, Parotid gland overdose Introduction During the course of intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), large anatomical variations may result in delivered doses differing from the planned dose [1]. The literature shows that while dose variations in the clinical target volume appear extremely low [2–5], the percentage of patients with estimated PG overdoses ranges widely from 5 to 70 % [1, 5–10]. With the aim of correcting these PG overdoses, an adaptive radiotherapy (ART) strategy involving one or several replannings during treatment has been investigated [1, 2]. These replannings are, however, time* Correspondence: 1 Centre Eugene Marquis, Radiotherapy, de la Bataille Flandre Dunkerque, F-35000 Rennes, France 2 Rennes University 1, LTSI, Campus de Beaulieu, Rennes F-35000, France Full list of author information is available at the end of the article consuming, as a complete delineation can take up to 2.5 h [11–13] and may not be beneficial for all patients. It is therefore crucial to identify patients with PG overdose and evaluate how ART benefits each individual. Ideally, replanning decisions should be based on early and simple anatomical criteria, such as weight loss or decrease in neck diameter, which have been identified as risk factors for overirradiation [10, 14–17]. However, a clear correlation between these markers and PG overdose has not yet been established [6]. After having identified early predictors of PG overdose, this dosimetric study had two objectives: 1) to generate a nomogram so as to predict PG overdose; 2) to quantify the benefits of weekly replanning, triggered by the nomogram, in terms of dose sparing and decrease in xerostomia risk. © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Castelli et al. Radiation Oncology (2016) 11:79 Page 2 of 11 Materials and methods Patients and tumors A total of 20 patients (mean age: 63; range: 50–77) were enrolled in this study. All patients presented with locally-advanced oropharyngeal cancer (Stage III or IV, American Joint Committee on Cancer 7th ed.). Patient, tumor, and treatment characteristics have been provided in Table 1. Treatment and planning All patients underwent IMRT with total doses of 70Gy (2Gy/fraction/day, 35 fractions), combined with a simultaneous integrated boost technique [18] and concomitant chemotherapy (cetuximab or platinum). Planning CTs (CT0) were performed with intravenous contrast agents using 2-mm slice thickness, from the vertex to the carina. Three target volumes were generated: CTV70, CTV63, and CTV56. The 70Gy clinical target volume (CTV70) was equal to the gross tumor volume plus a 5-mm 3D margin, adjusted to exclude the air cavities and all bone mass free of tumor invasion. CTV63 corresponded to the area at high-risk of microscopic spread, in particular the ipsilateral nodal level II, while CTV56 corresponded to the low-risk subclinical area. The planning target volume (PTV) was the CTVs plus a 5-mm 3D margin, limited at 3 mm from the skin surface in order to avoid the build-up region and therefore limit skin toxicity [19]. The minimum PTV covered by the 95 % isodose line was 95 %. Dose constraints were set according to the GORTEC group (the French group of radiation oncology for head and neck cancer) (Table 2). Parotid sparing was not conducted if considered to the detriment of PTV coverage or other essential organs at risk (OARs). During the treatment course, set-up errors >5 mm were corrected by weekly in-room stereoscopic kV imaging. Informed consent was obtained from all patients. This study was approved by the institutional review board (ARTIX study NCT01874587). Weekly dose estimations Each patient underwent six weekly CTs (CT1-CT6) using the same protocol as CT0 over the treatment course, except for some variations in intravenous contrast agent use, which was not systematically employed, Table 1 Patient, tumor, and treatment characteristics at initial planning (CT0) ID Gender Age TNM Tumor sublocation Chemotherapy Cetuximab Volume (cm3) Mean planned PG dose (Gy) Xerostomia NTCP (%) [23, 24] CTV70 ILP CLP ILP CLP ILP CLP 45.2 52.1 48.6 30.2 31.1 27.1 28.9 1 M 77 T4N0 Tonsil 2 F 61 T2N2 Base of tongue CDDP 26.3 31.1 27.5 31.4 26 29.7 19.1 3 M 70 T3N2c Oropharynx CDDP 181.5 24.9 20.7 37.9 31.1 45.1 29.1 4 F 66 T2N2c Oropharynx Cetuximab 107.2 27.8 23.4 32.9 27.9 33.1 22.5 5 M 57 T3N0 Velum CDDP 62.4 20.7 18 28.1 27.8 23 22.3 6 M 67 T (...truncated)