Research article
Dual-energy computed tomography for prediction of loco-regional recurrence after radiotherapy in larynx and hypopharynx squamous cell carcinoma

https://doi.org/10.1016/j.ejrad.2018.11.005Get rights and content

Abstract

Purpose

To investigate the role of quantitative pre-treatment dual-energy computed tomography (DECT) for prediction of loco-regional recurrence (LRR) in patients with larynx/hypopharynx squamous cell cancer (L/H SCC).

Methods

Patients with L/H SCC treated with curative intent loco-regional radiotherapy and that underwent treatment planning with contrast-enhanced DECT of the neck were included. Primary and nodal gross tumor volumes (GTVp and GTVn) were contoured and transferred into a Matlab® workspace. Using a two-material decomposition, GTV iodine concentration (IC) maps were obtained. Quantitative histogram statistics (maximum, mean, standard deviation, kurtosis and skewness) were retrieved from the IC maps. Cox regression analysis was conducted to determine potential predictive factors of LRR.

Results

Twenty-five patients, including 20 supraglottic and 5 pyriform sinus tumors were analysed. Stage I, II, III, IVa and IVb constituted 4% (1 patient), 24%, 36%, 28% and 8% of patients, respectively; 44% had concurrent chemo-radiotherapy and 28% had neodjuvant chemotherapy. Median follow-up was 21 months. Locoregional control at 1 and 2 years were 75% and 69%, respectively. For the entire cohort, GTVn volume (HR 1.177 [1.001-1.392], p = 0.05), voxel-based maximum IC of GTVp (HR 1.099 [95% CI: 1.001–1.209], p = 0.05) and IC standard deviation of GTVn (HR 9.300 [95% CI: 1.113–77.725] p = 0.04) were predictive of LRR. On subgroup analysis of patients treated with upfront radiotherapy +/- chemotherapy, both voxel-based maximum IC of GTVp (HR 1.127 [95% CI: 1.010–1.258], p = 0.05) and IC kurtosis of GTVp (HR 1.088 [95% CI: 1.014–1.166], p = 0.02) were predictive of LRR.

Conclusion

This exploratory study suggests that pre-radiotherapy DECT-derived IC quantitative analysis of tumoral volume may help predict LRR in L/H SCC.

Introduction

In the last decades, treatment approaches for larynx and hypopharynx squamous cell carcinoma (L/H SCC) have shifted toward organ-preserving strategies, with the aim of limiting functional impairments associated with total laryngectomy/pharyngolaryngectomy and improving patients’ quality of life [1]. While organ-preserving trials have provided strong evidence that well-selected patients with L/H SCC may benefit from organ-preservation strategies, there remains substantial controversy on the optimal management of these patients [2]. In fact, despite improvement in radiotherapy techniques and systemic treatments, relapse rates in locally advanced L/H SCC after organ-preserving treatment remain high, with rates of loco-regional recurrence (LRR) at 5 years reaching 30–40% [[3], [4], [5]]. In addition, observational data suggest that 5-year survival rates of L/H SCC have decreased [6].

Better tumor characterisation through use of imaging biomarkers has the potential to provide insightful information for outcome prediction and treatment selection in L/H SCC. Various functional imaging modalities assessing tumor metabolism, hypoxia, cellularity and perfusion have been investigated in HNC. These modalities notably comprise the use of positron emission tomography (PET), including 18F- fluorodeoxyglucose (FDG-PET) [[7], [8], [9]], 18F-fluoromisonidazole-PET (FMISO-PET) [8,10] or 18-F-fluoroazomycin arabinoside-PET (FAZA-PET) [11]; use of magnetic resonance imaging (MRI), including diffusion weighted imaging [12,13] or dynamic contrast-enhance MRI [11,12]; as well as use of CT perfusion imaging [14,15]. Assessment of tumor perfusion in HNC is considered a useful tool for non-invasive evaluation of intra-tumoral microvessel density and for characterisation of tumor angiogenesis [16,17].

Dual-energy computed tomography (DECT) is an advanced form of CT in which image acquisition is performed at 2 different energies. This technology allows tissue characterisation through material decomposition and voxel-to-voxel determination of iodine concentration, which can be used to derive a regional blood volume map [18,19]. The applications of DECT in head and neck cancer have been a growing area of interest, with several recent studies showing the benefit of iodine characterisation and virtual monoenergetic images for detection and delineation of head and neck tumor [20,21], differentiation between metastatic, inflammatory and benign cervical lymph nodes [22,23] or assessment of cartilage invasion [24,25]. However, the role of DECT-derived quantitative imaging to predict oncological outcomes in HNC has never been previously investigated. Yet the rich quantitative information provided by DECT offers a unique opportunity for functional biomarker analysis. As previously proposed in single energy CT studies [26], we hypothesized that higher tumor iodine content is indicative of increased blood volume and capillary hyperpermeability associated with neo-angiogenesis. The purpose of this study was to investigate the role of DECT-derived quantitative histogram analysis of pre-treatment for prediction of LRR in patients with L/H SCC.

Section snippets

Patient population

Patients with larynx or hypopharynx cancer treated with radiotherapy and that underwent a pre-treatment planning DECT between January 2015 and August 2016 at our institution, were included in this retrospective study. Inclusion criteria were: [1] histological diagnosis of SCC of the larynx or hypopharynx [2]; curative intent locoregional radiotherapy +/- concurrent chemotherapy; [3] pre-treatment contrast-enhanced planning DECT of the neck. Patients that received induction chemotherapy and had

Patients and treatments characteristics

In total, 25 patients met inclusion criteria. Twenty-five patients, including 20 supraglottic and 5 pyriform sinus tumors were analysed; 76% were male. Median age was 65 years (43–79). Median GTVp volume was 7.9 cm3 (range = 0.7–51.8 cm3) and median GTVn volume was 7.0 cm3 (range = 0.5–25.8 cm3). Stage I, II, III, IVa and IVb constituted 4% (1 patient), 24%, 36%, 28% and 8% of patients, respectively. Forty-four percent had concurrent cisplatin and 28% had neoadjuvant chemotherapy consisting of

Discussion

This pilot study explores the role of DECT-derived quantitative imaging for outcome prediction in HNC. In this study, we describe a method allowing for volumetric extraction of iodine fraction from each voxel of the primary tumor and involved lymph nodes in L/H SCC. Iodine concentration was used as a surrogate for regional blood volume, with the working hypothesis that increased tumor angiogenesis would result in higher iodine contrast enhancement, as previously supported in single energy CT

Conflicts of interest

This work was supported by Fonds de Recherche du Québec-Santé. Houda Bahig, Edith Filion and David Roberge received research grant from Varian Medical Systems, unrelated to current work. Houda Bahig and David Roberge received speakers Honoraria from Siemens Healthineers/Varian Medical Systems, unrelated to current work.

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