International GuidelineInternational guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma
Introduction
Radiation therapy (RT) is the primary treatment modality for nasopharyngeal carcinoma (NPC). Target delineation in NPC often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, despite the apparent radio-sensitivity of the tumour in many patients. Even in the contemporary era of intensity-modulated radiotherapy (IMRT) with extensive use of concurrent chemotherapy, dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome. A study by Ng et al. showed that the 5-year local failure-free rate dropped to 54% if more than 3 cc volume within the gross primary tumour was under-dosed to below 66.5 Gy, compared with 90% in patients with smaller under-dosed volumes (p < 0.001) [1].
With the anatomical proximity of critical organs-at-risk (OARs), the importance of appropriate contouring to attain optimal balance between the risk of tumour recurrence due to marginal miss and the risk of serious late damage cannot be over-emphasized. The first fundamental step is accurate delineation of the Gross Tumour Volume (GTV) for individual patients based on the best available investigation methods. With the well-known highly infiltrative behaviour of NPC, especially the common non-keratinizing subtype, the next critical step is proper delineation of the clinical target volume (CTV) to cover the sites at relatively high risk of microscopic involvement. However, there are marked variations in philosophy and practice among clinicians [2].
The Danish national guidelines for delineation of CTV for head and neck squamous cell carcinoma (2013) [3] proposed the concept of isocentric “5 + 5 mm” geometric expansion of the primary tumour Gross Tumour Volume (GTVp), with corrections for natural anatomic boundaries such as bone or air cavities [4]. The principle is to deliver the full therapeutic dose to the CTV1 that covers at least the GTV + 5 mm margin, and a lower (prophylactic or intermediate) dose to the CTV2 that covers CTV1 + an additional 5 mm rim of tissue. The use of these guidelines has led to much more homogeneous target volume delineation among centres, as noted in data collected by Hansen et al. [5]. However, as the editing was mainly proposed for natural boundaries only, it is expected that the Danish national guidelines result in the inclusion of more non-target tissues in the tumour CTV (CTVp) than should ideally be included. Further refinement has recently been initiated by Vincent Grégoire and Cai Grau, to comprehensively review the Danish national guidelines and to edit for each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity; and specifically, for each T-category within the TNM staging classification by incorporating knowledge of anatomy and the patterns of spread of disease into the geometric CTV delineation concept [6].
The key objective of this proposed guideline is to develop recommendations on delineation of CTV specific to NPC that will provide clinicians with a practical reference on treatment principles, with a fundamental goal of providing a reference for appropriate contouring to ensure adequate tumour coverage. This document is based on consensus built by review of available evidence, comparison of published guidelines [2], [7], [8], [9] and detailed consideration of opinions and successive rounds of consensus by international experts experienced in the treatment of NPC. This guideline represents the concerted efforts of key oncologists from Asia (China, Hong Kong, Korea, Singapore, Taiwan), Australia, North America (Canada, United States), Saudi Arabia and Europe (Belgium, Denmark, France, The Netherlands, Turkey, United Kingdom). The guideline should be applicable for all histological subtypes of NPC.
Section snippets
Acquisition of the planning CT
The patient should typically lie in the supine position on the flat table-top of the simulation CT scanner with the head and neck immobilized in a neutral neck position by a reproducible immobilization device, most commonly a 4–5 fixation point thermoplastic mask covering from skull vertex to shoulder [10].
Thin CT sections (preferably 2 mm thickness) should be acquired typically from vertex to 2 cm below the sternoclavicular joints. We suggest scanning from the vertex in order to include the
Patterns of spread
Nasopharyngeal carcinomas tend to arise from the fossa of Rosenmüller, spreading submucosally with early infiltration of the palatal muscles within the parapharyngeal space. Due to its highly infiltrative nature, it spreads easily through areas of lesser resistance within the pharyngobasilar fascia, and tends to infiltrate along neural pathways. Dubrulle et al. [12] described the routes of tumour extension of NPC based on review of MRI imaging, noting that the routes of spread are often well
Recommendations and consensus guidelines
Although guidelines on target volume delineation of nodal levels have been previously published [39], [40], [41], there have been new studies on refining the selection of levels in node-negative NPC patients [42], [43], [44]. There are also controversies on details of contouring that warrant consideration. Therefore, in this recommendation, we will address some common areas with significant variation among experts for contouring the CTV for nodal coverage.
The diagnostic criteria used for
Discussion on treatment extent after induction chemotherapy
We include a brief discussion on the recommended target volumes for patients with induction chemotherapy given, because this is a common concern particularly for patients with tumour abutting critical OAR. Specific data on clinical–pathological correlation are lacking. This summary of consensus among international experts provides a guidance, but a full analysis is outside the main scope of this paper.
Induction chemotherapy can be a useful modality for NPC, in particular, for those cases where
Concluding remarks
The current study reveals marked variation in philosophy and practice among international experts most experienced in radiation therapy for NPC. This provides a valuable platform for comprehensive review of available evidence and extensive exchange of opinions on various contentious issues to attain consensus on best possible recommendations for contouring of CTV for NPC, While there are limitations where clinical–pathological data specific for NPC are scanty or lacking, this set of consensus
Disclaimer
This set of guidelines is not meant to be a dogmatic protocol. We aim to provide practical suggestions on appropriate of treatment volumes coverage for patients with accurate localization and delineation of gross tumour extent based on optimal investigations. However, wider margins may be needed in cases with sub-optimal imaging or in case of doubt about possible tumour involvement. The final target volumes should be based on full consideration of individual patients’ factors as well as the
Conflicts of interest statement
All authors declare no conflicts of interests.
Author’s contribution
VG, CG conceived of the idea. AWL, WTN, JJP and JTW developed and executed the consensus development. All authors participated in the consensus development. AWL, WTN, JJP, JTW, VG and SSP were involved in the writing phase of the manuscript. All authors reviewed and approved the final manuscript.
Funding source
None to declare.
Ethical considerations
None to declare.
References (67)
- et al.
The impact of dosimetric inadequacy on treatment outcome of nasopharyngeal carcinoma with IMRT
Oral Oncol
(2014) - et al.
Consequences of introducing geometric GTV to CTV margin expansion in DAHANCA contouring guidelines for head and neck radiotherapy
Radiother Oncol
(2018) - et al.
Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines
Radiother Oncol
(2018) - et al.
Addition of bevacizumab to standard chemoradiation for locoregionally advanced nasopharyngeal carcinoma (RTOG 0615): a phase 2 multi-institutional trial
Lancet Oncol
(2012) - et al.
Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma
Int J Radiat Oncol Biol Phys
(2011) - et al.
Comparison of setup accuracy of three different thermoplastic masks for the treatment of brain and head and neck tumors
Radiother Oncol
(2001) - et al.
Extension of local disease in nasopharyngeal carcinoma detected by magnetic resonance imaging: improvement of clinical target volume delineation
Int J Radiat Oncol Biol Phys
(2009) - et al.
Evaluation of microscopic disease in oral tongue cancer using whole-mount histopathologic techniques: implications for the management of head-and-neck cancers
Int J Radiat Oncol Biol Phys
(2012) - et al.
Clinicopathological analysis of local spread of carcinoma of the tongue
Am J Surg
(1998) - et al.
Microscopic extensions of head and neck squamous cell carcinomas: impact for clinical target volume definition
Cancer Radiother
(2014)
Modality-specific target definition for laryngeal and hypopharyngeal cancer on FDG-PET, CT and MRI
Radiother Oncol
How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients?
Int J Radiat Oncol Biol Phys
A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma
Radiother Oncol
Nasopharyngeal carcinoma treated with reduced volume intensity modulated radiation therapy: report on the 3 year outcome of a prospective series
Int J Radiat Oncol Biol Phys
Ethmoid sinus cancer: twenty-nine cases managed with primary radiation therapy
Int J Radiat Oncol Biol Phys
Carcinoma of the maxillary antrum: A retrospective analysis of 110 cases
Radiother Oncol
State of the art on dose prescription, reporting and recording in Intensity-Modulated Radiation Therapy (ICRU report No. 83)
Cancer Radiother
CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC, RTOG consensus guidelines
Radiother Oncol
Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines
Radiother Oncol
Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck
Radiother Oncol
Is selective neck irradiation safe for node-negative nasopharyngeal carcinoma?
Int J Radiat Oncol Biol Phys
Results of a phase 2 study examining the effects of omitting elective neck irradiation to nodal levels IV and Vb in patients with N(0–1) nasopharyngeal carcinoma
Int J Radiat Oncol Biol Phys
Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes
Int J Radiat Oncol Biol Phys
Study of the medial group retropharyngeal node metastasis from nasopharyngeal carcinoma based on 3100 newly diagnosed cases
Oral Oncol
Magnetic resonance imaging of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma: patterns of spread
Int J Radiat Oncol Biol Phys
Patterns of retropharyngeal node metastasis in nasopharyngeal carcinoma
Int J Radiat Oncol Biol Phys
A population-based atlas and clinical target volume for the head-and-neck lymph nodes
Int J Radiat Oncol Biol Phys
Patterns of lymph node metastasis from nasopharyngeal carcinoma based on the 2013 updated consensus guidelines for neck node levels
Radiother Oncol
Patterns of level II node metastasis in nasopharyngeal carcinoma
Radiother Oncol
N-staging by magnetic resonance imaging for patients with nasopharyngeal carcinoma: pattern of nodal involvement by radiological levels
Radiother Oncol
Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase III multicentre randomised controlled trial
Eur J Cancer
Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial
Lancet Oncol
Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer
Int J Radiat Oncol Biol Phys
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These 4 authors contributed equally.