14 Nasopharynx Cancer

Nasopharynx Cancer

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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 10/09/2019

4. PATHOLOGY

In a small subset of cases, residual or recurrent disease persists in the nasopharynx and neck, either as a result of intrinsic radioresistance or suboptimal RT dose intensity due to the proximity to critical normal structures [Li, 2018]. Given the uniqueness of the nasopharynx anatomical topography, NPC has the potential to infiltrate critical neural structures intracranially via the porous base of skull and its foramens and laterally beyond ambiguous tissue planes to involve the masticator space. As a result, in cases where the tumour extends to these anatomical regions, optimal surgical resection with negative margins is not always feasible. When considering salvage RT, EBRT and brachytherapy techniques are possible options [Chua, 2016]. EBRT includes stereotactic radiosurgery (SRS) and IMRT. In principle, SRS is effective and safe in small recurrent tumours that are away fromcritical structures like the major neck vessels, cranial nerves and brainstem. The advent of IMRT has opened the possibility of re-irradiation in larger T3-4 recurrences, by its superior ability to conform radiation doses and derive sharp dose-gradients around critical normal tissues that had been previously irradiated. Several series have reported 3-year local control and survival rates of 60% and 50%, respectively, in recurrent NPC cases treated using this contemporary technique [Qiu, 2012, Tian, 2014, Li, 2018]. Nasopharyngeal brachytherapy, as described in literature, mostly entails intracavitary brachytherapy (ICBT) and 2D planning techniques. Invasive interstitial brachytherapy (ISBT) techniques have been described in older literature, but less invasive techniques incorporating endoscopic guidance, three- dimensional (3D) planning and high-dose-rate (HDR) delivery have been detailed in more recent publications. These advances could allow better coverage of deeper recurrences, as shall be discussed in subsequent sections. The nasopharynx is cuboidal in shape, and is bounded superiorly by the sphenoid sinus, posteriorly by the pharyngeal mucosa and longus colli muscles, laterally by the Eustachian cushion, in front of the fossa of Rosenmüller, and anteriorly and inferiorly by two arbitrary anatomical landmarks – the choanae, which links to the anterior nasal cavity and the caudal edge of the uvula, respectively (Figure 1). The nasopharynx is surrounded by critical normal organs. Superiorly, the porous base of skull and the clivus are barriers to the crucial cranial nerves (CN) in the cavernous sinus, including CN III, V, VI; the optic nerves (CN II) and the optic chiasm are also at risk in cases where the tumour involves the orbital apex and the sellar and parasellar spaces. Bulky tumours that extend laterally can also invade the pterygoid muscles and the masticator space, which would be associated with symptom of trismus. The nasopharyngeal region also harbours a rich lymphatic network, which would explain the frequent occurrence of nodal metastases (>60%); of note, the retropharyngeal and level II nodal stations are the first echelon of involvement [Ho, 2012]. 3. ANATOMICAL TOPOGRAPHY OF THE NASOPHARYNX

There exists in the nasopharynx an intermediate pseudostratified cuboidal type that is a transition between the pseudostratified columnar epithelium and the squamous epithelium. This intermediate epithelium is most susceptible to carcinogenesis, thus the propensity of NPC to grow in the lateral walls, posterior wall and anterior walls, in that order, corresponding to the predominance of this intermediate epithelium [Batsakis JG, 1980]. NPC is conventionally thought of as a tumour of squamous origin. Morphologically, the transformed cells are ovoid looking, with a distinct nucleoli and scanty chromatin, and often, there is an abundance of lymphoid cells that are admixed with the transformed epithelial cells. NPC is categorised into three pathological subtypes based on the degree of squamous differentiation. Type I – differentiated tumours with surface keratin; Type II – non-keratinising differentiated tumours; Type III – undifferentiated tumours. Of note, in regions where NPC is endemic, the non-keratinising subtypes (Types II and III) constitute the majority of cases (>95%). Interestingly, there is emerging evidence that Type II and III tumours are associated with EBV exposure, while some Type I tumours that are more common in the Western population may be associated with the human papilloma virus (HPV) [Lin 2013, Dogan, 2014]. All newly diagnosed NPC patients require a detailed clinical examination, which includes nasoendoscopic examination of the head and neck region, as well as a biopsy of the primary tumour. Laboratory investigations include routine complete blood count, a full renal and liver panel, and plasma cell-free EBV DNA titre. Of note, markers such as neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase, and EBV DNA have been proposed as prognostic biomarkers in NPC. Given the proclivity for nodal and distant metastases (lungs, liver, and bones), an MRI of the head and neck region, a CT of the thorax and abdomen, and bone scan are necessary to accurately stage the patient. For distant metastasis staging, 18FDG-PET is a superior modality to conventional CT and bone scans. At present, NPC is staged according to the 8th edition of the UICC/AJCC stage classification system (Table 1) [Pan, 2016]. 5. WORK UP

6. INDICATIONS AND CONTRAINDICATIONS

Given the principles of brachytherapy dosimetry, only superficial mucosal or submucosal lesions are amenable to this RT technique. Satisfactory outcomes had been observed with early brachytherapy techniques involving the use of radioactive gold grain (Au198) implants or insertion of iridium (Ir192) wires through a customised mould to treat superficial lesions. However, with the advent of remote after-loading, HDR intracavitary brachytherapy is favoured