Background

Chapter 1 Introduction

1.1 Background

Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma arising from the

epithelium of the nasopharynx. Nasopharyngeal carcinoma is rare in western

countries and its incidence is less than one per 100,000 population.¹ However, NPC

occurs much frequent in southern China, especially at the Guangdong province. Hong

Kong and Taiwan, which geographically located near the province of Guangdong, are

also with high incidence of NPC. The reported incidence of NPC among men and

women in Hong Kong is 20–30 per 100 000 and 15–20 per 100 000, respectively.² In

Taiwan, the crude annual incidence was 7.9 per 100,000 males and 3.3 per 100,000

female. The ratio between male to female was 2.4:1.³

The possible etiology of NPC includes genetic, ethnic and environmental factors.

Familial clustering of cases of NPC indicates the potential role for genetic factors.^4-6

The consumption of salted fish is associated with increased risk.^7-9 The Epstein-Barr

virus (EBV) has been implicated as an important causative agent in NPC. The EBV is

consistently found in tumor cells of NPC. The serum EBV DNA in patients of NPC

showed a strong correlation with disease stage and prognosis.^10,11

The histological classification of NPC proposed by WHO included 3 types and

subdivided into two groups, according to their relationship to EBV and disease

patterns (table 1.1).¹² Patients with keratinising squamous cell carcinomas (WHO type

I) have a reduced EBV titer, whereas those with non-keratinising carcinomas (WHO

type II or type III) have raised titers. The histology distribution of NPC in southern

Chinese and Taiwan were different from western countries, with a much higher

incidence of undifferentiated carcinoma. The distribution of type I, II and III NPC in

southern Chinese was 2%, 3%, and 95%, respectively.¹³ Patients with undifferentiated

carcinomas have a higher local control rate and higher distance metastasis rate than

those with differentiated carcinomas.

Table 1.1 Histological classification of nasopharyngeal carcinoma

Keratinising squamous-cell carcinoma WHO type I

Non-keratinising carcinoma

1. differentiated non-keratinising carcinoma WHO type II

2. undifferentiated carcinoma WHO type III

Radiotherapy (RT) is the standard treatment for NPC. In conventional

radiotherapy, 50 Gy is given to regions at risk for harboring subclinical disease and

65-75 Gy is given to the primary tumor and the involved neck nodes. Patients with

early stage NPC (stage I and stage II) generally have good treatment outcomes. For

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patients with advanced NPC (i.e., T3, T4 or node-positive diseases), RT alone is not

adequate. NPC is also a chemosensitive tumor, especially with cisplatin-based

regimens. A combination of chemotherapy with RT is the optimal way to treat

high-risk patients. Phase III trials have showed increased local control and survival

benefit with concurrent chemoradiation.^14-17 But the drug of choice, the timing,

dosage and duration of chemotherapy remain controversial.

The main principles of radiotherapy are the delivery of a tumoricidal dose to the

primary site and suspected lymphatic spread region with well recognition of normal

tissue tolerance. Radiotherapy results in some undesirable toxicity, including acute

and late complications. Acute effects develop during a standard 6- or 7- weeks course

of radiation therapy and the late effects develop weeks, months, or years after the end

of treatment. The acute RT reactions result from the injury of rapidly renewing normal

tissue. And the late reactions result from cell loss in nonregenerating or slowly

renewing normal tissues.¹⁸ The brain stem, spinal cord, pituitary gland, orbit,

paranasal sinuses, nasal cavities, parotid glands oral cavity, inner and middle ears all

located closely surround the nasopharynx. These are all inevitably injured by RT.

Survivors of NPC usually have impaired quality of life. The possible radiation

sequelae are xerostomia, trismus, rhinosinusitis, otitis media, cranial nerves palsies,

dysphagia, hearing loss or temporal lobe necrosis etc.^19-24

With the advances in computing and engineering techniques, newer techniques

of radiotherapy as 3D treatment planning and intensity-modulated radiotherapy

(IMRT) had replaced the conventional radiotherapy with the advantage of more

precision of aiming the radiation beam at irregular tumors. The IMRT techniques

improve the differential between the tumor and the dose–limiting organs, therefore

decrease toxicity for surrounding critical organs with improved loco-regional

control.^25,26 In recent years, its use has spread rapidly in both academic and

community radiation oncology facilities but its outcomes and follow-up reports are

still limited. IMRT in the head and neck is more feasible than in other sites because

organ motion is practically absent.^25,27,28 Some research had reported the IMRT had

reduced the severity of xerostomia after treatment in patients with head and neck

tumor.^29,30

Fang et al analyzed the quality of life (QOL) of patients who received

conventional RT or IMRT showed patients who received IMRT had better quality of

life.³¹ The authors analyzed the QOL of NPC patients with the European Organization

for the Research and Treatment of Cancer Core QOL questionnaire (EORTC

QOL-C30) and the Head and Neck QOL questionnaire (EORTC QOL-HN35).

However, these two questionnaires were not specific to some common sequelae of

NPC survivors as otitis media, rhinosinusitis temporal lobe necrosis or deafness.

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These undetected factors also contributed to the patients’ QOL.

Most studies about NPC were related to the treatment outcomes. Only few

reported the post-RT complications. An article published in 2005 by Wei et al² did a

rigorous review of researches about NPC. However, only a short paragraph in this

article discussed the radiation side effects because of lacking of associated reports.

The authors stated that cutting down the complications of treatment should be one of

the main objectives of future clinical trials.