NASOPHARYNGEAL CARCINOMA

Nasopharyngeal Carcinoma

DR.MAAMON AMEEN

Introduction NPC is a squamous-cell carcinoma arising from epithelial lining of the

nasopharynx. Most common malignancy in the nasopharynx Nasopharyngeal malignancies

SCCA (nasopharyngeal carcinoma) Lymphoma Salivary gland tumors Sarcomas

Race: More in Chinese & North African people

Sex: Male preponderance of 3:1 Age: -Its incidence rate starts to rise after the second decade of life. -Median age is 50 years .

Gross: Proliferative, Ulcerative & Infiltrative types

The most common location is Fossa of Rosenmuller

Introduction

Anatomy

Lymphatic drainage

Lateral Retropharyngeal L.N also called as nodes of Röuviere, are the first nodes in the lymphatic drainage of Nasopharynx.

Extends from base of skull to C3 cervical vertebra.

Endoscopic anatomy

Radiological anatomy

GENETIC

ENVIORMENTVIRAL

Etiology

Etiology

Genetic:

Commonest in Chinese population. Genomic studies have revealed 3 HLA locus. HLA A2; HLA B46; HLA B17 are associated with increased risk of NPC

Viruses:EBV- well documented viral “fingerprints” in tumor cells and also anti-

EBV serologies with WHO type II and III NPCHPV - possible factor in WHO type I lesions

Etiology

Environmental:

salted fish food contain nitrosamines: carcinogen Lack of vit C in diet Burning of incense & woods: polyaromatic hydrocarbon:carcinogen Alcohol consumption & Cigarette smoking occupational exposure to dust, smoke, and chemical fumes

W.H.O. classification of NPC

1- keratinizing squamous cell ( 25% ) 2. Type II is non-keratinizing squamous carcinomas 12 % 3. Type III is the undifferentiated carcinomas 60 %

Clinical Features Upper neck swelling 50%

Clinical Features

Nasal symptoms 30% Blood-stained post-nasal discharge progressive nasal obstruction, Epistaxis

Clinical Features

Otological symptoms: Hearing loss Otalgia Otorrhoea Tinnitus

Clinical Features

Ophthalmologic symptoms : Diplopia & ophthalmo-plegia (involvement of CN III, IV, VI), Proptosis (orbit invasion) & Blindness (involvement of CN II).

Clinical Features

Neurologic (25-40 %):

Headache: indicates skull base erosion

Facial pain - Trigeminal

Xerophthalmia - greater sup. petrosal n

Jugular foramen syndrome: CN IX, X, XI involved by lateral retropharyngeal

lymph node

Clinical Features

Other symptoms Weight loss Anorexia Trismus Distant metastasis: to bone, lung & liver

Clinical Features

Diagnostic Evaluation

High index of suspicion required for early diagnosis

• Clinical evaluation • Radiological evaluation • Laboratory evaluation• Histopathological evaluation


Clinical evaluation Detailed medical history Examination : General physical examination Complete head and neck examination

Diagnostic Evaluation Clinical examination of nasophyrnx: Indirect nasophayrngoscopy with mirror Direct nasopharyngoscopy with fiber-optic scopeRigid 0 and 30* Hopkins rod endoscope




Radiological Evaluation Help to make the correct diagnosis Help To know the disease stage Help to determine the target volume of radiotherapy Help to evaluate the treatment results Follow-up


CT Scan Extent of tumor Neck node involvement Skull base erosion

MRI – radiologic modality of choice Determine if any intracranial extension of the tumour involves the brain

parenchyma or the cavernous sinus MRI > CT for displaying both superficial and deep nasopharyngeal soft tissue

and for differentiating tumor from soft tissue.





Positron emission tomography (PET) : - Useful in diagnosing recurrent /residual lesion following RT. -Useful to exclude distant metastasis before major salvage . Chest x-ray:

To identify lung metastasis Abdominal ultrasound:

To find liver metastasis. Bone scan.




Laboratory evaluation CBC, LFT’s

Special diagnostic tests (for types II & III) IgA antibodies for viral capsid antigen (VCA) IgG antibodies for early antigen (EA) Antibody Dependent Cellular Cytotoxicity assay.


Biopsy : first necessary investigation for NPC Endoscopic biopsy : Ideally it shuold be carried out

during the patient’s ist outpatient visit in suspected cases.

The most common sites are roof of nasopharynx and fossae of Rosenmuller.

FNA biopsy : should be done in suspicious neck lump.

Histopathological Evaluation

T.N.M. staging

T1 = Tumour confined to the nasopharynx or extends to oropharynx and/or nasal cavity

T2 = Tumour with parapharyngeal extension

T3 = invasion of bony structures or P.N.S.

T4 = intracranial, involvement of orbit, cranial nerves, infratemporal fossa,

hypopharynx

T.N.M. staging

N0 = no evidence of regional lymph nodes

N1 = unilateral N2 = bilateral

(Both are above supraclavicular fossa & < 6 cm)

N3 = > 6 cm or in supraclavicular foss

N3a- greater than 6 cm in dimension

N3b- extension to the supraclavicular fossa

M0 = no evidence of distant metastasis

M1 = distant metastasis present

T.N.M. staging

Stage I = T1 N0 M0

Stage II = T2 or N1 M0

Stage III = T3 or N2 M0

Stage IV = T4 or N3 or M1

NPC

Treatment

The management of NPC is unique for two reasons:

1-Tumor is in a relatively inaccessible location 2-Tumors is extremely radiosensitive

Treatment

Treatment Modalities Radiotherapy (modality of choice) Chemotherapy : combination with radiotherapy in advance

disease Surgery :To salvage local and regional failure

Radiotherapy

Modes of radiotherapy Teletherapy or External beam radiotherapy :Radiation beams projected to the

target area through skin Brachytherapy :uses radioactive material which are placed in close contact with

tumor tissue . Interstitial: Radioactive source inserted into tumor tissue

Intracavitary: Radioactive source placed inside catheter or moulds & inserted into nasopharynx

Radiotherapy

Modes of radiotherapy Intensity modulated radiation therapy (IMRT): recent development in

delivery of radiotherapy where maximum dose can be delivered to the tumor but saving important normal structure

Stereotactic radiosurgery delivers radiation therapy precisely to the tumor using a machine called a gamma knife. This can be used to treat tumors that have invaded the base of the skull, or tumors that have recurred at the base of the brain or skull.

primary treatment

Radiotherapy External beam radiotherapy is most commonly delivered by opposed lateral

fields to encompass the primary tumor and upper neck Treatment field has to cover nasopharynx ,paraphryngeal

space ,oropharynx ,skull base,sphenoid sinus ,posterior ethmoid ,posterior half of maxillary sinus

Bilateral Cervical nodal irradiation is mandatory even in clinically node-negative patients

primary treatment

primary treatment

Radiotherapy 65-70 GY for primary 65-70 GY for positive L.N 50-60 GY for negative L.N It should be delivered single fraction daily ,five per week without interruption . Proper shielding of all critical structures as well as surrounding normal tissue is

important.

primary treatment

Radiotherapy

Radiation boosts in the form of intracavitary brachytherapy for T1 to T2 lesions have been used to improve local control rates

Stereotactic radiosurgery boosts may also be given for T3 and T4 lesions.

primary treatment

Chemotherapy Chemotherapy is believed to act as radiosensitizer. It helps to reduce the chance of distant metastasis. For locally advanced disease (stage III-IV ) chemotherapy in addition to

radiotherapy appears to improve overall results. Combination chemotherapy produces better responses combination cisplatin/5-flurouracil is the most widely used Indicates that concurrent chemoradiotherapy has a major role in advanced stage

NPC

primary treatment

Complications chemotharpy Bone marrow suppression Sensorineural hearing loss Renal impairment Hair loss Weight loss Nausea and vomiting

primary treatment

FOLLOW-UP PLAN: Close monitoring of the progress during and after treatment is necessary . Follow-up endoscopy at 6–8 weeks and imaging at 10–12 weeks after

completion of radiotherapy or chemoradiotherapy is recommended to document tumour responses.

malignancy detected after 10 weeks usually represents viable tumour and salvage treatment is indicated

primary treatment

FOLLOW-UP PLAN:

Close monitoring of the progress during and after treatment is necessary . The majority of relapses occur in first three years . After primary treatment, patient should be seen : Two-monthly for the first year Three –monthly for 2nd and third year Six –monthly thereafter. Lifelong follow-up is needed as very late recurrence may also occur

primary treatment

FOLLOW-UP PLAN:

The response of local disease is best followed up by repeated nasoendoscopy . Post-treatment biopsy indicated if there is any residual swelling at the primary

site . Imaging is often needed to evaluate regional disease .

Salvage treatment

Treatment of recurrence Recurrence at the primary site can be treated by surgery or re-irradiation. Further dose of ERT may be considered. Brachytherapy is preferred. Cervical nodal recurrences are best treated by surgery .

Salvage treatment

surgery• Due to deep location of nasopharynx, and anatomic proximity to critical

structures, radical surgery is typically not used• Limited to biopsy Neck dissections for persistently enlarged lymph nodes Nasopharyngectomy in persistent or recurrent disease

Salvage treatment

Nasopharyngectmy Surgical approaches to the nasopharynx: Anterior approaches Inferior approaches Lateral approaches

Salvage treatment

Anterior approaches : Lateral rhinotomy Transnasl transmaxillary Midfacial degloving Maxillary swing (most common approach )

Salvage treatment

Inferior approaches : Transplatal :For localized tumour in the lower part of the posterior wall of the nasopharynx Mandibular swing

lateral infratemporal fossa approach: When the main tumour bulk is located in the paranasopharyngeal space close or lateral to internal carotid artery

Salvage treatment

Surgical salvage for neck disease: If a neck node persists in the absence of distant

metastasis ,radical neck disection (RND)should be performed

Prognosis

Approximate 5 years survival rates for NPC

Prognostic factors

TNM EBV pathologic type Old age Cranial nerve palsy Level and Fixity of nodes

Complications of Radiotherapy

xerostomia Oropharyngeal mucositis Alopecia Otitis media with effusion(OME) Otitis externa Rhinosinusitis Trismus Neck stiffness Dysphagia sensorineural deafness

Thank you

Health & Medicine

NASOPHARYNGEAL CARCINOMA