Nasopharynx

Anatomy
Borders of the nasopharynx
-Superior: Floor of sphenoid sinus
-Inferior: Soft palate
-Anterior: Back of nasal cavity/choanae
-Posterior: Paravertebral fascia (?) covering body of C1
-Lateral: Torus tubarius - opening of Eustachian tubes; fossa of Rosenmuller lies posterior to the torus and is the most common site of origin
Skull base access through the foramen lacerum and foramen ovale then into the cavernous sinus
Cavernous sinus involvement is associated with CN III, IV, V-1. V-2, VI palsies
Parapharyngeal involvement can affect CN IX, X, XI, XII

Lymph node patterns of spread
>70% of patients have N+ disease
Most common: level II, RP, III, V, IV, I

Epidemiology
Endemic form (Southeast Asia): nonkeratinizing, incidence begins to increase in 30's, peaks in middle age, associated with EBV infection, possibly salted/preserved foods
Non-endemic form: keratinizing; bimodal age distribution (15-25 years and 50-59 years), associated with smoking

Pathology
WHO grading includes 3 distinct subtypes
Type 1 = keratinizing SCC
Type 2.1 = Nonkeratinizing but well differentiated
Type 2.2 = Nonkeratinizing, undifferentiated; lymphoepithelioma is a subtype of 2.2

Clinical
Nodal involvement in a large majority of patients (see above)
Most common site of metastasis is bone (unlike other SCC which like to go to the lung)
Symptoms: cranial nerve deficit (20%), hearing loss, epistaxis, stuffy nose
MRI gives better visualization of skull base structures than CT
Staging system is different from other SCC of the head and neck


Prognostic factors
T stage/volume of disease
N stage
Sex (female is better)
Age (younger better)
EBV titer (higher worse)
Histology (keratinizing worse)

Treatment, early stage disease
T1-2, N0-1
Gross disease gets 70Gy, clinically + neck 60Gy, prophylactic neck 50Gy
All patients should have prophylactic neck fields treated given the high rates of nodal mets
RP nodes and level V need to be covered

Treatment, advanced disease
T3-4Nx, TxN2-3
Chemoradiation
Intergroup regimen is the most commonly used (Intergroup 0099, PMID 9552031)
Cisplatin 100mg/m2 q3 weeks during RT to 70Gy
Then adjuvant cisplatin/5-FU
This was the first chemoradiation trial to show an OS benefit (47 vs 78% at 3yrs) in nasopharyngeal cancer. The trial has been criticized for a few reasons:
-RT only arm had worse survival than historical series
-High rate of distant metastatic disease
-High rates of toxicity with adjuvant chemo and late toxicities including hearing loss, endocrine insufficiency, and peripheral neuropathy
Subsequent meta-analysis also showed a benefit, but magnitude was much less (PMID 16377415)
Other regimens under study include induction chemo, altered fractionation

Common complications of nasopharynx cancer and therapy
Temporal lobe necrosis (associated with doses >2Gy/day, accelerated tx)
Cranial nerve palsy
Endocrinopathy
Hearing loss
Xerostomia
Carotid injury
Chronic epistaxis