World wide: Age is less than for other H&N ca's. Median age
50. 20% are under age 30. 3:1 Male:Female Very rare in USA an
incidence of 0.5 to 2 per 100,000, and an association with alcohol
and tobacco, classic risk factors for other head and neck tumors
Southeast China (Cantonese in Kwangtung, Hong Kong, Macao) has
~150x the incidence of the USA. Chinese-Americans have a risk at
least 6x greater than other ethnic groups. Also seen in Far
northern hemisphere (Greenland, Iceland, Inuit), intermediate
extent in North Africa, Middle East, Mediterranean
Slide 6
Etiology: Multifactorial: Viral, Genetic, and Environmental.
Multistep model of NPC carcinogenesis 1. An individual may carry a
genetic predisposed risk, via HLA type. 2. Nasopharyngeal
epithelium becomes infected with EBV early in life. 3. Viral gene
expression of proteins such as LMP1 & EBNA-1 stimulates the
nasopharynx epithelium. 4. Tumor suppressor genes on chromosome 3
may become modified such as salted fish.
Slide 7
EBV is the strongest etiologic factor identified. EBV is
associated with WHO type 2 and 3 npx ca's. Anti-EBV antibodies
found in the serum (VCA IgA, EA IgA) in most patients with
non-keratinized NPC. EBV DNA detectable in tumor cells and
metastases, by PCR EBV DNA found in preinvasive lesions (dysplasia
/ in-situ) - Clonal EBV DNA in 11/11 specimens examined by Olmi,
Italy. Epstein Barr Virus
Slide 8
Salted Fish In Hong Kong, eating salted fish at least once a
week at age 10 increase relative risk by 38%. Up to 90% of NPC in
Hong Kong may be attributable to childhood exposure of salted fish.
NPC and nasal cancer can be induced in rats fed salted fish
Slide 9
Genetic Presumed genetic susceptibility in certain races, i.e.
southern Chinese. Japanese do not have an increased risk HLA A2,
BW46, other haplotype associations Family aggregates in China,
Greenland
Slide 10
Other Factors Poor hygeine Herbal folk medicines based on
euphorbs may activate latent EB virus Wood fire smoke Tobacco
smoking not a risk factor in Asia However, in USA a veterans study
showed 4x risk for current smokers. Working in agriculture or as a
wood-cutter
Slide 11
Pathology: WHO Classification (Malignant Epithelial)
WHO-1:Squamous cell carcinoma WHO-2:Nonkeratinizing carcinoma
WHO-3:Undifferentiated carcinoma (lymphoepithelioma is a term to
describe Nonkeratinizing and Undifferentiated carcinoma) Alternate
Classification (Micheau, Krueger) 1. SCC 2. UCNT (Undifferentiated
Carcinoma of the Nasopharyngeal Type)
Slide 12
WHO-I (Keratinized) - proportionately more seen in North
America and Europe - some association with smoking - not associated
with EBV - local control is a significant problem - less distant
mets, especially at diagnosis - Poor survival WHO-II/III - endemic
form in Asia - etiology: genetics / EBV / salted fish - good local
control - high rate of distant mets, ~25% at presentation
Slide 13
UndifferentiatedKeratinized 55%76%LN + 79%29%Primary Control
85%76%Nodal Control 33%6%Met 51%6%survival
Petrosphenoidal Syndrome Involvement of CN 3,4,5,6, usually by
spread through the foramen lacerum to the cavernous sinus. Order of
involvement often.(6- 3-V1-V2-4) Ptosis, ophthalmoplegia, facial
pain / anesthesia. Villaret's Syndrome Syndrome of the retroparotid
space Extension into retropharyngeal space by involved
retropharyngeal nodes. Compresses CN 9,10,11,12 as they emerge from
base of skull into parapharyngeal space. Horner's may also
occur
Slide 16
Lymph Node Involvement at Presentation Unilateral :90%
Bilateral:Half Distant Metastases Distant mets are in 3% at
diagnosis, and eventually 30%. Most common sites are lung, bone,
liver. Risk increases with extent of nodal disease, and less so
with loco-regional relapse (40% vs 30%, Kwong). Risk of mets for
N0=15% N1=20% N2=35% N3=50%.
Slide 17
Diagnostic workup for carcinoma of the nasopharynx General
History Physical examination including careful inspection to
determine extent of primary tumor and palpation for neck node
metastases, testing of cranial nerves, and inspection of tympanic
membranes Special tests Indirect and direct nasopharyngoscopy
Multiple biopsies Baseline audiologic testing (as clinically
indicated) Radiographic studies Standard Computed tomography or
magnetic resonance scans of head and neck Chest radiograph
Complementary Bone scan: only if indicated by pain or tenderness or
elevation of heat-labile fraction of alkaline phosphatase Bone
radiographs: only if indicated by abnormal bone scan or symptoms
Liver scan: only if indicated by right upper quadrant pain,
enlarged liver by palpation, or elevation of liver chemistries
Laboratory studies Blood counts Blood chemistry profile Liver
function studies
Slide 18
American Joint Committee TNM staging system for nasopharyngeal
carcinoma Primary tumor TXPrimary tumor cannot be assessed T0No
evidence of primary tumor TisCarcinoma in situ T1Tumor confined to
the nasopharynx T2Tumor extends to soft tissues of oropharynx
and/or nasal fossa T2aWithout parapharyngeal extension T2bWith
parapharyngeal extension T3Tumor invades bony structures and/or
paranasal sinuses T4Tumor with intracranial extension and/or
involvement of cranial nerves, infratemporal fossa, hypopharynx, or
orbit Neck nodes a NxRegional lymph nodes cannot be assessed N0No
regional lymph node metastasis N1Unilateral metastasis in lymph
node(s), 6 cm in greatest dimension, above the supraclavicular
fossa N2Bilateral metastasis in lymph node(s), 6 cm in greatest
dimension, above the supraclavicular fossa N3Metastasis in a lymph
node(s): N3aGreater than 6 cm in dimension N3bExtension to the
supraclavicular fossa Metastases MXDistant metastasis cannot be
assessed M0No distant metastasis M1Distant metastasis present
Slide 19
ADVERSE PROGNOSTIC FACTORS Host Older age (>50) male worse
More symptoms (7 or more do worse) Longer duration of symptoms do
worse Histology WHO-1 (keratinized SCC) is worse Presence of
lymphoid component does not significantly affect prognosis,
although some studies have found lymphepithelioma better. Extent T1
and T2 behave similiarly Tumor filling nasopharynx, regional
extension does worse CN involvement worse than skull involvement
Intracranial extension particularly bad Low neck / supraclavicular
nodes do worse (below Ho's Line at thyroid notch) Bilateral neck
disease appears to be bad, 10% 5yS (Qin) Distant metastases
Treatment Related Dose of radiation. Perez found > 7000 cGy best
for T1/T2/T3.
Slide 20
ANATOMY - The nasopharynx is cuboidal in shape - 2 lateral
walls - a roof which slopes down to become the posterior wall.
Borders 1.inf. soft palate 2.sup. sphenoid sinus 3.ant nasal fossa
(post choana) 4.post C1/C2 Torus tubarius indicates the opening of
the Eustachian tubes.
Slide 21
ANATOMY Fossa of Rosenmuller lies posterior to the TT. Junction
of lateral wall and posterior wall Most common origin of NPC.
Useful site for "blind biopsies". Adenoids (pharyngeal tonsils) in
turn lie directly behind the fossa of R.
Lateral Parapharyngeal space Masticator space Carotid
space
Slide 28
Posterior Compartment Retropharyngeal space Prevertebral
space
Slide 29
MANAGEMENT Surgery Surgery may play a role in the diagnosis and
staging of NPC Surgery generally entails a skull base resection,
and is reserved for small local recurrences. Resection of the
primary can occasionally be done with a small adenoca or sarcoma.
It is also frequently used for juvenile angiofibromas, due to young
age of pt. RT is also effective. Neck dissections are usually not
necessary, as nasopharynx ca neck nodes are usually
radio-sensitive, and the neck is only rarely the site of isolated
failure. As well, the uppermost juctional nodes are not well
dissected by surgery. Neck disection may be useful for removal of 1
or 2 large masses after receiving a smaller xrt dose than usual,
i.e. 50-55 Gy.
Slide 30
MANAGEMENT Radiation Therapy The usual primary therapy for the
lesion and nodes. Standard external beam therapy is typically: 70
to 75 Gy to the primary tumor 66 to 70 Gy to involved lymph nodes
50 Gy to the uninvolved neck given in single daily fractions of 1.8
to 2.0 Gy five days per week over six to seven weeks. All patients
require treatment of both sides of the neck.
Slide 31
Slide 32
Slide 33
Slide 34
Slide 35
TOXICITY Radiotherapy Toxicity Similiar to other head and neck
sites Large field + High Doses = Significant Toxicity Acute
Mucositis Weight loss Dry/moist skin desquamation N & V Local
hair loss Late Xerostomia, caries Fibrosis (trismus, neck
induration, entrapment neuropathy) TMJ problems Eustachian tube
dysfunction Retinopathy / Optic nerve / Optic chiasm injury
Temporal lobe / brainstem necrosis Hypopituitarism, hypothyroidism
Pneumonitis Second Malignancies (osteosarcomas, meningiomas,
astrocytomas, etc)
Slide 36
Chemotherapy
Slide 37
Slide 38
Slide 39
RESULTS T1/T2 N0/N1 do very well. T4 has a high local failure
rate (~70%). N2/N3 has a high distant metastases rate (up to 50%).
5y Survival T185% T2or N160% T3 or N2 45% T4 or N3 30% Overall 50%
WHO-110% WHO-2,350%
Slide 40
Local Control T1 85% T280% Approx 20% better than survival for
T2,T3,T4 T365% T450% Squam Cell60% Lymphoepith90%
Slide 41
Chemotherapy for Metastatic Disease Several series Best
responses with Platinum based combination chemo Overall ~75%
response rate (20% CR) A few long term 5-10y survivors occur
Interferon has anti-viral properties but has not been successful
against NPC
