Nasopharynx

Question 1

What are typical age/sex demographics of NPC?

Answer 1

median age at dx: 50 y/o
Male predominant (2-3:1)

Question 2

What are the anatomical boundaries of the nasopharynx?

Answer 2

Superior: skull base
Inferior: soft palate
Posterior: clivus/C1-2
Anterior: posterior edge of choanae
Lateral walls are comprised of torus tubarius and fossa of Rosenmuller

Question 3

What is the typical superior pattern of spread for NPC?

Answer 3

invades cavernous sinus via foramen lacerum; initial CN involvement is CN VI

Question 4

What are two CN syndromes that can be associated with NPC?

Answer 4

• Petrosphenoidal syndrome: foramen lacerum/cavernous sinus: oculomotor sx (CN III, IV, VI)
• Retroparotidian syndrome: jugular foramen: lost gag reflex (CN IX), vocal cord paralysis (CN X), trap atrophy (CN XI), deviation of uvula (CN IX) and tongue (CN XII)

Question 5

What are the main histologic subtypes of NPC to know?

Answer 5

keratinizing (WHO type I; 25% of US population)

non-keratinizing, undifferentiated (WHO type III; >95% of endemic/Asian)

Question 6

What is the difference in pattern of spread and tx response between major NPC subtypes?

Answer 6

WHO I: worse LC, lower risk of mets

WHO III: better LC, higher risk of mets

Question 7

What are major sx to assess in NPC?

Answer 7

• neck mass (>60%)
• epistaxis, nasal congestion
• headache, diplopia, facial numbness, otalgia
• trismus

Question 8

What are the most common sites of distant mets in NPC?

Answer 8

• bone, lung (common)

- liver (uncommon)

Question 9

What is T staging for NPC?

Answer 9

T1: confined to nasopharynx, or extension to nasal cavity/oropharynx
T2: parapharyngeal space, muscle involvement (med/lat pterygoid, pre-vertebral)
T3: bone involvement (skull base, vertebra, pterygoid plate, paranasal sinus)
T4: CN involvement, further extension (intracranial, orbit, soft tissue lateral to lateral pterygoid muscle, parotid, hypopharynx)

Question 10

What is N staging for NPC?

Answer 10

N1: bilateral RPs, unilateral high neck (above cricoid), <6cm
N2: bilateral high neck, <6cm
N3: >6cm, OR low neck (below cricoid)

Question 11

What it the typical treatment paradigm for NPC?

Answer 11

stage I (T1N0): RT alone
stage II-IVA: CRT (concurrent cis, adjuvant cis/5-FU)

Question 12

What radiation dose levels are commonly used in definitive RT for NPC?

Answer 12

gross disease: 70Gy/35fx (or 33fx)
high risk CTV: 60Gy
low risk CTV: 54Gy

Question 13

What is the typical target volume in definitive RT for NPC?

Answer 13

• CTV primary: entire nasopharynx, inferior sphenoid sinus, posterior maxil sinus/nasal cavity, PPF/pterygoid plates, parapharyngeal space, skull base (foramen ovale/rotundum), ant clivus, soft palate
• CTV nodes: bilateral: RP, retrostyloid, level II-V; (some cover level Ib for node positive side, but MSK doesn’t)

Question 14

What are the most significant late toxicities of RT for NPC?

Answer 14

• brainstem necrosis, temporal lobe necrosis

- hearing loss

Question 15

What was the major finding of the Al-Sarraf trial? (INT-0099)

Answer 15

30% OS improvement (5-year) with CRT vs RT (70% vs 40%)

Question 16

What was the structure of the Al-Sarraf trial?

Answer 16

n = 200
P: stage III/IV NPC (included modern stage II (N1))
I: CRT + adj chemo
C: RT
O: OS/PFS

Question 17

What were the main criticisms of the Al-Sarraf trial?

Answer 17

• poor survival in RT-alone arm compared to historical controls
• included 25% keratinizing histology, more radioresistant and not present in endemic regions

Question 18

What other data supports the findings of the Al-Sarraf trial?

Answer 18

• multiple RCTs in endemic regions

- MAC-NPC meta-analysis showing 5% OS benefit to CRT vs RT at 5 years

Question 19

Is adjuvant chemo necessary in treatment of NPC?

Answer 19

• Adjuvant chemo generally used per Al-Sarraf (some think controversial)
• One RCT from China addressed adjuvant chemo directly; trial was negative but highly flawed (not non-inferior design, poor chemo compliance, RT dose reduction, tx delays)