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Oropharynx

Terms in this set (74)

What is incidence of orophaynx cancer (OPC) in US?
12,000 cases per yr
How does OPC incidence compare to other H/N sites?
increasing whereas others decreasing
Is there gender predilection for OPC?
male > female (3:1)
What are 4 subsites of oropharynx?
1. soft palate
2. tonsils
3. BOT
4. pharyngeal wall
From which subsite do most OPC arise?
Tonsil (ant tonsil pillar & fossa)
What are borders of oropharynx?
Ant: oral tongue / circumvallate papillae
Sup: hard palate / soft palate jxn
Inf: valleculae
Post: pharyngeal wall
Lat: tonsil
What 3 structures make up wall of tonsillar fossa?
1. Ant tonsillar pillar (palatoglossus muscle)
2. Post tonsillar pillar (palatopharyngeal muscle)
3. Inf glossotonsillar sulcus
What are 4 risk factors for OPC?
1. smoking
2. EtOH
3. HPV (16)
4. Betel nut
What is 1st echelon drainage for most OPC?
Level 2 (upper jugulodigastric) LN
Are skip mets common?
No. Very rare (< 1%)
What are 2 most common histologies in OPC?
SCC (90%)
NHL (10% tonsil, 2% BOT)
What are rare OPC histologies?
1. Lymphoepithelioma
2. Adenoid cystic carcinoma
3. Plasmacytoma
4. Melanoma
5. Small cell
What percent of pts with OPC fail locally / distantly?
Local: 50%
Distant: 50%
How prevalent is HPV infection in OPC?
40-80%
Which HPV serotype is most commonly associated with OPC?
16 (80-90%)
What is surrogate marker for HPV infection in OPC?
p16
- E7 protein inact Rb which upregulates p16
Which pt population is most likely to present with HPV-related OPC?
Nonsmokers, nondrinkers
Do HPV- or HPV+ OPC have a better prognosis?
HPV+
- RTOG 0129 showed longer OS3 82.4 vs. 57.1% and decreased risk of death for HPV+
- Smoking was independent risk factor
What is hypothesis as to why HPV+ have better prognosis?
Pts usually nonsmokers, nondrinkers so p53 not mutated
- p53 mutation predicts for poor response to tx (common in HPV- H/N cancers
What nerve is responsible for otalgia in cancers of oral tongue?
Auriculotemporal (V) >> pre-auricular area
What nerve is responsible for otalgia in cancers of BOT?
Jacobson (IX) >> tympanic cavity
What nerve is responsible for otalgia in cancers of larynx / hypopharynx?
Arnold (X) >> post-auricular area
What is most common presentation of OPC?
Neck mass (especially with HPV+)
What are common symp for cancer of BOT?
- sore throat
- dysphagia
- otalgia
- neck mass
What are common symp for cancer of tonsil?
- sore throat
- trismus
- otalgia
- neck mass
What are common symp for cancer of soft palate?
- leukoplakia
- sore throat with swallowing
- trismus / perforation
- phonation defect with advanced lesions
What are common symp for cancer of pharyngeal wall?
- pain / odynophagia
- bleeding
What is work-up for oropharynx mass?
- H&P (bimanual exam of FOM)
- labs
- direct laryngoscopy
- CT/MRI H&N
- bx
- CT chest
If neck mass bx is positive, is bx of primary necessary?
Yes.
What percent of OPC have clinically occult nodal mets?
30-50%
What percent of pts present with clinically +LN and what percent present with bilat LN?
Clinically +: 75%
Bilat dz: 30% (especially with BOT / midline lesions)
What is T staging for OPC?
T1: < 2cm
T2: 2-4 cm
T3: > 4cm
T4a: invade larynx deep/ext muscle of tongue, medial pterygoid, hard palate, mandible
T4b: invade lat pterygoid, pterygoid plate, lat nasopharynx, skull invasion, carotid encasement
What are 4 extrinsic tongue muscles and what are their anatomic spans?
1. Geniglossus (ant mandible to tongue)
2. Styloglossus (styloid to tongue)
3. Palatoglossus (palate to tongue; forms ant tonsillatr pillar)
4. Hyoglossus (hyoid bone to tongue)
What is N staging of OPC?
N1: single, IPSI, < 3cm
N2s: single, IPSI, 3-6 cm
N2b: mult, IPSI, < 6 cm
N2c: bilat or contralat, < 6cm
N3: > 6cm
Describe Stage grouping for OPC.
I: T1N0
II: T2N0
III: T3N0, T1-3N1
IVA: T4aN0-1, T1-4N2
IVB: T4b or N3
IVC: M1
What are OPC pts/stage groups that correspond to early, intermediate, and advanced?
Early: I-II (T1-2N0) & select T2N1
Intermediate: HPV+ III-IV (w/o T2N1) in nonsmoker / nondrinker, T3N0 (exophytic) regardless of HPV/smoking status
Advanced: HPV- smokers with III-IV dz, T4 regardless of HPV/smoking status
What is treatment for early (T1-2N0) OPC?
1. surgery >> +/- PORT
2. definitive RT alone
What is tx for intermediate OPC?
1. surgery +/- post-op chemoRT
2. alt fx RT +/- cetuximab
3. ChemoRT (conventional fx)
What is tx for advanced OPC?
ChemoRT +/- induction chemo
Is WLE alone appropriate for OPC?
Rarely. Only if small (< 1cm) ant tonsillar pillar lesion
Is tonsillectomy ever adequate tx for tonsil cancer?
No. Simple tonsillectomy is considered excisional bx and thus further definitive tx would be warranted. Radical tonsillectomy may be adequate in select cases but results in worse functional outcome than RT
When is PORT indicated for OPC?
+ margin
> 2 LN+
+ECE
PNI
LVSI
When can unilat neck tx be considered for OPC?
If well lateralized (at least 1.5cm from midline) & less than N2a
What data supports unilat neck RT for select OPC?
PMH data (O'Sullivan IJROBP 2001)
- 208 pts with tonsil lesions tx with IPSI LN RT
- most pts T1-2N0
- Contralat failure rate low (3.5% overall, 0% T1, 1.5% T2)
- Increasing risk to contralat neck if medial 1/3 of palate &/or BOT involved
What LN regions should be irradiated in pts with early T stage but N+ OPC?
Levels II-IV always included
- recent data (Sanguineti IJROBP 2009) suggests levels I, V can be omitted due to decreased risk of nodal spread
What is main indication for neck dissection after definitive RT?
Persistent nodal dz
- document via FNA, CT (4-6 wks post-RT), or PET/CT (10-12 wks post-RT)
What is recommended timing of neck dissection after chemoRT?
6-8 wks (12-15 weeks if eval by PET/CT)
What is pre-RT eval for OPC?
- dental eval / fluouride ppx
- speech & swallow eval
- nutrition eval
- PEG if pre-tx wt loss > 10% over last 3 months
What is classic superior RT field border for OPC?
N0: 2cm above angle of mandible
N+: above mastoid tip, floor of sphenoid sinus (ant), inf edge of ext auditory meatus (post). Include entier pterygoids if tonsillar / soft palate primary
What are classic inf / post RT field borders for OPC?
Inf: thyroid notch (junction above arytenoids, if possible, & avoid LN splitting if N+)
Post: behind spinous process
What is classic ant field border for OPC?
Should cover medial pterygoid muscle insertion on pterygoid plate, curve just ant to hard palate to the BOS sup, & end 2 cm beyond the tumor or at the 2nd molar inf
What are typical doses for OPC?
Gross dz: 70 (or 81.6 with hyperfx)
Positive margin: 66
Negative margin: 60
Low risk: 54
What is 2 yr LF rate after IMRT alone for early (T1-2N0-1) OPC?
RTOG 0022: accelerated hypofx IMRT
- LRF-2: 9%
- if major deviations 50%, otherwise 6%
What were RT doses employed in RTOG 0022?
Accelerated hypofx IMRT
- Primary PTV: 66 in 30 fx
- Secondary PTV: 54-60 in 30 fx
How was N stage established in RTOG 0022?
- clinical (not from CT)
- pts upstaged from CT also eligible
What did RTOG 90-03 study demonstrate about altered fx?
- n = 1073 (10% oral cavity, 60% oropharynx, 13% hypopharynx); Stage III/IV
- 70 QD vs. 81.6 BID vs. accelerated with split vs. concomittant boost (last 12 fx BID; 1.8 QAM, 1.5 QPM) to 72
- LRC 54 vs. 46% with altered fx
- no OS, DFS benefit
- worse acute toxicity in altered fx group. Late toxicity same
What studies show improved outcome with hyperfx RT over conventional fx?
RTOG 90-03 (Fu, IJROBP 2000)
EORTC 22791 (Horiot, RO 1992)
- 325 oropharynx
- 70 vs. 80.5 (at 1.15 BID)
- better LRC (60 vs. 40%) with hyperfx. LRC best for T3
- No OS benefit
What data showed good LRC with RT alone for select advanced (Stage III/IV) OPC?
MDACC (Garden, Cancer 2004)
- pts with small primaries but Stage III/IV due to +LN
- LF5 (15%), DM (19%), OS (64%)
What are 2 important RCT's that demonstrated the importance of adding chemo to conventionally fractionated RT?
GORTEC 94-01 (1999; n = 222, Stage III/IV)
- RT +/- carbo/5-FU
- OS3 (51 vs. 31%), DFS (30 vs. 15%), LC (66 vs. 42%)

Cleveland Clinic (2003; n = 295, Stage III/IV OC, OPX, HPX)
- RT +/- cis
- OS3 (37 vs 23%), DFS (51 vs. 33%)
What are the indications for adding chemo to PORT in H/N cancer?
+margin
ECE
What 2 RCT demonstrate importance of adding chemo to PORT for patients with +margin, ECE?
EORTC 22931 (2004; n = 334 OC, OPX)
- PORT +/- cis
- OS, DFS, LRC at 5 yrs better in chemo group

RTOG 95-01 (2004; n = 459)
- PORT +/- cis
- DFS2 (54 vs. 43%), LRC2 (82 vs. 72%)
- Trend toward OS benefit (63 vs. 57%; NS)
What study showed OS benefit with addition of Cetuximab to RT in H/N cancer?
Bonner NEJM 2006 (n = 424; OPX, larynx, HPX)
- RT +/- Cetuximab (RT = 70 QD, 72-76.8 BID, CB to 72)
- LRC3 (47 vs. 34%)
- OS2 (55 vs. 45%)
- Improvement mostly in OPX & altered fx
What 2 trials demonstrated benefit with induction taxane/platinum/5-FU (TPF) chemo >> RT or chemoRT in pts with unresectable H/N cancer?
TAX 324 (NEJM 2007; n = 501 III/IV OPX, OC, larynx, HPX)
- platinum + 5-FU or TPF >> chemoRT (carboplatin)
- OS3 (62 vs. 48%), MS (71 vs. 30 mos), LRC (70 vs. 62%) in TPF arm
- fewer tx delays in TPF arm depsite higher heme tox

TAX 323 (NEJM 2007; n = 358 III/IV OPX, OC, HPX, larynx)
- platinum + 5-FU or TPF >> RT
- PFS (11 vs. 8.2 mos), MS (1.8 vs. 14.5 mos)
- more thrombocytopenia, anemia, stomatitis, N/V, diarrhea, hearing loss, deaths in platinum/5-FU group
What are advantages / disadvantages of split-field IMRT (vs. whole-field IMRT) in tx of H/N cancers?
Advantage: potentially better laryngeal sparing
Disadvantage: have to junction RT dose through involved LN
What are advantages / disadvantages of IMRT "dose painting" (vs. sequential plans) in tx of H/N cancer?
Advantage: better conformality in a single plan
Disadvantage: non-standard fractionation used
How do unplanned RT interruptions in H/N cancer affect LRC? Why?
Each week of tx prolongation reduces LRC rate by 10-20% due to accelerated repopulation
What is the best way to compensate for several / few missed RT sessions and avoid tx time prolongation in H/N cancer?
- Tx BID on Fridays or extra fx on Saturday
- Can also dose/fx can be increased

(Beese IJROBP 2007)
What is the approximate long-term PEG dependency rate after chemoRT for OPC?
15-20% (can reduce with swallowing exercises & use of PEG on demand)
What are dose constraints for parotid?
- mean dose to either parotid < 26 Gy
- at least 50% of either parotid < 30 Gy
What is dose constraint for inner ear?
mean dose < 50 Gy
What percent of pts getting cisplatin-based chemo will have hearing loss?
~30%
What is dose constraint for larynx?
V50 < 30%
What were xerostomia rates for pts tx on RTOG 00-22?
55% at 6 months
25% at 1 year
16% at 2 years

- Salivary output did not recover over time
What is rate of osteoradionecrosis with accelerated hypofx IMRT in RTOG 00-22?
6% (higher than expected with IMRT)
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