Oropharynx Flashcards
Tobacco use and alcohol use are “both” considered as etiologic factors for oropharyngeal carcinoma.
TRUE or FALSE?
True.
They are considered the classic etiologic factors for Oropharyngeal Cancer.
What virus is associated with the development of oropharyngeal carcinoma?
HPV (Human Papillomavirus)
HPV-associated oropharyngeal cancers have a significantly worse prognosis compared to non-HPV-associated cancers.
TRUE or FALSE?
False.
HPV-associated cancers have a significantly more favorable prognosis that is platform dependent.
A reanalysis of RTOG 0129, a randomized study comparing cisplatin administered with either accelerated concomitant boost RT or conventionally fractionated RT, HPV status was independently associated with improved outcomes.
Epidemiology:
What percent of the annual, worldwide incidence of H&N SCC is comprised of oropharyngeal cancers?
Approximately 10%.
Incidence of oropharyngeal cancer is higher (and increasing) for developed countries than in developing countries.
TRUE or FALSE?
TRUE.
The putative cause of this is the increasing incidence of HPV-associated cancers.
Describe HPV’s morphology.
The HPV is a circular, double-stranded DNA virus.
What “is” the most common HPV type identified in human tumors and is associated with >90% of all HPV-associated related oropharyngeal cancers?
Infection with this type confers an approximate 14-fold increase in the risk of oropharyngeal cancer.
HPV 16
What are the three oncoproteins that the HPV genome encodes?
Which of them primarily mediate/s oncogenesis?
E5,6,7; E6 and 7
The HPV genome encodes three oncoproteins (E5, E6, and E7).
Oncogenesis is primarily mediated via the E6 and E7 proteins.
E7 is believed to be the major transforming oncogene during early carcinogenesis, with E6 functioning later.
What gender is predominantly affected by oropharyngeal cancers?
Male. With a M:F ratio of 4:1.
for HPV associated, it’s 3:1
What is the gold standard technique to detect HPV in oropharyngeal biopsy specimens?
demonstration of HPV E6/E7.
The gold standard is demonstration of HPV E6/E7 in clinical specimens. However, this approach is clinically impractical because it is very difficult to detect viral RNA from cytologic fluid and paraffin-embedded tissues.
Oropharyngeal cancer is usually detected in patients who are on their __to__ decades of life, and __to__ years younger for HPV-associated type.
Fifth and sixth decade.
5 to 10 years younger.
Describe the common histopathologic description of HPV-associated oropharyngeal cancers.
poorly-differentiated, nonkeratinizing or basaloid.
in contrast to NPC where HPV is more commonly associated with keratinizing histology
Which is “NOT” commonly associated with wild-type p53, p16 amplification and infrequent amplification of cyclin D?
Choices:
HPV-associated vs. HPV-unassociated
HPV-unassociated
What are the anatomic boundaries of the oropharynx?
anterior - oral cavity
posterior/inferior - larynx and hypopharynx
superior - nasopharynx
What are the three anatomic subregions of the oropharynx?
tonsil, base of tongue, and soft palate
Describe the mucosal lining of the palatine tonsil.
keratinized stratified squamous epithelial mucosal lining.
What are the borders of the base of tongue?
Anterior: circumvallate papillae
Posterior-inferior: hyoid and epiglottis
Lateral: glossopharyngeal sulci
What separates the base of tongue and the epiglottis which is a 1 cm mucosal strip that is considered part of the base of tongue?
Vallecula
What are the sensory innervation of the base of tongue?
Glossopharyngeal (CN IX)
and in part by the internal laryngeal nerve (CN X).
Anatomic boundaries of Neck Node Levels:
Level I
Bounded by posterior belly of digastric, hyoid bone inferiorly, and body of mandible superiorly
Anatomic boundaries of Neck Node Levels:
Level II
Bounded by skull base superiorly to level of hyoid bone inferiorly
Anatomic boundaries of Neck Node Levels:
Level III
Bounded by hyoid bone superiorly to cricothyroid membrane inferiorly
Anatomic boundaries of Neck Node Levels:
Level IV
Bounded by cricothyroid membrane superiorly to clavicle inferiorly
Anatomic boundaries of Neck Node Levels:
Level V
Bounded by anterior border of trapezius posteriorly, posterior border of SCM anteriorly, and clavicle inferiorly
Anatomic boundaries of Neck Node Levels:
Level VI
Bounded by level of hyoid bone superiorly to suprasternal notch inferiorly, lateral border formed by medial border of carotid sheath
Radiographic boundaries of Neck Node Levels:
(anterior, posterior, lateral, medial, cranial, caudal)
from level Ia to VI)
will add table later.
At what level are lymph node metastases from oropharyngeal cancers most commonly located?
“ipsilateral” level II
Distant metastatic spread of oropharyngeal cancer is relatively uncommon.
TRUE or FALSE?
True.
affecting only approx. 15% of all patients during the course of the disease.
What is the most common location of distant metastases in oropharyngeal cancers?
Lung parenchyma»_space; bone > liver
The risk of distant metastases is not affected by tumor stage and is more dependent on the extent of cervical lymphadenopathy.
TRUE or FALSE?
False.
It increase with T stage and cervical lymphadenopathy (N2-3)
Extranodal extension, lower cervical pathologic lymphadenopathy (level IV), and LVSI have also been associated with increased risk of distant metastases.
Skip cervical metastases are common in oropharyngeal cancers.
TRUE or FALSE?
False.
It is rare and is observed in usually 0.3 percent.
Oropharyngeal cancers present with painless neck mass which is usually mobile, firm, and nontender.
What does it usually indicate if this mass is fixed?
Extranodal extension or invasion into surrounding structures.
Why do trismus and regurgitation occur?
trismus - invasion of the pterygoids
regurgitation - invasion of the soft palate, inhibiting its ability to elevate during swallowing.
Synchronous second primaries are common in oropharyngeal cancers.
TRUE or FALSE?
True.
Especially in smokers.
Differentiate primary lung malignancy from lung metastases, given that synchronous primary malignancies are common.
Mets are usually well circumscribed and in the periphery.
Primary lung malignancies are more common in the hilar area and are usually spiculated.
Describe a pathologically involved node in CT.
enlarged
have lost a fatty hilum
enhance with contrast
and/or have a necrotic center.
PET and/or PET/CT imaging now “routinely” recommended for the “initial” staging of oropharyngeal cancer patients.
TRUE or FALSE
True.
The ability of this imaging modality to differentiate tumor from soft tissues is particularly useful when determination
of the extent of base of tongue or oral tongue invasion is needed.
What is this imaging modality?
MRI.
What is the most common histology of oropharyngeal cancer?
Squamous cell carcinoma
AJCC/IUCC 8th edition TNM
What is T0?
No primary identified
AJCC/IUCC 8th edition TNM
What is T1?
Tumor 2 cm or smaller in greatest dimension
AJCC/IUCC 8th edition TNM
What is T2?
Tumor larger than 2 cm but not larger than 4 cm in greatest dimension
AJCC/IUCC 8th edition TNM
What is T3?
Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis
AJCC/IUCC 8th edition TNM
What is T4?
Moderately advanced local disease; tumor invades the larynx, extrinsic muscle of tongue,
medial pterygoid, hard palate, or mandible or beyond
AJCC/IUCC 8th edition TNM for HPV-mediated oropharyngeal cancer (2017)
What is NX and c/pN0?
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
AJCC/IUCC 8th edition TNM for HPV-mediated oropharyngeal cancer (2017)
What is cN1?
One or more ipsilateral lymph nodes, none larger than 6 cm
AJCC/IUCC 8th edition TNM for HPV-mediated oropharyngeal cancer (2017)
What is cN2?
Contralateral or bilateral lymph nodes, none larger than 6 cm
AJCC/IUCC 8th edition TNM for HPV-mediated oropharyngeal cancer (2017)
What is cN3?
Lymph node(s) larger than 6 cm
AJCC/IUCC 8th edition TNM for HPV-mediated oropharyngeal cancer (2017)
What is pN1?
Metastasis in 4 or fewer lymph nodes
AJCC/IUCC 8th edition TNM for HPV-mediated oropharyngeal cancer (2017)
What is pN2?
Metastasis in more than 4 lymph nodes
AJCC/IUCC 8th edition CLINICAL STAGING for HPV-mediated oropharyngeal cancer (2017)
Stage I?
T1N0
T2N0
T0N1
T1N1
T2N1
All T2 and that is N1 and below
T0-2, N0-1
AJCC/IUCC 8th edition CLINICAL STAGING for HPV-mediated oropharyngeal cancer (2017)
Stage II?
T0N2
T1 N2
T2 N2
T3N0
T3N1
N3N2
All T3 and below that is N2 and below and is not Stage I
T0-2, N2 or T3 N0-2
AJCC/IUCC 8th edition CLINICAL STAGING for HPV-mediated oropharyngeal cancer (2017)
Stage III?
T0N3 T1N3 T2N3 T3N3 T4N3
T4N0
T4N1
T4N2
All T4 and below that is N3 and below that is not stage II
T1-3 N3, or T4 N0-3
AJCC/IUCC 8th edition CLINICAL STAGING for HPV-mediated oropharyngeal cancer (2017)
Stage IV
M1
What are the differences in AJCC/IUCC 8th edition CLINICAL STAGING for HPV-mediated oropharyngeal cancer (2017) vs. PATHOLOGIC staging?
T3N2 is Stage III already,
T4N1 is just stage II.
Describe the AJCC/IUCC 8th edition staging for p16(-) oropharyngeal cancer.
What is T4b?
Very advanced local disease
Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull
base or encases carotid artery
Describe the AJCC/IUCC 8th edition staging for p16(-) oropharyngeal cancer.
What is N1, N2a, N2b, N2c N3a, N3b?
(clinical and pathologic)
Clinical Regional Lymph Nodes (cN)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and
ENE(−)
N2 Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in
greatest dimension and ENE(−);
or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(−);
or in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension
and ENE(−)
N2a Metastasis in a single ipsilateral node larger than 3 cm but not larger than 6 cm in
greatest dimension and ENE(−)
N2b Metastasis in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and
ENE(−)
N2c Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(−)
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−);
or metastasis in any node(s) and clinically overt ENE(+)
N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−)
N3b Metastasis in any node(s) and clinically overt ENE(+)
Pathologic Regional Lymph Nodes (pN)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and
ENE(−)
N2 Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and
ENE(+);
or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(−);
or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(−); or in bilateral or contralateral lymph nodes, none larger than 6
cm in greatest dimension and ENE(−)
N2a Metastasis in single ipsilateral or contralateral node 3 cm or smaller in greatest dimension
and ENE(+);
or a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest
dimension and ENE(−)
N2b Metastasis in multiple ipsilateral nodes, none larger than 6 cm in greatest dimension and
ENE(−)
N2c Metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest
dimension and ENE(−)
N3 Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−);
or in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+);
or multiple ipsilateral, contralateral or bilateral nodes, any with ENE(+)
N3a Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(−)
N3b Metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+)
or multiple ipsilateral, contralateral, or bilateral nodes, any with ENE(+)
AJCC/IUCC 8th edition CLINICAL STAGING for HPV-mediated oropharyngeal cancer (2017)
Stage I, II, III, IVB, IVA, IVB, IVC?
All N0 disease corresponds to their respective T stage
(i.e T2 = St II)
All T1-T3 N1 - stage III
All T1-T3 N2 - stage IVA
All T1-T4B N3 - stage IVB
All M1 - stage IVC
Enumerate and describe the traditional surgical approaches for base of tongue tumors (3)
Traditional surgical approaches for base of tongue tumors include the midline
mandibulotomy (splitting the lip, mandible, and oral tongue midline), the lateral
mandibulotomy (dividing the mandible near the angle and approaching the base
of tongue from the side), and the floor drop procedure (elevating the inner
periosteum from the mandible from angle to angle, which releases the entire
floor of mouth and oral tongue into the neck exposing the base of tongue).
What pathologic features following surgical resection place patients at high risk for locoregional recurrence, in which case PORT can reduce the risk of relapse?
advanced primary T stage (3 or 4) positive margins LVSI PNI multiple pathologically involved cervical lymph nodes and ENE
Which of the following is considered to be the standard chemotherapy agent given as concurrent chemotherapy to PORT?
a. docetaxel
b. cetuximab
c. carboplatin
d. cisplatin
D. Cisplatin 100mg/m2 every 3 weeks.
-eortc and rtog trials
No prospective studies for the use of cetuximab or docetaxel yet. there are ongoing phase 3 trials.
carboplatin study had closed prior to accrual goals.
PORT dose for primary tumor bed with positive margins or nodal regions with extracapsular spread
60 to 66 Gy / 2 Gy daily fractions
PORT dose for areas at risk for microscopic involvement
50 to 54 Gy /2 Gy fractions
Accelerated RT
66 to 70 Gy delivered in
2 Gy daily fractions 6 days a week has been shown to benefit oropharyngeal cancer.
TRUE or FALSE
a randomized study comparing an accelerated regimen of 66 to 70 Gy delivered in
2 Gy daily fractions 6 days a week to the same dose delivered 5 days a week
with oropharyngeal cancer affecting the majority of patients demonstrated
improved locoregional control (42% vs. 30%, P = .004),
disease-free survival
(50% vs. 40%, P = .03),
and a trend toward improved overall survival (35% vs.
28%, P = .07).
Accelerated RT
1.8 Gy BID to 59.4 Gy has been shown to benefit oropharyngeal cancer.
TRUE or FALSE
False.
No statistical benefit in LRC or OS.
What is the significance of EORTC 22791 to oropharyngeal cancer treatment?
EORTC demonstrated significant improvements in LRC (5-year, 59% vs.
40%) without an increase in long-term toxicity for T2-3, N0-1 non base of tongue oropharyngeal cancers, with the use of HYPERFFRACTIONATED RT (80.5Gy/1.15 Gy bid)
vs. conventionally fractionated 70/35.
Additionally, there was a trend
toward improved overall survival (P = .08) particularly in stage 3 patients
What study compared conventional fractionation to hyperfractionation (HFX) (81.6 Gy [1.2 Gy BID]),
accelerated fractionation (AFX)(67.2 Gy [1.6 BID with a 2-week rest after 38.4 Gy]),
and accelerated fractionation
with concomitant boost regimen (72 Gy in 1.8 Gy fractions for 14 fractions
followed by 1.8 Gy morning and a 1.5 Gy afternoon boost to gross disease)?
RTOG 90-03
Which of the 4 arms of RTOG 90-03 showed less late toxicities?
HFX arm
Specifically in diseasefree
patients, at 5 years, only 4.8% of HFX patients had feeding tubes versus
13.0% of AFX-C patients.
Which of the 4 arms of RTOG 90-03 showed improvement in LRC with trends to improved DFS in the initial report?
HFX arm (37.6% vs. 31.7%, P = .067) and AFX-C arm (39.3% vs. 31.7%, P = .054)
Which arm of RTOG 90-03 showed improvement in survival at 5 years?
HFX arm
HR 0.81, P = .05
What study investigated the use of Simultaneous Integrated Boost (SIB) for early-stage oropharyngeal cancers?
RTOG 0022
What are the doses used for SIB (in RTOG 0022)?
2.2 GTV
2 for intermediate-risk PTV
1.8 for low-risk PTV
(in Gy)
What is the standard treatment for locoregionally advanced oropharyngeal cancer?
CCRT
What study supports the use of concurrent chemoRT in H&N cancers which showed a 6.2% absolute improvement in 5year OS for H&N ca in general.
subgroup of stages 3 to 4 (non metastatic) oropharyngeal cancer showed improvement in 5-year OS (HR 0.78 [95% CI = 0.72 to 0.85), P < .0001.
MACH-NC
meta-analysis of head and neck cancer.
What group investigated chemoRT in stage 3/4 oropharyngeal cancer and showed level 1 evidence of improved 5-year LRC for chemoRT vs. RT alone (22.4% vs. 15.8%)?
GORTEC
Groupe d’Oncologie Radiothérapie
Tête et Cou (GORTEC)
What is the chemotherapy regimen in the GORTEC study that investigated chemoRT vs RT alone for stage 3/4 oropharyngeal cancer?
daily bolus carboplatin and continuous
infusion 5-fluorouracil 600 mg/m2/d 5-day 1 to 4 every 3 weeks for three cycles.
What acute complication of CRT often impacts the patients’ QOL the most and is associated with poor nutritional status post treatment?
Dysphagia
Is there a proven role for neoadjuvant chemotherapy for oropharyngeal cancer patients set to undergo conventional RT/ composite surgery+PORT?
If yes, what is the advantage?
Yes. it improves 5-year OS.
Domenge C, Hill C, Lefebvre JL, et al. Randomized trial of neoadjuvant
chemotherapy in oropharyngeal carcinoma. French Groupe d’Etude des
Tumeurs de la Tete et du Cou (GETTEC). Br J Cancer 2000;83:1594–1598.
Major adverse reaction to cetuximab due to the response to galactose-alpha-1,3, galactose oligosaccharide on the Fab portion of cetuximab heavy chain?
severe anapahylactic reaction
RTOG 0522
studied AFX-C+cisplatin+cetuximab for oropharyngeal cancer (70% of patients).
no improvement in LRC, DFS, and OS, + increased grade 3-4 mucositis and skin reactions.
What is the margin from the GTV to form the high-dose CTV (RTOG)?
0.5 to 1 cm
When do you include RPN in the treatment volume?
3
gross RPN involvement,
extension to the NP and pterygoid region,
high level II lymphadenopathy
When do you include the SCF in the treatment volume?
level IV or Vb involvement
When do you consider ipsilateral neck RT for tonsillar cancers due to their low risk of contralateral progression?
well-lateralized (>1 cm from midline),
no involvement of soft palate or base of tongue,
preferably T1 or T2 only
Describe the wedge pair technique used for ipsilateral RT planning.
The wedge pair technique includes
ipsilateral anterior and posterior oblique fields with the head hyperextended to
move the orbits out of the treatment field. Adequate sparing of normal tissue
with this technique is achieved as the anterior beam spares the oral cavity and
the contralateral parotid gland, although usually contributes dose to the spinal
cord. The posterior field aperture also spares the contralateral parotid, although it
contributes dose to the spinal cord and oral cavity. With the wedge pair
technique, hot spots are typically located peripherally near the surface and are
between 110% and 115%. These hot spots can be reduced or eliminated if
necessary with the addition of a lightly weighted (10%) third, lateral field. The
contralateral parotid dose is usually negligible at 0% to 10%.
In the study comparing IMRT and conventional RT xerostomia (PARSPORT);
it was shown that IMRT patients had increased salivary flow post IMRT.
What is the OS benefit of IMRT vs conventional in this study?
Similar (IMRT78%, conv76%)
Nutting CM, Morden JP, Harrington KJ, et al. Parotid-sparing intensity
modulated versus conventional radiotherapy in head and neck cancer
(PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet
Oncol 2011;12:127–136.
What drug/s can be used to reduce xerostomia?
Pilocarpine and amifostine
Is there an OS benefit to AFX+chemotherapy compared to AFX alone?
(for GORTEC 99-02 and RTOG 0129)
Outcomes were similar.
There was no benefit to accelerated CRT compared to conventional CRT.
What is the recommended dose for HDR brachytherapy following EBRT?
ABS guidelines: 3 to 4 Gy/fx x 6-10 fx
after 45 to 60 Gy EBRT
GEC-ESTRO guidlines:
For oropharyngeal tumors, these guidelines recommend 45 to 50 Gy EBRT followed by 25 to 30 Gy boost for tonsillar tumors and 30 to 35 Gy boost to base of tongue tumors.
The total brachytherapy boost dose is fraction size dependent; 21 to 30 Gy/3Gy and 16 to 24 Gy/4Gy.
There are a few studies that investigated treatment deintensification for HPV+ oropharyngeal cancer patients.
- altered fractionation without chemo
- ECOG 1308
- shrinking/eliminating elective neck node RT
- reduced dose RT in chemoRT.
Describe ECOG 1308.
ECOG 1308 was a single-arm study basing postinduction chemotherapy
radiotherapy dose on response to induction chemotherapy. Those with a
complete response to cisplatin, docetaxel, and cetuximab induction
chemotherapy received 54 Gy with cetuximab, and those with a partial response
received 69.3 Gy with cetuximab. In those patients treated with reduced dose RT,
2-year locoregional control was 94%, and 2-year overall survival was 93%.
What are the recommended follow-up schedules after definitive treatment?
Current guidelines suggest examination every 1 to 3 months for the first-year post therapy, every 2-4 months in the second year, and every 4-6 months years 3 to 5.
Describe a radiologic complete response on CT imaging of the neck.
non-enhancing, non necrotic nodal tissue <1.5 cm.
(It is associated with 100% long-term disease control in the neck, and no further therapy is needed).
What can be used as the sole imaging modality post RT performed after 12 weeks?
PET/CT
With residual CT abnormalities in the neck, a negative PET scan at 12 weeks, defined as the
absence of metabolic activity, warrants further pathologic confirmation.
TRUE or FALSE?
FALSE.
With or without residual CT abnormalities in the neck, a negative PET scan at 12 weeks, defined as the
absence of metabolic activity, was associated with no isolated nodal
progression
