Flashcards in Chapter 45 Oropharynx Deck (84):
What is the etiology of oropharyngeal cancer in non smoker and non drinker?
What is the prognosis of HPV associated oropharyngeal cancers?
What is the HPV type most common in oropharyngeal cancer?
Infection with HPV 16 confers how many fold increase in risk of oropharyngeal cancer?
Oropharyngeal oncogenesis is primarily mediated by which HPV genome oncoproteins?
E6 and E7 oncoproteins
Name different technique used to detect HPV in oropharyngeal cancer?
1.PCR of HPV DNA High sensitivity but low specificity
2.ISH uses oligonucleotide probe designed to anneal to complementary HPV DNA in tumor specimen.
3.IHC staining for p16INK4A used as surrogate for HPV status
HPV associated oropharyngeal cancer are more likely to occur among men or women?
Name mutations demonstrated by HPV associated oropharyngeal cancer?
Infrequent expression of Cyclin D
Name mutations demonstrated by HPV associated oropharyngeal cancer with more extensive smoking history?
RTOG 0129 HPV associated vs unassociated oropharyngeal cancer what was the conclusion?
3 year OS 82%. 54%
LRP 13.6% 24.8%
PFS 71.8% 50.4%
Describe boundaries of oropharynx
Posteroinferior Larynx and Hypopharynx
Anterior Oral cavity
What are subregions of oropharynx
Base of tongue
Describe tonsillar region
Contains anterior(palatoglossal)and posterior(palatopharyngeal) tonsillar pillar, palatine tonsil
Describe boundary of base of tongue
Anterior circumvallate papillae
Posteroinferior hyoid and epiglottis
Lateral glossopharyngeal sulci
Describe boundary of soft palate
Anterior hard palate
Lateral anterior tonsillar pillar
Posteroinferior forms free edge and midline uvula
Soft palate are composed of which 5 different muscles?
Levator veli palatini
Tensor veli palatini
What are the sensory innervation of base of tongue?
CN IX and X(Internal Laryngeal Nerve)
What are nerve supply of soft palate?
Motor supply all muscles are supplied by CN IX and X except tensor veli palatini supplied by CN V2
Sensory supply CN IX
What are the functions of oropharynx?
What are the primary route of spread of oropharyngeal cancer?
Direct extension and lymphatic spread
What is the most common location of lymph node metastasis in oropharyngeal cancer?
What are high risk nodal metastasis in oropharyngeal cancer?
Level II, III, IV
What are the indications of Level I and V nodes involvement in oropharyngeal cancer?
When other levels are involved
What are the indications of bilateral node involvement in oropharyngeal cancer?
When tumor encroaches or crosses midline or involve posterior pharyngeal wall
What is the craniocaudal extension of RetroPharyngeal(RP) lymph nodes?
Base of skull to Cranial edge of body of hyoid bone
What is the most common location of distant metastatic spread of oropharyngeal cancer?
Lung followed by
Bone and Liver
What factors are responsible for distant metastatic spread of oropharyngeal cancer?
Locoregionally advanced or recurrent tumor
Primary tumor stage
Lower cervical lymphadenopathy(level IV)
How to differentiate pulmonary metastasis and primary pulmonary malignancy radiographically?
Pulmonary mets : well circumscribed peripherally located nodules
Primary pulmonary malignancy : spiculated irregularly shaped mass commonly associated with hilar and mediastinal lymphadenopathy
What should be the treatment approach when it is difficult to distinguish between primary and metastatic lesion in oropharyngeal cancer?
Physically fit patient should be given benefit of doubt and treated as if they are seperate primary tumors.
What is the treatment approach for physically fit patient with known oropharyngeal cancer with pulmonary mets?
Resection of pulmonary metastasis may improve survival
What is the treatment approach for nonsurgical patient with known oropharyngeal cancer with limited pulmonary mets?
Hypofractionated IGRT to all known metastatic sites
What is the cause of deep seated otalgia located within auditory canal in oropharyngeal cancer?
Pain mediated by irritation of CN IX with referral via petrosal ganglion to tympanic nerve of Jacobson
What is the sensitivity and specificity of PET scan in oropharyngeal cancer?
High sensitivity of 100%
Specificity 60%for pathologically proven tumor
What is the best imaging modality used in determination of extent of base of tongue or oral tongue invasion is needed?
What is the most common histologic subtype in 95% oropharyngeal cancers?
What T-stage in oropharyngeal cancer when medial pterygoid is involved?
What T-stage in oropharyngeal cancer when lateral pterygoid is involved?
What stage is T1N1M0 in oropharyngeal cancer?
RTOG 7303 what percentage of LRC was seen in postoperative RT in compared to preoperative in oropharyngeal cancer?
79% LRC postoperative
58% LRC preoperative
Based on available data, what is the standard chemotherapy used concurrently with adjuvant radiotherapy in oropharyngeal cancer?
Cisplatin 100mg/m2 every 3 weeks
What is recommended adjuvant RT dose in oropharyngeal cancer?
60-66Gy in 2Gy/Fx High risk area(primary tumor bed with positive margin or nodal regions with extra capsular spread)
50-54Gy areas of risk for microscopic involvement
Oropharyngeal cancer treated with RT alone, what should be the fractionation scheme?
EORTC 22791 Non base of tongue oropharyngeal cancer, what was the outcome when compared with conventionally fractionated(70Gy/2Gy)and hyper fractionated(80.5Gy/1.15Gy twice daily) RT?
Hyperfractionated RT was associated with statistically significant improvement in LRC(5 year, 59% vs 40%) and improved overall survival in stage III
Meta-analysis studies in oropharyngeal cancer what was the outcome of hyperfractionation over accelerated fractionation RT in OS?
Hyperfractionated RT has absolute 8.2% improvement in OS at 5 years compared to 2% in accelerated fractionation RT.
What are classic etiologic factors of oropharyngeal cancers?
RTOG 90-03 compared conventional fractionation with altered fractionation in oropharyngeal cancer. Which scheme resulted in trend towards improved disease free survival?
Hyperfractionation(81.6Gy in 1.2Gy twice daily) 37.6% vs 31.7%
Accelerated concomitant boost(72Gy in 1.8Gy for 14 fractions followed by 1.8Gy morning and 1.5Gy afternoon boost to gross disease) 39.3% vs 31.7%
RTOG 00-22 in oropharyngeal cancer, what was the stage used and outcome?
Early stage (T1-2, N0-2)
2 year risk of local progression 9%
2 year OS 95%
2 year DFS 82%
Name 2 studies that favors concurrent chemoradiation in oropharyngeal cancer?
1.MACH-NC(Meta-Analysis do Chemotherapy in Head-Neck Cancer)
MACH-NC study demonstrated what percentage of absolute improvement in 5 year OS from use of concurrent ChemoRT compared to RT alone in oropharyngeal cancer?
GORTEC study for oropharyngeal cancer used what chemotherapy regimen concurrently with RT?
Daily bolus carboplatin
Continuous infusion 5-FU 600mg/m2/day on day 1 through 4 every 3 weeks for 3 cycles
GORTEC study in oropharyngeal cancer, what was the outcome in 5 year OS and LRC?
5 year OS 15.8% RT alone vs 22.4% ChemoRT
5 year LRC 24.7% RT alone vs 47.6% ChemoRT
What is the most difficult acute complication of ChemoRT for Oropharyngeal cancer?
What should be done as a part of intervention in management of dysphagia as acute complication of ChemoRT in oropharyngeal cancer?
1.Depending on nutritional status, swallowing exercise designed to strengthen pharyngeal musculature
2.Specific dosimeteric threshold to pharyngeal constrictor or laryngeal apparatus should be incorporated in RT planning
What are the late toxicities of ChemoRT in oropharyngeal cancer?
Feeding tube dependence
Who are the candidates more likely to experience late toxicities with ChemoRT in oropharyngeal cancer?
Larger T3-4 tumors
Post treatment neck dissection
What is the standard of chemotherapy in oropharyngeal cancer?
Cisplatin at 100mg/m2 every 3 weeks for 2-3 cycles
GORTEC randomized study what alternative chemotherapy was chosen to Cisplatin to avoid its complications like tinnitus, renal dysfunction, emesis in oropharyngeal cancer?
Use of neoadjuvant chemotherapy followed by surgery vs RT alone. Phase III randomized trial, at median follow up of 5 years, what was the outcome?
Statistically significant improvement in OS at 5 years in favor of induction chemotherapy was 5.1 years vs 3.3 years
Induction chemotherapy is advocated by some followed by ChemoRT vs ChemoRT alone. Which patients will benefit from such regimen?
Patients with increased risk of distant metastasis
Single arm Phase II trial to support the role
Who are indicated with targeted agent(cetuximab) and RT?
KPS score >60
Normal hematopoietic, hepatic, renal function
What is the outcome of targeted therapy(cetuximab) and RT vs RT alone?
Improved 2 years locoregional control 50% vs 41%
Median locoregional disease free survival 49 months vs 23 months
Median OS >66 months vs 30.3 months
What targeted therapy can be used instead of cetuximab for its severe anaphylactic reaction?
Cytotoxic drugs + RT with / without targeted therapy(cetuximab) in oropharyngeal cancer. What was the outcome?
No improvement in outcome
Increased mucositis, skin reaction and dysphagia
No difference in outcome with difference in HPV status
Bevacizumab + Erlotinib and Cisplatin + RT(1.25Gy twice daily, 70Gy) in head and neck cancer including Oropharyngeal cancer. What is the outcome?
3 years locoregional control and OS 86% and 85% respectively
Fully humanized monoclonal antibody to EGFR
Synchronous dual inhibition of VEGF and EGFR
What are the indication of RetroPharyngeal coverage in oropharyngeal cancer?
Tumor extending to Nasopahrynx or pterygoid region
Gross RetroPharyngeal nodal involvement
High level II lymphadenopathy
Consensus guidelines for contouring endorsed by International Head and Neck Cancer groups including RTOG, EORTC, DAHANCA, GORTEC, NCIC for node positive head and neck cancer including oropharyngeal cancer
1.Coverage of supraclavicular fossa for patient with level IV or Vb lymphadenopathy and inclusion of entire thickness of muscles invaded by pathologic lymphadenopathy in the CTV.
2.Coverage of retrostyloid space for all patients with pathologic level II lymphadenopathy
3.Pathologic lymphadenopathy spanning adjacent levels should trigger inclusion of full extent of both levels in CTV.
4.Nondissected node positive patient, inclusion of muscles invaded by tumor.
Describe RTOG guidelines for radiotherapy volume in oropharyngeal cancer
GTV to high risk CTV margin 0.5-1 cm
CTV to PTV
0.5-1cm if standard weekly megavoltage port films guidance used
0.25-0.5cm if frequent kV image or cone-beam CT guidance used
What is the indication of ipsilateral RT in tonsillar cancer?
Well lateralized tonsillar cancer case not involving base of tongue
Minimal involvement of soft palate (>1cm margin between medial extent of tumor and midline)
What is the indication of contralateral RT in tonsillar cancer?
Extensive involvement of ipsilateral cervical lymph node
Tumor approaching or crossing midline(base of tongue, soft palate)
What percentage of early stage tonsillar cancer(T1-2, N0-1) would progress to contralateral neck?
Mean tolerance dose to parotid gland and submandibular gland
What is the volume of larynx and inferior pharyngeal constrictor associated with PEG tube insertion?
Inferior Pharyngeal wall V40-V65
What is the volume of pharynx and inferior pharyngeal constrictor associated with aspiration?
Inferior pharyngeal constrictor V60-V65
What is the mean dose to pharynx and inferior pharyngeal constrictor whose PEG tubed removed by 12 months?
Mean dose of 50Gy
What are the two randomized trials that showed no benefit to accelerated RT over conventionally fractionated RT with concurrent platinum based chemotherapy?
What is the ABS recommendation for brachytherapy head and neck including oropharyngeal cancer?
45-60 Gy EBRT followed by
HDR brachytherapy boost 3-4Gy/Fx for 6-10 doses
What is the GEC-ESTRO recommendation for brachytherapy head and neck including oropharyngeal cancer?
45-50Gy EBRT followed by
Tonsillar tumor 25-30Gy boost 3Gy/Fx
Base of tongue 30-35Gy boost 4Gy/Fx
What is the standard therapy for patient with recurrent or metastatic oropharyngeal cancer?
Systemic therapy with platinum based chemotherapy
Phase II studies, what are the single agent activity drugs in oropharyngeal cancer?
EXTREME study randomized recurrent and metastatic head and neck cancer including oropharyngeal cancer to chemotherapy alone vs chemotherapy and cetuximab. What was the outcome?
Median OS improved from 7.4 months to 10.1 months
Median progression-free survival 3.3 months to 5.6 months
Reirradiation for locally confined recurrent or second primary oropharyngeal cancer, what percentage of long term survival is shown with second course full dose RT with chemotherapy?