This document presents a case of oropharyngeal cancer and outlines its investigation, staging, management, and follow up. Investigations included imaging of the head and neck as well as biopsy of the primary tumor and lymph nodes. Staging involved assessing the extent of the primary tumor and evaluating for metastases. Management involved a multidisciplinary approach, with the main options being surgery followed by adjuvant radiation/chemoradiation or definitive chemoradiation. Follow up after curative treatment involved regular exams to monitor for recurrence. Key considerations in management included organ preservation and minimizing treatment-related toxicities such as dysphagia.

1. Case presentation on
Oropharyngeal cancers
By:Gebrekirstos H,COR-II
Moderator:Dr Edom S,Oncologist
AAU-CHS
July 30,2019

2. Outlines of presentation
• Case
• Investigations
• Staging
• Managements
• Complications of Rx
• Follow up
• Case critics
• References

3. Investigations of oropharyngeal ca
• Hx &PE-Hx of smoking, alcohol,other H & N ca ,
• CBC
• OFT
• HPV –test(p16 IHC,ISH)
• pan endoscopy (Risk of synchronous ca-,1-10%---field cancerization)
• H &N CT scan(with contrast)-to asses primary tumor
• H& N MRI- Differentiate tumor from soft tissues
- particularly useful in determine extent of base of tongue/oral tongue
invasion
-In pts with compromised RFT
• Chest CT-for >N2,locally advanced disease(T3,T4),low cervical LN,recurrent disease
• PET/CT - incorporate tumor physiology & anatomic information
used to detect primary with cervical secondry(level II&III), synchronous 2nd
primary, antitypical met out side met patterns
• Confirmatory primary biopsy &LN FNAC
• Dental & audiometric evaluation

6. Managements
• B/c of key role in speech, swallowing, and
breathing, oropharyngeal ca represents a Dx &
Rx challenging & requires individualized,
multidisciplinary approach for management.
• Goals of Rx:
- Eradicating the disease
-Preserving function
-Functionally rehabilitating(if needed)

7. Managements
• Pts with poor nutritional condition may need feeding tube(NGT
/PEG) before initiating Rx, particularly if CCRT is used.
• Prophylactic feeding tube not advice for anticipation of RT related
local toxicity in pts without significant baseline dysphagia/weight
loss----reactive strategy is preferred .
• Before any Rx,pts should be guided toward alcohol/smoking
cessation programs(has better Rx tolerate & outcome).
• Before any Rx dental evaluation should be done ,b/c pts are at
↑risk for dental caries,due to:
-Xerostomia
-↓PH
-Bacterial proliferations

8. pathologists
radiologists
H& N
surgeons
plastic
surgeons
medical
oncologists
radiation
oncologists
dentists
nurses
speech &
swallowing
therapists

9. Principles of Rx
• Surgery –traditional
-Tran-oral
• Radiotherapy -Adjuvant
-Definitive
-Palliative
-BT
• Chemotherapy -induction
-CCRT
-Adjuvant
-palatine
• Targeted -cetuximab

10. Management
• OPSCC for management purpose are
classified in to:
-Early (stage I& II)
-Locally advanced (III-IVB)
-Metastasis(IVC,M1)

11. Principle of management –Early stage
• Are well controlled with single modality local therapy (Sx or RT,
both equal survival out come but Sx less functional out come.)
• Selection of local modality is based on the :
-Size
-Extent of local spread
-Sub site involved
-Rx skill of the center
• Small tonsilar ca preferably treated
• Exophytic tongue ca with Sx
-Soft palate
-Endophytic tongue ca RT is prefered
-Infiltrative tongue ca –RT
-Pharyngeal wall

12. Principle of Rx –LA OPSCC
• Two appropriate treatment strategy is used:
-Surgery followed by adjuvant Rx( RT±CT)
-CCRT
For metastasis -palliative CT± palliative RT

13. Surgical approaches
• Traditional
-Midline mandibulotomy
-Lateral mandibulotomy
-Transhyoid
• Transoral surgery
-TORS-transoral robotic Sx
-TMS-trans oral laser micro Sx

14. Surgical Rx –Base of Tongue
• Has limited role as base of tongue are midline
tumor & also need near total/total glossectomy
w/c has high morbidity.
• But, for well lateralized/polypoid tumors with
minimal LAP partial glossectomy can be done.
• Due to high occult micro nodal met bilateral
cervical LND should be done.
• For tumors arising near the laryngeal apparatus
like vallecula,supraglotic/total laryngectomy
should be done for adequate margin.

15. Surgical Rx-tonsil
• For small(<1cm) wide local excision
• Tumors involving palatine tonsil need radical
tonsillectomy.
• In this cases tonsil is approached transorally,
with primary closure.

16. Sx Vs RT early OPSCC
• Results for tonsillar ca shows similar oncologic
outcomes between primary Sx & RT:
Sx vs RT
LC 70% 68%
LRC 65% 69%
5-year OS 47% 43%)
5-year CSS 57% 59%
(cause-specific survival)
But risk of complication were higher in Sx groups:
-severe complications 23% vs 6%
-fatal complications 3.2% vs 0.8%)

17. Surgical Rx –soft palate
• Surgery rarely indicated as initial Rx b/c:
-Associated with velopharyngeal incompetence w/c
is important both for swallowing & speech.
-Lymphatic drainage is bilaterally neck&
retropharyngeal LN w/c require elective
treatments(but RP LN not accessible for LND).
• But when surgery is performed, transoral
approached is used.
• Flaps/prostheses are used to preserve
velopharyngeal competence.

18. Contra-indications for Sx
• cT4b-technically unresectable
• Tumor extension to skull base
• Extension to superior & lateral nasopharynx
• Encasement/invasion of CCA/ICA
• Direct extension of neck disease to skin
• Extension to mediastinal structures,
prevertebral fascia, cervical vertebrae
• M1 disease

19. Principles of RT
• Adjuvant
• Definitive
• Palliative

20. Adjuvant RT
• Pts initially Rx with surgery w/c are at high risk for local
recurrence should receive PORT ± concurrent
CT(platinum-based) with in 6 wks of Sx for:
-Advanced primary T stage (T3 ,T4)
-LVI
-PNI
-Positive margin
-Multiple pathologically + cervical LN
-ECE(Extra capsular extension)
-Level IV& V LN involvement.

21. Adjuvant ---RT vs CCRT
• Addition of CT to PORT improve local control,
PFS,OS , but increase toxicity.
Stage III & IV H &N
SCC, post curative Sx
167 pts to
RT(66Gy in
6.5wks)
167 pts to same RTdose
+CT(Cis 100mg/m2)
Q3wksMedian FU
60 months
n engl j med350;19www.nejm.org may6, 2004

22. Characteristics RT only CCRT P values
5 yrs PFS 36 47 0.04
5 yrs OS 40 53
5yrs
Local/regional
Relapse
31 18 0.007
G-3/4 toxicity 21 41 0.001

23. Definitive RT
• For early stage OPSCC single modality RT has
good out come & functional preservation.
• No consensus on optimal dose fraction
schedule on single modality RT.
• But randomized data & meta-analyses support
OS benefit with the use of accelerated
fractionation or hyper fractionated RT

24. Conventional vs altered ≠ RT
• Meta analysis
• Methods –randomized trial compared conventional RT
with hyperfractionated , accelerated or both RT
-15 trails with 6515 pts
-median follow up 6 yrs
-most site oropharyngela & larynx(74%)
• End point-OS
• Result 5 yrs survival =↑3.4% altered ≠
= ↑ 8% hyper fractionated
= ↑ 2% accelerated ≠ without dose reduction
= ↑ 1·7% accelerated ≠ with dose reduction

26. Principle of Chemotherapy
• Adjuvant CCRT
• Definitive CCRT-Locoregionally Advanced
• Induction CT
• Palliative CT

27. Adjuvant CCRT
• Blanchard et al.-MACH-NC, comprehensive
analysis by tumour:
• Methods:87 randomized trial(16,192) b/n 1965
&2000
- median follow-up of 5.6 years
- Pts were : oral cavity, oropharynx,
hypopharynx and larynx
• Results: benefit of CT addition is consistent in all
tumor
-CT is more advantageous at CCRT , OPSCC,larynx

28. Definitive CCRT for LRA-OPSCC
• For loco-regional advanced OPSCC standard
Rx is CCRT.
• Resection when possible is not recommended
-Due to associated surgical morbidity
-As adjuvant CCRT will be indicated w/c has
same morbidity as definitive CCRT

29. Definitive RT vs CCRT
• Denis et al- Final Results of 94-01 French H &
N, phase III, multicenter, randomized
• Purpose to determine 5 yrs survival in locally
advanced (stage III & IV) OPSCC
222 pts
Arm A,113 pts
70Gy, in35≠
Arm B,109 pts
70Gy, in35≠ +
CT(Carboplatin
+5FU-D5)

31. Induction CT

33. Targeted agents
• Includes cetuximab & panitumumab
• Monoclonal Antibody; Epidermal Growth Factor Receptor
(EGFR) Inhibitor
• Addition of cetuximab is beneficial regardless of p16 status
& presence of a prominent rash is prognostic factor
• Indications:
-Stage ¾
-Non metastatic
-KPS > 60
-Normal CBC,RFT,LFT
cetuximab & RT(altered fractionation) is an alternative
treatment for pts who are not platinum candidate.

34. LA H& N ca,60%OPSCC
213 pts
High dose
RT only,70-
76.8Gy
211 pts, same RT
+cetuximab(loading
=400mg/m2 then
250mg/m2 weekly )
PEP-duration of LR control
SEP-OS,PFS, response rate &safety
Variable RT only RT+ Cetuximab P value
LR control 14.9mo 24.4months 0.005
OS 29.3 mo 49mon 0.03
PFS Significant 0.006
Sub group analysis for OPSCC only
Variable RT only RT+ Cetuximab P value
2 yrs LC control 41% 50%
Median LR DFS 23 mo 49 mo
Median OS 30.3 mon 66 mon
n engl j med 354;6 www.nejm.org february 9, 2006

35. Triple therapy (CT, RT & targeted Rx)
• To date no comparison of CT+RT with/with out
cetuximab for OPSCC specifically.
• RTOG 0522,for LA H& N ca ,70% OPSCC shows:
• Combination of cisplatin, cetuximab & RT
didn't improve LR control, DFS& OS.
• But , this triplet therapy is associated with
increased toxicity.

36. Neck Treatments
• Risk of occult neck metastases in early (T1/T2)
oropharyngeal ca relatively high.
• So, elective treatment of the neck is strongly
considered(either nodal dissection or RT).
• Early tonsilar with out palate or base of tongue
involvement are usually lateralized so elective
neck Rx is ipsilateral neck.
• ENI & END=equally effective in the Rx of the N0
neck, with control rates > 90%.

38. De-intensification of HPV+ OPSCC
• Due to better Rx outcome & toxicity of
combination Rx many are investigating
deintensified Rx in curative Rx of locoregionaly
advanced HPV+ OPSCC.
• Deintensification Rx in HPV associated OPSCC
remains experimental and should not be
considered standard of care.

39. Ma et al; june 4, 2019,ASCO
• Single arm , phase II
• Eligibility:
-p16-positive - Stage III/IV(7e)
-PE-EGOG≤1 - -ve margins
-Smoking history ≤10 pack-years
Purpose –if adjuvant RT dose de-escalation
from 60-66Gy to30-36Gy for HPV+ OPSCC can
maintain historical control with ↓toxicity

40. • 2
• 2yrs LRC-96.2% OS-98.7%. PFS-91.1%
• Rates of G≥3 toxicity at pre-RT (2.5),1yr(0%) &2yrs
post-RT (0%).
• Swallowing function -improved slightly b/n pre-RT
1yr post-RT, 1 pt requiring temporary feeding tube.
•
Sep 2013 to June 2016
Pt-80
Median Follow up-36months
Range 25.1-61.8mo
Arm
A(Intermediate
risk) 37 pts
30Gy,1.5Gy/≠
BID,over 2wks with
docetaxel15mg/m2
wkly
ArmB 43 pts
with ECE same
Rx+simulta LN
boost to
36Gy,1.8Gy/≠
End points
PEP-LRC at 2yrs
SEP-PFS,OS,toxicity,swallow fun,QOL at
2yrs

41. Toxicities CRT
• Depends up on field size, shape, dose, fraction ±CT,
comorbidty, smoking & divides in 02:
-Acute toxicities
-Late toxicities
Dysphagia :
-Most difficult acute & late complication of CRT
-Oropharyngeal pts are less affected than
laryngeal/hypopharyngeal
-Older & low performance pts worsening of their swallowing
following CRT.
-Pts with advanced ca improve their swallowing due to
reduction of tumor bulk.

42. Preventive/proactive swallowing
therapy
• Best practice for pts receiving RT for OPSCC
• central premise- ‘’Use It or Lose It”- to mitigate
muscular wasting and remodeling
• Encourages maximal use of the swallowing
musculature during Rx by:
- Avoiding NPO intervals
- Adhering to swallowing exercise
• To implement in clinical activities, routine pre-Rx
referral to a speech therapist is recommended

43. FOLLOW UP
• Regular post treatment follow-up is an essential part of
the care after curative Rx of oropharyngeal ca.
• Pts should be educated about possible signs and
symptoms of recurrence(hoarseness, pain, dysphasia,
bleeding & enlarged LNs)
• 80-90 % of recurrences occur with in 2-4 yrs (frequent
follow up)
• Late recurrence & 2nd primary common(FU >5yrs
recommended)
• These who continued smoking frequent & longer
duration of follow up( ↑ recurrence &2nd primary)

44. Case critics
Good
-Fair Documentation
-Early CT initiation
- Planned with Virtual simulation
Improve
-Ix-Biopsy of primary site
-LDH & Uric acid
-Chest CT
-HPV testing
-PET/CT
-Rx
-MDT
-Dental evaluations
-Pt can be Rx initially with CCRT
-Altered fractionation
-Induction CT—TPF
-Dose & duration of CT
-Width of laryngeal block

45. fffff Re References

46. Thank You!
Questions?