CA OROPHARYNX

CARCINOMA OROPHARYNX
MANAGEMENT
PRAGATHEESWARI G K

SYNOPSIS
1. MANAGEMENT GOAL
2. OUTLINE
3. RADIOTHERAPY
4. CHEMOTHERAPY
5. SURGERY
6. COMPLICATIONS
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PRAGATHEESWARI G K , MMC

Management Goal
• Oropharynx is a site involved in speech, swallowing,
airway conduit
• Maximize survival while minimizing morbidity
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OROPHARYNX
• In recent years occurs most frequently in young
patients, non smokers, non alcoholic
• Due to HPV infection,
• The crypts in tonsil favours the infection, proliferation of
HPV
• The incidence of HPV associated OP ca increased by
about 220%.
• There is variation in incidence, pattern of disease,
staging, prognosis in hpv,
• As of now no major difference in management
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OUTLINE – HPV neg
SITE/STAGE T1,T2- N0 N1 T3.T4a- N0- N3
TONSIL
BASE OF TONGUE
1.Surgery
2.Definitive RT
CCRT – cat 2B
1.CCRT
2.Surgery–> RT /CRT
Induction chemo – cat 3
SOFT PALATE 1.Definitive RT
2.Surgery
CCRT – cat 2B
-do-
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OUTLINE – HPV positive
Site / stage T1,T2, N0 N1 –
single <3cm
T1, T2 , N1-
multiple > 3cm
T3,T4a , N0 – N3
Tonsil/base of
tongue
1.Surgery
2.Definitive RT
CCRT – cat 2B
1.CCRT
2.Surgery–> RT /
->CRT (ENE + and or
+ve margin)
Induction chemo –
cat 3
-do-
Soft palate
1.Definitive RT
2.Surgery
CCRT – cat 2B
- do- -do-
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Definitive RT
• Early stage- single modality
• locally advanced – CCRT
Adjuvant RT
• Early stage – if margin +ve, ENE +ve
• Locally advanced stage - all cases
Palliative RT
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RT
• EBRT
• 2D
• conformal
• IMRT - parotid sparing (preferred)
• BRACHYTHERAPY (as a boost)
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DEFINITVE RT
• RT alone
• Is indicated only in
1. early T1 T2, NO , N1
2. in case of HPV N1(N1 -,3cm single node in HPV +)
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• Now advanced procedures
like trans oral techniques
available , but why RT ?
• The OS is equal in robotic
surgery and RT ,
• Complicaton were less in RT
• perment PEG feeding
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PRESCRIPTION
1. MODALITY - 2D/ 3D
/IMRT
• IMRT - reduces
incidence of acute and
late xerostomia
significantly
• NO survival benefit
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TIME DOSE AND FRACTIONATION
• Conventional - 66-70 Gy given as 2Gy /# - 5days /week
• Altered fractionation have been tried in OPC
• what are they ?
1. Hyper fractionation
2. Accelerated fractionation
3. Accelerated hyper fractionation
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Hyper fractionated RT
• HFX - twice daily fractions of small dose per fraction
given,
• EORTC 22791
• Here the total dose is more than the conventional dose
• 80.5 Gy HFX at 1.15Gy twice daily
• Result - 5yr LRC improved (59vs 40)
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ACCELERATED RT
• Acceleration - given for 6 days in a week
• DAHANCA 6&7 Trail
• here total dose not reduced
• 66-70 Gy in 2Gy/fraction 6 days a week
RESULT
• Loco regional control improved (42 vs30 %)
• LC for both p16+ & p16-
• late toxicities were similar in both arm
• acute toxicities high in accelerated arm
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CHART
• Continous Hyperfractionated,accelerated,RT
• 54Gy /36# - 12 days
• acute toxicities were , but settled soon
• late toxicities were less
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Comparing all
• All altered fractionation
showed benefits than
conventional ,which is
better?
• Rtog 9003 , LAHNC
• Hyper fractionation
improved os
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Volume - definitive RT
• Radical RT alone is given for early lesions
• Here , the target volume is primary with clearance
• Along with unilateral neck is irradiated. Level II - IV
• perez - level II to IV
• Nancy lee - level II to IV , RP node
• B/L -
• in case of tonsil tumors when base of tongue, floor of mouth
involved.
• Other tumors near/ involving midline
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RT - LAHNC
• In LA cases, Concurrent chemo radiation is given
• but when chemo deferred when RT alone is given
for LA caseS
• RT - 66gy - 70 Gy 2G/# for 5 days in week
• IMRT is preferred
• Hyper fractionation without reducing total dose
shows benefit than conventional RT alone in LAHNC,
with added toxicity - meta analysis - bourhis et al
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RT IN CCRT
• in locally advanced cancer - is RT alone not sufficient ?
• why to give CCRT ?
• GORTEC - 94 -01
• CCRT Improved LRC / OS than RT alone.
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• Conventional fraction
with 3w chemo is better
than split course RT
• CCRT - conventional RT is
better
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RT in CCRT
• Volume - tumor + clearance
• Neck - B/L level II - IV,RP node
• Level IB - when node is + or large II node , that cannot
rule out involvement of level IB , tumor extension into
oral cavity
• Level V - positive node , large matted Level IV
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RT - BOOST TECHIQUES
IMRT with SIB
● Conventional 2gy or 1.8 Gy /# to whole field
● Boost to gross disease - added gy/# ,dose painting
● Derived in a single fraction
● RTOG 00-22
● T1,2 N0,1
● PFS, 2yr OS benefits, particularly in patients with HPV + disease
Concomitant boost -
● Boost to gross disease - 1.5 gy/# ,
● Derived in a second daily fraction
Sequential boost
● conventional RT 60 gy to whole field f/b 6 gy to gross disease in second phase.
26

INTENSIFICATION
● CCRT >> RT
● Hyperfractionation >> conventional
● HFX RT > CCRT ???
27

1. Hfx RT vs CCRT (chemo - 5fu +CDDP) - BRIZEL et al
2. HFX RT vs CCRT ( low dose CDDP) - Brainslev et al
3. HFX vs Chemo HFX - RTOG 95-06
4. ccrt vs accelerated CCRT vs Accelerated RT alone (GORTEC
99-02)
28

● Acceleration / hyperfractionation of RT cannot
compensate for absence of chemotherapy
29

RT - ADJUVANT RT
• INDICATIONS
1.early stage - presence of adverse features
• adverse features -
• margin positive </= 1mm , (re resection if possible )
• close margin 2 to 5 mm
• PNI +
• LVSI+
• Nodes in level IV &V
• ENE +
2.advanced stage - T3,T4a, N2,N3
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VOLUME
• Bilateral neck and primary tumor site
• Completely resected margin neg, N+ --- can
also direct therapy only to neck
• margin positive, RND - N0 ----- direct
treatment for primary resection bed only is
tried
• Well lateralised tumors---- PORT to ipsilateral
neck only ,may be appropriate.
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Dose
• PORT -60 to 66Gy in 2Gy daily fractions to high risk
areas( primary tumor bed with positive margin or nodal
region with extra capsular spread) RTOG 95-01
• Microscopic involvement- 50 to 54 Gy/2Gy fractions
• IMRT is preferred
• RTOG 73-03, krammer et al
• PORT Vs preop rt
• LRC improved in PORT 70 vs 58 %
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REIRRADIATION OF LOCOREGIONALLY CONFINED
RECURRENT OR SECOND PRIMARY DISEASE
Indications
locoregionally confined recurrent disease
second primary disease
Locoregionally confined recurrent disease
Surgery recommended
• Following sx high risk pathology/ not surgical
candidates- second course full dose RT with CT- long
term survival 20 % pts
• High risk of normal tissue toxicity
20 % carotid rupture
15 % fatal toxicity
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• Prior RT should be more than 6 months
• Rare circumstances- reirradiation with IORT or brachy
considered
• ECOG- 0 to 1
• Incidence of myelopathy thought to increase after
cumulative BED of 120gy, but risk is increased with
large fraction size>/=2.5 gy/#
• Radiation volume should include only known
disease
• Prophylactic treatment of subclinical disease not
routinely recommended
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• Best outcomes- small tumors with no skin involvement
• Reirradiation dose
• Conventional fractionation
• Postop- 56 to 60 gy at 1.8- 2gy/#
• Definitive- 66 to 70 gy at 1.8-2 gy/#
• Accelerated fractionation
• 60-70gy at 1.2- 1.5 gy/# twice daily
• Careful pt selection needed if SBRT used for
reirradiation
• SBRT- 35 to 44gy using 5 #
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RT -PALLIATIVE RT
INDICATIONS
• advanced cancer with no curative intent
• widely metastatic disease
Use
• relief of symptoms
RT regimen
• 50 gy in 20 #
• 37.5 gy in 15#( if well tolerated , upto 50 gy)
• 30 gy in 10#
• 30gy in 5 # - 2 # per week with >/= 3 days between #s
• 44.4gy in 12 #, in 3 cycles( for each cycle, give 2 # 6 hrs
apart for 2 days in a row, and treatments must exclude the
spinal cord after 2nd cycle)
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WORK FLOW
Diagnosis & staging
Policy - tumor board concurrence
Simulation - send via LAN
Image registration - importing , fusion of diagnostic /
pre op images
Image segmentation - contouring
Planning
Plan verification
Execution
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RT - Brachytherapy
• The application of radioactive materials in close
proximity to tumors
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1. Done at 3-4 weeks interval from chemoRT completion
2. Tracheostomy placed to prevent from edema or
bleeding
3. Techniques
- loop technique
- gold button single strand technique
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4. Loop technique- similar to oral tongue
5.Initial extent of tumor prior to chemo+ residual at the
time of implant taken into account+ margin of approx.
1cm added
6.Not to implant catheter within 5mm of epiglottis, lateral
pharyngeal wall, or mandible
7.Loop technique not generally used for HDR because the
remote afterloading source may have difficulty in
navigating the loop
8.The gold button single stranded technique- used in
LDR/HDR
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CHEMO IN CCRT
• CCRT > RT
• Drug - cisplatin
• Dose - high - 100mg /m2
• Time- 3 weekly . days 1,22,43
• category 1 - NCCN
• Adelstein et al, intergroup trial , -
• improved overal survival,DFS
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• CDDP - cis -diammine dichloro platinum
• pre requisite - cc >60ml/min
• it is available as a powder form
• mixed using distilled water
• pre medication - anti emesis
• pre hydration
• cddp in 500ml NS over 2- 4 hours
• after hydration
• When only one drug is used, theMACH-NC indicates that the impact is
largest with a platin, - cisplatin .
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ALT. REGIMEN
• Drug - carboplatin, infusional 5FU
• 3cycles , 3 weekly
• category 1 - Gortec 94-01
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WEEKLY CISPLATIN
• Category 2A
• 40mg/m2
• phase 2 study - tried along with concomittant boost RT,
• radiosensitisizing effect
• Ja medina et al
• beckman et al
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combination regimen ?? - CCRT
• Platin + 5FU offered no clear advantage over cisplatin
alone
• MACHC , E1392 study
• 3weekly high dose single agent cisplatin regimen is
widely accepted and standard
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INDUCTION CHEMOTHERAPY
• induction chemo f/b RT is inferior than CCRT :MACH -
NC
• induction chemo f/b CCRT , doesn’t show any survival
advantage - PARADIGM trial
• if at all given TPF is the preferred regimen -
• TAXANE , PLATINUM, FU - DECIDE trial, tax 323
• as of now no role of induction chemotherapy in
oropharynx cancer
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MACH - NC
• CCRT >> RT , how much ?
• ans -- 6.5% at 5yrs.
• drug - single agent , high dose cisplatin.
• CCRT >> IC f/b RT, RT f/b adj CT
• inverse relation between age and
impact of CT, no benefit after 70 years
of age
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chemo - adjuvant ,
• Adjuvant CHEMO RT > Adj.RT alone
• Indications
• ENE +/- margin positivity
• drug -weekly cisplatin 40 mg / m2 (bachaud et al)
• cisplatin in eligible - docetaxel + cetuximab (cooper et l)
• trials - intergroup 0034, RTOG 9501,EORTC 22931
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Chemotherapy - RECURRENT/
REFRACTORY /METASTATIC
• IN combination with RT - carboplatin
• with no surgery or RT as option
• Targeted agents + chemotherapy
• meteronomic chemotherapy
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Meteronomic chemotherapy
• daily / frequent administration / with no interval
• 1/10 th to 1/3 rd of maximum tolerated dose of drug
• based mainly on anti - angiogenic property of the drug
• most often used are
• Methotrexate,capecitabine,cetuximab,gefinitinib,
• cyclophosphamide, etoposide
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Targeted Agents - Definitive treatment
• cetuximab - EGFR inhibitor
• RT alone vs RT +cetuximab
• showed imprved LRC
• Trial - bonner et al ,
• category 2B in definitive / post op setting
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Adding cetuximab to CCRT - RTOG 0522
arm A
• cetuximab + cisplatin RT
• toxicity more
• 3 yr OS - 72.9%
• here HPV positive has
better PFS than neg
• 72.8% vs 49.2%
arm B
• cisplatin RT
• 3yr os - 75 .8%
Adding CETUXIMAB to RT CDDP did not improve outcome - should not be prescribed
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• considering the fact that HPV positive
cancers has better response to Cetuximab
and
• cetuximab + RT > RT
• whether we can use cetuximab + RT
rather than Cisplatin + RT is studied, there
by we can reduce the toxicity associated
with cisplatin - De ESCAL aTE trial
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De - ESCALaTE trial
• low risk ( non smokers, <10 PY) HPV positive oropharynx
ca patients
• RT 70 Gy + CDDP vs RT + cetuximab
• primary outcome - toxicity
• no difference in acute and late toxicity.
• 2yr OS better with CDDP 97.5 % vs 89.4%
• so - when they are eligible for CDDP , CDDP + RT is
preffered in Low risk HPV + oropharyngeal patients.
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Targeted agents - recurrent and
metastatic disease
• not amenable for surgery and RT
• category 1 recommendation :
• first line - Pembrolizumab /CDDP or Carboplatin / 5FU
• second line - nivilomumab / pembrolizumab (if disease
progress on or after platinum , not used previously )
• Pembrolizumab - for tumor that express PDL - 1
(keynote - 012)
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SURGERY
• When it is operable- operate
• En bloc removal –primary with adequate margin
• Drainage is also addressed
• I/L ND --Well lateralised tonsillar tumors , not involving base
of tongue, floor of mouth and N0
• Tumors in the base of tongue , pharyngeal wall, soft palate
require consideration of B/L ND
• Midline tumors , N2c , N3b B/L ND,
• Vital function loss is the limitation – larynx, soft palate
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TONSIL
PROCEDURE:
●
Small lesions less than 1cm confined to anterior pillar - WIDE LOCAL
EXCISION
• Tumors involving the palatine tonsil - RADICAL TONSILLECTOMY
• Tonsil, tonsil at fossa, pillars, portion of soft palate , tongue and mandible -
COMPOSITE RESECTION
APPROACH:
• Trans oral approach
• Mandibulectomy - midline or partial
COMPLICATION:
• Impaired swallowing, fistula, flap failure, poor wound healing, and aspiration
occasionally leading to laryngectomy
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BASE OF TONGUE
PROCEDURE DONE :
● Large midline tumors – total glossectomy
● Well lateralised/ polypoidal lesions- PARTIAL GLOSSECTOMY
● Close to laryngeal apparatus which arise from the vallecula - SUPRAGLOTTIC
OR TOTAL LARYNGECTOMY
APPROACH :
• Midline mandibulotomy by spilting the lip , mandible and oral tongue
• Lateral mandibulotomy - division of mandible near angle
• Floor drop -elevating inner periosteum of mandible from angle to angle
COMPLICATION :
• Infection, fistula, bleeding, tongue sensory deficits, dysphagia, exposed
hardware, poor wound healing, and cranial nerve injuries.
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SOFT PALATE
• Definitive RT is preferred even in early lesions
PROCEDURE:
• WIDE LOCAL EXCISION for tumors confined to the soft
palate
• COMPOSITE RESECTION
• Reconstructed with flaps or protheses to preserve
velopharyngeal competence
APPROACH:
• Transoral approach
• Mandibulectomy - midline or partial
COMPLICATION:
• Nasal speech and regurgitation of food into the
nasopharynx are sequelae of full-thickness soft
palate resection.
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TRANS ORAL SURGICAL APPROACH
• Alternative to open surgical procedures
• Quick recovery time
• Less morbidity
TRANS ORAL LASER SURGERY
• Stage 1 to 2 cancers - transoral laser
microsurgery ± neck dissection +adjuvant RT
/CRT
• ↑ locoregional contol-87 to 100 %
• local recurrence in stage 2 to 4 - 20 to 30 %
COMPLICATIONS
• Post op haemorrhage
• Temporary tracheostomy
24/08/2022 73

TRANS ORAL ROBOTIC SURGERY
Da Vinci surgical system
3 surgical instruments and binocular endopscope
controlled by robotic arms and inserted under direct or
endoscopic guidance by surgeon from patient side apparatus
• surgeon controls from a console
• operative environment-virtual 3D
• surgeon movement translated as micromovements of
instruments.
ADVANTAGES
• motion scaling
• increase precision
• reduce hand tremors and fatigue
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• Here are no prospective randomized studies supporting
the use of
• Robotic surgery (TORS) for oropharyngeal tumor
resection over conventional surgery.
• Until mature prospective multi-institutional series and
randomized data are available, the true utility of trans
oral laser microsurgery and TORS remains unknown.
24/08/2022 76

NECK DISSECTION
• U/L – Well lateralised tonsil lesions, with NO infiltration
into floor of mouth, base of tongue.
• B/L – midline lesions,N2c, N3b.
1. NO- SND Level 1B- IV
2. N1,N2 - SND , Comprehensive if level IV, V nodes
positive.
3. N3- Comprehensive ND
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Types
• Radical/comprehensive :
• The superficial and deep cervical fascia with its
• enclosed lymph nodes (levels I to V) were removed
in continuity with the sternocleidomastoid muscle,
the omohyoid muscle, the internal and external jugular
veins, cranial nerve XI, and the submandibular gland.
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MRND/SND
• SNDs are more limited and include removal of lymph
node levels that are at greatest risk for nodal metastatic
spread.
• The type of SND is denoted by the lymph node levels
removed (e.g., SND II to IV).
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Complications
• The more extensive the neck dissection, the higher the
risk of complications. Complications after neck dissection
include
• Hematoma; seroma; lymphedema; wound infections and
dehiscence; damage to the 7th, 10th, 11th, and 12th cranial
nerves; phrenic nerve injury; brachial plexus injury; chyle
leak; and vascular injury.
• The main long-term complication of neck dissection is
caused by injury to the spinal accessory nerve, which can
result in shoulder and neck pain, weakness, loss of
range of motion, and decreased shoulder-related quality
of life.
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ACUTE toxicities of CHEMO RT
• Fatigue
• Nausea
• Emesis
• Thickened secretions
• Mucositis
• Xerostomia
• Dysphagia
• Odynophadia
• Alopecia
• Dermatitis
• Anemia,neutropenia
• Hoarseness
• infection
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LATE toxicities of CHEMO RT
• Dysphagia
• Trismus
• Xerostomia
• dental caries
• feeding tube dependence
• neuritis
• Fibrosis
• Osteoradionecrosis
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• the management goal - MAXIMIZE CURE , MINIMIZE
TOXICITY
• the more specific toxicities to treatment oropharynx
are
• TRISMUS, XEROSTOMIA, DYSPHAGIA
• trismus & dysphagia caused by disease , and treatment
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PREVENTION >> CURE
• Xerostomia- parotid sparing IMRT
• Trismus - mouth opening exercise from starting itself
• Dysphagia - PRV - pharyngeal constrictor muscles,
swallowing exercise from starting itself
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XEROSTOMIA
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TRISMUS
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DYSPHAGIA
• Prevention - dose constraints to pharyngeal constrictors
in contouring
• Treatment
• Direct methods - swallowing exercises
• Supportive measures- RT feeds, PEG tube, FJ tube .
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PHARYNGEAL CONSTRICTORS
• Contouring - EORTC guidelines
• Thickness - 3mm
• From caudal tip of pterygoid plates to caudal edge of
arytenoids
• Anterior - superior: hamulus of pterygoid plate; mandibula;
base of tongue; pharyngeal lumen. Middle: base of tongue;
hyoid. Inferior: soft tissue of supraglottic/glottic larynx
• Posterior - prevertebral muscles
• Lateral - superior: medial pterygoid muscle. Middle: greater
horn of hyoid bone. Inferior: superior horn of thyroid cartilage
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SWALLOWING EXERCISE
• Complete the following swallowing exercises times a day.
• Effortful Swallow: Gather saliva in your mouth, then swallow as hard as you can.
squeezing your throat muscles. Repeat times.
• Tongue retraction hold: Pull your tongue back like to say the /k/ sound, hold it tight in
that position for 5 seconds. Repeat times.
• Masako: Stick your tongue out and hold it gently between your teeth or lips. Swallow
while holding your tongue out. Repeat times.
• Mendelsohn: Swallow your saliva, but halfway through the swallow, hold your Adam's
apple up using your neck muscles or you can use a finger. Hold it up for 1-3 seconds.
Repeat times.
• Chin Tuck Against Resistance (CTAR): Place a squishy ball or rolled-up towel under your
chin, pressing lightly against your throat. Push your chin down hard on the ball/towel
and hold for 60 seconds. Relax. Repeat x2. Then, press your chin down hard and hold
for 3 seconds, relax, repeat x30..
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• Shaker: Lay flat on your back, no pillow. Raise your head to
look at your toes, keep shoulders flat, hold for 60 seconds.
Relax for 60 seconds. Repeat x2, Then, raise your head for 3
seconds, relax. Repeat x30
• Yawn: Yawn and when you get into a big stretch, hold that
position for 5 seconds. Repeat times
• Supraglottic Maneuver: Gather saliva in your mouth. Take a
deep breath and hold your breath. Swallow while holding
your breath. Immediately after you swallow, cough. Practice
with saliva prior to food or liquid. Repeat times.
• Effortful Pitch Glide: Say "eee" in as low a pitch as possible
and then gradually raise the pitch of your voice until the
highest tone possible. Hold for 5 seconds in the highest
pitch. Repeat times.
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FOLLOW UP RECOMMENDATIONS- NCCN
• After post chemoRT or RT-clinical assessment in 4-8 weeks
• If there is response- assess disease extent by FDG-PET/CT at minimum
12 weeks or CT of primary and neck or MRI withg contrast at 8-12 wks
• FDG PET/CT
-Negative- observation
- equivocal- observation or repeat PET/CT at 3-6 months- follow up
- strongly positive- CT/ MRI with contrast- BX or resection of primary
if feasible and/or neck dissection if nodal disease present
• CT/ MRI
- positive- FDG PET/CT>/= 12 wks OR neck dissection
- negative- observation
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• No response- residual/ persistant/ progression
• Assess disease extent or distant mets- CT/ MRI with
contrast or FDG PET/CT
• Confirmed residual / persistant/ progression
-resectable- resection of primary/ neck – follow up
- unresectable- treat with second line
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• H&P exam-complete head and neck exam, and mirror
and fiberoptic examination
-year 1, every 1-3 months
-year 2, every 2-6 months
-year 3-5 every 4-8 months
->5yrs, every 12 months
• Imaging
• TSH every 6-12 months if neck irradiated
• Dental evaluation of sites exposed to RT
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POST TREATMENT MANAGEMENT AND
SURVEILLANCE- perez
• Radiographic complete response defined as non
enhancing, non necrotic nodal tissue <1.5cm- 100 %
long term disease control- no furthur treatment
needed
• Surveillance CT of primary does not add additional
information to physical/ fiberptic examination- not
routinely performed
• PET/CT more widely available and often used as sole
imaging modality following RT
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TAKE HOME MESSAGE
1. OROPHARYNYX CARCINOMA
2. upfront surgeries are difficult and morbid, TORS yet to develope in our
country
3. NO role for induction chemo/NACRT at present
4. SO the management - RT/ CCRT
5. RT - hyperfractionation can be tried, CONVENTIONAL PAROTID SPARING
IMRT ALONG WITH HIGH DOSE CDDP IS THE RECOMMENDED REGIMEN
NOW.
6. unless for well lateralised early tonsil ca, B/L neck is irradiated.
7. Though the epidemiology, staging, prognosis of HPV associated OPC are
different, the cause specific treatment is yet to come.
8. For Oropharynx cancer the toxicities which affects QOL patients - should be
kept in mind ,prevent and treated accordingly.
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REFERENCE
• PEREZ & BRADYS TEXTBOOK OF ONCOLOGY
• DEVITA TEXT BOOK OF ONCOLOGY
• NCCN GUIDELINES
• PUBMED
• LANCET
• the MED SLP 2022
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ACKNOWLEDGEMENT
• ASST PROF - Dr. DURGA PRASAD MD RT
• PROF - Dr. JEEVA MD RT
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CA OROPHARYNX

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