OROPHARNYX AND HYPOPHARNYX

MODERATOR :- PROF. RAJEEV GUPTA

PRESENTER :- DR.VIJAY.P.RATURI

K.G.M.U RADIOTHERAPY DEPTT

• The anatomy of the head and neck is extremely complex.

• Supra- and infrahyoid neck

• The space is been divided into the nasopharynx, oropharynx, oral cavity, and hypopharynx.

• The larynx, located in the infrahyoid visceral space .

NORMAL ANATOMY OF OROPHARNYX

BOUNDARY OF OROPHARYNX :-

• Anterior -- Circumvallate papillae of the tongue and the anterior tonsillar pillars

• Posterior -- pharyngeal constrictor muscles

• Superior -- soft palate

• Inferior -- it is separated from the larynx by the epiglottis and glossoepiglottic fold and from the hypopharynx by the pharyngoepiglottic fold.

EPIDEMIOLOGY

• Approx 10% of annual worldwide incidence of head and neck sq.c.c.

• In U.S annual incidence is 4.8/lac

• Incidence INDIA 38601 , mortality 31784 (2012 Globocon)

• Tobacoo and alcohol continue to play a significant role.

• Incidence rate is higher for men than women (4:1), diagnosed commonly in 6th & 7th decade of life.

• Oropharyngeal CA in nonsmokers & non drinkers is caused by HPV predominantly in men(3:1)

ROUTE OF SPREAD

• The L.D of oropharynx & neck was 1st described by Rouviere in 1938 & has since been refined by others.

.

• Probability of lymphatic regional metastasis is related to size & location of primary tumor within oropharynx.

LYMPHATIC SPREAD :-

DISTANT METASTATIC SPREAD OF O.P C.A• It is uncommon , affecting Approx 15% of all pt during the course of their disease.

• M.c location of distant spread of metastasis of o.p CA are lung parenchyma followed by osseous & hepatic mets.

• Common in pt presenting with locally advanced disease or recurrent tumors, with the risk increasing with tumor stage as well as burden of LNpathy(N2 – N3 disease).

( ANAND R et al )

CLINICAL PRESENTATION

• Present with symptoms that depend on location of primary tumor , invasion of nearby organ, and extent of nodal disease.

• Pt often present with painless neck mass

• Otalgia

• Regurgitation of food

• Trismus

• Odynophagia & dysphagia

DIAGNOSTIC EVALUATION• PHYSICAL EXAMINATION – it is essential for diagnosis and under- standing of complete extent of disease.

• C.T SCAN – scan slice thickness <5mm -- path involved L.N are seen as enlarged ,enhance with contrast , and have a necrotic center.

• MRI – differentiate tumor from soft tissue , .

• P.E.T -- assess the locoregional burden of disease & detect and distant metastasis.

TNM STAGING

MANAGEMENT STRATEGIES

• Mx goal for all o.p.CA is functional organ preservation with minimal toxicity.

AJCC stage

LOCALY CONFINED DISEASE (STAGE 1 & 2)

- Early stage tumors are well controlled with single modality either <a> radiotherapy <b> surgery

- Selection of local modality is based on <a> tumor size <b> extent of local spread <c> subsite involved

LOCOREGIONALLY ADVANCED DISEASE (STAGE 3 & 4)

<a> Either Sx followed by R.T with/without C.T based on pathological risk factors

<b> R.T usually given with C.T

TRANSORAL Sx APPROACHES :- Incresingly being used Quicker recovery time , less morbidity

TRANSORAL LASER Sx :- High rates of locoregional control mainly for stage 1 & 2 pt although for stage 3 & 4 local recurrence is common. ( SALASSA et al)

TRANSORAL ROBOTIC Sx :- M.c robotic system is DA VINCI Sx system No prospective randomized studies suppourting the use of TORS for O.P tumor resection over conventional Sx.

SURGICAL APPROACHES

ADJUVANT T/T FOLLOWING DEFINITIVE Sx RESECTION

• PORT in RTOG 73-03 results in superior locoregional control (70% vs 58%) when compared to preoperative R.T but didn’t affect over all survival.

• Improved locoregional control & disease free survival with addition of C.T to PORT ( OZSAHIN et al , JONATHAN E. ALZIEA C et al)

CONCURRENT C.T REGIMENS FOR ADJUVANT C.R.T :-

• Schedule of bolus cisplatin 100mg/m2 was tested in 2 randomized trials one tested 50mg cisplation weekly, & other tested 20mg/m2

cisplatin with 5FU 600mg/m2

• No randomized data suppourt the use of taxanes or cetuximab in post –op settings. ( QUON H et al )

DEFINITE RADIOTHERAPY• For early OP. CA , use of R.T as single modality is asso with good outcome & functional preservation.

• Randomized data and meta analyses suppourt an overall survival benefit with the use of accelerated # or hyper# RT

HYPER # R.T :- 80.5Gy hyper # at 1.15 Gy twice daily , asso with satistically significant improvement in locoregional control.( 5year 59% vs 40) & improved O.S in stage 3 pt. (N ‘GUYEN , et al) ACCELERATED R.T :- 66 -70Gy in 2Gy daily # 6 days a week improve locoregional control(42% vs 30%) disease free survival (50% vs 40%), improved O.S(35% vs 28%) ( PETERS LJ et al)• When more intense regimen was used ( 1.8 Gy twice daily to 59.4Gy) in stage 3 & 4 H &N CA pt , no statistical benefit were seen in term of locoregional control , O.S.

ACCELERATED VS HYPER # RADIOTHERAPY

• 15 randomized studies (including 6,515 pt ) comparing conventional # RT to either accelerated RT or hyper # RT has been done.

• Altered # RT regimen were asso with a 3.4% absolute improvement in 5 year O.S

• Hyper # pt had an absolute 8.2% improvement in overall survival at 5 years compared to 2% absolute benefit with accelerated R.T ( AUDRY et al)

• Improvement in O.S were asso with increase in both acute & late toxicity in accelerated & hyper # t/t arm

CONCURRENT R.T FOR LOCOREGIONAL ADV OROPHARYNGEAL CA• Concurrent RT is std t/t.

• Meta analysis of CRT for stage 3& 4 in head & neck ( MACH- NC) demonstrated 6.2% absolute improvement in OS at 5 years ( MAILLARD et al )

• Conventional RT with concomitantly administered with daily bolus carboplatin & cont .infusion of 5FU 600mg/m2 with a median follow up of 5.5 years .( BARDET et al)

5 year OS ( 15.8 vs 22.4%) locoregional control ( 24.7 % vs 47.6%) severe late toxicity increased with combine modailty( 14% vs 9%)

TOXICITY OF CHEMO-RT

ACUTE

• Nausea , emesis • Thickened secretion• Mucositis, dysphagia • Odynophagia• Alopecia, dermatitis • Anemia ,neutropenia

• Dysphagia is most difficult acute complication of CRT

• Older pt & pt with worse performance status are more likely to have diff in swallowing

LATE

• Fibrosis• Osteoradionecrosis• Trismus• Xerostiomia• Dental caries• Feeding tube dependence• Neuritis

• Older pt with T3 & T4 tumors were more likely to experience late toxicity

INDUCTION C.T PRIOR TO DEFINITIVE LOCAL THERAPY

• A phase 3 study restricted to OROPHARYNGEAL CA compared

cisplatin 100mg/m2 on day 1 & 5FU 1gm/m2/day 1 through 5 ,repeated every 3 week for 3 cycle followed by definitive local therapy to definite local therapy alone , significant improvement in OS was seen in induction CT arm in 5 years --- ( LEFEBRE et al)

• Whether or not induction CT prior to concurrent CRT improves survival when compared to CRT is currently unknown and waiting maturation of data from completed randomized studies

TARGETED AGENTS AND RADIOTHERAPY • Radiotherapy 70 TO 76.8Gy with or without weekly CETUXIMAB

(loading dose of 400mg/m2 followed by 250mg/m2) for locoregional advanced Head & Neck CA --- ( GIRALT et al)

- improve locoregional control - disease free survival & O.S( > 66 month vs 30.3 month )

• Combination of cisplatin, cetuximab & RT did not improve locoregional control , disease free survival & OS. However this

triplet regimen was asso with increased musocitis , skin reaction (ROSENTHAL et al)

EXT BEAM RT SIMULATION AND T/T PLANING • CT simulation with contrast for distinction between vascular

structures and lymph nodes.

• Addition of metabolic imaging & MRI is complementary to GTV delineation ( SCHODER H et al)

RADIOTHERAPY VOLUMES :-

• Current RTOG guidelines specify extension of 0.5 -1cm from GTV to form CTV

• Typically one node beyond those path involved LN is included.

• Inclusion of RP node routinely in low risk is controversial as it often increase radiation dose to constrictors.(RASCH C et al)

• RP coverage should be done if OP tumor is extending to nasopharynx or pterygoid region , those with gross RP nodes ( GREGORIE V et al)

INDICATION OF I/L RADIOTHERAPY• Well lateralized tonsillar CA not involving the BOT and with minimal involvement of soft palate. CTV can be limited to I/L neck.

I/L EBRT PLANING TECHNIQUE

• Include wedge pair or mixed photon e- field arrangement

• Wedge pair tech includes I/L ant & post oblique field with head hyperextended to move orbit out of t/t field

• C/L parotid dose is usually negligible at 0 to 10%

• Combination of photon and e- can be delivered using two I/L field energy used is 14-16mev e- and 4-6 mev photon

• Use of IMRT for I/L only t/t has been increasing

B/L EBRT TECHNIQUES

• It should be performed with 3D CRT or IMRT

• Std beam arrangement are opposed lat upper fields that are exactly matched to low neck/supraclavicular field treated with either. single ANT or AP – PA field

INTENSITY MODULATED RADIOTHERAPY• Minimize dose to normal structure particularly pharyngeal

constrictor and parotid (asso with xerostomia and dysphagia) ( DAWSON LA et al )

IMPACT OF IMRT ON XEROSTOMIA

• It significantly reduce mean RT dose to I/L parotid( 47Gy vs 61 Gy) & C/L parotid ( 25 Gy vs 61 Gy)

• At 12 month only 38% pt had grade 2 xerostomia compared to 74%.

• Unstimulated & stimulated C/L parotid flow were increased in IMRT group.

• Locoregional progression (78% IMRT vs 80% CONVENTIONAL) overall survival (78% IMRT vs 76% CONVENTIONL) were similar in both ARM.

BRACHYTHERAPY• Osteoradionecrosis secondary to brachytherapy is significantly

reported ,has lead to decrease in utilization of brachy in Oropharyngeal tumors

• For OP tumors, brachy has historically played a role in boosting gross disease following ext beam RT as Oropharyngeal tumors have a high propensity to involve neck node.

• Prophylatic tracheostomy is recommended because posterior & large tumors are at risk to cause airway obstruction.

• Recommended EBRT 45-50Gy followed by HDR brachy boost 3-4Gy /# for 6-10 doses with locoregional control reaching 82% - 94%

• 25-30gy boost for tonsillar tumors, 30-35 gy boost to BOT tumors

POST T/T MANAGEMENT & SURVEILLANCE

• Current guideline suggest examination evry 1-3 month for 1st year every 2-4 month in 2nd year post therapy every 4-6 month in 3rd through fifth year

• TSH hormone level should be evaluated every 6 month

• Follow up imaging should be performed within the first 3 months

• PET/CT is often used as the sole imaging modality following completion of RT

• False +ve reading PET/CT is 1.8% as compared to 38% of CT scans

NORMAL ANATOMY OF HYPOPHARYNX

• The hypopharynx extends from the level of the hyoid bone and valleculae to the cricopharyngeus (inferior margin of the cricoid cartilage on imaging studies).

• Its three major anatomic subsites include

<a> pyriform sinus, <b> postcricoid area <c> posterior pharyngeal wall.

EPIDEMIOLOGY AND ETIOLOGY • Incidence rate in U.S was 0.7/lac from 2000 – 2008 acco to (SEER)

• Approx 3/4th occurs in men with mean age of 65 years

• Cigarette use, alcohol appers to potentiate carcinogenic effect of tobacco.

• FIELD CANCERIZATION

• Coal dust, steel dust, iron compounds shown an increase risk (SZESZENIA-DABROOWSKA et al)

• 20-25% test +ve for HPV DNA

• Increased risk of developing post cricoid CA with PLUMMER VINSON

TNM STAGING

PATTERN OF SPREAD

CLINICAL PRESENTATION• Dysphagia , sore throat , hoarseness ,weight loss >10 pounds & neck

mass

• Reflux symptoms can be common presentation.

PRE T/T EVALUATION AND STAGING WORKUP• Detailed History

• Dentition & oral health

• Size, number, location, texture & mobility of these nodes should be documented

• Panendoscopy( DL IN CONJUNCTION WITH OESOPHAGOSCOPY)

• CT with contrast (or MRI)

• FDG PET is increasingly used to assess extent of regional adenopathy and to survey for presence of distant metastasis.

• SCHWARTZ et al examined SUV of primary & nodal mets in H&N CA pt & their relationship to clinical outcome , primary tumor SUV>9 was asso with lower local recurrence free survival and DFS.

• Recent proscpective multicenter study of 223 Head and neck sq.c.c pt highligted impact of PET imaging on Head & neck scc management ( REYCHLER et al)

• PET & conventional workup revealed discordant TNM staging in 100pt

• PET was significantly more accurate than conventional staging & improved staging in 20% of pt.

MANAGEMENT

• Majority of pt present with stage 3 or 4 disease & requires multi modality t/t.

PRIMARY SURGERY T1 & T2 TUMORS• Indication – previous H/O H&N radiation, organ conservation, who refuses radiation.

• C/I to organ conservation Sx :- cartilage invasion, vocal cord fixation, post cricoid , deep pyriform invasion, extension beyond

larynx.

• In recent years , advancement of organ perservation Sx include the use of transoral laser microSx, transoral robotic SC

T3 OR T4 RESECTABLE TUMOR

• Most T3 & T4 HYPO CA that are t/t surgical will require TOTAL LARYNGECTOMY.

• This procedure create a gap between OP & oesophagus & must be reconstructed TUBED FASCIOCUTANEOUS FLAP.

• Laryngopharyngectomy along with oesophagectomy may be performed if it extends inferior to cricopharyngeus, in this

case , gastric pull up or colon interposition are done.

POST OP RADIATION THERAPY

• INDICATION : - T4 Primary tumors close or +ve margin, cartilage or bony invasion > 1 metastatic LN , presence of ECE

• Shrinkage field tech to deliver 54-63 Gy to all area at risk & boost to 60-66 Gy to regions of ECE or +ve margin

• RTOG & EORTC have evaluated role of concurrent CT along with post op RT in randomized trial , improvement in locoregional control & DFS seen but no significant benefit in absolute survival. ( FORASTIERE AA et al)

DEFINITIVE RADIOTHERAPY T1 & T2 TUMORS • Good potential for organ preservation without compromise in clinical outcome.

• Altered # tech, including hyper # & accelerated # have demonstrated improved LCR for Head &Neck CA

T3 & T4 TUMORS • Hypopharyngeal CA pt who are resectable may not undergo primary

Sx include age, comorbidity , unwillingness to accept T.laryngectomy.

INDUCTION CT & SEQUENTIAL CHEMORADIATION

• EORTC Study (TAX- 323) randomized pt with locoregional adv unresectable disease to either induction CIS + 5FU versus induction DOCE+ CIS + 5FU followed by definitive radiation alone.

• T/t with TPF improved median OS from 14.5 months to 18 months 5 year survival in TPF arm 52% vs 42% in PF arm(VANHERPEN C et al)

PALLIATIVE RADIOTHERAPY :-• Pt with poor performance status ,should be managed with palliative

RT

• Regimens – 4-5 gy in 5 # over 1 - 2 week with repeat of same 3 weeks.

• Recent study suggested using 3.7 Gy twice daily * 2 consecutive day for 3 cycle every 2-3 week as described in RTOG 85-02 have similar palliative efficacy with less toxicity.( NARAYAN S et al )

PALLIATIVE CHEMOTHERAPY

• Pt with good performance status should be consider for Palliative C.T

• Combination cisplation with cetuximab , improved OS from 7.4 month to 10.1 month over cisplation alone ( RIVERA F et al )

LONG TERM FOLLOW UP• Recommended guideline :- every 1- 3month during 1st year every 2-4 month for 2nd year every 4-6 month for 3-5 years every 6 month thereafter

• Imaging evaluation m.c with CT or MRI scan are done every 3-6 month during first 2 years

• FDG PET prove valuable to differentiate post T/T fibrosis from persistent disease or recurrent disease.

• Result of first POST RT FDG PET may be strong predictor of developing locoregional disease recurrence ( GRAHAM M et al)

MANAGEMENT OF RECURRENCE

• If recurrence is suspected , it is confirmed by BIOPSY

if biopsy is confirmed, pt should undergo complete RESTAGING

• Selected pt with low volume localized disease can be considered for transoral laser micro Sx or robotic Sx for recurrence after RT.

• 2 recent prospective RTOG studies have demonstrated that reirradiation to H&N is feasible.(HORWITZ EM et al , WHEELER RH et al)

• A retrospective study from MEMORIAL SLOAN KETTERING CANCER CENTER has suggested IMRT is beneficial local control in this settings ( BEKELMAN JE et al)