H&N III Larynx & Hypopharynx

Question 1

Anatomy of larynx

Answer 1

• larynx is divided into 3 distinct regions based on topographical landmarks
• supraglottis: consists of laryngeal epiglottis, false cords, ventricles, aryepiglottic folds and artenoids
• glottis: consists of true vocal cords, anterior and posterior commissures
• subglottis: starts 10mm below the free margin of the vocal cords and extended to the inferior edge of the cricoid cartilage

Question 2

Laryngeal spaces

Answer 2

• larynx cancer spreads via direct invasion through the laryngeal spaces
• 1. tumours at the base of the epiglottis spread via the pre-epiglottic space and have worse prognosis than those in the suprahyoid epiglottis
• 2. the paraglottic space is in continuity with the pre-epiglottic space and with the para-laryngeal tissue of the neck through the lateral cricothyroid space-extralaryngeal spread
• 3. Reinke’s space is part of the lamina propria of the mucosa over the true vocal cords and gives resistance to the spread of early glottic tumours (devoid of blood and lymph vessels)

Lamina propria covers true vocal cords. Glottic tumours present very early. No blood vessels, no lymphatics

Question 3

Lymphatic drainage - larynx

Answer 3

• levels II, III, IVa and IVb are involved in drainage of the larynx
• supraglottic larynx - vessels train into levels II and III. If bulky level II, then consider retrostyloid nodes (EviQ)
• subglottic larynx - vessels drain into pretracheal (into lower jugular nodes - level IVa) and medial supraclavicular nodes (level IVb). EviQ guidelines also recommend level VI inclusion for subglottic disease
• EviQ guidelines consider level IB and V on side(s) of lymphadenopathy
• glottic cancers - devoid of lymphatics - no nodal spread in early stage glottic cancers

Question 4

Histology - larynx

Answer 4

• 85-90% of all laryngeal tumours are squamous cell carcinomas (SCCs)
• most glottic tumours are moderate to well differentiated
• other histologic subtypes include:
  verrucous carcinomas
  chondrosarcoma
  mucoepidermoid carcinoma
  spindle cell carcinoma
  melanoma
• 5 year survival rate of SCC larynx is around 70%

Question 5

Aetiology - larynx

Answer 5

• smoking - those with a 40 pack year history are 13 times more likely to have larynx cancer than a non-smoker
• chronic alcohol use
• socio-economic status
• occupational hazards - inorganic and organic agents (metal dusts, tar products, furniture marking)
• chronic oesophagogastric reflux - anterior 2/3rds of vocal cords

Question 6

presenting signs and symptoms - larynx

Answer 6

• supraglottis: sore throat, odynophagia (pain on swallowing), change in voice quality, referred ear pain, enlarged neck nodes
• glottis: persistent hoarseness
• subglottis: hoarseness, stridor (difficulty in breathing) (if airway obstructed), enlarged neck nodes. Vary rare tumours (<5% of all larynx cancers)

Question 7

Definitive EBRT for glottic SCC

Answer 7

• Indications:
  -> SCC of the glottis
  -> T1N0M0-T2N0M0 (stage I and II)
  -> good performance status ECOG 0-2
• Treatment position:
  -> supine, neutral, shoulders down as much as possible
• Image acquisition for planning: scan from hard palate to manubriosternal joint in <= 3mm CT slices

Question 8

Definitive EBRT for glottic SCC
dose prescription:

Answer 8

T1 SCC of the glottis:
- 63Gy in 28# (2.25Gy/#) OR
- 60Gy in 25# (2.4Gy/#) 5#s per week

T2 SCC of the glottis:
- 65.25Gy in 29# (2.25Gy/#) 5#s per week

Question 9

surgery vs. RT early stage glottis

Answer 9

• similar outcomes for surgery and RT
• 3 systematic reviews (Higgins, Yoo, Abdurehim) have shown that endolaryngeal surgery provides similar larynx and voice preservation and survival rates as RT alone
• in RT, hypofractionated protocols are considered SoC as they show an improvement in locoregional control compared to standard fractionation, without an increase in toxicity (Yamazaki et al, Overgaard et al)

Question 10

definitive EBRT for glottic SCC
image verification:

Answer 10

• daily KV/MV planar imaging or CBCT matched or bone with a soft tissue check
• dose should be incorporated into treatment planning, especially dose close to critical structures (dose from CBCT 3-6cGy. 25# of 6cGy CBCT = 1.5Gy)
• weight changes need to be monitored to ensure target volume coverage and dose to OARs is not surpassed - ART

Question 11

definitive EBRT chemoradiation larynx (not glottis)

Answer 11

• For T3N0 or T1-3 N1-3 (Based on RTOG 91.11)
• larynx-preserving strategy
• exclusions:
  -> incompetent larynx
  -> extensive base of tongue involvement or penetration through laryngeal cartilage
• treatment position: supine, neutral, shoulders down as much as possible
• image acquisition for planning: contrast scan from vertex to 1cm below carina in <= 3mm CT slices

Question 12

Chemotherapy regimen - larynx

Answer 12

patients can receive any of the following concurrently:
- cisplatin (3 weekly cycle)
- cisplatin (weekly cycle) (PS decides chemo schedule. Kidney function also dictates chemo schedule - 3 weekly not as intense)
- cetuximmab (mono-clonal antibody. patients can get very itchy rash)
- carboplatin and fluorouracil
for patients unsuitable for chemotherapy, consider accelerated RT.

Question 13

Definitive chemoRT larynx pre-treatment

Answer 13

As per general guidelines: also should include:
- dental assessment with extraction of cavities (requires 2-3 weeks post-extraction healing). If multiple amalgam filings near primary site, consider extraction of same
- CT scan (+/- PET) for staging and assessment of synchronous primary lesions
- MRI for base of tongue involvement assessment
- Audiogram if platinum-based chemotherapy regimen used
- airway assessment for large tumours
- SALT, dietitian, psycho-oncology

Question 14

Definitive chemoRT larynx
Dose prescription:

Answer 14

• IMRT/VMAT is the standard technique
• Either a 2 dose level or 3 dose level technique can be used
• quite common to use the following SIB technique:
  CTV-P2: 70Gy in 35# (2.0Gy/#)
  CTV-High risk nodal: 63Gy in 35# (1.8Gy/#)
  CTV-Elective nodal: 56Gy in 35# (1.6Gy/#)
  Delivered with either 5-6 fractions per week at 6MV

Question 15

Definitive chemoRT larynx
Image verification:

Answer 15

• daily KV/MV planar imaging or CBCT matched on bone with a soft tissue check
• dose should be incorporated into treatment planning, especially with dose close to critical structures
• weight changes need to be monitored to ensure target volume coverage and dose to OARs is not surpassed - ART

Question 16

Postop RT +/- chemo larynx
Indications:

Answer 16

• SCC larynx, any stage excluding metastatic disease
• macroscopic complete resection +/- ipsilateral neck dissection
• good PS: ECOG 0-2
• has any of the following risk factors:
  -> T stage >=3
  -> positive or close margins (+ concurrent cisplatin)
  -> extracapsular spread (+ concurrent cisplatin)
  -> LV or PN invasion
  -> multiple positive LNs or node >3cm

Question 17

Postop RT +/- chemo larynx
Pre-treatment

Answer 17

as per general guidelines. Also should include:
- dental assessment with extraction of cavities (requires 2-3 weeks post-extraction healing). If multiple amalgam fillings near primary site, consider extraction of same
- CT scan for staging
- MRI, PET to aid in target delineation
- Audiogram if for cisplatin
- SALT, dietitian, psycho-oncology
- RT should begin as soon as adequate healing has occurred - ideally within 4-6 weeks but no longer than 8 weeks post-op
- if delayed, consider accelerated RT regimens

Question 18

Postop RT +/- chemo larynx

Answer 18

• Treatment position: supine, neutral, shoulders down as much as possible. Consider stent to immobilise tongue
• Image acquisition for planning: contrast scan from vertex to 1cm below carina in <= 3mm CT slices with surgical scars wired
• Dose prescription:
  -> CTV tumour bed: 60 (complete resection) to 66Gy (+ve margins or ECE) in 30-33 #s
  -> CTV surgical bed: 54-66Gy in 30-33#s (BED 2Gy Equivalent)
• CTV elective nodal: 50Gy in 30-33#s (BED 2Gy Equivalent)
  SIB technique at 6MV with IMRT/VMAT delivery

Question 19

Post-op target volumes larynx

Answer 19

• CTV 60-66Gy contains the tumour bed including the pre-operative GTV-P and the 5 + 5mm expansion as necessary
• CTV 54-56GyE contains the surgical bed
• CTV 50GyE contains the elective nodal areas
  PTVs on all as per departmental protocol (measured margins, typically 3-5mm)

Question 20

Post-op RT +/- chemo larynx
Image verification:

Answer 20

• daily kV/MV planar imaging or CBCT matched on bone with a soft tissue check
• dose should be incorporated into treatment planning, especially dose close to critical structures
• weight changes need to be monitored to ensure target volume coverage and dose to OARs is not surpassed - ART

Question 21

Anatomy of hypopharynx

Answer 21

• part of the pharynx that extends from level of hyoid cartilage superiorly to lower border of cricoid cartilage inferiorly
• divided into 3 subsites:
  -> piriform fossae
  -> postcricoid region
  -> posterior pharyngeal wall

Question 22

Lymphatic drainage of hypopharynx

Answer 22

• Levels II,III, IVa and IVb, VIa, VIb are involved in drainage of the hypopharynx
• If bulky level II, then consider retrostyloid nodes
• If extensive nodal disease, consider retropharyngeal node inclusions in CTV elective
• Consider levels Ib and V on side(s) of lymphadenopathy

Question 23

Histology - hypopharynx

Answer 23

• 99.5% of all hypopharyngeal tumours are SCCs
• occasional: sarcomas, chondrosarcomas, adenocarcinomas, lymphomas and melanomas have been reported

Question 24

Epidemiology and Gender Distribution - hypopharynx

Answer 24

• primary hypopharyngeal tumours are rare (10% of all SCCs of the upper aerodigestive tract)
• previously a high incidence in France relative to rest of Europe
• mean age at presentation is 60 years
• piriform fossa and posterior pharyngeal wall lesions have a male dominance
• postcricoid lesions have a slight female dominance

Question 25

Aetiology - hypopharynx

Answer 25

• smoking
• chronic alcohol use
• synergistic effect of alcohol and smoking
• previous radiation exposure has been implicated in postcricoid and posterior pharyngeal wall carcinomas

Question 26

presenting signs and symptoms - hypopharynx

Answer 26

Piriform fossa:
- unilateral sore throat and dysphagia
- otalgia (ear pain) - associated with invasion through the pharyngeal wall
- hoarseness-associated with involvement of laryngeal musculature (sign of more advanced disease)
- nodal metastases are early due to rich lymphatics so neck mass is common

Postcricoid:
- rapid (<3 months) onset of dysphagia
- voice change due to proximity to larynx
- large RP nodes may cause neck pain

Posterior Pharyngeal wall:
- primary symptom is neck mass
- dysphagia and sore throat are also common
- large RP nodes can produce neck pain
- 10% are asymptomatic and found incidentally

Question 27

Definitive EBRT chemoradiation Hypopharynx

Answer 27

• For T3 any N or T1-2 N1-3
• consider unfavourable T2N0
• exclusions:
  -> incompetent larynx (larynx that is not stable)
  -> extensive base of tongue involvement or penetration through laryngeal cartilage (pts are at high risk of aspirating)
• Treatment position: supine, neutral, shoulders down as much as possible
• Image acquisition for planning: contrast scan from vertex to 1cm below carina in <=3mm CT slices

Question 28

Chemotherapy regimen - hypopharynx

Answer 28

• patients can receive any of the following concurrently:
  -> cisplatin (3 weekly cycle)
  -> cisplatin (weekly cycle)
  -> cetuximab (mono-clonal antibody, not chemo)
  -> carboplatin and fluorouracil
• for patients unsuitable for chemo, consider accelerated RT

Question 29

definitive chemoRT hypopharynx pre-treatment

Answer 29

As per general guidelines, should also include:
- dental assessment with extraction of cavities (requires 2-3 weeks post-extraction healing). If multiple amalgam fillings near primary site, consider extraction of same
- CT scan (+/- PET) for staging and assessment of synchronous primary lesions
- MRI for base of tongue involvement assessment
- audiogram if platinum-based chemotherapy used
- airway assessment for large tumours
- SALT, dietitian, psycho-oncology

Question 30

definitive chemoRT hypopharynx
dose prescription

Answer 30

• IMRT/VMAT is the standard technique in developed regions
• either a 2 dose level or 3 dose level technique can be used
• quite common to use following SIB technique:
  -> CTV-P2: 70Gy in 35#s (2.0Gy/#)
  -> CTV-high risk nodal: 63Gy in 35#s (1.8Gy/#)
  -> CTV-elective nodal: 56Gy in 35#s (1.6Gy#)
• delivered with either 5-6 fractions per week at 6MV

Question 31

definitive chemoRT hypopharynx
image verification:

Answer 31

• daily kV/MV planar imaging or CBCT matched on bone with a soft tissue check
• dose should be incorporated into treatment planning, especially dose close to critical structures
• weight changes need to be monitored to ensure target volume coverage to OARs is not surpassed - ART

Question 32

post-op RT +/- chemo hypopharynx
indications:

Answer 32

• SCC hypopharynx, any stage excluding metastatic disease
• macroscopic complete resection +/- ipsilateral neck dissection
• good PS: ECOG 0-2
• has any of the following recurrence risk factors:
  -> T stage >= 3
  -> positive or close margins (+ concurrent cisplatin)
  -> extracapsular spread (+ concurrent cisplatin)
  -> LV or PN invasion
  -> multiple positive LNs or node >3cm

Question 33

post-op RT +/- chemo hypopharynx
pre-treatment

Answer 33

as per general guidelines, also should include:
- dental assessment with extraction of cavities (requires 2-3 weeks post-extraction healing). If multiple amalgam fillings near primary site, consider extraction of same
- CT scan for staging
- audiogram if for cisplatin
- SALT, dietitian, psycho-oncology
- RT should begin as soon as adequate healing has occurred - ideally within 4-6 weeks but no longer than 8 weeks post-op
- if delayed, consider accelerated RT regimens

Question 34

post-op RT +/- chemo hypopharynx

Answer 34

• treatment position: supine, neutral, shoulders down as much as possible. Consider stent to immobilise tongue
• image acquisition for planning: contrast scan from vertex to 1cm below carina in <= 3mm CT slices with surgical scars wired
• Dose prescription:
  -> CTV tumour bed: 60 (complete resection) to 66Gy (+ve margins or ECE) in 30-33#s
  -> CTV surgical bed: 54-55Gy in 30-33#s (BED 2Gy Equivalent)
  -> CTV elective nodal: 50Gy in 30-33#s (BED 2Gy Equivalent)
  SIB technique at 6MV with IMRT/VMAT delivery

Question 35

Post-op target volumes hypopharynx

Answer 35

• CTV 60-66Gy contains the tumour bed including the pre-operative GTV-P and the 5+5mm expansion as necessary
• CTV 54-56GyE contains the surgical bed
• CTV 50GyE contains the elective nodal areas
  PTVs on all as per departmental protocol (measured margins, typically 3-5mm)