H&N Cancers

Question 1

NPC
OP

Answer 1

Nasopharyngeal carcinoma
Oropharyngeal carcinoma (soft palate, tonsil, base of tongue)

Question 2

NPC Epidemiology

Answer 2

Rare in West; endemic in southern china/HK; intermediate risk = SEA, North Africa, Middle East
M:F = 2.5:1
Peak incidence 5th decade

Question 3

OP Epidemiology

Answer 3

123k+ incidence per year, 79k deaths per year
Smoking incidence decreasing; usuallly 60-70 y/o male
HPV infection increasing; younger, non-smoking; HPV-16 strain strongest association

Question 4

Risk Factors

Answer 4

Multifactor:
NPC = Epstein Barr Virus infection (can detect EBV DNA and gene expression in cells)
OP = HPV, smoking, alcohol
Environmental = preserved foods, salted fish (nitrosamines), smoking, genetics (familiar clustering)

Question 5

NPC Pathology

Answer 5

Carcinoma
WHO type 1 - Keratinizing squamous cell carcinoma: sporadic form
WHO type 2 – Non keratinizing carcinoma and differentiated.
WHO type 3 – Non keratinizing and undifferentiated: endemic form. Strongly associated with EBV. More favourable prognosis than other types.

Also rarely
salivary gland carcinoma eg adenoid cystic carcinoma
Basaloid type squamous cell carcinoma
Adenocarcinoma

Question 6

OP Pathology

Answer 6

Squamous cell carcinoma accounts for 90%+ of all OP
Carcinogen exposure results in premalignant changes which evolve to invasive carcinoma
HPV status is determined by P16 testing.
P16 +ve disease – better prognosis, more chemo and radiation sensitive. Maybe a role for treatment de-escalation

Question 7

Clinical Presentation

Answer 7

Headache
Diplopia
Cranial nerve palsy
Neck lump
Nasal obstruction with epistaxis
Serous otitis media
Weight loss
Pain
Metastases

Question 8

Natural History/Disease Progression

Answer 8

Local - Lateral wall (fossa of Rosenmuller), roof of NP, mucosa or submucosa (nasal cavity, skull base, optic pathway, sinuses)

Nodal - 90% overall, 60-85% at diagnosis, 40-50% bilateral

Distant - Lung, bone, liver
Incidence correlates with N stage (not T) (N0 – 20% , N3 – 75%)

Question 9

Work Up

Answer 9

History
Physical examination
Imaging – CT, MRI, PET
Endoscopic biopsy

Question 10

NPC TNM
Primary Tumour (T)

Answer 10

TX: Primary T cannot be assessed
T0: no T identified but EBV+ cervical node(s) involvement
Tis carcinoma in situ
T1: T confined to NP, or extension to OP and/or nasal cavity w/o parapharyngeal involvement
T2: T w/ extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebreal muscles)
T3: T w/ infiltration of bony structures at skull base, C vertebra, pterygoid structures and/or paranasal sinuses
T4: T w/ intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle

Question 11

NPC TNM staging
Regional lymph nodes (N) and Distant Metastasis (M)

Answer 11

NX: Regional LN cannnot be assessed
N0: No regional LN mets
N1: Uniltaeral mets in cervical LN(s) and/or unilateral or bilateral mets in retropharyngeal LN(s), 6cm or smaller in greatest dimension, above the caudal border of cricoid cartilage
N2: Bilateral mets in cervical LN(s), 6cm or smaller in greatest dimension, above the caudal border of cricoid cartilage

M0: No distant mets
M1: Distant mets

Question 12

Prognostic factors

Answer 12

Advanced stage
Bulky or bilateral nodal disease
WHO type I histology, keratinizing SCC
Cranial nerve involvement
Intracranial extension
Male sex
Age > 40-50 years
Interrupted treatment
Pre and post treatment serum levels of EBV DNA

Question 13

Management

Answer 13

Speech pathology, audiology, dietetics, dental, social work, psychology, smoking cessation

Early stage – RT alone
Locally advanced – Chemotherapy and radiotherapy

Surgery is NOT the mainstay

Question 14

CT Simulation

Answer 14

Supine
Head neutral w/ neck straight. Shoulders down as far as possible
Immobilisation mask, neck support/vacuum bag, knee supports
IV contrast
Consider wire to delineate surgical scars or skin involvement
Consider bolus to surgical neck sites or superficial disease

3DCT, less than 3mm slice thickness, scan from vertex to 1cm below carina

Other imaging: staging CT, MRI, PET/CT to aid in tumour delineation

Question 15

RT Dose

Answer 15

IMRT/VMAT single phase

6MV 70Gy/35# = 2Gy/# to primary, gross LNs CTV

6MV 63Gy/35# = 1.8Gy/# to high risk primary and LNs CTV

6MV 56Gy/35# = 1.6Gy to low risk nodes CTV

Question 16

Target Volumes

Answer 16

GTVp = all gross primary disease per diagnostic imaging, clinical information and endoscopic findings
GTVn = gross positive LN

CTVp70 = GTVp + 5mm
CTVn70 = GTVn + 5mm (consider 10mm if ECE)

CTV63 = GTVp70 + 10mm (2mm if tumour close to critical OARs)
Include: whole nasopharynx; nasal cavity at least 5mm from choana, maxillary sinuses at least 5mm from posterior wall; posterior ethmoid sinus: include vomer; skull bases: include vomer, cover formania ovale, rothundum, lacerum & petrous tip; cavernous sinus: if cT3-4 (involved side only); pterygoid fossae, parapharyngeal spaces: full coverage; sphenoid snius inferior 1/2 if cT1-2, whole if cT3-4; clivus 1/3 if no invasion whole if invasion
CTVn63 = CTVn70 + 5mm

CTV56= cover at least one level below the the involved LN levels
bilateral retropharyngeal and retrostyloid level II, III, IV, V LN (IV & Vb optional in node negative)
Ipsilateral level Ib LN if: Ib LN invovled, gross involvement of ipsilateral submandibular gland, ipsilateral IIa LN with ECE, structures that drain to level Ib as 1st echelon site
Consider including ipsilateral level Ib if ipsilateral IIa w/ maximal nodal axial diameter >2cm

Question 17

Target Verification

Answer 17

kV planar OR MV planar OR CBCT
DAILY
match bone, check soft tissue alignment

monitor pt contour through weight loss or tumour shrinkage, regular CBCT or repeat CT to check dose distribution

adaptive planning becoming more common place

Question 18

Outcomes NPC

Answer 18

Stage I - 90% 5-year OS (7% pts)
II - 84% OS (41% pts)
III - 75% OS (25%)
IVA-B 58% OS (28% pts)

Question 19

Acute Toxicity

Answer 19

skin reaciton/dermatitis
mucositis
fatigue
xerostomia
odynophagia
dysgeusia
dysphagia
anorexia
alopecia

Question 20

Late Toxicity

Answer 20

skin changes
xerostomia
dental caries
dysphagia
dysgeusia
trismus
lymphoedema
carotid artherosclerosis
endocrine dysfunction
soft tissue fibrosis and necrosis
myelopathy
cranial nerve palsy
osteoradionecrosis of the jaw/skull base
second malignancy
alopecia
cataract formation and blindness
eustachian tube dysfunction
hearing loss/ototoxicity
brainstem injury

Question 21

Oligometastases

Answer 21

A state where a few metastases exist at first before the malignant cells acquire widespread metastatic potential

If SABR can be delivered during oligometastatic state, the treatment could change disease progression and prognosis in patients who would otherwise be treated palliatively
Possible with better imaging, improved planning, stereotactic techniques
Compared to surgery, the QOL benefit of SABR maybe greater because of reduced toxicity and morbidity

Question 22

SABR Lung and liver oligomets

Answer 22

SABR data suggests 2 year local control rates for lung and liver mets are 70-90%
Some studies included patients with stable metastatic disease outside the treated area
Toxicity rates are low with less than 5% grade 3 toxicity