Block 1B - H+N Cancers (HPC, Salivary Gland, Oral Cavity)

ONCOL 310 - Clinical Oncology II. University of Alberta

What vertebral levels is the hypopharynx located

between C3-C6 (oropharynx → esophageal inlet)

what is the superior, inferior, anterior, posterior, and lateral borders of the hypopharynx

superior = hyoid bone

inferior = upper esophageal sphincter or inf. cricoid cartilage

anterior = larynx

posterior = retropharyngeal space (prevertebral fascia)

lateral = piriform sinus

what are the three anatomical regions of the hypopharynx?

• posterior pharyngeal wall

• pirifrom sinus

• postcricoid

what two cranial nerves are located in the hypopharynx

CN IX (glossopharyngeal)

CN X (vagus)

Hypopharynx Carcinoma (HPC) epidemiology

• how many cases in canada

• M:F

• age range

• 165 cases in canada (only make up 7% of all H+N cancers)

• M:F = 3:1

• Age range: 55-70 years

5 etiological factors of HPC

• excessive alcohol consumption + smoking

  • upper HPC

• iron + Vit C deficiencies

  • lower (post cricoid) HPC

• previous RT

• Plummer-Vinson syndrome

  • long-term iron def.

• HPV (unclear)

describe the natural history of HPC

HPC arises from the epithelial layer of the mucous membrane. they are aggressive and often have early metastasis (most pts have cervical LN presentation and 50% have a neck mass)

what percent of patients with HPC present with distant mets? and what percent of patients with HPC have synchronous second primary tumors

33%

• distant mets more common on HPC than any other H+N cancer

4-15% present with second primary tumors

why is HPC often asymptomatic

because there are many recesses and spaces in the larynx

clinical presentation of HPC

dysphagia, odynophagia, globus sensation, otalgia, neck mass, weight loss

how can large HPC tumors present

airway obstruction, hoarseness, or aspiration

describe the physical exam to assist in diagnosing HPC

palpation, direct or indirect laryngoscopy, fiberoptic endoscopy, CN function

what blood work can be done to diagnose HPC

CBC, liver function tests, blood chemistry

what is the main imaging modality to diagnose HPC

contrast enhanced CT and MRI to determine the extent of the primary tumor

• CXR may also be used to evaluate lung involvement

what would be the purpose of using an FDG-PET or PET-CT to diagnose HPC

FDG-PET is used to diagnose occult, residual, and recurrent tumors

PET-CT is used for high specificity post treatment

what are the three main prognostic indicators of HPC

• size of primary tumor

• extent of local spread of primary

• extent of involvement of regional LNs (mets)

what hypopharynx region has the highest incidence of HPC, what area has the lowest?

highest: piriform sinus

lowest: post-cricoid

what are three reasons why HPC has the lowest survival rate of H+N cancers

• poorly differentiated and asymptomatic presentation = advanced disease

• emergence of secondary primary

• development of distant mets

what are the three routes of spread of HPC

• local spread

  • to subsites of hypopharynx, larynx, and cartilage

• lymphatic spread

• hematogenous spread

what is the most common hematogenous metastatic site of HPC

lung

what is HPC’s mechanism of skip metastasis

the tumor can spread within mucosa beneath the epithelium and it will resurface at various locations

describe the 2 paths of lymphatic spread of HPC from the piriform sinus to the supraclav nodes

jugulodigastric → middle deep cervical chain or jugulo-omohyoid or paratracheal → lower deep cervical → supraclavicular

retropharyngeal → superior deep cervical →jugulodiagastric → middle deep cervical —> posterior cervical chain —> supra clav

describe the path of lymphatic spread of HPC from the posterior pharyngeal wall to the supraclav nodes

retropharyngeal → superior deep cervical →jugulodiagastric → middle deep cervical —> posterior cervical chain —> supra clav

what percent of HPC tumors are squamous cell carcinoma

95% of tumors

what percent of HPC are keratinizing? non-keratinizing?

60% keratinizing

33% non-keratinizing

Stage I HPC

Stage II HPC

Stage III HPC

Stage IV HPC

What three surgeries can be used stage I HPC

• partialy laryngectomy or pharyngectomy

• total laryngectomy

• laryngopharyngectomy

  • includes larynx, vocal cord and pharynx

  • typically used for T3 or T4 disease

what is the primary treatment for stage I and II HPC

ChemoRT with cisplatin

• to spare larynx and maintain speech

• may also irradiate cervical lymph nodes

when would RT be used alone in early stage HPC

if patient has comorbidities or early piriform sinus lesions

when would PORT be used for early stage HPC

if there is a high risk of recurrence

What are are two primary treatments for Stage I LN involved HPC

primary: RT bilateralal neck to include lateral cervical and retropharyngeal LN

also can do laryngopharyngectomy + neck dissection (loss of speech occurs)

what are the two primary treatments for Stage II HPC

surgery + PORT

RT bilateral neck (like stage I) with neoadjuvent chemotherapy

what are the two mainstay treatments of early stage HPC

surgery + RT are mainstays

• chemotherapy used more so for advanced disease

• each treatment plan is individualized

what is the main treatment of stage III HPC

Surgery + PORT (3-4 weeks after resection)

• surgical reconstructions need to be completed

what three types of surgical reconstructions can be done

• free flap transfer

• free jejunal autograft

• pec major myocutaenous flap

what neoadjuvent/adjuvent combined chemo can be used for stage III HPC

cisplatin + 5FU

what is the main treatment for stage IV resectable HPC

Laryngopharyngectomy + adjuvent chemoRT

or surgery ± adjuvent RT

what is the main treatment for Stage IV unresectable HPC

chemoRT with cisplatin or cetuximab (targeted therapy)

what potential treatment options can be used for recurrent HPC

surgery (if RT fails), chemotherapy (for mets), immunotherapy, salvage surgery

what is the superior, inferior, anterior, and posterior borders for HPC radiation

sup: inf border of mandible and mastoid process to base of skull

inf: inf of cricoid cartilage to encompass extent of tumor + 1.5-2.0 cm

ant: anterior to thyroid cartilage with a margin around tumor extension

post: post to the spinous processes with a margin around all nodal disease

how many phases did conventional RT treatment to HPC have

2 or three phases

• this is required to irradiatie the tumor and nodes to a radical dose while keeping spinal cord dose within tolerance

what should the fields cover in conventional HPC RT

should cover from the skull base to the cricoid cartilage with an anterior split neck field to treat LN below cricoid

after what dose should the fields be reduced posteriorly to avoid the spinal cord? what can be used to treat the level V nodes instead?

after 44-45 Gy

use electrons to treat these nodes instead

Modern HPC RT treatment

• energy

• technique

• D/F for high risk

• D/F for intermediate risk

• D/F for low risk

6 MV IMRT or VMAT

• 70 Gy / 33 f to high risk CTV

• 59.4 Gy / 33 f to intermediate risk

• 50-54 Gy / 33 for elective risk

describe the set-up for modern HPC RT treatment

AIO board with a 5 point shell, neutral head rest, arms by sides, knee and ankle rest

what D/F is used for Piriform Sinus HPC definitive RT ? what about for surgery + PORT

Definitive: 66-70 F / 30-33 fractions

PORT: 60/30 fractions

what D/F is used for pharyngeal wall definitive HPC RT? what about for surgery + PORT?

Definitive: 66-70 F / 30-33 fractions

PORT: 60/30 fractions

• same as for piriform sinus

acute side effects of HPC RT

erythema, dry and moist desquamation, xerostomai, mucositis, dysphagia, infection, cavities

chronic side effects of HPC RT

telangietasia, hypo/hyperpigmentation, fibrosis xerostomia, trismus, osteonecrosis, hypothyroidism

what is the new standard care for recurrent or metastatic H&N SCC?

immunotherapy

• first line therapies for H+N cancers should now include immunotherapy with pembrolizumab

what is the 5 year overal survival of HPC

25-40%

• poorest survival rate of all H+N cancers

what are the three major salivary glands?

sublingual, submandibular, and parotid gland

• there are also minor salivary glands beneath the mucosa of the buccal cavity

what are the 4 main ducts connected to the salivary glands

Stensen’s duct, wharton’s duct, Bartholin’s Duct, and Duct of Rivinus

what three cranial nerves are relevant for treating the salivary glands

CN III: oculomotor

CN V: trigeminal

CN VII: facial nerve

what arteries supply blood to the major salivary glands

maxillary, transverse facial, lingual, and facial arteries

• branches of the external carotid artery

Salivary gland cancer epidemiology

• what percent are benign

• where do 80% of tumors originate

• how rare are these cancers?

• M:F

• typical age range

• 65% benign

• originate in the parotid gland

• very rare: only make up 0.5% of all malignancies

• M:F = 1.1:1.6!!!

• > 50 years

what percent of _____ are malignant

• parotid gland

• submandibular gland

• sublingual gland

Parotid = 20-25%

submandibular = 35-40%

sublingual gland = > 90%

Although the etiology of salivary gland cancers is mostly unknown, what are three potential etiological factors?

• Radiation to the head and neck

• HIV infection —> lymphoma

• skin cancer spreading to salivary gland lymph nodes

describe the natural history of salivary gland cancers

the tumor starts as an asymptomatic malignant mass lasting on average 3-6 months before it begins to spread via local invasion to skin or cranial nerves

• high grade tumors can have up to 44% cervical LN involvement

what are the most common sites of mets for salivary gland tumors and what is is the route of spread?

lungs and bone are most common, and sometimes liver

• travels hematogenously

what is the typical clinical presentation of salivary gland cancers?

typically is a painless non-ulcerative mass in front of ear or in neck

• facial nerve paralysis, pain, ulceration, dysphagia, and difficulty articulating speech may occur as well

what is the most cost effective and readily available imaging modality for diagnosis of salivary gland tumors?

ultrasound

• can also due an aspiration along side the U/S

what 3 other imaging modalities can be used to diagnose salivary gland tumors

CT with contrast

Contrast enhanced MRI for soft tissue and neural involvement

PET-CT for high grade tumors, locoregional recurrence and metastatic disease

what type of biopsy is typically used to diagnose salivary gland tumors

FNAB

what are some favourable prognostic indicators of salivary gland cancers

tumor is in major salivary gland (parotid or submandibular)

small size, low grade, negative margins, node negative

• most early stage low grade tumors are curably be adequate surgical resection alone

what makes salivary gland cancers interesting pathologically

they are the most heterogenous group of tumors in any tissue of the body

what is the most common histology for salivary gland tumors

mucoepidermoid carcinoma

• most in parotid gland, 35% of malignant salivary gland tumors

what is the most common histology for salivary gland tumors in minor salivary glands

adenoid cystic cancer

what are some other examples of histological subtypes of salivary gland cancer

adenocarcinomas, hemangiomas, lipoma, sarcomas, lymphomas

what is the most common benign tumor subtype of parotid gland cancers

pleomorphic adenoma

Salivary Gland TNM Staging - T

as T increases, so does the size of tumor and the extent of invasion

• extraparenchymal extension = evidence of invasion of soft tissues or nerve

Salivary Gland TNM Staging - N

Salivary Gland TNM Staging - M

what are the three grades of salivary gland cancer

grade 1 = low grade: resembles normal SG cells. good prognosis

grade 2 = intermediate grade : moderately differentiated

grade 3 = high grade: does not resembel SG cells, grows ± spread quickly, poor prognosis

What is the cornerstone treatment of salivary gland tumors

surgery

• complete excision with preservation of neural structures is the goal

when is adjuvent RT used for treatment of salivary gland tumors

for high grade tumors at risk of locoregional failure

Describe the treatment of T1-2, N0 low grade parotid cancer

parotidectomy w/o nerve resection and neck node dissection

describe the treatment of T1-2 N0, high grade parotid cancer

parotidectomy ± nerve resection ± neck node dissection + adjuvent RT

describe the treatment of T3, N0 parotid cancer

extensive parotidectomy ± nerve resection ± neck node dissection + adjuvent RT

describe the treatment of T4 parotid cancer

extensive parotidectomy + nerve resection + neck node dissection + radiation therapy

when would adjuvent RT potentially be added to low grade parotid gland cancers

if there are positive margins or spillage or perineural invasion

how does the T3/T4 surgical treatment change for parotid gland vs salivary gland

parotid = total parotidectomy ± LN dissection

salivary = surgical resection ± LN dissection

if there is complete resection of the salivary gland tumor, what is then done?

typically only surveillance or chemoRT if the histology is adenocystic or there are adverse features (ECE, neural invasion, LN mets, etc)

if there is incomplete resection of the salivary gland tumor, what is then done

another surgical resection if possible or chemoRT

what treatment is done for unresectable T4a and T4b salivary gland tumors?

definitive RT or chemoRT

what are the major complication of total parotidectomy? what are some other complications

facial nerve paresis

• scarring, facial nerve damage, morbidity

what are two major complications of neck node dissections for salivary gland tumors

cervical lymphadenopathy nd facial nerve paralysis

what combination chemo can be used for treating salivary gland tumors

cisplatin/carbo + 5FU

70-80% of salivary gland tumors arise in what gland?

the parotid gland

what is the typical spread of parotid gland tumors

painless local spread infiltrating the whole gland

what cranial nerve has the biggest risk of invasion via a parotid gland tumor?

the facial nerve (CN VII)

motor, sensory, and parasympathetic functions of CN VII (facial nerve)

motor = facial expression

sensory = taste to anterior 2/3 of tongue

parasympathetic = innervates lacrimal, submandibular, and sublingual glands

clinical presentation of a parotid gland tumor invading the facial nerve

xerostomia, lagophtalmos (loss of ability to close eye completely), ageusia (loss of taste)

what are local symptoms of parotid gland tumors

swelling in parotid area, facial palsy, local pain, tenderness, rapid growth

what do the majority of parotid gland cancer patients present with

asymptomatic parotid mass

what are late/advanced stage symptoms of parotid gland tumors

trismus, severe pain, growth into parapharyngeal space encroaching on other cranial nerves

• this is very rare

what is the best predictor of nodal metastasis of parotid gland tumors

facial nerve involvement

• in addition to tumor grade