Head and Neck Cancers

Kazumi Chino, M.D.Radiation Oncology

Epidemiology

• 52,000 people diagnosed in the US annually• 3% of all cancers in the US• Men are twice as likely as women to develop a

head and neck cancer• Dx is most common after age 50

Risk Factors

• Tobacco – approx. 85% of H&N Ca related to tobacco

• Alcohol• HPV in oropharyngeal cancers• Epstein-Barr virus in nasopharyngeal cancers• Poor dental/oral hygiene • Poor nutrition – vit A and B deficiency• GERD in pharyngeal cancers

Histology

• 90% of H&N cancers are squamous cell carcinomas arising from the mucosal surfaces

• Salivary gland tumors are typically adenocarcinomas

Anatomy

Anatomy: Nasopharynx

• Eustachian tube• Torus Tubaris• Fossa of Rosenmuller

Anatomy: Oro/Hypopharynx

• From the uvula to hyoid bone• Palatine tonsils, tonsillar pillars• Base of tongue• Epiglottis and vallecula

Anatomy: Laryngopharynx

• From the epiglottis to the inferior cricoid cartilage

• Vocal cords, piriform sinuses, arytenoid cartilage and aryepiglottic folds

Anatomy: Laryngopharynx

Cervical Lymph Nodes

Presentation: Nasopharynx

Nasopharyngeal Cancer Sx’s

• Nasal obstruction, bleeding, discharge• Hearing problems if eustachian tube

obstructed, otitis media• Headaches• Cranial nerve palsy with involvement of the

base of skull• Neck mass, particularly at the mastoid tip

Staging: NasopharynxPrimary tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor confined to the nasopharynx, or tumor extends to oropharynx and/or nasal cavity without parapharyngeal extension (eg, without posterolateral infiltration of tumor)

T2 Tumor with parapharyngeal extension (posterolateral infiltration of tumor)

T3 Tumor involves bony structures of skull base and/or paranasal sinuses

T4 Tumor with intracranial extension and/or involvement of cranial nerves, hypopharynx, or orbit, or with extension to the infratemporal fossa/masticator space

Staging: NasopharynxRegional lymph nodes (N)

NX Regional nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Unilateral metastasis in cervical lymph nodes ≤6cm in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral retropharyngeal lymph nodes ≤6 cm in greatest dimension (midline nodes are considered ipsilateral nodes)

N2 Bilateral metastasis in cervical lymph nodes ≤6cm in greatest dimension, above the supraclavicular fossa (midline nodes are considered ipsilateral nodes)

N3 Metastasis in a lymph node >6cm and/or to the supraclavicular fossa (midline nodes are considered ipsilateral nodes)

N3a >6cm in dimension

N3b Extension to the supraclavicular fossa

Staging: NasopharynxStage T N M

0 Tis N0 M0

I T1 N0 M0

II T1 N1 M0

T2 N0 M0

T2 N1 M0

III T1 N2 M0

T2 N2 M0

T3 N0 M0

T3 N1 M0

T3 N2 M0

IVA T4 N0 M0

T4 N1 M0

T4 N2 M0

IVB T Any N3 M0

IVC T Any N Any M1

Tx & Prognosis: Nasopharynx

• Stage I/II tx’d RT alone: local control rates at 5 years for T1= 93%, T2 = 79%, T3 = 68% and T4 = 53%

• Intergroup 0099 compared RT alone vs cisplatin 100mg/ms day 1, 22, 43 + RT for Stage III/IV

• 3 yr progression free survival was 24% vs 69% in favor of concurrent chemo/RT

• 3 yr overall survival was 47% compared to 78% in favor or concurrent chemo/RT

– Similar trial JCO 2005 showed OS 65% 80% with chemo

Nasopharynx NCCN Guidelines

Recurrent or Persistent Dz

Prognosis: Nasopharnx

• Keratinizing squamous cell carcinoma has a higher risk of local recurrence after tx than non-keratinizing SCCa or undifferentiated

• High EBV DNA titers after tx are associated with an increased risk of recurrence

Presentation: Oropharynx

• Globus sensation• Difficultly swallowing• Slurred speech• Pain in throat or ear• Neck mass

Staging: OropharynxPrimary tumor (T)

Oropharynx:

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor ≤2cm in greatest dimension

T2 Tumor >2cm but ≤4cm in greatest dimension

T3 Tumor >4cm in greatest dimension or extension to lingual surface of the epiglottis

T4a •Moderately advanced, local disease Tumor invades the larynx, deep/extrinsic muscle of the tongue, medial pterygoid, hard palate, or mandible

T4b •Very advanced, local disease Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases the carotid artery

Staging: HypopharynxHypopharynx:

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor limited to 1 subsite of the hypopharynx and/or ≤2cm in greatest dimension

T2 Tumor invades more than 1 subsite of the hypopharynx or an adjacent site or measures >2cm but ≤4cm in greatest dimension, without fixation of the hemilarynx

T3 Tumor >4cm in greatest dimension or with fixation of the hemilarynx or extension to the esophagus

T4a •Moderately advanced, local disease Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus, or central compartment soft tissue (including prelaryngeal strap muscles and subcutaneous fat)

T4b •Very advanced, local disease Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

Staging: Oro/HypopharynxRegional lymph nodes (N)

NX Regional nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in a single ipsilateral lymph node ≤3cm in greatest dimension

N2 Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension; or in multiple ipsilateral lymph nodes, none >6cm in greatest dimension; or in bilateral or contralateral lymph nodes, none >6cm in greatest dimension

N2a Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension

N2b Metastasis in multiple ipsilateral lymph nodes, none >6cm in greatest dimension

N2c Metastasis in bilateral or contralateral lymph nodes, none >6cm in greatest dimension

N3 Metastasis in a lymph node >6cm in greatest dimension

Staging: Oro/HypopharynxStage T N M

0 Tis N0 M0

I T1 N0 M0

II T2 N0 M0

III T3 N0 M0

T1 N1 M0

T2 N1 M0

T3 N1 M0

IVA T4a N0 M0

T4a N1 M0

T1 N2 M0

T2 N2 M0

T3 N2 M0

IVB T Any N3 M0

T4b N Any M0

IVC T Any N Any M1

Tx & Prognosis: Oro/Hypopharynx

• RTOG 73-03 randomized advanced oropharyngeal tumors to surgery with or without post-op RT– Post-op RT better LRC (48 vs 65%) & OS (26% vs

38%)

• RTOG 90-03 and EORTC studies on locally advanced H&N Ca’s (excluding NPX) showed improved LC with concomitant boost with RT

Tx & Prognosis: Oro/Hypopharynx• GORTEC 94-01 (JCO 2004) for Stage III/IV showed

benefit of 3 cycles carboplatin/5-FU + RT vs RT alone– Chemo-RT improved LC (25 vs 48%), DFS (15 vs 27%)

OS (16 vs 23%) • Intergroup Trial (JCO 2003) and Duke trials (NEJM

1998) showed similar benefit for cisplatin +/- 5FU• Bonner (NEJM 2006) showed benefit of

cetuximab with RT over RT alone– Cetuximab increased 3 yr LRC (34 vs 47%) OS (45 vs

55%).

Tx & Prognosis: Oro/Hypopharnx

• EORTC 22931 Stage III/IV operable H&N Ca’s (excluding NPX) pT3-4 N0/+ Tl -2N2-3, or Tl-2 N0-1 with ECE, + margin, or PNI randomized to post-op cisplatin 100mg/ms days 1, 11, 43 + RT vs RT alone– Chemo RT improved 3/5 yr DFS (41/36 vs 59/47%) OS

(49/40 vs 65/53%) 5yr LRC (69 vs 82%)• RTOG 95-01 operable H&N cancer who had > 2 LN,

ECE, or + margin randomized to RT vs RT + cisplatin– Chemo-RT improved 2yr DFS (43 vs 54%), LRC (72 vs 82%)

& trend for improved OS (57 vs 63%) – No difference in distant mets for either study

NCCN Guidelines Orophyarnx

NCCN Guidelines Oropharyx

NCCN Guidelines Oropharynx

NCCN Guidelines Hypophyarnx

NCCN Guidelines Hypophyarnx

NCCN Guidelines Hypophyarnx

NCCN Guidelines Hypopharynx

Presentation: Larynx

• Hoarse voice• Stridor• Cough, hx of GERD• Trouble swallowing• For glottic tumors– T1-2 5% LN involvement– T3-4 20% LN involvement

Staging: LarynxSupraglottis:

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor limited to 1 subsite of the supraglottis, with normal vocal cord mobility

T2 Tumor invades mucosa of more than 1 adjacent subsite of the supraglottis or glottis or region outside the supraglottis (eg, mucosa of base of the tongue, vallecula, medial wall of piriform sinus), without fixation of the larynx

T3 Tumor limited to the larynx, with vocal cord fixation, and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of the thyroid cartilage

T4a •Moderately advanced, local disease Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)

T4b •Very advanced local disease Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging: LarynxGlottis:

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure), with normal mobility

T1a Tumor limited to 1 vocal cord

T1b Tumor involves both vocal cords

T2 Tumor extends to the supraglottis and/or subglottis, and/or with impaired vocal cord mobility

T3 Tumor limited to the larynx with vocal cord fixation and/or invasion of the paraglottic space and/or inner cortex of the thyroid cartilage

T4a •Moderately advanced, local disease Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)

T4b •Very advanced, local disease Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging: LarynxSubglottis:

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor limited to the subglottis

T2 Tumor extends to vocal cord(s), with normal or impaired mobility

T3 Tumor limited to the larynx, with vocal cord fixation

T4a •Moderately advanced, local disease Tumor invades cricoids or thyroid cartilage and/or invades tissues beyond the larynx (eg, trachea, soft tissues of the neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)

T4b •Very advanced, local disease Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Staging: LarynxRegional lymph nodes (N)

NX Regional nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in a single ipsilateral lymph node ≤3cm in greatest dimension

N2 Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension; or in multiple ipsilateral lymph nodes, none >6cm in greatest dimension; or in bilateral or contralateral lymph nodes, none >6cm in greatest dimension

N2a Metastasis in a single ipsilateral lymph node >3cm but ≤6cm in greatest dimension

N2b Metastasis in multiple ipsilateral lymph nodes, none >6cm in greatest dimension

N2c Metastasis in bilateral or contralateral lymph nodes, none >6cm in greatest dimension

N3 Metastasis in a lymph node >6cm in greatest dimension

Staging: LarynxStage T N M

0 Tis N0 M0

I T1 N0 M0

II T2 N0 M0

III T3 N0 M0

T1 N1 M0

T2 N1 M0

T3 N1 M0

IVA T4a N0 M0

T4a N1 M0

T1 N2 M0

T2 N2 M0

T3 N2 M0

T4a N2 M0

IVB T Any N3 M0

T4b N Any M0

IVC T Any N Any M1

Tx & Prognosis: Larynx

• Stage I tx’d with RT with salvage surgery if needed: 5 yr OS 80-98%

• Stage II tx’d with RT with salvage surgery: 5 yr OS 68-93%

• VA Laryngeal Trial: Stage III/IV laryngeal tumors randomized to surgery + post-op RT vs induction chemo with cisplatin/5FU followed by RT– 2 yr OS was 68% for both groups– Laryngeal preservation rate was 64% (36% in the

chemo/RT group required salvage laryngectomy)

Tx & Prognosis: Larynx

• RTOG 91-11 compared RT alone vs sequential chemo/RT vs concurrent chemo + RT – LRC 56% RT alone, 61% sequential, 78% concurrent– Decreased distant mets with chemo

• Bonner trial for cetuximab included laryngeal tumors as well

• RTOG 95-01 and EORTC 22931 for post-op chemoRT included laryngeal tumors– Benefit for > 2LN, T3-4, + ECE, + margins

NCCN Guidelines Supraglottic Larynx

NCCN Guidelines Supraglottic Larynx

NCCN Guidelines Supraglottic Larynx

NCCN Guidelines Supraglottic Larynx

NCCN Guidelines Supraglottic Larynx

NCCN Guidelines Supraglottic Larynx

NCCN Guidelines Glottic Larynx

NCCN Guidelines Glottic Larynx

NCCN Guidelines Glottic Larynx

NCCN Guidelines Glottic Larynx

NCCN Guidelines Glottic Larynx

Overview of Treatment• Surgery: First choice when possible, but often limited by

disfigurement and preservation of organ function such as speech and swallowing

• Radiation: Most head and neck cancer is sensitive to radiation while preserving organ function– Side effects can be severe; Mucositis, permanent xerostomia,

osteoradionecrosis of the mandible, altered taste, weight loss, and tooth decay

• Chemotherapy: Can have dramatic response to treatment, but is often not a durable response– Side effects can also be severe; decreased blood counts,

anemia, infections, weight loss, nausea, vomiting, and hair loss– Newer targeted therapies have lower side effects

IMRT

Recent Advances and Future Directions

• PET imaging may allow detection of occult LN metastasis negating the need for post-RT neck dissection

• Sentinel LN bx in the neck is showing use especially in oral cancers

• IMRT improves SE’s from radiation therapy• Taxanes are showing some promise with cisplatin• Targeted therapies: phase III trials with zalutumumab

and panitumumab, sorafenib (an inhibitor of the intracellular domain of VEGFR, PDGFR and c-Kit) and afatinib (an irreversible inhibitor of pan-HER tyrosine kinase)