1. Kazumi Chino, M.D. Radiation Oncology
Head and Neck Cancers
Kazumi Chino, M.D.
Radiation Oncology

2. 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

3. 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

4. Histology
90% of H&N cancers are squamous cell carcinomas arising from the mucosal surfaces
Salivary gland tumors are typically adenocarcinomas

5. Anatomy

6. Anatomy: Nasopharynx Eustachian tube Torus Tubaris
Fossa of Rosenmuller

7. Anatomy: Oro/Hypopharynx
From the uvula to hyoid bone
Palatine tonsils, tonsillar pillars
Base of tongue
Epiglottis and vallecula

8. Anatomy: Laryngopharynx
From the epiglottis to the inferior cricoid cartilage
Vocal cords, piriform sinuses, arytenoid cartilage and aryepiglottic folds

9. Anatomy: Laryngopharynx

10. Cervical Lymph Nodes

11. Presentation: Nasopharynx

12. 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

13. Staging: Nasopharynx Primary 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

14. Regional lymph nodes (N)
Staging: Nasopharynx
Regional 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

15. Staging: Nasopharynx Stage T N M Tis N0 M0 I T1 II N1 T2 III N2 T3 IVA
Tis N0 M0 I T1 II N1 T2
III N2 T3
IVA T4
IVB
T Any N3
IVC
N Any M1

16. 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

17. Nasopharynx NCCN Guidelines

18. Recurrent or Persistent Dz

19. 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

20. Presentation: Oropharynx
Globus sensation
Difficultly swallowing
Slurred speech
Pain in throat or ear
Neck mass

21. Staging: Oropharynx Primary 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

22. Staging: Hypopharynx Hypopharynx: TX Primary tumor cannot be assessed
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

23. Staging: Oro/Hypopharynx
Regional 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

24. Staging: Oro/Hypopharynx
Stage T N M
Tis N0 M0 I T1 II T2
III T3 N1
IVA
T4a N2
IVB
T Any N3
T4b
N Any
IVC M1

25. Tx & Prognosis: Oro/Hypopharynx
RTOG 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 and EORTC studies on locally advanced H&N Ca’s (excluding NPX) showed improved LC with concomitant boost with RT

26. Tx & Prognosis: Oro/Hypopharynx
GORTEC (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%).

27. Tx & Prognosis: Oro/Hypopharnx
EORTC 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
Chemo­RT improved 3/5 yr DFS (41/36 vs 59/47%) OS (49/40 vs 65/53%) 5yr LRC (69 vs 82%)
RTOG 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

28. NCCN Guidelines Orophyarnx

29. NCCN Guidelines Oropharyx

30. NCCN Guidelines Oropharynx

31. NCCN Guidelines Hypophyarnx

32. NCCN Guidelines Hypophyarnx

33. NCCN Guidelines Hypophyarnx

34. NCCN Guidelines Hypopharynx

35. Presentation: Larynx Hoarse voice Stridor Cough, hx of GERD
Trouble swallowing
For glottic tumors
T1-2 5% LN involvement
T3-4 20% LN involvement

36. Staging: Larynx Supraglottis: 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

37. Staging: Larynx Glottis: 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

38. Staging: Larynx Subglottis: 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

39. Regional lymph nodes (N)
Staging: Larynx
Regional 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

40. Staging: Larynx Stage T N M Tis N0 M0 I T1 II T2 III T3 N1 IVA T4a N2
Tis N0 M0 I T1 II T2
III T3 N1
IVA
T4a N2
IVB
T Any N3
T4b
N Any
IVC M1

41. 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)

42. Tx & Prognosis: Larynx
RTOG 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 and EORTC for post-op chemoRT included laryngeal tumors
Benefit for > 2LN, T3-4, + ECE, + margins

43. NCCN Guidelines Supraglottic Larynx

44. NCCN Guidelines Supraglottic Larynx

45. NCCN Guidelines Supraglottic Larynx

46. NCCN Guidelines Supraglottic Larynx

47. NCCN Guidelines Supraglottic Larynx

48. NCCN Guidelines Supraglottic Larynx

49. NCCN Guidelines Glottic Larynx

50. NCCN Guidelines Glottic Larynx

51. NCCN Guidelines Glottic Larynx

52. NCCN Guidelines Glottic Larynx

53. NCCN Guidelines Glottic Larynx

54. 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

55. IMRT

56. 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)