1. Clinical Management of Head and Neck Cancer
Joseph Califano, M.D. Associate Professor
Department of Otolaryngology Head and Neck Surgery
Johns Hopkins Medical Institutions
Baltimore, Maryland
USA

2. Normal Oral Cavity

3. Tongue cancer

4. What is Head and Neck Cancer
Cancer of the nose, mouth, lips, gums, tongue, throat, voicebox and other sites
Affects 50,000 people in the US each year
Curable 50% of the time

5. What causes head and neck cancer?
1) Smoking
2) Smoking
3) Tobacco and smoking
4) Alcohol
5) sexually transmitted virus (HPV 16), Environmental, hereditary

6. How To Treat Head and Neck Cancer
Find it, usually late
-over 80% of tumors are late stage
Surgery (cut it out)
Radiation (burn it)
Chemotherapy (selective poisoning)
Combine the above

7. The Key to Curing Cancer
Stop all smoking (causes more cancer deaths than any other factor)
Wait 30 years (time required for relative risk of lung cancer to return to 1 after smoking cessation)
Ignore cancers due to:
Low level exposures
Multifactorial genetic predisposition
Stochastic phenomena

8. Other Ways to Cure Cancer
Prevention
– definition of more subtle genetic and environmental risk factors
Targeted Therapy
Molecular and otherwise
Screening
Molecular Screening for early disease
Genetic screening for inherited cancer susceptibility
Conventional screening for non-genetic risk factors
Pap smear, colonoscopy, etc

9. Premalignant changes

10. Advanced Oral Cavity Squamous Cell Carcinoma
Definition of advanced oral cavity carcinoma
Historical data regarding therapy
Surgical vs. radiotherapy
Surgical approaches
Combined modality therapy
Therapy for advanced neck metastasis
Future therapies
Case Studies

11. UICC/AJCC Staging for Advanced Oral Cavity Cancer
Big Tumor
T3-4, any N
T3 > 4cm
T4a invasion of adjacent structures, cortical bone, deep tongue muscles, maxillary sinus, skin
T4b “unresectable” invasion of masticator space, pterygoid plates, skull base, or carotid encasement

12. UICC/AJCC Staging for Advanced Oral Cavity Cancer
Small Tumor with neck metastasis
T1-T2, N2-3
Tumor < 4 cm with 2 or more cervical metastasis, one or more contralateral cervical metastases, or cervical metastasis > 3cm

13. Primary Surgery + Radiation Indicated for Advanced Oral Cavity Cancer
Low local control for primary radiotherapy for advanced oral cavity (30-40%) and poor survival (25%)
Increased local control with surgery + radiotherapy (60%) and improved survival (55%)
Zelefsky et al, Head Neck Nov-Dec;12(6):470-5
Local control significantly improved for locally advanced T3, T4 oral cancers using surgery + postoperative radiotherapy vs. primary RT
Fein et al. Head Neck Jul-Aug;16(4):358-65

14. Surgical Approaches Transoral Visor
Lip Split with or without mandibulotomy
Lip Split with Mandibulectomy

15. Surgical Approaches Transoral and Visor Approaches Lip Splitting
Cosmetic but may limit exposure
Lip Splitting
Modest cosmetic disadvantage with excellent posterior exposure for mandibulotomy
Paramedian or midline mandibulotomy
Avoidance of alveolar nerve

16. Surgical Approaches Caveats
Approach determined before incision and mandibulectomy or mandibulotomy
Accurate assessment of bone erosion, involvement of neural structures

17. Surgical Resection Advances
Reconstruction
Free Tissue Transfer
Mandibular reconstruction (fibula, scapula, etc.)
Soft tissue/tongue (radial forearm, rectus abdominus, lateral thigh, etc.)
Resection is rarely limited by size or extent of tumor

18. Contraindications to Resection
T4b: invasion of masticator space, pterygoid plates, skull base, or carotid encasement
Patient perception of quality of life

19. Primary Surgical Therapy Followed by Postoperative Chemotherapy and Radiation I: EORTC Bernier et al. NEJM 2004
Previously untreated SCC, all head and neck sites, n=167, 5 year median follow up
100 mg/m2 cisplatinum day 1, 22, 43 during postoperative irradiation or postoperative radiation alone

20. Primary Surgical Therapy Followed by Postoperative Chemotherapy and Radiation I: EORTC Bernier et al. NEJM 2004
pT3 or pT4, any N, except T3N0 of the larynx, with negative resection margins
pT1 or T2, N2 or N3
T1 or T2 and N0 or N1 with pathological extranodal spread, positive resection margins, perineural involvement, or vascular tumor embolism
Oral cavity or oropharyngeal tumors with involved lymph nodes at level IV or V

21. EORTC Bernier et al. NEJM 2004
The overall survival rate 53% vs 40%, p=0.02
Locoregional failure 18% vs. 31%, p=0.007
Severe (grade 3 or higher) adverse effects 41% vs. 21% p=0.001

22. Postoperative Chemoradiation for Advanced Head and Neck Cancer
Clear advantage in locoregional control
Survival advantage
Difference in enrollment criteria may suggest survival advantage for locally aggressive tumors without significant nodal disease

23. New Trials : Molecular Targeted Therapy, EGF Inhibitors Bonner, et al, NEJM, 2005
Radiation only
Cetuximab+RT
p-value
Patients randomized
213
211
Median survival - Two-year survival - Three-year survival
28 mo 55% 44%
54 mo 62% 57%
0.02 (log-rank test)
Grade 3/4 mucositis
52%
55%
0.50 (Fisher's exact)
Grade 3/4 infusion reaction - 3%
0.01 (Fisher's exact)
Grade 3/4 skin reaction
18%
34%
(Fisher's exact)

24. Head and Neck Cancer
Multimodality therapy for all but very early stages: surgery, radiation with adjuvant chemotherapy
Significant morbidity due to therapy is possible: cosmesis, decreased saliva, swallowing dysfunction, social dysfunction
Novel molecular directed therapies incorporated into next generation trials

25. Case Presentation I
73 Y edentulous farmer with a right gingival lesion, otherwise asymptomatic
120 PY smoking history, currently smoking
Past Medical History: diabetes, coronary artery disease, myocardial infarction x 2, carotid endarterectomy, peripheral vascular disease, and hypertension, renal insufficiency
Exam shows a right lower gingival mass, 2.5 cm squamous cell carcinoma

26. Case Presentation I
CT demonstrates R mandibular invasion

27. Case Presentation I PET/CT demonstrates no evidence of metastasis
MR angiography demonstrates severe peripheral vascular disease in bilateral lower extremities

28. Case Presentation I Treatment Options
T4N0M0 squamous cell carcinoma of the right alveolus
Right Mandibulectomy (via visor or lip split), right neck dissection, fibula free flap, tracheotomy, postoperative radiation and chemotherapy
Transoral mandiblectomy, postoperative radiation to primary site and ipsilateral neck

29. Case Presentation I Therapy
Resection from paramedian to angle of mandible to encompass alveolar nerve

30. Case Presentation I Outcome
Oral alimentation at 5 days postop
External beam radiation to primary and ipsilateral neck onset 3 weeks post surgery
Acceptable cosmetic appearance
NED at 30 mo, died shortly after from MI

31. Case Presentation II
 A 41-year-old traffic manager with a left lateral tongue cancer.
2 years of leukoplakia with documented high grade dysplasia prior excisions x 3
Recent 1.5 cm lesion excised, demonstrated squamous cell carcinoma, with a positive deep margin
No history of smoking or ethanol intake

32. Case Presentation II
 Exam is unremarkable except for a small lesion on his left lateral/vental tongue

33. Case Presentation II PET/CT results
No uptake in the tongue
Moderate intensity uptake in a level II 9mm lymph node and a 7 mm level posterior IV lymph node
No evidence distant metastasis
Chromosomal breakage study negative

34. Case Presentation II Staging
T1N0M0 SCC left lateral tongue
T1N2bM0 SCC left lateral tongue (by PET)

35. Case Presentation II Treatment
Left partial glossectomy, transoral
Left neck dissection
Level I-V, sparing IJ, SCM, CN XI
Level V included to ensure excision of posterior level IV node found on PET

36. Case Presentation II Surgical Results
1.5 cm SCC in glossectomy specimen with negative margins
5/35 lymph nodes + SCC in neck dissection
2/5 level I lymph nodes + SCC
3/7 level II lymph node + SCC
pT1N2bM0, Stage IV

37. Case Presentation II Treatment
Left partial glossectomy
Left neck dissection levels I-V
Postoperative EBRT with concomitant cisplatinum days 1, 22,43