Transcript Clinical Management of Head and Neck Cancer

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
Normal Oral Cavity
Tongue cancer
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
What causes head and neck
cancer?
1) Smoking
2) Smoking
3) Tobacco and smoking
4) Alcohol
5) sexually transmitted virus (HPV 16),
Environmental, hereditary
How To Treat Head and Neck
Cancer
• Find it, usually late
-over 80% of tumors are late stage
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Surgery (cut it out)
Radiation (burn it)
Chemotherapy (selective poisoning)
Combine the above
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
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
Premalignant changes
Advanced Oral Cavity Squamous
Cell Carcinoma
• Definition of advanced oral cavity carcinoma
• Historical data regarding therapy
– Surgical vs. radiotherapy
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Surgical approaches
Combined modality therapy
Therapy for advanced neck metastasis
Future therapies
Case Studies
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
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
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. 1990 Nov-Dec;12(6):470-5
• Local control significantly improved for locally
advanced T3, T4 oral cancers using surgery +
postoperative radiotherapy vs. primary RT
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Fein et al. Head Neck. 1994 Jul-Aug;16(4):358-65
Surgical Approaches
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Transoral
Visor
Lip Split with or without mandibulotomy
Lip Split with Mandibulectomy
Surgical Approaches
• Transoral and Visor Approaches
– Cosmetic but may limit exposure
• Lip Splitting
– Modest cosmetic disadvantage with excellent
posterior exposure for mandibulotomy
• Paramedian or midline mandibulotomy
– Avoidance of alveolar nerve
Surgical Approaches
Caveats
• Approach determined before incision and
mandibulectomy or mandibulotomy
– Accurate assessment of bone erosion, involvement of neural
structures
Surgical Resection Advances
• Reconstruction
• 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
Contraindications to Resection
T4b: invasion of masticator space,
pterygoid plates, skull base, or
carotid encasement
Patient perception of
quality of life
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
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
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
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
New Trials : Molecular Targeted
Therapy, EGF Inhibitors
Bonner, et al, NEJM, 2005
Patients randomized
Median survival
- Two-year survival
- Three-year survival
Grade 3/4 mucositis
Grade 3/4 infusion
reaction
Grade 3/4 skin reaction
Radiation only
Cetuximab+RT
p-value
213
211
28 mo
55%
44%
54 mo
62%
57%
0.02 (log-rank test)
52%
55%
0.50 (Fisher's exact)
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3%
0.01 (Fisher's exact)
18%
34%
0.0003 (Fisher's
exact)
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
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
Case Presentation I
• CT demonstrates R mandibular invasion
Case Presentation I
• PET/CT demonstrates no evidence of
metastasis
• MR angiography demonstrates severe
peripheral vascular disease in bilateral
lower extremities
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
Case Presentation I
Therapy
• Resection from paramedian to angle of
mandible to encompass alveolar nerve
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
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
Case Presentation II
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Exam is unremarkable except for a small
lesion on his left lateral/vental tongue
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
Case Presentation II
Staging
• T1N0M0 SCC left lateral tongue
• T1N2bM0 SCC left lateral tongue (by PET)
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
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
Case Presentation II
Treatment
• Left partial glossectomy
• Left neck dissection levels I-V
• Postoperative EBRT with concomitant
cisplatinum days 1, 22,43