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10/03/2018
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Head & Neck Cancer
ReviewJoseph Rosales, MD
October 4, 2018
© 2014 Virginia Mason
INTRODUCTION
• Epidemiology/Risk Factors
• Anatomy
• Presentation/Workup
• Treatment
– Surgery vs Radiation
– Chemotherapy
– Side effects
• Special circumstances
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National Cancer Institute, SEER 18 Database
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© 2014 Virginia Mason
RISK FACTORS
• Tobacco
• Alcohol
• Viral – HPV, EBV
• Gender
• Age
• Poor oral/dental hygiene
• Malnutrition
• GERD
• Immunodeficiency7 8
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Presenting Symptoms
• Persistent/recurrent throat pain
• Dysphagia/odynophagia/globus sensation
• Hoarseness/change in phonation
• Sinus congestion/obstruction
• Epistaxis/epiphora
• Unexplained halitosis
• Pain
• Hemoptysis
• Neck mass10
In 24 months prior to diagnosis, patients
sought care 10.5 times
© 2014 Virginia Mason
PHYSICAL EXAM
• Skin/scalp
• Cranial Nerves
• Oral exam
– Remove dentures/appliances
– Manual exam
• Neck
– Signs of inflammation
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TREATMENT – General Principles
• Multidisciplinary Evaluation
• Determination of Resectability
– Post-operative QOL
• Neoadjuvant/Adjuvant Therapy
• Other Considerations
– Smoking/Alcohol cessation
– Dental Examination
– Nutritional Evaluation
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Surgery – General Principles
• Goal is clear margins
– Clear > 5mm
– Close < 5mm
– Positive = DCIS/Invasive tumor at margin
• En bloc resection preferred
• Nerve sparing possible?
• Laryngeal preservation possible?
• Reconstructive surgery
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Common Surgery Contraindications
• T4b – inability to obtain clear margins
• Pterygoid muscle involvement/cranial neuropathy
• Extension to skull base/cervical vertebrae
• Direct extension to nasopharynx/eustachian canal
• Encasement of common/internal carotid artery
• Direct extension to external skin
• Direct extension to mediastinal structures
• Subdermal metastases
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Surgery – Neck Management
• Extent of lymphatic evaluation depends on primary tumor
• Ipsilateral lymphatics dissected
• Bilateral lymph node dissection for base of tongue, palate,
supraglottic larynx, hypopharynx
• Sentinel lymph nodes for early stage oral cavity tumors
– If positive, neck dissection is required
– Inappropriate for some sites (floor of mouth, gingiva, hard
palate)
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Radiation Therapy – General Principles
• Post-operative
– Positive margins
– Extracapsular nodal extension
– Multiple nodal involvement, pT3/pT4 primary, invasion of
neural/lymphatic/vascular bundle, level 4/5 nodal involvement
• Definitive
– Anatomically unresectable tumor
– Physiologically poor surgical candidate
– Small volume local disease
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Higher RT DoseBetter Tumor Control
Increased tissue toxicity
Lower RT DoseLess Tumor ControlLess tissue toxicity
© 2014 Virginia Mason
Radiation Therapy
• Standard Dose
– 70 Gy in 2Gy fractions – total 6-7 weeks
– Lower dose to lower-risk areas – 44-64 Gy
• Other considerations
– 3D Conformal Radiation vs IMRT
– Brachytherapy
– Proton Beam Irradiation
– Stereotactic Body Radiation (SBRT)
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Conventional RT
IMRT
12 MONTHS 24 MONTHS
74% 83%
38% 29%
XEROSTOMIA
PARSPORT Clinical Trial, 2011
H+N SCCAT1-T4N0-N3
60-65 Gy30 Fractions
(n=98)
© 2014 Virginia Mason
Radiation Therapy - Toxicities
• Acute
– Skin reactions/breakdown
– Mucositis
– Dehydration
– Malnutrition/weight loss
• Late
– Xerostomia
– Secondary malignancies
– Lymphedema
– Tooth decay30
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Radiation Therapy - Lymphedema
• 2-6 months after end of treatment
• Risk Factors
– Total RT dose
– Extent of LN dissection
– Chemotherapy
– BMI, nutrition
• Treatment
– Manual lymphatic drainage – CDT
– Weight loss
– Positional
– Medications not generally helpful
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Radiation therapy – tooth decay
• Dental Evaluation
• Prevention!
– Oral moisturizaiton
– Baking soda mouthwash
– Avoid acidic/alcoholic oral intake
– Avoid dentures 32
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Systemic Therapy – General Principles
• Curative
– Concurrent with radiation therapy
– Induction chemotherapy
• Palliative
• Types of systemic therapy
– Cytotoxic chemotherapy
– Monoclonal antibody
– Immunotherapy (checkpoint inhibitors)
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Types of systemic therapy
• Chemotherapy
– Platinum (Cisplatin, Carboplatin)
– Taxanes (Paclitaxel, Docetaxel)
– 5-Fluorouracil
• Monoclonal antibody
– Cetuximab (Erbitux)
• Immunotherapy
– Pembrolizumab (Keytruda)
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Platinum
• Attaches to DNA and prevents replication
• Direct cytotoxic effect
• Chemosensitization
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Taxanes
• Bind microtubules and prevents depolymerization
• Interferes with mitosis
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Taxanes
• Common Toxicities
– Nausea/vomiting
– Myelosuppression
– Allergic reaction
• Paclitaxel
– Peripheral Neuropathy
• Docetaxel
– Nail dystrophy
– Ocular Canalicular Stenosis
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5-Fluorouracil
• Blocks thymidylate synthase
• Prevents generation of Cytosine and Thymidine
• Prevents DNA replication and cell division
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Cetuximab
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Cetuximab - toxicities
• Allergic reactions
• Dermatitis
• Hair/nail toxicity
• Pulmonary toxicity
• Infection/sepsis when combined with RT
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Cetuximab - dermatitis
• Treatment Options
– Clindamycin
– Steroids – hydrocortisone
– Doxycycline/Minocycline
– Discontinuation of therapy
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Chemotherapy Regimens
• High-dose cisplatin
• Cetuximab (single agent)
• Weekly cisplatin
• Carboplatin/5FU
• Carboplatin/Taxol
• Cisplatin/Docetaxel/5FU
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IMMUNOTHERAPY
• Nivolumab – Checkmate 141
– 361 patients, platinum refractory recurrent disease
– Nivolumab vs standard therapy (chemo or cetuximab)
– OS 7.5 months vs 5.1 months in favor of nivolumab
– Toxicities 13.1% vs 35.1% in favor of nivlumab
• Pembrolizumab – Keynote 12 (Phase 2 study)
– ORR 16%
– DoR > 6 months
– Keynote 40 – trend toward but not definitive improvement OS
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SPECIAL CIRCUMSTANCES
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Nasopharyngeal Cancer
• What’s so special?
– Less common in US
– EBV associated
– More likely to metastasize
– More likely to recur without
chemo
• How is treatment different?
– T1N0 – EBRT
– >T1N0 – ChemoRT + chemo
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Human papilloma virus (HPV p16)
• In oropharyngeal carcinoma, HPV is prognostic
– P16 positive patients had better survival & less toxicity
– P16 negative patients did worse with RT (vs surgery)
– P16 positive patients with metastatic disease had better
survival
• Consequently…
– P16 patients may need less aggressive therapy
– P16 patients may need to be in separate clinical trials
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INDUCTION CHEMOTHERAPY
• CONS:
– Did not result in improved survival
– Decreased ability to receive definitive chemo/RT
• PROS:
– Decreased metastatic recurrence
– Allowed for organ preservation
– Response to induction predicted survival
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