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Head & Neck Cancer

Review Joseph Rosales, MD

March 12, 2018

© 2014 Virginia Mason

INTRODUCTION

• Epidemiology/Risk Factors

• Anatomy

• Presentation/Workup

• Treatment

– Surgery vs Radiation

– Chemotherapy

– Side effects

• Special circumstances

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© 2014 Virginia Mason

RISK FACTORS

• Tobacco

• Alcohol

• Viral – HPV, EBV

• Gender

• Age

• Poor oral/dental hygiene

• Malnutrition

• GERD

• Immunodeficiency 7 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 mass 10

In 24 months prior to diagnosis, patients

sought care 10.5 times

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PHYSICAL EXAM

• Skin/scalp

• Cranial Nerves

• Oral exam

– Remove dentures/appliances

– Manual exam

• Neck

– Signs of inflammation

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© 2014 Virginia Mason

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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© 2014 Virginia Mason

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 Dose Better Tumor Control

Increased tissue toxicity

Lower RT Dose Less Tumor Control Less 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 SCCA T1-T4 N0-N3

60-65 Gy

30 Fractions

(n=98)

© 2014 Virginia Mason

Radiation Therapy - Toxicities

• Acute

– Skin reactions/breakdown

– Mucositis

– Dehydration

– Malnutrition/weight loss

• Late

– Xerostomia

– Secondary malignancies

– Lymphedema

– Tooth decay

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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

31 © 2014 Virginia Mason

Radiation therapy – tooth decay

• Dental Evaluation

• Prevention!

– Oral moisturizaiton

– Baking soda mouthwash

– Avoid acidic/alcoholic oral intake

– Avoid dentures 32

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© 2014 Virginia Mason

Systemic Therapy – General Principles

• Curative

– Concurrent with radiation therapy

– Induction chemotherapy

• Palliative

• Types of systemic therapy

– Cytotoxic chemotherapy

– Monoclonal antibody

– Immunotherapy (checkpoint inhibitors)

33 © 2014 Virginia Mason

Types of systemic therapy

• Chemotherapy

– Platinum (Cisplatin, Carboplatin)

– Taxanes (Paclitaxel, Docetaxel)

– 5-Fluorouracil

• Monoclonal antibody

– Cetuximab (Erbitux)

• Immunotherapy

– Pembrolizumab (Keytruda)

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© 2014 Virginia Mason

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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© 2014 Virginia Mason

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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© 2014 Virginia Mason

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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© 2014 Virginia Mason

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

51 © 2014 Virginia Mason

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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© 2014 Virginia Mason

INTRODUCTION

• Epidemiology/Risk Factors

• Anatomy

• Presentation/Workup

• Treatment

– Surgery vs Radiation

– Chemotherapy

– Side effects

• Special circumstances

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Thank You

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