Southwest OH Regional Updates - PowerPoint Presentation

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Southwest OH Regional Updates Internal Medicine

Head and Neck Cancer

M.

Kashif

Riaz

, MD

Assistant Professor of Medicine

Division of Hematology & Oncology

University of Cincinnati College of Medicine

Feb

3

rd

2018

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harynx

Larynx

Esophagus

Trachea

Salivary glands

Oral cavity

Nasal cavity

Head and Neck Anatomy

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Head and Neck Cancer

Pathology:

Squamous cell carcinoma

Nasopharyngeal carcinoma

2.

Salivary gland: adenocarcinoma,

acinic

cell, adenoid cystic,

mucoepidermoid

, benign mixed,…

3. Paranasal sinus:

esthesioneuroblastoma, SNUC, primary neuroendocrine,…4. Lymphoma, plasmacytomaThyroid cancersSarcoma, melanoma, metastatic cancers

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Risk FactorSmoking

Alcohol HPV ( oropharynx)

EBV ( nasopharynx)

Squamous Cell Head and Neck Cancer

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HPV-associated Head and Neck Cancer

I

n up to 72% of oropharynx (tongue base and tonsil) cancers in the U.S.

Tumor p16 expression by IHC is an excellent surrogate for HPV-positivity.

Tumor HPV-positivity is independent of tobacco and alcohol exposure.

Patients with HPV positive tumors are younger, and more often Caucasian.

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HPV+

HPV-

Median age

58 years

68 years

Race

Caucasian Uncommon in AA

Both Caucasian and AA

Sex

Male 3:1

Male 3:1

Subsite

Tonsil

Base of tongue

Oral tongue

Larynx/

Hypopharynx

Incidence

Increasing

Decreasing

Risk Factors

Sexual activity

Tobacco

Alcohol

Epidemiologically: Two different diseases

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T1

T2

T

3

T

4

N

0

N

1

N

2N

3

Stage IV(Includes any M1)

Stage IIIStage IStage II

Squamous Cell Head and Neck Cancer

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Years

% Survival

0

20

40

60

80

100

0

1

2

3

4

5

Stage I-II (n = 9)

Stage III (n = 17)

Stage IV (n = 63)

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Newly diagnosed H & N Squamous Cell Cancer

In patients with loco-regionally confined disease, treatment is given with curative intent.

The definitive treatments are surgery and radiation therapy

Single modality treatment is preferred in early stage disease.

4. Choice of modality is based on functional expectations and expertise.

Standard of Care

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Newly diagnosed H&N Squamous Cell Cancer

5. Both the primary site and the neck must be addressed.

6. Combined modality therapy is often required for advanced tumors

7. Chemotherapy is adjunctive, not definitive. It has no established role as single modality therapy in primary management.

Standard of Care

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How do we optimally integrate chemotherapy into curative multimodality treatment strategies for locoregionally confined disease?

Squamous Cell Head and Neck Cancer

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Induction Chemotherapy

Chemotherapy

Surgery / Radiation

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Concurrent

Chemoradiotherapy

Chemotherapy

Radiation

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Benefit of Concurrent Chemotherapy added to Radiation: Overall Survival and

Locoregional Control

Denis et al. JCO 2004; 22: 69

P=0.05

P=0.002

Survival

Locoregional

Control

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Recurrent or Metastatic HNSCC

If inoperable & previously radiated, or metastatic:

Combination chemotherapy

Targeted therapy (+/- chemotherapy)

Single agent chemotherapy/ immune therapy/ targeted therapy

Investigational therapy

Best supportive care

Standard of Care

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Vermorken

et al. NEJM 2008; 359:1116-1127

(Median 10.1 mos.)

Med.7.4

mos

Overall Survival

This is the first and only randomized trial to demonstrate a survival benefit from any intervention

in recurrent or metastatic head and neck cancer

.

Med.10.1 mos

.

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Systemic Therapy for Recurrent or Metastatic Disease

Squamous Cell Head and Neck Cancer

1. Cytotoxic agents:

Methotrexate Carboplatin Bleomycin Paclitaxel

Cisplatin

Docetaxel

5-Fluorouracil Gemcitabine

2.

Targeted therapy agents Cetuximab Afatinib3. Immune therapy agents Nivolumab Pembrolizumab

Many active drug combinations have been reported.

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Programmed Cell Death 1

PD1 binding to its ligand(s) PDL1 ( or PDL2) protects against infection-induced immune mediated damage to tissue and autoimmunity Cancer cells can exploit this mechanism to their benefit and escape immune system

PDL1 is highly expressed on HPV positive and negative disease

Pardoll

DM. Nat Rev Cancer. 2012

Badoual

C, et al. Cancer Res. 2013

PDL1, PDL2 have a role in HNSCC

recurrence and metastasis

Ferris

RL. JCO 2015Concha-Benavente F, et al. Cancer Res. 2016

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Immune Therapy versus Chemotherapy for recurrent or metastatic (R/M) HNSCC

Ferris, et al. NEJM. 2016

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Thyroid CancerRET

(MEN 2B)

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Question 151 yo M, w/ hx of 25 yrs smoking, quit

approx 10 yrs ago, p/w odynophagia for 3 months. He has been treated with multiple courses of Amoxicillin and Z-pak without much improvement in

symptoms

. He

recently

developed mild right

sided

otalgia and some dysphagia to solid food, requiring minor modifications in his diet.

On

exam, he has a mass in right base of tongue and multiple right cervical adenopathy in submandibular area and mid cervical levels. On CT scan, base of tongue infiltrative mass is measured around 4 cm and he is noted to have 3 separate lymph nodes, largest measuring 3 cm.

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The next most appropriate recommendation is:

Treat with a different antibiotic that has better coverage of anaerobic infections. Refer to Gastroenterology clinic for upper GI endoscopy and workup of odynophagia.

Obtain barium swallow test for better evaluation of dysphagia.

Obtain MRI of head and neck for better visualization of base of tongue mass and subsequently refer to ENT for a needle biopsy of base of tongue mass

Refer to ENT for needle biopsy of base of tongue mass or cervical adenopathy 

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Question 2Patient described above underwent a needle biopsy of the largest submandibular cervical adenopathy, which confirmed diagnosis of squamous cell carcinoma, positive for HPV 16 by ISH. A full body imaging does not reveal any other site of disease outside of head and neck area. You plan to refer the patient to oncology. As you discuss biopsy results with patient, he asks you about his prognosis based on current information.

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Question 2

He has a potentially curable disease, but his smoking history significantly lowers his chance of cure. He has a potentially curable disease, but his HPV 16 status significantly lowers his chance of cure

He does not have a curable disease and treatment will be of palliative intent.

There is not enough information to discuss prognosis

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Question 358 yo M, w/ hx of 20 pack-year smoking, p/w a new left neck mass since 4 weeks ago. He recalls symptoms of throat pain and runny nose 4-5 weeks ago, which has since resolved. He is feeling well otherwise and continues to work full time without any problems.

The mass is approximately 4 cm on exam, non –tender and firm. A detailed exam in office does not reveal any mucosal lesions or masses in head and neck area. Imaging studies reveal enlarged lymph nodes on left side of neck. FNA of left neck is positive for squamous cell carcinoma

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Question 3

Chemo radiation to neck as soon as possibleChemo radiation to the entire pharyngo-laryngeal axis and neck area as soon as possible

Patient should undergo full head and neck exam under anesthesia with random biopsies of suspicious area and bilateral tonsillectomies to define primary site of tumor

Patient does not need immediate treatment because he has an unknown primary cancer and is asymptomatic. He should be examined frequently and needs surveillance scans

Check the FNA sample for p16 (surrogate marker for HPV disease) and if positive, treat with radiation to oropharynx and neck

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Question 461 yo M, hx of 30 pack-year smoking, history of laryngeal carcinoma, completed chemo radiation 1 year ago, presents to your office for routine follow up. He

is eating much better, and is now able to swallow solid and liquid food without difficulty. He rarely chokes while eating. He has gained 10 Ib since last year and his most recent weight is 140 Ib, but is still not at his baseline weight before cancer diagnosis. ( 160 Ib) On exam he has a stiff neck with some fibrosis and scar. No mass or lesions noted.

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The next most appropriate recommendation is:

CT neck every 3-6 month to monitor closely for recurrence of diseaseAnnual TSH to screen for hypothyroid

Annual CEA to screen for cancer recurrence

Discuss feeding tube placement because he has not achieved his baseline after a year despite eating better

Discuss annual exam under anesthesia for complete head and neck evaluation