The Increasing Incidence of Head and Neck Cancer: Thyroid

Cancer and Oropharyngeal Cancer and the Magic of New

TechnologyJuly 18, 2015

Michael Medina, MDOtolaryngology-Head and Neck Surgery

Head and Neck InstituteCleveland Clinic Florida

Objectives

• To know the reason for the increasing incidence of head and neck cancers particularly thyroid and oropharyngeal cancers

• To know how new technology improves treatment modalities available for these cancers

ThyroidIncidence Rates by Race

Race/Ethnicity Male Female

All Races 5.9 per 100,000 men 17.3 per 100,000 women

White 6.2 per 100,000 men 18.3 per 100,000 womenBlack 3.3 per 100,000 men 10.1 per 100,000 womenAsian/Pacific Islander 5.3 per 100,000 men 17.7 per 100,000 womenAmerican Indian 3.2 per 100,000 men 10.9 per 100,000 women/Alaska Native Hispanic 4.2 per 100,000 men 16.0 per 100,000 women

Thyroid

Stage Distribution and 5-year Relative Survival by Stage at Diagnosis for 2002-2008, All Races, Both Sexes

Stage at Diagnosis Stage 5-year RelativeDistribution (%) Survival (%)

Localized 68 99.9(confined to primary site)

Regional 25 97.1(spread to regional lymph nodes)

Distant (cancer has metastasized) 5 53.9

Unknown (unstaged) 2 87.4

Thyroid Cancer

The joinpoint trend in SEER cancer incidence with associated APC(%) for cancer of the thyroid between 1975-2009,All Races

Male and Female Male Female

Trend Period Trend Period Trend Period6.1 1975-1977 -4.7* 1975-1980 6.7 1975-1977-6.5 1977-1980 1.9* 1980-1998 -5.9 1977-19802.4* 1980-1997 5.9* 1998-2009 2.6* 1980-19976.6* 1997-2009 7.0* 1997-2009

Thyroid cancer

The joinpoint trend in US cancer mortality with associated APC(%) for cancer of the thyroid between 1975-2009, All Races

Male and Female Male FemaleTrend Period Trend Period Trend Period-2.2* 1975-1988 -3.2* 1975-1983 -2.6* 1975-19880.8* 1988-2009 1.2* 1983-2009 0.4* 1988-2009

Thyroid Cancer

• JAMA. 2006 May 10;295(18):2164-7.• Increasing incidence of thyroid

cancer in the United States, 1973-2002.

• Davies L, Welch HG.• VA Outcomes Group

Thyroid Cancer

• “The increasing incidence of thyroid cancer in the United States is predominantly due to the increased detection of small papillary cancers. These trends, combined with the known existence of a substantial reservoir of subclinical cancer and stable overall mortality, suggest that increasing incidence reflects increased detection of subclinical disease, not an increase in the true occurrence of thyroid cancer.”

Age-Adjusted U.S. Mortality RatesBy Cancer SiteAll Ages, All Races, Both Sexes1975-2009

Year ThyroidRate Modeled Rate1975 0.5456 0.56671976 0.5614 0.55451977 0.5734 0.54261978 0.5460 0.53091979 0.5276 0.51951980 0.4824 0.5083….

Mortality source: US Mortality Files, National Center for Health Statistics, CDC.

Rates are per 100,000 and are age-adjusted to the 2000 US Std Population.

2003 0.4478 0.47962004 0.4734 0.48342005 0.4823 0.48712006 0.4930 0.49092007 0.4957 0.49472008 0.5149 0.49852009 0.5213 0.5024

Thyroid Cancer

• Cancer. 2009 Aug 15;115(16):3801-7. • Increasing incidence of differentiated thyroid

cancer in the United States, 1988-2005.• Chen AY, Jemal A, Ward EM.• Emory University

Thyroid cancer• Incidence rates increased for all sizes of

tumors. • Highest rate of increase was for primary

tumors <1.0 cm among men (1997-2005: APC, 9.9) and women (1988-2005: APC, 8.6).

• Trends similar - whites and blacks• Significant increases also were observed for

tumors > or =4 cm among men (1988-2005: APC, 3.7) and women (1988-2005: APC, 5.70) and for distant SEER stage disease among men (APC, 3.7) and women (APC, 2.3).

Thyroid cancer

• Summary:• There is increasing incidence of

Thyroid cancer brought mostly by increased diagnostic scrutiny, rather than an actual increase

• Mortality rates have remained stable• Further inquiry regarding Genetic &

Environmental factors are needed

Thyroid Cancer

• Treatment- Surgery- +/- RAI (Radioactive Iodine)- For advanced/aggressive cases

External beam Radiotherapy

- How is a diagnosis pre-op determined?

• US and US guided FNA- Radiologist, Endocrinologist, &

Surgeons

Am J Clin Pathol 2009;132:658-665

• Indeterminate 15-30%- Surgical/diagnostic lobectomy

• 70-80% benign• Genetic testing

- Afirma Gene Expression Classifier by Veracyte

- miRInform Thyroid by Asuragen

• Afirma- Highly Sensitive 85-100%- A negative test is most likely benign

(94%)- A positive test + indeterminate

cytology- 40% malignant (CCF Florida closer to 50%)

• Asuragen-Highly Specific 92%- Only 8% of a positive test will be

negative- A negative test- 22% possibility of

malignancy

Oropharyngeal cancer

• Cancer. 2008 Nov 15;113(10 Suppl):2901-9. • Burden of potentially human papillomavirus-

associated cancers of the oropharynx and oral cavity in the US, 1998-2003.

• Ryerson AB, Peters ES, Coughlin SS, Chen VW, Gillison ML, Reichman ME, Wu X, Chaturvedi AK, Kawaoka K.

• CDC

• 39 population-based registries that participate in the National Program of Cancer Registries and/or the Surveillance, Epidemiology, and End Results Program

• 38 states

TABLE 1

International Classification of Disease for Oncology 3rd Edition(ICD-O-3) Topography Codes Used to Define Sites of PotentiallyHPV-associated Oropharyngeal and Oral Cavity Cancersand Comparison Sites

Sites of Potentially HPV-Associated Cancers

Tonsil (including Waldeyer ring)C09.0 Tonsillar fossaC09.1 Tonsillar pillarC09.8 Overlapping lesion of tonsilC09.9 Tonsil, NOSC14.2 Waldeyer ring

Base of tongue and lingual tonsilC01.9 Base of tongue, NOSC02.4 Lingual tonsilOther oropharynx sitesC02.8 Overlapping lesion of tongueC10.2 Lateral wall of oropharynxC10.8 Overlapping lesion of oropharynxC10.9 Oropharynx, NOSC14.0 Pharynx, NOSC14.8 Overlapping lesion of lip, oral cavity and pharynx

Other oral cavity sitesC03.0 Upper gumC03.1 Lower gumC03.9 Gum, NOSC04.0 Anterior floor of mouthC04.1 Lateral floor of mouthC04.8 Overlapping lesion of floor of mouthC04.9 Floor of mouth, NOSC05.0 Hard palateC06.0 Cheek mucosaC06.1 Vestibule of mouthC06.2 Retromolar areaC06.8 Overlapping lesion of other and unspecified parts of mouthC06.9 Mouth, NOS

LarynxC32.0 GlottisC32.1 SupraglottisC32.2 SubglottisC32.3 Laryngeal cartilageC32.8 Overlapping lesion of larynxC32.9 Larynx, NOS

Other oropharynx sitesC05.1 Soft palate, NOSC05.2 UvulaC05.8 Overlapping lesion of palateC05.9 Palate, NOSC10.0 ValleculaC10.1 Anterior surface of epiglottisC10.3 Posterior wall of oropharynx

Comparison Sites

Oral tongueC02.0 Dorsal surface of tongue, NOSC02.1 Border of tongueC02.2 Ventral surface of tongue, NOSC02.3 Anterior 2/3 of tongue, NOSC02.9 Tongue, NOS

Oropharyngeal Cancer

• The annual incidence rates of potentially HPV-associated cancers of the tonsil and base of tongue both increased significantlyfrom 1998 through 2003 (annual percentage change [APC], 3.0; P<.05 for both sites), whereas the incidence rates of cancer at the comparison sites generally decreased.

Oropharyngeal cancer

• Similar trends were also seen in:• Canada:

- Cancer. 2010 Jun 1;116(11):2635-44. - Trends in oropharyngeal and oral cavity cancer incidence of human

papillomavirus (HPV)-related and HPV-unrelated sites in a multicultural population: the British Columbia experience.

• Australia:- Br J Cancer. 2011 March 1; 104(5): 886–891.- Head and neck cancer in Australia between 1982 and 2005 show increasing

incidence of potentially HPV-associated oropharyngeal cancers- J S Hocking,1,* A Stein,2 E L Conway,2 D Regan,3 A Grulich,4 M Law,5 and J M L

Brotherton6

• Increased in Men, age 55-64- Although increasing in women also

but at a slower rate• Risk factors:

- Oral sex- Multiple sex partners- Open mouth kissing

Oropharyngeal cancer

• Present in a more advanced stage• Higher regional node staging• Majority is HPV 16 but at much lower

rate compared to cervical infection

• Exposure to HPV-sexual contact• Most infections resolve however

persistent infection with oncogenic types lead to cervical, oropharyngeal, anal, vaginal/vulvar and penile cancer

Oropharyngeal cancer

• Treatment:- Chemo-radiation +/- salvage surgery- Surgery +/- radiation/chemoradiation

• Including Trans-oral robotic/laser surgery

- Compared to non-HPV associated cancers- better response and survival rates

• Prior to 2000• Standard treatment was Surgery +/-

post op XRT or Chemo XRT- University of Pittsburgh and

University of Florida- Similar survival with primary XRT and

primary surgery caused more complications

• Reason was the need to go through normal tissue (mandible/neck to reach the cancer)

• Chemotherapy + radiation boosted the results of primary radiation however increased complications:- Aspiration- Dysphagia and feeding tube

dependence

• Search for alternatives

Transoral Laser Microsurgery

Various laryngoscopes used to expose the tumor

CO2 laser (most often with micromanipulator) used to excise the tumor

Popularized by Prof. Steinerfrom GermanyTechnique published in 2000

It is microsurgery because it uses the microscope for magnification

Transoral laser microsurgery has been used for excision of oropharyngeal cancers at several US institutions

Mayo Clinic – Rochester

Mayo Clinic – Scottsdale and Jacksonville

Washington University – St. Louis

Transoral laser microsurgery (TLM)

Published data from:

Mayo Scotts/Jacks59 patients

Mayo Rochester20 patients (BOT)

Wash. University84 patients

Locoregional control

Disease specific survival

Post op bleed

Prolonged G-tube

Offered post op XRT

84% 10% 75%

66%8%5%84%88%

4%0%94%91%

87% 0%

73%Mayo Rochester102 patients (tonsil)

92% 4% 19% 93%94%

Grant DG, Salassa JR, et al. Carcinoma of the tongue base treated by transoral laser microsurgery, part one: untreated tumors, a prospective analysis of oncologic and functional outcomes. Laryngoscope. 2006;116:2150-2155.

Henstrom DK, Moore EJ, et al. Transoral resection for squamous cell carcinoma of the base of the tongue. Archives of Otolaryngology Head and Neck Surgery. 2009;135(12):1231-1238.

Moore EJ, Henstrom DK, et al. Transoral resection of tonsillar squamous cell carcinoma. Laryngoscope. 2009;119:508-515.

Rich JT, Milov S, et al. Transoral laser microsurgery (TLM) +/- adjuvent therapy for advanced stage oropharyngeal cancer: outcomes and prognostic factors. Laryngoscope. 2009;119:1709-1719.

Outcomes stratified by stage

Washington University (all stage III/IV)

5 year disease specific survivalT1/T2: 96%T3/T4: 82%

Locoregional controlT1/T2: 95%T3/T4: 91%

Mayo Scottsdale/Jacksonville

5 year disease specific survivalT1/T2: 90%T3/T4: 85%

Locoregional controlT1/T2: 92%T3/T4: 90%

Mayo Scottsdale/Jacksonville

5 year disease specific survival

Locoregional control

Stage I:

Stage II:

Stage III:

Stage IV:

100%

86%

100%

86%

100%

100%

89% 83%

Stage II

Stage I

Stage III

Stage IVa

Stage IVb

Locoregional control

5 year disease specific survival

100%

83%

64%

66% 52%

56%

76%

100%

100%100%

Univ of Florida XRT (Base of Tongue)

Comparison with primary radiation treatment

Hospital stay is about 3-5 days.

Majority of patients do not have tracheostomy.

NG tube placed short term in most patients, but prolonged G-tube need is rare (and more due to post op XRT)

Complication rate seems low

Trans-Oral Robotic Surgery (TORS)

The da Vinci Robot System

Currently on the da Vinci website, the following types of surgeries are advertised: cardiothoracic, colorectal, general surgery, gynecologic, urologic, and head/neck

“robot” comes from the Czech word “robota” which means ‘forced labor’

Transoral Robotic Surgery (TORS)

About 800 US hospitals own a da Vinci robot

Cost of the da Vinci Robot is about $1.5 million up front ($100,000 per year in maintenance)

$200 cost per case in disposable instruments

Movements of the surgeons wrist/hands are translated into movements of the robotic instruments

The surgeon has a detailed 3-D image of the operative field via a double video endoscope (0 and 30 degree endoscopes commonly used)

Transoral Robotic Surgery (TORS)

Mouth gags, like the Crowe-Davis are used for surgeries of the oropharynx

the F-K (FK-WO) retractor is used in surgeries of the tongue base, hypopharynx and larynx

TORS and TLM

The advantages of TORS:

with the use of angled telescopes the visualization of the operative field is better (compared with the straight line of sight method with TLM)

The surgeon’s hand tremors are filtered by the robot,therefore the tissue cuts are more precise

Similar characteristics:

Avoid damage to structures outside of the surgical field (comapared to open surgery), thereby minimizing physiologic side-effects

The surgery is more precise due to the magnification

White HN et al. Transoral Robotic-Assisted surgeryfor Head and Neck Squamous cell Carcinoma. ARCH OTOLARandNGOL HEAD NECK SURG/VOL 136 (NO. 12),1248-52

There have now been published reports regarding use of the da Vinci robot to treat oropharyngeal (and other upper aerodigestive tract neoplasms) from multiple centers the bulk of which are from:

University of Pennsylvania-pioneer

Mayo Clinic – Rochester

University of Alabama in Birmingham

Mount Sinai

Most of the data to this point is from trials with one treatment arm

Transoral Robotic Surgery (TORS)

Average hospital stay 3-5 days

Complications were low (post op bleeding in ~5% of patients)

Feeding tube dependence varies widely (some institutions place PEG tubes in every patient beginning cancer treatment; others place a short term NG tube at surgery and only place PEG if a patient is not tolerating oral nutrition)

Overall >80% of patients getting majority of nutrition orally within a few weeks of surgery (number goes down once post op radiation begins)

Moore EJ, Olsen KD, et al. Transoral robotic surgery for oropharyngeal squamous cell carcinoma: a prospective study of feasibility and functional outcomes. Laryngoscope. 2009;119:2156-2164

Boudreaux BA, Rosenthal EL, et al. Robot-assisted surgery for upper aerodigestive tract neoplasms. Archives of Otolaryngology Head and Neck Surgery. 2009;135(4):397-401.

Genden EM, Desai S, et al. Transoral robotic surgery for the management of head and neck cancer: a preliminary experience. Head and Neck. 2009;31(3):283-289.

Transoral Robotic Surgery (TORS)

Oncologic Results of TORS

Data of the University of Alabama (Birmingham) and the Mayo Clinic (Rochester, MN published in 12/10

patients that received TORS from March 2007 to December 2008.

A prospective study , mean follow-up is 26 months

89 patients, 71 (T1 or T2) and 18 (T3 or T4)oral cavity: 2oropharyngeal: 77Larynx: 11 (all supraglottic)

92% received TORS as primary treatment and the rest were salvage surgery after concurrent chemoradiation therapy

The over-all recurrence free survival is: 86.3% (89.3% with CRT as primary treatment)29% of T1-2/N0-1 did not receive adjuvant therapy

White HN et al. Transoral Robotic-Assisted surgeryfor Head and Neck Squamous cell Carcinoma. .ARCH OTOLARandNGOL HEAD NECK SURG/VOL 136 (NO. 12),1248-52

Oncologic Results of TORS The Mount Sinai (NY) experience

30 patients, 73% presented with stage III or IV

the follow-up was 18 months: locoregional control: 91%, disease free survival 78%, overall survival 90%

Genden et al . Transoral Robotic Resection and reconstruction for Head and neck Cancer.Laryngoscope Aug 2011. 121: 1668-1674

The University of Pennsylvania experience

47 patients with stage III or IV oropharyngeal cancer with no previous cancer treatments (TORS was the primary treatment)

Disease specific survival in one year is 98%, and in 2 years is 90%38% avoided chemotherapy and 11% did not receive any adjuvant treatments

Weinstein et al. Transoral Robotic surgery for Advanced oropharyngeal Carcinoma. Arch Otolarandngol Head Neck Surg. 2010 Nov;136(11):1079-85.

Conclusion

• There is an increasing rate of Thyroid cancer and Oropharyngeal cancer

• Early detection leads to better outcome• New technology has led to decreased

aggressive treatment either by better diagnostic (Thyroid cancer) or improved surgical treatments (Oropharyngeal cancer)