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)