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New Perspectives inNew Perspectives inThyroid CancerThyroid Cancer
New Perspectives inNew Perspectives inThyroid CancerThyroid Cancer
Jennifer Sipos, MDAssistant Professor of Medicine
Di i i f E d i lDivision of EndocrinologyThe Ohio State University
• Thyroid Nodules
OutlineOutline
• Thyroid Nodules• Thyroid Cancer Epidemiology• Initial management• Long-term follow up• Disease-free statusDisease free status
2
Incidence of thyroid nodulesIncidence of thyroid nodules
60
70
10
20
30
40
50
reva
len
ce (
%) Autopsy/
Ultrasound
Palpation
Likelihood of malignancy 14%1
0
10
0 20 40 60 80 100
P
Age (years)
Mazzaferri 1993 NEJM 328 (8): 553-9
Palpation
1Yassa 2007 Cancer Cytopathology 111:508-16
How good are we at finding nodules?
Ultrasound vs. Palpation
How good are we at finding nodules?
Ultrasound vs. Palpation
Nodules FOUND by palpation Nodules MISSED by palpation
15
202530
35
42%
s fo
un
d b
y U
S
50%
05
10
<1cm 1‐2cm >2cm
Brander 1992 J Clin Ultrasound 20: 37-42
# N
od
ule 94%
Nodule size by US
3
TSH predicts malignancy risk and cancer stage
TSH predicts malignancy risk and cancer stage
TNM stage
No. of patients
Mean TSH
pvalue
I and II 204 2.1±0.240.002III and IV 35 4.9±1.59
Boelaert 2006 JCEM 91:4295-4301 Haymart, et al. JCEM, March 2008, 93(3):809–814
*p<0.05**p<0.01***p<0.001
FNA Cytology Diagnostic CategoriesFNA Cytology Diagnostic Categories
National Cancer InstituteClassification
Alternateclassification
% Malignant
Benign <1%
Follicular Lesion of Undetermined Significance
Atypia 5-10%
Neoplasm Follicular NeoplasmHurthle Neoplasm
20-30%
Suspicious for malignancy 50-75%
Malignant 98-100%
Non-diagnostic Unsatisfactory
Baloch ZW., 2008 Diag Cytopath 36:425-437
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Percentages of thyroid carcinoma by
histologic subtype
Percentages of thyroid carcinoma by
histologic subtype
80%
11%
3%4% 2% Papillary
Follicular
Hurthle cell
Medullary
Anaplastic
Hundahl 1998 Cancer 83: 2368-48
Epidemiology of Thyroid Cancer
Epidemiology of Thyroid Cancer
• 48,020 new cases in 2011• 1 740 deaths1,740 deaths
• Females 5 year survival rates increasingsignificantly, from 93% in 1974 to 97.4% in 2001
• Survival rates in men have decreasedsignificantly, by 2.4%g y, y
• Rates of distant metastases in men were over 2-fold higher than women (9% vs 4%)
SEER Cancer Statistics Review, 1975-2001. http://seer.cancer.gov/csr/1975_2008/.
National Cancer Institute, http://www.cancer.gov/cancertopics/types/thyroid
Cancer Facts and Figures 2011
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2.4-fold increase
Sipos, Mazzaferri. 2010 Clinical Oncology 22: 395-404
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The prevalence of microcarcinoma in 24 autopsy series with 7,156 cases
The prevalence of microcarcinoma in 24 autopsy series with 7,156 cases
18-fold difference among studies
nce
r
10
15
20
25
30
35
wit
h t
hyr
oid
can
0
5
10
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Adapted from: Pazaitou-Panayiotou, et al. 2007 Thyroid 17 (11): 1085-92
Study Number
Per
cen
t
6
2521 6
The Prevalence of PTMC in 11 Surgical Series with 6,942 Cases
The Prevalence of PTMC in 11 Surgical Series with 6,942 Cases
17-fold difference among studiesnce
r
10
15
20
5.17.1 7.2
10.5
16.4 16.7
21.617-fold difference among studies
wit
h t
hyr
oid
can
0
5
1 2 3 4 5 6 7 8 9 10 11
1.3 1.8 2.23.8
5.1
Per
cen
t
Study NumberAdapted from: Pazaitou-Panayiotou, et al. 2007 Thyroid 17 (11): 1085-92
Incidence rates of PTC by tumor sizeIncidence rates of PTC by tumor size
tio
n10
0,00
0 p
op
ula
tR
ate
per
Year DiagnosedCramer et al 2010 Surgery 148: 1147-52
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Mortality and Mortality and Mortality and Mortality and yyRecurrence Rates Recurrence Rates for Thyroid Cancerfor Thyroid Cancer
yyRecurrence Rates Recurrence Rates for Thyroid Cancerfor Thyroid Cancer
Relative survival of papillary thyroid carcinoma by AMES risk levels
Relative survival of papillary thyroid carcinoma by AMES risk levels
“Low risk” deaths = 351“High risk” deaths = 191
erce
nt
surv
ival
Years after diagnosis
Hundahl et al 1998 Cancer 83: 2638
Pe
8
Ten year mortality by tumor size
Ten year mortality by tumor size
2018.7
6
8
10
12
14
16
18
20
2 1 6 1.54.1
9.5
0
2
4
<1 1‐1.9 2‐2.9 3‐3.9 4‐8.0 >8
2 1.6 1.5
Bilimoria 2007. Annals Surg 207: 375-84
10 Year recurrence rates by tumor size10 Year recurrence rates by tumor size
ates
52,173 patients with papillary thyroid cancer
10
15
20
25
4.6 7.18.6
11.6
17.2
24.8p<0.001 for each pair‐wise comparison
ve r
ecu
rren
ce r
a
Bilimoria 2007 Ann Surg 246: 375
0
5
<1 cm 1‐1.9 cm 2‐2.9 cm 3‐3.9 cm 4‐8 cm >8 cm
Cu
mu
lati
9
Initial TreatmentInitial TreatmentInitial Treatmentand
Long-Term Management
Initial Treatmentand
Long-Term Managementgg
es
50
N T4 RAI
Recurrence Rates as a Function of Treatment
Recurrence Rates as a Function of Treatment
cen
t R
ecu
rren
ce 40
30
20
10
No T4 or RAI
T4 alone
p<0.5
p<0.001
Years After Initial Therapy
Per
c 10
050 10 15 20 25 30 35 40
T4 + RAI
Mazzaferri 1994 Am J Medicine
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Levels of TSH SuppressionLevels of TSH Suppression
Disease Status
TSH(mU/L)
Duration of Therapy StrengthofStatus (mU/L) of
evidence
Persistent Disease
<0.1 Indefinitely in absence of contraindications
B
NED; High risk tumor
0.1-0.5 10 years then low risk range
C
NED; Low risk tumor
0.3-2.0 Indefinite in absence of recurrence
B
Derived from: Cooper et al. 2009 Thyroid 12: 1-48
Role of Thyroglobulin in Diagnostic F/U
Role of Thyroglobulin in Diagnostic F/U
• Important modality to monitor patients for residual or recurrent diseasefor residual or recurrent disease
• In absence of antibody interference, Tg has high sensitivity and specificity to detect thyroid cancer
Highest sensitivity is following thyroid• Highest sensitivity is following thyroid hormone withdrawal or stimulation using rhTSH
Cooper, D. S., et. al. 2009 Thyroid 19(12) 1-48.
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Diagnostic value of standard testingDiagnostic value of standard testing
Pacini 2003. JCEM 88 (8): 3668-3673.
Criteria for absence of persistent tumorCriteria for absence of persistent tumor
After total or near-total thyroidectomy and remnant ablation (RAI), disease-free status comprises ALL of
1.No clinical evidence of tumor.
2.No imaging evidence of tumor.
the following:
3.Undetectable serum Tg levels during TSH suppression and stimulation in the absence of interfering antibodies.
Cooper, et al 2009 Thyroid 12: 1-48
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Contemporary Surgical Contemporary Surgical Management of Differentiated Management of Differentiated
Thyroid CancerThyroid Cancer
Contemporary Surgical Contemporary Surgical Management of Differentiated Management of Differentiated
Thyroid CancerThyroid Cancer
Matthew Old, MD, F.A.C.S.Assistant Professor
Department of Otolaryngology-Head & Neck Surgery
Thyroid CancerThyroid CancerThyroid CancerThyroid Cancer
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital
and Richard J. Solove Research Institute
OutlineOutlineOutlineOutlinePreoperative Assessment
Risk Stratification
Goals
Surgical management
Neck Dissection
Complications and Minimizing Risks
Cases
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Preoperative AssessmentPreoperative Assessment
Preoperative AssessmentPreoperative Assessment
- Risk stratification
- Preoperative counseling/informed consent based on risk stratification
- Known or suspected cancer: Ultrasound contralateral lobe, central and lateral
k- necks
- FNA suspicious nodes
- Routine use of MRI, CT, PET not needed
Cooper, et al 2009 Thyroid 19: 1167-1214.
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Risk StratificationRisk Stratification
Risk StratificationRisk StratificationGoal: place patient in a low or high risk
category based on preoperative assessment
Example: Follicular or Hurthle cell neoplasm ~20% risk
High Risk Features
>4 cm>4 cm
Atypical features or suspicious on FNA
Family history
Radiation exposure
Cooper, et al 2009 Thyroid 19: 1167-1214.
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Surgical GoalsSurgical Goals
Goals Thyroid Cancer SurgeryGoals Thyroid Cancer Surgery
Curative vs Palliative
Remove primary tumory
Remove disease extending outside primary
Remove all nodes involved
Staging
Facilitate postoperative RAI
Permit adequate surveillance (WBS + Tg)
Minimize disease recurrence and mets
Cooper, et al 2009 Thyroid 19: 1167-1214.
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Extent of SurgeryExtent of SurgeryExtent of Surgery (lobectomy versus
total)
Extent of Surgery (lobectomy versus
total)
Extent of SurgeryExtent of SurgeryThyroid lobectomy – initial approach
- Low risk undiagnosed tumors- Low risk undiagnosed tumors
- DTC <1 cm without contralateral nodules or nodes on US and no high risk factors or features
- 1-2 cm DTC: 24% chance recurrence, 49% increased mortality with lobectomy aloney y
-Individuals >45 - total thyroidectomy for tumors <1cm
Cooper, et al 2009 Thyroid 19: 1167-1214.
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Extent of SurgeryExtent of SurgeryTotal thyroidectomy
- High risk stratification with unknown or
equivocal FNA
- Improved survival with increased extent of surgery
- All patients with >1cm thyroid cancer with no contraindication to surgery
Cooper, et al 2009 Thyroid 19: 1167-1214.
Neck Dissection(central +/- lateral)Neck Dissection
(central +/- lateral)
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Neck dissectionNeck dissection
+/-
Adopted from Gray’s Anatomy, Wikipedia Commons
LateralCentral
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Post-ND AnatomyPost-ND Anatomy
Neck dissectionNeck dissection- General teaching: PTC lymph node metastases in low-
risk patients not clinically significant
- 2 SEER studies recently demonstrated:
1) lymph node metastases, age >45 years, distant mets, larger tumors predicted poor outcome
2) lymph node mets independent for decreased survival only in follicular cancer and PTC in pts over age 45age 45.
- Regional recurrence higher with nodal mets and ECS
Podnos et al 2005 Am Surg 71: 731-734Cooper, et al 2009 Thyroid 19: 1167-1214.Zaydfudium et al 2008 133: 1070-1077
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Neck dissectionNeck dissection- Risks and benefits should be weighed with surgical
expertise
- Level I and VII (below manubrium) may be involved
- En-bloc, functional neck dissections favored over isolated
lymphadenectomy (“cherry-picking”) with some data to
suggest improved mortality and reduced recurrence
- Most common site of recurrence is in cervical
lymph nodes, which comprise the majority of
all recurrences
Cooper, et al 2009 Thyroid 19: 1167-1214.
Neck dissectionNeck dissection- Central neck dissection (VI) and lateral neck for
clinically involved nodes during total y gthyroidectomy: Rating B
- Consider prophylatic central neck dissection with clinically uninvolved central nodes: Rating C
- Total thyroidectomy without prophylatic central y y p p yneck dissection for T1 or T2, node-negative PTCs, and most follicular cancers: Rating C
Cooper, et al 2009 Thyroid 19: 1167-1214.
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Minimizing Risks + Maximizing OutcomeMinimizing Risks +
Maximizing Outcome- Preoperative counseling and assessment critical
Hypoparathyroidism bilateral central neck- Hypoparathyroidism – bilateral central neck
dissections
- Debate: preoperative and post-operative vocal
fold assessment
- Discussion of recurrent laryngeal nerve injuryy g j y
and sacrifice – higher incidence with thyroid
cancers
- Chyle leaks, hematomas
- Accessory (CNXI) paresis
ParapreservationParapreservation
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Post-nerve Dissection Anatomy
Post-nerve Dissection Anatomy
Level IV; Thoracic duct
Level IV; Thoracic duct
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Case1 –Low risk Case1 –Low risk
35 year old female
2 cm left nodule2 cm left nodule
No family history or risks
FNA – indeterminant
No vocal fold dysfunction
+/ D h i+/- Dysphagia
US – no lateral or central
adenopathy
Case 1 Case 1 Left thyroid lobectomy – frozen: follicular neoplasm
Nerve stuck to backsideNerve stuck to backside
of gland but dissected free
Patient did well without sequelae
Path: 2 cm angioinvasive
unencapsulated follicular thyroid carcinoma
Patient underwent completion thyroidectomy and is without evidence of disease
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Case 2 Case 2
60 year old male with hoarseness
Right neck and thyroid mass (5 cm)
Right vocal fold paralysis
No family history or risk factors
CT scan performed
Case 2 Case 2
FNA – papillary thyroid carcinoma
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Case 2 Case 2
Bilateral central and lateral disease; confirmed by US
Case 2 Case 2 Total thyroidectomy, bilateral central
d l t l k di tiand lateral neck dissections, sacrifice of right RLN and right IJ
Path: 5 cm PTC, capsular/perineural/lymphovasculacapsular/perineural/lymphovascular/ deep neck muscular invasion; 15/79 nodes positive with ECS
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Case 2 Case 2 Required vocal fold medialization
recovered near-normal voice
Post-operative RAI
No evidence of disease to date
Baseline functional status – voice, swallowing and function