1. Lessons from My one Year (2015) of Thyroid Cancer Practice
Vahab Fatourechi MD, FRCPC, FACP
Professor of Medicine
Mayo Clinic College of Medicine
Rochester Minnesota USA
Isfahan April 2016

2. DTC In Olmsted County VS Referral to Mayo Clinic
Papillary 82%
Papillary 82% 6% 7% 8% 3% 5% 5%
MTC
Olmsted County
(n=258)
HCC
FTC
MTC
Mayo Clinic

3. Adult PTC at Mayo Clinic in 8 Decades Size Distribution
1 cm or less
33%
>2.1cm
32%
1-2 cm
35%
N=4138

4. PTC Survival by TNM Stage
P=0.0001
Surviving papillary thyroid carcinoma (%)
TNM stage
I ,360 II
III IV
Years after initial treatment

5. My Thyroid Cancer Patients Seen in 2015
N= % original surgery at Mayo 50% another institution
Median age yrs.
Female/male ratio
Follow up range years
FH of thyroid cancer %
Radiation exposure % ( one from Chernobyl)
PTC %
Follicular cancer %
Hurtle cell cancer %
Medullary cancer % (10)

6. Initial Surgery date
Year
Number of patients
Before 1980 1
1980 to 1989 3
1990 t0 1999 13
2000 to 2009 47 97
2015 30

7. TNM Staging of Differentiated Thyroid Cancer
T Primary tumor <2cm.
T >2 cm and <4 cm
T >4 cm
T Any size tumor
beyond thyroid capsule

8. TNM Staging of Differentiated Thyroid Cancer
Regional and upper mediastinal nodes(N)
N Negative nodes
N1(a and b) Positive nodes
Distant Metastases(M)
M Absent
M Present

9. TNM Staging of Differentiated Thyroid Cancer
Staging Under age and older
Stage I Ant T, any N,M T1,N0,M0
Stage II Any T, any N,M T2,or T3, N0,M0
Stage III T4,N0,M0
Any T, N1,M0
Stage IVA T1-3 N1b , M0
Stage IVB T4B Any N MO
Stage IVC Any T any N M1

10. Staging of My Patients (2015)
Mayo initial surgery
Non Mayo Initial surgery
Stage % Stage %
Stage %
Stage IVA %
Stage IVC %
Stage %
Stage %
Stage %
Stage IVA %
Stage IVC %

11. Change of Staging at last visit
Staging stayed same (69%)
From NIa to NIb (16%)
N0 to NIa
Stage III to stage IV
M0 to M

12. 70% of cases of thyroid cancer in follow-up stay in the same stage
Lesson Learned
70% of cases of thyroid cancer in follow-up stay in the same stage
30 % go to higher stage

13. Lessons Learned
Most of my patients classified to higher stages of 3 and 4 had excellent outcome and cut off of age at 45 did not make sense
Good news : In new TNM classification under publication the age cut off will be raised to 55 from 45 and small nodal neck met will not be stage III and minor extra-thyroidal extension will not be stage III

14. Extremes of Behavior of PTC (Case 1)
Indolent disease for 50 years
Surgery for PTC age 14 partial thyroidectomy – unresectable
neck codes
Continued on suppressive thyroxin therapy
Seen at age 56 and followed from m 2009 to 2016
50 years of unresectable indolent significant calcified stable
metastatic neck disease
Asymptomatic Not progressive stable Tg 2.0

16. CT of Neck Showing Calcified Lesions

17. Extremes of Behavior of PTC (Case 2)
Lethal disease in 4 years
Diagnosed in with PTC tall cell features
Age 46
Died 2016 with heart and brain metastases

18. Right Ventricular Metastasis from PTC with Tall cell Features
CT Angiography

19. Micro-PTC with large lymph node Metastases(case 3).

20. Micro-PTC with large lymph node metastases
Rt upper neck PTC Mets
Micro-PTC with large lymph node metastases C
Rt lobe longitudinal
RT lobe transverse

21. Lesson Learned
(Case 1) Not all non-resectable PTC changes quality of life
(Case 2)Tall cell features of PTC may result in aggressive and unusual metastases
(Case 3) Micro-PTC can rarely have significant
metastases

22. Value of pre-op US for node Mapping Patients with initial Surgery at Mayo
Pre-op node suspect on US proven to be node positive %
Pre-op node negative and proven to be node positive 16%
Node negative pre-op and post op 51%
Most missed nodes central compartment or microscopic

23. Lesson Learned
Pre-op neck node mapping should be standard but may miss 16% of neck node metastases mostly in Level 6 and microscopic node involvement

24. PTC Characteristics Incidental diagnosis 31% Multifocal 45%
Bilateral %

25. Lesson Learned
36% of PTC after thyroidectomy will prove to be bilateral
If lobectomy is chosen for low risk PTC close follow up is still essential

26. Distant Metastases Distant met 21 10% Lung mets 19 9% Brain 1 0.05 %
Bone 4 2%
skin
0.05%
heart

27. 90% of distant metastases of DTC will be in the lungs
Lesson Learned
90% of distant metastases of DTC
will be in the lungs

28. Neck lymph node Metastases
F/U neck node recurrence if initially neg:
Mayo surgery %
Outside institution %

29. Lesson Learned
Surgery in specialized center may be associated by 7 fold less loco-regional metastases found later
( cofounding factor of referral bias to be considered)

30. Complications from Disease and Surgery
Mayo operated
Operation elsw
Hypoparathyroidism %
Vocal cord paralysis %
RAI therapy %
Hypoparathyroidism 7%
Vocal cord paralysis %
RAI therapy %

31. Lesson Learned
Surgery of thyroid cancer by experienced thyroid surgeons may be associated with half of surgical complications

32. RAI Therapy Patterns Lesson learned: Still RAI therapy is over
Operated at Mayo
Operated esw
N=100
Received RAI ( 50%)
Stage n= 39
Stage1 receiving RAI n=11
%stage 1 receiving RAI 28%
N=100
Received RAI (77%)
Stage n= 45
Stage1 receiving RAI N= 34
% stage1 receiving RAI 76%
Lesson learned: Still RAI therapy is over
utilized for low and intermediate risk thyroid cancer

33. Thyroglobulin Positive WBS negative Patients
40% on F/U WBS despite prior RAI therapy
were WBS negative and Tg positive
Lesson learned: Usual source of Tg was neck node
metastases detected by expert US

34. Relationship of Tg on T4 Therapy to Metastases All had received RAI
Patients that had Tg on thyroxine
between 0.1 to 1.9
No anatomic evidence of cancer Patients
Positive neck nodes
Suspect neck nodes or previously ablated
Lung mets
Treated ancient sacral follicular mets

35. Relationship of Tg on T4 Therapy to Metastases
All had Received RAI
Of 6 Patients that had Tg on thyroxine between 2-10
Tg neck possibly lungs
Tg neck mediastinum
Tg stable lungs
Tg no anatomic evidence
Tg suspect neck nodes

36. Relationship of Tg on T4 Therapy to Metastases
All had received RAI
Of 7 Patients that had Tg on thyroxine above 10
All had distant mets
Tg Skull skin neck
Tg lungs
Tg lungs
Tg lungs
Tg lungs neck
Tg lungs
Tg lungs –bone heart
Lesson learned: Tg >10 on suppressive therapy
indicates distant metastases

37. US Guided Ethanol Ablation of Neck Nodal Metastases
Since1993 over 200 patient had neck node ablation with ethanol injection
In long-term f/u of patients:
95% decreased in size with reduction of Tg
f/u 5.4 yrs.
No complications
Hay ID et al surgery 2013

38. Ethanol Ablation Loco-regional Metastases
39 lesions personal patients seen in 2015

39. Ethanol Ablation Loco-regional Metastases
Metastatic or recurrent neck nodes patients
Number of metastatic nodes lesions
Size of lesions
Range mm
Average mm
Median mm

40. Lesion disappeared 9 (23%) Lesion significantly shrunk 23 (59 %)
Long term Follow up of Ethanol Ablation for Loco-regional Metastases Personal patients
Lesion disappeared (23%)
Lesion significantly shrunk (59 %)
Remained stable (11%)
Lesion grew ( 7%)

41. Lessons learned
Ethanol ablation of loco regional metastases was highly effective in 93% of my cases and prevented surgery

42. Ethanol ablation for Primary lesions
Micro – PTC
2 patients

43. Ethanol Ablation of primary PTC 2010-2015
13 patients- 15 tumors
Tumor sized 4-13 mm
Volume CU (median 140)
F/U yrs.
All shrunk- mean volume decreased 73%
Non had neck node mets
No complications
6 not identifiable Ian Hay 2016

44. Ethanol Ablation of primary PTC
My 2015patients
2 patients 3 lesions
Results
One lesion from size 7 mm disappeared
One shrunk from size 12 to 8 mm
and one remained stable at 3 mm

45. Ethanol ablation of Micro-PTC

46. Disappearance of 7 mm PET Positive PTC

47. Lessons learned
Ethanol ablation of micro-PTC may be an alternative to lobectomy or active surveillance

48. Mass -spectrophotometry Tg assay
Is mass spectrophotometry for Thyroglobulin measurement helpful in Tg antibody positive patients? 22 personal Patients (2015)

49. Comparison of Tg Assays
Tg antibody positive patients
Mass spect Tg measurement n=22
3 positive Tg positive usual method
1 negative Tg low level positive RIA(0.7)
5 negative Proven evidence of disease
3 negative Indeterminate suspect neck lesions
10 negative No anatomic evidence of disease
Conclusion It did not help my practice but was somewhat
reassuring if negative:

50. Lesson I learned
The present Mass -spect assay for thyroglobulin positive patients was not helpful in my practice but gave some reassurance if negative

51. Medullary cancer Experience

52. Medullary Cancer N=10 all sporadic Incidental 2 F/m ratio 2.3
f/u duration average 11 yrs.
Average age range 36-52
2 had only lobectomy when genetic testing was negative
Lessons learned:
In sporadic cases lobectomy is adequate
And genetic testing is recommended prior to surgery

53. Medullary Cancer n-10 Initial neck node mets 7 Recurrent neck later 6
Repeat neck surgery
Ethanol neck node ablation
Undetectable calcitonin
Pelvic mass excision
Lung and bone mets no repose to TKI
Lesson learned : Majority of MTC patient with slowly increasing calcitonin and no anatomic detectable disease have excellent quality of life and no detectable disease for many years 6

54. Overall Conclusions
1-Third of PTC was incidentally diagnosed by imaging for
other issues
2-PTC is multifocal in 45% and bilateral in 36%
3-RAI therapy does not eliminate neck lymph node metastases

55. Conclusion 4-After RAI therapy Tg Positive WBS negative
patients almost always have neck node
metastases
5-Mayo practice is associated with less usage of
RAI remnant ablation, lesser complications of
initial surgery- This agrees with recent ATA
recommendation that thyroid cancer surgery should
be done with high volume thyroid surgeon >26/year

56. Conclusion
6-Ethanol ablation of neck node metastases less than 2 cm is an effective therapy in 93% of cases
7-Majority of sporadic Medullary cancer had an indolent course with good quality of life without clear anatomic evidence of metastases
despite persistent slowly increasing serum levels

57. Conclusion 8- Mass spectrometry Tg measurement in Tg antibody-positive
patient was not helpful in management of my patients
9-Outcome is better if initial surgery is done in a tertiary
care center although comparison may have the limitation of
referral bias despite similarity of baseline staging of 2 group

58. Conclusion
10- With current recommendations more lobectomy will be done
as opposed to total or near total thyroidectomy done in previous
Mayo surgical practice
Active surveillance and possibly ethanol ablation will be used
for low risk Micro-PTC less than cm in future reducing
surgical risks and need for life long Thyroxine therapy for low risk
PTC
11- With new upcoming TNM Staging raising age related risk to 55
most patients from Stage III and IVa-b will be classified Stage I
thus less aggressive unnecessary therapy

59. Thank you
Questions?

60. Left Lobectomy 2001 for 1.5 cm left PTC
2002
2008
3 mm hypoechoic
nodule nothing suspect
20110

61. Development of Micro –PTC in the rt Thyroid lobe
2010

62. Prognostic Schemes for DTC
AGES
AMES
MACIS
Age X X -- X
Sex -- --
Size X X
Multicentricity -- --
Grade X --
Histology
PTC
PTC
Invasion X X
Nodes -- --
Metastases X X
Complete excision -- X

63. ©Efficacy of UPEA in Treating 15 Tumor Foci of SIPC in 13 Intact Thyroids
©2015 MFMER | Efficacy of UPEA in Treating 15 Tumor Foci of SIPC in 13 Intact Thyroids

65. Olmsted County Minnesota Rising thyroid cancer incidence
Comparesd to
7.1 / A Rate to 13.7
53% asymptomatic incidental finding, neck imaging 36%,incidental for thyroid benign disease surgery26%, found on routine exam20%,investigation for unrelated symptoms12%
Exclusion of incidental brings rate to 6.3%
Brito JP et.al, Abstract ATA meeting Oct 2014

66. Olmsted County Minnesota Rising thyroid cancer incidence
Comparesd to
7.1 / A Rate to 13.7
53% asymptomatic incidental finding, neck imaging 36%,incidental for thyroid benign disease surgery26%, found on routine exam20%,investigation for unrelated symptoms12%
Exclusion of incidental brings rate to 6.3%
Brito JP et.al, Abstract ATA meeting Oct 2014

67. Characteristics of 28 Patients Receiving Ethanol Ablation
Neck node metastases at initial surgery
Neck node not sampled or unclear
Node negative at initial surgery
Prior surgical excision of recurrent nodes

68. Cause-Specific Mortality Rates in FCDC90
ATC
FTC
HCC
Dying of thyroid carcinoma (cumulative %)
PTC
Years after initial treatment

69. Outcome of 900 Micro PTC 1994-2004 Hay ID, surgery; 2008144:980
Median size 7 mm
85% bilateral lobectomy, RAI in 17%
30% neck node positive
0.3% distant mets, 0.6% incomplete excision
O.3% died of PTC, Recurrence rate in 40Yrs 6%
Higher recurrence in multifocal tumors, and node positives
More extensive surgery or RAI did not change outcome
99% not at risk of distant spread or mortality
RAI or bilateral lobectomy did not change outcome
Hay ID, surgery; :980

70. 14045 Micropapillary Cancer in Korea Single Institution 1986-2013
10-20yrs survivals 98% and 94%
Disease free survivals,97 and 94%
total 47%
less than total 53%
Central compartment node 27% lateral neck 4.9%
No difference between thyroidectomy total and less than total
Lee c et. All presented in Oct 2014 ATA meeting

71. Age of Patient and PTC
1235 patient chose observation
Progression lowest in over age 60
Highest in the younger <age 40
Young age independent predictor of progression
None of 1235 had distant mets or died from PTC
4% had TSH suppression, except one all clinically stable191 had surgery
Conclusion : Older patients with Micro PTC best candidates for obserrvation,
For younger under observation, it is not too late to surgery if progression
Ito Y et al thyroid 2014: 25:27

72. Thyroid carcinoma in USA 2013 Estimates
•Incidence 60, 220
–Papillary 80-85%
–Follicular 10-15%
–Medullary (MTC) 3-5%
–Anaplastic 1%
•Prevalence >400,000
•4% of all female cancer survivors
•Deaths 1850
Differentiated (DTC) 95%
Siegel + Jemal A. Cancer Statistics 2013
American Cancer Society accessed

73. PTM Treated during 1935-2014 extent of thyroid surgery
Total thyroidectomy
27%(367)
Near total
thyroidectomy
530
39%
Lobectomy 15%
(202)
Bilateral subtotal
18% (235)

74. 7 stage 2 Staging of Patients stage 3 4% Stage 1 98 52% 21 11% 32 17%
Stage IVA 28
15%
Stage IVC 7 4%
Staging of Patients
Tumor staging

75. Watchful F/U in Microcarcinoma of Thyroid (<1cm))
340 patients
74 months average f/u
15% grow more than 3 mm in 10 yr F/U
New nodal mets in 3.4% in 10 yrs
109 had surgery
Conclusion: Observation can be an option in cases of incidental micto PTC
Ito et al world J Surgery 2010

76. MACIS Calculation MACIS score 3.1 (if <40 years) or (0.08 x age)
+ (0.3 x size in cm)
+1 (if locally invasive)
+1 (if incompletely resected)
+3 (if distant metastases present)
Hay et al 1993

77. Thyroid cancer Trends In US 1974-2013 Cancer Registry program (SEERS)
Increased 3.6% per year all PTC
Mortality increased 11% per/year
Data consistent with true increase in US
Lim H, et al JAMA,,2017

79. Neck lymph node metastases
Positive nodes at initial surgery %
Persistent nodes %
F/U neck node recurrence if initially neg:
Mayo surgery %
Outside institution %

80. Ethanol Ablation Loco-regional Metastases
Metastatic or recurrent neck nodes patients
Number of metastatic nodes lesions
Node positive in initial surgery %
Repeat neck surgery %
Size of lesions
Range mm
Average mm
Median mm