1 Lessons from My one Year (2015) of Thyroid Cancer PracticeVahab 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 ClinicPapillary 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 Distribution1 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 2015N= % 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 CancerT 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 CancerRegional 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 CancerStaging 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 visitStaging 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 stageLesson 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
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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 FeaturesCT Angiography
19 Micro-PTC with large lymph node Metastases(case 3).
20 Micro-PTC with large lymph node metastasesRt 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 MayoPre-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 lungsLesson Learned 90% of distant metastases of DTC will be in the lungs
28 Neck lymph node MetastasesF/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 SurgeryMayo 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 overOperated 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 Patients40% 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 RAIPatients 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 MetastasesAll 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 MetastasesAll 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 MetastasesSince1993 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 Metastases39 lesions personal patients seen in 2015
39 Ethanol Ablation Loco-regional MetastasesMetastatic 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 lesionsMicro – PTC 2 patients
43 Ethanol Ablation of primary PTC 2010-201513 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 PTCMy 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 assayIs mass spectrophotometry for Thyroglobulin measurement helpful in Tg antibody positive patients? 22 personal Patients (2015)
49 Comparison of Tg AssaysTg 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 2.3f/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 6Repeat 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 negativepatients 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-positivepatient 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 PTC2002 2008 3 mm hypoechoic nodule nothing suspect 20110
61 Development of Micro –PTC in the rt Thyroid lobe2010
62 Prognostic Schemes for DTCAGES 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
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65 Olmsted County Minnesota Rising thyroid cancer incidenceComparesd 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 incidenceComparesd 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 AblationNeck 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; 2008144:980Median 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 1986-201310-20yrs 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
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 surgeryTotal 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
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79 Neck lymph node metastasesPositive nodes at initial surgery % Persistent nodes % F/U neck node recurrence if initially neg: Mayo surgery % Outside institution %
80 Ethanol Ablation Loco-regional MetastasesMetastatic 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