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Post-operative Management of follicular Cell Derived Thyroid Cancer (FCDTC)

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Title: Post-operative Management of follicular Cell Derived Thyroid Cancer (FCDTC)


1
Post-operative Management of follicular Cell
Derived Thyroid Cancer (FCDTC)
  • Vahab Fatourechi MD
  • Esfahan International Conference
  • Oct 2012

2
Case My cousin
  • My 26 yr old cousin she was unmarried comes to
    Mayo and had near total thyroidectomy 10 year ago
  • . Path showed a 2 cm PTC in the rt lobe and a 2
    mm PTC in the left and two1cm central compartment
    nodes (level VI) were positive

3
MY cousin
  • Do I remnant ablate with RAI?
  • What is the risk of neck node recurrence?
  • If there will be recurrence in the neck when is
    more likely to happen?
  • What is the likelihood mortality?
  • What if she was 45 years old?

4
The Points I will try to Make
  • Most FCDTCs are papillary (PTC)
  • Most PTCs are low risk
  • Most low risk PTCs do not need RAI remnant
    ablation
  • Post operative staging by TNM classification or
    Mayo MACIS score is helpful for choosing who
    needs RAI remnant ablation- Plus common sense
    and patient preference
  • Tg monitoring is helpful even if no RAI ablation

5
The Points I will try to Make
  • Level of and duration of T4 suppressive therapy
    relates to risk profile and disease status
  • Patients with sensitive Tg lt0.1 ng/ml
  • do not need withdrawal or rHTSH stimulated scan
  • Neck US is the best follow up test if no distant
    metastases
  • Tg Pos WBS neg patients with macroscopic
    residual disease should not get RAI therapy

6
The Points I will try to Make
  • Ethanol US guided injection of recurrent neck
    nodes in low risk PTC in selected cases is safe
    and effective
  • ATA guidelines thyroid 2009 is helpful and
    close to our institutions practice with some
    variation.
  • Expect new guidelines in 2013
  • Guidelines show the direction of practice and
    should be individualised

7
Differentiated Thyroid Carcinoma
  • Follicular cell derived thyroid carcinomas (PTC
    and FTC) comprise up to 95 of all thyroid
    carcinomas
  • The vast majority of these tumors are well
    differentiated

Grebe Hay 1995
8
Estimated Incidence of Thyroid Carcinoma in
2012 in USA
  • 56460 cases per year (was 36000 in 2009)
  • 43210 Female
  • 13250 Male F/M (3.3)
  • Estimated death 1780 (3.1)
  • Prevalence 496901(yr 2009)
  • 6 of Us population (18) million have micro PTC
  • Most patients with thyroid cancer are cured, or
    live with their disease

9
Cause-Specific Mortality Rates in FCDC
90
Dying of thyroid carcinoma (cumulative )
Years after initial treatment
10
Watchful F/U in Microcarcinoma of Thyroid (lt1cm))
  • 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
11
TNM Staging of Differentiated Thyroid Cancer
  • T1 Primary tumor lt2cm.
  • T2 gt2 cm and lt4 cm
  • T3 gt4 cm minimal extra thyroidal
    extension
  • T4a Any size tumor beyond thyroid capsule
  • T4b Invasion of pre-vertebral fascia, artery
    vocal cord
  • Tx Tumor size not known

12
Cervical Node-bearing Regions
13
TNM Staging of Differentiated Thyroid Cancer
  • Regional and upper mediastinal nodes (N)
  • N0 Negative nodes
  • NX Nodes not assesses
  • N1a Level VI
  • N1b Other levels and mediastinum
  • Distant Metastases(M)
  • M0 Absent
  • M1 Present

14
TNM Staging of DTC Age lt45
  • Stage I Any T Any N MO
  • Stage II Any T Any N M1

15
TNM Staging of DTC Agegt45
  • Stage I T1,N0,M0
  • Stage II T2,N0,M0
  • Stage III T3,N0,M0, T(1-3)N1a M0,
  • Stage IVA T4a,N0,M0,T4a,N1a, M0,
    T(1-4)N1b M0
  • Stage IVB T4b any N M0
  • Stage IVC Any T any N M1

16
PTC Survival by TNM Stage
n2,284 1940-97 P0.0001
Surviving papillary thyroid carcinoma ()
TNM stage
I 1,360 II 493 III 399 IV
32
Years after initial treatment
17
Cell Types Associated with Aggressive FCDTC Tumors
  • Follicular cancer with vascular invasion
  • Hurtle cell with vascular invasion
  • Columnar cell PTC
  • Insular cell PTC
  • Tall cell PTC
  • Solid PTC
  • Trabecular PTC
  • Higher grades of PTC Grade 2-4
  • Diffuse sclerosing PTC

18
MACIS Calculation
ID Hay
  • MACIS score (LOW RISKlt6)
  • 3.1 (if lt40 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
Should apply only to classic PTC
19
Cause-Specific Survival by MACIS Score 1940-97
lt6 (1,900 83)
6-6.99 (201 9)
Survival ()
7-7.99 (75 3)
n2,284 P0.0001 MACIS score
³8 (108 5)
Years after initial treatment
20
Cause Specific Mortality from PTC in High-and
Low-Risk Groups TNM, MACIS
TNM
III IV (431)
I II (1,853)
Dying of papillary carcinoma (cumulative )
MACIS
6 (384)
lt6 (1,900)
ID Hay
Years after initial treatment
21
Arbitrariness of Risk Factor Assessment
  • 43 year old T1 N1b M0 would be Stage I
  • 46 year old with the same disease will be Stage
    IVA
  • A 40 year old with pulmonary and bone metastases
    will be considered Stage II
  • An 80 year old operated for benign adenoma and 4
    mm incidental PTC with be MACIS 7.5 will be
    considered high risk

22
Arbitrariness of Risk Factor Assessment
  • 46 ys. 5 cm tumor N0 M0 MACIS
    5.1

  • TNM Stage III
  • 46 ys. 1cm N level VI MACIS
    3.6

  • TNM Stage III
  • 46 ys. 1cm tumor, N Level II MACIS
    3.6

  • TNM Stage IV A

Comment Risk assessment is helpful but consider
overall clinical presentation
23
Post-operative Management of Follicular Cell
Derived Thyroid Cancer
  • Completion thyroidectomy

24
Completion thyroidectomy
  • ATA accepts lobectomy alone under certain
    conditions
  • Not needed for occult incidental lt1.0 cm PTC
  • Not needed for follicular cancer with minimal
    capsular invasion and no vascular invasion
  • Ideally if needed should be done first week
    after initial surgery or after 2-3 months

25
Post-operative Management of Follicular Cell
Derived Thyroid Cancer
  • Post operative remnant RAI ablation

26
Impact of I131 on FCDTC Recurrence and Mortality
Mazzaferri 1997
Mazzaferri et al 1997
27
Problems with Mazzaferri Data Set
  • Various pathologies (PTC / FTC / HCC)
  • Various surgeries (Lobectomy / subtotal / total)
  • I-131 administered only to those with more
    complete surgery
  • No risk-group stratification
  • No evaluation of I-131 efficacy following
    adequate, complete surgery

28
I-131 Remnant Ablation
ATA Thyroid 2009
ATA Guidelines 2009
29
RAI Remnant Ablation (ATA 2009)
  • Non for tumorlt1 cm
  • Non for multifocal lt1 cm
  • May not be needed for small minimally invasive
    follicular
  • For 1-4 cm tumor selected patients with risk
    factors, node, cell type, age
  • For gt4 cm, M1
  • Gross extra thyroidal extention

30
I-131 Remnant Ablation (ATA 2009)
  • Either withdrawal or rhTSH
  • Low iodine diet 1-2 weeks
  • Pre-therapy scan useful
  • 30-100 mCi adequate for remnant
  • Residual disease 100-200 mCi
  • Start T4 on day 3
  • Post therapy scan recommended
    Sherman et al and Fatourechi et al 2000

31
National Thyroid Cancer Registry
Jonklass et al 2007
32
Recurrence in low risk PTC (Hay ID)
I131 Ablation
100
No Ablation
96
Relapse free survival ()
92
88
84
0
5
10
15
20
Years from diagnosis
1163 patients total or near-total TTX 1970 -
2000
33
Survival for low risk PTC (MACIS lt 6) (Hay ID)
100
95
Survival (cause-specific)
I131 Ablation (n498)
90
No Ablation (n665)
85
0
0
5
10
15
20
Years from diagnosis
1163 patients total or near-total TTX 1970 -
2000
34
Recurrence (TxN0M0, MACISlt6)
100
I131 Ablation
90
No Ablation
80
0
5
10
15
20
Years from diagnosis
636 node negative patients total or near-total
TTX 1970 - 2000
35
Carcinogenesis with I131
3 populations (Sweden, Italy, France) 6841
patients Mean dose I131 162 mCi Mean F/U of 13
years Incidence of 2nd malignancy
Dose dependent risk increase


Increased risk for cancer of Salivary
gland 7.5 Bone soft tissue 4.0 Uterus / female
genital 2.3 Colorectal 1.3
Bone and soft tissue
Rubino 2003
36
Secondary Cancer Risk after RAI
  • Comments
  • Dose related small risk of secondary cancers with
    doses above 50 mCi
  • Doses over 100 mCi cause 3 leukemia and 53 solid
    tumor /100,000/10Yr. Rubino Br J
    Cancer 2003
  • Meta analysis RR for leukemia
    2.5 For other not
    significant cancers. Sawka Thyroid 2009
  • Late increased mortality from non thyroid
    malignancy in long term F/U of children
    Hay world J surg 2010
  • When benefits questionable or controversial why
    risk it?

37
Arguments for a Selective Approach
  • Avoid overtreatment of patients who do not
    require aggressive therapy
  • Avoid under-treatment of patients at high risk of
    disease residue or recurrence
  • Avoid over-investigation (with associated
    expense, morbidity and psychological distress) of
    patients with low-risk of recurrence
  • Avoid under-evaluation of high risk patients

38
Conclusion
  • In low risk patients, remnant ablation is not
    required for interpretation or monitoring of Tg
  • SO LONG AS
  • Thyroidectomy is truly near total
  • Follow-up is primarily through US or other
    anatomic imaging, rather than isotope scans

39
Remnant Ablation Selection by MACIS Score
  • No Remnant ablation for MACIS lt6.0
  • Does not consider lymph node at any age, at any
    site, any size
  • Does not consider multifocality
  • Does not apply to high risk cell types
  • May apply to grade 1 PTC only
  • Does not consider minimal extra-thyroidal
    extension
  • Critics May apply to Mayo because of surgical
    expertise

40
External Beam Radiation (41B) (ATA 2009)
  • To be considered
  • Over age 45, extra thyroidal extension at surgery
    possibility of microscopic residual disease.
  • Gross residual tumor not likely responsive to
    surgery or RAI
  • For other unresectable disease in critical areas
    bone, CNS, mediastinal, pelvic
  • Comment For Neck should be delayed until
    surgical options exhausted. Applicable to unusual
    cell type, high grade PTC

41
Post Operative Management of follicular Cell
Derived Thyroid Cancer
  • Suppressive thyroxine therapy

42
Effect of TSH Suppression on Relapse-free
Survival in DTC
139 patients with DTC
45 patients with stable TSH
Similar findings in entire cohort of 141 patients
No differences in AJCC stage of patients in the
two groups
Pujol et al 1996
43
TSH Suppression and Outcomes
  • 683 patients with DTC followed at 14 institutions
    up to 10 years
  • Majority (90) were PTC
  • A Stage I II
  • B Stage III IV

A
TSH Suppression
Free of Progressive Disease
B
p 0.03
Cooper et al 1998
Follow-up
44
T4 Suppressive Therapy (ATA 2009)
  • High risk, intermediate risk TSH lt0.1
  • Low risk 0.1-0.5
  • Persistent disease TSHlt0.1 indefinitely
  • Disease free high risk, TSH 0.1-0.5, 5-10 yrs
  • Disease free low risk TSH 0.3-2.0
  • No RAI, disease free Tg undetectable TSH 0.3-2.0

45
Post-operative Management of follicular Cell
Derived Thyroid Cancer
  • Thyroglobulin monitoring

46
Thyroglobulin Monitoring (ATA 2009)
  • Every 6-12 months initially then yearly
    depending on risk
  • Even if not a TT or remnant ablation

47
Post Operative Management of follicular Cell
Derived Thyroid Cancer
  • Withdrawal or rhTSH stimulation testing

48
rhTSH Stimulation (ATA 2009)
  • After 6-12 months after remnant ablation
  • If US is neg. and stim-Tg is undetectable no need
    to repeat
  • Comment
  • Mayo experience with sensitive Tg lt0.1
  • rhTSH stimulated-Tg does not change management
    and may not be needed

49
Is rhTSH Helpful in Undetectable Sensitive Serum
Tg in Thyroid Cancer?
  • 163 patients , post thyroidectomy and RAI
    ablation , neg Tg antibodies
  • Tglt0.1 on T4
  • Medium 3.6 Yrs. F/U
  • Only 2 stimulated Tg gt2.0
  • 6 recurrences detected by US of the neck
  • AM Chindris, N Diel, J crook , V Fatourechi, R
    Smallridge JCEM Aug 2012

50
rhTSH in Undetectable Sensitive Serum Tg in
Thyroid Cancer is not Helpful
  • Conclusion
  • In pateints with FCDTC if T-4 suppressed Tg is
    lt0.1 ng/ml annual Tg- supp and periodic neck US
    are adequate
  • rhTSH testing and WBS do not change management
    and are not needed
  • By analogy same should apply to withdrawal
    Tg-stim and WBS
  • A. Chindris, N. Diel, J. crook , V. Fatourechi,
    R. Smallridge JCEM Aug 2012

51
No RAI remnant ablation 9 Cases of
Recurrence With Negative Tg Ab
Is Tg monitoring helpfu without RAI Ablation?
Plazcowski et al 2009
52
No RRA No Recurrence Average Tg During Follow-up
n150 MACISlt6 Complete surgical resection Near
total thyroidectomy
Is Tg monitoring helpful without RAI Ablation?
Plazcowski et al 2009
53
Post operative Management of Follicular Cell
Derived Thyroid Cancer
  • Neck Ultrasound

54
Neck US (ATA 2009)
  • After 6-12 months then periodically depending on
    risk and Tg
  • FNA for suspicious lesionsgt5-8 mm if changes
    management
  • Lesions 5-8 mm need F/U intervention if grow
  • Comments Frequency not clear annual for 5 years
    biannual 10 years? Expertise is important

55
Post Operative Management of follicular Cell
Derived Thyroid Cancer
  • Alcohol Ablation of recurrent
  • disease in the neck

56
US Guided Percutaneous Ethanol Ablation Neck Mets
In Stage 1 PTC
  • 88 patients, 133 recurrent nodes
  • Injection of mean of 0.8.cc ethanol, 5 yr F/U
  • 100 No doppler flow at last F/U, shruncken
  • 49 not visible
  • No complication. No permanent hoarseness
  • 4 needed surgery
  • Hay et al ATA 82th Ann meeting Abstract Sept
    2012

57
WBS (ATA 2009)
  • No F/U routine WBS needed if first stimulated Tg
    undetectable and neg US
  • For high risk and intermediate risk F/U WBS with
    I-123 or low dose I-131
  • Comments If remnant ablation is done only for
    high risk then WBS is needed since can change
    management

58
Tg WBS-negative Management (ATA 2009)
  • Empiric 100-200 mCi if Tg withdrawal gt10 and
    rhTSH stimulated gt5 and no imaging evidence of
    disease. No further RAI if post therapy neg
  • continue as long as there is uptake
  • IF Tg bellow above values and no structural
    disease only F/U
  • Comment is too aggressive, most patients with
    this level of Tg have microscopic disease in the
    neck

59
Tg WBS negative Comments
  • Low risk patients Most likely US of neck with
    follow up will show resectable disease in time
  • Progressive scan-neg disease needs referral for
    targeted therapy or off label TKI

60
Tg WBS negative
  • For high risk patient in with gross metastatic
    disease empiric RAI is not effective in WBS
    negative patients
  • Fatourechi et al
    JCEM 2002

61
FDG-PET (ATA)
  • Tg positive scanneg,Tggt10
  • Initial staging in poorly differentiated
  • As prognostic tool for evaluation of treatment
    response
  • Comment Most Tg positive scan neg low risk will
    have neck node by expert neck ultrasonographer

62
RAI for Metastases (ATA 2009)
  • No recommendations for dosimetry or empiric
    Insufficient data to recommend rhTSHstimulated
    RAI therapy for all patients
  • rhTSHstimulated RAI therapy for selected
    patients
  • Lithium adjunct therapy insufficient data to
    recommend

63
RAI Therapy (ATA 2009)
  • Pulmonary mico- mets with RAI at 6-12 months
    interval as long as there is uptake dose 100-200
    mCI empiric
  • Macro-mets same if objective reduction in size or
    reduced Tg
  • Bone mets with 100-200 but rarely curative

64
Complications of RAI Therapy (ATA 2009)
  • Small risk of leukemia and solid tumor gt500 mCi
  • Risk of secondary malignancies
  • Need basal CBC renal function prior to RAI

65
CNS Lesions (ATA 2009)
  • Complete excision regardless of RAI avidity
  • Non surgical lesions external beam or targeted
    therapies
  • RAI if there is uptake, prior external beam and
    corticosteroids strongly recommended

66
Other Points (ATA 2009)
  • Chemotherapy discouraged, not effective
  • Off-label TKI if all fails and progressive
    disease
  • Refer for trial of targeted therapy if all fails
  • Alternative local or palliative therapies
  • Bisphosphonate infusions for bone metastases

67
Case My cousin
  • My 26 yr old cousin she was unmarried comes to
    Mayo and had near total thyroidectomy 10 year ago
  • Path showed a 2 cm PTC in the rt lobe and a 2 mm
    PTC in the left and two1cm central compartment
    nodes (level VI) were positive

68
MY cousin
  • Do I remnant ablate with RAI?
  • What is the risk of neck node recurrence?
  • If there will be recurrence in the neck when is
    more likely to happen?
  • What is the likelihood mortality?
  • What if she was 45 years old?

69
Conclusions
  • Quality of initial surgery is the best predictor
    of outcome
  • Both surgical and post-surgical management should
    be coordinated by a knowledgeable
    endocrinologist, as part of a multidisciplinary
    team
  • The majority of non-medullary DTC patients have
    an excellent long-term prognosis.
  • It is important to target the occasional
    high-risk patient for more aggressive management.
  • Postoperative risk assessment is key

70
Conclusions
  • The current trend is to avoid RAI therapy for low
    risk patients (includes majority)
  • For RAI remnant ablation my personal bias is to
    use both MACIS, TNM classification, consider
    other clinical factors and use common sense and
    decide after discussion of controversy and ATA
    guidelines with the patient
  • Aggressive progressive cases not responding to
    1-131 therapy or surgery or EBRT are candidates
    for referral for trial of targeted therapies
  • Off label use of Tyrosine Kinase inhibitors may
    be appropriate if not a candidate for trial or
    no possibility of referral (Oncologists should be
    involved at this point)

71
.
  • Thank you

72
Summary
  • Low-risk thyroid cancer does not require RRA,
    WBS, rhTSH
  • Postop staging can guide adjuvant therapy and
    follow-up
  • Long-term, minimally harmful follow-up should be
    the goal
  • Most patients will live long and prosper!
  • High risk patients need to be identified, treated
    more aggressively and monitored using all of the
    tools that both Nuclear and Diagnostic Radiology
    can bring to bear
  • The goal should be to treat patients who will
    benefit from that treatment, while protecting
    those patients from harm who will not benefit
    from the therapy!

73
Defining Risk The tumor - host relationship
Tumor histology Tumor biology
Patient factors
Tumor extent
74
Defining Risk The tumor - host relationship
Tumor histology Tumor biology
Patient factors
Tumor extent
75
Distinguish Aggressive from Advanced
ADVANCED
Classic PTC 18-year old woman Nodes noted since
age 14
76
Primary Thyroid Carcinoma
FTC
PTC
ATC
HCC
77
Distinguish Aggressive from Advanced
AGGRESSIVE
ATC
Insular
TC PTC
78
Defining Risk The tumor - host relationship
Tumor histology Tumor biology
Patient factors
Tumor extent
79
Putting it all together
Tumor histology Tumor biology
Patient factors
Tumor extent Effectiveness of therapy
80
Weighing Risk and Benefit
  • If there is no measureable benefit, is there at
    least no measurable risk?

81
pTNM Staging for DTC
?45 years
?45 years
I
TxNxM0
T1N0M0
II
TxNxM1
T2N0M0
III
-
T3N0M0 / T1-3N1aM0
IVA
-
T4aNxM0 / T1-3N1bM0
IVB
-
T4bNxM0
IVC
-
TxNxM1
Greene et al 2003
82
Remember to Include Treatment Efficacy!
  • Adaptive risk-assessment
  • Treatment efficacy
  • Completeness of surgical resection
  • Postoperative Thyroglobulin
  • Initial postoperative USS
  • Other select imaging

83
pTNM Staging for DTC
?45 years
?45 years
I
TxNxM0
T1N0M0
II
TxNxM1
T2N0M0
III
-
T3N0M0 / T1-3N1aM0
IVA
-
T4aNxM0 / T1-3N1bM0
IVB
-
T4bNxM0
IVC
-
TxNxM1
Greene et al 2003
84
Remember to Include Treatment Efficacy!
  • Adaptive risk-assessment
  • Treatment efficacy
  • Completeness of surgical resection
  • Postoperative Thyroglobulin
  • Initial postoperative USS
  • Other select imaging

85
Case 1
35 y.o. woman with thyroid nodule 3.5cm PTC Total
thyroidectomy Central node dissection (node
ve) Chest X-ray negative Post-op Tg 0.2 ng/mL
(TSH 0.4)
86
Thyroid Carcinoma The Spectrum of the Disease
1.5mm Papillary microcancer
8cm grossly invasive FTC
87
MACIS Calculation
  • MACIS score
  • 3.1 (if lt40 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
88
Case 1
35 y.o. woman with thyroid nodule 3.5cm PTC Total
thyroidectomy Central node dissection (node
ve) Chest X-ray negative Post-op Tg 0.2 ng/mL
(TSH 0.4)
AJCC Stage 1 pT2N1aM0 MACIS 4.15 AGES low
risk AMES low risk
Radioactive Iodine Therapy?
89
Survival in PTC (TxN1M0, MACISlt6)
100
95
I131 Ablation (n303)
Survival (cause-specific)
90
No Ablation (n224)
85
0
0
5
10
15
20
Years from diagnosis
527 node positive patients total or near-total
TTX 1970 - 2000
90
Recurrence (TxN1M0, MACISlt6)
100
I131 Ablation
No Ablation
90
80
5
10
15
20
0
Years from diagnosis
527 node positive patients total or near-total
TTX 1970 - 2000
91
Yes, but thats just Mayo
They have better surgeons They do routine central
neck dissection or Theyre just crazy!
92
Occult (lt1.5cm) PTC
100
80
MACIS lt6 Unifocal Node negative n 582 p0.03
60
BLR I-131 (n 42)
Free of Recurrence ()
BLR only (n 540)
40
20
0
0
10
20
30
40
Years from Diagnosis
93
Occult (lt1.5cm) PTC
100
80
MACIS lt6 Unifocal Node negative n 582 p0.03
60
BLR I-131 (n 42)
Free of Recurrence ()
BLR only (n 540)
40
20
0
0
10
20
30
40
Years from Diagnosis
94
Occult (lt1.5cm) PTC
100
80
MACIS lt6 Unifocal Node positive n 248 p0.27
60
BLR I-131 (n 81)
Free of Recurrence ()
BLR only (n 167)
40
20
0
0
10
20
30
40
Years from Diagnosis
95
Occult (lt1.5cm) PTC
100
80
MACIS lt6 Multifocal Node negative n 190 p0.68
60
BLR I-131 (n 39)
Free of Recurrence ()
BLR only (n 151)
40
20
0
0
10
20
30
40
Years from Diagnosis
96
Occult (lt1.5cm) PTC
100
80
MACIS lt6 Multifocal Node positive n 159 p0.48
60
BLR I-131 (n 93)
Free of Recurrence ()
BLR only (n 66)
40
20
0
0
10
20
30
40
Years from Diagnosis
97
A Proposed Strategy Based on ATA Guidelines 2009
Low risk cancer
High risk cancer
Intermed. risk cancer
Young patient PTC Histology Non-invasive /-
central nodes Complete resection
Any Histology Grossly Invasive Metastatic
disease Incomplete resection
Older patient, low risk disease PTC minimally
invasive Non-PTC small, non-invasive Complete
resection Large nodes (PTC N1b)
Tg lt 1 ng/dL?
Tg lt 1 ng/dL?
Thyrogen
T4 Withdrawal
Yes
Yes
No
No
No I-131
Remnant Ablation
I-131 Therapy
98
Complications of I-131
  • Salivary gland injury
  • Nasolacrimal duct occlusion
  • Bone marrow suppression uncertain impact
  • Oligomenorrhea (20 30) increased miscarriage
    rate 6 12 mo. menopause earlier by 1 year
  • Oligospermia and male hypogonadism
  • Second primary malignancies
  • Benefits should outweigh the potential
    risks

99
Carcinogenesis with I131
3 populations (Sweden, Italy, France) 6841
patients Mean dose I131 162 mCi Mean F/U of 13
years Incidence of 2nd malignancy
Dose dependent risk increase


Increased risk for cancer of Salivary
gland 7.5 Bone soft tissue 4.0 Uterus / female
genital 2.3 Colorectal 1.3
6 GBq
Bone and soft tissue
Rubino 2003
100
Case 1
35 y.o. woman with thyroid nodule 3.5cm PTC Total
thyroidectomy Central node dissection (node
ve) Chest X-ray negative
AJCC Stage 1 (NTCR Stage 1) pT2N1aM0 MACIS
4.15 AGES low risk AMES low risk
Adjuvant I-131 Therapy?
101
Conclusions
  • Quality of initial surgery is the best predictor
    of outcome
  • The majority of non-medullary DTC patients have
    an excellent long-term prognosis.
  • It is important to target the occasional
    high-risk patient for more aggressive management.
  • Postoperative risk assessment is key
  • 2009 ATA guidelines are closer to current Mayo
    practice but not close enough

102
Additional Benefits of I-131
  • Improved ability to monitor for disease
    recurrence?
  • Tg basal
  • Tg stimulated

103
Case 2
21 y.o. man with thyroid nodule FNAB papillary
thyroid CA Total thyroidectomy, bilateral
neck Path 3.8cm, PTC, invasive 22 of 36 nodes
positive (II, III, IV) 10 of 16 nodes positive
(VI VII) 3 of 7 nodes positive (contralat. IV)
pT4N1bMx PTC M0 MACIS 5.24 M1 MACIS 8.24
Postoperative Tg 5064 ng/mL
104
(No Transcript)
105
Case 2 21 year old man
pT4aN1bM1 PTC AJCC Stage 2 MACIS 8.24
  • How much I-131?
  • How often?
  • When should we stop?
  • How should the patient be prepared?

106
Following I-131 Therapy
Total dose 640mCi
107
Management of Thyroid Cancer Works!
30 25 20 15 10 5 0
Mortality from PTC n2,444 P0.002
Recurrence, any site n2,305 Plt0.001
1940-49 (135)
Cumulative with occurrence
1940-49 (158)
1950-99 (2,170)
1950-99 (2,286)
0
5
10
15
20
0
5
10
15
20
Years after initial surgery
CP1018305-9
Hay et al 2006
108
Prognostic Scoring
109
Cause-Specific Survival by MACIS Score 1940-97 I
Hay
lt6 (1,900 83)
6-6.99 (201 9)
Survival ()
7-7.99 (75 3)
n2,284 P0.0001 MACIS score
³8 (108 5)
Years after initial treatment
110
American Thyroid Association Guidelines for
Management of Differentiated Thyroid
Cancer Committee of 13 experts Cooper et al,
Thyroid November 2009
  • .

111
ATA 2009 Recommendations for RAI Remnant
Ablation
112
Impact of I131 on Thyroid Cancer Mortality
263 patients in treatment group 50 patients in
control group
Redrawn from Varma et al 1970
113
National Thyroid Cancer Registry
Remember High risk patients do benefit from RAI
therapy
Jonklass et al 2007
114
PTC Survival by TNM Stage
n2,284 1940-97 P0.0001
Surviving papillary thyroid carcinoma ()
TNM stage
I 1,360 II 493 III 399 IV 32
Years after initial treatment
115
Accordance with ATA Guidelines Nationally
(n52964)
  • Highest for Stage II lt45 80
  • Lowest for Stage II gt45 52
  • Age gt65 and black lowest accordance
  • Surgical accordance 71
  • RAI 56

Famakinwa Am J Surg Feb 2010
116
Outcomes by AJCC Stage
Hundahl et al 1988
Stage IV
Stage IV
PTC (n 42,686)
FTC (n 6764)
gt99 5-year survival for Stages I II
117
Prognostic Schemes for DTC
EORTC
AGES
AMES
MACIS
OSU
SKMMC
X
X
Age
--
--
Sex
X
X
Size
--
--
Multicentricity
X
--
Grade
PTC
PTC
Histology
X
X
Invasion
--
--
Nodes
X
X
Metastases
--
X
Complete excision
118
Value of rhTSH Tg If T4 suppressed Tg lt0.1 with
sensitive Tg
  • 171 Pts.Tglt0.1 rhTSH stim F/U (461000)
  • Only one had stimTg gt2.0
  • One with neg-stim Tg had neck node and 7 with
    stim-Tg lt0.1-2.0 had neck node
  • US but not Stim-Tg detected neck node in 7
    patients Comment With sensitive Tg rhTSH
    stim-Tg not needed and baseline Tg and neck US
    more sensitive (31000)

Smallridg, chanders, Diehs, Cook and Fatourechi
ATA meeting Paris
119
A Selective Approach
Prognostic factor and risk group analysis makes
a selective approach to differentiated thyroid
cancer possible. Such an approach can spare many
patients the morbidity and expense of
unnecessarily aggressive surgery and treatment
and monitoring, without compromising oncologic
principles.
Loree TR Semin Surg Oncol 11246, 1995
120
2 year Risk assessment n 588, Median F/U 7 Ys.
  • Suppressed Tg lt1 ng
  • Stimulated Tg lt1ng
  • Negative imaging
  • No evidence of disease at final F/U
  • Low risk 97
  • Intermediate risk 94
  • High risk 82

Tuttle et. Al. Thyroid DEC 2010
121
MACIS and Cause-Specific Survival
Metastases
Age
Invasion
Size
C
Completeness
Hay et al 1993
122
American Thyroid Association(ATA) Risk of
Recurrence Classification
  • Low risk
  • No local or distant mets,
  • Complete resection, no local invasion,
  • No aggressive histology, no vascular invasion,
  • No 1-131 uptake outside of thyroid on post
    therapy scan

Thyroid 2009
123
ATA Risk of Recurrence Classification
  • High Risk
  • Macroscopic neck invasion
  • Incomplete resection
  • Distant metastases
  • Comments With positive neck nodes 10-30 have
    risk of neck node recurrence

Thyroid 2009
124
ATA Risk of Recurrence Classification
  • Intermediate Risk
  • Microscopic peri-thyroidal invasion
  • Lymph nodes mets
  • 131-1 uptake outside of thyroid,
  • Aggressive histology or vascular invasion

Thyroid 2009
125
Other Factors Influencing Prognosis
  • Definite
  • Age (Almost all studies)
  • Controversial
  • Gender (Univariate)
  • Uncertain
  • Immuno-suppression

126
Complications of RAI Therapy (ATA 2009)
  • Amifostine, sour candy first 24 hrs, hydration,
    cholinergic
  • Preventive measures with dental consult for dry
    mouth
  • Surgical procedure for nasolacrimal obstruction
  • Small risk of leukemia and solid tumor gt500 mCi
  • Need basal CBC renal function prior to RAI

127
Is rhTSH Helpful in Undetectable Sensitive Serum
Tg in Thyroid Cancer?
  • WBS not helpful
  • One stim 1g gt2
  • One stim Tg 0.8
  • 4 stim Tg lt0.5
  • On stim Tg lt0.1 Stage IV with lung mets
  • A. Chindris, N. Diel, J. crook , V. Fatourechi,
    R. Smallridge JCEM Aug 2012

128
Complications of RAI Therapy and Precautions
(ATA 2009)
  • No pregnancy 6-12 months
  • No RAI unless no lactation 6-8 wks
  • Dopaminergics for recently lactating
  • Dose above 200mCi exceeds safe dose for age over
    70

129
Post-operative Management of PTC Based on MACIS
Risk Assessment
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