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Management in 2006 of Patients with Low-Risk Papillary Thyroid Carcinoma

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Title: Management in 2006 of Patients with Low-Risk Papillary Thyroid Carcinoma


1
Management in 2006 of Patients with Low-Risk
Papillary Thyroid Carcinoma
  • Professor Ian D. Hay MB PhD FRCP
  • Mayo Clinic College of Medicine

2
Differentiated Thyroid CarcinomaManaged at Mayo
Clinic 1940-2000Histotype Distribution
Papillary (2,512) 82
8
5
5
Medullary (246)
n3,048 1940-2000
Follicular (155)
Hürthle cell (155)
CP1028491-8
3
2,512 Papillary Thyroid Carcinoma
PatientsManaged At Mayo Clinic During
1940-2000Presenting Disease
p TNM Stages
MACIS Scores
I (60)
lt6 (84)
II (21)
6 (16)
III (18)
IV (1)
n2,512 1940-2000
CP1028491-1
4
Managing Low-risk DTC in 2005A Day in the Life
of a Mayo PTC Specialist!
  • In an attempt, perhaps, to better define later a
    more rational approach to the postoperative
    management of low-risk differentiated thyroid
    cancer, let us first consider, by way of
    introduction, two cases of papillary thyroid
    microcarcinoma (PTM) seen on a recent Mayo
    clinic outpatient day

5
Case 1 Node-Positive PTM
  • 3/99 59y/o male 4hr op (TTx, central
    compartment exploration, (L)MND) for bilateral
    multicentric 1 cm PTM 20/46 pos nodes(Delphian,
    central, lat neck)
  • 5-9/99 30 100 mCi I-131 for ablation
  • 3/00 rhTSH-stimulated I-123 WBS and US neck
    negative Tg auto-ab pos

6
Case 1 Node-Positive PTM
  • 4/01-4/04 annual neck US showed 2 (L) bed
    lesions, initially 4 and 6 mm, but growing to 6,
    8mm with incr. flow, microcalcifications Tg
    0.3-0.6 Ab-pos
  • 4/04 Pos USGB (L) bed led to 2 hr op, excising
    2/2 pos (L) T/E groove nodes
  • 9/05 Ab-neg Tg lt0.1ng/mL US neck negative for
    recurrence at 78 p/op mo

7
Case 2 Recurrent node-positive PTC
  • 4/98 28y/o female TTx, central NLND for
    multifocal PTM 6/7 pos nodes
  • 5/98 175 mCi I-131 for 6.8 uptake
  • 1/99 re- exploration for palpable (L) lat nodes
    1/5 nodes pos at path exam
  • 10/99 200 mCi given for neck uptake
  • 4/00 rhTSH- WBS neg Tg (USC) lt1

8
Case 2 Another Uncooperative NNM
  • 2001-2003 multiple neg rhTSH-WBS but Tg rise
    after stim led to neg MRI of neck and whole body
    FDG-PET/CT
  • 2/03 Pos USGB of 7X4X3mm node, and pt sent to MC
    for possible PEI
  • 3/03 Tg 0.3(Ab-neg) 8X5X3mm (L) bed node
    treated with US-guided PEI

9
Case 2 Adequately Treated NNM
  • 7/03 node re-treated with 0.2cc EtOH
  • 11/03- 10/04 injected node no longer
    identifiable on repeated US exams
  • 10/05 TSH 0.1, Tg lt0.1 ng/mL neck US negative
    for recurrence at 90 mo

10
What do these cases illustrate?
  • Inadequacy of regional nodal resection at first
    neck exploration
  • Futility of p/op remnant ablation
  • Efficiency of PEI in nodal ablation

11
What clinical and research experiences would
justify such atypical views on postop management?
  • 23 years consulting on patients with thyroid
    malignancy at the Mayo Clinic
  • Daily experience in managing DTC patients now
    gt400 cases annually
  • Management approach also influenced by studying
    cohort of 2,512 PTC pts treated at Mayo during
    1940 to 2000

12
PTC Management in Five Decades
  • During 1950 through 1999, mortality and
    recurrence rates in 2,286 Mayo PTC patients did
    not progressively improve with successive decades
  • Outcome was excellent in low-risk (MACIS lt6) PTC
    patients treated by NTT, conservative nodal
    dissection, and not improved by increasing use of
    postoperative remnant ablation
  • World J Surg 26 879, 2002

13
Relevance of Epidemiology to Contemporary
Management
  • Presenting features (patient and tumor variables)
    permit outcome prediction tumor biology more
    powerful than therapy choices
  • Majority (85) of PTC patients at minimal risk of
    recurrence or cause-specific mortality
  • Logically, therefore, aggressive adjunctive
    treatments should be restricted to minority (15)
    at high-risk, i.e., applying the principle of
    letting the punishment fit the crime.
    Cady,B Am J Surg 174 462, 1997

14
APPLYING COMMON SENSE TO MANAGING PATIENTS
WITH LOW-RISK DIFFERENTIATED THYROID CANCER
15
Five Steps in Primary Management of LRPTC
  • I. Diagnosis cytologic and histopathologic
  • II. Primary surgical treatment
  • III. Staging and risk-group assignment
  • IV. Adjuvant therapy
  • V. Long-term surveillance

16
Many can biopsy but few can interpret thyroid
cytology
  • If an endocrinologist or surgeon is to serve
    well patients with NTD, then he/she must
    identify, ideally sited conveniently, a
    cytopathologist whose skills are associated with
    acceptably low rates of both false-positive and
    false-negative reports

17
Common Sense Approach to LRPTC Management
  • I. Diagnosis cytologic and histopathologic
  • II. Primary surgical treatment

18
2,512 Papillary Thyroid Carcinoma
PatientsManaged At Mayo Clinic During
1940-2000Trends in Extent of Primary Surgery
n2,512
Near-total thyroidectomy (1,324)
Unilateral lobectomy (293)
Initialthyroidoperations()
Total thyroidectomy (635)
Bilateral subtotal resection (220)
1940- 1954
1955- 1969
1985- 2000
1970- 1984
CP1028491-2
19
Appropriate Therapy for Low-risk Papillary Cancer
  • Low-risk PTC represents majority of FCDC in
    areas of iodine sufficiency
  • Such tumors multicentric, typically bilateral,
    often involving neck nodes
  • Reasonable, therefore, to employ a bilateral
    approach and to determine nodal status on
    treatment day one

20
320 Papillary Thyroid Carcinoma PatientsManaged
at Mayo Clinic during 1940-1954Impact of
Bilateral Lobar Resection
Recurrence, Any Site
Mortality from PTC
n320 P0.35
n296 Plt0.001
Unilateral lobectomy(176)
Unilaterallobectomy(160)
Cumulative with occurrence
Bilaterallobar resection(144)
Bilaterallobar resection(136)
0
10
20
30
40
0
10
20
30
40
Years after initial surgery
CP1029349-1
21
Impact of BLR on Mortality and Recurrence inLow-
and High-Risk PTCBy MACIS lt6 and 6
Mortality
Recurrence
1940-54 Plt0.001 n256
UL (135)
MACIS lt6 P0.31 n296
BLR (136)
UL (160)
BLR (121)
0
5
10
15
20
0
5
10
15
20
1940-2000 P0.015 n280
MACIS 6 P0.007 n391
Cumulative with occurrence
UL (60)
UL (39)
BLR (241)
BLR (331)
0
5
10
15
25
20
0
5
10
15
25
20
Years after initial surgery
CP1029349-2
22
Advantages of NT/TT in Papillary Thyroid Cancer
  • Bilateral lobar resection (BLR) reduces
    locoregional recurrences in all and reduces
    cause-specific mortality in high-risk PTC
  • Thus in 2006, a pre-op FNA dx of PTC should lead
    to BLR (NT/TT), with safeguarding of parathyroids

23
Importance of Neck Nodal Status in Low-Risk PTC
  • If a PTC patient has only a thyroidectomy and
    no inspection or exploration of the central
    compartment, with sampling of level VI nodes,
    then the patient has been ill-served, and has
    already fallen on only day one of treatment into
    a pitfall

24
Pre-op Ultrasound Mapping and the Lateral Neck
  • Preoperative neck ultrasound, with identification
    of nodal mets, permits planned appropriate nodal
    resection at the time of first neck exploration
  • Discovery of a lateral neck nodal met (removed at
    open biopsy, or positive on USGB or at FS) should
    lead to function-sparing modified neck dissection
    at first neck exploration

25
Role of Preoperative StagingATA 2006 Guidelines
  • R21. Preoperative neck ultrasound for the
    contralateral lobe and cervical (central and
    bilateral) lymph nodes is recommended for all
    patients undergoing thyroidectomy for malignant
    cytologic findings on biopsy Recommendation B
  • The ATA Guidelines
    Taskforce
  • Thyroid 16 (2)
    1-33, Feb 2006.

26
Expectations of Primary Neck Surgery in PTC
  • Avoidance of central compartment exploration no
    longer acceptable
  • Iatrogenic hypoparathyroidism unwarranted and
    avoidable in 2006
  • I-131 should not be used as a postoperative
    cure-all to mop up leftovers after inadequate
    surgery

27
Lymph Node Dissection in PTCATA 2006 Guidelines
  • R27. Routine central compartment (level VI) neck
    dissection should be considered for patients with
    PTC Recommendation B
  • R28. Lateral neck compartmental lymph node
    dissection should be performed for patients with
    biopsy-proven metastatic cervical lymphadenopathy
    detected clinically or by imaging, especially
    when they are likely to fail RAI treatment based
    on lymph node size, number, or other factors,
    such as aggressive histology of the primary tumor
    Recommendation B


28
Common Sense Approach to LRPTC Management
  • I. Diagnosis cytologic and histopathologic
  • II. Primary surgical treatment
  • III. Staging and risk-group assignment

29
Relevance of Post-op Assignment to Prognostic
Risk-Groups
  • Enables post-op counseling of an individual DTC
    patient
  • Helps make decisions about intensity of adjuvant
    therapies, frequency of follow-up visits, and
    allocation of resources

30
Role of Postoperative Staging SystemsATA 2006
Management Guidelines
  • R31. Because of its utility in predicting
    disease mortality, and its requirement for cancer
    registries, AJCC/UICC staging is recommended for
    all patients with differentiated thyroid cancer.
    The use of postoperative clinicopathologic
    staging systems is also recommended to improve
    prognostication and to plan follow-up for
    patients with differentiated thyroid carcinoma
    Recommendation B

  • Thyroid 16 1-33, 2006.

31
Utility of Staging and Prognostic Scoring
  • Clinicians caring for DTC patients should
    understand and try to use in practice the 2002
    TNM/AJCC stages!
  • AMES or MSKCC risk-groups for FTC
  • MACIS prognostic scoring system, permitting PTC
    classification into low-risk (scores lt6) or
    high-risk (6) patients (Surgery 114 1050-8,
    1993), employed at Mayo for past 13 years

32
Papillary Thyroid CarcinomaManaged at Mayo
Clinic 1940-2000Mortality by MACIS
lt6 (2,099)
Surviving death from PTC ()
6 (413)
MACIS Risk Groups n2,512
1940-2000 Plt0.001
Years after initial surgery
CP1028491-11
33
Common Sense Approach to LRPTC Management
  • I. Diagnosis cytologic and histopathologic
  • II. Primary surgical treatment
  • III. Staging and risk-group assignment
  • IV. Adjuvant therapy

34
Adjuvant Therapy in LRPTC Patients
  • Thyroid hormone suppressive therapy
  • Radioiodine remnant ablation (RRA)

35
Thyroxine Suppressive Therapy in DTC Management
  • Risk-group assignment can determine a precise
    goal level for suppression of serum TSH
  • Low-risk (MACIS lt 6 PTC) TSH typically in 0.1 -
    0.5 mIU/L range
  • High-risk (MACIS 6 PTC FTC/HCC) aiming for
    TSH of 0.1 mIU/L or less

36
Appropriate Degree of Initial TSH SuppressionATA
2006 DTC Management Guidelines
  • R40. Initial thyrotropin suppression to below
    0.1 mU/L is recommended for high-risk patients
    with thyroid cancer, while maintenance of the TSH
    at or slightly below the lower limit of normal
    (0.1-0.5 mU/L) is appropriate for low-risk
    patients Recommendation B
  • Thyroid 16
    1-33, 2006.

37
2,512 Papillary Thyroid Carcinoma
PatientsManaged During 1940-2000Therapeutic
Trends
Remnant ablation n662 1940-2000
Bilateral lobar resection(2,179)
n2,512 Plt0.001
Patients ()
46
32
Unilateral lobectomy(293)
3
1
1940-54
1955-69
1970-84
1985-2000
1940-54
1955-69
1970-84
1985-2000
CP1028491-3
38
Radioiodine Remnant Ablation in MACIS lt6 Low-Risk
PTC
  • Recent analysis of outcome in 1,163 patients
    treated during 1970-2000
  • When patients divided into 636 node-negative and
    527 node-positive, no differences in outcome
    (mortality and recurrence) were found between
    those having surgery alone and those also
    receiving postoperative RRA
  • Trans ACCA 113 241, 2002

39
Survival for low risk PTC (MACIS lt 6)
100
95
I131 Ablation (n498)
Survival (cause-specific)
90
No Ablation (n665)
85
0
0
5
10
15
20
Years from diagnosis
1163 patients total or near-total TTX 1970 -
2000
40
Survival (TxN0M0, MACISlt6)
100
95
I131 Ablation (n195)
Survival ()
No Ablation (n441)
90
85
0
5
10
15
20
0
Years from diagnosis
636 node negative patients total or near-total
TTX 1970 - 2000
41
Survival (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
42
Recurrence in low risk PTC
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
43
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
44
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
45
Selective Approach to Postoperative RRA
  • Current Mayo practice to restrict RRA to
    patients with high-risk (MACIS 6) PTC and to
    patients with FTC or HCC
  • Recent study of 6,841 European patients
    demonstrated increased risk of both solid tumors
    and leukemia after I-131 treatment and concluded
    that it seems necessary to restrict the use of
    I-131 to thyroid cancer patients in whom it may
    be beneficial
  • Br J Cancer 89 1638, 2003

46
Role of Postoperative RRAATA 2006 Guidelines
  • R32. Radioiodine ablation is recommended for
    patients with stage III and IV disease (AJCC 6th
    edition), all patients with stage II disease 45
    years or older, and selected patients with stage
    I disease, especially those with multifocal
    disease, nodal metastases, extrathyroidal or
    vascular invasion, and/or more aggressive
    histologies Recommendation B.

  • Thyroid 16 1-33, 2006.

47
Techniques for Postoperative RRA
  • Some American centers now favor blind
    administration of large (100 - 175 mCi) I-131
    doses without preceding diagnostic scan, and
    depend on utility of post-therapy WBS
  • In selected cases, Mayo practice now is to
    perform uptake quantitation during I-123 scan ,
    customize the I-131 therapy, follow with
    diagnostic I-123 scans after 3-6 months

48
Common Sense Approach to LRPTC Management
  • I. Diagnosis cytologic and histopathologic
  • II. Primary surgical treatment
  • III. Staging and risk-group assignment
  • IV. Adjuvant therapy
  • V. Long-term surveillance

49
Postoperative Surveillance in PTC
  • Thyroglobulin levels
  • Appropriate imaging

50
Thyroglobulin on or off thyroid hormone
suppression therapy?
  • Mail-in thyroid cascade (TSH-based) and Tg on
    every returning visit
  • Also, measure TSH and Tg, while off THST, at time
    of I-123 body scanning
  • Personally, do not favor stopping T4 or giving
    rhTSH only for the purpose of determining Tg
    increment

51
Stimulated Tg Levels in Low-Risk PatientsATA
2006 Guidelines
  • R45. In low-risk patients, who have had remnant
    ablation and negative cervical ultrasound and
    TSH-suppressed Tg 6 months after treatment, serum
    Tg should be measured after T4 withdrawal or
    rhTSH stimulation approximately 12 months after
    the ablation to verify absence of disease. The
    timing or necessity of subsequent stimulated
    testing is uncertain for those found to be free
    of disease Recommendation A.
  • Thyroid
    16 1-33, 2006.

52
rhTSH Stimulation and Presently Undetectable
Serum Tg Levels
  • A recent consensus (JCEM 881433, 2003) suggested
    that a serum Tg lt1 ng/mL measured on THST is
    misleading in a large proportion of patients
    with residual DTC
  • When Tg measured as lt0.1 ng/mL on THST, provides
    reassurance of a lack of relevant tumor
    recurrence in Ab-negative low-risk PTC
  • Soon, Tg assay detection limits will approach
    0.01 ng/mL therefore, likely making rhTSH
    stimulation a costly and unnecessary test

53
Detectable Tg and Tumor Recurrence
  • I personally consider a positive biopsy as
    proof of disease rediscovery, but I consider a
    detectable Tg at best a possible surrogate for
    tumor recurrence

54
Postoperative Surveillance in LRPTC
  • Appropriate imaging

55
Selective Use of Imaging in Postop Surveillance
  • I-131 therapy restricted to high-risk patients
    I-123 WBS used primarily to assess adequacy of
    I-131 therapy
  • CT, MRI, PET/CT not regularly employed
  • Heavy reliance on skilled sonographers to
    identify or exclude locoregional disease
  • Real-time US used to guide biopsies of possible
    neck recurrences, and to enable percutaneous
    ethanol ablation of nodes

56
Treatment Alternatives for PTC in
Persistent/Recurrent Neck Nodes
Traditional
Radioactive I131 therapy
Neck Dissection
External Radiation
57
Ablation of Papillary Nodal Metastasis
Technique
  • 95 ethanol
  • 25 g needle and Tb syringe
  • 0.1-0.8 cc (mean 0.3 ml)
  • Inject tiny amount until node becomes echogenic
  • Reinject next day in most pts

58
Results in Stage I PTC
60 Nodes Treated in 35 Pts
  • All 60 decreased in size 40 (67) no longer
    identified
  • Average decrease size 95

59
Common Sense Approach to LRPTC Management
  • I. Diagnosis cytologic and histopathologic
  • II. Primary surgical treatment
  • III. Staging and risk-group assignment
  • IV. Adjuvant therapy
  • V. Long-term surveillance

60
Five Golden Rules for LRDTC Management
  • I. Carefully choose your trusted, locally based,
    pathologist
  • II. Know the skills and/or limitations of your
    thyroid surgeons
  • III. Use TNM stages and apply scoring
  • IV. Try to use I-131 therapy selectively
  • V. Revere US scanning, and permit tolerance of
    detectable Tg levels

61
(No Transcript)
62
The end
  • Proceed to post test
  • Print post test
  • Complete post test
  • Return post test to
  • Dr. Sandra Oliver
  • 407i TAMUII

63
Post test
  • List the five Golden Rules for LRDTC
    Management
  • 1.
  • 2.
  • 3.
  • 4.
  • 5.
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