Dynamic Risk Stratification in Thyroid Cancer Management
Dynamic Risk Stratification
Dr Matthew Beasley, Consultant Clinical Oncologist
Setting the scene…
•
An era of individualised, risk stratified approach to
management of differentiated thyroid cancer
•
Current BTA Dynamic Risk Stratification post treatment
mandates stimulated Tg and neck ultrasound at 9-12
months
•
Applies to those who have had surgery and radio-iodine
ablation
•
Determines the TSH target for follow-up
Dynamic Risk Stratification
British Thyroid Association Guidelines 3
rd
Edition Clinical Endocrinology Volume 81. Issue s1. Pages 1-122 July 2014
ATA Dynamic Risk Stratification
•
ATA Guidelines Haugen BR et
al (2016) Thyroid 26 (1)
•
Suppressed Tg target <0.2
ng/L
•
Rising anti-Tg Abs implies
multiple readings?
Neck ultrasound
•
Asking our radiology
colleagues to make a
response assessment on
ultrasound
•
Operator dependent
Thyroglobulin (thyroid cancer blood tumour
marker)
Colloid
Thyroid Follicle
TG
+ iodine + tyrosine
90% T4
10% T3
Thyroglobulin measurement
•
3
m
a
i
n
m
e
t
h
o
d
s
1.
Radio-immuno assays first used
in the 1980s
2.
Novel highly sensitive 2 antibody
“sandwich” immunometric assays
introduced widely over the last
decade
3.
Liquid chromatography-tandem
mass spectroscopy
Y
Y
TG
Capture Ab
Signal Ab
Immunometric assay
Thyroglobulin assays
TSH target
Excellent response
•
achieved in 86%–91% of ATA low-risk patients
•
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•
ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1)
Indeterminate response
•
12%–29%of low-risk, 8%–23%of int-risk and 0%–4% of high-risk
•
15%–20% will have structural disease identified during follow-up
•
ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1)
Incomplete response
•
B
i
o
c
h
e
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p
l
e
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e
r
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s
p
o
n
s
e
•
Biochemical incomplete response in 15-20% of patients
•
At least 30% spontaneously resolve to no evidence of disease
•
20% achieve no evidence of disease after additional therapy
•
Up to 20% develop structural disease (<1% disease specific death)
•
S
t
r
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r
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s
p
o
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e
•
2%–6% low risk, 19%–28% int risk, 67%–75% high risk
•
50%–85% continue to have persistent disease despite additional therapy
•
Disease specific death rates as high as 11%
•
ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1)
Non-stimulated sensitive Tg assays to define an
excellent response
Good negative predictive value
Position statement from international
consensus panel 2012/2013
•
…an undetectable Tg value using a highly sensitive assay is
associated with an adequate sensitivity and negative predictive value
to obviate the need for measuring TSH-stimulated Tg concentrations.
•
…but detectable basal highly sensitive Tg level (i.e. between 0.1 and
1ug/L) can only be considered disease free after a negative TSH-
stimulated measurement.
•
As most patients… low-risk DTC data on patients with intermediate
and high risk tumours are less robust
•
Giovanella et al (2014) Eur J of Endocrinol 171:33-46
Current algorithm
Neck US and usTg at 9-12 months
Neck US equivocal
or anti-Tg Abs
Neck US shows
residual disease
Excellent response
Indeterminate response
Incomplete response
usTg≥ 1.0ug/L
usTg < 0.1
ug/L
Neck US no evidence of disease
usTg ≥0.1 but
<1.0 ug/L
sTg
sTg <1.0ug/L
sTg≥1.0ug/L
Current algorithm
Neck US and usTg at 9-12 months
Neck US equivocal
or anti-Tg Abs
Neck US shows
residual disease
Excellent response
Indeterminate response
Incomplete response
usTg≥ 1.0ug/L
usTg < 0.1
ug/L
Neck US no evidence of disease
usTg ≥0.1 but
<1.0 ug/L
sTg
sTg <1.0ug/L
sTg≥1.0ug/L
?
Dr. Matthew Beasley, a Consultant Clinical Oncologist, discusses the importance of Dynamic Risk Stratification in managing differentiated thyroid cancer. The process involves post-treatment monitoring through stimulated thyroglobulin (Tg) and neck ultrasound at specific intervals, aiding in determining the TSH target for follow-up. Responses are classified as Excellent, Indeterminate, or Incomplete, based on various criteria, helping in differentiating low, intermediate, and high-risk patients. The British Thyroid Association and ATA guidelines provide further insights into setting Tg targets and interpretations. Additional assessments like neck ultrasound and thyroglobulin measurements using immunometric assays play crucial roles in the management of thyroid cancer.
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Presentation Transcript
Dynamic Risk Stratification Dr Matthew Beasley, Consultant Clinical Oncologist
Setting the scene An era of individualised, risk stratified approach to management of differentiated thyroid cancer Current BTA Dynamic Risk Stratification post treatment mandates stimulated Tg and neck ultrasound at 9-12 months Applies to those who have had surgery and radio-iodine ablation Determines the TSH target for follow-up
Dynamic Risk Stratification Excellent Response Indeterminate Response Incomplete Response All of the following Suppressed and stimulated Tg < 1ug/l* Neck US without evidence of disease Cross sectional imaging and/or nuclear medicine imaging negative (if performed) Any of the following Suppressed Tg < 1ug/l and stimulated Tg 1 and < 10ug/l* Neck US with non specific changes or stable sub centimetre nodes Cross sectional imaging and/or nuclear medicine imaging with non-specific changes, although not completely normal Any of the following Suppressed Tg 1ug/l or stimulated Tg 10ug/l* Rising Tg Persistent or newly identified disease on cross-sectional and/or nuclear medicine imaging Low risk Intermediate risk High risk British Thyroid Association Guidelines 3rd Edition Clinical Endocrinology Volume 81. Issue s1. Pages 1-122 July 2014
ATA Dynamic Risk Stratification ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1) Suppressed Tg target <0.2 ng/L Rising anti-Tg Abs implies multiple readings?
Neck ultrasound Asking our radiology colleagues to make a response assessment on ultrasound Operator dependent
Thyroglobulin (thyroid cancer blood tumour marker) Thyroid Follicle TG + iodine + tyrosine Colloid 90% T4 10% T3
Thyroglobulin measurement 3 main methods Immunometric assay 1. Radio-immuno assays first used in the 1980s 2. Novel highly sensitive 2 antibody sandwich immunometric assays introduced widely over the last decade Capture Ab Signal Ab Y Y TG 3. Liquid chromatography-tandem mass spectroscopy
Thyroglobulin assays Assay RIA Immunometric LCMS Functional sensitivity (ug/L) 1.0 0.1 1.0 Antibody interference Resistant Problematic Absent Between method concordance Problematic Problematic Problematic Cost ++ + +++ Clinical evidence of utility ++ ++ ? Radio-activity + - -
TSH target Excellent response Indeterminate response Incomplete response Low normal range (within normal range but</=2.0) 0.1-0.5 <0.1
Excellent response achieved in 86% 91% of ATA low-risk patients risk of recurrence over 5 10 years of follow-up ranged from 1% to 4% (median 1.8%) in patients who had an excellent response to therapy by 6 18 months after total thyroidectomy and RAI remnant ablation (20 retrospective studies) intermediate-risk patients who achieve an excellent response, risk of recurrent/persistent disease decreased from 36% 43%(predicted by initial ATA risk stratification) to 1% 2% (predicted by response-to- therapy reclassification) The few high-risk patients that achieve an excellent response to therapy also have subsequent recurrence rates in the 1% 2% range ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1)
Indeterminate response 12% 29%of low-risk, 8% 23%of int-risk and 0% 4% of high-risk 15% 20% will have structural disease identified during follow-up ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1)
Incomplete response Biochemical incomplete response Biochemical incomplete response in 15-20% of patients At least 30% spontaneously resolve to no evidence of disease 20% achieve no evidence of disease after additional therapy Up to 20% develop structural disease (<1% disease specific death) Structural incomplete response 2% 6% low risk, 19% 28% int risk, 67% 75% high risk 50% 85% continue to have persistent disease despite additional therapy Disease specific death rates as high as 11% ATA Guidelines Haugen BR et al (2016) Thyroid 26 (1)
Non-stimulated sensitive Tg assays to define an excellent response Author/Year Patient No. Time of assessment post ablation Tg cut-off (ng/mL) Recurrence rate Malandrino (2011) 425 8-18 months <0.15 0% low risk, 1% int risk and 2.7% high risk Brassard M (2011) 589 3 months <0.27 1.5% Smallridge (2012) 163 1.8 years <0.1 4.3% low/int risk Gionvanella (2009) 185 6 months <0.2 (and normal US) 1.6% low risk Good negative predictive value
Position statement from international consensus panel 2012/2013 an undetectable Tg value using a highly sensitive assay is associated with an adequate sensitivity and negative predictive value to obviate the need for measuring TSH-stimulated Tg concentrations. but detectable basal highly sensitive Tg level (i.e. between 0.1 and 1ug/L) can only be considered disease free after a negative TSH- stimulated measurement. As most patients low-risk DTC data on patients with intermediate and high risk tumours are less robust Giovanella et al (2014) Eur J of Endocrinol 171:33-46
Current algorithm Neck US and usTg at 9-12 months Neck US no evidence of disease Neck US shows residual disease Neck US equivocal or anti-Tg Abs usTg < 0.1 ug/L usTg 0.1 but <1.0 ug/L usTg 1.0ug/L sTg sTg 1.0ug/L sTg <1.0ug/L Indeterminate response Excellent response Incomplete response
Current algorithm Neck US and usTg at 9-12 months Neck US no evidence of disease Neck US shows residual disease Neck US equivocal or anti-Tg Abs usTg < 0.1 ug/L usTg 0.1 but <1.0 ug/L usTg 1.0ug/L sTg ? sTg 1.0ug/L sTg <1.0ug/L Indeterminate response Excellent response Incomplete response
