3/27/2019 memorial sloan kettering cancer center new york...10 yrs 5% 8% 95% 92% - - 2% 4% japan 415...
TRANSCRIPT
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
1
Is immediate surgery always necessary for low risk differentiated thyroid cancer?
R Michael Tuttle, MD
Clinical Director, Endocrinology Service
Memorial Sloan Kettering Cancer Center
Professor of Medicine
Weill Medical College of Cornell University
Disclosures
No relevant conflicts of interest
When to operate, when to watch
Active Surveillance for Low Risk Papillary Thyroid Cancer
Minimalist Surgical Options for Low Risk Papillary Thyroid Cancer
Emphasis on Proper Patient Selection, Shared Decision Making, and Development of a Unified Management Philosophy
Overview Management Philosophies in Low Risk
Thyroid Cancer
Typical Case
82 year old man Avoided health care for more than 50 years Wife insisted on a carotid US for screening
Incidental thyroid nodule detected
Thyroid US confirms a single 5 mm thyroid nodule FNA confirms papillary thyroid cancer
What now?
Surgery Vs
Observation
Typical Case
65 year old man Diabetes, HTN, A fib
Metastatic colon cancer to lung, liver and bone
Thyroid US confirms a single 5 mm thyroid nodule FNA confirms papillary thyroid cancer
What now?
Surgery Vs
Observation
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
2
Typical Case
25 year old female Getting married in 3 months
Does not want a scar on her neck before the wedding
Thyroid US confirms a single 5 mm thyroid nodule FNA confirms papillary thyroid cancer
What now?
Surgery Vs
Observation
After wedding wants to wait another 3 months to go on her honeymoon
After honeymoon, wants to wait another 3 months because of new job
Framing the Issue
• Active surveillance (deferred intervention) – Active observation approach
– Patients with known or highly suspected disease
– Therapeutic delay (deferred intervention) has no clinically significant impact
– Therapy, when indicated, still effective
– Not palliative care/watchful waiting (non-curative)
– Classic example
• Small volume prostate cancer
• Urethral cancer
• Some lymphomas
Oda et al, Thyroid 2016; 26(1): 150-155 Ito et al. World J Surg. 2010;34(1):28-35.
Sugitani et al. World J Surg. 2010;34(6):1222-1231. Ito et al. Thyroid. 2013.
Observational Management Approach to Papillary Microcarcinoma
Dr Akira Miyauchi
Kuma Clinic
Japan
2,153 Low Risk Papillary Microcarcinoma Patients
Active Surveillance 1,179 (55%)
Immediate Surgery 974 (45%)
Continued Observation 1,085 (92%)
Surgery, Stable Disease
61 (5.2%)
Increase Size Primary Tumor
27 (2.3%)
Novel LN Metastasis 6 (0.5%)
Median Follow-up 4 yrs (range 1-10 yrs)
Salvage therapy is very effective
A cytology diagnostic for a primary thyroid malignancy will almost always lead to thyroid surgery. However, an active surveillance management approach can be considered as an alternative to immediate surgery in:
(a) patients with very low risk tumors (e.g. papillary
microcarcinomas without clinically evident metastases or local invasion, and no convincing cytologic evidence of aggressive disease),
(b) patients at high surgical risk because of co-morbid conditions, (c) patients expected to have a relatively short life span (e.g.
serious cardiopulmonary disease, other malignancies, very advanced age), or
(d) patients with concurrent medical or surgical issues that need to be addressed prior to thyroid surgery.
2015 ATA Guidelines
Haugen, Thyroid 2016
Observational Management Approach to Papillary Microcarcinoma
n Tumor
size
Follow-
Up
Increase
≥ 3 mm
Stable
± 3 mm
Decrease
≥ 3 mm
LN
Mets
USA 291 ≤ 1.5 cm 2 yrs 4% 92% 4% 0%
Korea 192 ≤ 1 cm 2.5 yrs 2% 95% 3% 0.5%
Korea 370 ≤ 1 cm 2.7 yrs 4% 96% - 1%
Japan 1,23
5
≤ 1 cm 5 yrs
10 yrs
5%
8%
95%
92%
-
-
2%
4%
Japan 415 ≤ 1 cm 6.5 yrs 6% 91% 3% 1%
Japan 61 1-2 cm 7 yrs 7% 93% - 3%
Japan 360 ≤ 1 cm 7 yrs 8% 92% - 1%
Columbia 57 ≤ 1.5 cm 1 yr 4% 96% - 0%
Tumor Progression During Active Surveillance
Ito, Thyroid 2014, Sugitani JCEM 2014, Kwon JCEM 2017, Sanabria JAMA
Oto 2018, Oh Thyroid 2018, Tuttle JAMA Oto 2017, Sakai Thyroid 2019
Tumor Volume: π/6 (length x width x height)
Thyroid cancers are three dimensional structures Usually ellipsoid (not spherical)
40 yr old male, PMC 1.03 x 0.64 x 0.93 cm
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
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Tuttle et al, JAMA Otolaryngology–Head & Neck Surgery, 2017
-200
-100
0
100
200
300
400
Percent Change in Tumor Volume
(n=291)
Individual Patients
Perc
en
t C
ha
ng
e i
n T
um
or
Volu
me
Decreased > 50%
(n=19)
7%
Increased > 50%
(n=36)
12%
Stable (± 50%)
(n=228)
79%
50
Reproducible Measurement Differences Diameter ± 3 mm Volume ± 50%
≥ 3 mm ≥ 100%
Observational Management Approach to Papillary Microcarcinoma
n Tumor
size
Median
Follow-
Up
Tumor
Volume
Increase
≥ 50%
Tumor
Volume
Stable
± 50%
Tumor
Volume
Decrease
≥ 50%
USA 291 ≤ 1.5 cm 2 yrs 12% 79% 7%
Korea 192 ≤ 1 cm 2.5 yrs 14% 69% 17%
Korea 370 ≤ 1 cm 2.7 yrs 23% 77% -
Japan* 169 ≤ 1 cm 10 yrs 25% 57% 17%
Japan 61 1-2 cm 7 yrs 11% 89% -
Japan 360 ≤ 1 cm 7 yrs 21% 79% -
Tumor Progression During Active Surveillance
Kwon JCEM 2017, Tuttle JAMA Otolaryngology 2017,
Oh Thyroid 2018, Sakai Thyroid 2019
*Miyauchi, Surgery 2018 (tumor volume doubling rate/year)
Active Surveillance of Low Risk Papillary Thyroid Cancer
Demonstrate remarkably consistent classic exponential growth curves
Tuttle et al, JAMA Otolaryngology–Head & Neck Surgery, 2017
Months
Lo
g V
olu
me
r = 0.99
DT: not applicable
15 to 13 mm, 1.0 to 0.9 mL
Months
Lo
g V
olu
me
r= 0.85
DT: 4 yrs
10 to 13 mm, 0.3 to 0.5 mL
Months
Log V
olu
me
r = 0.95
DT: 2.7 yrs
6 to 9 mm, 0.05 to 0.1 mL
40 yr old female Papillary Microcarcinoma
4 yrs of active surveillance
Kuma Hospital [http://www.kuma-h.or.jp/index.php?id=293]
Tuttle et al, JAMA Otolaryngology–Head & Neck Surgery, 2017
Date Volume (ml) 12/7/2011 0.25 6/25/2012 0.37 2/4/2013 0.33 12/27/2013 0.41 10/20/2014 0.51 11/18/2015 0.46
Tumor Volume of an Ellipse: π/6 (length x width x height)
42 yr old female Papillary Microcarcinoma
5 yrs of active surveillance
Kuma Hospital
http://www.kuma-h.or.jp/index.php?id=293
r = 0.85
100% (3 mm)
Tuttle et al, JAMA Otolaryngology–Head & Neck Surgery, 2017
50% (1-2 mm)
Indications for Transition from Active Surveillance to Surgical Intervention
• Increase in size of primary tumor*
• ≥ 3mm increase in tumor diameter and/or
• ≥ 100% increase in tumor volume
• Identification of metastatic disease
• Direct invasion into surrounding structures
• Patient preference
• Surgical intervention can be considered with a confirmed 50% increase in tumor volume based on factors such as (i) proximity of the tumor to the thyroid capsule, (ii) patient preference, or (iii) primary tumor size > 1 cm. • Conversely, even with documented increase in the size of the primary tumor by diameter or volume, surgery may be deferred in patients without other indications for intervention if they have (i) a maximum tumor diameter of < 15 mm , and/or (ii) a tumor volume doubling time > 2 years.
Tuttle/Miyauchi 2019, in Surgery of the Thyroid and Parathyroid glands, 3rd Edition, Greg Randolph, ed
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
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Key Factors in Clinical Decision Making
Active Surveillance of Known or Suspected Thyroid Cancer
Tumor Size (Tumor Volume)
Doubling Time (Rate of Change)
Location Patient
Preference
Tumor/US Characteristics
Patient Characteristics
Medical Team Characteristics
Implementing Active Surveillance in the US
Requires concurrent evaluation of three inter-related domains
Appropriate
Ideal
Inappropriate
A clinical framework to facilitate risk stratification when considering an active surveillance alternative to immediate
biopsy and surgery in papillary microcarcinoma. JP Brito, Y Ito, A Miyauchi, RM Tuttle. Thyroid 2015
Tumor/US Characteristics
Proper Patient Selection
JP Brito, Y Ito, A Miyauchi, RM Tuttle. Thyroid 2015
• Intrathyroidal PTC • Bethesda VI • Bethesda V with highly suspicious US • US highly suspicious subcentimeter US without FNA • BRAF V600E mutated Bethesda III/IV/V/VI
• Cytology interpretation and US examination at MSKCC • Primary tumor up to ≈1.5 cm • Acceptable Features
• Background thyroid abnormalities (Hashimoto’s, MNG) • BRAF V600E mutation (genetic testing not required)
• Without • Documented increase in size • LN metastases • Extrathyroidal extension • Subcapsular location adjacent to trachea/RLN
Relationship of Nodule to Thyroid Capsule
Ideal: normal thyroid tissue surrounding the PMC
Relationship of Nodule to Thyroid Capsule
Inappropriate
67 yr old female, right anterior superior pole, 8x7x9mm, definite anterior extrathyroidal extension, confirmed by
histology (7mm TCV PTC, minor ETE)
Relationship of Nodule to Thyroid Capsule
Appropriate
Nodule Abuts the Thyroid Capsule But Not Invasive
Posterior Capsule
Anterior Capsule
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
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Relationship of Nodule to Thyroid Capsule
Isthmus Nodules Rarely Appropriate
Usually Touch the Anterior and Posterior Thyroid Capsule
Nodule: 0.5 x 0.6 cm Isthmus: 0.3 cm wide
Nodule: 0.4 x 0.3 cm Isthmus: 0.5 cm wide
American College of Surgeons Operative standards for Cancer Surgery Thyroid Cancer, 2018
Course of the Recurrent Laryngeal Nerves Relative to the Intact Thyroid Gland
Anterior view of thyroid with isthmus divided
American College of Surgeons Operative standards for Cancer Surgery Thyroid Cancer, 2018
Course of the Recurrent Laryngeal Nerves Relative to the Intact Thyroid Gland
Left Lower Medial Pole Nodule (13x10x11mm)
American College of Surgeons Operative standards for Cancer Surgery Thyroid Cancer, 2018
Course of the Recurrent Laryngeal Nerves Relative to the Intact Thyroid Gland
Posterior Right Lobe Nodule (6x8x6mm)
American College of Surgeons Operative standards for Cancer Surgery Thyroid Cancer, 2018
Course of the Recurrent Laryngeal Nerves Relative to the Intact Thyroid Gland
Posterior Right Lobe Nodule (7x6x7mm)
American College of Surgeons Operative standards for Cancer Surgery Thyroid Cancer, 2018
Course of the Recurrent Laryngeal Nerves Relative to the Intact Thyroid Gland
Anterior view of thyroid with isthmus divided
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
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Tumor/US Characteristics
Patient Characteristics
Medical Team Characteristics
Implementing Active Surveillance in the US
Requires concurrent evaluation of three inter-related domains
JP Brito, Y Ito, A Miyauchi, RM Tuttle. Thyroid 2015
Multidisciplinary Management Team Shared Treatment Philosophy
Quality Ultrasonography Prospective Data Collection
Tracking System
Motivated Compliant
Supportive Family/Clinicians Differences in Patient Decision Making
BOTH
How do patients perceive initial treatment options?
D’Agostino et al. Psychooncology, 27:61-68, 2018. Slide from Elizabeth Grubbs, MD Anderson
SURGERY ACTIVE SURVEILLANCE
Sense of urgency
Perception as potentially
life‐threatening disease
Fear of disease progression
& uncertainty with
active surveillance
Surgery as a means of
control and potential cure
BOTH D’Agostino et al. Psychooncology, 27:61-68, 2018.
How do patients perceive initial treatment options?
Slide from Elizabeth Grubbs, MD Anderson
SURGERY ACTIVE SURVEILLANCE
Sense of urgency
Perception as potentially
life‐threatening disease
Fear of disease progression
& uncertainty with
active surveillance
Surgery as a means of
control and potential cure
View as a
common, indolent,
low‐risk disease
Concerns about adjusting
to life without a thyroid/
reliance on
hormone replacement
Openness to
reconsidering surgery
over the long run
BOTH D’Agostino et al. Psychooncology, 27:61-68, 2018.
How do patients perceive initial treatment options?
Slide from Elizabeth Grubbs, MD Anderson
SURGERY ACTIVE SURVEILLANCE
Sense of urgency
Perception as potentially
life‐threatening disease
Fear of disease progression
& uncertainty with
active surveillance
Surgery as a means of
control and potential cure
View as a
common, indolent,
low‐risk disease
Concerns about adjusting
to life without a thyroid/
reliance on
hormone replacement
Openness to
reconsidering surgery
over the long run
Deep level of trust
& confidence in
physician &
cancer center
Use of physician
& internet
as 1° sources
treatment‐related
info
SURGERY ACTIVE SURVEILLANCE
BOTH
How do patients perceive initial treatment options?
Slide from Elizabeth Grubbs, MD Anderson
Weighing the Risks and Benefits of Treatment
Medical Decision Making
Maximalists or
Minimalists
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
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Weighing the Risks and Benefits of Treatment
Medical Decision Making
Maximalists
“be ahead of the curve” “why wait”
“more is better”
Minimalists
“less is more” “unintended consequences
outweigh potential benefits”
Development of the Medical Maximizer-Minimizer Scale. Scherer et al, Health Psychology, 2016
Cancer
Blood pressure Cholesterol
Glucose BMI
Availability Bias is the tendency to let an example that comes easily to mind affect decision-making or reasoning. This can occur when a story you can readily recall plays
too big a role in how you reach your conclusion.
Availability Bias
Medical Decision Making
• My sister had thyroid surgery and gained 100 lbs • Dr Google says that thyroid hormone pills are ineffective • My thyroid support group says the sooner thyroidectomy is
done the better the outcome will be
• I had a patient with small thyroid cancer that had a brain metastasis (or lung metastasis/bone metastasis)
• Last month, one of my patients had bilateral vocal cord paralysis as a result of thyroidectomy for a 5 mm PTC
Tumor/US Characteristics
Patient Characteristics
Medical Team Characteristics
Implementing Active Surveillance in the US
Requires concurrent evaluation of three inter-related domains
JP Brito, Y Ito, A Miyauchi, RM Tuttle. Thyroid 2015
Multidisciplinary Management Team Shared Treatment Philosophy
Quality Ultrasonography Prospective Data Collection
Tracking System
Motivated Compliant
Supportive Family/Clinicians Differences in Patient Decision Making
Observational Management Strategy
JP Brito, Y Ito, A Miyauchi, RM Tuttle. Thyroid 2015
• Serial US evaluations of the thyroid and neck • Q 6 months for 2 years • Then less frequently
• TSH suppression is not recommended • Goal TSH 0.5-3 mIU/L
• Thyroid function tests • Yearly
• Indications for surgical intervention
• Increase in size of primary tumor*
• ≥ 3mm increase in tumor diameter and/or
• ≥ 100% increase in tumor volume
• Identification of metastatic disease
• Direct invasion into surrounding structures
• Patient preference
Typical Case
36 year old female Incidental finding of asymptomatic thyroid nodule
Normal thyroid function
Thyroid US confirms a single 2.0 cm thyroid nodule Contralateral lobe is normal, no abnormal lymph nodes
FNA confirms papillary thyroid cancer
What now?
Total Thyroidectomy Vs
Thyroid Lobectomy
Wants to avoid thyroid hormone replacement
Selecting Patients for Lobectomy
Appropriate
Ideal
Inappropriate
Tumor/US Characteristics
Patient Characteristics
Medical Team Characteristics
Intra-operative Findings
Post-operative Path Report
R. Michael Tuttle, Ling Zhang and Ashok Shaha, Expert Review of Endo & Metab, 2018.
R Michael Tuttle, MD Memorial Sloan Kettering Cancer Center New York
3/27/2019
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Selecting Patients for Lobectomy
Appropriate
Ideal
Inappropriate
Tumor/US Characteristics
Patient Characteristics
Medical Team Characteristics
Intra-operative Findings
Post-operative Path Report
Nixon Surgery 2012, Vaisman Clinical Endo (Oxf) 2011, Vaisman J Thyroid Res 2013, Kluijfhout Surgery 2017, Calcatera Endo Practice 2017
Immediate Completion 6-20%
Delayed Completion
5-10%
Effective Salvage Therapy
Post-operative Decision Making
Features
Ideal • Intrathyroidal classical PTC • FV-PTC without vascular invasion • NIFT-P • Minimally invasive FTC (capsular invasion only) • Pathology N0/Nx • Non-stimulated Tg < 30 ng/mL
Appropriate • Minor extrathyroidal extension • Clinical N0 but pN1 LN mets • Multifocality • Lymphovascular invasion • Minor vascular invasion • 1-2 cm potentially aggressive tumors (tall
cell, hobnail, columnar cell) • Non-stimulated Tg 5-30 ng/mL
Inappropriate • Extensive vascular invasion (FTC or HCC) • Gross extrathyroidal extension • Clinical N1 histologically confirmed LN mets • Non-stimulated Tg > 30 ng/mL
R. Michael Tuttle, Ling Zhang and Ashok Shaha, Expert Review of Endo & Metab, 2018.
A Practical Approach to Follow-up After Lobectomy
Tumor/Imaging characteristics
TSH goal • 0.5-2.5 mIU/mL • With or without levothyroxine
Clinic visits • Post-op (to review path, check TSH, Tg) • Then 6-12 month follow-up • Yearly for 2-3 years with exam • TSH, Free T4, Tg, TgAb with each clinic visit
Imaging • Neck US 6-12 months, 3 yrs, and 5 yrs • Then very rarely
Late completion thyroidectomy
• Physical exam findings • Neck US findings • Need for RAI • Sustained, serial rise in Tg over time
Excellent disease specific survival Highly sensitive disease detection techniques are not necessary
Risk Stratification in Thyroid Cancer
Thyroid Surgery
Adjuvant Therapy
Follow up Suspicious Nodule
Diagnosis
A dynamic, iterative, active process
AJCC 8th Edition Risk of death
Stage I, II, III, or IV
ATA Risk Recurrent/Persistent Disease Low, Intermediate, or High
Tuttle, Alzahrani, Mini-review, JCEM expected in early 2019
Ideal
Appropriate Inappropriate
Peri-Diagnostic Risk Assessment Candidates for Minimalistic Management
Indeterminate
Excellent
Biochemical Incomplete
Structural Incomplete
Response to Therapy Management recommendations