WTC 2013 Panel Discussion: Minimal disease Susan J. Mandel MD MPH Panelists Ken Ain Yasuhiro Ito Stephanie Lee Erich Sturgis Mark Urken
Faculty/Presenter Disclosure Relationships with commercial interests regarding content of this program: NONE
Case 1: 2002 45 y.o. woman incidentally found to thyroid nodules on an US ordered by her internist for goiter Thyroid exam normal TSH 1.93
2002: 45 y.o. woman incidentally found to thyroid nodules Transverse Sagittal Right lower 6x7x8mm Sagittal Transverse Right mid 7x8x10
2002: 45 y.o. woman incidentally found to thyroid nodules transverse sagittal Left mid 6x6x6mm
How to describe her nodules? Right mid 7x8x10 Right lower 6x7x8mm Left mid 6x6x6mm
Do you want more information? Would you recommend FNA of any of her nodules?
3.7.2.1. How to select nodules for FNA biopsy (Grade B) Of ANY SIZE with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives; previous thyroid surgery for cancer; increased calcitonin levels Of diameter smaller than 10 mm along with US findings associated with malignancy the coexistence of 2 or more suspicious US criteria greatly increases the risk of thyroid cancer AACE/AME/ETA guidelines for clinical practice for the diagnosis and management of thyroid nodules, Endocrine Pract 2010 16:supplement 1
R5a. HIGH Risk History FNA nodules >5mm 1) Family history of thyroid cancer (PTC, Medullary) 2) History of XRT or ionizing radiation as a child 3) Prior hemithyroidectomy with thyroid cancer 4) 18 FDG PET positive nodules Nodule WITH suspicious sonographic features >5mm Recommendation A Nodule WITHOUT suspicious sonographic features >5mm Recommendation I ATA Management guidelines for patients with thyroid nodules and differentiated thyroid cancer, Thyroid 2009 11:1167
2005: 48 y.o. woman F/U US Left mid 7 x6x6mm No abnl cervical LNS
2007: 50 y.o. woman F/U US Left mid 7x6x6mm, no abnl cervical LNs
2008: 51 y.o woman F/U US Left mid 7x6x7mm No abnormal cervical lymph nodes
Serum Calcium levels 2002 2005 2007 2008 9.1 mg/dl (2.28mmol/L) 9.2 mg/dl (2.30mmol/L) 10.1 mg/dl (2.53mmol/L) albumin 4.1gm/dL (41gm/L) 11.1mg/dL (2.78mmol/L) PTH 7.4 pmol/l [NL 1.3-6.8] 24 hour urine Calcium 410mg (103mmol/24hrs)
What next? FNA nodule Parathyroidectomy Left hemithyroidectomy Bilateral thyroid surgery Some combination of the above
US FNA nondx cytology, calcified nodule Patient opted for surgery Left hemithyroidectomy L superior parathyroidectomy Intra op PTH 12.3 1.2 pmol/l
Pathology LU parathyroid adenoma 949mg L thyroid 6mm PTC with one area of microscopic invasion into but not through thyroid capsule, completed excised 0/2 LNs T1aN0Mx
What next? Completion surgery Leave her alone
Cumulative % of tumor enlargement Proportion of patients in Ito entire series whose PMC showed enlargement by 3 mm or more 100 80 60 40 20 0 4.9% 8.0% 0 5 10 15 20 Follow-up times (yrs) Patients at risk 1,235 427 129 24
Cumulative % of appearance of lymph node metastasis Proportion of patients in Ito series whose PMC showed novel appearance of lymph node metastasis 100 80 60 40 20 0 1.7% 3.8% 0 5 10 15 20 Follow-up times (yrs) Patients at risk 1,235 438 136 27
Relationship between carcinoma progression and age of patients (%) Age of patients < 40 years 40-59 years > 60 years Total (young) (middle-aged) (old) (n = 169) (n = 570) (n = 496) (n = 1,235) Size enlargement 14 (5.9%) 33 (5.7%) 11 (2.2%) 58 p = 0.0014 New node metastasis 9 (5.3%) 8 (1.4%) 2 (0.4%) 19 p < 0.0001
Can we identify microptc with virulent potential? Are there predictors of outcome (recurrence, death) for micropapillary cancers?
Percent of Patients CLINICAL LN mets at presentation: WORSE outcome 40 35 30 25 20 15 10 5 0 n=190 Mean f/u 8.2 years Local recurrence Distant metastases LN neg LN pos P < 0.05 Death Sugitani, World J Surg 1998
Micropapillary cancers (<1cm) without clinically or sonographically apparent metastatic lymph nodes almost always remain indolent and only rarely become clinically significant For suspicious subcm thyroid nodules CHECK LNs with US Wada, Ann Surg 2003; Ito, Word J Surg 2004
Case 2: 51 yo man with 1.1 cm nodule found on carotid US No FHx of thyroid cancer or personal Hx of XRT TSH 1.9mIU/L PEX: thyroid normal size and consistency, no palpable enlarged LNS
Ultrasound Left lobe sagittal No other nodules present No abnormal lymph nodes imaged
What do you recommend? US FNA performed Cytology read as follicular neoplasm Molecular testing not available What next?
Patient underwent left hemithyroidetomy Pathology 9mm PTC confined to thyroid, no vascular invasion
What next? Completion surgery Leave him alone Something else
R26. For patients with thyroid cancer larger than 1 cm, the initial Extent surgical of thyroidectomy procedure should be a near-total or total thyroidectomy unless there are contraindications to this surgery. Thyroid lobectomy alone may be sufficient treatment for small (<1cm), 2 low risk, Unilateral unifocal, compared intrathyroidal to papillary carcinomas 1.8 Bilateral in the Surgery absence n=51,173 of prior head and neck 1.6 irradiation or radiologically or * clinically involved cervical 1.4 nodal * metastases. 1.2 Recommendation A Relative Risk 1 0.8 0.6 0.4 0.2 0 <1cm >1cm <1cm >1cm Recurrence ATA Guidelines 2006, 2009; Billmoria KY, Ann Surg 2007 Death
Patient underwent left hemithyroidetomy Pathology (variation #1) 9mm PTC confined to thyroid, no vascular invasion AND Delphian LN removed and <2mm micro PTC met
What next? Completion surgery Leave him alone Something else
Spectrum of LN metastases Spectrum from micrometastasis to gross bulky adenopathy Number dependent upon extent of surgery and pathologic dissection clinically apparent metastatic LNs definition: palpation v.s. ultrasound
Micromet LN almost replaced by tumor Extranodal extension
If routine neck dissection performed, small volume microscopic LNs present Up to 80% central neck ~35% lateral neck However, if not performed, this is NOT incidence of clinical recurrence Detection by Palpation examination (intraop, preop) Ultrasound Pathologic examination
Micromet on pathology and RECURRENCE 170 pts: near total thyrx, central and ipsilateral neck dissection, I-131 Rx Recurrence (%) 35 30 25 20 15 10 5 0 macro mets n=49 p=0.015 univariate * micro mets (<2mm) n=20 no mets n=101 Cranshaw Surg Oncol 2008 17:253-258
Ultrasound positive lateral neck LNS and RECURRENCE Disease-free survival (%) 460 pts thyrx, LATERAL neck dissection 11% 25% univariate US neg LNs 455 pts US+ LNs 105 pts 57% path pos 43% path neg 1 Ito, World J Surg 2005; 2 Ito, World J Surg 2004
Disease Free Survival (%) Moreno et al 2012 Thyroid 22: 347-55 Ultrasound positive central neck LNs and RECURRENCE CENTRAL neck dissection in: 79 pts with US pos central LNs 119 pts with US neg central LNs 100 75 p=ns p=0.0005 50 25 Normal US, NO dissection (n=133) Normal US, prophylactic dissection (n=119) 71% LN+, 29% LN neg Abnormal US, therapeutic dissection (n=79) 2 4 6 8 10 12 14 Years after surgery
Ultrasound positive LNS predict RECURRENCE US NEGATIVE, PATHOLOGY+ lateral or central neck LN mets: NO IMPACT on outcome Ito, Word J Surg 2004, 2005; Moreno Thyroid 2012
Patient underwent left hemithyroidetomy Pathology (Variation #2) 9mm PTC confined to thyroid, no vascular invasion AND BRAF V600E mutation positive
What next? Completion surgery Leave him alone Something else
BRAF V600E mutation and histopathology Meta analysis 32 studies and 6372 patients BRAF V600E mutation is associated with Lymph node mets Advanced stage Extrathyroidal extension Absence of tumor capsule Tall cell PTC Tumor size Classic PTC Multifocality Li et al J Clin Endocrinol Metab 2012 97:4559
BRAF V600E and outcome MULTIVARIABLE Analyses No difference in survival for Stage 1 1 No difference in recurrence for T1aN0M0 patients with or without I-131 RX 2 1 Xing JAMA 2013 309:1493 2 Elisei J Clin Endocrinol Metab 2012 97:4390
Patient underwent left hemithyroidetomy Pathology (Variation #3) 9mm PTC confined to thyroid, no vascular invasion 3 foci of micro PTC 1mm, 2mm, 4mm all confined to thyroid
What next? Completion surgery Leave him alone Something else
Case 3: 54 y.o. woman 2004 Thyroidectomy: left 1.6cm Papillary thyroid cancer follicular variant, confined to thyroid, right 9mm PTC confined Withdrawn from thyroid hormone and treated with 100mCi I-131, with post therapy scan reported to show significant uptake in the thyroid bed no labs or other info available
54 y.o. woman 8/05 Thyrogen stimulation Baseline TSH 0.03mIU/L Tg 0.6ng/ml Stimulated TSH 23mIU/L Tg 2.9ng/ml Whole body scan negative Ultrasound performed
2005 4x5x5mm 4x5x5mm
Nothing FNA What to do? US FNA performed FNA cytology PTC FNA Tg 1531ng/ml Now what?? Surgery? Observation? Something else
2007 4x4x5mm TSH 0.02mIU/L Tg 0.27ng/ml
2008 2012 3x4x6mm 3x3x4mm TSH 0.02mIU/L Tg 0.19ng/ml TSH 0.77mIU/L Tg 0.2ng/ml
Do small US suspicious cervical LNs grow? 166 PTC patients with sonographically abnl LNs outside thyroid bed followed for >1 yr Increased vascularity (41%), calcifications (40%), cystic (24%), absent hilus (22%), round shape (21%), hypoechoic (18%), heterogeneous (18%) Median LN size 1.3cm (range 0.5 to 2.7cm) Median f/u 3.5 yrs, median of 6 US exams 33 pts (20%) LN growth > 3mm 15 pts (9%) LN growth >5mm No sonographic or clinical feature reliably predicted LN growth Robenshtok et al, J Clin Endocrinol Metab epub May 25 2012
R48c Suspicious lymph nodes less than 5-8 mm in largest diameter may be followed without biopsy with consideration for intervention if there is growth or if the node threatens vital structures. Recommendation C ATA Guidelines 2009
Thanks to our panelists
Case 4: 42 yo woman with palpable left upper neck mass
right Thyroid US left No other abnormal Lymph nodes
FNA of L III Lymph node PTC What surgical procedure?
Thyroidectomy, Left VI, Left II-IV dissection Feb 2010 Thyroid: multifocal microptc Left 4 foci 1mm to 3mm Rigt 3 foci 1mm to 3mm Left VI dissection 4/6 Lymph nodes positive Left lateral neck dissection II 0/2 III 1/7 IV 0/8
42 yo woman with PTC Stage 1, T1a N1b, Mx April 2010 TSH 0.2mIU/L Tg 1.0ng/ml (RIA) TgAb 7.2 rhtsh preparation and Rx with 102mCi I-131 May 2010 TSH 0.12mI/L Tg 0.7ng/ml (RIA) Tg Ab 2.1 Submandibular salivary glands Thyroid remnant Post Rx WBS
42 yo woman with PTC Stage 1, T1a N1b, Mx June 2010 Ultrasound Right thyroid bed