5/12/2015

Thyroid Cancer Surgery 2015

Greg Randolph MD, FACS, FACE

Harvard Medical School

Thyroid Cancer Panel Chair: Hossein Gharib, MD a. Radioisotope Imaging in Thyroid Cancer Jolanto Durski, MD b. Surgical Therapy Gregory Randolph, MD c. Radioiodine Therapy: Douglas Van Nostrand, MD d. Recurrent Thyroid Cancer: Michael Tuttle, MD

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Relevant Financial Disclosures- None

Thyroid Surgical Therapy   1‐Initial Thyroid Surgery:  ‐FNA  ‐degree of thyroid surgery

2‐Mapping for LN ‐macro/micro ‐US/CT

3‐ Surgical  Complications

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The Bethesda Cytopathologic categories 1‐6 Dx  Category1

Cytologic Diagnosis1

Expected  Rate of  Dx1

Expected Risk of  Malignancy1

Evidence of Risk of Malignancy

Suggested Management1

1000

hotspots • 42 fusion types •16 genes for expression Gene Mutations (DNA) NRAS 

RET

HRAS

TSHR

KRAS

AKT1

BRAF

TP53

PIK3CA

GNAS

PTEN

CTNNB1

TERT

EIF1AX

Gene Fusions (RNA) RET PPARG NTRK1 NTRK3 BRAF ALK Other

Gene expression (RNA) PGK1 KRT7 TG TTF1 SLC5A5 (NIS) Calcitonin PTH KRT20 Other

Performance of ThyroSeq v2 Mutation Panel in  Nodules with AUS/FLUS (Bethesda III) Cytology •13 mutations identified: NRAS x2; HRAS x2; BRAF x2;  EIF1AX x2; TSHR; PAX8/PPARG; ETV6/NTRK3 •3 false‐positive (NRAS, EIF1AX; TSHR) – all FA •2 false‐negative (EFV PTC; OFC, MI) •Overall performance: Sensitivity  83.3% (CI: 52‐97%) Specificity  94.3% (CI: 84‐99%) PPV              76.9% (CI: 46‐97%) NPV             96.2% (CI: 87‐99%) Accuracy     92.3% (CI: 87‐99%)

Nikiforov et al. (manuscript in preparation)

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Asuragen -Oncogene panel ~70% BRAF

PAX8/PPARγ

RAS (common hotspots)

RET/PTC (types 1 and 3)

Asuragen • RULE IN TEST –high specificity/PPV –if + its Cancer • Overall Sensitivity 63.7%, NPV ~ 72% Specificity 98% Spec Braf-100% Ras-83% RET/PTC 100% PPAR Gamma 100% Rule In • High PPV 100% Braf, RET, PPAR, successful PPV ~ 85-87% Ras Ferraz JCEM 2011 Nikiforov JCEM 2008,2010 Cantara JCEM 2012 Nikiforov Nat Rev Endocrinol 2011.

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Cost • Afirma ~$3000 • Asuragen ~$2250 • Thyroseq v.2 ~$2200

2015 American Thyroid Association  Management Guidelines for Patients with  Thyroid Nodules and Differentiated Thyroid  Cancer Bryan R. Haugen, M.D.(Chair), Erik K. Alexander, M.D., Keith C. Bible,  M.D., Ph.D., Gerard M. Doherty, M.D., Susan J. Mandel, M.D., M.P.H.,  Yuri E. Nikiforov, M.D., Ph.D., Furio Pacini, M.D., Gregory W. Randolph,  M.D., Anna M. Sawka, M.D., Ph.D., Martin Schlumberger, M.D., Kathryn  Schuff, M.D., Steven I. Sherman, M.D., Julie Ann Sosa, M.D., David L.  Steward, M.D., R. Michael Tuttle, M.D., and Leonard Wartofsky, M.D.

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2015 RECOMMENDATION 15 • (A) For nodules with AUS/FLUS cytology, after consideration of worrisome clinical and sonographic features, investigation such as repeat FNA or molecular testing may be used to supplement malignancy risk assessment in lieu of proceeding directly with a strategy of either surveillance or diagnostic surgery. Informed patient preference and feasibility should be considered in clinical decision-making. (Weak recommendation, Moderate-quality evidence) •

(B) If repeat FNA cytology and/or molecular testing are not performed or inconclusive, either surveillance or diagnostic surgical excision may be performed for an AUS/FLUS thyroid nodule, depending on clinical risk factors, sonographic pattern, and patient preference. (Strong recommendation, Low-quality evidence)

2015 RECOMMENDATION 16 •

• •

(A) Diagnostic surgical excision is the long-established standard of care for the management of follicular neoplasm/suspicious for follicular neoplasm (FN) cytology nodules. However, after consideration of clinical and sonographic features, molecular testing may be used to supplement malignancy risk assessment data, in lieu of proceeding directly with surgery. Informed patient preference and feasibility should be considered in clinical decision-making. (Weak recommendation, moderate-quality evidence) (B) If molecular testing is either not performed or inconclusive, surgical excision may be considered for removal and definitive diagnosis of an FN/SFN thyroid nodule. (Strong recommendation, Low-quality evidence)

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2015 RECOMMENDATION 17 •

(A) If the cytology is reported as suspicious for papillary carcinoma (SUSP), surgical management should be similar to that of malignant cytology, depending on clinical risk factors, sonographic feastures, patient preference, and possibly results of mutational testing (if performed). (Strong recommendation, Lowquality evidence)

•

(B) After consideration of clinical and sonographic features, mutational testing for BRAF or the mutation marker panel (BRAF, RAS, RET/PTC, PAX8/PPARγ, etc.) may be considered in nodules with SUSP cytology if such data would be expected to alter surgical decision-making. (Weak recommendation, Moderate-quality evidence)

One possible Algorithm Monitor Benign thyroid nodule

Benign 2-8% AUS/FLUS 6-30%

Thyroid nodule FNA

Afirma Thyroseq

Follicular Neoplasm 15-30% Suspicious 50-80% Dx PTC 93-100%

Asuragen Oncogene Panel

Clinical Assessment -desire for surgery Monitor Benign -other thyroid clinical data nodule (-) VCP,US,XRT (+) Lobectomy (-)Clinical Assessment -desire for Total thyroid -otherTotal clinical data (+) +/- CND age,VCP,US,XRT

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Thyroid Surgical Therapy   1‐Initial Thyroid Surgery:  ‐FNA  ‐degree of thyroid surgery

2‐Mapping for LN ‐macro/micro ‐US/CT

3‐ Surgical  Complications

ATA -Degree of Thyroid Surgery

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2015 RECOMMENDATION 35 • A) For patients with thyroid cancer >4 cm, or with gross extrathyroidal extension (clinical T4), or clinically apparent metastatic disease to nodes (clinical N1) or distant sites (clinical M1), the initial surgical procedure should include a near-total or total thyroidectomy and gross removal of all primary tumor unless there are contraindications to this procedure. (Strong Recommendation, Moderate-quality evidence) – Total thyroidectomy as the primary initial surgical treatment option for nearly all differentiated thyroid cancers has been reported to have improved survival a, low recurrence rates b-d, allows for routine use of RAI remnant ablation, and facilitated detection of recurrent/persistent disease during follow-up

a.Bilimoria KY, Bentrem DJ, Ko CY, Stewart AK, Winchester DP, Talamonti MS, Sturgeon C 2007 Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246:375-381 b.Grant CS, Hay ID, Gough IR, Bergstralh EJ, Goellner JR, McConahey WM 1988 Local recurrence in papillary thyroid carcinoma: is extent of surgical resection important? Surgery 104:954-962 c. Hay ID, Grant CS, Bergstralh EJ, Thompson GB, van Heerden JA, Goellner JR 1998 Unilateral total lobectomy: is it sufficient surgical treatment for patients with AMES low-risk papillary thyroid carcinoma? Surgery 124:958-964 d. Mazzaferri EL, Kloos RT 2001 Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 86:1447-1463

2015 RECOMMENDATION 35 • B) For patients with thyroid cancer >1 cm and 50% LN 8‐10 mm  in the smallest diameter should be performed to confirm malignancy if  this would change management. (Strong recommendation, Moderate‐ quality evidence) • C)  The addition of FNA‐Tg washout in the evaluation of suspicious  cervical lymph nodes is appropriate in select patients, but interpretation  may be difficult in patients with an intact thyroid gland. (Weak  recommendation, Low‐quality evidence)

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2015 RECOMMENDATION 33 Preoperative use of cross‐sectional imaging  studies (CT, MRI) with intravenous contrast  is  recommended as an adjunct to ultrasound for patients 

• A)

with clinical suspicion for advanced disease including invasive primary  tumor, or clinically apparent multiple or bulky lymph node  involvement.  (Strong recommendation, low‐quality evidence) • B)  Routine preoperative FDG‐PET scanning is not recommended.  (Strong  recommendation, low‐quality evidence)

CT SCAN-axial fine cut repeatable-

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2015 RECOMMENDATION 33 Preoperative use of cross‐sectional imaging  studies (CT, MRI) with intravenous contrast  is  recommended as an adjunct to ultrasound for patients 

• A)

with clinical suspicion for advanced disease including invasive primary  tumor, or clinically apparent multiple or bulky lymph node  involvement.  (Strong recommendation, low‐quality evidence)

Bad nodal disease

• B)  Routine preoperative FDG‐PET scanning is not recommended.  (Strong  recommendation, low‐quality evidence)

Axial CT and nodal extent of disease • US evaluation • is operator-dependent , deep anatomic structures and

those acoustically shadowed by bone or air. • Patients displaying bulky or widely distributed nodal

disease may present with involvement of nodal regions beyond typical cervical regions some of which maybe difficult to visualize on routine preoperative ultrasound including the : • mediastinum, infra-clavicular, retropharyngeal and parapharyngeal regions and central neck In a study of 37 the sensitivity of CT was better than US for the evaluation central and lateral compartment lymph nodes examined together (77% vs 62%, p=0.002)Ahn JE, Lee JH, Yi JS, et al. Diagnostic accuracy of CT and ultrasonography for evaluating metastatic cervical lymph nodes in patients with thyroid cancer. World J Surg. 2008;32(7):1552-1558.) • In a series of 299 consecutively registered patients with pathologically proven papillary thyroid cancer who underwent preoperative CT and ultrasound, ultrasound was more accurate than CT in predicting extrathyroidal tumor extension and multifocal, bilobar disease (p