2014 American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer Ronen Gurfinkel February 25,

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  • 2014 American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer Ronen Gurfinkel February 25, 2015 2015
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  • Objectives Review guidelines and updates on Preoperative staging Initial surgical management of DTC Staging and risk stratification Radioiodine therapy Assessing response to therapy Long term Follow-up
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  • ATA Guidelines Thyroid nodule and DTC treatment guidelines first developed 1996 Revised in 2006 and 2009 Draft update released 2014 Endorsed by AACE, American College of Endocrinology, BAHNO, ENDO Society, EACMFS, EANM, ESES, ESPE
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  • 2009 Guidelines
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  • 2015 Guidelines
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  • 2015 ATA Guidelines - Organization A.Thyroid nodule guidelines Recommendations 1-31 B.DTC: Initial management guidelines Recommendations 32-61 C.DTC: Long-term management guidelines and advanced cancer management guidelines Recommendations 33-101 D.Directions for future research
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  • Preoperative Assessment
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  • Preoperative Staging Role of preop neck U/S? 20-50% of DTC patients have cervical LN mets Preop U/S identifies suspicious LN in 20-31% Can confirm LN mets with U/S-guided FNA Measuring Tg in FNA needle washout fluid may be helpful if select cases Cystic LN Inadequate cytology Discordant U/S and cytology results
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  • Preoperative Staging Recommendation 32 A.Preop neck US (central + lateral compartments) (Strong/Moderate) B.US-guided biopsy of suspicious LNs ( 8-10 mm) if would change management (Strong/Moderate) C.(NEW) FNA-Tg washout appropriate in select patients, but ? difficult to interpret (Weak/Low)
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  • Preoperative Staging 2009 guidelines recommended against routine preop CT, MRI, or PET Choi et al (2009) 299 PTC patients, compared U/S vs CT U/S better for ETE, multifocal/bilobar disease U/S more accurate for staging Lesnick et al (2014) U/S + CT better than U/S alone for lateral LN MRI and PET have poor sensitivities for LNs (30-40%) Cross-sectional imaging is better for locally invasive tumours
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  • Preoperative Staging Recommendation 33 (CHANGED) A.Cross-section imaging (CT, MRI) with contrast recommend as adjunct to U/S if suspicious for advanced disease (Strong/Low) B.Routine preop FDG-PET no recommended (Strong/Low)
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  • Preoperative Staging Preop Anti-Tg Ab do not predict stage, disease-free survival No data that preop Tg impact on management or outcomes Recommendation 34 Routine preop Tg and Anti-Tg Ab are not recommended (Weak/Low)
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  • Initial Surgical Management
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  • Surgery for Biopsy Proven DTC 2009 guidelines TC > 1 cm total or near-total thyroidectomy TC < 1 cm lobectomy (unifocal, no other RFs) Based on retrospective data that bilateral surgery Improved survival Decreased recurrence Allowed for routine RAI Facilitated follow-up
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  • 52,173 patients in National Cancer Data Base (1985-1998) Bilimoria et al, Ann Surg 2007
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  • 52,173 patients in National Cancer Data Base (1985-1998) Bilimoria et al, Ann Surg 2007
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  • Surgery for Biopsy Proven DTC Recent data showed similar outcomes between unilateral vs. bilateral surgery (in selected patients) Unilateral surgery less LT4 Rx and less complications 2015 guidelines use RAI more selectively and RAI scans used less in follow-up
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  • Lobectomy vs Total Thyroidectomy Mendelsohn et al, Arch Otolaryngol Head Neck Surg 2010 22,724 PTC patients SEER 1988-2001 No survival difference
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  • 1,810 patients in MSKCC database (1986- 2005) Nixon et al, Surgery 2012
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  • Surgery for Biopsy Proven DTC Recommendation 35 (CHANGED) A.Total or near-total thyroidectomy if TC > 4cm Gross extrathyroidal extension Clinically apparent LN mets (cN1) Clinicaly apparent distant mets (cM1) (Strong/Moderate) B.Either lobectomy or thyroidectomy if TC 1-4 cm AND cN0 Thyroid lobectomy alone may be sufficient initial treatment for low risk papillary and follicular carcinomas; however, the treatment team may choose total thyroidectomy to enable RAI therapy or to enhance follow- up based upon disease features and/or patient preferences. (Strong/Moderate) C.Lobectomy if TC < 1cm (no ETE, cN0, no other RFs) (Strong/Moderate)
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  • Lymph Node Dissection Recommendation 36 A.Therapeutic central neck dissection (CND) for cN1 (Strong/Moderate) B.Consider prophylactic CND for PTC with cN0 but T3 or T4, cN1b, or if info will change management (Weak/Low) C.No prophylactic CND may be appropriate for noninvasive T1 or T2 tumours, cN0, and most follicular cancer (Strong/Moderate)
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  • Lymph Node Dissection Recommendation 37 Therapeutic lateral LN dissection in biopsy-proven lateral cervical LN mets (Strong/Moderate)
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  • Completion Thyroidectomy Recommendation 38 A.Offer if bilateral thyroidectomy would have been recommended if diagnosis was available before initial surgery. Therapeutic CND if cN1 (Strong/Moderate) B.RAI in lieu of completion thyroidectomy not recommended (except select cases) (Weak/Low)
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  • Staging and Risk Stratification
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  • Postoperative Staging Recommendation 47 AJCC/UICC staging for all DTC patients, based on utility in predicting mortality, and its requirement in cancer registries (Strong/Moderate)
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  • ATA Initial Risk Stratification AJCC stage unable to predict recurrence 2009 guidelines introduced the Initial Risk Stratification system
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  • ATA Initial Risk Stratification Risk in each category can vary based on other features Histology Multifocality Extent of vascular invasion Extent of LN mets Genetic markers
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  • Modified Initial Risk Stratification System
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  • BRAF V600E Mutation BRAF V600E shown to predict higher risk, but is also linked to other clinico-pathologic features Tufano et al, Medicine 2012 Meta-analysis 14 studies, 2,470 PTC patients Higher recurrence in BRAF V600E compared to wild type (24.9% vs 12.6%) Sensitivity to detect recurrence was 65% But PPV 25%
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  • Postoperative Risk Stratification Recommendation 48 (CHANGED) A.ATA 2009 Initial Risk Stratification system for postop DTC patients based on utility in predicting risk of recurrence/persistence (Strong/Moderate) B.May use additional prognostic variables in Modified Initial Risk Stratification System; incremental benefit not established (Weak/Low) C.BRAF testing not routinely recommended for initial postop risk stratification (adds little incremental prognostic value) (Weak/Moderate)
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  • Dynamic Risk Assessment Initial staging and risk assessments provide single point estimates and can be used to guide initial therapy No current system modifies initial risk estimate using follow-up data Systems that incorporate response to therapy have improved ability to predict long term outcomes Limitations Not validated in certain subgroups (eg no RAI, lobectomy) Lack of prospective data Inconsistency between authors in defining significant Tg levels or imaging findings
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  • Vaisman et al, Clin Endocrinol 2012
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  • Validation of Dynamic Risk Assessment Tuttle et al, Thyroid 2010
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  • Dynamic Risk Assessment Excellent response: no clinical, biochemical or structural evidence of disease Biochemical incomplete response: abnormal thyroglobulin or rising anti-thyroglobulin antibody levels in the absence of localizable disease Structural incomplete response: persistent or newly identified loco-regional or distant metastases Indeterminate response: non-specific biochemical or structural findings which cannot be confidently classified as either benign or malignant. This includes patients with stable or declining anti-thyroglobulin antibody levels without definitive structural evidence of disease
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  • Response to Treatment ATA RiskExcellentIncomplete Biochemical Incomplete Structural Indeterminate Low86-91%11-19%2-6%12-29% Intermediate57-63%21-22%19-28%8-23% High14-16%16-18%67-75%0-4%
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  • Postoperative Risk Assessment Recommendation 49 Initial recurrence risk estimates should be continually modified during follow-up, because the risk of recurrence and disease specific mortality can change over time as a function of the clinical course of the disease and the response to therapy (Strong/Low)
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  • Postoperative Radioactive Iodine Therapy
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  • Decision for RAI Therapy 2009 guidelines recommended postop RAI therapy mainly on the basis of tumour pathology (esp size) Postoperative