What s New in the ATA 2015 Thyroid Cancer Guidelines

Transcription

1 1/9/ AACE Advances in Thyroid Cancer Course: SMALL GROUPS Dr. Brian W Kim has no industry disclosures. What s New in the ATA 2015 Thyroid Cancer Guidelines Brian W Kim, MD Rush University Medical Center Chicago, IL Newer Data, Revised Guidelines Evolving understanding of the natural history of PTCA Increasing molecular understanding of PTCA Clinical trial data supporpng less tespng and less surgical / radio-iodine treatment FDA approved systemic therapy for advanced disease 2015 American Thyroid Associa=on Management Guidelines for Adult Pa=ents with Thyroid Nodules and Differen=ated Thyroid Cancer The American Thyroid AssociaPon (ATA) Guidelines Taskforce 101 RecommendaPons 133 pages 1078 references New* Sonographic Risk Groups Part I US GUIDED RISK STRATIFICATION (SHORT VERSION FOLLOWING DR. GHARIB) 1

2 2015 Table 6: Risk vs. FNA size threshold Poll on Re-FNA: PaPent with no hx risk fx: 1.6 cm, solid, very hypoechoic, irregular margins, FNA benign 9 months ago - Repeat ultrasound: STABLE SIZE and s=ll HIGH RISK SONOGRAPHIC APPEARARNCE - Do you repeat the FNA? - A. Usually - B. Some=mes - C. Not if the nodule is stable on ultrasound In Surveillance: US Pa[ern > Growth Rec 23A HIGH SUSPICION US pa[ern, a^er BENIGN FNA, repeat the US guided FNA within 12 months No requirement for growth for high risk US nodules (growth spll applies to low - intermediate risk US pa[ern nodules) US pa[ern is a be[er predictor of FALSE NEGATIVE FNAs than growth Lack of validapon of growth as a risk factor Lack of agreement in serial measurements AACE repeat FNA for High Risk US or suspicious clinical features US Surveillance: not forever ATA 2015 Rec 23D: a^er 2 BENIGN FNAs, further surveillance is no longer indicated same as AACE ATA 2015 Rec 27B: growing nodules that are benign a^er FNA should be regularly monitored Two Specific AddiPons since Rec 5: PET+ nodule > 1 cm = FNA PET diffuse uptake = no FNA 2015 Rec 6: Ultrasound of nodular thyroid should ROUTINELY include lymph nodes (2015 Rec 32: US should be done for LN analysis pre-operapvely also per AACE 7.2.1) Wikipedia From Jay Shendure & Hanlee Ji Nature Biotechnology 26, (2008) Illumina website Part 1 Special Men9on MOLECULAR GENETIC TESTS: THE KNOWN UNKNOWNS 2

3 1/9/18 Molecular GenePc Tests: Mother May I? Example: Thyroseq in a B4 Mrs O, a 50 yo woman; 2 cm nodule, no Hx risk fx Cytology B4 FN; but she doesn t want surgery 2009 Rec 8: markers may be considered for indeterminate cytology, rapng C ATA 2015 = Permissive Language, not DirecPve: R13 -- If you consider MGTs, talk to papent strong rec, low quality evidence R14 -- use a CLIA/CAP cerpfied lab R15 -- AUS/FLUS, consider all data, may use molecular tespng R16 -- Foll neoplasm, consider all data, may use molecular tespng R17 Susp for malig, consider all data, may use molecular tespng; BRAF or muta=on panel may be used if this would change surgery Risk about 1 in 3 for cancer? (at the insptupon?) Re-FNA B4 + ThyroSeq v2: KRAS Q61R; 182 A> G 80% risk of LOW risk PTCA / (NIFTP)???* [valid?] What if the MGT had been Nega=ve? What is her residual risk? Long-term outcome data proving clinical uplity are needed A^er the Guidelines: NIFT-P Role of Post-surgical Molecular TesPng? NonInvasive Follicular Thyroid (neoplasm) (with) Papillary-like (nuclear) (features) Well DEMARCATED? Image from Wikipedia Molecular signature? Giant NIFTP? ATA 2015 REC 48 C: While not rou=nely recommended for ini=al postopera=ve risk stra=fica=on in DTC, the mutaponal status of BRAF, and potenpally other mutapons such as TERT, have the potenpal to refine risk espmates when interpreted in the context of other clinico-pathologic facotrs (Weak rec/mod evid) Image Thyroid Cancer Genome Atlas ConsorPum, Cell 2014 (right) Lobectomy only? For who? 2009: 2009 Rec 26: thyroid cancer >1cm, do near-total or total thyroidectomy Lobectomy may be sufficient for: small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas Part II TO HALVE, OR HALVE NOT: THE LOBECTOMY ISSUE No prior head and neck irradia=on No radiologically or clinically involved cervical nodal metastases. Recommenda9on ra9ng: A Images from Wikipedia 3

4 Poll: Would you agree that lobectomy is reasonable for an asymptomapc 60 yo male papent with a 3.9 cm FNA-B6 tumor with no other nodules, no clinically involved (imaging or exam) lymph nodes, no FHx of thyroid cancer, and no prior h/o radiapon? A Yes, less is more B No, I want the pa=ent to live A New Paradigm: selec9ve lobectomy ATA 2015 Rec 35B For papents with thyroid cancer >1 cm and <4 cm without extrathyroidal extension, and without clinical evidence of any lymph node metastases (cn0*), the ini=al surgical procedure can be either a bilateral procedure (near-total or total thyroidectomy) or a unilateral procedure (lobectomy) con9nued: A New Paradigm: 2015 Rec 35B Thyroid lobectomy alone may be sufficient inipal 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 pa=ent preferences. (Strong Recommenda=on, Moderate-quality evidence) SPll a lot of leeway! How Much Recurrence is Too Much? PTCA o^en mulpfocal / bilateral SPll Loco-regional recurrence rates of less than 1-4% and complepon thyroidectomy rates of less than 10% can be achieved following thyroid lobectomy [ATA 2015 text] The Argument for Rec 35B, ConPnued ATA 2015 Sec=on B7 suppor=ng Rec 35B: In properly selected low to intermediate risk papents the extent of inipal thyroid surgery probably has li[le impact on disease specific survival since salvage therapy is quite effec=ve in the few papents that recur a^er thyroid lobectomy, a conservapve management approach to complepon surgery, acceppng a slightly higher risk of loco-regional recurrence, is an acceptable management strategy. Other pracpcal considerapons re: lobectomy Will papent/doctor be comfortable knowing surveillance with TG no longer sensipve? Is a mid-normal TSH op=mal if you ve had low risk PTCA? Or need L-T4 anyway? Before diagnospc lobectomy, should we do FNA of contralateral nodules NOT meepng normal criteria? e.g. small but hypoechoic BIOPSY??? 4

5 Who should get I-131? Conceptually unchanged vs 2009: LOW risk for recurrence = don t need it Part III HISTOPATHOLOGIC RISK STRATIFICATION AND I THE TIPPING POINTS Images from Wikipedia INTERMEDIATE risk may benefit HIGH risk are expected to benefit (POORLY differenpated probably won t benefit) 2015 ATA low risk proposed changes* Papillary Thyroid Cancer (with all of the following) Clinical N0 or 5 pathologic N1 micrometastases (<0.2 cm in largest dimension)* Intrathyroidal, encapsulated follicular variant of papillary thyroid cancer* (now called NIFTP) Intrathyroidal, well differenpated follicular thyroid cancer with only capsular invasion* Intrathyroidal, well differenpated follicular thyroid with minor vascular invasion* Intrathyroidal, papillary microcarcinoma, unifocal or muldfocal, including V600E BRAF mutated (if known)* BRAF: not quite ready for primepme? 2015 Rec 48C: Since BRAF mutaponal status appears to add li[le incremental prognospc value to clinicopathological staging systems, BRAF tes=ng is not rou=nely recommended for ini=al post-opera=ve risk stra=fica=on in DTC. (Weak recommendapon, Moderate-quality evidence) +BRAF in microcarcinomas doesn t seem to increase risk of recurrence (unless +ETE) 2015 Fig 4: PTCA > 1cm; BRAF+ ~10% risk; associates with more aggressive features Ongoing trials look at BRAF in otherwise LOW risk PTC 2015: Intermediate Risk proposed changes Microscopic invasion of tumor into the perithyroidal so^ Pssues* Clinical N1 or >5 pathologic N1 with all involved lymph nodes < 3 cm in largest dimension* RAI avid metastapc foci in the neck on the first post-treatment whole-body RAI scan Aggressive histology (e.g., tall cell, hobnail variant, columnar cell carcinoma) Papillary thyroid cancer with vascular invasion. Intrathyroidal, PTC, primary tumor 1-4 cm, V600E BRAF mutated (if known)* Fig only MulPfocal papillary microcarcinoma with extrathyroidal extension and V600E BRAF mutated (if known)* 5

6 PracPcal considerapons for I-131 Decision Note the difference between CLINICAL, RADIOLOGIC and PATHOLOGIC nodal involvement (the la[er known only post-op) You can feel it You see it clearly on US or CT pre-op Vs Found via histologic secpon on microscope not the same negapve prognosis I-131? The Tipping Point: ATA 2015 Table 14 (who gets I-131) looks new but the principles are the same; minimal condipons: EXTRATHYROIDAL EXTENSION, even microscopic ( but more research needed )(MSKCC does not RAI for minor ETE alone Oral Onc 2013) NODAL INVOLVEMENT, extent is arguable extrathyroidal extension may be minimal/focal, vs significant? Table 14 for I-131: smaller tumors with microscopic ETE may not require I-131 You can somepmes see if tumor is extrathyroidal on pre-op imaging(!) Change: Lower AcPviPes ATA 2015 Rec 55 - (Malick et al., Schlumberger et. al 30mCi vs 100mCi) If radioacpve iodine remnant ablapon is performed a^er total thyroidectomy for ATA low risk thyroid cancer or intermediate risk disease with lower risk features (i.e. low volume central neck nodal metastases with no other known gross residual disease nor any other adverse features), a low administered dose acpvity of approximately of 30 mci is generally favored over higher administered dose acpvipes. (Strong recommenda=on, Highquality evidence) Fewer Iodine Scans 2015 Rec 66: A^er the first post-treatment WBS performed following RAI remnant ablapon or adjuvant therapy, low-risk and intermediate-risk papents (lower risk features) with an undetectable Tg on thyroid hormone with negapve anpthyroglobulin anpbodies and a negapve US (excellent response to therapy) do not require roupne diagnospc WBS during follow-up. (Strong recommenda=on, Moderate-quality evidence) Grey areas in I-131 Recs When would aggressive histology ma[er? What if microcarcinoma but tall cell? Table 14: NO I-131 for MICROCARCINOMA. No benefit of disease specific survival OR diseasefree survival but Table 14: if tumor >1cm, histology maqers; I-131 not roupnely recommended, but may be increased disease-free survival; consider for aggressive histology or lymphovascular invasion i.e. aggressive histology can qualify papent as ATA intermediate risk (and thus possibly a candidate for I-131) 6

7 1/9/18 The Future Is Soon? Tailored therapy? Part IV NEW DEVELOPMENTS - TKIS, REDIFFERENTIATION? Images from Wikipedia (le^), Thyroid Cancer Genome Atlas ConsorPum, Cell 2014 (right) TKIs Table 16: TKI Guidance (only PFS not OS) When to start? What to watch for? - x TG rising; stable pulmonary mets; only PET nodes Thank You!!! 7