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Post-operative Management of follicular Cell Derived Thyroid Cancer (FCDTC)

Post-operative Management of follicular Cell Derived Thyroid Cancer (FCDTC). Vahab Fatourechi MD Esfahan International Conference Oct 2012. Case My cousin. My 26 yr old cousin she was unmarried comes to Mayo and had near total thyroidectomy 10 year ago

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Post-operative Management of follicular Cell Derived Thyroid Cancer (FCDTC)

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  1. Post-operative Management of follicular Cell Derived Thyroid Cancer (FCDTC) Vahab FatourechiMD Esfahan International Conference Oct 2012

  2. CaseMy cousin • My 26 yr old cousin she was unmarried comes to Mayo and had near total thyroidectomy 10 year ago . Path showed a 2 cm PTC in the rt lobe and a 2 mm PTC in the left and two1cm central compartment nodes (level VI) were positive

  3. MY cousin • Do I remnant ablate with RAI? • What is the risk of neck node recurrence? • If there will be recurrence in the neck when is more likely to happen? • What is the likelihood mortality? • What if she was 45 years old?

  4. The Points I will try to Make • Most FCDTCs are papillary (PTC) • Most PTCs are low risk • Most low risk PTCs do not need RAI remnant ablation • Post operative staging by TNM classification or Mayo MACIS score is helpful for choosing who needs RAI remnant ablation- Plus common sense and patient preference • Tg monitoring is helpful even if no RAI ablation

  5. The Points I will try to Make • Level of and duration of T4 suppressive therapy relates to risk profile and disease status • Patients with sensitive Tg <0.1 ng/ml do not need withdrawal or rHTSH stimulated scan • Neck US is the best follow up test if no distant metastases • Tg Pos WBS neg patients with macroscopic residual disease should not get RAI therapy

  6. The Points I will try to Make • Ethanol US guided injection of recurrent neck nodes in low risk PTC in selected cases is safe and effective • ATA guidelines “thyroid 2009” is helpful and close to our institution’s practice with some variation. • Expect new guidelines in 2013 • Guidelines show the direction of practice and should be individualised

  7. Differentiated Thyroid Carcinoma • Follicular cell derived thyroid carcinomas (PTC and FTC) comprise up to 95% of all thyroid carcinomas • The vast majority of these tumors are well differentiated Grebe & Hay 1995

  8. Estimated Incidence of Thyroid Carcinoma in 2012 in USA • 56460 cases per year (was 36000 in 2009) • 43210 Female • 13250 Male F/M (3.3%) • Estimated death 1780 (3.1%) • Prevalence 496901(yr 2009) • 6 % of Us population (18) million have micro PTC Most patients with thyroid cancer are cured, or live with their disease

  9. ATC FTC HCC PTC Cause-Specific Mortality Rates in FCDC 90 Dying of thyroid carcinoma(cumulative %) Years after initial treatment

  10. Watchful F/U in Microcarcinoma of Thyroid (<1cm)) • 340 patients • 74 months average f/u • 15% grow more than 3 mm in 10 yr F/U • New nodal mets in 3.4% in 10 yrs • 109 had surgery Conclusion: Observation can be an option in cases of incidental micto PTC Ito et al world J Surgery 2010

  11. TNM Staging of Differentiated Thyroid Cancer • T1 Primary tumor <2cm. • T2 >2 cm and <4 cm • T3 >4 cm minimal extra thyroidal extension • T4a Any size tumor beyond thyroid capsule • T4b Invasion of pre-vertebral fascia, artery vocal cord • Tx Tumor size not known

  12. Cervical Node-bearing Regions

  13. TNM Staging of Differentiated Thyroid Cancer Regional and upper mediastinal nodes (N) • N0 Negative nodes • NX Nodes not assesses • N1a Level VI • N1b Other levels and mediastinum Distant Metastases(M) • M0 Absent • M1 Present

  14. TNM Staging of DTC Age <45 • Stage I Any T Any N MO • Stage II Any T Any N M1

  15. TNM Staging of DTC Age>45 • Stage I T1,N0,M0 • Stage II T2,N0,M0 • Stage III T3,N0,M0, T(1-3)N1a M0, • Stage IVA T4a,N0,M0,T4a,N1a, M0, T(1-4)N1b M0 • Stage IVB T4b any N M0 • Stage IVC Any T any N M1

  16. PTC Survival by TNM Stage n=2,284 1940-97 P=0.0001 Surviving papillary thyroidcarcinoma (%) TNM stage I 1,360 II 493 III 399 IV 32 Years after initial treatment

  17. Cell Types Associated with Aggressive FCDTC Tumors • Follicular cancer with vascular invasion • Hurtle cell with vascular invasion • Columnar cell PTC • Insular cell PTC • Tall cell PTC • Solid PTC • Trabecular PTC • Higher grades of PTC : Grade 2-4 • Diffuse sclerosing PTC

  18. MACIS Calculation ID Hay MACIS score (LOW RISK<6) • 3.1 (if <40 years) or (0.08 x age) • + (0.3 x size in cm) • +1 (if locally invasive) • +1 (if incompletely resected) • +3 (if distant metastases present) Hay et al 1993 Should apply only to classic PTC

  19. Cause-Specific Survival by MACIS Score 1940-97 <6 (1,900 : 83%) 6-6.99 (201 : 9%) Survival (%) 7-7.99 (75 : 3%) n=2,284 P=0.0001 MACIS score ³8 (108 : 5%) Years after initial treatment

  20. Cause Specific Mortality from PTC in High-and Low-Risk Groups TNM, MACIS TNM III + IV (431) I + II (1,853) Dying of papillary carcinoma(cumulative %) MACIS 6+ (384) ID Hay <6 (1,900) Years after initial treatment

  21. Arbitrariness of Risk Factor Assessment • 43 year old T1 N1b M0 would be Stage I • 46 year old with the same disease will be Stage IVA • A 40 year old with pulmonary and bone metastases will be considered Stage II • An 80 year old operated for benign adenoma and 4 mm incidental PTC with be MACIS 7.5 will be considered high risk

  22. Arbitrariness of Risk Factor Assessment • 46 ys. 5 cm tumor N0 M0 MACIS 5.1 TNM Stage III • 46 ys. 1cm N level VI MACIS 3.6 TNM Stage III • 46 ys. 1cm tumor, N Level II MACIS 3.6 TNM Stage IVA Comment: Risk assessment is helpful but consider overall clinical presentation

  23. Post-operative Management of Follicular Cell Derived Thyroid Cancer Completion thyroidectomy

  24. Completion thyroidectomy • ATA accepts lobectomy alone under certain conditions • Not needed for occult incidental <1.0 cm PTC • Not needed for follicular cancer with minimal capsular invasion and no vascular invasion • Ideally if needed should be done first week after initial surgery or after 2-3 months

  25. Post-operative Management of Follicular Cell Derived Thyroid Cancer Post operative remnant RAI ablation

  26. Impact of I131 on FCDTC Recurrence and Mortality Mazzaferri 1997 Mazzaferri et al 1997

  27. Problems with Mazzaferri Data Set • Various pathologies (PTC / FTC / HCC) • Various surgeries (Lobectomy / subtotal / total) • I-131 administered only to those with more complete surgery • No risk-group stratification • No evaluation of I-131 efficacy following adequate, complete surgery

  28. ATA Thyroid 2009 I-131 Remnant Ablation ATA Guidelines 2009

  29. RAI Remnant Ablation(ATA 2009) • Non for tumor<1 cm • Non for multifocal <1 cm • May not be needed for small minimally invasive follicular • For 1-4 cm tumor selected patients with risk factors, node+, cell type, age • For >4 cm, M1 • Gross extra thyroidal extention

  30. I-131 Remnant Ablation (ATA 2009) • Either withdrawal or rhTSH • Low iodine diet 1-2 weeks • Pre-therapy scan useful • 30-100 mCi adequate for remnant • Residual disease 100-200 mCi • Start T4 on day 3 • Post therapy scan recommended Sherman et al and Fatourechi et al 2000

  31. National Thyroid Cancer Registry Jonklass et al 2007

  32. Recurrence in “low risk” PTC (Hay ID) I131 Ablation 100 No Ablation 96 Relapse free survival (%) 92 88 84 0 5 10 15 20 Years from diagnosis 1163 patients; total or near-total TTX; 1970 - 2000

  33. Survival for “low risk” PTC (MACIS < 6)(Hay ID) 100 95 I131 Ablation (n=498) Survival (cause-specific) 90 No Ablation (n=665) 85 0 0 5 10 15 20 Years from diagnosis 1163 patients; total or near-total TTX; 1970 - 2000

  34. Recurrence (TxN0M0, MACIS<6) 100 I131 Ablation 90 No Ablation 80 0 5 10 15 20 Years from diagnosis 636 node negative patients; total or near-total TTX; 1970 - 2000

  35. Carcinogenesis with I131 3 populations (Sweden, Italy, France) 6841 patients Mean dose I131 162 mCi Mean F/U of 13 years Incidence of 2nd malignancy Dose dependent risk increase * * Increased risk for cancer of: Salivary gland 7.5 Bone & soft tissue 4.0 Uterus / female genital 2.3 Colorectal 1.3 Bone and soft tissue Rubino 2003

  36. Secondary Cancer Risk after RAI • Comments: • Dose related small risk of secondary cancers with doses above 50 mCi • Doses over 100 mCi cause 3 leukemia and 53 solid tumor /100,000/10Yr. Rubino Br J Cancer 2003 • Meta analysis: RR for leukemia 2.5 For other not significant cancers. Sawka Thyroid 2009 • Late increased mortality from non thyroid malignancy in long term F/U of childrenHay world J surg 2010 • When benefits questionable or controversial why risk it?

  37. Arguments for a Selective Approach • Avoid overtreatment of patients who do not require aggressive therapy • Avoid under-treatment of patients at high risk of disease residue or recurrence • Avoid over-investigation (with associated expense, morbidity and psychological distress) of patients with low-risk of recurrence • Avoid under-evaluation of high risk patients

  38. Conclusion • In low risk patients, remnant ablation is not required for interpretation or monitoring of Tg SO LONG AS: • Thyroidectomy is truly “ near total” • Follow-up is primarily through US or other anatomic imaging, rather than isotope scans

  39. Remnant Ablation Selection by MACIS Score No Remnant ablation for MACIS <6.0 • Does not consider lymph node at any age, at any site, any size • Does not consider multifocality • Does not apply to high risk cell types • May apply to grade 1 PTC only • Does not consider minimal extra-thyroidal extension • Critics: May apply to Mayo because of surgical expertise

  40. External Beam Radiation (41B) (ATA 2009) To be considered: • Over age 45, extra thyroidal extension at surgery possibility of microscopic residual disease. • Gross residual tumor not likely responsive to surgery or RAI • For other unresectable disease in critical areas: bone, CNS, mediastinal, pelvic • Comment: For Neck should be delayed until surgical options exhausted. Applicable to unusual cell type, high grade PTC

  41. Post Operative Management of follicular Cell Derived Thyroid Cancer Suppressive thyroxine therapy

  42. Effect of TSH Suppression on Relapse-free Survival in DTC 139 patients with DTC 45 patients with stable TSH Similar findings in entire cohort of 141 patients No differences in AJCC stage of patients in the two groups Pujol et al 1996

  43. TSH Suppression and Outcomes • 683 patients with DTC followed at 14 institutions up to 10 years • Majority (90%) were PTC A: Stage I & II B: Stage III & IV A TSH Suppression % Free of Progressive Disease B p = 0.03 Cooper et al 1998 Follow-up

  44. T4 Suppressive Therapy (ATA 2009) • High risk, intermediate risk : TSH <0.1 • Low risk: 0.1-0.5 • Persistent disease TSH<0.1 indefinitely • Disease free high risk, TSH 0.1-0.5, 5-10 yrs • Disease free low risk TSH 0.3-2.0 • No RAI, disease free Tg undetectable TSH 0.3-2.0

  45. Post-operative Management of follicular Cell Derived Thyroid Cancer Thyroglobulin monitoring

  46. Thyroglobulin Monitoring (ATA 2009) • Every 6-12 months initially then yearly depending on risk • Even if not a TT or remnant ablation

  47. Post Operative Management of follicular Cell Derived Thyroid Cancer Withdrawal or rhTSH stimulation testing

  48. rhTSH Stimulation(ATA 2009) • After 6-12 months after remnant ablation • If US is neg. and stim-Tg is undetectable no need to repeat • Comment: Mayo experience: with sensitive Tg <0.1 rhTSH stimulated-Tg does not change management and may not be needed

  49. Is rhTSH Helpful in Undetectable Sensitive Serum Tg in Thyroid Cancer? • 163 patients , post thyroidectomy and RAI ablation , neg Tg antibodies • Tg<0.1 on T4 • Medium 3.6 Yrs. F/U • Only 2% stimulated Tg >2.0 • 6 recurrences detected by US of the neck AM Chindris, N Diel, J crook , V Fatourechi, R Smallridge JCEM Aug 2012

  50. rhTSH in Undetectable Sensitive Serum Tg in Thyroid Cancer is not Helpful Conclusion In pateints with FCDTC if T-4 suppressed Tg is <0.1 ng/ml annual Tg- supp and periodic neck US are adequate rhTSH testing and WBS do not change management and are not needed By analogy same should apply to withdrawal Tg-stim and WBS A. Chindris, N. Diel, J. crook , V. Fatourechi, R. Smallridge JCEM Aug 2012

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