1. Management in 2006 of Patients with Low-Risk Papillary Thyroid Carcinoma Management in 2006 of Patients with Low-Risk Papillary Thyroid Carcinoma Professor Ian D. Hay MB PhD FRCP Mayo Clinic College of Medicine

2. Differentiated Thyroid Carcinoma Managed at Mayo Clinic 1940-2000 Histotype Distribution CP1028491-8 n=3,048 1940-2000 n=3,048 1940-2000 8% 5% Papillary (2,512) 82% Medullary (246) Follicular (155) Hürthle cell (155)

3. 2,512 Papillary Thyroid Carcinoma Patients Managed At Mayo Clinic During 1940-2000 Presenting Disease p TNM Stages MACIS Scores I (60%) III (18%) II (21%) IV (1%) <6 (84%) 6+ (16%) CP1028491-1 n=2,512 1940-2000 n=2,512 1940-2000

4. Managing Low-risk DTC in 2005 A Day in the Life of a Mayo PTC Specialist! In an attempt, perhaps, to better define later a more rational approach to the postoperative management of low-risk differentiated thyroid cancer, let us first consider, by way of introduction, two cases of papillary thyroid microcarcinoma (PTM) seen on a recent Mayo clinic outpatient day In an attempt, perhaps, to better define later a more rational approach to the postoperative management of low-risk differentiated thyroid cancer, let us first consider, by way of introduction, two cases of papillary thyroid microcarcinoma (PTM) seen on a recent Mayo clinic outpatient day

5. Case 1: Node-Positive PTM Case 1: Node-Positive PTM 3/99: 59y/o male; 4hr op (TTx, central compartment exploration, (L)MND) for bilateral multicentric 1 cm PTM; 20/46 pos nodes(Delphian, central, lat neck) 3/99: 59y/o male; 4hr op (TTx, central compartment exploration, (L)MND) for bilateral multicentric 1 cm PTM; 20/46 pos nodes(Delphian, central, lat neck) 5-9/99: 30 + 100 mCi I-131 for ablation 5-9/99: 30 + 100 mCi I-131 for ablation 3/00: rhTSH-stimulated I-123 WBS and US neck negative; Tg auto-ab pos 3/00: rhTSH-stimulated I-123 WBS and US neck negative; Tg auto-ab pos

6. Case 1: Node-Positive PTM 4/01-4/04: annual neck US showed 2 (L) bed lesions, initially 4 and 6 mm, but growing to 6, 8mm with incr. flow, microcalcifications; Tg 0.3-0.6 Ab-pos 4/01-4/04: annual neck US showed 2 (L) bed lesions, initially 4 and 6 mm, but growing to 6, 8mm with incr. flow, microcalcifications; Tg 0.3-0.6 Ab-pos 4/04: Pos USGB (L) bed led to 2 hr op, excising 2/2 pos (L) T/E groove nodes 4/04: Pos USGB (L) bed led to 2 hr op, excising 2/2 pos (L) T/E groove nodes 9/05: Ab-neg Tg <0.1ng/mL; US neck negative for recurrence at 78 p/op mo 9/05: Ab-neg Tg <0.1ng/mL; US neck negative for recurrence at 78 p/op mo

7. Case 2: Recurrent node-positive PTC 4/98: 28y/o female: TTx, central NLND for multifocal PTM ; 6/7 pos nodes 4/98: 28y/o female: TTx, central NLND for multifocal PTM ; 6/7 pos nodes 5/98: 175 mCi I-131 for 6.8% uptake 5/98: 175 mCi I-131 for 6.8% uptake 1/99: re- exploration for palpable (L) lat nodes: 1/5 nodes pos at path exam 1/99: re- exploration for palpable (L) lat nodes: 1/5 nodes pos at path exam 10/99: 200 mCi given for neck uptake 10/99: 200 mCi given for neck uptake 4/00: rhTSH- WBS neg; Tg (USC) <1 4/00: rhTSH- WBS neg; Tg (USC) <1

8. Case 2: Another Uncooperative NNM 2001-2003: multiple neg rhTSH-WBS but Tg rise after stim led to neg MRI of neck and whole body FDG-PET/CT 2001-2003: multiple neg rhTSH-WBS but Tg rise after stim led to neg MRI of neck and whole body FDG-PET/CT 2/03: Pos USGB of 7X4X3mm node, and pt sent to MC for possible PEI 2/03: Pos USGB of 7X4X3mm node, and pt sent to MC for possible PEI 3/03: Tg 0.3(Ab-neg); 8X5X3mm (L) bed node treated with US-guided PEI 3/03: Tg 0.3(Ab-neg); 8X5X3mm (L) bed node treated with US-guided PEI

9. Case 2: Adequately Treated NNM 7/03: node re-treated with 0.2cc EtOH 7/03: node re-treated with 0.2cc EtOH 11/03- 10/04: injected node no longer identifiable on repeated US exams 11/03- 10/04: injected node no longer identifiable on repeated US exams 10/05: TSH 0.1, Tg <0.1 ng/mL; neck US negative for recurrence at 90 mo 10/05: TSH 0.1, Tg <0.1 ng/mL; neck US negative for recurrence at 90 mo

10. What do these cases illustrate? Inadequacy of regional nodal resection at first neck exploration Inadequacy of regional nodal resection at first neck exploration Futility of p/op remnant ablation Futility of p/op remnant ablation Efficiency of PEI in nodal ablation Efficiency of PEI in nodal ablation

11. What clinical and research experiences would justify such atypical views on postop management? 23 years consulting on patients with thyroid malignancy at the Mayo Clinic 23 years consulting on patients with thyroid malignancy at the Mayo Clinic Daily experience in managing DTC patients; now >400 cases annually Daily experience in managing DTC patients; now >400 cases annually Management approach also influenced by studying cohort of 2,512 PTC pts treated at Mayo during 1940 to 2000 Management approach also influenced by studying cohort of 2,512 PTC pts treated at Mayo during 1940 to 2000

12. PTC Management in Five Decades PTC Management in Five Decades During 1950 through 1999, mortality and recurrence rates in 2,286 Mayo PTC patients did not progressively improve with successive decades During 1950 through 1999, mortality and recurrence rates in 2,286 Mayo PTC patients did not progressively improve with successive decades Outcome was excellent in low-risk (MACIS <6) PTC patients treated by NTT, conservative nodal dissection, and not improved by increasing use of postoperative remnant ablation Outcome was excellent in low-risk (MACIS <6) PTC patients treated by NTT, conservative nodal dissection, and not improved by increasing use of postoperative remnant ablation World J Surg 26: 879, 2002

13. Relevance of Epidemiology to Contemporary Management Presenting features (patient and tumor variables) permit outcome prediction; tumor biology more powerful than therapy choices Presenting features (patient and tumor variables) permit outcome prediction; tumor biology more powerful than therapy choices Majority (85%) of PTC patients at minimal risk of recurrence or cause-specific mortality Majority (85%) of PTC patients at minimal risk of recurrence or cause-specific mortality Logically, therefore, aggressive adjunctive treatments should be restricted to minority (15%) at “high-risk,” i.e., applying the principle of “letting the punishment fit the crime.” Cady,B Am J Surg 174: 462, 1997 Logically, therefore, aggressive adjunctive treatments should be restricted to minority (15%) at “high-risk,” i.e., applying the principle of “letting the punishment fit the crime.” Cady,B Am J Surg 174: 462, 1997

14. APPLYING “COMMON SENSE” TO MANAGING PATIENTS WITH LOW-RISK DIFFERENTIATED THYROID CANCER

15. Five Steps in Primary Management of LRPTC I.Diagnosis: cytologic and histopathologic II.Primary surgical treatment ** III.Staging and risk-group assignment * IV.Adjuvant therapy *** V.Long-term surveillance ***

16. “Many can biopsy but few can interpret thyroid cytology” If an endocrinologist or surgeon is to serve well patients with NTD, then he/she must identify, ideally sited conveniently, a cytopathologist whose skills are associated with acceptably low rates of both false- positive and false-negative reports If an endocrinologist or surgeon is to serve well patients with NTD, then he/she must identify, ideally sited conveniently, a cytopathologist whose skills are associated with acceptably low rates of both false- positive and false-negative reports

17. “Common Sense” Approach to LRPTC Management I.Diagnosis: cytologic and histopathologic II.Primary surgical treatment

18. CP1028491-2 2,512 Papillary Thyroid Carcinoma Patients Managed At Mayo Clinic During 1940-2000 Trends in Extent of Primary Surgery Initial thyroid operations (%) 1940- 1954 1940- 1954 1955- 1969 1955- 1969 1985- 2000 1985- 2000 1970- 1984 1970- 1984 n=2,512 Unilateral lobectomy (293) Unilateral lobectomy (293) Near-total thyroidectomy (1,324) Total thyroidectomy (635) Bilateral subtotal resection (220) Bilateral subtotal resection (220)

19. Appropriate Therapy for Low-risk Papillary Cancer “Low-risk” PTC represents majority of FCDC in areas of iodine sufficiency “Low-risk” PTC represents majority of FCDC in areas of iodine sufficiency Such tumors multicentric, typically bilateral, often involving neck nodes Such tumors multicentric, typically bilateral, often involving neck nodes Reasonable, therefore, to employ a bilateral approach and to determine nodal status on treatment day one Reasonable, therefore, to employ a bilateral approach and to determine nodal status on treatment day one

20. 320 Papillary Thyroid Carcinoma Patients Managed at Mayo Clinic during 1940-1954 Impact of Bilateral Lobar Resection Cumulative % with occurrence n=320 P=0.35 n=320 P=0.35 Unilateral lobectomy (176) Recurrence, Any Site Bilateral lobar resection (144) Years after initial surgery CP1029349-1 010203040 Bilateral lobar resection (136) 010203040 Mortality from PTC n=296 P<0.001 n=296 P<0.001 Unilateral lobectomy (160)

21. Impact of BLR on Mortality and Recurrence in Low- and High-Risk PTC By MACIS <6 and 6+ CP1029349-2 Cumulative % with occurrence Years after initial surgery Mortality 05 Recurrence UL (60) BLR (331) 101525 1940-2000 P=0.015 n=280 1940-2000 P=0.015 n=280 UL (39) BLR (241) 200510152520 0510152005101520 MACIS 6+ P=0.007 n=391 MACIS 6+ P=0.007 n=391 1940-54 P<0.001 n=256 1940-54 P<0.001 n=256 UL (135) BLR (121) MACIS <6 P=0.31 n=296 MACIS <6 P=0.31 n=296 UL (160) BLR (136)

22. Advantages of NT/TT in Papillary Thyroid Cancer Bilateral lobar resection (BLR) reduces locoregional recurrences in all and reduces cause-specific mortality in ‘high-risk’ PTC Bilateral lobar resection (BLR) reduces locoregional recurrences in all and reduces cause-specific mortality in ‘high-risk’ PTC Thus: in 2006, a pre-op FNA dx of PTC should lead to BLR (NT/TT), with safeguarding of parathyroids Thus: in 2006, a pre-op FNA dx of PTC should lead to BLR (NT/TT), with safeguarding of parathyroids

23. Importance of Neck Nodal Status in Low-Risk PTC If a PTC patient has only a thyroidectomy and no inspection or exploration of the central compartment, with sampling of level VI nodes, then the patient has been ill-served, and has already fallen on only day one of treatment into a “pitfall” If a PTC patient has only a thyroidectomy and no inspection or exploration of the central compartment, with sampling of level VI nodes, then the patient has been ill-served, and has already fallen on only day one of treatment into a “pitfall”

24. Pre-op Ultrasound Mapping and the Lateral Neck Preoperative neck ultrasound, with identification of nodal mets, permits planned appropriate nodal resection at the time of first neck exploration Preoperative neck ultrasound, with identification of nodal mets, permits planned appropriate nodal resection at the time of first neck exploration Discovery of a lateral neck nodal met (removed at open biopsy, or positive on USGB or at FS) should lead to function-sparing modified neck dissection at first neck exploration Discovery of a lateral neck nodal met (removed at open biopsy, or positive on USGB or at FS) should lead to function-sparing modified neck dissection at first neck exploration

25. Role of Preoperative Staging ATA 2006 Guidelines R21. “Preoperative neck ultrasound for the contralateral lobe and cervical (central and bilateral) lymph nodes is recommended for all patients undergoing thyroidectomy for malignant cytologic findings on biopsy – Recommendation B R21. “Preoperative neck ultrasound for the contralateral lobe and cervical (central and bilateral) lymph nodes is recommended for all patients undergoing thyroidectomy for malignant cytologic findings on biopsy – Recommendation B The ATA Guidelines Taskforce The ATA Guidelines Taskforce Thyroid 16 (2): 1-33, Feb 2006. Thyroid 16 (2): 1-33, Feb 2006.

26. Expectations of Primary Neck Surgery in PTC Avoidance of central compartment exploration no longer acceptable Avoidance of central compartment exploration no longer acceptable Iatrogenic hypoparathyroidism unwarranted and avoidable in 2006 Iatrogenic hypoparathyroidism unwarranted and avoidable in 2006 I-131 should not be used as a postoperative cure-all to ‘mop up leftovers’ after inadequate surgery I-131 should not be used as a postoperative cure-all to ‘mop up leftovers’ after inadequate surgery

27. Lymph Node Dissection in PTC ATA 2006 Guidelines “R27. Routine central compartment (level VI) neck dissection should be considered for patients with PTC: Recommendation B” “R27. Routine central compartment (level VI) neck dissection should be considered for patients with PTC: Recommendation B” “R28. Lateral neck compartmental lymph node dissection should be performed for patients with biopsy-proven metastatic cervical lymphadenopathy detected clinically or by imaging, especially when they are likely to fail RAI treatment based on lymph node size, number, or other factors, such as aggressive histology of the primary tumor – Recommendation B” “R28. Lateral neck compartmental lymph node dissection should be performed for patients with biopsy-proven metastatic cervical lymphadenopathy detected clinically or by imaging, especially when they are likely to fail RAI treatment based on lymph node size, number, or other factors, such as aggressive histology of the primary tumor – Recommendation B”

28. “Common Sense” Approach to LRPTC Management I.Diagnosis: cytologic and histopathologic II.Primary surgical treatment III.Staging and risk-group assignment

29. Relevance of Post-op Assignment to Prognostic Risk-Groups Enables post-op counseling of an individual DTC patient Enables post-op counseling of an individual DTC patient Helps make decisions about intensity of adjuvant therapies, frequency of follow-up visits, and allocation of resources Helps make decisions about intensity of adjuvant therapies, frequency of follow-up visits, and allocation of resources

30. Role of Postoperative Staging Systems ATA 2006 Management Guidelines “R31. Because of its utility in predicting disease mortality, and its requirement for cancer registries, AJCC/UICC staging is recommended for all patients with differentiated thyroid cancer. The use of postoperative clinicopathologic staging systems is also recommended to improve prognostication and to plan follow-up for patients with differentiated thyroid carcinoma – Recommendation B” “R31. Because of its utility in predicting disease mortality, and its requirement for cancer registries, AJCC/UICC staging is recommended for all patients with differentiated thyroid cancer. The use of postoperative clinicopathologic staging systems is also recommended to improve prognostication and to plan follow-up for patients with differentiated thyroid carcinoma – Recommendation B” Thyroid 16: 1-33, 2006. Thyroid 16: 1-33, 2006.

31. Utility of Staging and Prognostic Scoring Clinicians caring for DTC patients should understand and ‘try to’ use in practice the 2002 TNM/AJCC stages! Clinicians caring for DTC patients should understand and ‘try to’ use in practice the 2002 TNM/AJCC stages! AMES or MSKCC risk-groups for FTC AMES or MSKCC risk-groups for FTC MACIS prognostic scoring system, permitting PTC classification into low-risk (scores <6) or high-risk (6+) patients (Surgery 114; 1050-8, 1993), employed at Mayo for past 13 years MACIS prognostic scoring system, permitting PTC classification into low-risk (scores <6) or high-risk (6+) patients (Surgery 114; 1050-8, 1993), employed at Mayo for past 13 years

32. Years after initial surgery CP1028491-11 Papillary Thyroid Carcinoma Managed at Mayo Clinic 1940-2000 Mortality by MACIS Surviving death from PTC (%) MACIS Risk Groups n=2,512 1940-2000 P<0.001 MACIS Risk Groups n=2,512 1940-2000 P<0.001 <6 (2,099) 6+ (413)

33. “Common Sense” Approach to LRPTC Management I.Diagnosis: cytologic and histopathologic II.Primary surgical treatment III.Staging and risk-group assignment IV.Adjuvant therapy

34. Adjuvant Therapy in LRPTC Patients Thyroid hormone suppressive therapy Thyroid hormone suppressive therapy Radioiodine remnant ablation (RRA) ***** Radioiodine remnant ablation (RRA) *****

35. Thyroxine Suppressive Therapy in DTC Management Risk-group assignment can determine a precise goal level for suppression of serum TSH Risk-group assignment can determine a precise goal level for suppression of serum TSH Low-risk (MACIS < 6 PTC): TSH typically in 0.1 - 0.5 mIU/L range Low-risk (MACIS < 6 PTC): TSH typically in 0.1 - 0.5 mIU/L range High-risk (MACIS 6+ PTC; FTC/HCC): aiming for TSH of 0.1 mIU/L or less High-risk (MACIS 6+ PTC; FTC/HCC): aiming for TSH of 0.1 mIU/L or less

36. Appropriate Degree of Initial TSH Suppression ATA 2006 DTC Management Guidelines “R40. Initial thyrotropin suppression to below 0.1 mU/L is recommended for high- risk patients with thyroid cancer, while maintenance of the TSH at or slightly below the lower limit of normal (0.1-0.5 mU/L) is appropriate for low-risk patients – Recommendation B” “R40. Initial thyrotropin suppression to below 0.1 mU/L is recommended for high- risk patients with thyroid cancer, while maintenance of the TSH at or slightly below the lower limit of normal (0.1-0.5 mU/L) is appropriate for low-risk patients – Recommendation B” Thyroid 16: 1-33, 2006. Thyroid 16: 1-33, 2006.

37. 2,512 Papillary Thyroid Carcinoma Patients Managed During 1940-2000 Therapeutic Trends CP1028491-3 Remnant ablation n=662 1940-2000 Remnant ablation n=662 1940-2000 Patients (%) n=2,512 P<0.001 n=2,512 P<0.001 1940-54 Bilateral lobar resection (2,179) Unilateral lobectomy (293) 1955-691970-841985-20001940-541955-691970-841985-2000 46% 32% 3% 1%

38. Radioiodine Remnant Ablation in MACIS <6 Low-Risk PTC Recent analysis of outcome in 1,163 patients treated during 1970-2000 Recent analysis of outcome in 1,163 patients treated during 1970-2000 When patients divided into 636 node- negative and 527 node-positive, no differences in outcome (mortality and recurrence) were found between those having surgery alone and those also receiving postoperative RRA When patients divided into 636 node- negative and 527 node-positive, no differences in outcome (mortality and recurrence) were found between those having surgery alone and those also receiving postoperative RRA Trans ACCA 113: 241, 2002

39. Survival for “low risk” PTC (MACIS < 6) 85 90 100 05101520 0 95 Survival (cause-specific) Years from diagnosis I 131 Ablation (n=498) No Ablation (n=665) 1163 patients; total or near-total TTX; 1970 - 2000

40. Survival (T x N 0 M 0, MACIS<6) 05101520 Years from diagnosis Survival (%) I 131 Ablation (n=195) No Ablation (n=441) 85 90 100 0 95 636 node negative patients; total or near-total TTX; 1970 - 2000

41. Survival (T x N 1 M 0, MACIS<6) 85 90 100 05101520 0 95 Survival (cause-specific) Years from diagnosis I 131 Ablation (n=303) No Ablation (n=224) 527 node positive patients; total or near-total TTX; 1970 - 2000

42. Recurrence in “low risk” PTC 05101520 84 88 92 96 100 Years from diagnosis Relapse free survival (%) I 131 Ablation No Ablation 1163 patients; total or near-total TTX; 1970 - 2000

43. Recurrence (T x N 0 M 0, MACIS<6) 05101520 Years from diagnosis I 131 Ablation No Ablation 80 90 100 636 node negative patients; total or near-total TTX; 1970 - 2000

44. Recurrence (T x N 1 M 0, MACIS<6) 5101520 Years from diagnosis I 131 Ablation No Ablation 0 80 90 100 527 node positive patients; total or near-total TTX; 1970 - 2000

45. Selective Approach to Postoperative RRA Current Mayo practice: to restrict RRA to patients with high-risk (MACIS 6+) PTC and to patients with FTC or HCC Current Mayo practice: to restrict RRA to patients with high-risk (MACIS 6+) PTC and to patients with FTC or HCC Recent study of 6,841 European patients demonstrated increased risk of both solid tumors and leukemia after I-131 treatment and concluded that “it seems necessary to restrict the use of I-131 to thyroid cancer patients in whom it may be beneficial” Recent study of 6,841 European patients demonstrated increased risk of both solid tumors and leukemia after I-131 treatment and concluded that “it seems necessary to restrict the use of I-131 to thyroid cancer patients in whom it may be beneficial” Br J Cancer 89: 1638, 2003

46. Role of Postoperative RRA ATA 2006 Guidelines “R32. Radioiodine ablation is recommended for patients with stage III and IV disease (AJCC 6 th edition), all patients with stage II disease 45 years or older, and selected patients with stage I disease, especially those with multifocal disease, nodal metastases, extrathyroidal or vascular invasion, and/or more aggressive histologies – Recommendation B”. “R32. Radioiodine ablation is recommended for patients with stage III and IV disease (AJCC 6 th edition), all patients with stage II disease 45 years or older, and selected patients with stage I disease, especially those with multifocal disease, nodal metastases, extrathyroidal or vascular invasion, and/or more aggressive histologies – Recommendation B”. Thyroid 16: 1-33, 2006. Thyroid 16: 1-33, 2006.

47. Techniques for Postoperative RRA Some American centers now favor “blind” administration of large (100 - 175 mCi) I-131 doses without preceding diagnostic scan, and depend on utility of post-therapy WBS Some American centers now favor “blind” administration of large (100 - 175 mCi) I-131 doses without preceding diagnostic scan, and depend on utility of post-therapy WBS In ‘selected’ cases, Mayo practice now is to perform uptake quantitation during I-123 scan, ‘customize’ the I-131 therapy, follow with diagnostic I-123 scans after 3-6 months In ‘selected’ cases, Mayo practice now is to perform uptake quantitation during I-123 scan, ‘customize’ the I-131 therapy, follow with diagnostic I-123 scans after 3-6 months

48. “Common Sense” Approach to LRPTC Management I.Diagnosis: cytologic and histopathologic II.Primary surgical treatment III.Staging and risk-group assignment IV.Adjuvant therapy V.Long-term surveillance

49. Postoperative Surveillance in PTC Thyroglobulin levels Thyroglobulin levels Appropriate imaging Appropriate imaging

50. Thyroglobulin: on or off thyroid hormone suppression therapy? Mail-in thyroid cascade (TSH-based) and Tg on every returning visit Mail-in thyroid cascade (TSH-based) and Tg on every returning visit Also, measure TSH and Tg, while off THST, at time of I-123 body scanning Also, measure TSH and Tg, while off THST, at time of I-123 body scanning Personally, do not favor stopping T4 or giving rhTSH only for the purpose of determining Tg increment Personally, do not favor stopping T4 or giving rhTSH only for the purpose of determining Tg increment

51. Stimulated Tg Levels in Low-Risk Patients ATA 2006 Guidelines “R45. In low-risk patients, who have had remnant ablation and negative cervical ultrasound and TSH-suppressed Tg 6 months after treatment, serum Tg should be measured after T4 withdrawal or rhTSH stimulation approximately 12 months after the ablation to verify absence of disease. The timing or necessity of subsequent stimulated testing is uncertain for those found to be free of disease – Recommendation A.” “R45. In low-risk patients, who have had remnant ablation and negative cervical ultrasound and TSH-suppressed Tg 6 months after treatment, serum Tg should be measured after T4 withdrawal or rhTSH stimulation approximately 12 months after the ablation to verify absence of disease. The timing or necessity of subsequent stimulated testing is uncertain for those found to be free of disease – Recommendation A.” Thyroid 16: 1-33, 2006. Thyroid 16: 1-33, 2006.

52. rhTSH Stimulation and Presently Undetectable Serum Tg Levels A recent consensus (JCEM 88:1433, 2003) suggested that a serum Tg <1 ng/mL measured on THST is “misleading in a large proportion of patients with residual DTC” A recent consensus (JCEM 88:1433, 2003) suggested that a serum Tg <1 ng/mL measured on THST is “misleading in a large proportion of patients with residual DTC” When Tg measured as <0.1 ng/mL on THST, provides reassurance of a lack of relevant tumor recurrence in Ab-negative low-risk PTC When Tg measured as <0.1 ng/mL on THST, provides reassurance of a lack of relevant tumor recurrence in Ab-negative low-risk PTC Soon, Tg assay detection limits will approach 0.01 ng/mL ; therefore, likely making rhTSH stimulation a costly and unnecessary test Soon, Tg assay detection limits will approach 0.01 ng/mL ; therefore, likely making rhTSH stimulation a costly and unnecessary test

53. Detectable Tg and Tumor Recurrence “I personally consider a ‘positive’ biopsy as proof of disease rediscovery, but I consider a detectable Tg at best a possible ‘surrogate’ for tumor recurrence” “I personally consider a ‘positive’ biopsy as proof of disease rediscovery, but I consider a detectable Tg at best a possible ‘surrogate’ for tumor recurrence”

54. Postoperative Surveillance in LRPTC Appropriate imaging Appropriate imaging

55. Selective Use of Imaging in Postop Surveillance I-131 therapy restricted to high-risk patients; I-123 WBS used primarily to assess adequacy of I-131 therapy I-131 therapy restricted to high-risk patients; I-123 WBS used primarily to assess adequacy of I-131 therapy CT, MRI, PET/CT not regularly employed CT, MRI, PET/CT not regularly employed Heavy reliance on skilled sonographers to identify or exclude locoregional disease Heavy reliance on skilled sonographers to identify or exclude locoregional disease Real-time US used to guide biopsies of possible neck recurrences, and to enable percutaneous ethanol ablation of nodes Real-time US used to guide biopsies of possible neck recurrences, and to enable percutaneous ethanol ablation of nodes

56. Treatment Alternatives for PTC in Persistent/Recurrent Neck Nodes Neck Dissection Radioactive I 131 therapy Radioactive I 131 therapy External Radiation Traditional Alcohol Ablation Alternative

57. Technique 95% ethanol 25 g needle and Tb syringe 0.1-0.8 cc (mean 0.3 ml) Inject tiny amount until node becomes echogenic 95% ethanol 25 g needle and Tb syringe 0.1-0.8 cc (mean 0.3 ml) Inject tiny amount until node becomes echogenic Reinject next day in most pts Ablation of Papillary Nodal Metastasis

58. Results in Stage I PTC All 60 decreased in size; 40 (67%) no longer identified Average decrease size = 95% All 60 decreased in size; 40 (67%) no longer identified Average decrease size = 95% 60 Nodes Treated in 35 Pts Avg. 0.5 cm 3 before inj. Avg. 0.02 cm 3 after inj. at 24 mo Avg. 0.02 cm 3 after inj. at 24 mo

59. ‘Common Sense’ Approach to LRPTC Management I.Diagnosis: cytologic and histopathologic II.Primary surgical treatment III.Staging and risk-group assignment IV.Adjuvant therapy V.Long-term surveillance

60. Five “Golden Rules” for LRDTC Management I.Carefully choose your trusted, locally based, pathologist II.Know the skills and/or limitations of your thyroid surgeons III.Use TNM stages and apply scoring IV.Try to use I-131 therapy selectively V.Revere US scanning, and permit tolerance of ‘detectable’ Tg levels

62. The end Proceed to post test Proceed to post test Print post test Print post test Complete post test Complete post test Return post test to Return post test to  Dr. Sandra Oliver  407i TAMUII

63. Post test List the five “Golden Rules” for LRDTC Management: List the five “Golden Rules” for LRDTC Management: 1. 1. 2. 2. 3. 3. 4. 4. 5. 5.