Thyroid Cancer A Multidisciplinary Approach

Transcription

1 Thyroid Cancer A Multidisciplinary Approach Shuvendu Sen, MD, MS, FACP Associate Program Director, Internal Medicine Residency Program Director, Medical Education Raritan Bay Medical Center, Rutgers University Affiliate

2 Courtesy: R Michael Tuttle, MD, Memorial Sloan Kettering Memorial Center, NCCN Thyroid carcinoma Guidelines Update

3 A Clinical Conundrum Primary care practice Surgery Radiology Endocrinology Pathology Nuclear Medicine Oncology

4 The beginning

5 Caveats of Thyroid Cancer Although the most common endocrine organ to undergo malignant degeneration, thyroid carcinoma accounts for only 1% of diagnosed neoplasms in the United States each year. [1, 2] The annual detection rate of clinically significant thyroid cancer in the general population is only 0.004%. Only 5-10% of thyroid cancers are clinically palpable

8 The American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer

9

10

11

12 Shift to radiology The suspicious Ultra sonogram

13 hypoechogenicity (fewer echos than the normal thyroid) hypervascularity on color Doppler (greater blood flow than the normal thyroid), irregular margins a nodule that is taller than wide microcalcifications. (correlation between osteopontin messenger RNA expression and the formation of microcalcification )

14 Nuclear Images

15 Fine Needle Aspiration Biopsy

16 Bethesda System

17

18 Current recommendations based on FNA results Category I: non-diagnostic. Repeat FNA. If still non-diagnostic consider surgery. Alternatively consider molecular diagnostic testing. Category II: benign. No surgery, follow with ultrasound. If the nodule increases in volume by >50% repeat FNA. Categories III & IV: Atypia/follicular lesion of undetermined significance and follicular neoplasm/suspicious for follicular neoplasm. Perform I-123 scan, especially if TSH is low or low normal. If the nodule is functional (hot on scan) no surgery, follow TSH. If the nodule is non-functional (cold on scan) consider surgery or careful follow-up. Alternatively consider molecular diagnosis testing as the first option. Categories V & VI suspicious for malignancy and malignant. Total thyroidectomy since almost all will be papillary thyroid cancers.

19 The multidisciplinary meet

20 Shift to Surgery The Quintessential Points Focal/Multifocal Capsular extension Vascular invasion Surgical margins Lymph Nodes Extra nodal extensions

22 FNA grades III and IV Lobectomy on the side of the suspicious nodule. If the nodule proves to be a thyroid cancer a completion thyroidectomy (removal of the remaining thyroid lobe) is performed at a later date Completion thyroidectomy need not be performed for thyroid cancer variants, including follicular cancer with no vascular invasion and the encapsulated follicular variant of papillary thyroid cancer. Central compartment node dissections are not routinely performed in patients with grade III or IV FNA since node metastases are uncommon in patients with follicular thyroid cancer or the follicular variant of papillary thyroid cancer.

23 FNA grades V and VI Total thyroidectomy is the recommended procedure Central compartment dissection that removes the lymph nodes from the area around the thyroid. Lymph node metastases are detected in the lateral neck on pre-op ultrasound or at surgery a modified neck dissection is performed

24

25 Shift to Nuclear To Ablate Or Not To Ablate Both Papillary and Follicular Thyroid Cancer Age Patients under age 45 have a very low risk death After 45 there is a linear increase in risk of death with increasing age Sex Risk of recurrence and death is higher in males

26 Papillary thyroid cancer Size of primary cancer (greatest dimension) Linear increase in risk with increase in size Minimal risk for cancers < 10mm Extrathyroidal invasion Gross invasion into soft tissue significantly increases risk Microscopic invasion slightly increases risk Lymph node metastases Risk increases with number of nodes and size of metastases Minimal increase in risk for <3 nodes and metastases < 5 mm in size Vascular invasion Any vascular invasion significantly increases risk Invasion of lymphatics does not increase risk More aggressive variants significantly increase risk Tall cell variant Columnar cell variant Diffuse sclerosing variant

27 Follicular Thyroid Cancer Vascular invasion Gross vascular invasion significantly increases risk Minimal vascular invasion confers slightly increased risk Capsular invasion alone does not confer increased risk Distant metastases present at the time of diagnosis Significantly increase risk

28 Emergence of rhtsh Recombinant human TSH is commercially available as thyrotropin alfa It is a heterodimeric glycoprotein produced by recombinant DNA technology in a genetically modified Chinese hamster ovary cell line. Recombinant human TSH comprises two non-covalently linked subunits, an alpha subunit of 92 amino acid residues containing two N-linked glycosylation sites,and a beta subunit of 118 residues containing one N linked glycosylation site. The amino acid sequence of thyrotropin alfa is identical to that of human pituitary TSH (ptsh) Unlike ptsh which is secreted as a mixture of sialylated and sulfated forms, thyrotropin alfa is sialylated but not sulfated. RhTSH is supplied as a sterile, non-pyrogenic and white to off-white lyophilized form for intramuscular administration after reconstitution with sterile water for injection

29

30 Timeline 1998: First approved by FDA for use in differentiated thyroid carcinomas (DTC) (a) the evaluation of serum thyroglobulin (Tg) (b)body iodine (WBI) scans in follow-up cases of DTC 2005: European Association approved for ablation of low risk patients with 100 mci radioactive iodine. 2007, US FDA also approved it for ablation without specifying radioactive iodine dose. 2009: Revised European guidelines stated rhtsh to be indicated for pre-therapeutic stimulation with 100 mci for remnant ablation without evidence of distant metastasis after NTT or TT.

31 And quiet flows the Hudson

32 rhtsh versus THW

33

34 Data from Mazzaferri, EL, Jhiang, SM, Am J Med 1994; 97:418.

35

36

37 Protocol for the post-surgical ablation with recombinant TSH (rhtsh). Whole-body scan (WBS) after the administration of 50 mci 131 I Courtesy: Medicina (B. Aires) v.69 n.1 Ciudad Autónoma de Buenos Aires ene./feb. 2009

38

39 30 mci et al.

40 May 3, 2012 Vol. 366 et al. 30 mci

41 Comparison of Procedure Guidelines for I-131 Therapy of Patients with Thyroid Carcinoma SNM Guideline: For treatment of presumed thyroid cancer in the neck or mediastinal lymph nodes: activity in the range of GBq ( mci) is typically administered. EANM Guideline: For patients undergoing retreatment for residual disease or local recurrence, somewhat larger administered activities (in the range of 5500 MBq (150 mci) are often used.

42 Best Approach to Determine the Optimal Radioactive Iodine Dose Based upon assessment of risk of residual disease and likelihood of recurrence, mci of 131 I is pre-selected as an ablative/therapeutic dose for patients not known to have metastatic disease. Pre-Rx WB scan with 2 mci 123 I or 131 I is performed to exclude surprises. Post-Rx scan is performed at 7-10 days.

43 Common side effects nausea (10.5%) headache (7.3%) asthenia (3.4%) vomiting (2.1%) dizziness (1.6%) Paraesthesia (1.6%).

44

45

46 Pre/post ablation images

47

48

49

50

51 External beam radiotherapy Patients over age 45 Grossly visible extrathyroidal extension at the time of surgery A high likelihood of microscopic residual disease For those patients with gross residual tumor in whom further surgery or radioactive iodine would likely be ineffective The American Thyroid Association guidelines

52 Radionuclide Imaging in the Management of Thyroid Carcinoma In 2013, the diagnosis of thyroid cancer is usually made on biopsy or at surgery Nuclear imaging with 131 I or 123 I is usually requested and performed post-op to exclude or identify residual disease rtsh is available; it is no longer necessary to withdraw thyroid hormone replacement Serum thyroglobulin is essential component of follow-up (before and after rtsh) 18 FDG PET imaging is useful to identify Thyroglobulin + (pos), 131 I (or 123 I) (neg) tumor

53 Future

54 Shift to Molecular Biology Molecular profiling is not yet clinically indicated to direct therapy of established thyroid cancers Commercially available to help distinguish benign from malignant thyroid nodules using RNA from cells obtained by fine needle aspiration biopsy It is anticipated that the accuracy of this molecular testing will improve rapidly over the next several years.

55 Papillary Thyroid Cancer Gene mutations and rearrangements lead to activation of the mitogen activated protein kinase (MAPK) that promotes cell division. Rearrangements of RET and NTRK1 tyrosine kinases Activating mutations of BRAF Activating mutations of RAS

56 Follicular Thyroid Cancer Over expression of normal c-myc and c-fos genes Mutations of HRAS, NRAS, and KRAS protooncogenes Translocation (t(2;3)[q13;p25]) results in fusion of part of the DNA-binding segment of the PAX8 gene and (PPAR-gamma-1) gene

57 Metastatic unresponsive differentiated thyroid cancer Enrollment in a clinical trial of therapies Oral tyrosine kinase inhibitors have been studied in placebocontrolled randomized trials: Sorafenib/Vandetanib In 2013, sorafenib was approved by the US Food and Drug Administration for the treatment of locally recurrent or metastatic, progressive DTC that no longer responds to radioactive iodine treatment Vandetanib is available in the United States through a Risk Evaluation and Mitigation Strategy (REMS) program for the treatment of unresectable locally advanced or metastatic medullary thyroid cancer

58 So what s the crossroad

59 American Thyroid Association Guidelines Asymptomatic metastatic tumors generally less than 1 to 2 cm in diameter Growing in diameter less than 20 percent per year: Continued treatment with TSH suppression (with TSH levels as low as the patient can tolerate). Imaging of known sites of metastatic disease by computed tomography (CT) or magnetic resonance imaging (MRI) every six months Potential new sites of disease to be imaged every 12 to 24 months.

60 American Thyroid Association Guidelines For patients with metastatic tumors at least 1 to 2 cm in diameter, Growing by at least 20 percent per year Patients with symptoms related to multiple metastatic foci that cannot be alleviated with surgery or external beam radiotherapy, Administer systemic treatment in the context of a clinical trial.

61 American Thyroid Association Guidelines For patients who cannot participate in a clinical trial Oral tyrosine kinase inhibitors For patients who cannot tolerate or who fail one tyrosine kinase inhibitor, a BRAF inhibitor Cytotoxic chemotherapy ( doxorubicin)

62 Faces of Thyroid Cancer Treatment

63 THANK YOU