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Thyroid Cancer And Thymoma Flashcards

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1
Q

What is one main risk factor for thyroid cance?

A

Ionizing radiation

- risk greater with younger age at exposure

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2
Q

Frequency difference in gender for thyroid cancer?

A

Male: Female = 1:3

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3
Q

What are the different types of thyroid cancer? And their frequency

A

1) Differentiated thyroid cancer
- Papillary Thyroid Cancer 80%
- Follicular Thyroid Cancer 10%
» Hurthle cell carcinoma is classified as a subset of FTC
- Poorly differentiated thyroid cancer
2) Medullary Thyroid Cancer 2%
3) Anaplastic Thyroid Cancer

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4
Q

How often do you find thyroid cancer in all the thyroid nodules investigated ?

A

5%

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5
Q

In the evaluation of thyroid nodules, what would you order?

A

1) Thyroid function testing
2) Thyroid US
3) FNAC

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6
Q

What are the ultrasound features of a thyroid cancer?

A 
Peripheral halo absent
Irregular Border
Extra-thyroidal extension
Spongiform nodules 
Size
Solid aspect
Shape (Taller than wide in transverse plane)

Hypechogenicity
Intranodular Blood Flow
MicrocalcaIcifications

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7
Q

What are the limitations of FNAC?

A

Inadequate samples

Yielding of follicular neoplasia

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8
Q

What are the high-risk clinical features for thyroid nodules?

A

Radiation exposure (as child, adolescent)
First degree relative with thyroid cancer/MEN2
FDG Pet-scan avid
Thyroid-ca associated conditions (FAP, Carney Complex, Cowden)
Hx of thyroid cancer in lobectomy

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9
Q

What constitutes a spongiform thyroid nodules?

A

Aggregation of multiple micro cystic components in >50% of the volume of the nodule

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10
Q

What are some of the follicular lesions that you know about

A

Follicular neoplasm
Hurthle cell neoplasm
Atypical of unknown significance (AUS)
Follicular lesions of undetermined significance (FLUS)

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11
Q

How does Levothyroxine work in the management of thyroid cancer?

A

TSH is a trophies hormone that can stimulate the growth of cells from thyroid follicular epithelium.

When Levothyroxine is taken, this suppresses the level of TSH, and hence the cancer.

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12
Q

What are the potential toxicities a/w Levothyroxine ?

A 
Cardiac arrhythmias (ESP in elderly)
Bone demineralization (ESP in post-menopausal women)
Frank symptoms of thyrotoxicosis
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13
Q

What needs to be given concurrent with Levothyroxine?

A 
Calcium (1200 mg/day) 
Vitamin D (1000 units/day)
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14
Q

What are the principles of kinase inhibitor therapy in Advanced thyroid cancer?

A

Oral kinase inhibitors demonstrate clinically significant activity in RCTs for locally recurrent Unresectable and metastatic medullary thyroid cancer (MTC) and in radio-iodine-refractory differentiated thyroid cancer (DTC)

Oral kinase inhibitors can be a/w PFS, but not curative.
Expected to cause s/e RT may affect QoL
Natural history of MTC/DTC is variable, with rates of disease progression ranging from a few months to many years.

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15
Q

What sort of US imaging of the thyroid/neck you need?

A

Thyroid and neck ultrasound

Including central and lateral compartments

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16
Q

What are the indications for total thyroidectomy intraooperatively?

A

Any present would suffice:

Bilateral nodularity 
Tumor >4cm in diameter
Poorly differentiated
Extrathyroidal extension 
Cervical LN mets 
Known distant mets
Consider for radiation history
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17
Q

If a prior lobectomy + Isthmusectomy was done before, what are the indications for completion thyroidectomy to be done?

A 
Any of the following would suffice:
Tumor >4cm 
Positive resection margins
Gross extrathyroidal extension
Macroscopic Multifocal disease
Macroscopic nodal mets
Vascular invasion
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18
Q

When is completion thyroidectomy not required ?

A

Small volume pathologic N1 micro mets

I.e. 5 or less involved LN with no micro mets >0.5cm in largest dimension

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19
Q

If a papillary CA was found post-lobectomy, what are the indications for completion thyroidectomy?

A 
Tumor >4cm
Positive resection margins
Gross extra-thyroidal extension
Macroscopic Multifocal disease
Confirmed nodal mets (but no need if small volume pathologic N1 micro mets) 
Confirmed Contralateral disease
Vascular invasion 
Poorly differentiated
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20
Q

When is RAI typically recommended?

A

If any present:
Gross extrathyroidal extension
Primary tumor > 4cm
Postoperative unstimulated Tg > 5-10 Ng/mL
- Tg values obtained 6-12 weeks after total thyroidectomy

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21
Q

When is RAI typically NOT recommended?

A

If ALL present:
Classic papillary thyroid carcinomas (PTC)
Primary tumor

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22
Q

In the work up of thyroid malignancy, what are the molecular testing you will send off for and why.

A

BRAF, RAS, RET/PTC and PAX8/PPAR mutations

  • presence of which strongly a/w cancer
  • 97% of mutation positive nodules had malignancy
  • can help in evaluating pt with indeterminate FNA, but indeterminate results ESP in suspicious nodule would necessitate surgery
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23
Q

What are the advantages of Thyroidectomy?

A

1) Better disease control
- foci of papillary CA in both lobes in 35-85% of patients
- 5-10% chance of recurrences in Contralateral lobe
- RAI ablation and treatment of met disease is better if as much thyroid tissue is resected
2) Better follow up
- US of Contralateral lobe may pick up non-spec abnormalities
- monitoring of Tg, RAI scan can only be done in thyroidectomy patient
3) RAI therapy

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24
Q

What are the advantages of lobectomy?

A

1) ?similar OS in “low risk” disease
2) lesser complications of hypoPTH and recurrent laryngeal nerve injury
3) US of thyroid is reasonably accurate

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25
What are the main complications to total thyroidectomy?
1) Injury to recurrent laryngeal nerve (3% risk) | 2) Hypoparathyroidism (long term risk 3 %)
26
What is the general prognosis for papillary thyroid cancer?
5y OS 100% for stage I and II 5y OS >90% for stage III 5y OS 50% for stage IV
27
Tell me about the N staging?
N1 regional lymph node mets N1a: Level VI (pretracheal, paratracheal, pre laryngeal (=Delphian LN) N1b: unilateral/bilateral/Contralateral Cervical or retro pharyngeal or superior mediastinal LN
28
Tell me about the T staging
T1: Tumor 2 cm or less, limited to thyroid T2: Tumors >2cm - 4cm, limited to thyroid T3: - >4 cm in size, limited to the thyroid - Any tumor with minimal extrathyroid extension T4a: - Moderately advanced disease - any size that extends beyond the thyroid capsule to invade subcutaneous soft tissue, larynx, trachea, esophagus or recurrent laryngeal nerve - Intrathyroid anaplastic carcinoma T4b: - Very advanced disease - invades pre vertebral fascia or encases carotid artery or mediastinal vessels - anaplastic carcinoma with gross extrathyroid extension
29
Tell me some generalizations of the staging in TNM?
A) Under 45yo - Stage 1: Tx Nx M0 - Stage 2: Tx Nx M1 B) 45 yo and above: Stage I: T1 N0 M0 Stage II: T2 N0 M0 Stage III: T3N0M0 - once N1a, at least stage III - once T4a, at least stage IVA Stage IV: - Once T4b, at least stage Ivb - once N1b, at least stage IVA Stage IVC: TxNxM1
30
What is the Initial American Thyroid Association risk of recurrence classification?
Like the ETA guidelines, this estimates recurrence risk 3 risk groups: (1) Low Risk (all must be present) - No local/distant mets - All macroscopic tumor has been resected - No invasion of locoregional tissues - No aggressive histology - No vascular invasion - No 131-I uptake outside thyroid bed on post-treatment scan (2) Intermediate Risk (any present): - Microscopic invasion into perithyroidal soft tissues - Cervical LN mets or 131-I uptake outside thyroid bed on post-treatment scan done after thyroid remnant ablation - Tumor with aggressive histology/vascular invasion (3) High Risk (Any present): - Macroscopic tumor invasion - Incomplete Tumor resection with gross residual disease - Distant mets
31
What constitutes aggressive histology?
``` Tall cell Insular carcinoma - well-defined nidi of small uniform cells with frequent areas of tumor necrosis and micro follicles with thyroglobulin . Poorer prognosis Columnar cel carcinoma Hurthle cell carcinoma Follicular thyroid cancer ```
32
Name me some scoring systems for prognosis/survival
1) AMES (Age, mets, extent, size) 2) MACIS 3) AJCC/TNM
33
What is the MACIS score?
It is a scoring system for prognosis and survival ``` M.A.C.I.S Mets outside neck (distant mets) - Yes = 3 points, No =0 Age at time of diagnosis - 40yo, score = 0.08xage Invasion into surrounding areas of neck as seen by naked eye - Yes =1 ; No =1 Completeness of surgical resection of tumor - Incomplete = 1; Complete =0 Size of tumor - Score = 0.3x size in cm ``` Sum of MACIS Score correlate with 20yr survival - 8 = 20%
34
What is the required TSH suppression levels?
Normal range 0.65 - 3.7 mU/L Low risk disease = 0.1 - 0.5 Intermediate to high risk disease =
35
What is the utility of Radio-iodine therapy in DTC?
1) Ablate normal thyroid remnant - facilitates long-term surveillance based on serum Tg and diagnostic WBS 2) Adjuvant ablation of residual tumor - decreases locoregional recurrence risk 3) Treatment of known residual or met thyroid cancer 4) Imaging for possible met/recurrent disease with diagnostic whole body 131-I scan
36
What are the 2 methods to stimulate TSH?
1) Thyroxine hormone withholding 2) Recombinant human TSH (rhTSH), while LT4 is continued - less functional impairment - needs 2 doses
37
What preparation is needed for RAI imaging and treatment?
Admit 3 days prior Avoid all iodine-containing medications Limit dietary intake of iodine for 1 week Avoid CT scan with IV contrast 6-8 weeks prior (high iodine load) Preferred cumulative iodine dose in a patient is
38
What are some iodine-containing medications:
Aminodarone Phenytoin Carbamazepine Lithium
39
What food contains iodine?
``` Seaweed COD Iodized salt Baked potato with peel Milk Shrimp Fish sticks Turkey breast Beans Tuna canned in oil Egg Cured food Chocolates Pizza ```
40
What does serum TG detect?
Thyroid tissue
41
What if a patient has high Tg but negative RAI scan?
False negative scan: - Inadequate TSH stimulation - Iodine contamination - Tumor deposits too small - loss of iodine uptake via tumor de differentiation Consider for neck USS/Chest CT (without iodinated contrast) If Stimulated Tg >10 Ng/ml, consider PET scan NO Evidence that treating in Tg+/Scan NED patients benefit survival
42
What constitutes RAI -refractory disease?
Lack of uptake on WBS after Diagnostic/Therapeutic RAI Progression of lesions documented by conventional imaging after therapeutic RAI Cumulative dose >600 mCi of 131-I FDG avid lesions on FDG PET
43
What is the most common genetic alteration in thyroid cancer?
BRAF V600E point mutation - most common in 50-80% of PTC, less common in FTC BRAF oncogene activates MAPK pathway
44
Is RAS mutation more common in PTC or FTC?
FTC. Up to 40%
45
Which TKI can cause QTC prolongation ?
Vandetanib
46
Tell me about the DECISION trial
Marcia Brose et al Lancet 2014 N=400 RAI-refractory locally advanced or metastatic DTC 2 arms: 1) Sorafenib 400 mg BD 2) Placebo Cross-over allowed. Results: Median PFS 11m vs 6m (placebo) HR 0.6 and p significant. * Median PFS longer in those with BRAF Mutations 20m vs 9m * wt BRAF med PFS also doubled 9m vs 4m OS ~ 70% crossover to Sorafenib ORR 10% vs 0.5% (Placebo)
47
How often does DTC developed metastatic disease?
5-20%
48
What does Sorafenib inhibit?
VEGFR-1, VEGFR-2, VEGFR-3 RET RAF PDGFR-Beta
49
Tell me about the SELECT trial
Schlumberger NEJM 2015 N=260 RAI Refractory progressive thyroid cancer 2 arms: 1) Lenvatinib 24mg OD Q28days 2) Placebo Crossover allowed RESULTS: Median PFS 18m vs 3.6m (placebo), HR 0.2 and p significant RR 65% vs 1.5%
50
What does Lenvatinib inhibit?
``` VEGFR 1,2,3 FGFR 1-4 PDGFRA RET KIT ```
51
Which codon in RET mutation is considered the highest risk for MTC, such that prophylactic thyroidectomy should be offered earlier rather than later?
Codon 634
52
What are some of the bad prognosticators in medullary Thyroid cancer ?
Calcitonin doubling time
53
What are the 2 blood tests done to surveil MTC?
Basal Calcitonin | CEA
54
Tell me about Vandetanib
Used for advanced Medullary Thyroid Cancer. Samuel Wells JCO 2011 N=300 2 arms: Vandetanib (300mg/day) vs placebo, cross over allowed Incl criteria: - measurable, Unresectable, locally advanced/met, hereditary or sporadic MTC - PS 0-2 - Serum calcitonin 500 pg/mL or more RESULTS: PFS 19m (placebo) not reached but estimated to be 30m for Vandetanib. PFS at 6m 80% vs 60%
55
How frequent are sporadic RET mutations in MTC?
50% | - of these, 85% will have M918T mutation
56
What is Hepaocyte growth factor receptor also known as?
MET
57
Tell me about Cabozaninib in MTC
Rossella JCO 2013 N=300 Radiological PD of met MTC 2arms: A) Cabozantinib (140 mgOD) B) Placebo RESULTS: Median PFS 11m vs 4m (placebo) HR 0.3 p sig PFS 1y 50% vs 10% RR 30% vs 0% (Placebo)
58
What does Cabozantinib inhibit?
Hepatocyte growth factor receptor (MET) VEGFR2 Rearranged during Transfection (RET)
59
What are the side effects o Cabozantinib?
``` Nausea, LOW LOA PPE Diarrhea Fatigue ```
60
What is the usual presentation of anaplastic thyroid cancer?
Large hard mass, with invasion to neck Compressive symptoms 50% with distal mets at presentation
61
What is the WHO classification of thymic tumors based on? | And what does it correlate to?
1) Morphology of epithelial tumor cells - increasing atypical from A to C 2) proportion of lymphocytic involvement 3) Resemblance to normal thymic tissue ``` Correlates with 5-y OS A/AB/B1: 90-95% B2: 75% B3: 70% C: 50% ```
62
What is the WHO Classification of Thymic Malignancies?
A (Medullary) = neoplastic oval/spindle cells; no atypia; no lymphocytes AB (Mixed) = Type A with foci of lymphocytes B1 (Predominantly Cortical) = Plump epithelioid cells resembling normal thymic medulla B2 (Cortical) = scattered foci of atypical epithelial cells with lymphocytes B3 (well-diff Thymic carcinoma) = round/polygonal epithelial cells with mild atypia with minor component of lymphocytes C (High-grade Thymic Carcinoma) = Thymic carcinoma (histological subs ping needed)
63
What are the histological subtypes of Thymic carcinoma that you know of?
1) Squamous cell 2) Lymphoepithelioma-like 3) Clear-cell 4) Basaloid 4) Mucoepidermoid 5) Papillary 6) Undifferentiated carcinoma
64
What is the staging that we used for Thymic malignancies?
Masoka staging. - focuses on integrity of Thymic capsule. - micro vs macroscopic invasion into adjacent structures
65
What is the Masoka staging?
I: - Macroscopically completely encapsulated tumor - No microscopic capsular invasion II: some degree of invasion IIA: microscopic invasion into capsule IIB: Macroscopic invasion into surrounding fatty tissue/mediastinal pleural III: Macroscopic invasion into neighboring organs - pericardium, great vessels, lung IV: Systemic disease IVA: pleural/pericardial dissemination IVB: lymphatogenous or hematogenous mets
66
What are the differences between Thymoma and Thymic cancers?
Stage at Dx: Early for Thymoma with no mets, but Thymic cancers are locally adv/met 5y OS: >80% for Thymoma 40% for Thymic cancer Response to chemo: Good for Thymoma Poor for Thymic cancers Spread: Thymoma: rarely beyond pleura/lung Thymic CA: often with pleural pericardial effusions Treatment: Thymoma: post-op RT dependent on extent of resection Thymic ca: post-op RT required regardless of margins, extent of resection Chemo choices: Thymoma: CAP, ADOC Thymic Ca: Pac/Carbo, ADOC Molecular abnormalities: Thymic C: C-Kit over expressed, IGF-1R expression
67
What are the associated autoimmune syndromes?
1) Myasthenia Gravis - 30-50% of thymomas 2) Pure red cell aplasia - 5-15% of thymomas 3) Hypogamaglobulinemia -
68
What is the role of adjuvant therapy post-op for Thymic malignancies?
R0 = Not required for stage I Thymomas/Thymic Ca unless; - capsular invasion - close margins - WHO Grade B tumor - tumor adherent to pericardium * If any of above, then to consider adjuvant RT* R1 = PORT - 45-50Gy R2 = PORT - up to 60Gy Stage III - recommend PORT No adjuvant chemo unless Thymic carcinoma in R1 and R2
69
What are the common chemo agents?
Cisplatin - RR 10% - OS 76 weeks Ifosfamide - RR 40-50%, 5y OS 60% - Retrospective study Pemetrexed - RR 10-20% - Thymoma RR 25%
70
What are the combination chemo agents that you know for Thymic malignancies ?
1) ADOC (Doxo, CDDP, Vincristine, Cyclophosphamide) - RR 80-90%, OS 15-45m 2) CAP - ORR 50% - OS > 30 m 3) EP - OR 56% 4) VIP - OR 30% 5) Pac/Cabo - RR 40% in Thymoma; 20% in Thymic Carcinoma No standard 2nd line treatment
71
What is Carney Complex?
Multiple neoplasia and Lentiginosis syndrome, which affects endocrine glands
72
When is a lobectomy sufficient?
``` Papillary Microcarcinomas (<1cm) No extrathyroidal extension No Vascular invasion No LN mets Unifocal disease No previous exposure to radiation, no other risk factors No distant mets Minimally invasive follicular Thyroid cancer ```
73
When is completion thyroidectomy indicated?
``` Tumor >4cm Positive margins Gross extrathyroidal extension Macroscopic multifocal disease Macroscopic nodal mets Contralateral disease Vascular invasion When remnant ablation is anticipated If long-term f/u is planned with serum Tg determinations +/- Whole body 131I imaging ```
74
What is the function of the thymus gland?
The thymus gland is involved in the processing and maturation of lymphocytes The lymphocytes become T-lymphocytes upon release into the circulation
75
What is the thymus composed of?
1) Epithelial cells 2) Hassall's corpuscles - degenerated keratinised epithelial cells 3) Myoid cells 4) Thymic lymphocytes = Thymocytes 5) B-lymphocytes

Medical oncology (53 decks)

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