Thyroid Cancer And Thymoma Flashcards Preview

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Flashcards in Thyroid Cancer And Thymoma Deck (75):
1

What is one main risk factor for thyroid cance?

Ionizing radiation
- risk greater with younger age at exposure

2

Frequency difference in gender for thyroid cancer?

Male: Female = 1:3

3

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

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

4

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

5%

5

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

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

6

What are the ultrasound features of a thyroid cancer?



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

7

What are the limitations of FNAC?

Inadequate samples
Yielding of follicular neoplasia

8

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

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

9

What constitutes a spongiform thyroid nodules?

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

10

What are some of the follicular lesions that you know about

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

11

How does Levothyroxine work in the management of thyroid cancer?

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.

12

What are the potential toxicities a/w Levothyroxine ?

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

13

What needs to be given concurrent with Levothyroxine?

Calcium (1200 mg/day)
Vitamin D (1000 units/day)

14

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

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.

15

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

Thyroid and neck ultrasound
Including central and lateral compartments

16

What are the indications for total thyroidectomy intraooperatively?

Any present would suffice:

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

17

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

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

18

When is completion thyroidectomy not required ?

Small volume pathologic N1 micro mets
I.e. 5 or less involved LN with no micro mets >0.5cm in largest dimension

19

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

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

20

When is RAI typically recommended?

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

21

When is RAI typically NOT recommended?

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

22

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

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

23

What are the advantages of Thyroidectomy?

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

24

What are the advantages of lobectomy?

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

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