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Medical oncology > Thyroid Cancer And Thymoma > Flashcards

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
Q

What are the main complications to total thyroidectomy?

A

1) Injury to recurrent laryngeal nerve (3% risk)

2) Hypoparathyroidism (long term risk 3 %)

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26
Q

What is the general prognosis for papillary thyroid cancer?

A

5y OS 100% for stage I and II
5y OS >90% for stage III
5y OS 50% for stage IV

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27
Q

Tell me about the N staging?

A

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

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28
Q

Tell me about the T staging

A

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
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29
Q

Tell me some generalizations of the staging in TNM?

A

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

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30
Q

What is the Initial American Thyroid Association risk of recurrence classification?

A

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

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31
Q

What constitutes aggressive histology?

A 
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
Q

Name me some scoring systems for prognosis/survival

A

1) AMES (Age, mets, extent, size)
2) MACIS
3) AJCC/TNM

33
Q

What is the MACIS score?

A

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
Q

What is the required TSH suppression levels?

A

Normal range 0.65 - 3.7 mU/L

Low risk disease = 0.1 - 0.5
Intermediate to high risk disease =

35
Q

What is the utility of Radio-iodine therapy in DTC?

A

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
Q

What are the 2 methods to stimulate TSH?

A

1) Thyroxine hormone withholding
2) Recombinant human TSH (rhTSH), while LT4 is continued
- less functional impairment
- needs 2 doses

37
Q

What preparation is needed for RAI imaging and treatment?

A

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
Q

What are some iodine-containing medications:

A

Aminodarone
Phenytoin
Carbamazepine
Lithium

39
Q

What food contains iodine?

A 
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
Q

What does serum TG detect?

A

Thyroid tissue

41
Q

What if a patient has high Tg but negative RAI scan?

A

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
Q

What constitutes RAI -refractory disease?

A

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
Q

What is the most common genetic alteration in thyroid cancer?

A

BRAF V600E point mutation
- most common in 50-80% of PTC, less common in FTC

BRAF oncogene activates MAPK pathway

44
Q

Is RAS mutation more common in PTC or FTC?

A

FTC. Up to 40%

45
Q

Which TKI can cause QTC prolongation ?

A

Vandetanib

46
Q

Tell me about the DECISION trial

A

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
Q

How often does DTC developed metastatic disease?

A

5-20%

48
Q

What does Sorafenib inhibit?

A

VEGFR-1, VEGFR-2, VEGFR-3
RET
RAF
PDGFR-Beta

49
Q

Tell me about the SELECT trial

A

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
Q

What does Lenvatinib inhibit?

A 
VEGFR 1,2,3 
FGFR 1-4
PDGFRA
RET
KIT
51
Q

Which codon in RET mutation is considered the highest risk for MTC, such that prophylactic thyroidectomy should be offered earlier rather than later?

A

Codon 634

52
Q

What are some of the bad prognosticators in medullary Thyroid cancer ?

A

Calcitonin doubling time

53
Q

What are the 2 blood tests done to surveil MTC?

A

Basal Calcitonin

CEA

54
Q

Tell me about Vandetanib

A

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
Q

How frequent are sporadic RET mutations in MTC?

A

50%

- of these, 85% will have M918T mutation

56
Q

What is Hepaocyte growth factor receptor also known as?

A

MET

57
Q

Tell me about Cabozaninib in MTC

A

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
Q

What does Cabozantinib inhibit?

A

Hepatocyte growth factor receptor (MET)
VEGFR2
Rearranged during Transfection (RET)

59
Q

What are the side effects o Cabozantinib?

A 
Nausea,
LOW 
LOA
PPE
Diarrhea
Fatigue
60
Q

What is the usual presentation of anaplastic thyroid cancer?

A

Large hard mass, with invasion to neck
Compressive symptoms
50% with distal mets at presentation

61
Q

What is the WHO classification of thymic tumors based on?

And what does it correlate to?

A

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
Q

What is the WHO Classification of Thymic Malignancies?

A

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
Q

What are the histological subtypes of Thymic carcinoma that you know of?

A

1) Squamous cell
2) Lymphoepithelioma-like
3) Clear-cell
4) Basaloid
4) Mucoepidermoid
5) Papillary
6) Undifferentiated carcinoma

64
Q

What is the staging that we used for Thymic malignancies?

A

Masoka staging.

  • focuses on integrity of Thymic capsule.
  • micro vs macroscopic invasion into adjacent structures
65
Q

What is the Masoka staging?

A

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
Q

What are the differences between Thymoma and Thymic cancers?

A

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
Q

What are the associated autoimmune syndromes?

A

1) Myasthenia Gravis
- 30-50% of thymomas
2) Pure red cell aplasia
- 5-15% of thymomas
3) Hypogamaglobulinemia
-

68
Q

What is the role of adjuvant therapy post-op for Thymic malignancies?

A

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
Q

What are the common chemo agents?

A

Cisplatin

  • RR 10%
  • OS 76 weeks

Ifosfamide

  • RR 40-50%, 5y OS 60%
  • Retrospective study

Pemetrexed

  • RR 10-20%
  • Thymoma RR 25%
70
Q

What are the combination chemo agents that you know for Thymic malignancies ?

A

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
Q

What is Carney Complex?

A

Multiple neoplasia and Lentiginosis syndrome, which affects endocrine glands

72
Q

When is a lobectomy sufficient?

A 
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
Q

When is completion thyroidectomy indicated?

A 
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
Q

What is the function of the thymus gland?

A

The thymus gland is involved in the processing and maturation of lymphocytes

The lymphocytes become T-lymphocytes upon release into the circulation

75
Q

What is the thymus composed of?

A

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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