Management of thyroid cancer

1. Management of Thyroid Cancer
Dr. Shreya Singh
JR-III
Department of Radiation Oncology
IMS, BHU 1

2. Anatomy :
• Shield shaped, highly vascular
organ situated in the neck
• Adults avg. weight – appx. 20
gms, brown in color
• Located posterior to the strap
muscles in the neck
• Located at level of 2nd & 3rd
tracheal rings
2

3. Relations of Thyroid Gland :
3

4. Etiology :
RADIATION EXPOSURE-
• Accidental
o 1945 Hiroshima Nagasaki bomb
o 1954 Marshal Islander Radioactive Fallout
o 1986 Chernobyl(USSR) N.Reactor accident
• Therapeutic irradiation
o Tonsil
o Nodular ds. of thyroid
o Hodgkin's lymphoma
– Prepubertal exposure is associated with higher risk
– MC type ass. with radiation exposure is papillary carcinoma
Chernobyl 1986
Nagasaki 1945
4

5. • Hereditary –
20% of Medullary thyroid cancer are associated with Familial
MEN syndrome
• Genetic predisposition-
mutations of the RET protooncogene on chromosome 10 are
associated with MEN 2 syndrome
• Endemic goiter
5
Etiology :

6. Pathological Classification (WHO):
BASIS - Cell of Origin
I. Follicular Epithelial Cell
A. Well-differentiated thyroid cancer
1. Papillary thyroid cancer
a. Classic
a. Follicular variant
b. Papillary microcarcinoma
c. Oncocytic Variant
d. Unfavorable Variants
i. Diffuse sclerosing
ii. Tall cell variant
iii. Columnar cell variant
iv. Hobnail
2. Follicular cancer
a. Classic
b. Hürthle cell variant
B. Poorly differentiated thyroid cancer
-Insular carcinoma
C. Undifferentiated thyroid cancer
-Anaplastic carcinoma
II . Parafollicular cell (C cell)
-Medullary carcinoma
6

7. TNM Classification :
T1 T2 T3
7

8. TNM Classification :
T4bT4a
8

9. TNM Classification :
N stage Description
Nx Regional lymph nodes cannot be assessed
N0 No evidence of regional lymph node metastasis
N0a: One or more cytologic or histologically confirmed benign lymph nodes
N0b: No radiologic or clinical evidence of locoregional lymph node metastasis
N1 Metastasis to regional nodes
N1a: Metastasis to level VI or VII (pretracheal, paratracheal, prelaryngeal /
Delphian or upper mediastinal) lymph nodes; this can be unilateral or bilateral
disease
N1b: Metastasis to unilateral, bilateral or contralateral lateral neck lymph
nodes (levels I, II, III, IV or V) or retropharyngeal lymph nodes
9

10. TNM Classification :
Metastasis Description
M0 No distant metastasis
M1 Distant metastasis
Differentiated Tumor Staging
10

11. TNM Classification :
Anaplastic :
11

12. Clinical Presentation :
• A lump in the front of neck
• Dysphagia
• Dyspnoea
• Hoarseness of voice
• Swollen lymph nodes in neck
• Pain in throat or neck
• Fracture/ cord compression or other
symptoms depending on site of metastasis.
12

13. Diagnostic Work-up
13

14. USG Neck :
•Features –
o Solid vs Cystic lesion
o Hypoechoic lesions
o Irregular lesions
o Microcalcifications
o Vascularity on doppler
•Advantages-
o Easy for follow up
o Identify lymph node mets
o Sensitive for intrathyroid lesion
o Pick up asymptomatic nodules
o Economical
14
Sensitivity – 90 %
Specificity – 82%

15. FNAC
• Neck US with Doppler and FNAC
arestandard diagnostics fot thyroid
nodules
• Accurate for Papillary and Medullary
carcinoma, but not for follicular cancer
• Accuracy 70-95% (guided) for nodule
>2cm
• Advantage –
o Minimally invasive
o Evaluation of non-palpable nodules
o Visualisation of suspicious nodules
• Drawback – can’t differentiate between
follicular adenoma & follicular carcinoma
15

16. Excisional Biopsy :
Indicated for :
• Follicular carcinoma
• In distinguishing follicular carcinoma from benign
adenomas
• To establish the diagnosis for Hürthle cell carcinoma
• To distinguish anaplastic carcinoma from
undifferentiated variants .
16

17. MRI / CT :
• Advantages-
– Detect otherwise clinically occult nodule
– Useful in pre-surgical planning
– Disease extent to assess the need for extended neck dissection
• MRI superior to CT :
-local extent of disease
-no interference with subsequent I-131 therapy
• In CT, if contrast used, I-131 therapy delayed for adequate efficacy
17

18. Thyroglobulin :
• By normal thyroid tissue & most non medullary thyroid cancers
• Elevated serum thyroglobulin in
o Grave’s disease
o Hashimoto’s thyroiditis
o Benign nodule
o Malignant nodule
• Not useful for initial diagnosis
• Useful in follow up after thyroidectomy for detection of recurrence
or progression of disease
18

19. Nuclear Medicine Studies
• Radioactive Uptake Study (RAIU)
• Diagnostic Whole Body Scan
• Post-treatment Whole Body Scan
• Thyroid Scan 19

20. RAIU
• To quantify the RAI-concentration
ability of remnant thyroid tissue.
• Patient preparation :
o Withdraw thyroid hormone at
least 2 wk
o No prior contrast study 4-6 wk
o No amiodarone, betadine
o Fasting ~ 2 hr
• Radiotracer : I-123 200-400 µCi (oral)
• Uptake detected by Gamma probe
• Normal – 15% uptake after 6 hours
20

21. Diagnostic / Post-Rx Whole Body Scan
• Indications :
Evaluate residual thyroid tissue
Evaluate functioning metastasis
To determine therapeutic dose of I-131
Evaluate treatment response
Surveillance following initial treatment
• Arguments against whole body scans :
Low sensitivity
Stunning of residual cancer cells
Unnecessary radiation exposure
21

22. Diagnostic / Post-Rx Whole Body Scan
• Patient preparation :
 Thyroid hormone withdrawal for 4 weeks
 TSH > 30 mIU/L
 Low-iodine diet 1-2 weeks
• Radiotracer
 Diagnostic - I-131 (1 to 3 mCi)
 Post-Rx – I-131 (30 to 250 mCi)
• Detection by Gamma camera
 Diagnostic - 3 days after I-131 administration
 Post-Rx – 7 days after I-131 administration
 Records images of distribution of RAI in entire body
22

23. Diagnostic Whole Body Scan
23
No uptake
in thyroid
bed
Negative
WBS

24. Post-Rx Whole Body Scan
24
Multiple foci of uptake in the left thyroid bed, lungs, right humerus,
ribs, acetabulum, and femurs Follicular thyroid carcinoma with multiple
bone metastases

25. Thyroid Scan
• Radiotracer- I-123, I-131 or
Tc-99
• Thyroid imaged with gamma
camera
• Use-
Evaluation of thyroid nodule
– functional or not (hot or
cold)
25
Hot Nodule
Cold Nodule

26. Treatment Modalities :
Surgery
I-131 Therapy
Hormone Therapy
EBRT
26

27. Surgery
• Mainstay of treatment for most thyroid cancer
• Total thyroidectomy is usually recommended
• Lobectomy is used for -
o Low-risk cases
o Solitary differentiated lesion <1 cm
o With no evidence of vascular invasion,
capsule involvement or suspicious nodes
27

28. Surgery
•In higher-risk features : complete thyroidectomy
should be undertaken (followed by remnant ablation)
•Remnant ablation with 131-I should not be performed after
lobectomy
• For DTC-
Near total or Total thyroidectomy + modified radical neck
dissection (if metastatic Lymphadenopathy)
28

29. Rationale behind NTT or TT vs. Limited surgery
• High survival rate in lesions >1.5cm ( rate of local
recurrence < 2% vs 14%)
• Multicentricity
• DTC which do not concentrate Iodine
• Success rate with I-131 ablation of remnant thyroid or
functioning mets increases
• Post op follow up with serum thyroglobulin
29

30. Early post-surgical Management
• T3 –
o 20 mg tds
o After total / near-total thyroidectomy
o Stop before radioiodine scan or 131 I ablation
• Check serum calcium
• Check baseline post-op serum Tg at least 6
weeks after surgery
30

31. Radioactive-Iodine Therapy
31

32. Radioactive Decay of I-131 :
32

33. Post-op I-131 Ablation :
• Consider if-
o Residual tumor
o Extension beyond the capsule
o Unfavourable histology
o Consider factors like age, mets, invasion, completeness of excision,
co-morbidities
• Goals-
o Thyroid remnant ablation
o Adjuvant therapy for residual microscopic disease
o Increased sensitivity of Tg measurements
33

34. Patient Preparation :
34
COMPONENT DESCRIPTION
Low iodine diet A diet that is low in iodine (≤50 μg/d)
for 2 wk before, and 2 d after, I-131
administration
IV contrast exposure In patients who have received iv iodinated
contrast within 3 mo of the planned date of
treatment, urine iodine level is measured 1-2
wk before the planned date of
administration
Urinary iodine
Measurement
Ideally, urine iodine is ≤50 μg/L before
cancer treatment with I-131
rhTSH instead of T4
deprivation
rhTSH 0.9-mg intramuscular injection twice
(2 d and 1 d) before I-131 administration

35. Patient Preparation :
35
COMPONENT DESCRIPTION
T4 deprivation instead of
rhTSH
Stop all thyroid hormone (usually
levothyroxine, T4) replacement for as
long as it takes to raise the TSH level to ≥
30 μU/Ml
Lithium Lithium increases radiation dose in target
tissue by increasing iodine retention time
preferentially in normal and malignant
thyroid
Others :
o Scopolamine
o Avoid sour candy

36. Patient Preparation :
• Exclude pregnancy
• Consider pre-treatment sperm banking (if patient likely to
have more than two high dose I-131 therapies)
• If a pre-ablation scan is felt to be absolutely necessary, Tc-99m
pertechnetate scan preferable to I-131 to reduce risk of
stunning
36

37. Dose of I-131
• Approaches :
Empiric –
All patients with the same disease risk factors gets the same
dose
Dosimetric –
Patients undergo tests of iodine metabolism to customise the
dose based on individual physiology
• Recommended-
Empiric dosing except in cases of renal insufficiency or
multiple prior I-131 treatment
37

38. Dose
Remnant ablation :
– No prior I-131 treatment and no visible residual tumor
– I-131 administered soon after total thyroidectomy
38
Active surveillance
No I-131 treatment
All must be present
• pT1-2, pN0-1a, M0
• ≤ 3 positive nodes
• No ENE
• Negative margin
• Postoperative Tg <1.0 ng/mL

39. Dose
30 mCi to 150 mCi If any are present :
• pT3b
• ≥ 4 positive nodes
• ENE that is not extensive
• Positive margin and post-op Tg ≥1.0 ng/mL
200 mCi If any are present :
• pT4
• Extensive ENE
• M1(with the exception of large-volume disease)
39

40. Biochemical recurrence :
- Recurrent tumor based only on serum thyroglobulin level with no
visible disease following at least one prior I-131 treatment
- Observation without additional I-131 treatment is always a reasonable
option
• Observation–
 Life expectancy is <5 y
 When the risk of additional I-131 treatment is high-
o renal insufficiency
o peripheral blood count deficiency
o substantial dry eye from prior I-131 treatment
• 150 mCi is standard dose for biochemical recurrence
40

41. Visible residual recurrent tumor
o Visible tumor on Ultrasound, CT, MRI, or PET, following salvage
surgery if applicable
o Includes –
 distant metastasis
 unresectable disease in the neck
 no visible residual disease following salvage neck surgery but
pathologic findings suggesting a high risk of recurrence (positive
margin, multiple positive nodes, extranodal extension)
• Not to retreat with I-131 when the risk of another I-131 treatment
is high
• 200 mCi is the standard dose when treating visible recurrent
tumor
41

42. Post - Treatment
• Discharge 3 days after radioiodine Tx ( when dose rate at 1 metre is
<0.07 mSv/hr)
• Commence thyroxine on discharge
• Post-ablation scan 3-10 days later
• Instructions on Discharge for 3 days after I-131 treatment-
o Avoid contact lenses
o well-hydrated
o at least 1 bowel movement each day
o Avoid things that stimulate saliva production chew gum or candy
42

43. Side Effects of Post-op I-131 Ablation
43
Temporary side effects –
• Swelling of the saliva glands or neck:
o Usually goes away in 3-5 d
• Taste change:
o Returns to normal within 3 wk after taking I-131
• Nausea:
o For 1-3 d after taking I-131
o Nausea medications

44. Side Effects of Post-op I-131 Ablation
44
Permanent side effects :
• Decrease in saliva and tears causing dry mouth, tooth
decay (cavities), and dry eyes
• Bone marrow damage
• I-131 can cause cancer to develop
• Damage to testicles or ovaries :
In women -early menopause
In men - impotence or decrease fertility

45. External Beam Radiotherapy For
Thyroid Cancer
45

46. Indications :
46
AGE INDICATIONS
Age ≤ 18 y • Painful metastases
• Impending normal tissue damage from a
growing tumor
Age >18 y with visible and unresectable
tumor
• When surgery is not able to result in the
removal of all visible tumor with
acceptable morbidity
• In cases not suitable forRAI

47. Indications :
47
AGE INDICATIONS
Age >18 yr
adjuvant treatment soon after
thyroidectomy
• Most cases with stage T4 primary tumor
or nodal metastases with extensive
extranodal extension
• Age is a deciding factor
Age > 18 y: after gross total resection of a
recurrence following initial
therapy
• After complete resection, EBRT may be
considered in select patients >45-y old
with a high likelihood of microscopic
residual disease
• In cases not suitable forRAI

48. Moderate Risk of Recurrence
• For cases with no evidence of visible residual tumor, ENE or positive
margins
• Standard fractionation : 60/54 Gy prescriptions
• CTV 60 Gy (at 2 Gy) –
o Post-op areas at high risk for recurrence - where recurrent tumor was
resected plus 1 cm margin
o dissected nodal stations with pathologically positive nodes
• CTV 54 Gy (at 1.8 Gy) -
Undissected nodal stations at >10% risk of recurrence
• PTVs = CTV+0.3 cm
48

49. High Risk of Recurrence
• For cases with visible residual tumor, extranodal extension of
tumor, or positive surgical margin
• CTV 70 Gy (at 2 Gy)-
visible residual tumor and/or postoperative areas with positive
margin or extranodal extension plus 1 cm margin
• CTV 63 Gy (at 1.8 Gy)-
dissected nodal stations with pathologically positive nodes
• CTV 56 Gy (at 1.6 Gy)-
undissected nodal stations at >10% risk of recurrence
• PTVs = CTV+0.3 cm
49

50. 50

51. TSH Suppression for Differentiated
Thyroid Carcinoma
• Administration of supratherapeutic doses of T4 to drive the TSH
below detectable limits
• Degree of TSH suppression is associated with improved relapse-free
survival
• Major limitation – Thyrotoxicosis
• Recommendation –
o For high-risk - TSH below 0.1 mU/L
o For low risk - TSH at or slightly below the lower limit of
normal (0.1–0.5 mU/L)
51

52. Management of Medullary
Thyroid Carcinoma
• All patients with MTC should be tested for RET mutations
• Initial primary management of localized MTC is total thyroidectomy
- only completely effective therapy
• Central neck dissection should be performed in all cases and lateral
neck dissection is indicated when clinically involved
• There is no role for adjuvant RAI therapy
• All patients should be followed with serum calcitonin – marker for
residual disease
52

53. Management of Anaplastic
Thyroid Carcinoma
• Goal of initial therapy- - Complete surgical excision
• Surgery should be avoided if complete excision is not possible
• No role of RAI
• EBRT -
o Standard of care for palliation of local symptoms
o Adjuvant therapy in completely resected tumor (total dose of 60
to 75 Gy)
• Even with hyperconcomitant chemoradiotherapy ( docetaxel,
paclitaxel, vincristine, cisplatin, or doxorubicin) outcomes remain
grim. 53

54. Post Treatment Follow-up :
• Voice dysfunction –
o Direct / indirect laryngoscopy
• Monitor calcium
• Suppression of serum thyrotrophin-
o Levothyroxine to maintain TSH < 0.1 mIU/ml
o Average dose is 175 mcg to 200 mcg
• Measurement of serum thyroglobulin
54

55. Long-term follow-up :
Lifelong follow-up is important because:
• Disease has a long natural history
• Late recurrences can occur which are readily
amenable to Tx
55

56. Long Term Follow-up :
• High risk patients warrant more vigorous follow up and many will
require retreatment
• Every 6 to 12 months following primary therapy –
o Neck US
o Serum Tg
• Serum Tg is the most sensitive means of detecting persistent or
recurrent tumor after surgery and RAI
• DxWBS and PET-CT scans are utilized only when clinically indicated
56

57. 57