classification,diagnosis,prognostic scoring,and management

1. Thyroid Cancer
Presenter
Dr. Shashank Bansal
PGT MD Radiation Oncology
Department Of Radiation Oncology
Dr . B. Borooah Cancer Institute

2. Anatomy of the Thyroid Gland
• Two lateral lobes
• 50% have Pyramidal lobe:- Remnant of
Thyroglossal duct
• Weighs 10-20 gm , size 5*5 cm
• Extension:- Mid Thyroid cartilage to 6th Tracheal
ring
• Recurrent laryngeal nerves, sympathetic trunks,
vagus and phrenic Nerve lies posteriorly

3. • Arterial supply :-
• Superior thyroid artery
• Inferior thyroid artery
• Venous drainage :-
• Superior thyroid vein and middle
thyroid vein
• Inferior thyroid vein
• Lymphatics :-
• First Echelon nodes Level 6
• Second echelon nodes Level 3-4,
supraclav LN, Level 7 LN
• Lesser extent Level 2
• Rarely Level 1

4. Microscopic Picture of the Thyroid Gland

5. Thyroid Cancer Classification (cell of origin)
1. Follicular epithelial cell
A. Differentiate Thyroid cancers
a. Papillary and mixed papillary variants
b. Follicular cancer
B. Poorly differentiated thyroid cancer
• Insular carcinoma
C. Undifferentiated Thyroid cancer
2. Parafollicular cell
A. Medullary Carcinoma
Papillary variants
• Classic
• Papillary microcarcinoma
• Encapsulated
• Follicular variant
• Aggressive variant
• Diffuse sclerosing
• Tall cell variant
• Columnar cell variant
Follicular
• Classic
• Hurthle cell variant

6. Classification (ability to concentrate RAI)
A. Usually concentrate RAI
• Classic papillary
• Encapsulated papillary
• Follicular variant and mixed follicular papillary
• Follicular variant
B. Frequently do not concentrate RAI
• Tall cell and columnar cell variant of papillary carcinoma
• Hurthle cell
• Poorly differentiated
C. Never concentrate RAI
• Anaplastic
• Medullary

7. • Exposure to radiation in childhood #
• Increased risk of well differentiated cancer (0.1Gy)
• Latent period 3-5 yrs
• Risk remain apparent even after 40 yrs
• Victims of nuclear disaster
• Family history (first degree relatives)
• History of thyroid cancer syndromes
• Familial Adenomatous polyposis
• Cowden disease
• Carney complex
• Medullary cancer thyroid syndromes (MEN2A/MEN2B)
• Hashimoto thyroiditis (thyroid lymphoma)
Risk factors
# Schneider AB et al,Radation-induced endocrine tumor Cancer treat res 1997;89:141

8. Epidemiology
• Most common endocrine malignancy
• Incidence 7.7 per 1lakh
• Females 3 times more commonly affected than males.(5th most common cancer in
females)
• Most common histology papillary thyroid cancer
• DTC (90%), Medullary (5-9%), Anapalstic (1-2%), lymphoma (1-3%), sarcoma (<1%).
• Mean age of presentation 40-45 yrs (females), 65-69 yrs (males).
• In India relative frequency of thyroid cancer 0.1%–0.2%.
• The AAR per 100,000 is about 1 for males and 1.8 for females as per the Mumbai Cancer
Registry, which covered a population of 9.81 million subjects.
• Highest incidence is in Thiruvanantpuram district.

9. • Thyroid nodule (m/c), incidental finding
• Increased suspicion of malignancy :-
• Rapid growth
• Firmness
• Fixation
• Vocal cord paralysis
• Dysphagia
• Cervical adenopathy
• Advance cases presents with :-
• Airway compromise
• Hoarseness of voice
• Pain
• Weight loss
• Respiratory distress
Presentation

10. Diagnosis
• Laboratory Studies :-
• CBC
• RFT/LFT
• Serum TSH
• Thyroglobulin, T3 and T4
• Serum calcitonin (Medullary Thyroid cancer)
• Cervical (Neck) Ultrasound
• Ultrasound Guided FNA (for both palpable and incidental finding)
• Sensitivity (100%), Specificity (67%)
• Positive predictive value (87%), Negative predictive value (100%)
• Limitation :- Inability to distinguish benign follicular adenomas from FC and Follicular PTC.
• CT scan and MRI
• Generally not recommended because of the use of iodinated contrast, which hamper RAI therapy.

11. Ultrasound findings subjected to FNA
Characteristic Tumour size requiring Biopsy
Size > 1cm All
Spherical shape <1cm
Hypoechoic <1 cm
Micro-calcification <1 cm
Irregular, indistinct margins <8 mm
Increased Doppler flow <8 mm
Suspicious LN <8 mm
Invasion into surrounding <8 mm

13. Papillary thyroid cancer
• Orphan Annie eye Nuclei
• Psuedoinclusion

14. • Nuclear Medicine studies
• Radioactive Iodine Uptake
• Historical importance
• To quantify RAI concentrating ability of remnant thyroid tissue
• Diagnostic whole body scan
• Some used as apart of surveillance
• Utility controversial
• Drawback :- Low sensitivity, stunning of residual cancer cell, unnecessary radiation exposure
• Therapeutic whole body scan
• Done in every patient receiving RAI
• Used to detect gross residual disease
• RAI concentrating ability of diseased tissue
• FDG PET
• Predictive value of PET is not well defined
• Used to detect metastases

16. Prognosis
• Histologic classification
• Age
• Gender
• Primary tumour size
• Multifocality and extra thyroidal extension
• Lymph node and Distant metastases
• RAI concentrating ability

17. Prognostic scoring systems
• AGES
• Age
• Tumour Grade
• Tumour Extent
• Tumour Size
• AMES
• Age
• Metastases
• Extra thyroidal extension
• Size
• MACIS
• Metastases
• Age
• Completion of resection
• Local Invasion
• Tumour Size

18. TNM staging

19. Management
• Surgery
• Primary treatment
• Total thyroidectomy is preferred
• Complications:-
• Recurrent laryngeal nerve injury
• Hypoparathyroidism
• Injury to Vagus nerve, spinal accessory nerve, superior laryngeal nerve

20. • Lobectomy Indications: (NCCN 2011 guidelines)
• Patients Age 15-45 yrs
• Tumour size <4 cm without prior RT
• Lymph nodes or Distant metastases
• Extra thyroidal extension
• Aggressive histology
• Indications of surgical evaluation in non diagnostic thyroid nodule :
• Suspicious cytology for PTC
• Cytology contains follicular cells with no concordant functioning nodule on RAI scan
• Cytology contain Hurthle cell Neoplasm
• Growing nodule

22. • Radio active iodine therapy
Goals
• Thyroid remnant ablation
• Adjuvant therapy for residual microscopic disease

23. • Patient Selection for RAI
• Distant metastases
• Gross extra Thyroidal extension
• Tumour size 1-4 cm with
• LN metastases
• High risk features
• Age >45 yrs
• Intrathyroidal vascular invasion
• Multifocal disease
• Aggressive histological variants
• Follicular and Hurthle cell variants are high risk tumors always requiring RAI
• Not recommended when
• Tg <1 ng/ml
• Anti Tg antibodies and RAI imaging are negative

24. Role of Radiotherapy
• No Randomise trial to indicate benefit of RT
• European multicentre study on DTC trial was planned but terminated prematurely
• Converted to prospective cohort study but fails to show any benefit
• In general patients with unresectable Thyroid cancer are treated with primary
EBRT
• Palliation in symptomatic metastatic tumours (20-30 Gy in 5 -10 #).

25. Now What To doAny Specific guidelines ???

26. ATA Guidelines University of Florida
Age <18 yrs Metastases that are symptomatic or in critical
location that are otherwise unresectable
Painful metastases or impending
normal tissue damage
Age 19-45 yrs Metastases that are symptomatic or in critical
location that are otherwise unresectable
Gross unresectable tumours resistant
to Iodine131 #
Age >45 yrs Gross ETE, high likelihood microscopic residual or
gross residual tumour not amenable to surgery
Adjuvant treatment after surgery :
patient at high risk of locoregional
recurrence ,T4 primary, nodal mets
with ECE, gross residual disease
Salvage of recurrent disease:
Gross unresectable tumour with
resistance to RAI.
# resistance means recurrence after at least one >100 mci treatment under optimal condition.

27. • EBRT planning
• A custom head and neck mould with shoulder straps for head and
immobilization and to depress the shoulder level.
• Bolus material applied over scars.
• Conventional Treatment
• Conventional AP/PA or Lateral fields are used for treatment with bolus
material .
• Conformal treatment
• CT simulation done with patient lying supine with arms on side and neck
extended
• Axial images obtained from base of skull to middle of chest.

28. Target volumes :
• Gross tumour Volume :- residual gross disease
• High Risk CTV :- positive margins , Extra Thyroidal extension, Lymph node
with extra capsular disease, gross residual disease.
• Standard risk CTV :- region at moderate risk for residual disease (electively
irradiated nodal regions)

31. Doses
• 66 to 70 Gy in high risk PTV
• 54 to 56 Gy in standard risk PTV
Toxicity
• Mucositis , Taste Changes, xerostomia, Pharyngitis, Dysphagia,
Hoarseness, Radiation dermatitis, Weight loss, Malnutrition.
• Late complication : Fibrosis, Atrophy of skin, Neck musculature,
Tracheal and oesophageal stenosis.

32. Chemotherapy
• Indicated in patients refractory to Radioiodine therapy and rapidly
progressive disease.
• Drugs approved by FDA :- Doxorubicin, Sunitinib
• Newer drugs :-
• Vandetanib
• Pazopanib
• Selumetanib (MEK inhibitor) shown to reverse the loss of RAI avidity.

33. Follow up
• Every 6-12 month:
• Serum Tg analysis (Negtive predictive value of 99%)
• Neck USG
• DxWBS and PET CT when clinically indicated (Elevated Tg)

34. Recurrence
• Locoregional and nodal recurrence :- MRND or central Neck
dissection .
• More aggressive surgery in case of aero-digestive tract invasion.
• Tracheal stents and tracheostomy for unresectable cancer.
• For smaller LN not amenable to surgery:- USG guided ethanol
ablation.
• For radioiodine avid metastasis :- I131 is used as long as disease
responds .
• Few patients may require metastasectomy, laser ablation and EBRT for
palliation.

35. Anaplastic Thyroid Cancer
• Rare but more aggressive
• Poor Prognosis (Median OS < 6 months)
• Female > Male
• All classified as Stage IV
• IV A limited to thyroid
• IV B with local invasion
• IV C distant mets (Lungs and Bones m/c)

36. • Symptoms :- Rapidly progressing mass with LN met causing compression.
• Diagnosis :- USG guided FNA  Core biopsy
• Workup:- USG Neck, CT scan (neck thorax and brain), PET CT.
• Management:- surgery if resectable , unresectable NACT+ EBRT surgery.
• Adjuvant radiotherapy with or without chemo should be started as soon as possible.
• Chemo :- Doxorubicin + Platins (first line)
• Ongoing Trials:-
• Pazopanib + paclitaxel
• Imatinib
• Fosbretabulin
• Erlotinib
• Geftinib

37. Medullary Thyroid carcinoma
• Should be tested for RET mutations.
• Genetic screening and testing indicated.
• Primary management  Surgery (total thyroidectomy).
• Central neck dissection should be done in all cases.
• No role of adjuvant RAI therapy
• Follow up by serum calcitonin level  marker for residual.

38. • EBRT
• Children Age <18 yrs :- RT reserved for palliation.
• Adults :-
• Unresectable gross disease
• High risk of microscopic disease (positive margin, T4, nodal mets, extracapsular
extension.)
• No role of cytotoxic systemic therapy.
• Promising preclinical and early clinical results with TKI.

41. Conclusion
• Management of thyroid cancer is a multidisciplinary strategy and a close coordination
and cooperation is essential in diagnosis and long term follow-up.
• Surgery and the judicious use of radioactive iodine, as described in the guidelines, is
sufficient treatment for the majority of patients with differentiated thyroid cancer.
• A rigorous and prolonged that is life -long observation should be mandatory and this
should be indicated to the patients as well as family by the treating doctor.
• A minority of these patients experience progressive, life threatening growth and metastatic
spread of the disease. For these individuals, experimental treatments may be considered.

42. Greetings for Ambubachi

43. Thanks