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.
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
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
15.
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
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
21.
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 #).
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)
29.
30.
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.
39.
40.
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.
