PRE-OPERATIVE INVESTIGATIONS:

• Indirect laryngoscopy
• XRay neck- AP and lateral (in large goitre for airway assessment)
• XRay Chest
• USG neck for neck nodes and status of opposite lobe
• CT scan for assessing adjacent structures. (avoid iodinated contrast)
• Thyroid function tests when clinically indicated
• Serum thyroglobulin (Tg) – limited role with thyroid gland in situ.

Extent of Surgery:
Surgery remains the mainstay of treatment of DTC. However, the extent of surgery (Hemi or total thyroidectomy) has been a matter of considerable debate.

Arguments in favour of total thyroidectomy:
1) 5-10% recurrence rate in the opposite lobe following lobectomy alone.
2) > 10% incidence of distant metastases with conservative surgery
3) An increased rate of local/regional recurrence (14 and 19% for lobectomy vs. 2% and 6% for total thyroidectomy)
4) The inability to use I131 therapy and thyroglobulin for follow up
5) Risk of de-differentiation (anaplastic transformation)

Arguments favouring Hemi-Thyroidectomy:
1) Differentiated thyroid cancer is an indolent disease and in a majority of patients has a very low recurrence and mortality rate.
2) Permanent hypoparathyroidism and recurrent laryngeal nerve injury (incidence- 0-25%) are potential complications of total thyroidectomy.

These may be unacceptable especially in patients with good long term survival.

Recommendation
Hemithyroidectomy in
• All differentiated cancers < 1.5cm in size without extrathyroidal extension (ETS)
• No distant metastasis

Total thyroidectomy in
• All high risk patients (using staging systems)
• Nodule >4cm
• Age >45 yrs
• Distant metastasis
• Unfavourable histology- tall cell variant, diffuse sclerosing, insular variant, poorly differentiated, Hurthle cell carcinoma and follicular cancer(except microinvasive)
• Prior EBRT to the neck

Controversy for nodules between sizes1.5-4cm, however majority of surgeons, endocrinologists and most guidelines are in favour of a total thyroidectomy

RISK FACTORS AND STAGING SYSTEMS
There are a number of prognostic factors identified in the management of differentiated thyroid cancers. Most information on these prognostic indicators has been derived from large retrospective uncontrolled studies. Age, gender, tumour size, histologic grade, type, local invasion, multicentricity and the presence of metastatic disease are found to be independent predictors of prognosis. Based on these, risk group schemes have been suggested to stratify patients into high or low risk groups. Some of the risk group staging systems have been contrasted in the Table below.

• AGES, MACIS – Only papillary Ca.
• ETS and distant metastases in all
• Ohio state University + TNM use nodal metastases

However, the three most widely quoted and used scoring systems are the AMES, AGES and MACIS. The details of these three systems have been summarised in the table below.

Tx - Primary tumour cannot be assessed
T0 - No evidence of primary tumour

All histological types except undifferentiated carcinoma
T1 - Tumour 2 cm or less in largest dimension, limited to the thyroid
T2 - Tumour more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid
T3 - Tumour more than 4 cm in greatest dimension, limited to the thyroid or any tumour with minimal extrathyroidal extension (e.g. extension into sternothyroid muscle or perithyroid soft tissues)
T4a - Tumour extends beyond the thyroid capsule and invades any of the following, subcutaneous soft tissues, larynx, trachea, oesophagus, recurrent laryngeal nerve.
T4b - Tumour invades prevertebral fascia, mediastinal vessels or encases the carotid artery.

Regional Nodes - N
Nx - Regional lymph nodes cannot be assessed.
N0 - No regional lymph node metastases
N1a - Metastasis in Level VI (pretracheal, paratracheal, including prelaryngeal and Delphian lymph node)
N1b - Metastasis in other unilateral, bilateral, or contralateral cervical or upper/superior mediastinal lymph nodes

Distant Metastasis M
Mx - distant metastasis cannot be assessed
M0 - No distant metastasis
M1 - Distant metastasis

LYMPH NODES IN DTCs

Incidence of lymph node metastasis
Papillary cancer- 50%
Follicular cancer- 10%
Hurthle cell variant- 25%

Surgical Management
– No role for ‘Berry picking’
– Sample nodes in central compartment and Levels II-IV
– In node positive cases
         – Central compartment (Level VI) clearance
         – Lateral neck dissection (levels II-V), sparing the IJV, SCM and SA nerve
– RND rarely required

Prognostic implications of nodal metastases in thyroid cancer.

• In younger patients has no influence on long term overall survival. However bulky metastases have a higher incidence of distant metastasis and regional recurrence post treatment.
• In older patients presence of large lymph nodes is a poor prognostic marker.

Adjuvant therapy Radioiodine ablation

Indications in the post-op management of thyroid carcinoma:
• Imaging for functioning residual tissue
• Ablation of residual thyroid tissue.
• Treatment of residual/recurrent thyroid carcinoma.
• Treatment of metastatic disease.

Goals of I-131 treatment:
• Destroy any microscopic foci of disease after surgery.
• Destroy remnant normal thyroid.
     1. To improve the value of Thyroglobulin (Tg) as a marker.
     2. To increase specificity of I-131 scanning for detection of recurrence or metastasis.

Radioiodine therapy for distant metastasis

• Mainstay of treatment to control distant metastasis for more than 50 years
• Lungs, spine, and appendicular bone: most common distant metastatic sites
• Bone metastasis generally resistant to radioiodine (May be related to the mass of bone metastasis at presentation)

Method of administration of RI
1. Empiric dose: 100-300 mCi empiric dose
2. Dosimetry: Dose tailored according to dosimetric studies
-Whole body blood dosimetry is best reserved for therapy of widely metastatic thyroid carcinoma that exhibits radioiodine avidity.

No evidence to establish the superiority of one regime over the other. Majority protocols in favour of Empiric dose type.

RI fixed dose protocol
(TMH/RMC protocol)

1) If uptakes high, then dose of I131 to be decreased
2) Total permissible cumulative dose of I131 is 1 curie
3) 5-10% thyroid cancers do not concentrate RI

STRATEGIES TO ENHANCE UPTAKE OF RADIOIODINE

1) Low iodine diet for radioiodine therapy of metastatic disease
2) Lithium (10 mg/kg/day for 7 days. To keep S. Lithium levels at 0.8-1.2 mmol/L)
3) Retinoic acid (1.2 mg/kg/day)
4) Other agents
Histone deacetylate inhibitors
Demethylating agents

RECOMBINANT THYROTROPIN (rTSH) VS. THYROID HORMONE WITH DRAWL (THW) FOR MONITORING & TREATMENT.

– rTSH – Approved for use in diagnostic testing by US FDA
– Sensitivity & specificity of diagnostic testing using rTSH is comparable to thyroid hormone withdrawal.
– No significant difference between Positive Predictive value and Negative predictive value.

Indications

– Alternative to thyroid hormone withdrawal to circumvent problems due to hypothyroidism (pulmonary and cardiac disease)
– Patients unable or unwilling for withdrawal
– In patients with demonstrated inability to generate endogenous TSH secretion due to hypothalamic or pituitary disease.
– to improve sensitivity of thyroglobulin during follow up
– in cases of life or limb threatening metastasis (spine, mediastnum, brain)

rTSH administration protocol

• rTSH 0.9 mg IM on 2 consecutive days
• Dosimetry on the 3rd day
• Whole body scan and Rx on 5th day

ROLE OF POST OPERATIVE RT:
Indications

• High grade tumours that do not concentrate radioiodine
• T4 tumours
• Gross evidence of residual disease (especially if not concentrating radioiodine).
• Palliation of locally advanced, inoperable tumours
• Palliation of metastatic disease in the bone, brain, spine

Currently, recommended doses are 50-60 Gy in 25-30 fractions over 5-6 weeks

Radiotherapy techniques and volumes

• A clinical target volume from hyoid to suprasternal notch is determined
• Technique using two anterolateral oblique wedged fields is used
• Phase I- The initial volume includes regional lymph nodes from mastoid tip to the carina including the thyroid bed. The Phase I volume may consist of parallel opposing antero-posterior/posterior-anterior fields to 40-46 Gy.
• Phase II- The volume should include the tissues considered at highest risk to a total dose of 14 Gy (cumulative total dose of 60Gy)