Thyroid cancer and its

management
Dr. Nurun Nahar
CMO
Head, Thyroid Division
INMU

Carcinoma of the thyroid gland

Uncommon cancer (0.6%-1.6% of all cancers).

Common malignancy of endocrine system.
Female : male = 2:1
Differentiated tumors (papillary or follicular) are highly
treatable and usually curable.
Poorly differentiated tumors (medullary or anaplastic)
are

Much less common,

Aggressive,
Metastasize early,
Have poorer prognosis.

Usually occurs in people between the ages of 25 and 65

years.

DTC
Most common presentation - asymptomatic
thyroid nodule or neck mass.
Commonly presents as a cold nodule.
Overall incidence of cancer in a cold nodule
is 12% to 15%, but it is higher in people
younger than 40 years and in people with
calcifications present on preoperative USG.

Risk Factors for Ca thyroid

Patients with a history of radiation administered in
infancy and childhood for benign conditions of the head
and neck.
Radiation exposure as a consequence of nuclear fallout,
especially in children.
A history of goiter.
Family history of thyroid disease (MTC).
Female gender.
Asian race.
Presence of a nodule with;

Voice change.
Dysphagia.
Fixed nodule.
Rapid tumour growth.

Nodules having low incidence of

malignancy

Involving entire lobe.

Large, soft nodule with smooth boarder.
Associated with hyperthyroidism.
MNG.

Investigations of thyroid nodule

Lab test: TSH, Tg, Calcitonin

Radioisotope Scan
USG
FNAC

Lab test:
TSH - Abnormal thyroid function does not
exclude the possibility of malignancy, but
decrease the suspicion
Thyroglobulin (Tg) - may be elevated in all
other goitorous conditions, not a valuable tool
in differential diagnosis. Its value in follow up.
Several reports recommend routine
measurement of calcitonin in patients with
nodule for medullary thyroid cancer

Thyroid scan
Scan provides a measure of the iodine-trapping function of the
nodule
cold,warm or hot
Hot nodules are unlikely to be malignant (>1%). Warm
nodules can be malignant in 5-8% of cases. Possibility of
malignancy in cold nodules may be up to 40%.
Nodules smaller than 1cm in size are below the
discriminating power of most of the available scanning
devices.
Different isotopes available
123I (best for diagnostic purpose),
technetium and
131I.
problem - discordant technetium and iodine scans

USG

Differentiate cystic nodule from solid.

Guide FNA biopsy.
Follow-up of both benign and malignant thyroid lesions.
Positive predictive criteria of malignancy in sonography
include
solid hypoechoic nodules,
presence of calcifications,
irregular shape,
absence of halo and
absence of cystic elements.

FNAC

Safe, less expensive.

Leads to a better selection of patients for surgery.
Distinguish benign and malignant nodules.
Decreased the number of unnecessary surgery by more than
50% and
Doubling the incidence of finding malignancy in resected
specimens.
Experience and good technique are important for obtaining
an adequate sample
should be reviewed by an experienced cytopathologists

Diagnostic scheme for management

of thyroid nodule
FNAC

Malignant

surgery

Indeterminate

Scan

Hot-F/U
Cold - surgery

Benign

Suppress

Continued
growth

surgery

Insufficient
sample

Repeat FNAC

Histology
Well-differentiated carcinomas (85%)

Papillary
Follicular
Mixed
Anaplastic carcinomas (5%)
(Undifferentiated)
Medullary thyroid cancer (5-10%)
Sarcoma
Lymphomas
Metastatic carcinomas (breast, RCC)

Prognostic Factors
Age: younger age, better prognosis. Though tumour recurrence
increased in both extreme ages, children respond well to
therapy.
Sex: common in female, more aggressive in male.
Histology: among DTC, PCT has better prognosis than FCT
Size: Primary tumor larger than 4 cm
Capsular invasion: no or minimal invasion, better prognosis.
The prognostic significance of lymph node status is
controversial. Some studies, have shown that regional lymph
node involvement had no adverse effect on survival.
Distant metastases: Present or not.

TNM classification
T1= tumour diameter upto 2 cm
T2= 2 4 cm
T3 = > 4 cm, confined to thyroid or minimal
extra thyroidal invasion
T4 = tumour of any size extending beyond
thyroid capsule
Tx= primary tumour size unknown but no extra
thyroidal invasion

TNM classification
Contd.

N0= No metastatic node

N1a= Mets to level IV LNs (pretracheal,
paratracheal, prelaryngeal )
N1b= Mets to cervical or sup mediastinal
LNs
NX= Mets to LNs not assessed

TNM classification
Contd.

M0= No dist mets

M1=dist mets present
MX=dist mets not assessed

Staging of thyroid cancer

Stage I
A
B

Unilateral
Bilateral or multifocal

Stage II
A
B

Unilateral LN
Bilateral or mediastinal LN

Stage III

Local cervical invasion with or without

LN

Stage IV

Distant mets

Risk Stratification
Low-risk patients
no local or distant metastases
all macroscopic tumor resected
no tumor invasion of locoregional tissue
tumor does not have aggressive histology (e.g.,
tall cell, insular, columnar cell carcinoma) or
vascular invasion
if 131I given, no uptake outside the thyroid bed on
the first post treatment whole-body RAI scan

Risk Stratification
Intermediate-risk patients
microscopic invasion of tumor into the peri
thyroidal soft tissues at initial surgery
cervical lymph node metastases or 131I
uptake outside the thyroid bed on the post
Rx WBS
tumor with aggressive histology or vascular
invasion

Risk Stratification
High-risk patients
macroscopic tumor invasion
incomplete tumor resection
distant metastases
Tg out of proportion to what is seen on the
post treatment scan.

 A retrospective study of 1,019 patients

showed that the 20 year survival rate is 98%
for low-risk patients and 50% for high risk
patients.
10 year overall relative survival rates for
patients in the United States are 93% for
papillary cancer, 85% for follicular cancer,
75% for medullary cancer, and 14% for
undifferentiated/anaplastic cancer.

Management
Total/near total thyroidectomy followed by
I-131 ablation is the treatment of choice.

Post surgical & pretherapeutic

evaluation
(2 wks after surgery)

TSH
Tg
USG
Isotope Scan
I-131 Uptake
S. calcium
PTH

I-131 therapy
Systemic administration of I-131 for selective
irradiation of thyroid remnant, microscopic DTC
or other non-resectable DTC or incompletely
resectable DTC or both purposes.
Radioiodine ablation post-surgical adjuvant
modality
Radioidine treatment of non-resectable or
incompletely resectable lesions curative or
palliative therapy

The Goal of Post-operative RAI

Remnant Ablation
To decrease the recurrence rate and
possibly the mortality rate.
To facilitate the early detection of
recurrence based on serum Tg measurement
and eventually on I-131 WBS.
High activity of I -131 permits highly
sensitive post therapy WBS, 25 days after
its administration, and this may reveal
previously undiagnosed tumors.

RAI - Indication for Remnant

Ablation
To ablate residual normal thyroid tissue
in all cases of DTC
Tumour >= 1.5 cm in solitary, non invasive
Ca (some opinion)
Evidence of Extra-thyroidal invasion
Cervical LNs Metastases
Distant Metastases

Pt preparation for ablation therapy

TSH to be raised upto 30 IU/mL or more to
stimulate I-131 uptake by functioning mets.
24 hrs uptake should be < 5%
Small amount of residual tissue in thyroid bed
seen by USG & scan
A low-iodine diet (50 ug/day) for 12 weeks is
recommended for patients undergoing radioiodine
remnant ablation, particularly for those patients
with high iodine intake.
Drugs interfering RAIU should be avoided

Dose of RAI

Confined to Thyroid = 75 - 100 mCi

Cervical LN Mets = 150 mCi
Lung Mets = 150 mCi
Bone Mets = 200-250 mCi
30 mCi low dose has been advocated by some authors.
advantages
Isolation may be avoided.
Radiation dose to whole body & gonads is reduced.

Disadvantages
Lower ablation rate.
Micrometastasis may receive inadequate radiation.

Post therapy management

Pt should stay in isolated room with toilet
facility.
Drugs to avoid nausea, vomiting & gastric
irritation.
Sufficient fluid intake.
Sour candy to stimulate salivary glands &
wash out.
Thyroxine replacement after 24 - 48 hrs
starting with low dose and gradually raised
to suppression dose.

Post-therapy Scan
Recommended after radioiodine remnant
ablation, 58 days after the therapeutic dose .
To see uptake in residual tissue in thyroid bed.
To find out any mets.

Follow up
Tg, TSH, FT3 , S. calcium after 3 months.
Tg twice in a yr.
On thyroxine, if Tg <10 ng/mL OK
Tg> 10 ng/mL large dose WBSpositive
metastatic protocol.
Tg> 10 ng/mL large dose WBSnegative further
imaging, US, CT, MRI, 201Tl scan, PET CT.

Rising Tg, suspicious.

Large dose WBS at the end of 1st & 2nd yr and then
5 yearly if Tg low. Off thyroxine Tg also to be
done.

Long-term management
After total or near-total thyroidectomy and
thyroid remnant ablation, disease-free status
comprises all of the following:
No clinical evidence of tumor.
No imaging evidence of tumor (no uptake outside the
thyroid bed on the initial post treatment WBS or if
uptake outside the thyroid bed was present, no
imaging evidence of tumor on a recent diagnostic scan
and neck US.
Undetectable serum Tg levels during TSH
suppression and stimulation in the absence of
interfering antibodies.

Serum Tg should be measured

every 612 months
Should be assessed in the same laboratory using
the same assay
Tg antibodies should be quantitatively assessed
with every measurement of serum Tg
In low-risk patients who have had remnant
ablation and negative cervical US and
undetectable TSH-suppressed Tg within the first
year after treatment, serum Tg should be
measured after thyroxine withdrawal or on
thyroxine approximately 12 months after the
ablation to verify absence of disease .

Tg-positive & RAI scannegative

patients
18FDG-PET scanning may be done:
as part of initial staging in poorly differentiated thyroid
cancers and invasive Hurthle cell carcinomas, especially
those with other evidence of disease on imaging or because
of elevated serum Tg levels
as a prognostic tool in patients with metastatic disease to
identify those patients at highest risk for rapid disease
progression and disease-specific mortality
as an evaluation of post treatment response following
systemic or local therapy of metastatic or locally invasive
disease

Augmentation of radiation dose

Increased serum TSH By withdrawing thyroid replacement
Using thyrogen or recombinant TSH

Decreasing serum iodide pool

Reducing uptake
Increasing excretion of iodine

Prolonging tumour retention of iodine

Lithium may be used

Management of DTC patients with

pulmonary mets
Pulmonary micro mets should be treated with RAI therapy, and
repeated every 612 months as long as disease continues to
concentrate RAI and respond clinically. Highest rates of complete
remission are reported in these subgroups.
RAI dose for pulmonary micrometastases can be empiric (150
mCi) or estimated by dosimetry to limit whole-body retention to
80 mCi at 48 hours and 200 cGy to the red bone marrow.
Radioiodine-avid macronodular metastases should be treated with
RAI and treatment should be repeated when objective benefit is
demonstrated (decrease in the size of the lesions, decreasing Tg),
but complete remission is not common and survival remains poor.

Management of DTC patients

with others mets
Complete surgical resection of isolated symptomatic metastases
has been associated with improved survival and should be
considered, especially in patients <45 years old with slowly
progressive disease.
When skeletal metastatic lesions arise in locations where acute
swelling may produce severe pain, fracture, or neurologic
complications, external radiation and the concomitant use of
glucocorticoids to minimize potential TSH induced and/or
radiation-related tumor expansion should be strongly considered.
If CNS metastases concentrate RAI, then RAI could be
considered. If RAI is being considered, prior external beam
radiotherapy and concomitant glucocorticoid therapy are
strongly recommended to minimize the effects of a potential
TSH-induced increase in tumor size and the subsequent
inflammatory effects of the RAI .

Management of Tg-positive,
RAI scan-negative patients
Empiric radioactive iodine therapy (100
200mCi) might be considered in patients in
whom imaging has failed to reveal a potential
tumor source with
elevated Tg levels after T4 withdrawal of 10 ng/mL or
higher,
5 ng/mL or higher on T4 or
rising serum Tg levels

If the post therapy scan is negative, no further

RAI therapy should be administered.

Management of Tg-positive,
RAI scan-negative patients
contd.
If persistent non resectable disease is localized
after an empiric dose of RAI, and there is
objective evidence of significant tumor reduction,
then RAI therapy should be repeated until the
tumor has been eradicated or the tumor no longer
responds to treatment.
The risk of repeated therapeutic doses of RAI
must be balanced against uncertain long-term
benefits.

Management of Tg-positive,
RAI scan-negative patients
contd.

If an empiric dose (100200 mCi) of RAI

fails to localize the persistent disease,
further imaging like US, CT, MRI, 201Tl
scan, 18FDG-PET/CT scanning should be
considered, especially in patients with
unstimulated serum Tg levels >1020
ng/mL or in those with aggressive
histologies, in order to localize metastatic
lesions that may require treatment or
continued close observation.

In cases of
.
No structurally evident disease,
Tg<10 ng/mL with thyroid hormone
withdrawal
Tg <5ng/mLwith thyroid hormone
To be followed with continued LT4 therapy
alone, reserving additional therapies for those
patients with rising serum Tg levels over time
or other evidence of structural disease
progression.

Complications of I-131
Short term complications:

Sialoadenitis
Radiation gastritis
Thyroid storm
Vocal cord paralysis
Bone marrow depression
Temporary ovarian failure
Local effects
Pain, oedema

How to avoid/ minimize

Complications of I-131
Long term complications(rare):

Myelogenous leukaemia
Parotid gland tumour
Azoospermia
Pulmonary fibrosis, in case of lung mets

The end