1. New Development in Diagnosis and
treatment of Thyroid Cancer
Ihsanullah
2nd Semester
IBMS, KMU

2. Contents
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Cancer
Thyroid cancer
Types of TC
TNM staging
Diagnosis of Cancer
Treatment

3. Cancer
• Cancer is a class of diseases characterized by
out-of-control cell growth.
• There are over 100 different types of
cancer, and each is classified by the type of
cell that is initially affected.

4. Why cell become Cancerous
• B/c damage to DNA.
• In normal cells Damaged DNA either repair
the cell/dies.
• In cancer the damaged DNA nor repair neither
dies but keep on growing abnormal cells.

6. Thyroid Gland
Highly vascular,
brownish red gland,
located anteriorly in
the lower neck

7. Two types of cells
a) Follicular cells- use iodine from blood to make
thyroid hormone which helps regulate a person
metabolism.
• Hyperthyroidism
• Hypothyroidism
• TSH
b) Para follicular cells; make calcitonin, a
hormone that control the Calcium.

8. Thyroid Cancer
• Most common
endocrine neoplasm.
• Mostly occur in younger
age and in women
expose to radiations.

9. Types of Thyroid Cancer
Many of DNA mutation have been found
in this type. having changes in specific
part of RET gene, many PTC have BRAF
mutation but that is less common in
children and is not mutated.
FTC Acquired changes in
the RAS oncogene have a
role in causing some
follicular thyroid
cancers.
IN ATC These have mutation
in RAS, RET gene and often
have changes in
the TP53 tumor suppressor
gene and the CTNNB1
oncogene as well.
People who have medullary thyroid
carcinoma (MTC) have mutations in
different parts of
the RET gene compared with
papillary carcinoma patients.

10. TNM staging
The most common system used to describe the stages of thyroid
cancer is the American Joint Committee on Cancer (AJCC) TNM
system. The TNM system is based on 3 key pieces of information:
• T indicates the size of the main (primary) tumor and whether
it has grown into nearby areas.
• N describes the extent of spread to nearby (regional) lymph
nodes.
• M indicates whether the cancer has spread (metastasized) to
other organs of the body.
(The most common sites of spread of thyroid cancer are the
lungs, the liver, and bones.)

11. Tumor Grading

12. Diagnosis of Cancer
Imaging Tests
• Ultrasound- to check the no, and size of nodules. also helpful in determine
that nodule is solid/filled with fluid.
• Radioiodine scan
They are also often used in people who have already been diagnosed with
differentiated (papillary, follicular, or Hürthle cell) thyroid cancer to help show
if it has spread.
Hot nodules that absorb more radiations and are Not cancerous.
Cold Nodule that absorb less radiations and may b benign/ malignant
Note ( Radioiodine scan work well if patient have high blood levels TSH or
thyrotropin.
• MRI scan
• Positron Emission Tomography Scan
B) Blood Tests
• TSH
• T3 & T4 and Throglobulin
A)

13. Contd
• MRI Scan
• Positron emission tomography-For a PET scan, a radioactive
substance (usually a type of sugar related to glucose, known
as Fluorodeoxyglucose( FDG) is injected into the blood. The
amount of radioactivity used is very low.
• Because cancer cells in the body grow quickly, they absorb
more of the sugar than normal cells.
• This test can be very useful if your thyroid cancer is one that
doesn’t take up radioactive iodine.

14. Diagnosis of cancer
• Biopsy- Fine needle Aspiration therapy
For those nodules having
size> 1cm. ( big enough to
Be felt)

15. Treatment
• Surgery
• Radioactive iodine treatment
• Thyroid hormone therapy
• External beam radiation therapy
• Chemotherapy
• Targeted Therapy

16. Surgery
• It’s the main treatment in nearly every case of
thyroid cancer, Except for some Anaplastic
thyroid cancers.
• If thyroid cancer is diagnosed by FNA biopsy
then surgery to remove the tumor and all or
part of remaining thyroid is usually
recommended.

17. Contd
• Lobectomy
this operation is sometimes used to
treat differentiated thyroid cancers
that are small and show no signs of
spread beyond the thyroid gland.
It is often sometimes used to diagnose TC if an
FNA biopsy result doesn’t provide a clear
diagnosis.

18. contd
• Thyroidectomy- this is most common surgery for TC.
a) Total thyroidectomy
When the thyroid gland is
removed then called
b) sub- total thyroidectomy- when most of thetotal
gland is
thyroidectomy
removed.
• Lymph node removal;
when cancer spread to lymph node- especially
important for MTC & Anaplastic cancer
(where surgery is an optional)

19. Radioactive Iodine
• radioactive iodine also known as I-131, is taken into
the body in liquid or capsule form, it concentrates in
thyroid cells.
• The radiation can destroy the thyroid gland and any
other thyroid cells (including cancer cells) that take
up iodine, with little effect on the rest of your body.
• This treatment can be used to ablate (destroy) any
thyroid tissue not removed by surgery or to treat
some types of thyroid cancer that have spread to
lymph nodes and other parts of the body.
• Note( we have to increase the level of TSH)

20. Thyroid hormone therapy
Taking daily pills of thyroid hormone (thyroid hormone therapy)
can serve 2 purposes:
• It can help maintain the body’s normal metabolism (by
replacing missing thyroid hormone after surgery).
• It can help stop any remaining cancer cells from growing (by
lowering TSH levels).
After a thyroidectomy, the body can no longer make the thyroid
hormone it needs, so patients must take thyroid hormone
(levothyroxine) pills to replace the loss of the natural hormone.

21. External beam radiation therapy
• External beam radiation therapy uses high-energy rays (or
particles) to destroy cancer cells or slow their growth.
• It is more often used as part of the treatment for medullary
thyroid cancer and anaplastic thyroid cancer.
Note ( It is used for those cancer cells which can’t take iodine)

22. Chemotherapy
• thyroid cancers do not respond well to chemotherapy. But
exciting data are emerging about some newer targeted drugs.
• Targeted therapies;
Unlike standard chemotherapy drugs, which work by attacking
rapidly growing cells (including cancer cells), these drugs attack
specific targets on cancer cells.
Tyrosine kinase inhibitors:
as tyrosine kinase inhibitors (TKIs) may help treat thyroid cancer
cells with mutations in certain genes, such as BRAF and RET/PTC.
Many of these drugs also affect tumor blood vessel growth (see

24. • In Papillary TC, cells have changes in BRAF gene which help
them Grow.
• Drugs that target cells with BRAF gene changes.
• TKIs that have shown early promise against thyroid cancer in
clinical trials .
sorafenib (Nexavar®),
sunitinib (Sutent®),
pazopanib (Votrient®),
cabozantinib (Cometriq),
motesanib (AMG 706),
axitinib (Inlyta®),
vandetanib (Caprelsa®).
vemurafenib (Zelboraf®),
dabrafenib,
and selumetinib,

25. contd
• TK’s inhibitors shown to be helpful in the treatment of
medullary thyroid cancer (MTC) in clinical trials, and are now
approved for use against advanced forms of the disease.
• Others TKI’s already approved to treat
Other types of cancer and might be useful
Vandetanib and
Against MTC & DTC if other drugs are not
cabozantinib
Working.
sunitinib,
sorafenib,
pazopanib

26. ADR’s of TKI’s

27. Mitogen activated protein kinases(MAPK)
• MAPK target specific oncologic Pathway in DTC progression
• Low Toxicity Profile
• many of the targeted MAPK drugs block the Raf kinases in
patients with RET or BRAF mutations.
• Sorafenib stabilize disease
Progression and lower Serum TG
Sorafenib
Level.

28. Anti angiogenesis drugs
• Anti-angiogenesis drugs work by disrupting these new blood
vessels. TKIs l such as
• axitinib,
• motesanib,
• sunitinib,
• sorafenib,
• pazopanib,
• cabozantinib,

29. Histone deacetylation Inhibitors
• Histone acetylation results in a more open chromatin
configuration and gene transcription. Many different types of
cancer cells have been found to have deregulated histone
acetyltransferase or histone deacetylase enzymes.
• Several histone deacetylate Inhibitors.
• Valporic acid increase expression of the
sodium-iodide symporter and radioiodine vorinostat, dep
sipeptide, valp
uptake
roic acid

30. FDA Approved novel therapy
• Vandetanib. Vandetanib (AZD6474/ZD6474,Zactima) is an
orally bioavailable inhibitor of RET, VEGFR-2 and epidermal
growth factor receptor (EGFR) [Carlomagno et al.
2002;Wedgeet al.2002].

31. Investigational therapies
Drug
targets
Refrence
Dosage
DTC
MTC
ATC
Axitinib
VEGFR13, PDGFR,
KIT
Cohenet
al.
[2008b]
300 mg
daily
77%
18%
3%
Motesani
b
VEGFR13, PDGFR,
KIT, RE
Shermane
t al.
[2008
125 mg
daily
100%
Pazopanib VEGFR1-3, Bibleet al.
PDGFR,
[2010]
KIT
800 mg
daily
100%
Tipifarnib
sorafenib
Farnesyltr
ansferas
Honget
al. [2011]
MTD
200mg
(+600mg)
63%
37%
Gefitinib
EGFR
Pennellet
al. [2008]
250 mg
daily
67%
15%
19%