Make your own free website on Tripod.com

Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Thyroid Cancer

Home

Should we treat or not???
Performace Status
Antiemetics
Growth Factors
Calculations
Chemo Precautions
TOXICITY CRITERIA
Antidepressants
Chemoprotection
MESNA
Dexrazoxane
Radioprotectants
Hypercalcemia of malignancy
Mucositis
Neutropenic Fever
Palliative Care
Radiation Oncology
<<<<<<<<<>>>>>>>>>
ALL
AML
Anal
Bladder Cancer
Brain Cancer
Breast (risk category)
Breast (adjuvant)
Breast (metastatic)
Breast (Xeloda)
Breast (hormonal)
Breast Cancer Genetics
Carcinoid
CLL
CML
COLON CANCER
Endometrial
Esophagous
Gastric
Gestational Trophoblastic Disease
Germ Cell (Ovary)
Hairy Cell Leukemia
Head/Neck
Head/Neck: ChemoRT abstracts
Head/Neck: Larynx
Head/Neck:Nasopharyngeal
Hodgkins
Islet Cell Tumors
Kidney
Liver
LUNG, NSC
Stage III Unresectable NSC Lung Cancer
Lung, SC
Lymphoma, Aggressive
Lymphoma, AIDS
Lymphoma, Burkitts
Lymphoma, CNS
Lymphoma, Cutaneous
Lymphoma, Indolent
Lymphoma, MALT
Lymphoma, Mantle cell
Lymphoma, Mediastinal B-Cell
Lymphoma, Refractory NHL
Melanoma
Mesothelioma
Multiple Myeloma
MDS
NHL
Ovarian
Pancreas
Prostate
Prostate (Hormonal)
Rectal Cancer
Sarcoma
Sarcoma, Ewing's
Sarcoma, Osteogenic
Skeletal Metastasis
Testicular Cancer
Thymoma
Thyroid Cancer
Waldenstrom's
Unknown Primary
<<<<<<<<<>>>>>>>>>
Molecular Genetics
Oncogenes, the list!
Immunoperoxidase stains
Tumor Markers
Bleomycin
Cisplatin
Etoposide
Ifosfamide
Methotrexate
Temazolamide
Mechanism of Action
Dose Modifications (Renal)
Dose Modifications (hepatic)
MDR

Undifferentiated Thyroid Cancer
Medullary Thyroid Cancer
Differentiated Thryoid Cancer
---Thyroxine Therapy
---T3 treatment prior to I-131 scans
---rhTSH
---Serum thyroglobulin
Genes involved in thyroid cancer
Histological comparison

____________________________________________
ANAPLASTIC THYROID CANCER

~50% of patients with anaplastic cancer have either a
prior or coexistent differentiated carcinoma. Anaplastic carcinoma develops from more differentiated tumors as a result of one or more dedifferentiating steps, particularly loss of the p53 tumor suppressor protein.
Patients often present with extensive local invasion. Distant metastases are found at initial disease presentation in 15-50% of patients. The lungs & pleura in up to 90% of patients with distant disease; 5 -15% have bone metastases; 5% have brain metastases; other sites include the skin, liver, kidneys, pancreas, heart, & adrenal glands.

TREATMENT. There is no effective therapy for anaplastic carcinoma. The disease is uniformly fatal. Median survival from diagnosis: 3-7 months. 1 & 5
year survival rates: 25% & 5%, respectively.
SURGERY. If the tumor is small & confined entirely
to the thyroid, total thyroidectomy with complete tumor resection may prolong survival.

XRT. Administered in conventional doses, it does not prolong survival. even though ~40% of patients may
respond initially to XRT, most will have local recurrence.

CHEMOTHERAPY. Single-drug chemotherapy does not improve survival or control of disease in the neck. However, ~20% of patients have some response in distant metastases. Active chemotherapy agents are doxorubicin & paclitaxel.

DOXORUBICIN
Doxorubicin 45-75 mg/m2 IVB* day 1 Q21 days
*Doxorubicin may be given in a single dose or divided into 3 consecutive daily doses.
REF= Gottlieb J, et al: NEJM 290:293 (1974)

CHEMORADIOTHERAPY. Hyperfractionated XRT, combined with radiosensitizing doses of doxorubicin,
may increase the local response rate to about 80%, with subsequent median survival of 1 year. However, distant metastases becomes the leading cause of death.

____________________________________________
MEDULLARY THYROID CANCER (MTC)

DIAGNOSTIC TESTS. Do not forget to rule out pheochromocytopenia & hyperparathyroidism that may coexist as part of MEN-IIA & MEN-IIB.

INITIAL TREATMENT Total thyroidectomy is indicated in all patients with MTC, given the high frequency of bilateral disease in both sporadic & familial disease.
Once an MTC tumor is palpable, there is a high frequency of metastasis to adjacent nodal tissue. Even if there is no clinically detectable nodal metastases, central neck compartment dissection should be performed in all patients, & ipsilateral
lateral neck &/or mediastinal dissections should be considered when the primary tumor is > 1 cm or when central compartment disease is present.

ADJUVANT XRT. Should be considered in
patients after maximal surgical therapy who are considered at high risk for regional recurrence.

FOLLOW UP. Serum calcitonin & CEA should be measured periodically:
----If calcitonin level <10 pg/mL then perform stimulation testing with calcium infusion. About 80% of
patients with palpable MTC & 50% of those with nonpalpable but macroscopic MTC who undergo supposedly curative resection have stimulated serum calcitonin values of at least 10 pg/mL, indicative of
residual disease.
----If calcitonin level near-normal values then monitor the patient.
----If calcitonin level > 100 pg/mL then evaluate for either residual resectable disease in the neck or for the presence of distant metastases.
----If calcitonin level > 1,000 pg/mL & no obvious MTC in the neck or upper mediastinum then most likely there is distant metastases, most likely in the liver.

PROPHYLACTIC SURGERY FOR GENE CARRIERS Prophylactic thyroidectomy is recommended for at-risk family members who are found to be carriers of a ret gene mutation. Most experts advocate prophylactic thyroidectomy before the age of 6 years in MEN-2A carriers. Some, however recommend surveillance with stimulated calcitonin meaasurements rather than surgery for young gene carriers without evidence of
MTC. This approach perhaps should be avoided in children with the more virulent ret mutations (i.e. in exons 10 & 11).

____________________________________________
Differentiated Thyroid Cancers

Thyroxine Therapy
---If primary tumor >1 CM then keep TSH between 0.05-0.5 mU/L.
---In patients with extrathyroidal invasion or extracervical metastasis, keep TSh <0.05 mU/L
---Patients who remain disease-free for 5-10 years may have their degree of TSH suppression reduced by lowering their doses of thyroid hormone. Other factors such as concurrent cardiac disease may also necessitate lowering degree of TSH suppression.


Liothyronine Therapy (T3)
T3 can be used as thyroid replacement for those who are awaiting I-131 scans/ablation. However, T3 must be stopped at least 2 weeks prior to dosing for I-131 scan.
Dose: 0.25 ug PO BID (caution in elderly)

rhTSH
Recombinant human TSH can be used instead of thyroid hormone withdrawal to avoid symptomatic hypothyroidism.

Serum thyrogolobulin (Tg) monitoring
---After thyroid resection and ablation, serum Tg levels should approach the limits of assay detectibility.
---Serum Tg levels may correlate with TSH levels. Therefore, it is best to check the levels when TSH is high (for example, thyroid hormone withdrawal). Sensitivity may approach 90% if TSH is high. It may be reduced to 50% during TSH suppression.
---It may be necessary to check anti-Tg antibody levels. A low Tg level may be secondary to the development of neutralizing antibody production. Its presence in the absence of detectable Tg may indicate presence of disease.

____________________________________________


Genes involved in Thyroid Cancer:

PAPILLARY THYROID CANCER
---RET
in transgenic mice activated ret transfer can cause papillary thyroid cancer!
---TRK

MEDULLARY THYROID CANCER (MTC)
---RET (cell-membrane associated tyrosine kinase receptor for glial cell-derived neurotrophic factor)
ret mutation is present in up to 95% of familial forms of MTC.

MEN IIA & IIB
---RET

Differences between various histologic forms in differentiated thyroid cancer
------------------------------------------------------------------------------
PAPILLARY THYROID CANCER
papillae consist of a welldefined fibrovascular core surrounded by 1-2 layers of tumor cells. Follicles & colloid are usually absent. Nuclei tend to be large,
oval, & appear crowded & overlapping on microscopic sections. The nuclei contain hypodense "powdery" chromatin, cytoplasmic pseudoinclusions due to a redundant nuclear membrane, & nuclear grooves.
FOLLICULAR VARIANT OF PAPILLARY
The follicular variant accounts for ~10% of all papillary carcinomas. The cells are organized into follicles rather than papillae, but cytologically, they display the typical nuclear features of papillary carcinomas. Note that rates of recurrence & survival with the follicular variant are very similar to those of patients with common-type papillary carcinomas.
------
INSULAR CARCINOMAS
They are often placed in the category of "poorly differentiated" thyroid carcinomas, which implies a status between that of differentiated & anaplastic carcinomas. However, insular carcinoma can concentrate I-131 & are therefore treated as differentiated cancers.

------
HURTHLE CELL THYROID CANCER
Hürthle cell neoplasms are formed by cells containing numerous mitochondria, which impact a granular, eosinophilic appearance to their cytoplasm. Most have a follicular architecture & are diagnosed as adenomas
or carcinomas by the same criteria applied to other follicular neoplasms. A Hürthle cell variant of papillary carcinoma is much less common & tends to be more aggressive than typical papillary carcinomas.
------