postoperative radioiodine ablation in thyroid cancer

Postoperative Radioiodine

Ablation in Thyroid Cancer

Dr. Mamoon Ameen

Introduction Thyroid carcinomas are classified

as: papillary 70~80% follicular 15% medullary 5~10% undifferentiated or anaplastic 5%

Pathology

Well-differentiated papillary and follicular carcinomas are slow-growing and carry a relatively good prognosispoorly differentiated follicular and anaplastic carcinomas are aggressive tumors with a poor prognosis

Pathology

Papillary carcinomas are more likely to be found in regional nodes(36%) than follicular carcinoma(13%),but follicular tumors are more often distantly metastasis than papillary carcinomaEighty-five percent of thyroid cancers will be functional papillary or follicular carcinomas, capable of concentrating iodine

Clinical patterns

These tumors usually present as a firm neck mass, or accompanying palpable lymphadenopathyScans of thyroid nodules showed that the nodule was cold 84%of the timeairway obstruction , dysphagia, and hoarseness indicate invasive disease

Prognostic Risk Classification for Patients with Well-Differentiated Thyroid Cancer (GAMES )

High Risk Low Risk

Poorly Differentiated Well Differentiated Grade • >40 >40 Age

• Regional or Distant None

Mets • Capsular invasion,

extrathyroidalNo local extension

intrathyroidal Extent • Male Female Sex

Treatment modalities for thyroid cancer

• Surgery• Radioactive iodine • External beam radiotherapy • Thyroxin therapy • Chemotherapy

Iodine Metabolism• Dietary iodine is absorbed in the GI tract,

then taken up by the thyroid gland (or removed from the body by the kidneys).

• The transport of iodide into follicular cells is dependent upon a Na+/I- co-transport system.

• Iodide taken up by the thyroid gland is oxidized by thyroid peroxidase in the lumen of the follicle

•Oxidized iodine can then be used in production of thyroid hormones.

Iodine isotope -I 123 • half life= 13 hrs • gamma emitter -used for thyroid gland imaging

-I 124 • half life= 4 days • Positron emitter -used in PET –scan imaging and

dosimetry in thyroid cancer I 131 • Half life= 8 days and emit • Gamma radiation 10% –diagnostic and post therapy scan• Beta particles 90% –therapeutic ,ablation• B-particles do not penetrate deep into tissue(2 mm in

depth, at most)

I 131

• 131I is available for oral ingestion as sodium iodine

• As liquid solution or in capsules.• Each capsule accounts for 50 micro curie• Capsules safer than liquid- less

radioactivity released into air during handling.

• Also result in less oral mucosal irritation• Rapidly and completely absorbed in the

upper intestine

I 131 • Tissues that often take up iodine

and can be misconstrued as metastases include the– salivary glands in the mouth,– esophagus (as a result of swallowing

radioactive saliva),– thymus gland,– breasts in some women, – liver, stomach, colon, bladder

CANCER VS NORMAL CELLS

• Metabolism of radioiodine in papillary and follicular carcinoma is profoundly altered when compared with normal thyroid tissue.

• Several defects are present in cancer tissue:– iodine uptake, via the sodium-iodide

symporter (NIS), is always decreased and is undetectable in about a third of patients;

– Iodine organification is markedly reduced;– Effective half-life of iodine in tumor tissue is

always shorter

Radioiodine ablation

• What is radioiodine ablation?Radioiodine ablation is radiation therapy in which radioactive iodine is administered to destroy or ablate residual healthy thyroid tissue remaining after thyroidectomy.

• What is radioiodine treatment?Radioiodine treatment is radiation therapy in which radioactive iodine is administered to destroy suspected or known thyroid cancer by irradiating that tissue.

Radioiodine ablation

• Radioactive iodine therapy improves the survival rate of patients with differentiated thyroid cancer (papillary or follicular types) that has spread to the neck or other body parts

• Radioactive iodine therapy cannot be used to treat anaplastic (undifferentiated) and medullary thyroid carcinomas because these types of cancer do not take up iodine

RATIONALE

• Eliminate the postsurgical thyroid remnant • Destroys microscopic foci of carcinoma cells

within thyroid remnant• Reduces risk of local recurrence• Aids interpretation of serum thyroglobulin

measurements during follow-up• Facilitates detection and early treatment of

persistent or metastatic disease in the absence of normal thyroid tissue.

RADIOIODINE ABLATION LABORATORY WORKUP

• TSH• Thyroglobuline(Tg) • CBC• Serum BUN/CREATININE• URINALYSIS• SERUM CALCIUM• BETA HCG(serum pregnancy test –in

women of child bearing age)• Chest x-ray (screen for pulmonary met.

ATA recommendations

• RAI ablation is recommended for all patients with – known distant metastases, – gross extra-thyroidal extension of the tumor

regardless of tumor size, or – Primary tumor size >4 cm even in the

absence of other higher risk features

ATA recommendations

• RAI ablation is recommended for selected patients with– 1–4cm thyroid cancers confined to the thyroid,– have documented lymph node metastases,– Combination of some Higher risk features.• the presence of intra-thyroidal vascular invasion,• the finding of gross or microscopic multifocal

disease

ATA recommendations

• RAI ablation is not recommended for patients with unifocal cancer <1 cm without other higher risk features.

• RAI ablation is not recommended for patients with multifocal cancer when all foci are <1 cm in the absence other higher risk features.

CONTRAINDICATION

Absolute :• Pregnancy • Breast feedingRelative :• High grade bone marrow depression • Pulmonary function restriction • Salivary gland function restriction• severe hepatic and renal insufficiency

PREREQUISITES

• Raising the TSH level to >30 mu/l to stimulate uptake of iodine.

• 2 ways• 1-) Withdrawal of thyroid hormone• 2-)Given Recombinant TSH (Thyrogen®), which increases TSH levels without this period of hypothyroidism

PREREQUISITES

• Isolation – admission in hospital and accommodation in room with private toilet facilities

• Avoidance of iodine containing foods and medicines before ablation

• Avoidance of any radiological investigations which use iodine containing contrast media in preceding 3 weeks

• Pregnancy must be ruled out• Lactating mothers must stop breastfeeding

their infants

THYROXINE WITHDRAWALPROTOCOL

• Thyroxine therapy is stopped 6 weeks prior to ablation

• Liothyronine (20µg TDS) is given for 4 weeks• All thyroid hormone therapy is withdrawn 2

weeks prior to ablation• This causes TSH to rise• At maximal TSH stimulation, thyroglobulin is

measured

THYROXINE WITHDRAWALPROTOCOL

• 1-3 mCi of I131 is administered• Patient is scanned for residual iodine uptake

24-72 hours later. – PRE THERAPY SCAN• Therapeutic dose of I131 is given• Thyroxine and regular diet can be started 2

days after I131 dose• Whole body scan is done 1 week after the

therapy dose . - POST-THERAPY SCAN• Post treatment scan identifies metastatic

disease not visualized on diagnostic scan

RECOMBINANT TSH PROTOCOL

• Avoids severe hypothyroidism• Low iodine diet is started 2 weeks prior to

therapy• Thyroxine stopped only 2 days before the

procedure• Two IM doses of recombinant TSH are given –

day 1 and day 2• Day 3:

– Thyroglobulin and TSH levels are drawn– Therapeutic dose is given

• Suppressive dose of thyroxine and regular diet is started 3 days after the therapy

DOSE OF RAI

The dosing of 131I for ablation is somewhat

controversial. • Low-dose ablation with 30-50 mCi

• For low-risk young patients

• High-dose ablation with100 to150 mCi

• For high-risk patients

• 150-200 mCi • For all patients with metastatic disease that treated with

repeated therapeutic doses of 131I

Pre therapy whole body iodine scan:

If performed, a pre-therapy scan should use a low dose

of 131I (1 to 5 mCi) or 123I.

• To detect residual thyroid tissue,

thyroid cancer, and metastatic foci

• To reduce stunning

Stunning: is defined as a reduction in uptake of the 131I therapy dose induced by a pre treatment

diagnostic dose.

Following treatment with 100 mCi of I-131 the post-therapy scan demonstrated almost no evidence of tracer uptake in the neck indicative of thyroid stunning.

SIDE EFFECTS

• As a general rule, side effects increase in frequency and severity with increasing dosage and frequency of administration of I131.

• Immediate• Delayed

• Nausea ,vomiting • Gastritis • Neck swelling/edema • Acute

Sialadenitis(Swelling ,tenderness of salivary gland)

• Xerostomia /caries

Immediate

Delayed

• Pancytopenia • Leukemia • Chronic hypospermia • Pulmonary pneumonitis and fibrosis• Secondary malignancy• Chronic sialadenitis with xerostomia

RADIATION SAFETY:

The RAI is removed from the body in the sweat, saliva, and urine. For this reason, patients who are not being hospitalized for the therapy should prepare for the following precautions they will need to follow in the first 5 days after the therapy:

• Avoid close contact with young children, elderly, and pregnant women

• Avoid sharing a toilet or bathroom.• Avoid sharing food.• Avoid sharing a bed.• Wash clothes, towels, and linens separately.• Wash hands and the rest of the body often.

Follow up

Successful remnant ablation is usually defined as an absence of visible RAI uptake on subsequent diagnostic RAI scan or an undetectable stimulated serum thyroglobuline Diagnostic radioiodine scan is performed 6months following ablationIn cases with aggressive disease, scan may be done at 3 months

Follow up• In case of uptake, a therapy dose of 150 mci of I131 is

given• Thereafter, follow up is with serial thyroglobulin

measurements and whole body scan and suppressive thyroxine replacement (200-250 ug daily)

• As disease may recur after decades, surveillance should be for life

Figure : Whole-body scan of a 15-year old girl with metastatic DTC before (left) and after (right) effective radioiodine therapy

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postoperative radioiodine ablation in thyroid cancer

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