Transcript dr.ahmad ramadan RAI therapy

RADIOACTIVE IODINE
THERAPY IN THE TREATMENT
OF DIFFERENTIATED THYROID
CANCER
By
Ahmed Ramadan
Assistant Lecturer
Clinical Oncology & Nuclear Medicine Dep.
Mansoura University
Anatomy
2 lobes connected with
“isthmus”
Anterior to 2nd-4th tracheal
rings- C5-T1 vertebrae
Thyroid tends to increase
weight with age (N=20g)
Arteries: Superior, inferior
thyroid A.
Veins: Superior, middle, &
inferior thyroid V.
Hypothalamic-Pituitary-Thyroid Axis
Thyroid Cancer
Epidemiology



Papillary and follicular cancers are rare in
children and adolescents, and their incidence
increases with age in adults.
The median age at diagnosis is 45 to 50 years.
Thyroid carcinomas are two to four times as
frequent in women as in men.
Risk Factors
Radiation: High dose xrays or radioactive
Accident.
 Family History: Goiters or
Colon Growths
(Familial polyposis)
 Mutated RET gene
 Gender: Females
 Low iodine Levels
 Seafood/Shellfish
Consumption

Chernobyl (26-04-1986,
1:23 a.m.)
Pathological Types
Papillary Carcinoma
80%
 Follicular Carcinoma
15%
 Medullary Carcinoma
3%
 Anaplastic Carcinoma
2%

Differentiated Thyroid cancer
DTC
Papillary





unencapsulated tumor.
papillary and follicular structures
multicentric in 20 to 80 percent
of patients.
bilateral in about one third.
spreads through the lymphatics
within the thyroid to the regional
lymph nodes and, less frequently,
to the lungs.
Follicular





Encapsulated.
Follicular differentiation.
ranging from a welldifferentiated pattern to a poorly
differentiated pattern
Multicentricity and lymph-node
involvement are less frequent.
metastases to the lungs and
bones (20%) from hematologic
spread.
Presentation

Early disease:

Thyroid nodules or masses.
Cervical Lymph-nodes

Advanced disease:





Hoarseness,
Dysphagia,
Cough & dyspnea
Bony pains
Diagnosis

Imaging:

Ultrasound.
CT scan.
Thyroid scan

Laboratory:



TFTs, Ca
Routine labs
Thyroglobulin, Calcitonin

Pathological:



FNAC.
Trucut biopsy
Frozen

Endoscopy:




Laryngoscopy
Esophagoscopy
Prognosis





85% of patients with DTC :disease-free after initial
treatment
10–15% : recurrent disease
5%: distant metastases
Distant metastases :lungs (50%), bones (25%), lungs
and bones (20%) ,10-year-survival rates ranging from
25% to 42%
Overall 20yr survival 95%
Prognostic Factors
Clinical



Age: at diagnosis.
Recurrences common in
patients diagnosed when
they were less than 20 years
or older than 60 years.
Gender: Men are twice more
likely as women to die.
Tumor size: greater than 4 cm
have higher recurrence,
death.
Pathological



Certain histologic subtypes of PTC
have a worse prognosis (tall cell
variant, columnar cell variant, diffuse
sclerosing variant). Other poorly
differentiated aggressive tumor
histologies include trabecular, insular,
and solid subtypes
Local invasion: portends poorer
prognosis.
Distant metastases: associated with
an increase in the rate of disease
specific death.
Treatment Options
Surgery
 Thyroid Hormone
Suppressive Therapy
 External Beam
Radiation Therapy
 Radioactive Iodine
Therapy

Surgery



Completeness of surgical resection is an important
determinant of outcome, while residual metastatic lymph
nodes represent the most common site of disease
persistence or recurrence
Accurate postoperative staging is a crucial
element in the management of patients with
DTC
Both RAI whole-body scanning (WBS) and measurement
of serum Tg are affected by residual normal thyroid
tissue. Where these approaches are utilized for long-term
monitoring, near-total or total thyroidectomy is required
Surgery

There is agreement that therapeutic central and
lateral lymph node dissections should be performed
at the time of total thyroidectomy when lymph
nodes are suspicious or proved to harbor cancer by
sonographic appearance or by FNA analyses
preoperatively or when suspicious lymph nodes are
found at operation. Prophylactic lateral lymph node
dissections were common in the past, but have been
abandoned for several decades or longer.
Surgery
Surgery
Staging (TNM)
Primary Tumor (T)
Regional lymph nodes (N)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor 2 cm or less in greatest
dimension limited to the thyroid
T2: Tumor more than 2 cm but not
more than 4 cm in greatest
dimension limited to the thyroid
T3: Tumor more than 4 cm in greatest
dimension limited to the thyroid
T4: Tumor of any size extending
beyond the thyroid capsule
NX: Regional lymph nodes cannot be
assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
N1a: Metastasis in level VI cervical lymph
node(s)
N1b: Metastasis in unilateral, bilateral, or
contralateral cervical or mediastinal
lymph node(s)
Distant metastases (M)
MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis
Staging
Under 45 years:
Stage I
Any T, any N, M0
 Stage II
Any T, any N, M1

45 years and older:
Stage I :T1, N0, M0
 Stage II:T2, N0, M0
 Stage III: T3, N0, M0,
T1-3, N1a, M0
 Stage IV, T4,N0, M0
Any T, any N1b, M1

Risk Stratification
External Beam Radiotherapy
(EBRT)
The use of external beam irradiation to treat the primary
tumor should be considered in patients over age 45 with
grossly visible extrathyroidal extension at the time of
surgery and a high likelihood of microscopic residual
disease, and for those patients with gross residual tumor in
whom further surgery or RAI would likely be ineffective.
The sequence of external beam irradiation and RAI therapy
depends on the volume of gross residual disease and the
likelihood of the tumor being RAI responsive.
Recommendation rating: B
External Beam Radiotherapy
(EBRT)
Indications
 Non iodine avid disease.
 Cervical or mediastinal bulky nodes.
 Bone metastasis.
 Brain metastasis.
 Locally inoperable massive disease.
 Superior Vena Cava Obstruction.
Thyroid Suppressive Therapy
Low TSH levels reduce tumor growth rates and
reduce recurrence rates.
 Thyroxine, in the form of levothyroxine sodium,
should be given to all patients with thyroid
carcinoma, whatever the extent of thyroid
surgery and other treatment.
 The effective dose in adults is between 2.2 and
2.8 ug per kilogram of body weight.
 The adequacy of therapy is monitored by
measuring serum TSH three months after
treatment is begun.

Thyroid Suppressive Therapy

Initial TSH suppression to below
0.1mU/L is recommended for highrisk and intermediate-risk thyroid
cancer patients, while maintenance
of the TSH at or slightly below the
lower limit of normal (0.1–0.5mU/L)
is appropriate for low-risk patients.
RAI Treatment For
Thyroid Disorders









Thyroid Cancer: (DTC)
Papillary carcinoma
Mixed papillary-follicular carcinoma
Follicular carcinoma
(Hurthle’s cell carcinoma)
Hyperthyroidism:
Graves’ disease
Toxic adenoma
Multinodular toxic goiter (Plummer’s disease)
RAI 131





Physical half-life of 131I is 8.02 d.
Mainly emit B rays– 90% of radioactivity of 131I,
(and Gama rays).
Most of the radiation dose is delivered by Bparticles.
B-particles do not penetrate deep into tissue(2 mm
in depth, at most).
131I is available for oral ingestion as sodium iodine.
As liquid solution or in capsules.
RAI 131
RAI Treatment for DTC
Rationales of I-131 Ablation:
1. To destroy any residual microscopic
disease.
2. To increase specificity of subsequent 131I
scanning for detection of recurrent or metastatic disease
by elimination of uptake by residual normal tissue
3. To improve the value of measurements of serum
thyroglobulin as a serum marker derived only from
malignant thyroid cells.
4. The use of a large amount of iodine-131 for therapy
permits postablative iodine-131 total-body scanning, a
sensitive test for detecting persistent carcinoma.
RAI Treatment for DTC
Benefits of I-131 Therapy:
 Decreases local recurrence


Improves survival in patients following
local recurrence
Improve patients’ conditions with bone
metastases
RAI Treatment for DTC
Indications:
 Based on Risk stratification of individual patient, the
primary goal of the first dose of RAI after total
thyroidectomy may be
 Remnant ablation (to facilitate detection of recurrent
disease and initial staging),
 Adjuvant therapy (to decrease risk of recurrence and
disease specific mortality by destroying suspected, but
unproven metastatic disease)
 RAI therapy (to treat known persistent disease).
ESMO
American Thyroid Association
(ATA)
NCCN
RAI Treatment for DTC
Absolute Indications:
 RAI ablation is recommended for all patients with:

Inoperable tumour.
 Postoperative gross residual disease
 known nodal or distant metastases,
 gross extrathyroidal extension of the tumor regardless
of tumor size, or
 Primary tumor size >4 cm even in the absence of other
higher risk features
 Postoperative unstimulated Tg more than 5-10ng/L
RAI Treatment for DTC
Relative Indications:
 RAI ablation is recommended for selected patients with:

1–4cm thyroid cancers confined to the thyroid, have
documented lymph node metastases.
 other higher risk features( combination of age, tumor size,
lymph node status, and individual histology predicts an
intermediate to high risk of recurrence or death)
 histologic subtypes (such as tall cell, columnar, insular, and
solid variants, as well as poorly differentiated thyroid
cancer),
 the presence of intrathyroidal vascular invasion,
 the finding of gross or microscopic multifocal disease
RAI Treatment for DTC
Not indicated in:
 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.
RAI Treatment for DTC
RAI Dose prescription
 For ablation: 30-100 mCi
 Invasive properties adjuvant: 150 mCi
 LN met : 150 mCi
 Lung met: 150 mCi
 Bone met: 200 mCi
RAI Treatment for DTC
Dose Calculation (ATA recommendations):


The minimum activity (30–100 mCi) necessary to
achieve successful remnant ablation should be
utilized, particularly for low-risk patients.
If residual microscopic disease is suspected or
documented, or if there is a more aggressive tumor
histology (e.g., tall cell, insular, columnar cell
carcinoma), then higher activities(100–200 mCi)
may be appropriate.
RAI Treatment for DTC
Procedures:
 If > 30 mCi : Patient isolation for a few days
(usually 2-3 days) is necessary, ie. ADMISSION is
required!
 A post-therapy scan is recommended following RAI
remnant ablation - typically done 2–10 days after
therapeutic dose is administered
 Additional metastatic foci have been reported in
10–26% of patients scanned following high dose
RAI treatment compared with the diagnostic scan.
RAI Treatment for DTC
Procedures:
 Patient preparation: withdraw T4 for 4-6 weeks, or
T3 for 2 weeks before RAI Rx
 Low iodine-containing diet intake for 1 Wk
 On admission, prepare sour candies or fruits, etc
 Avoid radioactivity contamination to the body and
the room
 Frequent voiding after Rx esp. in the first few days.
RAI Treatment for DTC
Complications
 Early complications
 Acute radiation sickness
 Acute sialoadenitis
 Radiation thyroiditis
 Pain, hemorrhage & swelling in the metastases
 Transient BM suppression
 Late complications

Malignancies- leukemia 2% vs 0.1%
Follow-up of DTC Pts








Clinical history & physical examination
Blood Tests:
Serum thyroid hormones levels (TSH 0.1- 0.4 mIU/L)
Tumor marker ie. Tg (N < 1 ng/ml) & TgAb (N < 25
mIU/L)
Calcium balance, CBC
I-131 TBS at 6 mo-1 yr post Rx until till 2 scans are
normal
Other investigations eg. CXR-yearly, CT scan, MRI
Repeat RAI Rx: at least 6-12 months interval
Follow-up of DTC Pts




The protocol for follow-up of patients with well
differentiated thyroid cancer will differ from center to
center
initially seen at 6 month intervals
thyroid cancer has been successfully treated, with no
evidence for residual disease on physical examination,
scanning, or thyroglobulin testing, follow-up may be
scheduled at yearly intervals
At the same time as the scan is done, a blood test for
TSH and the thyroglobulin protein should also be done
Follow-up of DTC Pts
Follow-up of DTC Pts
Follow-up of DTC Pts
Follow-up of DTC Pts
Serum Thyroglobulin Measurements





Thyroglobulin is a glycoprotein that is produced only by
normal or neoplastic thyroid follicular cells.
It should not be detectable in patients who have undergone
total thyroid ablation, and its detection in such patients
signifies the presence of persistent or recurrent disease (an
excellent prognostic indicator).
The production of thyroglobulin is in part dependent on TSH.
Thus, when interpreting the serum thyroglobulin value, one
should take into account the serum TSH value, as well as the
presence or absence of thyroid remnants (neck US) .
If the serum thyroglobulin concentration is detectable during
thyroxine treatment, it will increase after the treatment has
been withdrawn.
Follow-up of DTC Pts
Locally Recurrent


For recurrent or regional nodal metastases
discovered on follow up WBS surgery is typically
used in the presence of bulky disease and
amenable to surgery on anatomic imaging.
RAI may be used adjunctively following surgery if
residual RAI avid disease is present or suspected.
Take Home Messages





DTC should be treated by a multidisciplinary team
including thyroid surgeon, nuclear medicine specialist,
endocrinologist, medical oncologist and radiation
oncologist.
DTC is a curable disease with long high survival rates
RAI131 therapy is a cheap, available and highly
effective treatment.
Surgery is the main station in treatment of DTC.
Most of cases will need ablative or adjuvant RAI
therapy.