3. ⢠Physical half-life of 131I is 8.02 d.
⢠Mainly emit B raysâ 90% of radioactivity of
131I, (and Gama rays)
⢠131I is available for oral ingestion as sodium
iodine
4. ⢠Most of the radiation dose is delivered by Bparticles
⢠B-particles do not penetrate deep into tissue(2
mm in depth, at most)
⢠Gama-radiation contributes only 10% of the total
radiation dose, fraction of gama-rays âabsorbed
by functioning tyhroid tissue and vast majority
leaving via skin surface-Detected by a radiation
detector
5. ⢠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
⢠Simultaneous ingestion large amounts of water
attenuates radiation dose emitted to gastric wall
⢠Rapidly and completely absorbed in the upper
intestine
7. 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- cotransport system.
⢠Iodide taken up by the thyroid gland is oxidized by
peroxide in the lumen of the follicle:
peroxidase
I-
I+
⢠Oxidized iodine can then be used in production of
thyroid hormones.
8.
9. 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:
â iodine uptake, via the sodium-iodide symporter (NIS),
is always decreased and is undetectable in about a
third of patients;
â Iodine organification is markedly reduced;
â Effective half-life of iodine in tumor tissue is always
shorter
10. ⢠Tissues that often take up iodine and can be
misconstrued as metastases include the
â salivary glands in the mouth,
â esophagus (as a result of swallowing radioactive
saliva),
â thymus gland,
â breasts in some women,
â liver, stomach, colon, bladder
11. Prerequisites
⢠TSH of >30mU/L is associated with increased
RAI uptake in tumors
â withdrawal of LT-3for 2 weeks, or
â discontinuation of LT-4for 3 weeks
â rhTSH stimulation
12. Enhancing radioiodine uptake
⢠Low iodine diet
⢠Lithium - 10 mg/kg/day for 7 days. To keep S. Lithium levels at
0.8-1.2 mmol/L)
â Lithium had been shown to reduce exit of iodine from
normal thyroid cells
⢠Retinoic acid (1.2 mg/kg/day) â retinoids -apparently
redifferentiate thyroid cancer cells - enhanced
radioiodine uptake
Other agents:
⢠Based on increasing NIS expression in thyroid cancer cells
Histone deacetylate inhibitors
Demethylating agents
14. ⢠Post operative diagnostic I 131 scan â
â Doses less than 5 mCi â unlikely to miss out
treatable foci of disease
â Large dose causes stunning
We use 50 micro curie 131I(one capsule orally)
Do the neck uptake scan using a rectilinear scan.
If uptake <4% - proceed with WBS
WBS- 2 mci used as a solution. Drink with straw.
15. Stunning effect
⢠Stunning is defined as a reduction in uptake of
the 131I therapy dose induced by a
pretreatment diagnostic activity.
⢠Occurs most prominently with higher activities
(5â10 mCi) of 131I ,with increasing time
between the diagnostic dose and therapy
⢠Does not occur if the treatment dose is given
within 72 hours of the scanning dose.
16. ATA guidelines
⢠Based on Risk stratification of individual
patient,
⢠The primary goal of the first dose of RAI after
total thyroidectomy may be
â Remnant ablation (to facilitate detection of
recurrent disease and initial staging),
â Adjuvant therapy (to decrease risk of recurrence
and disease specific mortality by destroying
suspected, but unproven metastatic disease)
â RAI therapy (to treat known persistent disease).
17. Radio iodine abalation
Ablation of small amount of residual normal thyroid
remaining after surgery, left behind inadverently
or deliberately
May facilitate the
â early detection of recurrence based on serum Tg
â RAI WBS
18. ATA recommendations
⢠RAI ablation is recommended for all patients
with
â known distant metastases,
â gross extrathyroidal extension of the tumor
regardless of tumor size, or
â Primary tumor size >4 cm even in the absence of
other higher risk features
19. ATA recommendations
⢠RAI ablation is recommended for selected
patients with
â 1â4cm thyroid cancers confined to the thyroid,
â have documented lymph node metastases,
â 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
20. 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.
22. MD anderson experience
⢠1599 patient outcome analysis for various
treatment for differentiated thyroid Ca
⢠46% had radioiodine therapy
⢠Treatment with radioiodine was the single most
powerful prognostic indicator for increased DFS
(p< 0.001)
⢠Its use significantly increased the survival both
low and high risk group
⢠Adult patients , females with intrathyroidal
papillary carcinoma treated with TT + RAI
between 20-59yrs â best prognosis
J Clin Endocrinol Metab. 1992 Sep;75(3):714-20.
23. ⢠Decision analytic model -examine whether
apparently localized thyroid carcinoma pts
should receive RAI
â RAI modestly improves life expectancy by 2 to 15
months.
â benefit of reduction in likelihood of recurrence
outweighs risk of leukemia.
Wong et al ,Endocrinol Metab Clin North Am. 1990 Sep;19(3):741-60
Ablative radioactive iodine therapy for apparently localized thyroid
carcinoma,Massachusetts..
24. ⢠1004 dtc- Followed up with
â RAI â 151
â thyroid hormone alone 755
â no postoperative medical therapy -98
Tumor recurrence ~ threefold lower p < 0.001in RAI vs
other treatment
Fewer patients developed distant metastases (p < 0.002)
Significantly more pronounced in t>/=1.5cm
Mazzaferri EL et al: Thyroid remnant 131I ablation for papillary and
follicular thyroid carcinoma; Thyroid. 1997 Apr;7(2):265-71
25. ⢠Methods of abalation
â Low dose â 30mCi
â 0-92% complete abalation.
Adv:Low cost, Reduced radiation exposure
â High dose â 80-150mCi
â Given as inpatient therapy
â Calculated dose abalation
â Individualised treatment- not a standard dose of
RAI but a standard dose of radiation to the bed.
26. National Thyroid Cancer Treatment Cooperative
Study Group (NTCTCSG)
⢠2936 patients , median follow-up of 3years
⢠Near-total thyroidectomy followed by RAI therapy
and aggressive thyroid hormone suppression
therapy predicted improved overall survival of
patients with NTCTCSG stage III and IV disease
⢠Also beneficial for patients with NTCTCSG stage II
disease
⢠No impact of therapy was observed in patients
with stage I disease
27.
28. Mayo clinic experience
⢠Review of more than 2,500 patients at the Mayo
Clinic between 1940 and 2000 having under gone
surgery and RRA
⢠RRA did not significantly improve the outcome
(either Cause specific mortality or Tumour
Reccurence ) in low-risk (MACIS < 6) patients
previously treated with initial near-total or total
thyroidectomy
⢠They discouraged the routine use of RRA in such
patients.
29. HiLo trial
⢠Multicentric study in UK
â Comparing low dose vs high dose radio iodine
â Thyrotropin alpha vs thyroid hormone withdrawal
⢠Inclusion Criteria
â stage T1 to T3N0/N+ but no distant metastasis
â total thyroidectomy, with or without central
lymph-node dissection
30. ⢠4 arms
â low-dose(220) or high-dose radioiodine(218),
â each combined with thyrotropin alfa (219)or
thyroid hormone withdrawal(219).
Thyroid hormone withdrawal, thyroxine was
discontinued 4 weeks before ablation
Thyrotropin alfa-intramuscular injection (0.9
mg)x2days prior to scan
31.
32. ⢠Preablation radionuclide scan technetium99m pertechnetate IV-to assess remnant size
⢠Whole-body iodine-131 scan- performed 3 to
7 days after ablation -gamma camera
⢠Diagnostic whole-body scan- performed 6 to 9
months after ablation â with iodine-131
33. ⢠Primary end point
â success rate for ablation -defined as both a
negative scan (<0.1% uptake over the thyroid bed)
and a thyroglobulin level of less than 2.0 ng per
milliliter at 6 to 9 months.
â One of these criteria used if other not available
⢠Secondary end points
â were the number of days of hospitalization;
adverse events during ablation and 3 months after
ablation
34. Results
⢠Ablation was successful in
â 182 / 214 patients (85.0%) in low-dose radioiodine vs
â 184 / 207 patients (88.9%) in the high dose groups
⢠The difference in the success rate for this
comparison was
â â2.7 percentage points on the basis of scanning
results alone and
â â3.8 percentage points on the basis of both scanning
results and thyroglobulin level
35. Results
⢠Success rates were also similar in thyrotropin
alfa vs thyroid hormone withdrawal successful ablation
â 183 of 210 patients (87.1%) in the thyrotropin
alfa group versus
â 183 of 211 patients (86.7%) in the group
undergoing thyroid hormone withdrawal
36. ⢠The treatment effects for stage T3 tumors or
lymph-node involvement were consistent with
those for all patients.
⢠â0.7 percentage points for patients with stage
T3 tumors and 4.9 percentage points for those
with lymph-node involvement
37. ⢠Adverse events were 21% in the low-dose
group versus 33% in the high-dose group
(P=0.007)
⢠More patients in the high-dose group than in
the low-dose group were hospitalized for at
least 3 days (36.3% vs. 13.0%, P<0.001)
38. Draw backs
⢠Exclusion criteria
â the presence of aggressive malignant variants,
including tall-cell, insular, poorly differentiated,
and diffuse sclerosing thyroid cancer
⢠Results relate to ablation success at 6 to 9
months and do not address future recurrences
40. ATA recommendations
⢠The minimum activity (30â100 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(100â200 mCi) may be appropriate.
41. ⢠A posttherapy scan is recommended following
RAI remnant ablation - typically done 2â10
days after therapeutic dose is administered
⢠Additional metastatic foci have been reported
in 10â26% of patients scanned following high
dose RAI treatment compared with the
diagnostic scan.
42. ⢠Disease not visualized on DxWBS, regardless of
the activity of 131I employed, may occasionally
be visualized on RxWBS images.
⢠Following RAI ablation, when the posttherapy
scan does not reveal uptake outside the thyroid
bed, subsequent DxWBS have low sensitivity and
are usually not necessary in low-risk patients who
are clinically free of residual tumor and have an
undetectable serum Tg
43. ⢠Post 1st RxWBS(post RAI), low-risk patients
with an undetectable Tg on thyroid hormone
with no Anti Tg antibodies , negative US do
not require routine DxWBS during follow-up
44. Radio iodine therapy
⢠For regional nodal metastases discovered on
DxWBS
⢠Surgery is typically used in the presence of bulky
disease and amenable to surgery on anatomic
imaging
⢠RAI may be employed âadjunctively following
surgery for regional nodal disease or aero
digestive invasion if residual RAI avid disease is
present or suspected.
45. ⢠Three approaches to 131I therapy:
â empiric fixed amounts,
â therapy determined by the upper bound limit of
blood and body dosimetry and
â quantitative tumor dosimetry
46. Indications of RAI therapy
â˘
â˘
â˘
â˘
â˘
Inoperable tumour
Postoperative gross residual disease,
Extrathyroidal spread,
Locoregional spread to the nodes
Distant metastasis
47. ⢠Max safe dose: <200 to blood
⢠Retained not more than 120mCi-whole body 48hrs
51. Immediate:
1)Neck swelling/edema 24-48 hrs
⢠More if there is substantial mass of thyroid
left behind
⢠Responds well to steroids
⢠Rarely may need tracheostomy, may develop
thyroid storm.
2) Sialadenitis âplenty of water, lemon.
52. Side effects
⢠Nausea, Loss of taste or dysgeusia- often last
few days
⢠Sialadenitis-pain and enlargement of salivary
glands, rarely progress to chronic xerostomia
â Prophylaxis -ingestion of large quantities of fluids
sialogogues- lemon juice or chewing gum
⢠Teratogenicity - recommended that
conception be delayed for 1 y after
therapeutic administrations of I131