Thyroid abalation
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This document discusses the use of radioactive iodine (131I) for diagnosis and treatment of thyroid cancer. Some key points: - 131I localizes in thyroid tissue and can be used to ablate thyroid remnants after surgery or treat thyroid cancer metastases. It emits beta and gamma radiation. - For remnant ablation, lower doses (30-100 mCi) are usually sufficient while higher doses (100-200 mCi) may be needed for more aggressive cancers. Success rates are similar between low vs high doses and thyroid hormone withdrawal vs rhTSH. - Post-therapy scans 2-10 days after treatment can identify additional metastases not seen on diagnostic scans in 10-26% of
Thyroid abalation
- 2. • Introduced by Seidlin et al. in 1946
- 3. • Physical half-life of 131I is 8.02 d. • Mainly emit B rays– 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 –absorbed 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
- 6. • Picture of the capsule to be added
- 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.
- 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: – 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
- 10. • 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
- 11. Prerequisites • TSH of >30mU/L is associated with increased RAI uptake in tumors – withdrawal of LT-3for 2 weeks, or – discontinuation of LT-4for 3 weeks – 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) – Lithium had been shown to reduce exit of iodine from normal thyroid cells • Retinoic acid (1.2 mg/kg/day) – 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
- 13. To be avoided • FOOD SUPPPLEMENTS • Iodised salt/Salty food-potato chips,nuts • Sea food • • • • DRUGS 1)iodex 2)amiodarone 3)Contrast medias(avoid CT scans)
- 14. • Post operative diagnostic I 131 scan – – Doses less than 5 mCi – unlikely to miss out treatable foci of disease – 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 (5–10 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 – 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).
- 17. Radio iodine abalation Ablation of small amount of residual normal thyroid remaining after surgery, left behind inadverently or deliberately May facilitate the – early detection of recurrence based on serum Tg – RAI WBS
- 18. ATA recommendations • RAI ablation is recommended for all patients with – known 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
- 19. ATA recommendations • 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
- 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.
- 21. ATA guidelines
- 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 – 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 – RAI modestly improves life expectancy by 2 to 15 months. – 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 – RAI – 151 – thyroid hormone alone 755 – 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 – Low dose – 30mCi – 0-92% complete abalation. Adv:Low cost, Reduced radiation exposure – High dose – 80-150mCi – Given as inpatient therapy – Calculated dose abalation – 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
- 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 – Comparing low dose vs high dose radio iodine – Thyrotropin alpha vs thyroid hormone withdrawal • Inclusion Criteria – stage T1 to T3N0/N+ but no distant metastasis – total thyroidectomy, with or without central lymph-node dissection
- 30. • 4 arms – low-dose(220) or high-dose radioiodine(218), – 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
- 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 – with iodine-131
- 33. • Primary end point – 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. – One of these criteria used if other not available • Secondary end points – were the number of days of hospitalization; adverse events during ablation and 3 months after ablation
- 34. Results • Ablation was successful in – 182 / 214 patients (85.0%) in low-dose radioiodine vs – 184 / 207 patients (88.9%) in the high dose groups • The difference in the success rate for this comparison was – −2.7 percentage points on the basis of scanning results alone and – −3.8 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 – 183 of 210 patients (87.1%) in the thyrotropin alfa group versus – 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. • −0.7 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 – 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
- 39. Meta Analysis
- 40. 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.
- 41. • A posttherapy 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.
- 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 –adjunctively 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: – empiric fixed amounts, – therapy determined by the upper bound limit of blood and body dosimetry and – quantitative tumor dosimetry
- 46. Indications of RAI therapy • • • • • 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
- 48. Cervical nodes • Fixed dose format – 150 mci – upto 200 • Quantitative dosimetry Pulmonary metastasis Skeletal metastasis
- 49. • The most common distant metastatic sites are lungs, spine, and appendicular bone.
- 50. Side effects • Immediate • Delayed
- 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 –plenty 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 – 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