Radioactive Iodine therapy in the treatment of differentiated Thyroid cancer - PowerPoint Presentation

Radioactive Iodine therapy in the treatment of differentiated Thyroid cancer By Ahmed Ramadan Assistant Lecturer Clinical Oncology & Nuclear Medicine Dep. Mansoura University

Anatomy2 lobes connected with “isthmus” Anterior to 2nd-4th tracheal rings- C5-T1 vertebraeThyroid 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 1% of all cancers Very high survival rates Many treatment options Papillary and follicular (differentiated) thyroid carcinomas are among the most curable cancers. DTC: Slow growing, TSH sensitive, take up iodine, TSH stimulation produces thryroglobulin response.

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 x-rays or radioactive Accident. Family History: Goiters or Colon Growths (Familial polyposis)Mutated RET geneGender: 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 cancerDTC 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. Encapsulated. Follicular differentiation. ranging from a well-differentiated pattern to a poorly differentiated pattern Multicentricity and lymph-node involvement are less frequent. metastases to the lungs and bones (20%) from hematologic spread. Papillary Follicular

Presentation Early disease: Thyroid nodules or masses. Cervical Lymph-nodes Advanced disease: Hoarseness, Dysphagia , Cough & dyspnea Bony pains

Diagnosis Imaging: Ultrasound. CT scan.Thyroid scanLaboratory: 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 TherapyRadioactive 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 recurrenceAccurate postoperative staging is a crucial element in the management of patients with DTCBoth 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

SurgeryThere 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) 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 Regional lymph nodes (N) 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 high-risk 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 ForThyroid Disorders Thyroid Cancer: (DTC) Papillary carcinomaMixed papillary-follicular carcinomaFollicular carcinoma ( Hurthle’s cell carcinoma) Hyperthyroidism: Graves’ disease Toxic adenomaMultinodular 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 B-particles.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 tissue3. 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 recurrenceImprove 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 beRemnant 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 diseaseknown 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 DTCNot 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 mCiInvasive properties adjuvant: 150 mCiLN met : 150 mCiLung 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 administeredAdditional 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 WkOn admission, prepare sour candies or fruits, etcAvoid radioactivity contamination to the body and the roomFrequent voiding after Rx esp. in the first few days.

RAI Treatment for DTC Complications Early complications Acute radiation sicknessAcute sialoadenitisRadiation thyroiditisPain, 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, CBCI-131 TBS at 6 mo-1 yr post Rx until till 2 scans are normalOther investigations eg. CXR-yearly, CT scan, MRIRepeat 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 RecurrentFor 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 MessagesDTC 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.

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