Radioiodine dosage and modality

John T. Koutsikos, MD, PhDNuclear Medicine Physician

Conflict of Interest

NOTHING TO DECLARE

Introduction

Radioiodine has been used in the management of patients with well-differentiated thyroid cancer since the 1940s.

Saul Hertz

Introduction

Iodine (I-131) causes acute thyroid-cell death by emission of short path-length (1 to 2 mm) beta rays.

I-131 must be taken up by thyroid tissue to be effective.

As a result, it is of no value in patients whose thyroid cancers do not concentrate iodine, i.e. patients with medullary cancer, lymphoma, or anaplastic cancer.

General treatment recommendations

The treatment of choice for patients diagnosed with thyroid cancer is surgery, when possible.

Usually, surgery is followed by treatment with radioiodine and thyroxine therapy.

Generally, radiation therapy and chemotherapy do not have a prominent role in the treatment of thyroid cancer.

Goals of initial therapy of DTC

The basic goals of initial therapy for patients with DTC are to: improve overall and disease-specific survival, reduce the risk of persistent/recurrent disease and

associated morbidity, permit accurate disease staging and risk

stratification, while minimizing treatment-related morbidity and unnecessary

therapy.

Staging and Treatment of DTC

The recommended treatment depends on the stage of

differentiated thyroid cancer and the risk of

recurrence.

This risk varies from very low to high.

The treatment may differ from the general statements,

for reasons related to patients’ individual

circumstances.

Systems of staging / risk evaluation

They are similar to one another but not identical,

indicating our lack of precise long-term outcome

data for all the variables

They remain valuable for prognostic purposes

and in considering therapeutic options.

Using several prognostic fractors such as age,

grade, tumor size, metastasis, etc.

GUIDELINES

Can we rely on staging systems

very much?

Goals of radioiodine administration

2015 ATA guidelines

Post-Surgical RAI Indicated?

2015 ATA guidelines

Post-Surgical RAI Indicated?

Post-Surgical RAI Indicated?

2012SNMMIguidelines

Selection of Activity

2012 SNMMI guidelines

2012 SNMMI guidelines Ablation of thyroid bed remnants

30-100 mCi

Treatment of DTC in the cervical or mediastinal lymph nodes– 150-200 mCi

Treatment of distant metastases– 200 mCi or more

Limited Use Selected Use Definite UseATA low-risk ATA low-

intermediate riskATA high-risk

<45 yrs<2 cm

≥45 yrs≥2cm

Gross invasionResidual disease

No LN or invasion

Positive LN LN invasionDistant mets

No RAI (or 30mCi?)

rhTSH RAI(30-50 mCi)

Wthdr RAI(dosimetry?)

RemnantAblation

Adjuvant Therapy

Therapy

2015 ATA guidelines

ESTIMABL (Fr) and HiLo (UK) studiesN Engl J Med, May 2012

Both randomised studies have shown effective remnant ablation using lower RAI dose (30 mCi)

Low vs High RAI dose for remnant ablation: a Meta-Analysis Cheng W et al, JCEM 98:1353, 2013

9% lower successful ablation rate was identified in low doses than

in high doses, though not reaching any significance (RR, 0.91;

95% CI, 0.79–1.04; P = 0.15).

Clin Nucl Med. 2015 Oct;40(10):774-9.

The rate of complete ablation of high activities was statistically significant higher than that of low

activities (RR, 0.89; 95% CI, 0.81–0.97; P = 0.008)

J Clin Endocrinol Metab 99: 4487– 4496, 2014

1298 DTC patients were included (698 low risk, 434 high risk M0, and 136 M1)

grouped according to ablation activity– I ≤ 54 mCi– II 54 – 81 mCi– III > 81 mCi

subdivided by age ( <45 y and >45 y at diagnosis)

There were no long-term (10-15 year) overall survival or disease-specific survival differences in younger patients (<45 yo) who received lower administered activities of 131I (≤54 mCi) compared with those receiving higher administered activities

The older patients (> 45 yo), however, who received lower administered activities of 131I (≤54 mCi) did have a lower disease-specific survival compared with those receiving higher administered activities.

DTC-specific survival in low-risk patients Recurrence-free survival in high-risk patients

without distant metastases

DTC-specific survival in high-risk pts

without distant metastases

older patients> 45 yo

 

Fallahi B. et al.Low versus high radioiodine dose in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid carcinoma: a large randomized clinical trial.

In the low-dose group, more patients needed a second dose of I-131, resulting in a higher cumulative activity (median, 4810 vs. 3700 MBq, P<0.0001).

The higher dose of I-131 (3700 MBq) resulted in successful ablation more often than the low dose (1110 MBq).

Nucl Med Commun. 2012 Mar;33(3):275-82.

Can we rely on guidelinesvery much?

Radioactive iodine uptake measurements

Neither the ATA or ETA guidelinesrecommend this test

SNMMI

2012

Radioactive iodine uptake measurements

“…, depending on the radioiodine uptakemeasurement and amount of residualfunctioning tissue present”

Case 1

Female, 20 y.o. June 2014 total thyroidectomy (general surgeon) Histology: papillary carcinoma

– 0.9 cm l.l. (diffuse sclerosing) and– 0.5 cm r.l. – 2 ln’s not metastatic

Case 1

I-131? YES What dose? > 100 mCi

Case 1

U/S: no findings (no residual thyroid tissue, no ln’s) TSH 127.8 μIU/ml Tg 19.2 ng/ml Anti-Tg: (-)ve Uptake measurement Yes? No?

Uptake measurement (60 μCi I-131)

Thyroid Uptake = 14,3 %

Next what?

Surgery ?

Low Dose I-131 ?

30 mCi I-131

Post ablation WBS

Follow-up

June 2015 TSH 0.2 μIU/ml Tg < 0.1 ng/ml Anti-Tg: (-)ve U/S: (-)ve WBS (5 mCi I-131) with rh-TSH

WBS (5 mCi I-131)

Tg = 0.2 ng/ml

Guidelines usually are formulated by physicians from international centers of excellence, and may not be fully applicable elsewhere

HOMESWEETHOME

U/S

SurgeonEndocrinologist

Frangos S, Iakovou IP, et. alEur J Nucl Med Mol Imaging. 2015 Dec;42(13):2045-55

“… putatively “low-risk” DTC patients frequently had higher-risk features, or characteristics confounding risk stratification. This finding suggests that outside international centres of excellence, limitations in surgical experience and in histopathology reporting may cast important doubt on such patients’ “low-risk” classification.”

Can we rely on guidelinesvery much?

Part II - Modality

Molecular Marker Status

Low-iodine diet

Hormone withdrawl

rh-TSH

What is the role of molecular marker status in therapeutic RAI decision-making?

Has yet to be established.

Can’t be recommended at this time.

The ESTIMABL2 study will analyze the

relevance of BRAF status on outcome.

Of the 97 T1aN0M0 pts who received post-op RAI, the rate of biochemical persistence of disease (defined by a stimulated thyroglobulin of >1 ng/mL), was 13% in the 39 BRAF positive patients and 1.7% in the BRAF negative patients.

To distinguish those pts who require less or more aggressive treatments.

J Clin Endocrinol Metab. 2012; 97:4390- 4398

Low-iodine diet

The purpose of a low-iodine diet is to

deplete the body of its stores of iodine, to

help increase the effectiveness of the

radioactive iodine 

Is a low-iodine diet necessary before remnant ablation?

Dietary Sources of Significant Amounts of Iodine

Pharmaceuticals Blocking Radioiodine Uptake

To withdraw or not to withdraw[To rhTSH or not to rhTSH]

ESTIMABL (Fr) and HiLo (UK) studiesN Engl J Med, May 2012

Both studies have shown equal results either using withdrawal or rhTSH stimulation of RAI uptake

As a result of these studies the use of rhTSH was expanded for the RAI range 30-100 mCi in Europe (Dec 2012)

Recurrence rate in the same subgroups

Take home message

70 years Nuc Med & DTC

Thank you!