Both radioactive iodine and

external beam radiation can

play roles in well-differentiated

thyroid cancer.

Rebecca Kinkead. Hula No. 3 (detail), 2010. Oil on canvas, 45⬙ × 37⬙.

A Risk-Adapted Approach to the Use of

Radioactive Iodine and External Beam Radiation in the
Treatment of Well-Differentiated Thyroid Cancer
R. Michael Tuttle, MD, Geneviève Rondeau, MD, and Nancy Y. Lee, MD

Background: Both radioactive iodine (RAI) and external beam radiation therapy (EBRT) offer important clinical
benefits in properly selected patients with differentiated thyroid cancer. With the increased emphasis on a risk-adapted
model for the management of thyroid cancer, it is important to identify which patients are most likely to benefit from
radiation therapies given in the adjuvant setting and as treatment of gross residual disease.
Methods: This review compares the authors’ current management practices with the recommendations of published
guidelines from both the National Comprehensive Cancer Network and the American Thyroid Association.
Results: Because of the lack of prospective randomized studies on either RAI or EBRT in differentiated thyroid cancer,
recommendations must be based on retrospective cohort studies that vary in selection criteria, histologies, sample
size, inclusion criteria, and follow-up.
Conclusions: RAI has an important adjuvant therapy and treatment function in properly selected patients. Likewise,
EBRT is associated with increased locoregional control and palliative therapeutic effects in high-risk patients.

Introduction proach to thyroid cancer management, a risk-adapted

While certainly not a new concept, a risk-adapted ap- approach relies on a more precise understanding of the
proach in the management of thyroid cancer has received clinicopathological factors that predict the risk of recur-
renewed interest in the last 10 years. A risk-adapted ap- rence and/or mortality. In this approach, the risks and
proach tailors the extent and intensity of initial therapy benefits of potential additional therapies are balanced
according to individualized risk estimates of recurrence against the specific risks of recurrence and mortality, as
and mortality.1-3 As opposed to a “one size fits all” ap- well as the response to therapy for individual patients.
This risk-adapted approach is easily identified in the
From the Departments of Endocrinology (RMT, GR) and Radiation updated American Thyroid Association (ATA) guidelines,4
Oncology (NYL) at the Memorial Sloan-Kettering Cancer Center, where the most important initial management recom-
New York, New York. mendations are based on specific clinicopathologic risk
Submitted March 15, 2010; accepted August 11, 2010. factors rather than being a uniform recommendation
Address correspondence to R. Michael Tuttle, MD, Endocrinology for all thyroid cancer patients regardless of risk analysis.
Service, Department of Medicine, Memorial Sloan-Kettering Cancer
Center, Zuckerman Building, Room 834, 1275 York Avenue, New These include recommendations with regard to extent
York, NY 10021. E-mail: tuttlem@mskcc.org of initial surgery (recommendation 26), degree of initial
Dr Tuttle receives grants/honoraria from Genzyme Corp and also thyroid-stimulating hormone (TSH) suppression (rec-
serves as a consultant. Dr Rondeau receives research support from ommendation 40), indications for central neck dissec-
Genzyme Corp. Dr Lee reports no significant relationship with the
companies/organizations whose products or services may be refer- tion (recommendation 27), completion thyroidectomy
enced in this article. (recommendation 29), radioactive iodine (RAI) remnant

April 2011, Vol 18, No. 2 Cancer Control 89

ablation (recommendation 37), and external beam radia- ease in the neck or distant metastases).9 In the adjuvant
tion therapy (EBRT) (recommendation 41). Furthermore, setting, the goals of radiation therapy are to reduce the
the most important management issues with regard to risk of both locoregional and distant recurrence and to
the clinical follow-up of thyroid cancer patients are also prolong overall survival. In addition, the ablation of any
based on the risk of recurrence and disease-specific mor- residual normal thyroid tissue with RAI may also facilitate
tality for individual patients. These issues range from the initial staging (post-therapy RAI whole body scanning)
need for stimulated thyroglobulin (Tg) during follow-up and allow for more sensitive detection of recurrent dis-
(recommendation 45) to the role of diagnostic whole ease (suppressed and TSH-stimulated Tg measurements)
body scans (recommendations 46 and 47), neck ultra- in properly selected patients.4 When used to treat gross
sonography (recommendation 48), long-term TSH goals residual disease, radiation therapy is seldom curative but
(recommendation 49), and additional therapies (recom- can have significant palliative effects with regard to local
mendations 59 and 77). invasive or compressive symptoms and pain control.9,10
Similarly, the NCCN guidelines also provide recom-
mendations based on risk of recurrence and disease- The Role of RAI in the Treatment of
specific mortality regarding many of the most impor- Differentiated Thyroid Cancer
tant management decisions. For example, individualized RAI as Adjuvant Therapy
recommendations based on risk are provided for the While the first dose of RAI administered after a total
degree of TSH suppression (THYR-A), extent of initial sur- thyroidectomy has traditionally been referred to as RAI
gery (PAP-1), indications for completion thyroidectomy remnant ablation, we prefer to describe the primary
(PAP-2), indications for RAI ablation (PAP-3), administered function of this first dose as either remnant ablation,
activity of RAI (PAP-4), and the need for stimulated Tg, adjuvant therapy or therapy of macroscopic disease.
whole body scanning, and other cross-sectional imaging Remnant ablation is used to define the clinical scenario
for detection of disease recurrence (PAP-5). in which the goal of therapy is simply to destroy the re-
The most commonly used risk stratification sys- sidual thyroid tissue in an effort to facilitate staging and
tems, such as MACIS (metastases, age, completeness of follow-up. These patients are not thought to be at high
resection, invasion, and size) and the TNM system of risk for persistent micrometastatic disease and therefore
the American Joint Committee on Cancer (AJCC), were are given the lowest administered activity that is likely to
designed to predict disease-specific mortality rather achieve ablation of the normal thyroid remnant (usually
than risk of recurrence.5,6 Therefore, the updated ATA between 50 and 75 mCi). We use the term adjuvant
guidelines recommend using a separate postoperative therapy to refer to the first dose of RAI given in patients
clinicopathologic staging system, in addition to the AJCC we consider to be at significant risk of having as yet unde-
TNM system, to improve prognostication and to better tected micrometastases.8 In these patients, administered
tailor follow-up for differentiated thyroid cancer patients activities between 100 and 150 mCi of RAI will not only
(recommendation 31).4 facilitate initial staging and follow-up, but also provide
It is our view that accurate risk estimates coupled a potentially tumoricidal dose of RAI that could result
with realistic expectations of the benefits and risks of in lower recurrence rates and improved overall survival.
proposed therapies allow the clinician and the patient Finally, the phrase therapy of macroscopic disease refers
to develop a treatment and follow-up plan designed to to those few patients with persistent macroscopic dis-
provide maximum benefit to high-risk patients while min- ease remaining after total thyroidectomy and appropriate
imizing treatment-related side effects and unnecessary lymph node dissection (either locoregional disease or
treatments in low-risk patients. To this end, we review distant metastases) in whom the primary goal of treat-
a risk-adapted approach to the use of RAI and EBRT in ment is destruction of macroscopic disease. In these
the management of differentiated thyroid cancer in order patients, higher administered activities of RAI may be
to compare our current management practices with the warranted depending on the amount of residual normal
current recommendations published by the ATA4 and tissue in the thyroid bed, the age of the patient, comorbid
the National Comprehensive Cancer Network (NCCN).7 disease status, and the expectation that the tumor will be
RAI-avid. Obviously, the distinction between the three
Potential Roles of Radiation Therapy RAI functions (ablative, adjuvant therapy, and therapy of
(EBRT or RAI) in Thyroid Cancer macroscopic disease) is somewhat arbitrary and overlap-
From an oncologic perspective, there are two major po- ping. However, we find that the use of these terms helps
tential roles for radiation therapy in the management of define the goals of initial therapy, thereby significantly
differentiated thyroid cancer: as adjuvant therapy for impacting the recommended administered activity.4
potential, residual microscopic disease remaining after The data with regard to the impact of adjuvant RAI
appropriate surgical resection8 or as part of multimodal- therapy on recurrence and overall survival are conflicting
ity therapy for gross residual disease not amenable to at best.4,11 Without randomized prospective clinical tri-
definitive surgical resection (either as locoregional dis- als to address this issue, treatment recommendations are

90 Cancer Control April 2011, Vol 18, No. 2

largely based on several large retrospective clinical stud- from RAI ablation. However, for many of the TNM stages,
ies, each with its own associated strengths, weaknesses, data are “conflicting” with regard to whether or not a
and treatment biases. In most studies, low-risk patients benefit can be expected in terms of decrease in recur-
seemed to gain little or no improvement in recurrence rence from the use of RAI as adjuvant therapy. Because
rates or overall survival from the routine use of RAI as of conflicting data, it is impossible to provide a definitive
adjuvant therapy. Conversely, most studies demonstrate recommendation either for or against the routine use of
benefit from RAI in patients with high risk of recurrence RAI in these subgroups. Therefore, clinical judgment is
or death. In an effort to conceptualize the expected ben- required to determine when the risk of recurrence is
efits of the first dose of RAI across the wide spectrum of high enough to warrant adjuvant RAI therapy, in which
thyroid cancer presentations, the updated ATA guidelines support in the literature is best described as “conflicting.”
taskforce developed a table that provides the rationale Additional factors that could sway a decision toward
for therapy as well as the strength of evidence either RAI as adjuvant therapy in these groups with conflict-
for or against the use of adjuvant RAI based on the TNM ing data could include other high-risk features such as
staging system (Table 1 and Table 2).4 more aggressive histologies (eg, follicular thyroid cancers
As can be seen from Table 1, routine use of RAI as ad- with more than minimal capsular invasion, Hürthle cell
juvant therapy is consistently associated with a decreased thyroid cancers, tall cell variants, poorly differentiated
risk of recurrence and death only in those patients with histologies), the presence of vascular invasion, or the
high-risk disease (older patients with T3 lesions, any age presence of significant microscopic extrathyroidal exten-
with gross extrathyroidal extension, or the presence of sion not appreciated as gross extrathyroidal extension
distant metastases). With regard to decreasing the risk of intraoperatively.
recurrence, there is uniform agreement that small tumors While RAI has been safely used in the therapy of thy-
confined to the thyroid (T1a, < 1 cm, N0) do not benefit roid cancer for more than 50 years, it is not without side

Table 1. — Major Factors Impacting Decision Making in RAI Remnant Ablation

Factors Description Expected Benefit RAI Ablation Usually Strength of

Recommended Evidence**
Decrease Risk of Decrease Risk of May Facilitate Initial
Death Recurrence Staging and Follow-up
T1a 1 cm or less, No No Yes No E
intrathyroidal
T1b 1 to 2 cm, No Conflicting data* Yes Selective use* I
intrathyroidal
T2 > 2 to 4 cm, No Conflicting data* Yes Selective use* C
intrathyroidal
T3 > 4 cm
age < 45 yrs No Conflicting data* Yes Yes B
age ≥ 45 yrs Yes Yes Yes Yes B
Any size, any age, No Inadequate data* Yes Selective use* I
minimal extrathyroidal
extension
T4 Any size with gross Yes Yes Yes Yes B
extrathyroidal extension
Nx, N0 No metastatic nodes No No Yes No I
documented
N1 age < 45 yrs No Conflicting data* Yes Selective use* C
age ≥ 45 yrs Conflicting data* Conflicting data* Yes Selective use* C
M1 Distant metastasis Yes Yes Yes Yes A
present

* Because of either conflicting or inadequate data, we cannot recommend either for or against RAI ablation for this entire subgroup. However, selected
patients within this subgroup with higher risk features may benefit from RAI ablation (see modifying factors in the text).
** See Table 2 on page 92 for a description of rankings.
From the American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM,
et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid.
2009;19(11):1167-1214. Courtesy of Mary Ann Liebert, Inc.

April 2011, Vol 18, No. 2 Cancer Control 91

effects. Multiple doses can be associated with a low but metastases or other higher risk features when the com-
statistically significant increase risk of secondary malig- bination of age, tumor size, lymph node status, and indi-
nancies.12-14 Transient effects on gonads, salivary glands, vidual histology predicts an intermediate to high risk of
and bone marrow are well described.15,16 While most of recurrence or death from thyroid cancer.
the side effects resolve within weeks to months after RAI
ablation, persistent dry mouth and salivary gland issues • Radioiodine ablation is not recommended for pa-
can continue in up to 5% of patients.15 Furthermore, a tients with unifocal cancer less than 1 cm without other
mild but statistically significant decline in white blood higher risk features.
cell count and platelets is seen up to 1 year after routine
RAI ablation.16 So while RAI is considered to be a safe • Radioiodine ablation is not recommended for pa-
therapy, it carries the potential for long-term side effects. tients with multifocal cancers when all foci are less than
In an effort to summarize the data in Table 1 into 1 cm in the absence of other higher risk features.
clinical usable recommendations and to balance the
risk/benefit ratio with regard to RAI ablation, the new While these bullet points provide strong recommen-
ATA guidelines provide the following advice regarding dations for routine use of RAI ablation in high-risk pa-
the role of RAI ablation after total thyroidectomy (rec- tients and against RAI ablation in very low-risk patients,,
ommendation 32).4 It should be noted that the term many of the patients we evaluate fall into the conflicting
ablation as used in the recommendations from the ATA data category described in the second bullet. Therefore,
broadly refers to all three functions of the first dose of the decision regarding the risks and benefits of routine
RAI (remnant ablation, adjuvant therapy, and therapy of use of RAI in these patients with intermediate risk of
macroscopic disease). recurrence will continue to be controversial and must
be made on an individual basis with each patient.
• Radioiodine ablation is recommended for all pa- While the NCCN guidelines provide less specific de-
tients with known distant metastases, gross extrathyroidal tail with regard to indications for RAI ablation, they also
extension of the tumor regardless of tumor size, or pri- use a risk-stratified approach to the use of RAI adjuvant
mary tumor size greater than 4 cm even in the absence therapy, recommending ablation/adjuvant therapy for
of other higher risk features. individual patients based on risk of recurrence and risk
of death. Consistent with the distinction between RAI
• Radioiodine ablation is recommended for selected ablation and RAI adjuvant therapy, the NCCN guidelines
patients with 1 cm to 4 cm thyroid cancers confined note that RAI ablation is not routinely required for pa-
to the thyroid and who have documented lymph node tients with a postoperative Tg < 1 ng/mL and a negative

Table 2. — Strength of the Panelists’ Recommendations Based on Available Evidence*

Rating (Grade) Definition

A Strongly recommends. The recommendation is based on good evidence that the service or intervention can improve important
health outcomes. Evidence includes consistent results from well-designed, well-conducted studies in representative populations
that directly assess effects on health outcomes.

B Recommends. The recommendation is based on fair evidence that the service or intervention can improve important health
outcomes. The evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the
number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence on
health outcomes.

C Recommends. The recommendation is based on expert opinion.

D Recommends against. The recommendation is based on expert opinion.

E Recommends against. The recommendation is based on fair evidence that the service or intervention does not improve important
health outcomes or that harms outweigh benefits.

F Strongly recommends against. The recommendation is based on good evidence that the service or intervention does not improve
important health outcomes or that harms outweigh benefits.

I Recommends neither for nor against. The panel concludes that the evidence is insufficient to recommend for or against providing
the service or intervention because evidence is lacking that the service or intervention improves important health outcomes,
the evidence is of poor quality, or the evidence is conflicting. As a result, the balance of benefits and harms cannot be determined.

* The US Preventive Services Task Force revised its ranking system in 2007, and revisions of the thyroid cancer screening recommendations are in
progress.
From the American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM,
et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid.
2009;19(11):1167-1214. Courtesy of Mary Ann Liebert, Inc.

92 Cancer Control April 2011, Vol 18, No. 2

diagnostic whole body scan.7 The complete total thy- ally, glucocorticoids are often used to minimize swelling
roidectomy in these patients has rendered RAI ablation during the period that the TSH is elevated and for 2 to 3
as an unnecessary therapy in the absence of other indi- weeks after RAI therapy.
cations suggesting a high risk of persistent disease that
may benefit from the adjuvant therapy function of RAI. Other Considerations Regarding RAI Therapy
Therefore, a careful review of the data presented in In the past, thyroid hormone withdrawal was required
Table 1 will at least allow us to provide reasonable es- to allow for the TSH elevation necessary to enhance the
timates of the potential benefit for each patient with uptake of RAI into the cells. More recently, the US Food
regard to risk of recurrence, risk of death, and facilita- and Drug Administration (FDA) approved recombinant
tion of staging and follow-up. By balancing the potential human TSH (rhTSH, Thyrogen) for both diagnostic uses
benefit with the risk of side effects and the risk of disease (diagnostic whole body scan and stimulated Tg determi-
recurrence or death, an individualized management plan nation) and adjuvant therapy uses (RAI remnant ablation
can be developed. in the absence of known distant metastases). Our ap-
proach to the method of preparation, the use of a low
RAI as Therapy for Gross Residual Disease iodine diet for 7 to 10 days, and the selection of admin-
While RAI is commonly used to treat recurrent disease istered activity is consistent with that recommended in
and distant metastases, excellent therapeutic results are both the ATA and NCCN guidelines.4,7
usually limited to patients with small-volume RAI-avid For routine remnant ablation in which the goal is to
disease.17 These are usually young patients with small- destroy the residual normal thyroid tissue to facilitate
volume pulmonary metastatic deposits of well-differen- initial staging and follow-up, 50 to 75 mCi of iodine-131 is
tiated thyroid cancer. In these patients, repeated doses administered orally following rhTSH stimulation.19 When
of RAI at 6- to 18-month intervals (as long as the patient adjuvant therapy is planned, 100 to 150 mCi of iodine-131
continues to have a clinically measurable response) are is given following rhTSH stimulation. Post-therapy whole
reasonable as the highest rates of disease remission are body scans are routinely performed 5 to 10 days after
seen in these patients. administration of the therapeutic dose.
Macronodular RAI-avid pulmonary metastases and Since rhTSH is not approved by the FDA as an ad-
bone metastases should be treated with RAI if there is junct to RAI therapy for distant metastases, most of
objective evidence of benefit following the previous these patients should still undergo traditional thyroid
therapy dose.4,7 Unfortunately, RAI is seldom curative in hormone withdrawal followed by RAI, with the admin-
this setting and overall survival remains poor. Addition- istered activity determined either by whole body RAI
ally, the presence of fluoro-2-deoxy-D-glucose (FDG)-avid clearance studies (dosimetry) or empirically determined
metastases is a marker of resistance to RAI therapy and activities ranging from 150 to 200 mCi depending on
a poor prognostic sign.18 Brain metastases are seldom RAI avidity of the tumor, volume of the tumor, age of
RAI-avid and are therefore best treated with either surgi- the patient, and cardiovascular-renal function status of
cal resection or EBRT.4,7 the patient.4,7
RAI therapy is often considered for patients with
cervical lymph node recurrence after initial therapy. In The Role of EBRT in the Treatment of
our experience, RAI is unlikely to destroy lymph node Differentiated Thyroid Cancer
metastases greater than 1 cm, so surgery is the preferred As with the use of RAI, the lack of prospective random-
treatment option in this setting. Subcentimeter meta- ized clinical trials renders it nearly impossible to provide
static lymph nodes are generally treated with additional definitive recommendations with regard to the role of
RAI only if the lesional dosimetry is high enough to allow EBRT in the therapy of patients with differentiated thy-
visualization of the metastatic lesions on a diagnostic roid cancer.9,10 Most published studies are retrospective
RAI scan. analyses of small groups of patients with wide selection
In addition to the side effects associated with RAI bias with regard to patient selection, EBRT technique,
ablation, the use of RAI in the setting of gross residual EBRT dosing, and irradiated volume. Furthermore, EBRT
disease has the potential to cause rapid growth or swell- is usually used in combination with surgical resection
ing of metastatic lesions (either secondary to the elevated and RAI therapy, making it difficult to define the specific
TSH necessary for RAI therapy or as a consequence of benefit of EBRT alone. Most authors agree that EBRT is
the inflammation and edema that develops in the sev- not required in young patients (under 45 years of age)
eral days following effective RAI therapy). Therefore, with microscopic residual disease that is likely to be
metastatic deposits in areas in which swelling could be RAI-avid, but it probably improves locoregional control
associated with significant neurovascular compromise in the setting of non–RAI-avid, unresectable gross residual
(eg, metastases to the brain, spinal cord, near other major disease in patients of any age. However, considerable
nerves or vasculature) should be treated with surgery controversy exists regarding the role of EBRT in the man-
or EBRT before proceeding with RAI therapy. Addition- agement of microscopic residual disease remaining after

April 2011, Vol 18, No. 2 Cancer Control 93

appropriate surgical intervention in older patients.9,10,20 EBRT as Adjuvant Therapy
It is also important to balance the potential for significant Because of local extension or locoregional metastases,
EBRT- and RAI-associated morbidities (such as mucositis, it is often not possible to resect all microscopic thyroid
pharyngitis, xerostomia, thick saliva, skin fibrosis, tracheal cancer at the time of the initial surgery. For RAI-avid
stenosis, and esophageal stricture) with the potential tumors, RAI is used as adjuvant therapy in an attempt
benefit in terms of local control without an overall sur- to destroy this microscopic residual disease. However,
vival benefit.9,10,20 high-risk patients with gross extrathyroidal extension
apparent at the time of initial surgery with involvement
EBRT for Gross Locoregional Residual Disease of the trachea, larynx, great vessels, esophagus, or other
EBRT does appear to improve locoregional control rates major structures often have microscopic residual disease
in high-risk patients who have gross residual non–RAI- that is likely to develop an early recurrence and unlikely
avid disease remaining after attempted surgical resec- to respond to RAI. Several studies have demonstrated
tion.9,10,20 However, despite obtaining reasonable local improved locoregional control when EBRT is used fol-
control for several years, these high-risk patients often lowing complete resection of all visible disease (often in
die of progressive distant metastatic disease.10,21 conjunction with RAI) in older patients demonstrating
Based on these findings, we consider EBRT to be gross extrathyroidal extension at the time of initial surgi-
an integral part of the therapy for most patients with cal intervention.9,10,20,22 In our view, minor extrathyroidal
gross disease remaining after attempted surgical resec- extension into surrounding adipose tissue or skeletal
tion. EBRT appears to be particularly important in older muscle noted only on histological evaluation is not ad-
patients with poorly differentiated thyroid cancers that equate justification for the use of EBRT in the absence
are likely to be both more aggressive and non–RAI-avid. of other high-risk features. Likewise, we do not believe
These tumors tend to be positive on FDG positron emis- that lymph node involvement, by itself, is an indication
sion tomography (PET). Using radiotherapy techniques for EBRT since recurrences in cervical lymph nodes can
such as intensity-modulated radiation therapy (IMRT), it effectively be treated with additional surgery in the future
is possible to deliver radiation doses as high as 70 Gy to if they do not respond to RAI.9 In the setting of micro-
the gross disease, in particular to the PET-avid disease, scopic extrathyroidal extension and cervical lymph node
without exceeding the tolerance of surrounding critical involvement, we generally consider that the risks and side
structures. Postoperative EBRT is not usually indicated effect profile of EBRT outweigh the potential benefit of
in the few young patients with an incomplete tumor decreasing the risk of a locoregional recurrence that is
resection as these tumors are usually still RAI-avid and likely to be adequately treated with additional surgery
can often be effectively treated with RAI. Therefore, in the future if needed.
EBRT in the management of gross residual disease in Therefore, we agree with the approach recommend-
young patients is reserved for those few patients who ed by Brierley et al,10 the NCCN guidelines,7 and the
have significant local progression after RAI therapy or ATA guidelines4 in which EBRT (in addition to surgical
the uncommon young patient with locally aggressive resection, RAI, and TSH suppression) is strongly consid-
poorly differentiated thyroid cancer.9,10,22 ered for most older patients (> 45 to 50 years) who had
These recommendations are consistent with both a complete surgical resection of all visible non–RAI-avid
the updated ATA thyroid cancer guidelines, which rec- tumor in the setting of gross extrathyroidal extension
ommend that EBRT be considered in patients over 45 into surrounding major structures.9 This approach is
years of age with gross residual tumor in whom further particularly important in patients with poorly differenti-
surgery or RAI would likely be ineffective, and the NCCN ated tumors that are unlikely to respond to RAI therapy.
guidelines, which recommend EBRT for gross residual In the absence of other very high-risk features, we do
disease if RAI is likely to be ineffective.7 not routinely recommend EBRT as adjuvant therapy for
patients younger than 45 years of age, for patients with
EBRT as Palliative Therapy for Metastatic Lesions microscopic extrathyroidal extension noted only on his-
In addition to its role in the management of locoregional tological examination, or for patients with locoregional
disease, EBRT is important in the palliation of individual lymph node involvement in the absence of other very
metastatic lesions.4,7 EBRT has been successfully used to high-risk features.
slow disease progression and provide dramatic pain relief
in metastatic bone lesions. Brain metastases that cannot be Other Considerations Regarding EBRT
resected can also be treated with EBRT. While lung metas- Maximizing locoregional control is paramount in patients
tases are not generally amenable to EBRT because of the in whom EBRT is offered. Therefore, it is important to
size, number, and extent of malignant leisons, EBRT can be deliver the highest dose of radiation possible without
used to provide symptomatic relief of dominant pulmonary causing injury to the surrounding normal tissues, eg, spinal
metastases causing either hemoptysis or local compressive cord. This is easily achieved with targeted radiation tech-
symptoms on the airway, heart, or major vessels. niques such as IMRT. Furthermore, image-guided IMRT

94 Cancer Control April 2011, Vol 18, No. 2

(IG-IMRT, or commonly known as IGRT), can improve malignancies up to three decades after the treatment of differentiated thyroid
cancer. J Clin Endocrinol Metab. 2008;93(2):504-515.
the precision of radiation delivery by capturing real-time 13. Rubino C, de Vathaire F, Dottorini ME, et al. Second primary malig-
positional films of the treatment volume during radia- nancies in thyroid cancer patients. Br J Cancer. 2003;89(9):1638-1644.
14. Sawka AM, Thabane L, Parlea L, et al. Second primary malignancy
tion delivery. Typically, when radiation is delivered in the risk after radioactive iodine treatment for thyroid cancer: a systematic review
postoperative setting, the target volume should include and meta-analysis. Thyroid. 2009;19(5):451-457.
15. Grewal RK, Larson SM, Pentlow CE, et al. Salivary gland side effects
the preoperative tumor volume and the postoperative commonly develop several weeks after initial radioactive iodine ablation. J
bed, paying attention to ensure coverage not only of the Nucl Med. 2009;50(10):1605-1610.
16. Molinaro E, Leboeuf R, Shue B, et al. Mild decreases in white blood
trachea-esophageal groove and neck to the level of the cell and platelet counts are present one year after radioactive iodine remnant
carina, but also of the anterior mediastinum. The doses ablation. Thyroid. 2009;19(10):1035-1041.
17. Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444
typically range from 60 to 66 Gy. When resection is incom- patients with distant metastases from papillary and follicular thyroid carci-
plete, the target volume is the same except that in regions noma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab.
2006;91(8):2892-2899.
of gross disease, the dose of radiation is increased to 70 18. Robbins RJ, Wan Q, Grewal RK, et al. Real-time prognosis for metastatic
Gy. PET scan obtained at the time of radiation planning thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emis-
sion tomography scanning. J Clin Endocrinol Metab. 2006;91(2):498-505.
can guide the appropriate dose levels to the target volume. 19. Tuttle RM, Brokhin M, Omry G, et al. Recombinant human TSH-
assisted radioactive iodine remnant ablation achieves short-term clinical
recurrence rates similar to those of traditional thyroid hormone withdrawal.
Conclusions J Nucl Med. 2008;49(5):764-770.
Risk stratification allows clinicians to select patients at 20. Strasser JF, Raben A, Koprowski C. The role of radiation therapy in the
management of thyroid cancer. Surg Oncol Clin N Am. 2008;17(1):219-
high risk of recurrence and death from thyroid cancer. 232, x.
In addition, by risk stratifying with regard to the likeli- 21. Terezakis SA, Lee KS, Ghossein RA, et al. Role of external beam
radiotherapy in patients with advanced or recurrent nonanaplastic thyroid
hood that our initial therapies are likely to be effective cancer: Memorial Sloan-Kettering Cancer Center experience. Int J Radiat
(surgical resection and RAI therapy), we can identify Oncol Biol Phys. 2009;73(3):795-801.
22. Mazzarotto R, Cesaro MG, Lora O, et al. The role of external beam
patients most likely to benefit from additional therapy radiotherapy in the management of differentiated thyroid cancer. Biomed
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and perhaps even improve disease-specific survival. By
carefully weighing the risk of recurrence and death with
the potential benefits and risks of additional therapies,
the clinician can develop an individualized, risk-adapted
management and follow-up plan for patients with dif-
ferentiated thyroid cancer.

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