2017 Section 7 Green Book

and surveillance bias.

5,8

A recent meta-analysis com-

prising more than 16,000 patients found that the

risk of developing NSPM in DTC survivors treated

with RAI therapy was increased compared to those

not treated with RAI.

However, this meta-analysis,

because of its relative strict inclusion criteria, only

included 2 population-based studies, both of which

revealed an increased risk of NSPM in those treated

by RAI compared to those not treated by RAI.

5,6

There have been other studies, not included in

the meta-analysis, that failed to reveal an associa-

tion between cumulative RAI activity and risk of

NSPM and no risk difference associated with RAI

treatment.

8,10,11

Given the existing conflicting evidence---and in

light of our previous analysis showing an increased

risk of NSPM in DTC survivors

---the aims of the

present study were to evaluate the association be-

tween RAI therapy and development of NSPM

and to examine whether the risk of NSPM in radi-

ation-na

€

ıve DTC survivors treated with RAI is in-

creased relative to that of the general population.

METHODS

Patients.

Between 1971 and 2009, 1,122 patients

with DTC were managed at our institution. Of

these, 98 (8.7%) had clinically occult microcarci-

noma, 41 (3.7%) had a documented history of

radiotherapy or radiation exposure before the

diagnosis of DTC, and 88 (7.8%) received ERT as

adjuvant treatment for DTC. For the purpose of

the present study, they were excluded, and there-

fore a total of 895 radiation-na

€

ıve patients were

eligible for analysis. All eligible patients had at

least 1 year of follow-up. There were 643 patients

who received at least 1 course of RAI (RAI

group)

and 252 who received no RAI at all during the

study period (RAI group).

Methods.

The present study protocol was ap-

proved by the local institutional review board. The

protocol for I

131

or RAI ablation remained un-

changed throughout the study period, and details

were described previously.

Patients with

1 risk

factors, such as tumor size

1 cm, lymph node me-

tastasis, age

40 years, presence of extrathyroidal

extension, macroscopic postoperative residual dis-

ease in the neck, or distant metastasis, were con-

sidered for RAI ablation 8–10 weeks after

thyroidectomy by either T4 withdrawal or the use

of recombinant thyroid-stimulating hormone. Di-

agnostic whole body I

131

scans were performed

approximately 6 months after RAI therapy. Three

giga-Becquerels (GBq) or 80 millicuries (mCi)

131

were administered as a standard ablative dose

for all postsurgical patients, but higher doses

were considered in the presence of extensive

lymph node involvement or distant metastasis.

Subsequent RAI therapy of 5.5 GBq (or 150 mCi)

was administered periodically at 4- to 6-month in-

tervals until uptake was no longer visible or disease

progressed despite treatment. The cumulative RAI

dose or activity for each individual patient was cal-

culated. Although the above protocol was closely

followed throughout the study period, individual

patient preference was considered and respected.

To ensure an accurate and updated follow-up

status of all patients, a careful manual search of all

patients’ status in the territory-wide Clinical Man-

agement System (CMS) was performed. The CMS

is a computerized database linking all 41 public

hospitals in Hong Kong that provides inpatient

medical records corresponding to more than

90% of inpatient bed days in the region.

Specific

variables including the latest date of follow-up or

the date of death, date of birth, cause of death, di-

agnosis date, and type of second nonthyroidal pri-

mary malignancy were retrieved. Clinicopathologic

data and management details relating to the DTC

were prospectively collected since 1995. As of Janu-

ary 2011, 805 (81.9%) were still alive and being

monitored. The other 178 patients died; in 66

cases, DTC was the cause of death.

Statistical analysis.

For patients who developed

2 nonthyroidal primary malignancies after DTC,

only the earliest occurred malignancy was re-

corded. The time to developing a second primary

malignancy was calculated from the date of DTC

diagnosis to the diagnosis date of the second

malignancy. A second malignancy that occurred

within 12 months of the date of DTC diagnosis was

considered synchronous and was excluded from

analysis. The time at risk for NSPM was calculated

from the date of DTC to the date of NSPM, the

date of death, or the date of last follow-up, which-

ever came first. To evaluate the relationship be-

tween patient characteristics, treatment, tumor

stage, and risk of NSPM, 2 approaches were used.

First, the cumulative proportion of NSPM as a

function of time after DTC diagnosis was estimated

using the Kaplan–Meier method. The relations

between the time of NSPM occurrence and con-

comitant variables, such as sex, age, period of DTC

diagnosis, tumor stage, ERT, and RAI therapy was

assessed using the Cox proportional hazards re-

gression model, which accounts for the length of

follow-up. Second, the cancer incidence of both

RAI

and RAI groups were compared to that of

the general population by calculating the stan-

dardized incidence ratios (SIRs) for all sites/types

of NSPMs. The SIRs of NSPM after DTC were

Surgery

Volume 151, Number 6

Lang