2017 Section 7 Green Book

Lang et al

Surgery Volume 151, Number 6

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. 9 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 4 ---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. 12 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) I 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. 13 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

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