Pilot Study of a Web-based Decision Tool on Post-operative Use of Radioactive Iodine

European Endocrinology, 2017;13(1):26–9 DOI: https://doi.org/10.17925/EE.2017.13.01.26

Abstract:

Background: The Thyroid Cancer Care Collaborative developed a web-based clinical decision-making module (CDMM) to inform riskadjusted decisions on post-thyroidectomy radioactive iodine (RAI) use in papillary thyroid cancer (PTC). Methods: In a pilot study, we evaluated the CDMM in 19 PTC cases representing low- (five), intermediate- (seven) and high-risk (seven) disease. Two PTC experts and 10 PTC physicians reviewed cases and assigned risk level and RAI recommendation. The experts used a standard approach while the others used the CDMM. We assessed agreement between responses using a weighted Kappa. Results: Between experts, risk-assignment was concordant in 100%, 57% and 86% of low-, intermediate- and high-risk cases, respectively. Between CDMM users, risk-assignment was concordant in 100%, 29% and 14% in low-, intermediate- and high-risk cases, respectively (p=0.01). CDMM-assigned risk agreed with the expert-assigned risk in 100%, 25% and 0% of low-, intermediate- and high-risk cases, respectively (Kappa=0.69). For RAI use, the experts agreed in 15 cases while CDMM users agreed in eight. On further analysis, interpretation of extrathyroidal extension and lymph node staging led to discrepancies with the CDMM. Conclusions: For a web-based CDMM to accurately inform appropriate use of RAI in PTC, standard pathological and surgical reports are necessary.

Keywords: Thyroid cancer, radioactive iodine, thyroidectomy, decision-making, web-based
Disclosure: Shrujal S Baxi has a consulting role with BMS and serves on an advisory board for AstraZeneca. Leonard Wartofsky has been a consultant for Asuragen, Eisei, IBSA and Interpace Diagnostics. He has received speaker honoraria from Genzyme. R Michael Tuttle is a consultant for AstraZeneca, Bayer/Onyx, Genzyme, Novo Nordisk and Veracyte. Rachel Kurtzman, Anne Eaton, Eliza Dewey, Craig Bickford and Stephanie Fish have nothing to disclose in relation to this paper.
Acknowledgments: This work was supported by a Cancer Center Support Grant from the National Cancer Institute to Memorial Sloan Kettering Cancer Center award number P30 CA008748.

Compliance with EthicsThis case study was performed in accordance with the responsible committee on human experimentation and with the Helsinki Declaration of 1975. Institutional Review Board approval was obtained.

Received: January 23, 2017 Accepted March 09, 2017
Correspondence: Shrujal S Baxi, Head and Neck Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, 1459, New York, NY 10065, US. E: baxis@mskcc.org
Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.

The incidence of thyroid cancer is increasing at a rate of 7% a year; there were an estimated 62,450 cases diagnosed in the US in 2015 alone. The majority of this rise in incidence is explained by the growing number of incidentally detected well-differentiated, early-stage or ‘low-risk’ papillary thyroid cancers (PTCs).3 There is a growing awareness that many thyroid cancers may indeed be relatively benign in their behaviour and can be followed without any intervention.4 As a result, the management of differentiated thyroid cancer has undergone a major paradigm shift over the last two decades from a ‘one size fits all’ to a ‘risk-adapted’ approach. The American Thyroid Association (ATA) has led this effort by developing and publishing evidence-based guidelines on thyroid cancer management. The ATA guidelines incorporate tumour and patient characteristics to estimate the initial risk of recurrence (prognostication) and then use this information to inform recommendations on the use of adjuvant radioactive iodine (RAI) or remnant ablation therapy and the intensity and method of surveillance.5 One major goal of the ATA guidelines is to minimise potential harm from overtreatment for low-risk patients, while appropriately treating high-risk patients.

In well-differentiated thyroid cancer, adjuvant RAI is an effective method of attempting to address microscopic disease both in the thyroid bed (remnant thyroid) and distant metastatic sites. The phrases remnant ablation and adjuvant therapy are often used interchangeably, but there are distinct differences. A lower dose of RAI, 30 to 50 mCi (or 1,110 to 1,850 MBq) is used for remnant ablation while a higher dose, 100 to 150 mCi (3,700 to 5,550 MBq) is reserved for adjuvant therapy in patients deemed at high risk of micrometastatic disease.6 The use of RAI improves survival and decreases recurrence rates for high-risk patients with extensive disease, but does not change the already excellent prognosis of patients with low-risk disease.7–9 The use of post-thyroidectomy RAI has dramatically risen over the last three decades as part of the first course of therapy for thyroid cancer from 6.1% of cases treated in 1973 to 48.7% of cases treated in 2006.10< During the same time frame, an increasing proportion of patients have been diagnosed with low-risk thyroid cancer raising the question of benefit of added RAI therapy.3

Early recommendations on RAI use were shaped by retrospective studies completed in the 1970- 80’s that reported decreased risk of recurrence in patients who received RAI therapy compared with those treated with surgery and thyroid suppression alone.11,12 In 2009, the ATA released their first guidelines with the definitive recommendation against RAI use in low-risk populations. A 2014 study showed that these 2009 guidelines only modestly reduced the use of RAI for the very-low- risk subgroup of patients.13 To improve dissemination of the new 2015 guidelines into clinical practice, the Thyroid Cancer Care Collaborative (TCCC) created 12 online clinical decision-making modules (CDMM), which ask clinicians to respond to clinical questions on a variety of clinical decisions. The CDMM used for this study (‘When to Administer Remnant Ablation’) uses responses to clinical questions to provide a guideline-based recommendation regarding administration of postoperative RAI. Similar to the Adjuvant! Online tool used by oncologists to determine post-surgical management in breast cancer, the CDMM incorporates demographic, surgical and pathological characteristics into algorithms to categorise risk of recurrence (low, intermediate and high) and to provide clinical guidance on recommendations regarding use of post-thyroidectomy RAI. In this pilot study, we aimed to assess the usability of CDMM in determining the use of RAI in a heterogeneous series of patients with resected well-differentiated PTC.

Methods
The TCCC is an online Health Insurance Portability and Accountability Act (HIPAA)-compliant, cloud-based portal and registry that enhances the quality of care for patients with thyroid disease and improves the communication between physicians. The TCCC provides portability of information for patients and centralises all of their relevant clinical records. Data entry modules incorporate time-saving features and focus on specific aspects of the thyroid cancer management. The application is also an educational tool for both patients and physicians, delivering informative videos and CDMMs.

The TCCC developed the CDMMs in partnership with the experts who developed the most-recent version of the ATA guidelines. The overall process in the development of the CDMMs was first to isolate data pertinent to the specific clinical decision, and then to determine the necessary questions to ask to collect that data. Next, the applicable ATA clinical practice guidelines were reviewed to create a flow chart algorithm of decisions for the outcomes. Several iteration tests were run in order to verify the logic and to check for any gaps in the algorithm. Each outcome was cited and supported with a guideline footnote from the ATA clinical practice guidelines. The CDMM used for this study (‘When to Administer Remnant Ablation’) asks only five questions, one with a follow up if necessary, designed to isolate data points required to assess risk of recurrence based on the ATA guidelines ( see Figure 1). Then, based on these responses, the CDMM provides a risk level (low, intermediate or high) and one of three recommendations on use of RAI (yes, no or consider). If the answer is ‘consider’, there is some additional information on which groups may benefit from RAI, but no definitive conclusion due to a lack of consensus in the field.

The Institutional Review Board (IRB) at Memorial Sloan Kettering Cancer Center (MSKCC) approved this study. We identified study cases from an institutional database of 407 consecutive patients treated with a total thyroidectomy for PTC and stratified by ATA risk of recurrence from 2000 to 2002. We originally selected 20 cases from this dataset using a random number generator. Due to clerical inconsistency in one case upon later review, we only used 19 cases from this database (five from low-risk and seven each from intermediate- and high-risk) for analysis. Only cases with complete clinical information were included (e.g, surgical report, a pathology report, thyroid laboratories pre and post-surgery and records of all pre-surgical radiology).

For each selected case, a de-identified file containing the relevant clinical information that would have been available at time of a decision regarding adjuvant RAI was created. These files were provided to two experts (RMT, LW) who were asked to render a ‘yes’ or ‘no’ decision on the use of RAI for each case. The gold standard was deemed to be an agreement decision between two experts. Ten thyroid cancer fellows from endocrinology and surgery in fellowship at a specialised cancer centre were invited to participate (five endocrinology; five head and neck surgical fellows) and asked to use the CDMM to render a response of ‘yes’, ‘no’ or ‘consider’ regarding adjuvant RAI for the same 19 cases.

References:
1. Simard EP, Ward EM, Siegel R, Jemal A, Cancers with increasing incidence trends in the United States: 1999 through 2008, Cancer J Clin, 2012;62:118–28.
2. Siegel RL, Miller KD, Jemal A 2015 Cancer Statistics, Cancer J Clin, 2015;65:5–29.
3. Davies L, Welch HG, Current thyroid cancer trends in the United States, JAMA Otolaryngol Head Neck Surg, 2014;140:317–22.
4. Tufano RP, Noureldine SI, Angelos P, Incidental thyroid nodules and thyroid cancer: considerations before determining management, JAMA Otolaryngol Head Neck Surg, 2015;141:566–72.
5. Haugen BR, Alexander EK, Bible KC, et al., 2005 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer, Thyroid, 2016;26:1–133.
6. Tuttle RM, Rondeau G, Lee NY, A risk-adapted approach to the use of radioactive iodine and external beam radiation in the treatment of well-differentiated thyroid cancer, Cancer Control, 2011;18:89–95.
7. Sacks, W, Wong RM, Bresee C, Braunstein GD, Use of evidencebased guidelines reduces radioactive iodine treatment in patients with low-risk differentiated thyroid cancer, Thyroid, 2015;25:377–85.
8. Morris DM, Boyle JP, Stidley CA, et al., Localised welldifferentiated thyroid carcinoma: survival analysis of prognostic factors and (131)I therapy, Ann Surg Oncol, 1998;5:329–37.
9. Hay ID, Selective use of radioactive iodine in the postoperative management of patients with papillary and follicular thyroid carcinoma, J Surg Oncol, 2006;94:692–700.
10. Iyer NG, Morris LG, Tuttle RM, et al., Rising incidence of second cancers in patients with low-risk T1N0 thyroid cancer who receive radioactive iodine therapy, Cancer, 2011;117:4439–46.
11. Samaan NA, Maheshwari YK, Nader S, et al., Impact of therapy for differentiated carcinoma of the thyroid: an analysis of 706 cases, J Clin Endocrinol Metab, 1983;56:1131–8.
12. Mazzaferri EL, Young RL, Oertel JE, et al., Papillary thyroid carcinoma: the impact of therapy in 576 patients, Medicine, 1977;56:171–96.
13. Roman BR, Feingold JH, Patel SG, et al., The 2009 American Thyroid Association guidelines modestly reduce radioactive iodine use for thyroid cancers less than 1 cm, Thyroid, 2014;24:1549–50.
14. Rosai J, Carcangiu MS, De Lellis RA, et al., Recommended Reporting Format for Thyroid Carcinoma, Am J Clin Pathol, 2000;114:684–6.
15. Ozanne EM, Braithwaite D, Sepucha K, et al., Sensitivity to input variability of the Adjuvant! Online breast cancer prognostic model, J Clin Oncol, 2009;27:214–9.
Keywords: Thyroid cancer, radioactive iodine, thyroidectomy, decision-making, web-based