Abstract

Background: Tumor volume (TV) of papillary thyroid carcinoma (PTC) increases exponentially during active surveillance, and the growth rate differs for each patient. TV doubling time (TVDT) is considered a strong dynamic marker for the prediction of the growth rate and progression of the tumor.
Methods: This cohort study analyzed 273 PTC patients who underwent active surveillance for more than one year rather than immediate thyroid surgery. TVDT was calculated in each patient, and patients were divided into two groups: rapid-growing (TVDT <5 years) and stable (TVDT ≥5 years). Clinical and initial ultrasonography (US) features between the two groups were compared.
Results: The median patient age was 51.1 years (interquartile range [IQR] 42.2–61.0 years), and 76% of the patients were women. The initial TV of PTC was 62.1 mm3 (IQR 28.1–122.8 mm3). During a median of 42 months (IQR 29–61 months) of active surveillance, 10.3% of the patients had a TVDT of less than two years, 5.1% had a TVDT between two and three years, 6.2% had a TVDT between three and four years, 6.6% had a TVDT between four and five years, and 71.8% had a TVDT of five years or more. Patients in the rapid-growing group (77 patients; 28.2%) were significantly younger (p = 0.004) than those in the stable group (196 patients; 71.8%). Being younger than 50 years of age was significantly associated with rapid tumor growth of PTC (odds ratio = 2.31 [confidence interval 1.30–4.31], p = 0.004) in multivariate analysis. In ultrasound findings, macrocalcification was independently associated with rapid tumor growing of PTCs (odds ratio = 4.98 [confidence interval 2.19–11.69], p < 0.001).
Conclusions: TVDT is a good indicator for presenting the growing velocity of PTCs during active surveillance. Younger age and macrocalcification in the initial US were associated with rapid-growing PTCs. Determination of TVDT during the early phase of active surveillance may be helpful for the prediction of rapidly progressing PTCs and deciding whether to adopt an early surgical approach.

Get full access to this article

View all available purchase options and get full access to this article.

References

1. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L 2016 2015 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 26:1–133.
2. Ito Y, Miyauchi A, Inoue H, Fukushima M, Kihara M, Higashiyama T, Tomoda C, Takamura Y, Kobayashi K, Miya A 2010 An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg 34:28–35.
3. Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fujimoto Y 2010 Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg 34:1222–1231.
4. Kwon H, Oh HS, Kim M, Park S, Jeon MJ, Kim WG, Kim WB, Shong YK, Song DE, Baek JH, Chung KW, Kim TY 2017 Active surveillance for patients with papillary thyroid microcarcinoma: a single center's experience in Korea. J Clin Endocrinol Metab 102:1917–1925.
5. Kim TY, Shong YK 2017 Active surveillance of papillary thyroid microcarcinoma: a mini-review from Korea. Endocrinol Metab (Seoul) 32:399–406.
6. Tuttle RM, Fagin JA, Minkowitz G, Wong RJ, Roman B, Patel S, Untch B, Ganly I, Shaha AR, Shah JP, Pace M, Li D, Bach A, Lin O, Whiting A, Ghossein R, Landa I, Sabra M, Boucai L, Fish S, Morris LGT 2017 Natural history and tumor volume kinetics of papillary thyroid cancers during active surveillance. JAMA Otolaryngol Head Neck Surg 143:1015–1020.
7. Sabra MM, Sherman EJ 2017 Tumor volume doubling time of pulmonary metastases predicts overall survival and can guide the initiation of multikinase inhibitor therapy in patients with metastatic, follicular cell-derived thyroid carcinoma. 123:2955–2964.
8. Kim JK, Kim H-D, Jun M-J, Yun S-C, Shim JH, Lee HC, Lee D, An J, Lim Y-S, Chung Y-H, Lee YS, Kim KM 2017 Tumor volume doubling time as a dynamic prognostic marker for patients with hepatocellular carcinoma. Digest Dis Sci 62:2923–2931.
9. Kuroishi T, Tominaga S, Morimoto T, Tashiro H, Itoh S, Watanabe H, Fukuda M, Ota J, Horino T, Ishida T, et al. 1990 Tumor growth rate and prognosis of breast cancer mainly detected by mass screening. Jpn J Cancer Res 81:454–462.
10. Veronesi G, Maisonneuve P, Bellomi M, Rampinelli C, Durli I, Bertolotti R, Spaggiari L 2012 Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: a cohort study. Ann Intern Med 157:776–784.
11. Nam SY, Shin JH, Han BK, Ko EY, Ko ES, Hahn SY, Chung JH 2013 Preoperative ultrasonographic features of papillary thyroid carcinoma predict biological behavior. J Clin Endocrinol Metab 98:1476–1482.
12. Jeon MJ, Chung MS, Kwon H, Kim M, Park S, Baek JH, Song DE, Sung TY, Hong SJ, Kim TY, Kim WB, Shong YK, Lee JH, Kim WG 2017 Features of papillary thyroid microcarcinoma associated with lateral cervical lymph node metastasis. Clin Endocrinol (Oxf) 86:845–851.
13. Gweon HM, Son EJ, Kim JA, Youk JH 2017 Predictive factors for active surveillance of subcentimeter thyroid nodules with highly suspicious US features. Ann Surg Oncol 24:1540–1545.
14. Oh HS, Ha J, Kim HI, Kim TH, Kim WG, Lim DJ, Kim TY, Kim SW, Kim WB, Shong Y, Chung JH, Baek JH 2018 Active surveillance of low-risk papillary thyroid microcarcinoma: a multi-center cohort study in Korea. Thyroid 28:1587–1594.
15. Choi YJ, Baek JH, Hong MJ, Lee JH 2015 Inter-observer variation in ultrasound measurement of the volume and diameter of thyroid nodules. Korean J Radiol 16:560–565.
16. Na DG, Baek JH, Jung SL, Kim JH, Sung JY, Kim KS, Lee JH, Shin JH, Choi YJ, Ha EJ, Lim HK, Kim SJ, Hahn SY, Lee KH, Choi YJ, Youn I, Kim YJ, Ahn HS, Ryu JH, Baek SM, Sim JS, Jung CK, Lee JH 2017 Core needle biopsy of the thyroid: 2016 consensus statement and recommendations from Korean Society of Thyroid Radiology. Korean J Radiol 18:217–237.
17. Shin JH, Baek JH, Chung J, Ha EJ, Kim JH, Lee YH, Lim HK, Moon WJ, Na DG, Park JS, Choi YJ, Hahn SY, Jeon SJ, Jung SL, Kim DW, Kim EK, Kwak JY, Lee CY, Lee HJ, Lee JH, Lee JH, Lee KH, Park SW, Sung JY 2016 Ultrasonography diagnosis and imaging-based management of thyroid nodules: revised Korean Society of Thyroid radiology consensus statement and recommendations. Korean J Radiol 17:370–395.
18. Cibas ES, Ali SZ 2017 The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid 27:1341–1346.
19. Jung CK, Min HS, Park HJ, Song DE, Kim JH, Park SY, Yoo H, Shin MK 2015 Pathology reporting of thyroid core needle biopsy: a proposal of the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group. J Pathol Transl Med 49:288–299.
20. Jung CK, Baek JH 2017 Recent advances in core needle biopsy for thyroid nodules. Endocrinol Metab (Seoul) 32:407–412.
21. Frates MC, Benson CB, Charboneau JW, Cibas ES, Clark OH, Coleman BG, Cronan JJ, Doubilet PM, Evans DB, Goellner JR, Hay ID, Hertzberg BS, Intenzo CM, Jeffrey RB, Langer JE, Larsen PR, Mandel SJ, Middleton WD, Reading CC, Sherman SI, Tessler FN 2006 Management of thyroid nodules detected at US: Society of Radiologists in Ultrasound consensus conference statement. Ultrasound Q 22:231–238; discussion 239–240.
22. Oh HS, Kwon H, Song E, Jeon MJ, Song DE, Kim TY, Lee JH, Hong SJ, Kim WB, Shong YK, Baek JH, Kim WG 2018 Preoperative clinical and sonographic predictors for lateral cervical lymph node metastases in sporadic medullary thyroid carcinoma. Thyroid 28:362–368.
23. Jeong WK, Baek JH, Rhim H, Kim YS, Kwak MS, Jeong HJ, Lee D 2008 Radiofrequency ablation of benign thyroid nodules: safety and imaging follow-up in 236 patients. Eur Radiol 18:1244–1250.
24. Fukuoka O, Sugitani I, Ebina A, Toda K, Kawabata K, Yamada K 2016 Natural history of asymptomatic papillary thyroid microcarcinoma: time-dependent changes in calcification and vascularity during active surveillance. World J Surg 40:529–537.
25. Doubling time and progression calculator. Available at: www.kuma-h.or.jp/english/about/doubling-time-progression-calculator/ (accessed August 18, 2003).
26. Landis JR, Koch GG 1977 The measurement of observer agreement for categorical data. Biometrics 33:159–174.
27. Collins VP, Loeffler RK, Tivey H 1956 Observations on growth rates of human tumors. Am J Roentgenol Radium Ther Nucl Med 76:988–1000.
28. Miyauchi A, Matsuzuka F, Kuma K, Takai S, Nakamoto K, Nakamura K, Nanjo S, Maeda M 1988 Evaluation of surgical results and prediction of prognosis in patients with medullary thyroid carcinoma by analysis of serum calcitonin levels. World J Surg 12:610–615.
29. Yi KH 2016 The revised 2016 Korean Thyroid Association guidelines for thyroid nodules and cancers: differences from the 2015 American Thyroid Association guidelines. Endocrinol Metab (Seoul) 31:373–378.
30. Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L 2017 European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. Eur Thyroid J 6:225–237.
31. Kumar V, Abbas AK, Aster JC 2015 Robbins and Cotran Pathologic Basis of Disease. Ninth edition. Elsevier/Saunders, Philadelphia, PA.
32. Miyauchi A, Kudo T, Ito Y, Oda H, Sasai H, Higashiyama T, Fukushima M, Masuoka H, Kihara M, Miya A 2018 Estimation of the lifetime probability of disease progression of papillary microcarcinoma of the thyroid during active surveillance. Surgery 163:48–52.
33. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A 2014 Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid 24:27–34.

Information & Authors

Information

Published In

cover image Thyroid®
Thyroid
Volume 29Issue Number 5May 2019
Pages: 642 - 649
PubMed: 30864894

History

Published online: 13 May 2019
Published in print: May 2019
Published ahead of print: 8 April 2019
Published ahead of production: 13 March 2019

Permissions

Request permissions for this article.

Topics

Authors

Affiliations

Hye-Seon Oh
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Endocrinology and Metabolism, National Police Hospital, Seoul, Republic of Korea.
Hyemi Kwon
Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Eyun Song
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Min Ji Jeon
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Tae Yong Kim
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jeong Hyun Lee
Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Won Bae Kim
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Young Kee Shong
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Ki-Wook Chung
Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Jung Hwan Baek [email protected]
Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Notes

Address correspondence to: Won Gu Kim, MD, PhD, Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea [email protected]
Jung Hwan Baek, MD, PhD, Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea [email protected]

Author Disclosure Statement

No competing financial interests exist.

Metrics & Citations

Metrics

Citations

Export citation

Select the format you want to export the citations of this publication.

View Options

Get Access

Access content

To read the fulltext, please use one of the options below to sign in or purchase access.

Society Access

If you are a member of a society that has access to this content please log in via your society website and then return to this publication.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF/EPUB

View PDF/ePub

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media

Back to Top