Skip to main content
Top
Published in: European Radiology 11/2020

01-11-2020 | Ultrasound | Ultrasound

Papillary thyroid carcinoma: an ultrasound-based nomogram improves the prediction of lymph node metastases in the central compartment

Authors: Xiaoqi Tian, Qing Song, Fang Xie, Ling Ren, Ying Zhang, Jie Tang, Yan Zhang, Zhuang Jin, Yaqiong Zhu, Mingbo Zhang, Yukun Luo

Published in: European Radiology | Issue 11/2020

Login to get access

Abstract

Objectives

To develop a nomogram based on postoperative clinical and ultrasound findings to quantify the probability of central compartment lymph node metastases (CLNM).

Methods

A total of 952 patients with histologically confirmed papillary thyroid carcinoma (PTC) were included in this retrospective study and assigned to three groups based on sex and age. The strongest predictors for CLNM were selected according to ultrasound imaging features, and an ultrasound (US) signature was constructed. By incorporating clinical characteristics, a predictive model presented as a nomogram was developed, and its performance was assessed with respect to calibration, discrimination and clinical usefulness.

Results

Predictors contained in the nomogram included US signature, US-reported LN status and age. The US signature was constructed with tumour size and microcalcification. The nomogram showed excellent calibration in the training dataset, with an AUC of 0.826 (95% CI, 0.765–0.887) for male patients, 0.818 (95% CI, 0.746–0.890) for young females and 0.808 (95% CI, 0.757–0.859) for elder females. For male and young female patients, application of the nomogram to the validation cohort revealed good discrimination, with AUCs of 0.813 (95% CI, 0.722–0.904) and 0.814 (95% CI, 0.712–0.915), respectively. Conversely, for elderly female patients, the nomogram failed to show good performance with an AUC of 0.742 (95% CI, 0.661–0.823).

Conclusion

This ultrasound-based nomogram may serve as a useful clinical tool to provide valuable information for treatment decisions, especially for male and younger female patients.

Key Points

• Age, gender, US-reported LN status and US signature were the strongest predictors of CLNM in PTC patients and informed the development of a predictive nomogram.
• Microcalcification was the strongest predictor in the US signature, as CLMN was identified in approximately 92% of patients characterised by diffuse microcalcification.
• Stratified by sex and age, this nomogram achieved good performance in predicting CLNM, especially in male and young female patients. This prediction tool may be useful as an imaging marker for identifying CLNM preoperatively in PTC patients and as a guide for personalised treatment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34CrossRef Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34CrossRef
2.
go back to reference Lee YK, Hong N, Park SH et al (2019) The relationship of comorbidities to mortality and cause of death in patients with differentiated thyroid carcinoma. Sci Rep 9:11435CrossRef Lee YK, Hong N, Park SH et al (2019) The relationship of comorbidities to mortality and cause of death in patients with differentiated thyroid carcinoma. Sci Rep 9:11435CrossRef
3.
go back to reference Zhao L, Pang P, Zang L et al (2019) Features and trends of thyroid cancer in patients with thyroidectomies in Beijing, China between 1994 and 2015: a retrospective study. BMJ Open 9:e023334CrossRef Zhao L, Pang P, Zang L et al (2019) Features and trends of thyroid cancer in patients with thyroidectomies in Beijing, China between 1994 and 2015: a retrospective study. BMJ Open 9:e023334CrossRef
4.
go back to reference Wu X, Li B, Zheng C, He X (2018) Risk factors for central lymph node metastases in patients with papillary microcarcinoma. Endocr Pract 24:1057–1062CrossRef Wu X, Li B, Zheng C, He X (2018) Risk factors for central lymph node metastases in patients with papillary microcarcinoma. Endocr Pract 24:1057–1062CrossRef
5.
go back to reference Xu Y, Xu L, Wang J (2018) Clinical predictors of lymph node metastasis and survival rate in papillary thyroid microcarcinoma: analysis of 3607 patients at a single institution. J Surg Res 221:128–134CrossRef Xu Y, Xu L, Wang J (2018) Clinical predictors of lymph node metastasis and survival rate in papillary thyroid microcarcinoma: analysis of 3607 patients at a single institution. J Surg Res 221:128–134CrossRef
7.
go back to reference Lee J, Song Y, Soh EY (2014) Central lymph node metastasis is an important prognostic factor in patients with papillary thyroid microcarcinoma. J Korean Med Sci 29:48–52CrossRef Lee J, Song Y, Soh EY (2014) Central lymph node metastasis is an important prognostic factor in patients with papillary thyroid microcarcinoma. J Korean Med Sci 29:48–52CrossRef
8.
go back to reference Haugen BR, Alexander EK, Bible KC et al (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 26:1–133CrossRef Haugen BR, Alexander EK, Bible KC et al (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 26:1–133CrossRef
9.
go back to reference Conzo G, Tartaglia E, Avenia N et al (2016) Role of prophylactic central compartment lymph node dissection in clinically N0 differentiated thyroid cancer patients: analysis of risk factors and review of modern trends. World J Surg Oncol 14:149CrossRef Conzo G, Tartaglia E, Avenia N et al (2016) Role of prophylactic central compartment lymph node dissection in clinically N0 differentiated thyroid cancer patients: analysis of risk factors and review of modern trends. World J Surg Oncol 14:149CrossRef
10.
go back to reference Michalaki M, Bountouris P, Roupas ND et al (2016) Low-risk papillary thyroid carcinoma patients who underwent near-total thyroidectomy without prophylactic central compartment lymph node dissection and were ablated with low-dose 50mCi RAI had excellent 10-year prognosis. Hormones (Athens) 15:511–517 Michalaki M, Bountouris P, Roupas ND et al (2016) Low-risk papillary thyroid carcinoma patients who underwent near-total thyroidectomy without prophylactic central compartment lymph node dissection and were ablated with low-dose 50mCi RAI had excellent 10-year prognosis. Hormones (Athens) 15:511–517
11.
go back to reference Ito Y, Miyauchi A, Kudo T, Kihara M, Fukushima M, Miya A (2017) The effectiveness of prophylactic modified neck dissection for reducing the development of lymph node recurrence of papillary thyroid carcinoma. World J Surg 41:2283–2289CrossRef Ito Y, Miyauchi A, Kudo T, Kihara M, Fukushima M, Miya A (2017) The effectiveness of prophylactic modified neck dissection for reducing the development of lymph node recurrence of papillary thyroid carcinoma. World J Surg 41:2283–2289CrossRef
12.
go back to reference Viola D, Materazzi G, Valerio L et al (2015) Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab 100:1316–1324CrossRef Viola D, Materazzi G, Valerio L et al (2015) Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study. J Clin Endocrinol Metab 100:1316–1324CrossRef
13.
go back to reference Aydin OU, Soylu L, Ozbas S et al (2016) The risk of hypoparathyroidism after central compartment lymph node dissection in the surgical treatment of pT1, N0 thyroid papillary carcinoma. Eur Rev Med Pharmacol Sci 20:1781–1787PubMed Aydin OU, Soylu L, Ozbas S et al (2016) The risk of hypoparathyroidism after central compartment lymph node dissection in the surgical treatment of pT1, N0 thyroid papillary carcinoma. Eur Rev Med Pharmacol Sci 20:1781–1787PubMed
14.
go back to reference Takami H, Ito Y, Okamoto T, Onoda N, Noguchi H, Yoshida A (2014) Revisiting the guidelines issued by the Japanese Society of Thyroid Surgeons and Japan Association of endocrine surgeons: a gradual move towards consensus between Japanese and western practice in the management of thyroid carcinoma. World J Surg 38:2002–2010CrossRef Takami H, Ito Y, Okamoto T, Onoda N, Noguchi H, Yoshida A (2014) Revisiting the guidelines issued by the Japanese Society of Thyroid Surgeons and Japan Association of endocrine surgeons: a gradual move towards consensus between Japanese and western practice in the management of thyroid carcinoma. World J Surg 38:2002–2010CrossRef
15.
go back to reference Cho SJ, Suh CH, Baek JH, Chung SR, Choi YJ, Lee JH (2019) Diagnostic performance of CT in detection of metastatic cervical lymph nodes in patients with thyroid cancer: a systematic review and meta-analysis. Eur Radiol 29:4635–4647CrossRef Cho SJ, Suh CH, Baek JH, Chung SR, Choi YJ, Lee JH (2019) Diagnostic performance of CT in detection of metastatic cervical lymph nodes in patients with thyroid cancer: a systematic review and meta-analysis. Eur Radiol 29:4635–4647CrossRef
16.
go back to reference Lee DH, Kim YK, Yu HW, Choi JY, Park SY, Moon JH (2019) Computed tomography (CT) for detecting cervical lymph node metastasis in patients who have papillary thyroid microcarcinoma with tumor characteristics appropriate for active surveillance. Thyroid. https://doi.org/10.1089/thy.2019.0100 Lee DH, Kim YK, Yu HW, Choi JY, Park SY, Moon JH (2019) Computed tomography (CT) for detecting cervical lymph node metastasis in patients who have papillary thyroid microcarcinoma with tumor characteristics appropriate for active surveillance. Thyroid. https://​doi.​org/​10.​1089/​thy.​2019.​0100
17.
go back to reference Liu Z, Xun X, Wang Y et al (2014) MRI and ultrasonography detection of cervical lymph node metastases in differentiated thyroid carcinoma before reoperation. Am J Transl Res 6(2):147–154PubMedPubMedCentral Liu Z, Xun X, Wang Y et al (2014) MRI and ultrasonography detection of cervical lymph node metastases in differentiated thyroid carcinoma before reoperation. Am J Transl Res 6(2):147–154PubMedPubMedCentral
18.
go back to reference Hwang HS, Orloff LA (2011) Efficacy of preoperative neck ultrasound in the detection of cervical lymph node metastasis from thyroid cancer. Laryngoscope 121:487–491CrossRef Hwang HS, Orloff LA (2011) Efficacy of preoperative neck ultrasound in the detection of cervical lymph node metastasis from thyroid cancer. Laryngoscope 121:487–491CrossRef
19.
go back to reference Stulak JM, Grant CS, Farley DR et al (2006) Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg 141:489–494 discussion 494-496CrossRef Stulak JM, Grant CS, Farley DR et al (2006) Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Arch Surg 141:489–494 discussion 494-496CrossRef
20.
go back to reference Yeh MW, Bauer AJ, Bernet VA et al (2015) American Thyroid Association statement on preoperative imaging for thyroid cancer surgery. Thyroid 25:3–14CrossRef Yeh MW, Bauer AJ, Bernet VA et al (2015) American Thyroid Association statement on preoperative imaging for thyroid cancer surgery. Thyroid 25:3–14CrossRef
21.
go back to reference Siddiqui S, White MG, Antic T et al (2016) Clinical and pathologic predictors of lymph node metastasis and recurrence in papillary thyroid microcarcinoma. Thyroid 26:807–815CrossRef Siddiqui S, White MG, Antic T et al (2016) Clinical and pathologic predictors of lymph node metastasis and recurrence in papillary thyroid microcarcinoma. Thyroid 26:807–815CrossRef
22.
go back to reference Wang Y, Guan Q, Xiang J (2018) Nomogram for predicting central lymph node metastasis in papillary thyroid microcarcinoma: a retrospective cohort study of 8668 patients. Int J Surg 55:98–102CrossRef Wang Y, Guan Q, Xiang J (2018) Nomogram for predicting central lymph node metastasis in papillary thyroid microcarcinoma: a retrospective cohort study of 8668 patients. Int J Surg 55:98–102CrossRef
23.
go back to reference Nie X, Tan Z, Ge M (2017) Skip metastasis in papillary thyroid carcinoma is difficult to predict in clinical practice. BMC Cancer 17:702CrossRef Nie X, Tan Z, Ge M (2017) Skip metastasis in papillary thyroid carcinoma is difficult to predict in clinical practice. BMC Cancer 17:702CrossRef
24.
go back to reference Adler DD, Carson PL, Rubin JM, Quinn-Reid D (1990) Doppler ultrasound color flow imaging in the study of breast cancer: preliminary findings. Ultrasound Med Biol 16:553–559 Adler DD, Carson PL, Rubin JM, Quinn-Reid D (1990) Doppler ultrasound color flow imaging in the study of breast cancer: preliminary findings. Ultrasound Med Biol 16:553–559
25.
go back to reference Fisher SB, Perrier ND (2018) The incidental thyroid nodule. CA Cancer J Clin 68:97–105CrossRef Fisher SB, Perrier ND (2018) The incidental thyroid nodule. CA Cancer J Clin 68:97–105CrossRef
26.
go back to reference Wu LM, Gu HY, Qu XH et al (2012) The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node metastases in patients with papillary thyroid carcinoma: a meta-analysis. Eur J Radiol 81:1798–1805CrossRef Wu LM, Gu HY, Qu XH et al (2012) The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node metastases in patients with papillary thyroid carcinoma: a meta-analysis. Eur J Radiol 81:1798–1805CrossRef
27.
go back to reference Sauerbrei W, Royston P, Binder H (2007) Selection of important variables and determination of functional form for continuous predictors in multivariable model building. Stat Med 26:5512–5528CrossRef Sauerbrei W, Royston P, Binder H (2007) Selection of important variables and determination of functional form for continuous predictors in multivariable model building. Stat Med 26:5512–5528CrossRef
28.
go back to reference Kramer AA, Zimmerman JE (2007) Assessing the calibration of mortality benchmarks in critical care: the Hosmer-Lemeshow test revisited. Crit Care Med 35:2052–2056CrossRef Kramer AA, Zimmerman JE (2007) Assessing the calibration of mortality benchmarks in critical care: the Hosmer-Lemeshow test revisited. Crit Care Med 35:2052–2056CrossRef
29.
go back to reference Thompson AM, Turner RM, Hayen A et al (2014) A preoperative nomogram for the prediction of ipsilateral central compartment lymph node metastases in papillary thyroid cancer. Thyroid 24:675–682CrossRef Thompson AM, Turner RM, Hayen A et al (2014) A preoperative nomogram for the prediction of ipsilateral central compartment lymph node metastases in papillary thyroid cancer. Thyroid 24:675–682CrossRef
30.
go back to reference Oh HS, Park S, Kim M et al (2017) Young age and male sex are predictors of large-volume central neck lymph node metastasis in clinical N0 papillary thyroid microcarcinomas. Thyroid 27:1285–1290CrossRef Oh HS, Park S, Kim M et al (2017) Young age and male sex are predictors of large-volume central neck lymph node metastasis in clinical N0 papillary thyroid microcarcinomas. Thyroid 27:1285–1290CrossRef
31.
go back to reference Xu SY, Yao JJ, Zhou W, Chen L, Zhan WW (2019) Clinical characteristics and ultrasonographic features for predicting central lymph node metastasis in clinically node-negative papillary thyroid carcinoma without capsule invasion. Head Neck 41:3984–3991CrossRef Xu SY, Yao JJ, Zhou W, Chen L, Zhan WW (2019) Clinical characteristics and ultrasonographic features for predicting central lymph node metastasis in clinically node-negative papillary thyroid carcinoma without capsule invasion. Head Neck 41:3984–3991CrossRef
32.
go back to reference 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 24:27–34CrossRef 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 24:27–34CrossRef
33.
go back to reference Wang F, Zhao S, Shen X et al (2018) BRAF V600E confers male sex disease-specific mortality risk in patients with papillary thyroid cancer. J Clin Oncol 36:2787–2795 Wang F, Zhao S, Shen X et al (2018) BRAF V600E confers male sex disease-specific mortality risk in patients with papillary thyroid cancer. J Clin Oncol 36:2787–2795
34.
go back to reference Al Afif A, Williams BA, Rigby MH et al (2015) Multifocal papillary thyroid cancer increases the risk of central lymph node metastasis. Thyroid 25:1008–1012CrossRef Al Afif A, Williams BA, Rigby MH et al (2015) Multifocal papillary thyroid cancer increases the risk of central lymph node metastasis. Thyroid 25:1008–1012CrossRef
35.
go back to reference Huang XP, Ye TT, Zhang L et al (2018) Sonographic features of papillary thyroid microcarcinoma predicting high-volume central neck lymph node metastasis. Surg Oncol 27:172–176CrossRef Huang XP, Ye TT, Zhang L et al (2018) Sonographic features of papillary thyroid microcarcinoma predicting high-volume central neck lymph node metastasis. Surg Oncol 27:172–176CrossRef
36.
go back to reference Zhao L, Yan H, Pang P et al (2019) Thyroid nodule size calculated using ultrasound and gross pathology as predictors of cancer: a 23-year retrospective study. Diagn Cytopathol 47:187–193CrossRef Zhao L, Yan H, Pang P et al (2019) Thyroid nodule size calculated using ultrasound and gross pathology as predictors of cancer: a 23-year retrospective study. Diagn Cytopathol 47:187–193CrossRef
37.
go back to reference Bai Y, Zhou G, Nakamura M et al (2009) Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma. Mod Pathol 22:887–894CrossRef Bai Y, Zhou G, Nakamura M et al (2009) Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma. Mod Pathol 22:887–894CrossRef
39.
go back to reference Pyo JS, Kang G, Kim DH, Park C, Kim JH, Sohn JH (2013) The prognostic relevance of psammoma bodies and ultrasonographic intratumoral calcifications in papillary thyroid carcinoma. World J Surg 37:2330–2335CrossRef Pyo JS, Kang G, Kim DH, Park C, Kim JH, Sohn JH (2013) The prognostic relevance of psammoma bodies and ultrasonographic intratumoral calcifications in papillary thyroid carcinoma. World J Surg 37:2330–2335CrossRef
40.
go back to reference Jang JY, Kim DS, Park HY et al (2019) Preoperative serum VEGF-C but not VEGF-A level is correlated with lateral neck metastasis in papillary thyroid carcinoma. Head Neck 41:2602–2609CrossRef Jang JY, Kim DS, Park HY et al (2019) Preoperative serum VEGF-C but not VEGF-A level is correlated with lateral neck metastasis in papillary thyroid carcinoma. Head Neck 41:2602–2609CrossRef
41.
go back to reference Tu DG, Chang WW, Jan MS, Tu CW, Lu YC, Tai CK (2016) Promotion of metastasis of thyroid cancer cells via NRP-2-mediated induction. Oncol Lett 12:4224–4230CrossRef Tu DG, Chang WW, Jan MS, Tu CW, Lu YC, Tai CK (2016) Promotion of metastasis of thyroid cancer cells via NRP-2-mediated induction. Oncol Lett 12:4224–4230CrossRef
42.
go back to reference Vickers AJ, Cronin AM, Elkin EB, Gonen M (2008) Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak 8:53CrossRef Vickers AJ, Cronin AM, Elkin EB, Gonen M (2008) Extensions to decision curve analysis, a novel method for evaluating diagnostic tests, prediction models and molecular markers. BMC Med Inform Decis Mak 8:53CrossRef
43.
go back to reference Xu JM, Xu XH, Xu HX et al (2016) Prediction of cervical lymph node metastasis in patients with papillary thyroid cancer using combined conventional ultrasound, strain elastography, and acoustic radiation force impulse (ARFI) elastography. Eur Radiol 26:2611–2622CrossRef Xu JM, Xu XH, Xu HX et al (2016) Prediction of cervical lymph node metastasis in patients with papillary thyroid cancer using combined conventional ultrasound, strain elastography, and acoustic radiation force impulse (ARFI) elastography. Eur Radiol 26:2611–2622CrossRef
44.
go back to reference Lee JH, Ha EJ, Kim JH (2019) Application of deep learning to the diagnosis of cervical lymph node metastasis from thyroid cancer with CT. Eur Radiol 29:5452–5457CrossRef Lee JH, Ha EJ, Kim JH (2019) Application of deep learning to the diagnosis of cervical lymph node metastasis from thyroid cancer with CT. Eur Radiol 29:5452–5457CrossRef
Metadata
Title
Papillary thyroid carcinoma: an ultrasound-based nomogram improves the prediction of lymph node metastases in the central compartment
Authors
Xiaoqi Tian
Qing Song
Fang Xie
Ling Ren
Ying Zhang
Jie Tang
Yan Zhang
Zhuang Jin
Yaqiong Zhu
Mingbo Zhang
Yukun Luo
Publication date
01-11-2020
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 11/2020
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-020-06906-6

Other articles of this Issue 11/2020

European Radiology 11/2020 Go to the issue