Association of Lymph Node Density With Survival of Patients With Papillary Thyroid Cancer | Endocrine Surgery | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.207.129.82. Please contact the publisher to request reinstatement.
1.
Davies  L, Welch  HG.  Increasing incidence of thyroid cancer in the United States, 1973-2002.  JAMA. 2006;295(18):2164-2167.PubMedGoogle ScholarCrossref
2.
Grebe  SK, Hay  ID.  Thyroid cancer nodal metastases: biologic significance and therapeutic considerations.  Surg Oncol Clin N Am. 1996;5(1):43-63.PubMedGoogle ScholarCrossref
3.
Nam-Goong  IS, Kim  HY, Gong  G,  et al.  Ultrasonography-guided fine-needle aspiration of thyroid incidentaloma: correlation with pathological findings.  Clin Endocrinol (Oxf). 2004;60(1):21-28.PubMedGoogle ScholarCrossref
4.
Qubain  SW, Nakano  S, Baba  M, Takao  S, Aikou  T.  Distribution of lymph node micrometastasis in pN0 well-differentiated thyroid carcinoma.  Surgery. 2002;131(3):249-256.PubMedGoogle ScholarCrossref
5.
Leboulleux  S, Rubino  C, Baudin  E,  et al.  Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis.  J Clin Endocrinol Metab. 2005;90(10):5723-5729.PubMedGoogle ScholarCrossref
6.
Bhattacharyya  N.  A population-based analysis of survival factors in differentiated and medullary thyroid carcinoma.  Otolaryngol Head Neck Surg. 2003;128(1):115-123.PubMedGoogle ScholarCrossref
7.
Podnos  YD, Smith  D, Wagman  LD, Ellenhorn  JD.  The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer.  Am Surg. 2005;71(9):731-734.PubMedGoogle Scholar
8.
Agrama  MT, Reiter  D, Cunnane  MF, Topham  A, Keane  WM.  Nodal yield in neck dissection and the likelihood of metastases.  Otolaryngol Head Neck Surg. 2003;128(2):185-190.PubMedGoogle ScholarCrossref
9.
Patel  SG, Amit  M, Yen  TC,  et al; International Consortium for Outcome Research (ICOR) in Head and Neck Cancer.  Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.  Br J Cancer. 2013;109(8):2087-2095.PubMedGoogle ScholarCrossref
10.
Lee  SR, Kim  HO, Son  BH, Shin  JH, Yoo  CH.  Prognostic significance of the metastatic lymph node ratio in patients with gastric cancer.  World J Surg. 2012;36(5):1096-1101.PubMedGoogle ScholarCrossref
11.
Partelli  S, Fernandez-Del Castillo  C, Bassi  C,  et al.  Invasive intraductal papillary mucinous carcinomas of the pancreas: predictors of survival and the role of lymph node ratio.  Ann Surg. 2010;251(3):477-482.PubMedGoogle ScholarCrossref
12.
Qu  N, Shi  RL, Lu  ZW,  et al.  Metastatic lymph node ratio can further stratify risk for mortality in medullary thyroid cancer patients: a population-based analysis.  Oncotarget. 2016;7(40):65937-65945.PubMedGoogle Scholar
13.
Ryu  IS, Song  CI, Choi  SH, Roh  JL, Nam  SY, Kim  SY.  Lymph node ratio of the central compartment is a significant predictor for locoregional recurrence after prophylactic central neck dissection in patients with thyroid papillary carcinoma.  Ann Surg Oncol. 2014;21(1):277-283.PubMedGoogle ScholarCrossref
14.
Jiang  T, Huang  C, Xu  Y,  et al.  Ratio of positive lymph nodes: the prognostic value in stage IV thyroid cancer.  Oncotarget. 2017;8:79462-79468.Google Scholar
15.
Robbins  KT, Shaha  AR, Medina  JE,  et al; Committee for Neck Dissection Classification, American Head and Neck Society.  Consensus statement on the classification and terminology of neck dissection.  Arch Otolaryngol Head Neck Surg. 2008;134(5):536-538.PubMedGoogle ScholarCrossref
16.
Pathology Group. Guidelines for the examination and reporting of head and neck cancer specimens. Leeds, UK: Yorkshire Cancer Network; 2010. http://www.angcn.nhs.uk/download/1ac80ad8-643d-4721-a7a3-06dfde2fb219. Accessed October 11, 2017.
17.
Peto  R, Pike  MC, Armitage  P,  et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.  Br J Cancer. 1977;35(1):1-39.PubMedGoogle ScholarCrossref
18.
Haugen  BR, Alexander  EK, Bible  KC,  et al.  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. 2016;26(1):1-133.PubMedGoogle ScholarCrossref
19.
Cox  D.  Regression models and life-tables.  J R Stat Soc [Ser A]. 1982;34(2):187-220.Google Scholar
20.
Xiao  LB, Yu  JX, Wu  WH, Xu  FF, Yang  SB.  Superiority of metastatic lymph node ratio to the 7th edition UICC N staging in gastric cancer.  World J Gastroenterol. 2011;17(46):5123-5130.PubMedGoogle ScholarCrossref
21.
Espín  F, Bianchi  A, Llorca  S,  et al.  Metastatic lymph node ratio versus number of metastatic lymph nodes as a prognostic factor in gastric cancer.  Eur J Surg Oncol. 2012;38(6):497-502.PubMedGoogle ScholarCrossref
22.
Etzioni  R, Kooperberg  C, Pepe  M, Smith  R, Gann  PH.  Combining biomarkers to detect disease with application to prostate cancer.  Biostatistics. 2003;4(4):523-538.PubMedGoogle ScholarCrossref
23.
Heagerty  PJ, Lumley  T, Pepe  MS.  Time-dependent ROC curves for censored survival data and a diagnostic marker.  Biometrics. 2000;56(2):337-344.PubMedGoogle ScholarCrossref
24.
Heaton  CM, Chang  JL, Orloff  LA.  Prognostic implications of lymph node yield in central and lateral neck dissections for well-differentiated papillary thyroid carcinoma.  Thyroid. 2016;26(3):434-440.PubMedGoogle ScholarCrossref
25.
Robinson  TJ, Thomas  S, Dinan  MA, Roman  S, Sosa  JA, Hyslop  T.  How many lymph nodes are enough? assessing the adequacy of lymph node yield for papillary thyroid cancer.  J Clin Oncol. 2016;34(28):3434-3439.PubMedGoogle ScholarCrossref
26.
Kim  M, Kim  WG, Oh  HS,  et al.  Comparison of the 7th and 8th editions of the AJCC/UICC TNM staging system for differentiated thyroid cancer.  Thyroid. 2017;27(9):1149-1155.PubMedGoogle ScholarCrossref
27.
Hughes  DT, White  ML, Miller  BS, Gauger  PG, Burney  RE, Doherty  GM.  Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer.  Surgery. 2010;148(6):1100-1106.PubMedGoogle ScholarCrossref
28.
Randolph  GW, Duh  QY, Heller  KS,  et al; American Thyroid Association Surgical Affairs Committee’s Taskforce on Thyroid Cancer Nodal Surgery.  The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension.  Thyroid. 2012;22(11):1144-1152.PubMedGoogle ScholarCrossref
29.
Lundgren  CI, Hall  P, Dickman  PW, Zedenius  J.  Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study.  Cancer. 2006;106(3):524-531.PubMedGoogle ScholarCrossref
30.
Slidell  MB, Chang  DC, Cameron  JL,  et al.  Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis.  Ann Surg Oncol. 2008;15(1):165-174.PubMedGoogle ScholarCrossref
31.
Baek  SK, Jung  KY, Kang  SM,  et al.  Clinical risk factors associated with cervical lymph node recurrence in papillary thyroid carcinoma.  Thyroid. 2010;20(2):147-152.PubMedGoogle ScholarCrossref
32.
Beasley  NJ, Lee  J, Eski  S, Walfish  P, Witterick  I, Freeman  JL.  Impact of nodal metastases on prognosis in patients with well-differentiated thyroid cancer.  Arch Otolaryngol Head Neck Surg. 2002;128(7):825-828.PubMedGoogle ScholarCrossref
33.
Amar  A, Rapoport  A, Curioni  OA, Dedivitis  RA, Cernea  CR, Brandão  LG.  The density of metastatic lymph node as prognostic factor in squamous cell carcinoma of the tongue and floor of the mouth.  Braz J Otorhinolaryngol. 2012;78(3):86-90.PubMedGoogle ScholarCrossref
34.
Kim  SY, Nam  SY, Choi  SH, Cho  KJ, Roh  JL.  Prognostic value of lymph node density in node-positive patients with oral squamous cell carcinoma.  Ann Surg Oncol. 2011;18(8):2310-2317.PubMedGoogle ScholarCrossref
35.
Rudra  S, Spiotto  MT, Witt  ME, Blair  EA, Stenson  K, Haraf  DJ.  Lymph node density—prognostic value in head and neck cancer.  Head Neck. 2014;36(2):266-272.PubMedGoogle ScholarCrossref
36.
Chen  CC, Lin  JC, Chen  KW.  Lymph node ratio as a prognostic factor in head and neck cancer patients.  Radiat Oncol. 2015;10:181.PubMedGoogle ScholarCrossref
37.
Beal  SH, Chen  SL, Schneider  PD, Martinez  SR.  An evaluation of lymph node yield and lymph node ratio in well-differentiated thyroid carcinoma.  Am Surg. 2010;76(1):28-32.PubMedGoogle Scholar
38.
Schneider  DF, Chen  H, Sippel  RS.  Impact of lymph node ratio on survival in papillary thyroid cancer.  Ann Surg Oncol. 2013;20(6):1906-1911.PubMedGoogle ScholarCrossref
39.
Wang  LY, Palmer  FL, Nixon  IJ,  et al.  Lateral neck lymph node characteristics prognostic of outcome in patients with clinically evident N1b papillary thyroid cancer.  Ann Surg Oncol. 2015;22(11):3530-3536.PubMedGoogle ScholarCrossref
40.
Vas Nunes  JH, Clark  JR, Gao  K,  et al.  Prognostic implications of lymph node yield and lymph node ratio in papillary thyroid carcinoma.  Thyroid. 2013;23(7):811-816.PubMedGoogle ScholarCrossref
41.
Trimble  EL, Abrams  JS, Meyer  RM,  et al.  Improving cancer outcomes through international collaboration in academic cancer treatment trials.  J Clin Oncol. 2009;27(30):5109-5114.PubMedGoogle ScholarCrossref
Original Investigation
November 30, 2017

Association of Lymph Node Density With Survival of Patients With Papillary Thyroid Cancer

Author Affiliations
  • 1Division of Surgery, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston
  • 2Division of Internal Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston
  • 3Division of Surgery, Department of Endocrine Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston
JAMA Otolaryngol Head Neck Surg. 2018;144(2):108-114. doi:10.1001/jamaoto.2017.2416
Key Points

Question  Is there an association between lymph node density (LND)—the ratio of the number of positive lymph nodes to the total number of nodes excised—and survival in patients with papillary thyroid cancer?

Findings  In a cohort of 2542 patients, central neck LND reliably stratified patients according to risk of death. Incorporating LND into the current American Joint Committee on Cancer staging system successfully stratified risk groups compared with the traditional TNM staging system.

Meaning  Lymph node density can be used as a complementary prognostic tool to assess risk of disease-related death in patients with papillary thyroid cancer.

Abstract

Importance  Lymph node metastases are common in papillary thyroid cancer (PTC), yet the impact of nodal metastases on survival remains unclear. Lymph node density (LND) is the ratio between the number of positive lymph nodes excised and the total number of excised lymph nodes. Lymph node density has been suggested as a prognostic factor in many types of cancer.

Objective  To evaluate the prognostic role of LND in PTC.

Design, Setting, and Participants  This cohort study reviewed medical records of patients with PTC who were treated at the University of Texas MD Anderson Cancer Center between January 1, 2000, and December 31, 2015. Survival and recurrence outcomes were calculated by using the Kaplan-Meier method. Significant variables on univariate analysis were subjected to a Cox proportional hazards regression multivariate model.

Main Outcomes and Measures  Primary study outcome was disease-specific survival (DSS); other measurements included overall survival (OS).

Results  The study cohort included data for 2542 patients (1801 [71%] female; median age, 48 years [range, 18-97 years]) with a median follow-up of 55 months (range, 4-192 months). The 10-year disease-specific survival rate was 98% for patients with LND of 0.19 or less, compared with 90% for those with LND greater than 0.19 (effect size, 8%; 95% CI, 4%-15%). The 10-year overall survival was 87% for patients with LND of 0.19 or less, compared with 79% for patients with LND greater than 0.19 (effect size, 8%; 95% CI, 3%-15%). Multivariable analysis revealed that LND greater than 0.19 was independently associated with an adverse DSS (hazard ratio [HR], 4.11; 95% CI, 2.11-8.97) and OS (HR, 1.96; 95% CI, 1.24-4.11). Subgroup analysis of patients with 18 or more lymph nodes analyzed revealed that LND greater than 0.19 remained a significant marker for DSS (HR, 2.94; 95% CI, 1.36-9.81) and OS (HR, 2.26; 95% CI, 1.12-5.34). Incorporating LND into the current American Joint Committee on Cancer staging system successfully stratified risk groups compared with the traditional TNM staging system.

Conclusions and Relevance  This single-institute study demonstrates the reproducibility of LND as a predictor of outcomes in PTC. Lymph node density can potentially assist in identifying patients with poorer survival who may benefit from more aggressive adjuvant therapy.

×