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Original Article |

Extrathyroidal Extension in Well-Differentiated Thyroid Cancer Macroscopic vs Microscopic as a Predictor of Outcome FREE

Amanda Hu, MD; Jonathan Clark, MBBS, BSc, FRACS; Richard J. Payne, MD, MSc, FRCSC; Spiro Eski, MD; Paul G. Walfish, MD, FRCPC; Jeremy L. Freeman, MD, FRCSC
[+] Author Affiliations

Author Affiliations: Department of Otolaryngology, University of Western Ontario, London (Dr Hu); Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia (Dr Clark); and Department of Otolaryngology (Drs Payne, Eski, and Freeman) and Endocrine Division and Head and Neck Oncology Program, Department of Medicine (Dr Walfish), Mount Sinai Hospital, Toronto, Ontario, Canada.


Arch Otolaryngol Head Neck Surg. 2007;133(7):644-649. doi:10.1001/archotol.133.7.644.
Text Size: A A A
Published online

Objective  To examine the prognostic difference in well-differentiated thyroid cancer between macroscopic extrathyroidal extension (ETE), which is appreciated in the operating room, vs microscopic ETE, which is only appreciated under the microscope by the pathologist.

Design  Retrospective medical record review.

Setting  Tertiary care academic hospital.

Patients  Among 582 patients, those who were surgically treated for stage III well-differentiated thyroid cancer with a minimum 5-year follow-up were included. Fifty-five patients (10%) (17 males and 38 females [mean age, 53.1 years]) met the selection criteria.

Main Outcome Measures  Disease-specific survival and overall survival.

Results  Thirty-two patients (58%) had macroscopic ETE, while 23 patients (42%) had microscopic ETE. Twenty-year disease-specific survival in the macroscopic group was 47% (8 of 17) and 45% (5 of 11) in the microscopic group (P = .45). Twenty-year overall survival in the macroscopic group was 27% (3 of 11) and 24% (4 of 17) in the microscopic group (P = .59). The only confounding factor was external beam radiation therapy (EBRT). More patients with macroscopic ETE were treated with EBRT (P = .007). When survival was stratified according to EBRT, patients with macroscopic ETE who did not receive EBRT had diminished disease-specific survival (P = .07) and overall survival (P = .12). On multivariate analysis, EBRT was the only predictor of improved disease-specific survival (P = .02) and overall survival (P = .06).

Conclusions  In selected patients with macroscopic ETE, we recommend postoperative EBRT. Further investigation is required to determine whether macroscopic ETE vs microscopic ETE is an independent predictor of outcome.

Figures in this Article

Extrathyroidal extension (ETE) is defined as extension of the primary tumor outside of the thyroid capsule and invasion into the surrounding structures (eg, strap muscles, trachea, larynx, vasculature, esophagus, and recurrent laryngeal nerve).1,2 The incidence of ETE in well-differentiated thyroid cancer (WDTC) varies in different series but ranges from 5% to 34%.1,2 Extrathyroidal extension is well established as an important adverse prognostic factor111 and is used in several staging systems, including the EORTC (European Organization Research Treatment Cancer),12 TNM classification,13 system by DeGroot et al,14 AGES (age, grade, ETE, and size),15 AMES (age, metastasis, ETE, and size),16 and MACIS (metastasis, age, completeness of resection, invasion, and size).17 Although ETE has been extensively studied, it is unclear whether microscopic ETE carries the same adverse outcome as macroscopic ETE. The objective of this study was to examine the prognostic difference between macroscopic ETE, which is appreciated in the operating room, vs microscopic ETE, which is only appreciated under the microscope by the pathologist.

A retrospective medical record review of the Mount Sinai Hospital, Toronto, Ontario, Canada, thyroid cancer database was performed. The database contained 582 patients who had undergone surgery for WDTC between January 1, 1963, and December 31, 2000. All patients surgically treated for stage III WDTC, as defined by the system by DeGroot et al14 (ie, ETE), with a minimum of 5 years of follow-up were included. Duration of follow-up was defined as the time from the first surgery to the last contact. The mean follow-up was 10.9 years. This project received ethical approval from the ethics board at Mount Sinai Hospital.

Statistical analysis was performed using SPSS version 13.0 software (SPSS Inc, Cary, North Carolina). Normally distributed data were analyzed using (unpaired) t test, and nonparametric data were analyzed using Mann-Whitney test. Nominal variables with 2 categories were presented as percentages of patients and were analyzed using χ2 test. Nominal variables with more than 2 categories were presented as percentages of patients and were analyzed using analysis of variance. Survival and recurrence were calculated using the Kaplan-Meier method, and differences were compared using log-rank test. Multivariate analysis was performed using Cox proportional hazards models.

Patient demographic, clinicopathological, and treatment data are summarized in Table 1. The presence of ETE was examined for all 582 patients. Sixty-one of 582 patients (11%) had stage III WDTC between 1963 and 2000. Six patients had less than 5 years of follow-up and were excluded. The final sample size was 55 patients (10%). Thirty-two patients (58%) had macroscopic ETE, while 23 patients (42%) had microscopic ETE. Structures involved were muscle (34 of 55 [62%]), nerve (14 of 55 [25%]), trachea (13 of 55 [24%]), blood vessels (9 of 55 [16%]), esophagus (6 of 55 [11%]), lymphatics (3 of 55 [6%]), and other (20 of 55 [36%]). Other locations included adipose tissue and thymus. There were no differences in demographic or clinicopathological data between the 2 study groups; however, there was a significant difference in the rate of external beam radiation therapy (EBRT); 83% (25 of 30) of patients with macroscopic ETE were treated with EBRT compared with 48% (11 of 23) of patients with microscopic ETE (P = .007).

Table Graphic Jump LocationTable 1. Univariate Analysis of Demographic, Clinicopathological, and Treatment Data in the Macroscopic vs Microscopic Extrathyroidal Extension (ETE) Groups a

In Table 2, patients who received EBRT are compared with patients who did not receive EBRT relative to established risk factors for thyroid carcinoma.1517 There was no significant difference between the 2 groups in sex, age at surgery, distant metastases, pathologic type (eg, papillary), maximum tumor size, or incompleteness of resection.

Table Graphic Jump LocationTable 2. Univariate Analysis of Risk Factors for Thyroid Carcinoma in the Groups With and Without External Beam Radiation Therapy (EBRT) a

Recurrence and survival data are summarized in Table 3. Overall survival (OS) and disease-specific survival (DSS) at 20 years were 25% (7 of 28) and 46% (13 of 28), respectively. There was no significant difference in DSS and OS according to type of ETE, as shown in Figure 1 and Figure 2, respectively. However, when survival was stratified according to whether patients received adjuvant EBRT, DSS (P = .07 [Figure 3]) and OS (P = .12 [Figure 4]) were diminished for patients with macroscopic ETE who did not receive EBRT. On multivariate analysis (Table 4) using the 2 covariates of ETE and EBRT, EBRT was a significant predictor of DSS (P = .02) and was a nonsignificant predictor of OS (P = .06).

Place holder to copy figure label and caption
Figure 1.

Kaplan-Meier curves for disease-specific survival (DSS) vs extrathyroidal extension (ETE). There was no significant difference in DSS between the macroscopic ETE group and the microscopic ETE group (P = .82).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Kaplan-Meier curves for overall survival (OS) vs extrathyroidal extension (ETE). There was no significant difference in OS between the macroscopic ETE group and the microscopic ETE group (P = .97).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Kaplan-Meier curves for disease-specific survival (DSS) vs extrathyroidal extension (ETE) among patients without external beam radiation therapy. Macroscopic ETE was associated with decreased DSS (P = .07).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Kaplan-Meier curves for overall survival (OS) vs extrathyroidal extension (ETE) among patients without external beam radiation therapy. Macroscopic ETE was associated with decreased OS (P = .12).

Graphic Jump Location
Table Graphic Jump LocationTable 3. Univariate Analysis of Outcome Data in the Macroscopic vs Microscopic Extrathyroidal Extension (ETE) Groups a
Table Graphic Jump LocationTable 4. Multivariate Analysis Using the 2 Covariates of Extrathyroidal Extension (ETE) and External Beam Radiation Therapy (EBRT)

The effect of the location of ETE was also analyzed. There was no difference in recurrence or survival according to structures involved by ETE, including the trachea (P = .39 for recurrence and P = .77 for DSS). When survival was stratified according to whether patients received adjuvant EBRT, there was a significant decrease in DSS (P = .008) and an increase in recurrence (P < .001) among patients with tracheal invasion who did not receive EBRT.

There is convincing evidence that the presence of ETE is a predictor of negative outcomes in patients with WDTC.211 Despite this evidence, there are few data comparing the effect of macroscopic and microscopic ETE. Table 5 summarizes the present results and those of previous studies13,5,7,16,18,19 of patients with WDTC and ETE; we found a 10% (61 of 582) incidence of ETE; however, the literature reports a range of 2% to 45%, which may reflect the variation in definitions used for ETE.

Table Graphic Jump LocationTable 5. Previous Studies of Patients With Well-Differentiated Thyroid Cancer (WDTC) and Extrathyroidal Extension (ETE) a

On preliminary analysis, there was no difference in survival between patients with macroscopic and microscopic ETE. However, EBRT was a significant confounding factor, as more patients in the macroscopic ETE group were treated with EBRT (P = .007). For other established prognostic factors for WDTC, there was no difference in the rate of EBRT (Table 2). To address this confounding factor, the patients were stratified according to EBRT. Among patients with macroscopic ETE who received EBRT, there was no difference in survival; among patients with macroscopic ETE who did not receive EBRT, there was nonsignificant decreased DSS (P = .07) and OS (P = .12). In multivariate analysis, EBRT was the only predictor of DSS (P = .02) and OS (P = .06). In contrast to other studies,2022 we were unable to demonstrate a difference in outcome according to structures involved by ETE of WDTC. However, in patients with tracheal invasion, there were differences in disease control and in survival according to whether patients received EBRT. This suggests that EBRT negated the adverse effect of tracheal invasion.

To our knowledge, only 1 previous study23 has examined the prognostic difference between macroscopic and microscopic ETE. Gemsenjäger et al23 retrospectively reviewed 265 patients with WDTC and concluded that macroscopic ETE, but not microscopic ETE, was a significant risk factor for survival in papillary thyroid cancer (< .001) and for disease-free survival in follicular thyroid cancer (< .001). The results of the present study support this finding but also suggest that EBRT is effective in improving outcomes in patients with macroscopic ETE.

The following are indications for EBRT: (1) locally advanced unresectable disease or macroscopic residual disease after thyroidectomy, (2) palliative treatment of selected distant metastatic sites (ie, brain and bone), (3) radioactive iodine-resistant progressive disease, and (4) adjuvant treatment of local relapse for high-risk patients.2428 Determining which patients are at sufficiently high risk of local relapse to justify the short-term and long-term toxic effects of radiation therapy is controversial.2430 Brierley et al31 retrospectively reviewed 729 patients who were seen at Princess Margaret Hospital, Toronto, during 40 years. For patients older than 60 years with ETE, adjuvant EBRT resulted in statistically higher 10-year cause-specific survival (P = .04) and 10-year locoregional relapse-free (P = .01) rates. This is supported by Farahati et al,32 who retrospectively studied 238 patients with WDTC. Among 169 patients included in the study, 99 patients received EBRT, while the other 70 patients did not. They determined that patients older than 40 years with ETE and lymph node involvement from papillary carcinoma benefited the most from EBRT.

Unfortunately, the present study did not have a sufficient sample size to perform a subset analysis to determine which patients with macroscopic ETE derive the greatest benefit from EBRT. Some authors have suggested that invasion into the trachea, esophagus, nerves, and major vasculature is an appropriate indication for EBRT.26 Certainly, minimal strap muscle invasion is common, and it is unlikely that adjuvant EBRT is necessary when disease can be completely resected. Further investigation is required to determine the specific indications for local radiation therapy beyond gross residual disease after thyroidectomy.

In conclusion, for selected patients with macroscopic ETE, we recommend postoperative EBRT. Further investigation is required to determine whether macroscopic vs microscopic ETE is an independent predictor of outcome.

Correspondence: Jeremy L. Freeman, MD, FRCSC, Department of Otolaryngology, Mount Sinai Hospital, 600 University Ave, Ste 401, Toronto, ON M5G 1X5, Canada (jfreeman@mtsinai.on.ca).

Submitted for Publication: August 5, 2006; final revision received January 1, 2007; accepted March 1, 2007.

Author Contributions: Drs Clark and Payne had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hu, Clark, Payne, and Freeman. Acquisition of data: Hu, Payne, and Eski. Analysis and interpretation of data: Hu, Clark, Payne, and Walfish. Drafting of the manuscript: Hu, Clark, Payne, and Eski. Critical revision of the manuscript for important intellectual content: Hu, Clark, Payne, Walfish, and Freeman. Statistical analysis: Clark. Obtained funding: Freeman. Administrative, technical, and material support: Hu, Payne, Eski, and Freeman. Study supervision: Payne, Walfish, and Freeman.

Financial Disclosure: Dr Walfish has received unrestricted educational grants from Abbott Laboratories (Canada) and Genzyme (Canada).

Funding/Support: This study was supported in part by unrestricted educational grants from the Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases at Mount Sinai Hospital (Dr Walfish), the Temmy Latner/Dynacare Family Foundation, and the Julius Kuhl Family Foundation (Dr Walfish).

Previous Presentation: This study was presented at the American Head and Neck Society 2006 Annual Meeting and Research Workshop on the Biology, Prevention and Treatment of Head and Neck Cancer; August 19, 2006; Chicago, Illinois.

Ortiz  SRodriguez  JMSoria  T  et al.  Extrathyroid spread in papillary carcinoma of the thyroid: clinicopathological and prognostic study. Otolaryngol Head Neck Surg 2001;124 (3) 261- 265
PubMed Link to Article
Andersen  PEKinsella  JLoree  TRShaha  ARShah  JP Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 1995;170 (5) 467- 470
PubMed Link to Article
Carcangiu  MLZampi  GPupi  ACastagnoli  ARosai  J Papillary carcinoma of the thyroid: a clinicopathologic study of 241 cases treated at the University of Florence, Italy. Cancer 1985;55 (4) 805- 828
PubMed Link to Article
Cody  HS  IIIShah  JP Locally invasive, well-differentiated thyroid cancer: 22 years' experience at Memorial Sloan-Kettering Cancer Center. Am J Surg 1981;142 (4) 480- 483
PubMed Link to Article
Mazzaferri  EL Papillary thyroid carcinoma: factors influencing prognosis and current therapy. Semin Oncol1987143315332 [published correction appears in Semin Oncol. 1988;15(3):x]
PubMed
McCaffrey  TVBergstralh  EJHay  ID Locally invasive papillary thyroid carcinoma 1940-1990. Head Neck 1994;16 (2) 165- 172
PubMed Link to Article
McConahey  WMHay  IDWoolner  LBvan Heerden  JATaylor  WF Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc 1986;61 (12) 978- 996
PubMed Link to Article
Mizukami  YNuguchi  MMichigishi  T  et al.  Papillary thyroid carcinoma in Kanazawa, Japan: prognostic significance of histological subtypes. Histopathology 1992;20 (3) 243- 250
PubMed Link to Article
Jukkola  ABloigu  REbeling  TSalmela  PBlanco  G Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications. Endocr Relat Cancer 2004;11 (3) 571- 579
PubMed Link to Article
Palme  CEWaseem  ZRaza  SN  et al.  Management and outcome of recurrent well-differentiated thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2004;130 (7) 819- 824
PubMed Link to Article
Cushing  SLPalme  CEAudet  NEski  SWalfish  PGFreeman  JL Prognostic factors in well-differentiated thyroid carcinoma. Laryngoscope 2004;114 (12) 2110- 2115
PubMed Link to Article
Byar  DPGreen  SBDor  P  et al.  A prognostic index for thyroid carcinoma: a study of the E.O.R.T.C. Thyroid Cancer Cooperative Group. Eur J Cancer 1979;15 (8) 1033- 1041
PubMed Link to Article
Greene  FLPage  DLFleming  ID  et al AJCC Cancer Staging Handbook. 6th ed. Philadelphia, PA: Springer Publishing Co Inc; 2002
DeGroot  LJKaplan  ELMcCormick  MStrauss  FH Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 1990;71 (2) 414- 424
PubMed Link to Article
Hay  IDBergstralh  EJGoellner  JREbersold  JRGrant  CS Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 1993;114 (6) 1050- 1058
PubMed
Cady  BRossi  R An expanded view of risk-group definition in well differentiated thyroid carcinoma. Surgery 1988;104 (6) 947- 953
PubMed
Hay  IDGrant  CSTaylor  WFMcConahey  WM Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987;102 (6) 1088- 1095
PubMed
Shah  JPLoree  TRDharker  DStrong  EWBegg  CVlamis  V Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 1992;164 (6) 658- 661
PubMed Link to Article
Herrera  MFLopez-Graniel  CMSaldana  J  et al.  Papillary thyroid carcinoma in Mexican patients: clinical aspects and prognostic factors. World J Surg 1996;20 (1) 94- 100
PubMed Link to Article
Kowalski  LPFilho  JG Results of the treatment of locally invasive thyroid carcinoma. Head Neck 2002;24 (4) 340- 344
PubMed Link to Article
McCaffrey  JC Aerodigestive tract invasion by well-differentiated thyroid carcinoma: diagnosis, management, prognosis, and biology. Laryngoscope 2006;116 (1) 1- 11
PubMed Link to Article
Czaja  JMMcCaffrey  TV The surgical management of laryngotracheal invasion by well-differentiated papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 1997;123 (5) 484- 490
PubMed Link to Article
Gemsenjäger  EHeitz  PUSeifert  BMartina  BSchweizer  I Differentiated thyroid carcinoma: follow-up of 264 patients from one institution for up to 25 years. Swiss Med Wkly 2001;131 (11-12) 157- 163
PubMed
Mazzarotto  RCesaro  MGLora  ORubello  DCasara  DSotti  G The role of external beam radiotherapy in the management of differentiated thyroid cancer. Biomed Pharmacother 2000;54 (6) 345- 349
PubMed Link to Article
Brierley  JDTsang  RW External-beam radiation therapy in the treatment of differentiated thyroid cancer. Semin Surg Oncol 1999;16 (1) 42- 49
PubMed Link to Article
Simpson  WJ Radioiodine and radiotherapy in the management of thyroid cancers. Otolaryngol Clin North Am 1990;23 (3) 509- 521
PubMed
Brierley  JDTsang  RW External radiation therapy in the treatment of thyroid malignancy. Endocrinol Metab Clin North Am 1996;25 (1) 141- 157
PubMed Link to Article
Wilson  PCMillar  BMBrierley  JD The management of advanced thyroid cancer. Clin Oncol (R Coll Radiol) 2004;16 (8) 561- 568
PubMed Link to Article
Schuck  ABiermann  MPixberg  MK  et al.  Acute toxicity of adjuvant radiotherapy in locally advanced differentiated thyroid carcinoma: first results of the Multicenter Study Differentiated Thyroid Carcinoma (MSDS). Strahlenther Onkol 2003;179 (12) 832- 839
PubMed Link to Article
Phlips  PHanzen  CAndry  G  et al.  Postoperative irradiation for thyroid cancer. Eur J Surg Oncol 1993;19 (5) 399- 404
PubMed
Brierley  JTsang  RPanzarella  TBana  N Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years. Clin Endocrinol (Oxf) 2005;63 (4) 418- 427
PubMed Link to Article
Farahati  JReiners  CStuschke  M  et al.  Differentiated thyroid cancer: impact of adjuvant external radiotherapy inpatients with perithyroidal tumor infiltration (stage pT4). Cancer 1996;77 (1) 172- 180
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Kaplan-Meier curves for disease-specific survival (DSS) vs extrathyroidal extension (ETE). There was no significant difference in DSS between the macroscopic ETE group and the microscopic ETE group (P = .82).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Kaplan-Meier curves for overall survival (OS) vs extrathyroidal extension (ETE). There was no significant difference in OS between the macroscopic ETE group and the microscopic ETE group (P = .97).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Kaplan-Meier curves for disease-specific survival (DSS) vs extrathyroidal extension (ETE) among patients without external beam radiation therapy. Macroscopic ETE was associated with decreased DSS (P = .07).

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Kaplan-Meier curves for overall survival (OS) vs extrathyroidal extension (ETE) among patients without external beam radiation therapy. Macroscopic ETE was associated with decreased OS (P = .12).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Univariate Analysis of Demographic, Clinicopathological, and Treatment Data in the Macroscopic vs Microscopic Extrathyroidal Extension (ETE) Groups a
Table Graphic Jump LocationTable 2. Univariate Analysis of Risk Factors for Thyroid Carcinoma in the Groups With and Without External Beam Radiation Therapy (EBRT) a
Table Graphic Jump LocationTable 3. Univariate Analysis of Outcome Data in the Macroscopic vs Microscopic Extrathyroidal Extension (ETE) Groups a
Table Graphic Jump LocationTable 4. Multivariate Analysis Using the 2 Covariates of Extrathyroidal Extension (ETE) and External Beam Radiation Therapy (EBRT)
Table Graphic Jump LocationTable 5. Previous Studies of Patients With Well-Differentiated Thyroid Cancer (WDTC) and Extrathyroidal Extension (ETE) a

References

Ortiz  SRodriguez  JMSoria  T  et al.  Extrathyroid spread in papillary carcinoma of the thyroid: clinicopathological and prognostic study. Otolaryngol Head Neck Surg 2001;124 (3) 261- 265
PubMed Link to Article
Andersen  PEKinsella  JLoree  TRShaha  ARShah  JP Differentiated carcinoma of the thyroid with extrathyroidal extension. Am J Surg 1995;170 (5) 467- 470
PubMed Link to Article
Carcangiu  MLZampi  GPupi  ACastagnoli  ARosai  J Papillary carcinoma of the thyroid: a clinicopathologic study of 241 cases treated at the University of Florence, Italy. Cancer 1985;55 (4) 805- 828
PubMed Link to Article
Cody  HS  IIIShah  JP Locally invasive, well-differentiated thyroid cancer: 22 years' experience at Memorial Sloan-Kettering Cancer Center. Am J Surg 1981;142 (4) 480- 483
PubMed Link to Article
Mazzaferri  EL Papillary thyroid carcinoma: factors influencing prognosis and current therapy. Semin Oncol1987143315332 [published correction appears in Semin Oncol. 1988;15(3):x]
PubMed
McCaffrey  TVBergstralh  EJHay  ID Locally invasive papillary thyroid carcinoma 1940-1990. Head Neck 1994;16 (2) 165- 172
PubMed Link to Article
McConahey  WMHay  IDWoolner  LBvan Heerden  JATaylor  WF Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc 1986;61 (12) 978- 996
PubMed Link to Article
Mizukami  YNuguchi  MMichigishi  T  et al.  Papillary thyroid carcinoma in Kanazawa, Japan: prognostic significance of histological subtypes. Histopathology 1992;20 (3) 243- 250
PubMed Link to Article
Jukkola  ABloigu  REbeling  TSalmela  PBlanco  G Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications. Endocr Relat Cancer 2004;11 (3) 571- 579
PubMed Link to Article
Palme  CEWaseem  ZRaza  SN  et al.  Management and outcome of recurrent well-differentiated thyroid carcinoma. Arch Otolaryngol Head Neck Surg 2004;130 (7) 819- 824
PubMed Link to Article
Cushing  SLPalme  CEAudet  NEski  SWalfish  PGFreeman  JL Prognostic factors in well-differentiated thyroid carcinoma. Laryngoscope 2004;114 (12) 2110- 2115
PubMed Link to Article
Byar  DPGreen  SBDor  P  et al.  A prognostic index for thyroid carcinoma: a study of the E.O.R.T.C. Thyroid Cancer Cooperative Group. Eur J Cancer 1979;15 (8) 1033- 1041
PubMed Link to Article
Greene  FLPage  DLFleming  ID  et al AJCC Cancer Staging Handbook. 6th ed. Philadelphia, PA: Springer Publishing Co Inc; 2002
DeGroot  LJKaplan  ELMcCormick  MStrauss  FH Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 1990;71 (2) 414- 424
PubMed Link to Article
Hay  IDBergstralh  EJGoellner  JREbersold  JRGrant  CS Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 1993;114 (6) 1050- 1058
PubMed
Cady  BRossi  R An expanded view of risk-group definition in well differentiated thyroid carcinoma. Surgery 1988;104 (6) 947- 953
PubMed
Hay  IDGrant  CSTaylor  WFMcConahey  WM Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987;102 (6) 1088- 1095
PubMed
Shah  JPLoree  TRDharker  DStrong  EWBegg  CVlamis  V Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 1992;164 (6) 658- 661
PubMed Link to Article
Herrera  MFLopez-Graniel  CMSaldana  J  et al.  Papillary thyroid carcinoma in Mexican patients: clinical aspects and prognostic factors. World J Surg 1996;20 (1) 94- 100
PubMed Link to Article
Kowalski  LPFilho  JG Results of the treatment of locally invasive thyroid carcinoma. Head Neck 2002;24 (4) 340- 344
PubMed Link to Article
McCaffrey  JC Aerodigestive tract invasion by well-differentiated thyroid carcinoma: diagnosis, management, prognosis, and biology. Laryngoscope 2006;116 (1) 1- 11
PubMed Link to Article
Czaja  JMMcCaffrey  TV The surgical management of laryngotracheal invasion by well-differentiated papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 1997;123 (5) 484- 490
PubMed Link to Article
Gemsenjäger  EHeitz  PUSeifert  BMartina  BSchweizer  I Differentiated thyroid carcinoma: follow-up of 264 patients from one institution for up to 25 years. Swiss Med Wkly 2001;131 (11-12) 157- 163
PubMed
Mazzarotto  RCesaro  MGLora  ORubello  DCasara  DSotti  G The role of external beam radiotherapy in the management of differentiated thyroid cancer. Biomed Pharmacother 2000;54 (6) 345- 349
PubMed Link to Article
Brierley  JDTsang  RW External-beam radiation therapy in the treatment of differentiated thyroid cancer. Semin Surg Oncol 1999;16 (1) 42- 49
PubMed Link to Article
Simpson  WJ Radioiodine and radiotherapy in the management of thyroid cancers. Otolaryngol Clin North Am 1990;23 (3) 509- 521
PubMed
Brierley  JDTsang  RW External radiation therapy in the treatment of thyroid malignancy. Endocrinol Metab Clin North Am 1996;25 (1) 141- 157
PubMed Link to Article
Wilson  PCMillar  BMBrierley  JD The management of advanced thyroid cancer. Clin Oncol (R Coll Radiol) 2004;16 (8) 561- 568
PubMed Link to Article
Schuck  ABiermann  MPixberg  MK  et al.  Acute toxicity of adjuvant radiotherapy in locally advanced differentiated thyroid carcinoma: first results of the Multicenter Study Differentiated Thyroid Carcinoma (MSDS). Strahlenther Onkol 2003;179 (12) 832- 839
PubMed Link to Article
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