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Published in: Annals of Surgical Oncology 8/2015

01-08-2015 | Endocrine Tumors

Postoperative Nomogram for Predicting Cancer-Specific Mortality in Medullary Thyroid Cancer

Authors: Allen S. Ho, MD, Lu Wang, MS, Frank L. Palmer, BA, Changhong Yu, MS, Arnbjorn Toset, MD, Snehal Patel, MD, Michael W. Kattan, PhD, R. Michael Tuttle, MD, Ian Ganly, MD, PhD

Published in: Annals of Surgical Oncology | Issue 8/2015

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Abstract

Background

Medullary thyroid cancer (MTC) is a rare thyroid cancer accounting for 5 % of all thyroid malignancies. The purpose of our study was to design a predictive nomogram for cancer-specific mortality (CSM) utilizing clinical, pathological, and biochemical variables in patients with MTC.

Methods

MTC patients managed entirely at Memorial Sloan-Kettering Cancer Center between 1986 and 2010 were identified. Patient, tumor, and treatment characteristics were recorded, and variables predictive of CSM were identified by univariable analyses. A multivariable competing risk model was then built to predict the 10-year cancer specific mortality of MTC. All predictors of interest were added in the starting full model before selection, including age, gender, pre- and postoperative serum calcitonin, pre- and postoperative CEA, RET mutation status, perivascular invasion, margin status, pathologic T status, pathologic N status, and M status. Stepdown method was used in model selection to choose predictive variables.

Results

Of 249 MTC patients, 22.5 % (56/249) died from MTC, whereas 6.4 % (16/249) died secondary to other causes. Mean follow-up period was 87 ± 67 months. The seven variables with the highest predictive accuracy for cancer specific mortality included age, gender, postoperative calcitonin, perivascular invasion, pathologic T status, pathologic N status, and M status. These variables were used to create the final nomogram. Discrimination from the final nomogram was measured at 0.77 with appropriate calibration.

Conclusions

We describe the first nomogram that estimates cause-specific mortality in individual patients with MTC. This predictive nomogram will facilitate patient counseling in terms of prognosis and subsequent clinical follow up.
Appendix
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Literature
1.
go back to reference Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules. Ann Intern Med. 2005;142:926-31.PubMedCrossRef Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules. Ann Intern Med. 2005;142:926-31.PubMedCrossRef
2.
go back to reference American Thyroid Association Guidelines Task Force1, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612. American Thyroid Association Guidelines Task Force1, Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612.
3.
go back to reference Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107:2134-42.PubMedCrossRef Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107:2134-42.PubMedCrossRef
4.
go back to reference Tuttle RM, Ball DW, Byrd D, et al. Medullary carcinoma. J Natl Compr Cancer Netw. 2010;8:512-30. Tuttle RM, Ball DW, Byrd D, et al. Medullary carcinoma. J Natl Compr Cancer Netw. 2010;8:512-30.
5.
go back to reference Dottorini ME, Assi A, Sironi M, et al. Multivariate analysis of patients with medullary thyroid carcinoma. Prognostic significance and impact on treatment of clinical and pathologic variables. Cancer 1996;77:1556-65.PubMedCrossRef Dottorini ME, Assi A, Sironi M, et al. Multivariate analysis of patients with medullary thyroid carcinoma. Prognostic significance and impact on treatment of clinical and pathologic variables. Cancer 1996;77:1556-65.PubMedCrossRef
6.
go back to reference Scopsi L, Sampietro G, Boracchi P, et al. Multivariate analysis of prognostic factors in sporadic medullary carcinoma of the thyroid. A retrospective study of 109 consecutive patients. Cancer. 1996;78:2173-83.PubMedCrossRef Scopsi L, Sampietro G, Boracchi P, et al. Multivariate analysis of prognostic factors in sporadic medullary carcinoma of the thyroid. A retrospective study of 109 consecutive patients. Cancer. 1996;78:2173-83.PubMedCrossRef
7.
go back to reference Fialkowski E, DeBenedetti M, Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma. World J Surg. 2008;32:754-65.PubMedCrossRef Fialkowski E, DeBenedetti M, Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma. World J Surg. 2008;32:754-65.PubMedCrossRef
8.
go back to reference Ukkat J, Gimm O, Brauckhoff M, et al. Single center experience in primary surgery for medullary thyroid carcinoma. World J Surg. 2004;28:1271-4.PubMedCrossRef Ukkat J, Gimm O, Brauckhoff M, et al. Single center experience in primary surgery for medullary thyroid carcinoma. World J Surg. 2004;28:1271-4.PubMedCrossRef
9.
go back to reference Weber T, Schilling T, Frank-Raue K, et al. Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery. 2001;130:1044-9.PubMedCrossRef Weber T, Schilling T, Frank-Raue K, et al. Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas. Surgery. 2001;130:1044-9.PubMedCrossRef
10.
go back to reference Cupisti K, Wolf A, Raffel A, et al. Long-term clinical and biochemical follow-up in medullary thyroid carcinoma: a single institution’s experience over 20 years. Ann Surg. 2007;246:815-21.PubMedCrossRef Cupisti K, Wolf A, Raffel A, et al. Long-term clinical and biochemical follow-up in medullary thyroid carcinoma: a single institution’s experience over 20 years. Ann Surg. 2007;246:815-21.PubMedCrossRef
11.
go back to reference Iasonos A, Schrag D, Raj GV, et al. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008;26:1364-70.PubMedCrossRef Iasonos A, Schrag D, Raj GV, et al. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008;26:1364-70.PubMedCrossRef
13.
go back to reference Specht MC, Kattan MW, Gonen M, et al. Predicting nonsentinel node status after positive sentinel lymph biopsy for breast cancer: clinicians versus nomogram. Ann Surg Oncol. 2005;12:654-9.PubMedCrossRef Specht MC, Kattan MW, Gonen M, et al. Predicting nonsentinel node status after positive sentinel lymph biopsy for breast cancer: clinicians versus nomogram. Ann Surg Oncol. 2005;12:654-9.PubMedCrossRef
14.
go back to reference Ross PL, Gerigk C, Gonen M, et al. Comparisons of nomograms and urologists’ predictions in prostate cancer. Semin Urol Oncol. 2002;20:82-8.PubMedCrossRef Ross PL, Gerigk C, Gonen M, et al. Comparisons of nomograms and urologists’ predictions in prostate cancer. Semin Urol Oncol. 2002;20:82-8.PubMedCrossRef
15.
go back to reference Kawachi MH, Bahnson RR, Barry M, et al: NCCN clinical practice guidelines in oncology: prostate cancer early detection. J Natl Compr Cancer Netw. 2010;8:240-62. Kawachi MH, Bahnson RR, Barry M, et al: NCCN clinical practice guidelines in oncology: prostate cancer early detection. J Natl Compr Cancer Netw. 2010;8:240-62.
16.
go back to reference Edge SB, Compton CC: The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471-4.PubMedCrossRef Edge SB, Compton CC: The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471-4.PubMedCrossRef
18.
go back to reference Barbet J, Campion L, Kraeber-Bodere F, et al. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2005;90:6077-84.PubMedCrossRef Barbet J, Campion L, Kraeber-Bodere F, et al. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2005;90:6077-84.PubMedCrossRef
19.
go back to reference Qi XP, Ma JM, Du ZF, et al. RET germline mutations identified by exome sequencing in a Chinese multiple endocrine neoplasia type 2A/familial medullary thyroid carcinoma family. PLoS One. 2011;6:e20353.PubMedCentralPubMedCrossRef Qi XP, Ma JM, Du ZF, et al. RET germline mutations identified by exome sequencing in a Chinese multiple endocrine neoplasia type 2A/familial medullary thyroid carcinoma family. PLoS One. 2011;6:e20353.PubMedCentralPubMedCrossRef
20.
go back to reference Agrawal N, Jiao Y, Sausen M, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab. 2013;98(2):364–369. Agrawal N, Jiao Y, Sausen M, et al. Exomic sequencing of medullary thyroid cancer reveals dominant and mutually exclusive oncogenic mutations in RET and RAS. J Clin Endocrinol Metab. 2013;98(2):364–369.
21.
go back to reference Meijer JA, le Cessie S, van den Hout WB, et al. Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: a structured meta-analysis. Clin Endocrinol (Oxf). 2010;72:534-42.PubMedCrossRef Meijer JA, le Cessie S, van den Hout WB, et al. Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: a structured meta-analysis. Clin Endocrinol (Oxf). 2010;72:534-42.PubMedCrossRef
22.
go back to reference Bellantone R, Boscherini M, Lombardi CP, et al. Medullary thyroid carcinoma: surgical management of primary tumor and locoregional recurrence. Rays. 2000;25:267-71.PubMed Bellantone R, Boscherini M, Lombardi CP, et al. Medullary thyroid carcinoma: surgical management of primary tumor and locoregional recurrence. Rays. 2000;25:267-71.PubMed
23.
go back to reference Laure Giraudet A, Al Ghulzan A, Auperin A, et al. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol. 2008;158:239-46.PubMedCrossRef Laure Giraudet A, Al Ghulzan A, Auperin A, et al. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol. 2008;158:239-46.PubMedCrossRef
24.
go back to reference Wang TS, Ocal IT, Sosa JA, et al. Medullary thyroid carcinoma without marked elevation of calcitonin: a diagnostic and surveillance dilemma. Thyroid. 2008;18:889-94.PubMedCrossRef Wang TS, Ocal IT, Sosa JA, et al. Medullary thyroid carcinoma without marked elevation of calcitonin: a diagnostic and surveillance dilemma. Thyroid. 2008;18:889-94.PubMedCrossRef
25.
go back to reference Dora JM, Canalli MH, Capp C, et al. Normal perioperative serum calcitonin levels in patients with advanced medullary thyroid carcinoma: case report and review of the literature. Thyroid. 2008;18:895-9.PubMedCrossRef Dora JM, Canalli MH, Capp C, et al. Normal perioperative serum calcitonin levels in patients with advanced medullary thyroid carcinoma: case report and review of the literature. Thyroid. 2008;18:895-9.PubMedCrossRef
26.
go back to reference Busnardo B, Girelli ME, Simioni N, et al. Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer. 1984;53:278-85.PubMedCrossRef Busnardo B, Girelli ME, Simioni N, et al. Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer. 1984;53:278-85.PubMedCrossRef
27.
go back to reference Pellegriti G, Leboulleux S, Baudin E, et al. Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging. Br J Cancer. 2003;88:1537-42.PubMedCentralPubMedCrossRef Pellegriti G, Leboulleux S, Baudin E, et al. Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging. Br J Cancer. 2003;88:1537-42.PubMedCentralPubMedCrossRef
28.
go back to reference Ito Y, Miyauchi A, Yabuta T, et al. Alternative surgical strategies and favorable outcomes in patients with medullary thyroid carcinoma in Japan: experience of a single institution. World J Surg. 2009;33:58-66.PubMedCrossRef Ito Y, Miyauchi A, Yabuta T, et al. Alternative surgical strategies and favorable outcomes in patients with medullary thyroid carcinoma in Japan: experience of a single institution. World J Surg. 2009;33:58-66.PubMedCrossRef
29.
go back to reference Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol (Oxf). 1998;48:265-73.PubMedCrossRef Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’etude des tumeurs a calcitonine. Clin Endocrinol (Oxf). 1998;48:265-73.PubMedCrossRef
30.
go back to reference Kattan MW, Scardino PT. Evidence for the usefulness of nomograms. Nat Clin Pract Urol. 2007;4:638-9.PubMedCrossRef Kattan MW, Scardino PT. Evidence for the usefulness of nomograms. Nat Clin Pract Urol. 2007;4:638-9.PubMedCrossRef
31.
go back to reference Weiser MR, Landmann RG, Kattan MW, et al. Individualized prediction of colon cancer recurrence using a nomogram. J Clin Oncol. 2008;26:380-5.PubMedCrossRef Weiser MR, Landmann RG, Kattan MW, et al. Individualized prediction of colon cancer recurrence using a nomogram. J Clin Oncol. 2008;26:380-5.PubMedCrossRef
32.
go back to reference Stephenson AJ, Scardino PT, Eastham JA, et al. Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol. 2005;23:7005-12.PubMedCentralPubMedCrossRef Stephenson AJ, Scardino PT, Eastham JA, et al. Postoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. J Clin Oncol. 2005;23:7005-12.PubMedCentralPubMedCrossRef
33.
go back to reference Rudloff U, Jacks LM, Goldberg JI, et al. Nomogram for predicting the risk of local recurrence after breast-conserving surgery for ductal carcinoma in situ. J Clin Oncol. 2010;28:3762-9.PubMedCrossRef Rudloff U, Jacks LM, Goldberg JI, et al. Nomogram for predicting the risk of local recurrence after breast-conserving surgery for ductal carcinoma in situ. J Clin Oncol. 2010;28:3762-9.PubMedCrossRef
34.
go back to reference Brennan MF, Kattan MW, Klimstra D, et al. Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas. Ann Surg. 2004;240:293-8.PubMedCentralPubMedCrossRef Brennan MF, Kattan MW, Klimstra D, et al. Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas. Ann Surg. 2004;240:293-8.PubMedCentralPubMedCrossRef
35.
go back to reference International Bladder Cancer Nomogram C, Bochner BH, Kattan MW, et al. Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol. 2006;24:3967-72.CrossRef International Bladder Cancer Nomogram C, Bochner BH, Kattan MW, et al. Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol. 2006;24:3967-72.CrossRef
36.
go back to reference Walz J, Gallina A, Saad F, et al. A nomogram predicting 10-year life expectancy in candidates for radical prostatectomy or radiotherapy for prostate cancer. J Clin Oncol. 2007;25:3576-81.PubMedCrossRef Walz J, Gallina A, Saad F, et al. A nomogram predicting 10-year life expectancy in candidates for radical prostatectomy or radiotherapy for prostate cancer. J Clin Oncol. 2007;25:3576-81.PubMedCrossRef
37.
go back to reference Lambert LA, Ayers GD, Hwang RF, et al. Validation of a breast cancer nomogram for predicting nonsentinel lymph node metastases after a positive sentinel node biopsy. Ann Surg Oncol. 2006;13:310-20.PubMedCrossRef Lambert LA, Ayers GD, Hwang RF, et al. Validation of a breast cancer nomogram for predicting nonsentinel lymph node metastases after a positive sentinel node biopsy. Ann Surg Oncol. 2006;13:310-20.PubMedCrossRef
38.
go back to reference Steyerberg EW, Roobol MJ, Kattan MW, et al. Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol 2007;177:107-12; discussion 112.PubMedCrossRef Steyerberg EW, Roobol MJ, Kattan MW, et al. Prediction of indolent prostate cancer: validation and updating of a prognostic nomogram. J Urol 2007;177:107-12; discussion 112.PubMedCrossRef
39.
go back to reference Nuhn P, May M, Sun M, et al. External validation of postoperative nomograms for prediction of all-cause mortality, cancer-specific mortality, and recurrence in patients with urothelial carcinoma of the bladder. Eur Urol 2012;61:58-64.PubMedCrossRef Nuhn P, May M, Sun M, et al. External validation of postoperative nomograms for prediction of all-cause mortality, cancer-specific mortality, and recurrence in patients with urothelial carcinoma of the bladder. Eur Urol 2012;61:58-64.PubMedCrossRef
Metadata
Title
Postoperative Nomogram for Predicting Cancer-Specific Mortality in Medullary Thyroid Cancer
Authors
Allen S. Ho, MD
Lu Wang, MS
Frank L. Palmer, BA
Changhong Yu, MS
Arnbjorn Toset, MD
Snehal Patel, MD
Michael W. Kattan, PhD
R. Michael Tuttle, MD
Ian Ganly, MD, PhD
Publication date
01-08-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 8/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-4208-2

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