Survival and Long-Term Biochemical Cure in Medullary Thyroid Carcinoma in Denmark 1997–2014: A Nationwide Study

Mathiesen, Jes Sloth; Kroustrup, Jens Peter; Vestergaard, Peter; Stochholm, Kirstine; Poulsen, Per Løgstrup; Rasmussen, Åse Krogh; Feldt‐Rasmussen, Ulla; Schytte, Sten; Londero, Stefano Christian; Pedersen, Henrik C.; Hahn, Christoffer Holst; Bentzen, Jens; Möller, Sören; Gaustadnes, Mette; Rossing, Maria; Nielsen, Finn C.; Brixen, Kim; Frederiksen, Anja Lisbeth; Godballe, Christian

doi:10.1089/thy.2018.0564

Cited by 47 publications

(28 citation statements)

References 54 publications

(66 reference statements)

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“…Patients achieving biochemical cure had a median of 2 versus 16 metastases at initial operation, and 4 versus 12 metastases at repeat surgery, compared with patients without biochemical cure. These data compare favourably against corresponding median values of 3·5 versus 10 node metastases from the Norwegian national registry, and against absolute thresholds of four node metastases for biochemical cure from the Danish national registry. The number of node metastases was also more powerful in predicting biochemical cure than MLNR or AJCC node category.…”

Section: Discussionmentioning

confidence: 76%

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Prediction of biochemical cure in patients with medullary thyroid cancer

Machens

Lorenz

Dralle

2020

British Journal of Surgery

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Background: The impact of number of node metastases versus metastatic lymph node ratio versus AJCC node category on biochemical cure in medullary thyroid cancer (MTC) is not well defined. Methods: Multivariable logistic regression analysis was used to determine clinical and histopathological variables that contribute to biochemical cure in node-positive MTC.Results: Some 584 of 1026 patients with MTC underwent systematic lymph node dissections for node-positive disease; 27⋅4 per cent (54 of 197) were biochemically cured after the initial operation and 13⋅5 per cent (42 of 310 patients) after repeat surgery. Cured patients had significantly less extrathyroid extension (11-14 versus 33⋅2-55⋅6 per cent), fewer lymph node metastases (median 2-4 versus 12-16), a lower metastatic lymph node ratio (median 0⋅05-0⋅08 versus 0⋅23-0⋅28), and were less likely to have AJCC pN1b disease (56-76 versus 89⋅9-91⋅6 per cent) and distant metastases (0 versus 28⋅4-37⋅1 per cent) than patients who were not cured. Biochemical cure curves advanced steadily up to 7-12 node metastases and a metastatic lymph node ratio of 0⋅33, eventually levelling off after 16-17 node metastases and metastatic lymph node ratios of 0⋅45-0⋅65. In logistic regression analysis, number of lymph node metastases (odds ratio (OR) 17⋅24 for more than 20 metastases, OR 5⋅28 for 11-20 metastases, OR 2⋅22 for 6-10 metastases), preoperative basal serum calcitonin (OR 6⋅24 for over 1000 pg/ml), reoperation (OR 5⋅34) and extrathyroid extension (OR 2⋅42) independently predicted failure to reach biochemical cure.Conclusion: Number of lymph node metastases, unlike metastatic lymph node ratio or AJCC node category, determines likelihood of biochemical cure after initial and repeat surgery for node-positive MTC.

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Section: Discussionmentioning

confidence: 76%

“…Usually biochemical cure cannot be achieved when more than ten nodes are involved. Data from the Norwegian and Danish national registries showed a median of 3·5 lymph node metastases in patients who were biochemically cured, and an absolute threshold of four node metastases for postoperative biochemical cure.…”

Section: Introductionmentioning

confidence: 99%

Prediction of biochemical cure in patients with medullary thyroid cancer

Machens

Lorenz

Dralle

2020

British Journal of Surgery

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“…Although MEN2 is rare, recognition of the syndrome by RET testing is crucial, as early thyroidectomy before MTC has spread beyond the thyroid often confers the best chance for cure. 13,24,37 In this nationwide study, we report a completeness of RET testing in >80% of patients diagnosed with MTC in Denmark from 1997 to 2013. We found no change in completeness when comparing completeness in periods before and after publication of the first Danish guidelines on the subject.…”

Section: Discussionmentioning

confidence: 92%

Completeness of<em> RET</em> testing in patients with medullary thyroid carcinoma in Denmark 1997–2013: a nationwide study

Mathiesen¹,

Kroustrup²,

Vestergaard³

et al. 2019

CLEP

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Background: The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to assess the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested. Methods: The study included 200 patients identified from the nationwide Danish MTC cohort 1997-2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994-2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested. Results: Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81-0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76-0.88; 131/158). Completeness was 88% (95% CI: 0.75-0.95; 42/48) and 81% (95% CI: 0.72-0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested. Conclusion: The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test.

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“…The over-representation in this cohort of MEN2A index cases presenting with PHPT as first manifestation is expected, as carriers of codon 634 mutations are regarded as having the highest penetrance of PHPT (6,46). Given the fact, that longterm biochemical cure only rarely occurs in node-positive MTC (49), the likelihood of cure as indicated by our cohort is supposedly very low for MEN 2A index cases that present with PHPT as their first manifestation. Due to the high prevalence of regional lymph node metastases in these cases, neck dissection is often warranted already at primary surgery for better local control.…”

Section: Characteristics Of Casesmentioning

confidence: 84%

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

Larsen

Mirebeau‐Prunier

Imai

et al. 2020

Endocrine Connections

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Objective Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. Design and methods An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. Results Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Conclusions Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

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Survival and Long-Term Biochemical Cure in Medullary Thyroid Carcinoma in Denmark 1997–2014: A Nationwide Study

Cited by 47 publications

References 54 publications

Prediction of biochemical cure in patients with medullary thyroid cancer

Prediction of biochemical cure in patients with medullary thyroid cancer

Completeness of<em> RET</em> testing in patients with medullary thyroid carcinoma in Denmark 1997–2013: a nationwide study

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

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Survival and Long-Term Biochemical Cure in Medullary Thyroid Carcinoma in Denmark 1997–2014: A Nationwide Study

Cited by 47 publications

References 54 publications

Prediction of biochemical cure in patients with medullary thyroid cancer

Prediction of biochemical cure in patients with medullary thyroid cancer

Completeness of<em> RET</em> testing in patients with medullary thyroid carcinoma in Denmark 1997&ndash;2013: a nationwide study

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

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Completeness of<em> RET</em> testing in patients with medullary thyroid carcinoma in Denmark 1997–2013: a nationwide study