Integration of a postoperative calcitonin measurement into an anatomical staging system improves initial risk stratification in medullary thyroid cancer

Yang, Ji Hyun; Lindsey, Susan C.; Camacho, Cleber; Valente, Flávia O. F.; Germano-Neto, Fausto; Machado, Aline Fernanda Perez; Mamone, Maria Conceição; Brodskyn, Fábio; Biscolla, Rosa Paula M.; Tuttle, R. Michael; Silva, Magnus R. Dias da; Maciel, Rui M. B.

doi:10.1111/cen.12657

Cited by 28 publications

(15 citation statements)

References 20 publications

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“…Unlike pathological TNM staging, which is contingent on the tumour being surgically removed (what has been taken out), postoperative serum calcitonin levels reflect the residual tumour load after operation (what has been left behind). Using response to therapy variables, including postoperative serum calcitonin levels, to adjust risk estimates over time, dynamic risk stratification provides more useful clinical prognostic information than static initial anatomical staging in MTC. For patients who reach biochemical cure after the initial operation, this allows adequate monitoring by means of basal serum calcitonin measurements alone.…”

Section: Discussionmentioning

confidence: 99%

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer

Machens

Lorenz

Dralle

2019

British Journal of Surgery

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Background: It remains unclear when postoperative serum calcitonin levels should be measured in patients with medullary thyroid cancer (MTC) and, specifically, whether this decision should be based on the preoperative calcitonin level or nodal status. Methods:A cohort of patients with previously untreated MTC was studied. Kaplan-Meier analyses, stratified by preoperative calcitonin level, nodal status and number of nodal metastases, were performed to determine time to calcitonin normalization after initial surgery, with statistical analysis by means of the log rank test.Results: Some 213 patients with node-negative and 182 with node-positive MTC were included in the study. Postoperative calcitonin levels normalized in a mean of 3⋅5 versus 3⋅7 days respectively among patients with preoperative calcitonin levels of 10-100 pg/ml (P = 0⋅815); 4⋅8 versus 5⋅3 days in those with preoperative calcitonin levels of 100⋅1-500 pg/ml (P = 0⋅026); 5⋅3 versus 9⋅9 days in patients with preoperative calcitonin levels of 500⋅1-1000 pg/ml (P = 0⋅004); and 6⋅6 versus 57⋅7 days among those with preoperative calcitonin levels exceeding 1000 pg/ml (P < 0⋅001). Calcitonin levels normalized in a mean of 4⋅7 days when nodal metastasis was not present, 5⋅2 days in those with one to five nodal metastases, 7⋅0 days in patients with six to ten nodal metastases, and 57⋅1 days among patients with more than ten nodal metastases. Postoperative calcitonin normalization curves paralleled each other in patients with node-negative MTC, but diverged in those with node-positive disease and with more nodal metastases.Conclusion: Calcitonin levels typically normalize within 1 week; and within a fortnight in those with node-positive MTC and preoperative calcitonin levels of 500⋅1-1000 pg/ml. With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.

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Section: Discussionmentioning

confidence: 99%

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer

Machens

Lorenz

Dralle

2019

British Journal of Surgery

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“…Recently, DRS has been accepted for MTC. [ 3 , 4 , 6 , 9 , 10 ] We evaluated the clinical importance of DRS for MTC patients at our single institution. Both the DRS and TNM staging systems predicted clinical outcomes of MTC patients.…”

Section: Discussionmentioning

confidence: 99%

Dynamic risk stratification in medullary thyroid carcinoma

et al. 2018

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Recently, dynamic risk stratification has been found to be more valuable than static anatomic staging system in nonmedullary thyroid cancer and this strategy has also been accepted in medullary thyroid cancer (MTC). The present study was designed to compare the clinical usefulness of response to initial therapy stratification with a traditional anatomic staging system.From August 1982 to December 2012, a total of 144 MTC patients underwent thyroidectomy in Yonsei University Hospital. Among them, 117 (82.2%) patients with complete clinical data and sustained follow-up were enrolled in this study. Clinicopathological features and surgical outcomes were analyzed by retrospective medical chart review. Mean follow-up duration was 85.78 ± 62.51 months.In this study, mean tumor size was 1.94 ± 1.40 cm and 22 (18.9%) patients had hereditary MTC; 95 (81.1%) patients had sporadic MTC. Stage I patients had highest probability of excellent response to initial therapy (92.1%). Stage IV patients had highest probability of biochemical and structural incomplete response to initial therapy (57.5% and 30.3%) and lowest probability of excellent response to initial therapy (12.1%). Both response to initial therapy stratification and TNM staging system offered useful prognostic information in this study. The TNM staging system provided risk stratification pertaining to disease-free survival (DFS), disease-specific survival (DSS), and the probability of having no evidence of disease at final outcome, but did not provide risk stratification pertaining to the probability of having biochemical persistent/recurrence disease at final outcome. However, response to initial therapy stratification provided risk stratification pertaining to not only DFS, DSS, and the probability of having no evidence of disease at final outcome but also the probability of having biochemical persistent/recurrence disease at final outcome.In this study, we demonstrated that dynamic risk stratification with adjusted response to initial therapy system can offer more useful prognostic information than anatomic staging system in MTC.

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“…M edullary thyroid carcinoma (MTC) is a rare and challenging malignancy that often presents with loco-regional metastases and less commonly with distant metastases. Not infrequently these patients have persistent biochemical or structural evidence of disease after primary surgery that often displays a protracted indolent course (1)(2)(3). Prognosis largely depends on the presenting clinico-pathologic features as reflected by the American Joint Committee on Cancer (AJCC) staging (4), and on the completeness of surgical resection of the primary tumor and regional lymph nodes as assessed by the post-operative serum calcitonin (CT) (5-8).…”

Section: Introductionmentioning

confidence: 99%

“…Because serum CT is recognized to be a reliable biomarker of the presence, volume, and extent of disease in MTC (9)(10)(11), both the American Thyroid Association (ATA) and National Comprehensive Cancer Network (NCCN) guidelines post-operative CT and CEA values as the primary response to therapy variables that determines the type and intensity of follow up evaluations (2,3,8,12). While the ATA and NCCN guidelines recommend evaluating response to therapy at 2-3 months after initial therapy, several studies demonstrate that following curative surgery, serum calcitonin levels begin a rapid decline within hours after surgery (13) often achieving undetectable levels within the first few post-operative days (14-17).…”

Section: Introductionmentioning

confidence: 99%

Serum calcitonin nadirs to undetectable levels within 1 month of curative surgery in medullary thyroid cancer

Andrade¹,

Rondeau²,

Boucai³

et al. 2019

Archives of Endocrinology and Metabolism

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Objective: Because serum calcitonin (CT) is a reliable marker of the presence, volume, and extent of disease in medullary thyroid cancer (MTC), both the ATA and NCCN guidelines use the 2-3 month post-operative CT value as the primary response to therapy variable that determines the type and intensity of follow up evaluations. We hypothesized that the calcitonin would nadir to undetectable levels within 1 month of a curative surgical procedure. Subjects and methods: This retrospective review identified 105 patients with hereditary and sporadic MTC who had at least two serial basal CT measurements done in the first three months after primary surgery. Results: When evaluated one year after initial surgery, 42 patients (42/105, 40%) achieved an undetectable basal calcitonin level without additional therapies and 56 patients (56/84, 67%) demonstrated a CEA within the normal reference range. In patients destined to have an undetectable CT as the best response to initial therapy, the calcitonin was undetectable by 1 month after surgery in 97% (41/42 patients). Similarly, in patients destined to have a normalize their CEA, the CEA was within the reference range by 1 month post-operatively in 63% and by 6 months in 98%. By 6 months after curative initial surgery, 100% of patients had achieved a nadir undetectable calcitonin, 98% had reached the CEA nadir, and 97% had achieved normalization of both the calcitonin and CEA. Conclusion: The 1 month CT value is a reliable marker of response to therapy that allows earlier risk stratification than the currently recommended 2-3 month CT measurement.

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Integration of a postoperative calcitonin measurement into an anatomical staging system improves initial risk stratification in medullary thyroid cancer

Abstract: Including the first postoperative calcitonin measurement with the anatomical staging system can better predict the clinical outcome of patients with MTC and refine the follow-up of these patients.

Cited by 28 publications

References 20 publications

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer

Dynamic risk stratification in medullary thyroid carcinoma

Serum calcitonin nadirs to undetectable levels within 1 month of curative surgery in medullary thyroid cancer

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