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In Reply

University of Nantes, Nantes, France

In their letter to the editor, Machens and Dralle comment on our recent article on medullary thyroid carcinoma (MTC) patients treated with radioimmunotherapy.¹ They question the practicality of calcitonin doubling time (DT) measurements as a prognostic marker. All MTC patients have calcitonin measurements before and after surgery, and some show persistent calcitonin levels after surgery, sometimes rising with time. In practice, probably because there is no established therapeutic option when surgery has failed, serial calcitonin measurements are performed before a treatment is proposed. Then, in most cases, assessing calcitonin DT with a reasonable precision is not a problem. If the DT is short (poor prognosis), a series of measurements over a couple of months may suffice; if it is long, then more time is required, but the prognosis is good in the absence of treatment.

In an article not cited by Machens and Dralle, which offers more information on a group of 65 MTC patients monitored for years and not given any treatment because none was available, we investigated both calcitonin and carcinoembryonic antigen (CEA) as potential prognostic serum markers.² Although CEA and calcitonin DT were reasonably well correlated, and despite CEA measurements showing less fluctuation, CEA was found to be slightly less predictive than calcitoinin as a prognostic serum marker in a group of 46 patients in whom both CEA and calcitonin DT were available. However, identical conclusions could be reached by examining CEA or calcitonin: patients with DT shorter than 2 years are high-risk patients. The actual reason why calcitonin was chosen as the primary marker in our current study was because among the 65 MTC patients, 12 patients had normal CEA levels over the entire history of their disease (and thus no DT could be calculated), including 4 patients in the poor prognostic group (DT < 2 years), of whom two died of MTC.

As to the expression of CEA by MTC cells, many studies with radiolabeled anti-CEA antibodies, diagnostic or therapeutic, have shown that it is quite consistent, and that a normal circulating CEA level does not mean that tumor cells do not express CEA at their membrane.³ More likely, small tumor mass and slow CEA secretion rates result in serum CEA levels that are considered normal because low circulating CEA is present in the normal population.

Machens et al cite their work in press that preoperative CEA levels predict the chance that surgery will be successful in eradicating the disease.⁴ For all patients we have studied, whether in the untreated controls or in the treated group, surgery failed when postoperative calcitonin levels remained elevated. For a large number of these patients, preoperative data were scarce and in most cases only preoperative calcitonin was available. Thus, unfortunately, we cannot answer their question, but agree that preoperative CEA levels should be documented in future studies. The fact that patients with high postoperative CEA levels, thus presumably high preoperative CEA levels, may have a variable prognosis in accordance with the biomarkers DT indicates that both markers should be monitored for a global management of MTC.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Chatal JF, Campion L, Kraeber-Bodéré F, et al: Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: A collaborative study with the French Endocrine Tumor Group. J Clin Oncol 24:1705-1711, 2006[Abstract/Free Full Text]

2. Barbet J, Campion L, Kraeber-Bodere F, Chatal JF, et al: Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 90:6077-6084, 2005[Abstract/Free Full Text]

3. Barbet J, Peltier P, Bardet S, et al: Radioimmunodetection of medullary thyroid carcinoma using indium-111 bivalent hapten and anti-CEA x anti-DTPA-indium bispecific antibody. J Nucl Med 39:1172-1178, 1998[Abstract/Free Full Text]

4. Machens A, Ukkat J, Hauptmann S, et al: Abnormal carcinoembryonnic antigen levels and medullary thyroid progression: A multivariate analysis. Arch Surg (in press)

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chatal, J. F. Search for Related Content PubMed Articles by Chatal, J. F. Social Bookmarking                            What's this?