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The Role of High Frequency Dynamic Threshold (HiDT) Serum Carcinoembryonic Antigen (CEA) Measurements in Colorectal Cancer Surveillance: A (Revisited) Hypothesis Paper.

Grossmann I, Verberne C, De Bock G, Havenga K, Kema I, Klaase J, Renehan A, Wiggers T - Cancers (Basel) (2011)

Bottom Line: A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies.Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency.Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ Eindhoven, the Netherlands. irenegrossmann@me.com.

ABSTRACT
Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoembryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.

No MeSH data available.


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Results from the phase II trial.
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f1-cancers-03-02302: Results from the phase II trial.

Mentions: Recurrences after curative treatment, until now, were found in 28 patients (12%). Of 28 patients with recurrent disease, 12 patients (43%) were eligible for curative treatment (Figure 1). The sensitivity of HiDT serum CEA measurements was 79% and the specificity was 88% in a range between 2.5 and 10 ng/mL. Mean increase factor per month was 1.48 in the recurrence group. In a subgroup analysis of patients from the first hospital who had false positive rises in CEA values (n = 8), other causes, such as inflammatory disease (n = 3) and dysplastic polyps (n = 2), were found as the cause of the rise; in these patients CEA values decreased after treatment. The mean increase factor per month in the group of patients with false positive rises in CEA was 1.25. The dynamic threshold value applied in the study is probably too low; approximately half of the patients with a rise in CEA did not have recurrent disease. A solution for this problem—Besides alteration of the threshold value—is to focus additional diagnostics on possible recurrence, inflammatory diseases and dysplastic polyps.


The Role of High Frequency Dynamic Threshold (HiDT) Serum Carcinoembryonic Antigen (CEA) Measurements in Colorectal Cancer Surveillance: A (Revisited) Hypothesis Paper.

Grossmann I, Verberne C, De Bock G, Havenga K, Kema I, Klaase J, Renehan A, Wiggers T - Cancers (Basel) (2011)

Results from the phase II trial.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757419&req=5

f1-cancers-03-02302: Results from the phase II trial.
Mentions: Recurrences after curative treatment, until now, were found in 28 patients (12%). Of 28 patients with recurrent disease, 12 patients (43%) were eligible for curative treatment (Figure 1). The sensitivity of HiDT serum CEA measurements was 79% and the specificity was 88% in a range between 2.5 and 10 ng/mL. Mean increase factor per month was 1.48 in the recurrence group. In a subgroup analysis of patients from the first hospital who had false positive rises in CEA values (n = 8), other causes, such as inflammatory disease (n = 3) and dysplastic polyps (n = 2), were found as the cause of the rise; in these patients CEA values decreased after treatment. The mean increase factor per month in the group of patients with false positive rises in CEA was 1.25. The dynamic threshold value applied in the study is probably too low; approximately half of the patients with a rise in CEA did not have recurrent disease. A solution for this problem—Besides alteration of the threshold value—is to focus additional diagnostics on possible recurrence, inflammatory diseases and dysplastic polyps.

Bottom Line: A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies.Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency.Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ Eindhoven, the Netherlands. irenegrossmann@me.com.

ABSTRACT
Following curative treatment for colorectal cancer (CRC), 30% to 50% of patients will develop recurrent disease. For CRC there are several lines of evidence supporting the hypothesis that early detection of metachronous disease offers a second opportunity for cure. This paper revisits the potential role of serum carcinoembryonic antigen (CEA) in follow-up. A comprehensive review of the literature (1978-2008) demonstrates that the initial promise of serum CEA as an effective surveillance tool has been tarnished through perpetuation of poorly designed studies. Specific limitations included: testing CEA as only an 'add-on' diagnostic tool; lack of standardization of threshold values; use of static thresholds; too low measurement frequency. Major changes in localizing imaging techniques and treatment of metastatic CRC further cause a decrease of clinical applicability of past trial outcomes. In 1982, Staab hypothesized that the optimal benefit of serum CEA as a surveillance tool is through high-frequency triage using a dynamic threshold (HiDT). Evidence supporting this hypothesis was found in the biochemical characteristics of serum CEA and retrospective studies showing the superior predictive value of a dynamic threshold. A multi-centred randomized phase III study optimizing the usage of HiDT against resectability of recurrent disease is commencing recruitment in the Netherlands.

No MeSH data available.


Related in: MedlinePlus