Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM)

Our plain-English summary of Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM), by K. Yoneda, F. Tanaka, N. Kondo, et al (Annals of Surgical Oncology, 2014).

The study

• Authors: K. Yoneda, F. Tanaka, N. Kondo, M. Hashimoto, T. Takuwa, S. Matsumoto, Y. Okumura, N. Tsubota, A. Sato, T. Tsujimura, K. Kuribayashi, K. Fukuoka, C. Tabata, T. Nakano, S. Hasegawa
• Journal: Annals of Surgical Oncology
• Published: 2014;21 Suppl 4:S472-80
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM).

Methods: We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule.

Results: Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523-0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥ 1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530-5.511; P = 0.001) for epithelioid MPM patients.

Conclusions: CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

In plain English

This prospective Japanese study tested whether blood tumor-cell counts could help diagnose malignant pleural mesothelioma and predict survival. From September 2007 to July 2010, 139 consecutive patients with suspected disease gave blood samples; most had a history of asbestos exposure. Of 136 eligible patients, 104 had mesothelioma and 32 nonmalignant pleural disease. Tumor cells were found in 34 of 104 mesothelioma patients (32.7%) and 3 of 32 others (9.4%). Counting one or more cells as positive, sensitivity was 32.7% and specificity 90.6%; the authors called discrimination insufficient (area under the curve 0.623, 95% confidence interval 0.523 to 0.723). In all mesothelioma patients, the unadjusted survival difference was not statistically significant, but adjusted analysis linked a positive test to poorer survival (hazard ratio 2.343, 95% confidence interval 1.362 to 4.030). In epithelioid-subtype patients, median survival was 22.3 months without detected cells and 12.6 months with them. Here a positive test independently predicted poorer survival (hazard ratio 2.904, 95% confidence interval 1.530 to 5.511). The authors concluded the test was promising, especially in epithelioid mesothelioma, and that validation studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective single-hospital study of the diagnostic and prognostic value of a blood test for circulating tumor cells (CellSearch system, which captures cells carrying the EpCAM marker)
• Who was studied: 139 consecutive patients with suspected malignant pleural mesothelioma who were referred for pleural biopsy at Hyogo College of Medicine Hospital, Japan, from September 2007 to July 2010. 3 patients were excluded because they had lung adenocarcinoma. Of the 136 eligible patients, 104 had mesothelioma and 32 had nonmalignant pleural disease.
• Exposure: The factor studied was the circulating tumor cell count in 7.5 mL of blood. Asbestos exposure history was recorded: 97 of 104 mesothelioma patients (93.3%) and 28 of 32 nonmalignant patients (87.5%) had a history of exposure. No fiber types were reported.
• Main results:
  • Circulating tumor cells were detected in 34 of 104 mesothelioma patients (32.7%) and in 3 of 32 nonmalignant-disease patients (9.4%). Each of those 3 had a count of 1.
  • In distinguishing mesothelioma from nonmalignant disease, the area under the ROC curve was 0.623 (95% confidence interval 0.523 to 0.723; P = 0.036). With a cut-off of 1 or more cells, sensitivity was 32.7% and specificity 90.6%.
  • At a cut-off of 1 cell, the positive predictive value was 91.9% and the negative predictive value was 29.3%. At a cut-off of 2, specificity was 100% but sensitivity fell to 13.5%.
  • Among mesothelioma patients, tumor cells were detected in 31 of 78 (39.7%) with the epithelioid subtype and in 3 of 26 (11.5%) with nonepithelioid subtypes (P = 0.016).
  • Even in stage IV mesothelioma, tumor cells were detected in only 19 of 50 patients (38%): 18 of 37 epithelioid cases and 1 of 13 nonepithelioid cases.
  • Across all mesothelioma patients, in the unadjusted comparison, median overall survival was 12.7 months for the CTC-negative group and 7.6 months for the CTC-positive group. This difference was not statistically significant (P = 0.160).
  • In a multivariate analysis of all mesothelioma patients (all histologic types), the hazard ratio for a positive test was 2.343 (95% confidence interval 1.362 to 4.030; P = 0.002).
  • In epithelioid mesothelioma patients, survival was 22.3 months for the CTC-negative group (n = 47) and 12.6 months for the CTC-positive group (n = 31) (P = 0.004, log-rank).
  • In a multivariate analysis of epithelioid patients, a positive test was an independent predictor of poorer survival (hazard ratio 2.904; 95% confidence interval 1.530 to 5.511; P = 0.001).
  • In nonepithelioid patients, the test was not a significant predictor of survival: 5.1 months for the CTC-negative group (n = 23) and 5.0 months for the CTC-positive group (n = 3) (P = 0.649).
• The authors' conclusion: The authors concluded that the circulating tumor cell test was a promising marker for diagnosing mesothelioma and predicting prognosis, especially in epithelioid mesothelioma, and that future validation studies should be done.
• Limitations the authors state:
  • The test had low sensitivity (32.7%) and low negative predictive power (29.3%).
  • The system captures cells that carry EpCAM, which mesothelioma cells may not carry. This could explain the low detection rate, especially in nonepithelioid subtypes.
  • The authors described the test's ability to discriminate mesothelioma from nonmalignant disease as insufficient.
  • The reason for the 3 positive results in nonmalignant patients is unclear. One of these patients developed mesothelioma 2 years after the initial biopsy.
  • Future validation studies are needed to establish the test's prognostic performance.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, confidence interval, Epithelioid, Prognosis, Median Overall Survival, Multivariate Analysis, Hazard Ratio.

Related studies

• Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM) — K. Yoneda, F. Tanaka, et al. (2012)
• Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma — K. Yoneda, T. Kuwata, et al. (2019)
• EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip' — Y. Chikaishi, K. Yoneda, et al. (2017)
• Detection of circulating tumour cells in peripheral blood of patients with malignant pleural mesothelioma — J. Raphael, C. Massard, et al. (2015)
• A liquid biopsy for detecting circulating mesothelial precursor cells: A new biomarker for diagnosis and prognosis in mesothelioma — B.T.V. Duong, L. Wu, et al. (2020)
• Practical approaches to diagnose and treat for T0 malignant pleural mesothelioma: a proposal for diagnostic total parietal pleurectomy — S. Hasegawa, N. Kondo, et al. (2012)

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