Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden

Our plain-English summary of Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden, by J. Creaney, R.J. Francis, I.M. Dick, et al (Clinical Cancer Research, 2011).

The study

• Authors: J. Creaney, R.J. Francis, I.M. Dick, A.W. Musk, B.W. Robinson, M.J. Byrne, A.K. Nowak
• Journal: Clinical Cancer Research
• Published: 2011;17(5):1181-9
• Cited by: 90 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma.

Experimental Design: A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival.

Results: Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20-4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ(2) = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001).

Conclusion: These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma.

©2010 AACR.

In plain English

The authors recruited 97 patients with malignant pleural mesothelioma at a Western Australian oncology service from October 2003 until 2007; two were ineligible, leaving 95. The article does not report asbestos exposure. The study compared repeated blood mesothelin levels with tumor stage, PET tumor size, chemotherapy response and survival. Baseline levels above 5 nmol/L carried a hazard ratio for death of 2.25 (95% CI 1.20–4.21) versus levels below 1 nmol/L. Levels rose modestly with CT stage and correlated with PET tumor volume. Once PET measures were taken into account, mesothelin no longer significantly predicted survival. After chemotherapy, changes in mesothelin, from the pre-treatment level to the lowest level during treatment, tracked radiological response in 55 patients and PET tumor volume changes in the 28 with PET assessment. Patients whose level rose more than 25% had a hazard ratio of 23.03 (95% CI 7.47–70.92) versus those whose level fell 25% or more. The authors concluded that mesothelin changes show potential for prognosis and monitoring, and called for larger multicenter studies. They noted small numbers and varied treatments.

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 longitudinal cohort study of imaging and blood biomarkers. The mesothelin work was a pilot substudy of a study powered to answer imaging questions.
• Who was studied: 97 patients with confirmed malignant pleural mesothelioma were recruited from October 2003 until 2007 at a tertiary outpatient oncology service in Western Australia. Two were ineligible because other tumors were found on PET, leaving 95 (11 female and 84 male per Table 1; median age 66).
• Exposure: Not asbestos. The factor studied was serum soluble mesothelin, measured with the MESOMARK assay at baseline and serially during best supportive care, chemotherapy (gemcitabine or pemetrexed with a platinum agent), or extrapleural pneumonectomy. The article does not report asbestos exposure.
• Main results:
  • Baseline mesothelin above 5 nmol/L was associated with shorter survival than a level below 1 nmol/L (univariate HR 2.25; 95% CI 1.20–4.21). Median survival from diagnosis was 20 (0–57) months in the lowest tertile and 12.5 (1–44) months in the highest tertile (P = 0.012).
  • After adjustment for PET tumor measures, baseline mesothelin was not a significant predictor of survival.
  • Baseline mesothelin was modestly higher with more advanced CT stage (P = 0.008). There was no significant difference between patients with metastatic disease (n = 16) and those without it (n = 70) (P = 0.118).
  • In 52 patients, mesothelin correlated with PET total glycolytic volume (Spearman r = 0.419; P = 0.002), with tumor volume (r = 0.409; P < 0.001), and with SUVmax (r = 0.291; P < 0.05).
  • In 5 patients sampled before surgery and 24 to 72 hours after extrapleural pneumonectomy, mesothelin fell to a mean of 54% of baseline (range 27% to 83%).
  • Of 55 chemotherapy patients, comparing the pre-chemotherapy level with the lowest level during treatment, mesothelin fell by 25% or more in 24, stayed within 25% of baseline in 23, and rose by more than 25% in 8. These changes correlated with radiological response (chi-square 11.32; P = 0.023).
  • Of 17 patients with a partial response to chemotherapy, 12 had a fall in mesothelin and none had a rise.
  • In the 28 of the 55 patients who also had PET assessment, percentage change in mesothelin correlated with percentage change in PET total glycolytic volume (r = 0.58) and in tumor volume (r = 0.61).
  • The comparison group was patients whose mesothelin fell by 25% or more. Against that group, the stable group (within 25% of baseline) had an HR of 2.02 (95% CI 1.10–3.13), and the group whose level rose by more than 25% had an HR of 23.03 (95% CI 7.47–70.92). Each 10% change in mesothelin gave an HR of 1.05 (95% CI 1.02–1.07). The abstract reports a median survival of 19 months with a fall and 5 months with a rise (P < 0.001); the Figure 4 legend gives a different median for the rise group.
• The authors' conclusion: The authors concluded that changes in mesothelin levels show potential value for prognosis and for monitoring treatment response. They added that the prognostic information from baseline mesothelin comes mainly from its relationship to tumor volume. They stated that larger multicenter confirmatory studies are needed before routine clinical use.
• Limitations the authors state:
  • Small patient numbers.
  • Patients received varied clinical treatments.
  • Some patients had mesothelin below the detection limit, which reduced the number with quantifiable results.
  • The study was designed and powered to answer a different primary question (imaging).
  • The further decline and the lowest point of mesothelin after surgery were unknown, because later postoperative samples were not available.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelin, Pleural Mesothelioma, Tumor Burden, Chemotherapy, Median Survival, Mesothelioma.

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• Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma — K. Hollevoet, K. Nackaerts, et al. (2011)
• Comparison of fibulin-3 and mesothelin as markers in malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2014)
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