Serum Survivin Levels and Outcome of Chemotherapy in Patients with Malignant Mesothelioma

Our plain-English summary of Serum Survivin Levels and Outcome of Chemotherapy in Patients with Malignant Mesothelioma, by K. Goričar, V. Kovač, A. Franko, et al (Disease Markers, 2015).

The study

• Authors: K. Goričar, V. Kovač, A. Franko, M. Dodič-Fikfak, V. Dolžan
• Journal: Disease Markers
• Published: 2015;2015:316739
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Survivin is an inhibitor of apoptosis protein involved in the regulation of cell proliferation that could be used as a marker for cancer diagnosis or prognosis. Our aim was to evaluate whether serum survivin levels influence the outcome of cisplatin-based chemotherapy in patients with malignant mesothelioma (MM).

Methods: Serum survivin levels were determined using human survivin enzyme-linked immunosorbent assay in 78 MM patients before chemotherapy, after chemotherapy, and at disease progression. The influence on tumor response and survival was evaluated using nonparametric tests and Cox regression.

Results: A median serum survivin level at diagnosis was 4.1 (0-217.5) pg/mL. Patients with a progressive disease had significantly higher survivin levels before chemotherapy (p = 0.041). A median serum survivin level after chemotherapy was 73.1 (0-346.2) pg/mL. If survivin levels increased after chemotherapy, patients had, conversely, better response (p = 0.001, OR = 5.40, 95% CI = 1.98-14.72). Unexpectedly, patients with increased survivin levels after chemotherapy also had longer progression-free (p < 0.001, HR = 0.33, 95% CI = 0.20-0.57) and overall survival (p = 0.001, HR = 0.29, 95% CI = 0.14-0.58).

Conclusions: These results suggest that serum survivin levels before and during chemotherapy could serve as a biomarker predicting MM treatment response.

In plain English

This study measured a blood protein called survivin in 78 patients with malignant mesothelioma treated with cisplatin-based chemotherapy in Ljubljana, Slovenia, between 2007 and 2013. Of these, 63 had asbestos exposure and 15 had none known. Survivin was measured before and after chemotherapy in all 78, and at disease progression in 61. Median levels were 4.1 pg/mL before and 73.1 pg/mL after chemotherapy. Levels rose after chemotherapy in 35 patients (44.9%). At diagnosis, patients without known asbestos exposure had higher levels than exposed patients (median 303.8 versus 0 pg/mL). Patients whose disease progressed during chemotherapy had higher levels before chemotherapy than patients whose disease was controlled (p = 0.041). Patients whose levels rose after chemotherapy had 5.40 times greater odds of a good response than patients whose levels decreased (95% CI 1.98–14.72). Compared with patients whose levels stayed the same or fell, they also had longer progression-free survival (HR 0.33, 95% CI 0.20–0.57) and longer overall survival (HR 0.29, 95% CI 0.14–0.58). The authors concluded that survivin levels could serve as a biomarker predicting treatment response. They called this a pilot study needing confirmation in an independent group of patients.

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: Panel study (the authors also call it a pilot study) measuring serum survivin repeatedly in patients receiving chemotherapy
• Who was studied: 78 patients with histologically proven malignant mesothelioma treated with cisplatin-based chemotherapy at the Institute of Oncology, Ljubljana, Slovenia, between 1 January 2007 and December 2013. 66 were men and 12 were women. 7 had peritoneal mesothelioma. 63 (80.8%) were asbestos-exposed and 15 (19.2%) were unexposed.
• Exposure: The study examined serum survivin levels, measured by ELISA before chemotherapy, after the last cycle and at disease progression. Patients received gemcitabine plus cisplatin (53) or pemetrexed plus cisplatin (25). Asbestos exposure was recorded at clinical interview as occupational, environmental, occasional or none known. No fiber types were reported.
• Main results:
  • Samples from before and after chemotherapy were available for all 78 patients. Samples at disease progression were available for 61 (78.2%).
  • Across all patients, median serum survivin was 4.1 pg/mL (0 to 217.5) at diagnosis and 73.1 pg/mL (0 to 346.2) after chemotherapy. The methods describe the bracketed spreads as interquartile ranges.
  • Survivin levels increased after chemotherapy in 35 of 78 patients (44.9%).
  • At diagnosis, patients without known asbestos exposure had significantly higher survivin levels (median 303.8 pg/mL) than asbestos-exposed patients (median 0 pg/mL), p = 0.006.
  • Patients whose disease progressed during chemotherapy had significantly higher survivin levels before chemotherapy than patients with disease control (p = 0.041).
  • In all patients, those whose survivin increased after chemotherapy had 5.40 times greater odds of a good (complete or partial) response than those whose levels decreased (OR 5.40, 95% CI 1.98–14.72).
  • Among asbestos-exposed patients, an increase in survivin after chemotherapy was linked to 8.22 times greater odds of a good response (OR 8.22, 95% CI 2.54–26.63).
  • In the whole cohort, an increase in survivin after chemotherapy was associated with longer progression-free survival (p < 0.001, HR 0.33, 95% CI 0.20–0.57).
  • In the whole cohort, an increase in survivin after chemotherapy was associated with longer overall survival (p = 0.001, HR 0.29, 95% CI 0.14–0.58).
  • In the whole cohort, patients with decreased survivin had median overall survival of 15.1 months and median progression-free survival of 6.7 months. Patients with increased survivin had median overall survival of 47.8 months and median progression-free survival of 13.1 months.
  • Among all patients, survivin level before chemotherapy did not have a substantial effect on progression-free survival (HR 1.01, 95% CI 0.99–1.04 per 100 pg/mL increase). It was not associated with overall survival (p = 0.444).
• The authors' conclusion: The authors concluded that serum survivin levels before and during chemotherapy could serve as a biomarker predicting treatment response in malignant mesothelioma.
• Limitations the authors state:
  • Survivin was measured with one commercial ELISA kit, and the results were not validated with other methods.
  • The results need to be confirmed in an independent patient cohort.
  • The authors describe the work as a pilot study.

Topics

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

Medical terms in this study, explained in our Lexicon: Chemotherapy, Mesothelioma, Apoptosis, Prognosis, Cisplatin, Disease Progression, Overall Survival, Biomarker.

Related studies

• Is survivin expression prognostic or predictive in malignant pleural mesothelioma? — J. Hmeljak, N. Erčulj, et al. (2013)
• BIRC5 promoter SNPs do not affect nuclear survivin expression and survival of malignant pleural mesothelioma patients — J. Hmeljak, N. Erčulj, et al. (2011)
• Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma — M. Meerang, K. Bérard, et al. (2016)
• Preclinical development of HIvax: Human survivin highly immunogenic vaccines — P.R. Hoffmann, M. Panigada, et al. (2015)
• Survivin is a negative prognostic factor in malignant pleural effusion — E. Arellano-Orden, B. Romero-Romero, et al. (2018)
• Fowlpox-based survivin vaccination for malignant mesothelioma therapy — P. Bertino, M. Panigada, et al. (2013)

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