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The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

Hooper CE, Lyburn ID, Searle J, Darby M, Hall T, Hall D, Morley A, White P, Rahman NM, De Winton E, Clive A, Masani V, Arnold DT, Dangoor A, Guglani S, Jankowska P, Lowndes SA, Harvey JE, Braybrooke JP, Maskell NA - Br. J. Cancer (2015)

Bottom Line: Patients of similar performance status opting for best supportive care were included as a comparator group.Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002).Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).

View Article: PubMed Central - PubMed

Affiliation: 1] Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK [2] North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK.

ABSTRACT

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.

Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.

Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).

Interpretation: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

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Related in: MedlinePlus

Patient enrolment, withdrawal and primary end point acquisition.
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fig1: Patient enrolment, withdrawal and primary end point acquisition.

Mentions: Seventy-three patients were recruited between September 2008 and December 2011. Patient enrolment, withdrawal and primary end-point acquisition is summarised in Figure 1. Median time from diagnosis to trial entry was 11 days (IQR 7–44). Of the enrolled patients, 63 (86%) were male, and 50 (68%) had epithelioid subtype histology. Baseline characteristics of all enrolled patients are summarised in Table 1.


The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

Hooper CE, Lyburn ID, Searle J, Darby M, Hall T, Hall D, Morley A, White P, Rahman NM, De Winton E, Clive A, Masani V, Arnold DT, Dangoor A, Guglani S, Jankowska P, Lowndes SA, Harvey JE, Braybrooke JP, Maskell NA - Br. J. Cancer (2015)

Patient enrolment, withdrawal and primary end point acquisition.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385956&req=5

fig1: Patient enrolment, withdrawal and primary end point acquisition.
Mentions: Seventy-three patients were recruited between September 2008 and December 2011. Patient enrolment, withdrawal and primary end-point acquisition is summarised in Figure 1. Median time from diagnosis to trial entry was 11 days (IQR 7–44). Of the enrolled patients, 63 (86%) were male, and 50 (68%) had epithelioid subtype histology. Baseline characteristics of all enrolled patients are summarised in Table 1.

Bottom Line: Patients of similar performance status opting for best supportive care were included as a comparator group.Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002).Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).

View Article: PubMed Central - PubMed

Affiliation: 1] Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol BS10 5NB, UK [2] North Bristol Lung Centre, Southmead Hospital, North Bristol NHS Trust, Bristol BS10 5NB, UK.

ABSTRACT

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.

Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.

Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).

Interpretation: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

Show MeSH
Related in: MedlinePlus