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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

Change in serum mesothelin (nM) between baseline and 6–8 weeks in the comparator (n=15) and chemotherapy (n=46) groups (all patients with serial mesothelin results available are included).
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fig6: Change in serum mesothelin (nM) between baseline and 6–8 weeks in the comparator (n=15) and chemotherapy (n=46) groups (all patients with serial mesothelin results available are included).

Mentions: A falling mesothelin level between baseline and 6–8 weeks (after two cycles of chemotherapy) was significantly associated with longer TTP (P<0.001). A falling mesothelin level between baseline and completion of chemotherapy (15–17 weeks) was significantly associated with longer OS (481 days (IQR 192–525) compared with those with a rising level (293 days (IQR 204–493) (HR 0.46; 95% CI: 0.22–0.93; χ2=4.66; d.f.=1; P=0.031) (Table 2, Figure 6 and Supplementary Information 6online). Sensitivity analysis, in which patients with a low mesothelin (<1 nM) level at baseline were included and excluded, did not alter these results, neither did defining thresholds for a rising or falling mesothelin.


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)

Change in serum mesothelin (nM) between baseline and 6–8 weeks in the comparator (n=15) and chemotherapy (n=46) groups (all patients with serial mesothelin results available are included).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Change in serum mesothelin (nM) between baseline and 6–8 weeks in the comparator (n=15) and chemotherapy (n=46) groups (all patients with serial mesothelin results available are included).
Mentions: A falling mesothelin level between baseline and 6–8 weeks (after two cycles of chemotherapy) was significantly associated with longer TTP (P<0.001). A falling mesothelin level between baseline and completion of chemotherapy (15–17 weeks) was significantly associated with longer OS (481 days (IQR 192–525) compared with those with a rising level (293 days (IQR 204–493) (HR 0.46; 95% CI: 0.22–0.93; χ2=4.66; d.f.=1; P=0.031) (Table 2, Figure 6 and Supplementary Information 6online). Sensitivity analysis, in which patients with a low mesothelin (<1 nM) level at baseline were included and excluded, did not alter these results, neither did defining thresholds for a rising or falling mesothelin.

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