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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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Percentage change in TGV between baseline and 6-week PET-CT scan in comparator (n=13) and chemotherapy (n=41) patients for whom interval PET-CT scans were available.
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fig4: Percentage change in TGV between baseline and 6-week PET-CT scan in comparator (n=13) and chemotherapy (n=41) patients for whom interval PET-CT scans were available.

Mentions: Higher values of all baseline PET-CT parameters were significantly associated with shorter survival. Considering a division at the median TGV of 1800, in the chemotherapy group, patients with a baseline TGV⩾1800 had a significantly shorter median survival of 266 (IQR 180–479) days compared with 456 (IQR 266–653) days in patients with TGV <1800 (HR 3.00; 95% CI: 1.53–5.88; χ2=13.53; d.f.=1; P=0.001). Total glycolytic volume was independently predictive of survival in a multivariable Cox proportional hazards model including histological subtype (P<0.001). Data are given in online Supplementary Information 4. Total glycolytic volume fell between baseline and the 6-week PET-CT in 38 out of 41 (93%) chemotherapy patients and 2 out of 13(15%) comparator patients for whom interval PET-CT scans were available (see Figure 4).


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)

Percentage change in TGV between baseline and 6-week PET-CT scan in comparator (n=13) and chemotherapy (n=41) patients for whom interval PET-CT scans were available.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Percentage change in TGV between baseline and 6-week PET-CT scan in comparator (n=13) and chemotherapy (n=41) patients for whom interval PET-CT scans were available.
Mentions: Higher values of all baseline PET-CT parameters were significantly associated with shorter survival. Considering a division at the median TGV of 1800, in the chemotherapy group, patients with a baseline TGV⩾1800 had a significantly shorter median survival of 266 (IQR 180–479) days compared with 456 (IQR 266–653) days in patients with TGV <1800 (HR 3.00; 95% CI: 1.53–5.88; χ2=13.53; d.f.=1; P=0.001). Total glycolytic volume was independently predictive of survival in a multivariable Cox proportional hazards model including histological subtype (P<0.001). Data are given in online Supplementary Information 4. Total glycolytic volume fell between baseline and the 6-week PET-CT in 38 out of 41 (93%) chemotherapy patients and 2 out of 13(15%) comparator patients for whom interval PET-CT scans were available (see Figure 4).

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