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

C E Hooper; I D Lyburn; J Searle; M Darby; T Hall; D Hall; A Morley; P White; N M Rahman; E De Winton; A Clive; V Masani; D T Arnold; A Dangoor; S Guglani; P Jankowska; S A Lowndes; J E Harvey; J P Braybrooke; N A Maskell

doi:10.1038/bjc.2015.62

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

C E Hooper, I D Lyburn, J Searle, M Darby, T Hall, D Hall, A Morley, P White, N M Rahman, E De Winton, A Clive, V Masani, D T Arnold, A Dangoor, S Guglani, P Jankowska, S A Lowndes, J E Harvey, J P Braybrooke, N A Maskell

Research output: Contribution to journal › Article (Academic Journal) › peer-review

38 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1175-82
Number of pages	8
Journal	British Journal of Cancer
Volume	112
Issue number	7
DOIs	https://doi.org/10.1038/bjc.2015.62
Publication status	Published - 31 Mar 2015

Structured keywords

Memory

Keywords

Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Carboplatin
Cisplatin
Cohort Studies
Female
Glutamates
Guanine
Humans
Lung Neoplasms
Lymphocytes
Male
Mesothelioma
Multimodal Imaging
Neutrophils
Pemetrexed
Positron-Emission Tomography
Prognosis
Prospective Studies
Survival Analysis
Tomography, X-Ray Computed
Treatment Outcome
Clinical Trial
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't

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Hooper, C. E., Lyburn, I. D., Searle, J., Darby, M., Hall, T., Hall, D., Morley, A., White, P., Rahman, N. M., De Winton, E., Clive, A., Masani, V., Arnold, D. T., Dangoor, A., Guglani, S., Jankowska, P., Lowndes, S. A., Harvey, J. E., Braybrooke, J. P., & Maskell, N. A. (2015). The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication: The South West Area Mesothelioma and Pemetrexed trial. British Journal of Cancer, 112(7), 1175-82. https://doi.org/10.1038/bjc.2015.62

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title = "The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication: The South West Area Mesothelioma and Pemetrexed trial",

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.",

keywords = "Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Carboplatin, Cisplatin, Cohort Studies, Female, Glutamates, Guanine, Humans, Lung Neoplasms, Lymphocytes, Male, Mesothelioma, Multimodal Imaging, Neutrophils, Pemetrexed, Positron-Emission Tomography, Prognosis, Prospective Studies, Survival Analysis, Tomography, X-Ray Computed, Treatment Outcome, Clinical Trial, Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't",

author = "Hooper, {C E} and Lyburn, {I D} and J Searle and M Darby and T Hall and D Hall and A Morley and P White and Rahman, {N M} and {De Winton}, E and A Clive and V Masani and Arnold, {D T} and A Dangoor and S Guglani and P Jankowska and Lowndes, {S A} and Harvey, {J E} and Braybrooke, {J P} and Maskell, {N A}",

year = "2015",

month = mar,

day = "31",

doi = "10.1038/bjc.2015.62",

language = "English",

volume = "112",

pages = "1175--82",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "7",

}

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 2015, 'The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication: The South West Area Mesothelioma and Pemetrexed trial', British Journal of Cancer, vol. 112, no. 7, pp. 1175-82. https://doi.org/10.1038/bjc.2015.62

The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication : The South West Area Mesothelioma and Pemetrexed trial. / Hooper, C E; Lyburn, I D; Searle, J et al.

In: British Journal of Cancer, Vol. 112, No. 7, 31.03.2015, p. 1175-82.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication

T2 - The South West Area Mesothelioma and Pemetrexed trial

AU - Hooper, C E

AU - Lyburn, I D

AU - Searle, J

AU - Darby, M

AU - Hall, T

AU - Hall, D

AU - Morley, A

AU - White, P

AU - Rahman, N M

AU - De Winton, E

AU - Clive, A

AU - Masani, V

AU - Arnold, D T

AU - Dangoor, A

AU - Guglani, S

AU - Jankowska, P

AU - Lowndes, S A

AU - Harvey, J E

AU - Braybrooke, J P

AU - Maskell, N A

PY - 2015/3/31

Y1 - 2015/3/31

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Biomarkers, Tumor

KW - Carboplatin

KW - Cisplatin

KW - Cohort Studies

KW - Female

KW - Glutamates

KW - Guanine

KW - Humans

KW - Lung Neoplasms

KW - Lymphocytes

KW - Male

KW - Mesothelioma

KW - Multimodal Imaging

KW - Neutrophils

KW - Pemetrexed

KW - Positron-Emission Tomography

KW - Prognosis

KW - Prospective Studies

KW - Survival Analysis

KW - Tomography, X-Ray Computed

KW - Treatment Outcome

KW - Clinical Trial

KW - Journal Article

KW - Multicenter Study

KW - Observational Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/bjc.2015.62

DO - 10.1038/bjc.2015.62

M3 - Article (Academic Journal)

C2 - 25756396

VL - 112

SP - 1175

EP - 1182

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 7

ER -