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

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.

British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma

“…A falling SMRP level at completion of chemotherapy is strongly associated with a longer survival 75 . Baseline SMRP was unable to predict survival.…”

The Neutrophil to Lymphocyte Ratio May Predict Benefit from Chemotherapy in Lung Cancer

“…Systemic inflammation in patients with malignancy is considered to reflect the cytokine profile produced both by the tumour and as a component of the host response to the tumour [34]. Increased levels of systemic inflammation have been shown to correlate with worse survival and a poor response to treatment in a number of solid organ tumours [35, 36].…”

Megakaryocyte Potentiating Factor as a Predictive Biomarker for Therapies Against Malignant Mesothelioma

“…We used a more stringent cutoff value of a −50% change in MPF to define the biomarker response compared with the previous reports 17–21 ; this cutoff was supported by our correlative analysis of CT and MPF responses in patients with MM. Such a stringent cutoff correlates with the mRECIST criterion of a 30% reduction in the sum for all target lesions and thus leads to a significant reduction of false-positive reports during monitoring.…”

“…15,16 Previous studies showed correlations between the computed tomography (CT) response and arbitrarily chosen 10% to 25% reduced serum mesothelin after chemotherapy. 17–21 Such low cutoff values are incompatible with a 30% reduction in tumor determined with CT, would contribute to high degrees of false signals, and would make it more difficult to correlate with clinical outcomes.…”