Continued pemetrexed and platin-based chemotherapy in patients with malignant pleural mesothelioma (MPM): Value of 18F-FDG-PET/CT

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Abstract

Purpose

To prospectively analyze different FDG-PET/CT-parameters (modified RECIST, SUVmax, TLG, PETvol) in patients with malignant pleural mesothelioma (MPM) under continued pemetrexed and platin based treatment.

Methods

Patients with biopsy proven MPM undergoing treatment with pemetrexed and platin based treatment were prospectively included in the study. Integrated FDG-PET/CT imaging was performed within 2 weeks before therapy and after every three consecutive cycles of combined chemotherapy. All CT-images were evaluated according to the modified RECIST (modRECIST) criteria. All FDG-PET/CT images were analyzed using SUVmax (maximum Standard Uptake Value) according to the EORTC criteria, change in Total Lesion Glycolysis (TLG) and FDG volume (PETvol). Percent change in all parameters compared to the initial, pre-therapeutic and the previous FDG–PET/CT scan. ModRECIST, EORTC guidelines, increase or decrease in TLG and PETvol was correlated with overall survival (OS) using the Log Rank Test.

Results

41 patients with MPM were prospectively included in this study. The median OS of the study population is 439 days (111–1128). 41 patients had initial staging, 41 patients completed 3 cycles, 28 patients completed 6 cycles, 19 patients completed 9 cycles, 11 patients completed 12 cycles, 5 patients completed 15 cycles, 4 patients completed 18 cycles and 1 patient completed 21 cycles of chemotherapy. Chemotherapy was well tolerated up to 21 cycles. SUVmax showed a high variance over time for individual patients and change in SUVmax using EORTC guidelines did not predict OS at any time point. Ongoing morphological response in CT using modRECIST had highest correlation with OS and predicted survival up to the 15th cycle of continued permetrexed and platin based treatment. The correlations of response of the volume based PET parameters (TLG and PETvol) and OS are inferior to the morphological modRECIST parameter.

Conclusion

Permetrexed and platin based treatment in MPM patients can be given over a prolonged time with good tolerance. Therapy response should be assessed by modRECIST in CT but not with SUVmax in FDG-PET. Long term permetrexed and platin therapy should be considered in MPM patients with good tolerance of treatment and ongoing morphological response in CT.

Introduction

Malignant pleural mesothelioma (MPM) is an aggressive tumor arising from the thoracic pleura with poor prognosis and an increasing incidence as a result of widespread exposure to asbestos. Due to the very long latency period of 30–40 years between occurrence of MPM and the asbestos exposure in the last century the incidence of this disease in on the rise [1], [2]. MPM initially grows localised and when detected in early stages, MPM can be treated in a multimodality setting including extrapleural pneumonectomy and neoadjuvant or adjuvant chemotherapy [3], [4]. However, the diagnosis of MPM is usually made in advanced stages and most patients qualify only for systemic chemotherapy.

The effect of chemotherapy for patients with MPM has been documented in several studies. Mitomycin C, vinblastine and cisplatin resulted in an objective response of 13.5%, however approximately 70% of the patients reported a benefit in clinical symptoms [5]. The addition of permetrexed to cisplatin resulted in a significant better response (17% versus 41%) and overall survival (median survival 9.3 months versus 12.1 months) compared to cisplatin alone [6]. An EORTC proved ralitrexed, another folate antagonist, to be superior to cisplatin alone concerning response (14 versus 24%) and survival (8.8 versus 11.1 months) [7].

18FDG-PET/CT-imaging is a widely used cancer imaging modality [8]. The diffuse growth pattern of advanced MPM makes careful staging a challenge and the standard RECIST criteria have been identified partly as inadequate [9], [10]. The new widely accepted modified RECIST (modRECIST) criteria use two CT measurements of tumor thickness perpendicular to the chest wall at three different levels. It is predictive for survival in MPM patients undergoing treatment with cisplatin and gemcitabine and is used for continued follow-up measurements in the course of the disease [11]. Additionally, FDG-PET and PET/CT have been proposed as a tool for response evaluation in patients with MPM. However, in different studies different PET-response parameters (Standard Uptake Value (SUV), tumor lesion glycolysis (TLG), volume determined by glucose uptake (PETvol)) have been found predictive for survival when measured at a specific time point during the course of disease [12], [13]. It is currently unclear what type of measurement in MPM would optimally be used for response assessment.

The aim of our study was to evaluate how long and how many cycles chemotherapy might still be beneficial for treatment of patients with MPM and to evaluate different FDG-PET/CT-parameters (modRECIST criteria, SUVmax, TLG, PETvol) concerning their usefulness in prediction of outcome in patients with continued permetrexed and platin-based chemotherapy.

Section snippets

Patients and selection

All patients had biopsy proven MPM and were undergoing treatment with pemetrexed combined with cisplatin or carboplatin chemotherapy. All patients were treated in the Clinic and Policlinic of Oncology, University Hospital of Zürich from December 2002 until June 2004. As part of the expanded access program they were evaluated by FDG-PET/CT every third cycle of chemotherapy. All included patients had at least three cycles and a maximum of 21 cycles of chemotherapy. All patients with talk

Patients characteristics

41 patients with MPM were prospectively included in this study. The median overall survival of the study population is 439 days (111–1128). 41 patients had initial staging, 41 patients completed 3 cycles, 28 patients completed 6 cycles, 19 patients completed 9 cycles, 11 patients completed 12 cycles, 5 patients completed 15 cycles, 4 patients completed 18 cycles and 1 patient completed 21 cycles of chemotherapy. Fifteen patients received talc pleurodesis prior to initiation of therapy. The mean

Discussion

We analyzed MPM patients under continued pemetrexed and platinum-based treatment with serial FDG-PET/CT every three cycles and attempted to find out how many cycles of continued permetrexed and platin-based chemotherapy might be beneficial. Permetrexed and platin-based chemotherapy was tolerated up to 21 cycles. Ongoing partial response in modRECIST compared to the staging FDG-PET/CT was the most reliable parameter to predict overall survival, while SUVmax response using the EORTC guidelines

Conflict of interest

The authors of the manuscript declare that they have no conflict of interest concerning this study.

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