Continued pemetrexed and platin-based chemotherapy in patients with malignant pleural mesothelioma (MPM): Value of 18F-FDG-PET/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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Cited by (24)
The efficacy of [<sup>18</sup>F]FDG PET/CT in monitoring disease progression in malignant pleural mesothelioma
2023, Revista Espanola de Medicina Nuclear e Imagen MolecularFDG PET/CT for Staging and Restaging Malignant Mesothelioma
2022, Seminars in Nuclear MedicineCitation Excerpt :Already during the first evaluations, the modality proved able to assess responders and non-responders to therapy, even at early time points.66,68-74 The use of either metabolic response criteria, that is, EORTC (European Organization for Research and Treatment of Cancer) and PERCIST (PET Response Criteria in Solid Tumors)75-78 or semi-quantitative and volumetric analyses, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), allowed predicting response and patients prognosis.66,68,69-74,79 Similarly though to initial staging, [18F]FDG PET/CT evaluation after therapy is negatively impacted by previous talc pleurodesis, especially in case of volumetric computation of metabolically avid lesions.
PET-CTBased Quantitative Parameters for Assessment of Treatment Response and Disease Activity in Cancer and Noncancerous Disorders
2022, PET ClinicsCitation Excerpt :This software provided an automated tumor volume delineation by using an isocontour threshold method, and they found MTV and TLG as independent predictive factors for tumor progression in patients with mesothelioma. Veit-Haibach et al36 and Schaefer and colleagues37 used similar methods for calculation of volume-based parameters on 18F-FDG PET in patients with mesothelioma. Both investigators used a commercially available workstation (Advanced Workstation, General Electrics); they determined volume-based parameters by drawing a rectangular VOI over the corresponding hemithorax in all 3 planes with minimal SUV of 2.5 levels and found that these parameters were predictor of overall survival in patients with mesothelioma treated with chemotherapy.
“PET/CT Variants and Pitfalls in Lung Cancer and Mesothelioma”
2021, Seminars in Nuclear MedicineCitation Excerpt :Consequently, response assessment is commonly based on modified Response Evaluation Criteria in Solid Tumors (RECIST), firstly adapted by Burne and Novak in 2004,80 and recently adjusted with new recommendations based on RECIST 1.1 criteria.81 The use of metabolic criteria for MPM response assessment has mostly been limited to the EORTC criteria74 and at some extent to volumetric analyses, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), prompted to better delineate the variation of tumor burden during the course of treatment.49–51,65,68,69,82 Semi-automated iterative threshold-based region-growing algorithm49 or liver-based threshold method68 have been used for contouring.
Response evaluation in mesothelioma: Beyond RECIST
2015, Lung Cancer<sup>18</sup>F-FDG-PET/CT in malignant mesothelioma
2013, Biomedicine and PharmacotherapyCitation Excerpt :Considering a possible interference of TP on post-chemotherapy disease evaluation with an increase of FDG uptake, the study concluded that the metabolic response measured by SUVmean seems to be in better agreement with the radiological response. Another paper by Schaefer et al. [12] analyzed different FDG-PET/CT parameters – modified RECIST, SUVmax according to the EORTC criteria, Total Lesion Glycolysis (TLG) and FDG volume (PETvol) – for assessing treatment response in 41 patients under continued therapy with pemetrexed and platin. 18F-FDG-PET/CT scans were performed within 2 weeks before therapy and after every three consecutive cycles of combined chemotherapy.
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Equally contributed.