Elsevier

Lung Cancer

Volume 67, Issue 3, March 2010, Pages 311-317
Lung Cancer

Combined FDG-PET/CT in response evaluation of malignant pleural mesothelioma

https://doi.org/10.1016/j.lungcan.2009.04.015Get rights and content

Abstract

Purpose

Based on the complex growth pattern of MPM, conventional response evaluation in this cancer entity is challenging. Therefore, there is growing interest in therapy response evaluation with FDG-PET/CT. The aim of the study was to evaluate the value of several FDG-PET/CT-parameters in therapy response evaluation concerning prediction of survival at baseline and after three cycles of therapy.

Patients and methods

The study was performed in accordance with the regulations of the local ethics committee. Forty-one patients with proven MPM and treated with palliative pemetrexed and platinum-based chemotherapy were included. All patients were evaluated by FDG-PET/CT at baseline and after three cycles of chemotherapy. Responders and non-responders were evaluated based on modified RECIST- and EORTC-criteria. Additional PET-parameters (SUVmean, tumor lesion glycolysis (TLG) and tumor volume (PETvol)) were evaluated. Results were evaluated using the COX regression and the Kaplan–Meier method.

Results

None of the baseline CT-measurements or the initial PET-parameters were predictive for survival. Based on CT, after three cycles of therapy 10 patients were categorized as responders, 30 were classified as stable disease and 1 had progressive disease. Based on PET-evaluation, 14 responders were identified, 23 patients with stable disease and 4 patients were progressive. CT-response after 3 cycles of chemotherapy was significantly related to overall survival (p = 0.001). However, neither SUVmax-response (p = 0.61) nor SUVmean-response (p = 0.68) were related to survival. A decrease of TLG and PETvol, however, was found to be predictive (TLG: p = 0.01; PETvol: p = 0.002).

Conclusion

Response evaluation based on modified RECIST by CT as well as response evaluation by TLG and PETvol in FDG-PET, but not SUVmax-measurements are predictive for survival in MPM.

Introduction

Malignant pleural mesothelioma (MPM) is a thoracic neoplasm arising from the pleural lining. In the majority of patients, a history of occupational exposure to asbestos can be identified. Taking into account a latency period of 15–50 years and a decline in workplace exposure in Europe only since the 1990s, it is estimated that the number of patients with mesothelioma will continue to increase and reach a peak between 2015 and 2020 [1], [2]. MPM tend to grow localized over the serosal surface, penetrating into interlobar fissures and finally encasing the lung. The most common sites of spread are hilar, internal mammary and mediastinal lymph nodes; distant metastases are clinically rarely apparent. About 50–65% of MPM are of epitheloid type, the remaining being mixed or sarcomatoid [3].

The palliative effect of combination chemotherapy for patients with pleural mesothelioma has been documented in a study from the UK. An update of the experience from the Royal Marsden Hospital described the palliative benefits of mitomycin C, vinblastine and cisplatin. While the rate of objective responses was only 13.5% and the median survival only 7 months, 69% of patients reported an improvement of symptoms. The symptoms best responding to treatment were pain in 71%, cough in 62% and dyspnoea in 50% [4]. Two large randomized trials have demonstrated a survival benefit of the addition of the folate antagonists pemetrexed or altitrexed to cisplatin chemotherapy [5], [6]. The study of Vogelzang comparing cisplatin alone to cisplatin and pemetrexed demonstrated a significant better response (17% vs. 41%) and survival (median survival 9.3 months vs. 12.1 months) for the cisplatin pemetrexed combination. This has lead to the approval of pemetrexed for treatment of MPM in many countries. For patients with less advanced disease, multimodality therapy including extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy is a therapeutic option [7], [8].

The growth pattern of MPM provides a challenge to measure response to chemotherapy and standard RECIST-criteria have been felt to be inadequate for response evaluation [9], [10], [11]. However, modified RECIST-criteria for MPM proposed by Byrne and Nowak based on two CT-measurements of tumor thickness perpendicular to the chest wall at three different levels have become widely accepted and were also used the Vogelzang study. Response measured by modified RECIST was predictive for survival after treatment with cisplatin and gemcitabine [12]. In addition to CT, contrast-enhanced MRI as another anatomic imaging method has also been evaluated and found to give comparable results to CT [13].

Recently, metabolic 18FDG-PET-imaging has been proposed as a promising alternative for response evaluation in MPM [14], [15], [16].

These studies were performed with small patient populations and comparisons of PET-measurements and modified RECIST parameters are only partly available. Additionally, no comparisons concerning the predictive value of CT-imaging and/or PET-imaging have been made so far. Co-registered FDG-PET/CT-imaging might be superior to either methodology alone in the evaluation of thoracic malignancies [17], [18]. The purpose of our study in patients with MPM was firstly, to evaluate whether pre-therapeutic PET-parameters or CT-parameters were predictive of survival; secondly, whether the change of PET-parameters or CT-parameters after three cycles of chemotherapy with pemetrexed combined with cisplatin or carboplatin by using EORTC FDG/PET-response criteria or modified RECIST-criteria were related to survival; and thirdly: if alternative parameters (TLG, PETvol, SUVmean) or categories were predictive for overall survival.

Section snippets

Patient selection

This report includes the prospective data of sequential patients treated at the Clinic and Policlinic of Oncology, University Hospital of Zürich from December 2002 until June 2004. Inclusion/exclusion criteria: patients with biopsy proven MPM undergoing chemotherapy with pemetrexed combined with cisplatin or carboplatin as part of the expanded access program were evaluated by FDG-PET/CT before and after every third cycle of chemotherapy. Patients were staged clinically using the TNM-staging

Patients characteristics

The data of 41 consecutive patients were evaluated. The patients characteristics are listed in Table 1. Thirty-four patients received first line chemotherapy, 7 patients received second line chemotherapy, all of those at relapse after neoadjuvant chemotherapy with cisplatin, gemcitabine and surgery (2 × partial resection, 4 × pleuropneumectomy, 1 × extrapleural pneumectomy). Pemetrexed was combined with cisplatin in 14 patients and with carboplatin in 27 patients. Fifteen patients received talc

Discussion

Our results demonstrate that response evaluation in MPM after three cycles of therapy with pemetrexed and platinum-based chemotherapy by CT-determined modified RECIST and by FDG-PET-determined TLG- and PETvol-measurements are predictive for overall survival.

The growth pattern of MPM growing as a pleural rind provides a challenge to measure response to chemotherapy. While mesothelioma-specific guidelines have been developed for CT, there are no mesothelioma-specific criteria described for

Conflict of interest

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

Acknowledgements

We thank Victor Kalff, MD and Ujwal Bhure, MD for their valuable comments and helpful and valuable contribution to this study. The study was partly funded by Eli Lilly Suisse S.A., Vernier, Switzerland.

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