Eur Radiol (2008) 18: 1635–1643 DOI 10.1007/s00330-008-0918-9
Christian Plathow Michael Klopp Christian Thieke Felix Herth Andreas Thomas Astrid Schmaehl Ivan Zuna Hans-Ulrich Kauczor
Received: 30 October 2007 Accepted: 2 February 2008 Published online: 28 March 2008 # European Society of Radiology 2008
C. Plathow (*) Department of Nuclearmedicine, University of Freiburg, Hugstetter 55, 79106 Freiburg, Germany e-mail:
[email protected] Tel.: +49-761-2707421 C. Plathow . I. Zuna . H.-U. Kauczor Department of Radiology, German Cancer Research Center Heidelberg, Heidelberg, Germany M. Klopp Department of Thoracic Surgery, Clinic for Thoracic Diseases, Heidelberg, Germany C. Thieke Department of Radiation Oncology, German Cancer Research Center Heidelberg, Heidelberg, Germany F. Herth Department of Pneumology, Clinic for Thoracic Diseases, Heidelberg, Germany A. Thomas Department of Oncology, Clinic for Thoracic Diseases, Heidelberg, Germany
CHEST
Therapy response in malignant pleural mesothelioma-role of MRI using RECIST, modified RECIST and volumetric approaches in comparison with CT
A. Schmaehl Department of Radiology, Clinic for Thoracic Diseases, Heidelberg, Germany
Abstract To evaluate and compare early therapy response according to RECIST (response evaluation criteria in solid tumours) and modified RECIST criteria using MRI techniques in patients with malignant pleural mesothelioma (MPM) in comparison with CT. Fifty patients with MPM (32 male/18 female) were included in this study. Early therapy response was evaluated after 9 weeks [three of six chemotherapy (CHT)] cycles. Additionally patients were examined before chemotherapy, 4 weeks after early therapy response evaluation and after six cycles to evaluate diagnostic follow-up. RECIST and modified RECIST criteria were applied using CT and MRI (HASTE, VIBE, T2-TSE sequences). In MRI additionally a volumetric approach measuring tumour weight (overall segmented tumour volume) was applied. Additionally vital capacity (VC) was measured for correlation. Image interpretation was performed by three independent readers independently and in consensus. The ‘gold standard’ was follow-up
examination. Twenty-eight patients showed partial response, 12 patients stable disease and 10 patients progressive disease at early therapy response evaluation. In the follow-up these results remained. For MRI, in 46 cases patients were identically classified using RECIST and modified RECIST criteria. Modified RECIST criteria were identically classified as gold standards in all cases, whereas using RECIST criteria in four cases there was a mismatch (partial response vs. stable disease). Modified RECIST kappa values showed better interobserver variability compared with RECIST criteria (κ=0.9–1.0 vs. 0.7– 1.0). For CT, in 44 cases patients were identically classified using RECIST and modified RECIST criteria. Modified RECIST criteria were identically classified as in gold standards in 48 out of 50 patients, whereas using RECIST criteria in 6 cases there was a mismatch (partial response vs. stable disease). Modified RECIST kappa values showed better interobserver variability compared with RECIST criteria (κ=0.9–1.0 vs. 0.6–1.0). Modified RECIST criteria especially in combination with high-resolution MRI is a very accurate and reproducible technique to correctly evaluate early therapy response in MPM. Keywords Mesothelioma . RECIST . MRI . Tumour volumetry . Validation
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Introduction
Materials and methods
Despite international efforts, occupational exposure to asbestos in industrialized countries remains a major cause of morbidity and mortality from both lung cancer and malignant pleural mesothelioma (MPM) [1]. Incidence of MPM currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades [2]. The incidence is increasing, and prognosis for the disease is uniformely dismal. The major problem encountered in the treatment of MPM is poor local control [3]. To determine disease control an early reproducible and correct measurement of tumour response to treatment is vital, especially for the development of new drugs and therapeutic combinations [4]. Conventional response criteria are CT based and have always been difficult to apply to MPM due to its unique pattern of growth. MPM most commonly grows as a rind around the pleural surface and does not produce spherical lesions with bidimensionally measurable diameters. Thus, WHO criteria are poorly suited to evaluating response in MPM, as they were developed principally to assess bidimensionally measurable disease. The RECIST (response evaluation criteria in solid tumours [5]) criteria are more suited to tumour size of MPM, as they specify the use of unidimensional measurements [6]. However the selection of measurement sites in MPM is difficult [7]. Thus, in CT modified RECIST criteria that are specifically designed to address the unique growth pattern of MPM have been introduced [8]. It could be shown that using these criteria, difficult and ambiguous situations that arise in response interpretation can be avoided. Volumetric approaches measuring tumour weight (segmented overall tumour volume) have also been proposed to monitor tumour volume and therapy response, but still these semiautomatic techniques are time consuming and therefore not applied in clinic. Thus, recently a high precision, high reproducibility and a significant correlation of MR-base lung volumetry with vital capacity (VC) in patients with MPM also in the follow-up could be proven [9]. Even though MRI has been frequently shown to have certain advantages compared to CT [10, 11] in correctly delineating MPM, CT still is the most frequently applied method in clinic [12]. With the improvement of MR high resolution and dynamic imaging techniques together with new post-processing techniques, the potential of MRI has further increased [13–15]. However, so far there is no study that evaluated response criteria in MPM using MRI. In this study RECIST and modified RECIST criteria using CT and MRI techniques in MPM were compared at an early time point after the start of chemotherapy (CHT). Follow-up controls were performed for verification; also VC was measured and compared with a volumetric approach using multireader analysis.
Fifty patients with a histologically proven MPM and a confirmed long-term asbestos exposure (32 males; 18 females; mean age 59 years; range 45 to 73 years, Karnofsky Index >80) were included in this study. After the nature of the procedure had been fully explained, informed consent was signed by all participants under an institutionally approved subject research protocol approved by the local ethical committee. After histological verification of the tumour, no treatment had been performed before CHT (combination of pemetrexed and cisplatin [16], there was no change of CHT during our investigations) in all patients. Early therapy response was evaluated after three out of six CHT cycles (9 weeks). All patients had at least four MRI and CT examinations: before chemotherapy (I), after three out of six cycles (9 weeks) (II), 4 weeks later (III) to reevaluate response criteria and after six cycles (follow-up control) (IV). Therapy response and the comparison between CT and MRI using RECIST and modified RECIST criteria were evaluated after three out of six cycles (time point II). MRI and CT All examinations were performed using a clinical 1.5-T whole-body MR system (Magnetom Symphony, Siemens Medical Solutions, Erlangen, Germany) equipped with eight receiver channels, a six channel coil and a high performance gradient system (30 mT/m) using a six-channel coil. For morphologic examination the following MRI sequences were applied (duration about 25 min): HASTE (half-Fourier single-shot fast spin-echo sequence) was acquired in coronal and and transversal planes [TR/TE: 554/28 ms; flip angle: 180°; receiver bandwidth: 610 Hz/ pixel; GRAPPA acceleration factor: 2; field of view (FOV): 144×256; slice thickness: 6 mm]. VIBE [3-dimensional (3D) gradient-recalled echo (GRE) volumetric interpolated breath-hold examination] was acquired before and after contrast media application in coronal and transversal planes [TR/TE: 6.49/2.63 ms; flip angle: 10°; receiver bandwidth: 300 Hz/pixel; field of view (FOV): 256×384; slice thickness: 4 mm]. T2-TSE (turbo-spin echo) with respiratory gating was acquired in coronal planes [TR/TE: 775/18 ms; flip angle: 160°; receiver bandwidth: 257 Hz/pixel; GRAPPA acceleration factor: 2; field of view (FOV): 333×512; slice thickness: 4 mm] [17, 18]. Altogether patients had to hold breath for about 10 to 15 s at each sequence. This was tested and trained in each patient before MRI examination. For RECIST evaluation and volumetric segmentation HASTE sequence was used. CT imaging of the thorax was performed using a standard CT system (Somatom Plus 16 Volume Zoom, Siemens Medical Solutions, Erlangen, Germany). Highresolution (1-mm slice thickness, 137 kV, 110 mAs) and
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contrast-enhanced CT images were acquired (5-mm slice thickness, 137 kV, 180 mAs, 80 ml contrast medium iomeprol; Imeron® 300, BRACCO-Altana, Konstanz, Germany). Native, arterial, portal venous and late phases were performed. The time interval between CT and MRI did not exceed 1 week. Image interpretation was performed by three independent experienced readers assessing tumour response according to the tumour response criteria (see below). All three readers were residents in a department focused on chest diseases (CT and MRI experience >2 years). The presets for CT images were as follows: soft tissue window, width + 360, level + 40; lung parenchyma/ pleural window, width + 2000, level – 300. All images were jointly randomised and showed the readers in order of randomisation. All readers were blinded to clinical data as well as the interpretations of other readers. After individual scoring a consensus scoring was performed.
in consensus, and at the same levels on subsequent following images. This technique has been recently proposed for image interpretation in MPM by Byrne and Nowak [9]. RECIST criteria For unidimensionally measurable lesions, the dimensions of the pleural tumour were measured at two separate sites on each of the three levels, and the six measurements were summated to produce a total measurement. A pleural effusion was not considered a measurable lesion. Tumour response was defined as: complete response (CR)–disappearance of all visible disease; partial response (PR)–a >=30% decrease in the sum of linear tumour measurements on two observations not less than 4 weeks apart; no change (NC) a decrease in the sum of unidimensional measurements of
