Inadequacy of the RECIST criteria for response evaluation in patients with malignant pleural mesothelioma
Introduction
Objective tumor shrinkage has been widely adopted as a standard end-point to select effective anticancer drugs. Therefore, monitoring and quantitating of tumors responses to treatment plays a pivotal role in cancer treatment research. Standardised criteria for measuring therapeutic response were adopted in 1981, but have been modified by various organisations [1], [2], [3]. The World Health Organisation (WHO), the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer (EORTC) have recently adopted a new set of response criteria (Response Evaluation Criteria in Solid Tumors, RECIST) [4]. Tumor size has according to the WHO response criteria traditionally been estimated by the product of the longest diameter (LD) and its perpendicular diameter for each tumor, but the RECIST criteria uses a simplified one-dimensional measurement (sum of the LD of tumors). The differences in the criteria for best response according to WHO or RECIST are summarised in Table 1. The RECIST method assumes that the length, width and height of a tumor have equivalent percent reductions or increases in length under treatment, assuming that tumors are spherical. However, if some percent change in tumor's LD do not reflect changes in other dimensions, then measuring two-dimensions would be better than one in estimating tumor volume [5].
Malignant pleural mesothelioma (MPM) is a nearly invariably lethal tumor of the pleura, whose origin is linked to the exposure to asbestos fibres. Pleural mesothelioma typically shows a parietal growth pattern and often presents radiographically with unilateral pleural fluid, pleural masses or diffuse pleural thickening. Due to this parietal growth pattern, often no circumscribed tumor mass can be delineated. This makes response evaluation in MPM patients notoriously difficult. So far, for MPM the WHO response evaluation has been used as the standard method, but with the introduction of the RECIST criteria the question arises if these criteria are also valid for MPM. Pleural mesotheliomas may change predominantly in their perpendicular axis to the chest wall, without major changes in the broader basis (LD) as is illustrated by index case #9 (Fig. 1).
Purpose of this study is to evaluate in a prospective manner the performance and validity of the RECIST criteria compared to the traditional WHO criteria in 34 consecutive MPM patients with both pleural and non-pleural bidimensionally measurable lesions. To investigate if the performance of WHO and RECIST differs between pleural and non-pleural lesions, WHO response evaluation will be compared with RECIST and a modified RECIST response evaluation in a subgroup of 24 MPM patients with bidimensionally measurable pleural lesions only.
Section snippets
Patient population
The response to chemotherapy was evaluated in 34 consecutive patients with histologically proven MPM treated between May 2000 and December 2001. Eighteen of them were enrolled in the multicenter phase II study with Gemcitabine (1250 mg/m2) and Cisplatin (80 mg/m2) [6], and 16 patients were enrolled in the ongoing phase III study EORTC 08983 with either Cisplatin alone (80 mg/m2) or Cisplatin plus Tomudex (3 mg/m2) every 3 weeks. In all subjects the histological diagnosis of MPM was confirmed by
Results
Comparison of the WHO and RECIST criteria took place after two courses (n=34), four courses (n=25) and six courses (n=13) of chemotherapy, and after one (n=9), two (n=4) and three (n=2) follow-up response evaluations. The 34 MPM patients had in total 40 pleural bidimensional measurable lesions, two bidimensionally measurable tumor locations within the chest wall, and 35 bidimensional measurable local and distant metastases.
Table 2 shows that in 27% (9/34) a discrepancy was found between the WHO
Discussion
The newly introduced RECIST, which relies on a single largest dimension of tumor rather than on the product of perpendicular diameters, is intended to further simplify the assessment of tumor response [4]. RECIST is based on the assumption that tumors are spherical and that the responding patients have equivalent percentage reductions in the measures of length, width and depth of the tumor, which makes no difference in defining a PR based on changes in largest dimension or the product of
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2019, Journal of Thoracic OncologyCitation Excerpt :Even though it may not be feasible to acquire tumor tissue from more than one site, acquisition of tissue from two sites, one showing response and another site with stable disease or progression, can help understand mechanisms of response and resistance. Response assessment in MPM has been associated with a high degree of intraobserver variability, largely due to the circumferential rind-like morphology of disease growth.47,48 Development of mesothelioma-specific mRECIST criteria provided guidelines on the acquisition of measurements that better account for this growth pattern, thus improving the standardization of response assessment.34