Inadequacy of the RECIST criteria for response evaluation in patients with malignant pleural mesothelioma

doi:10.1016/S0169-5002(03)00292-7

Lung Cancer

Volume 43, Issue 1, January 2004, Pages 63-69

https://doi.org/10.1016/S0169-5002(03)00292-7 Get rights and content

Abstract

The newly introduced Response Evaluation Criteria in Solid Tumors (RECIST), which relies on a single largest dimension of tumor rather than on the product of perpendicular diameters World Health Organisation (WHO) is intended to simplify the assessment of tumor response. Purpose: Is to evaluate the performance and validity of the RECIST compared to the WHO criteria. Design: Thirty-four consecutive patients with bidimensionally measurable malignant pleural mesothelioma (MPM) were evaluated prospectively. Results: In 27% (9/34) a discrepancy was found between the WHO and RECIST response evaluation 9% (3/34) concerned best responses and 18% (6/34) objective confirmed responses. In 24% (8/34) disease progression was missed by RECIST. The percentage of patients in whom one or more discordance's between WHO and RECIST were detected was 47, 88% due to underscoring by RECIST. In a subgroup of 24 MPM patients with bidimensionally measurable pleural lesions only, the discrepancy rate was 29%, always due to underscoring by RECIST. However, when in the same subgroup the modified RECIST response evaluation was used the discrepancy rate was 21% and in all cases due to underscoring by WHO. Conclusion: For MPM bidimensional WHO response evaluation cannot automatically be replaced by RECIST because MPM has a non-spherical growth pattern. Our recommendation is to use the WHO criteria for bidimensional measurable lesions, RECIST for unidimensional measurable lesions and a modified RECIST response evaluation, in which the short axis perpendicular to the chest wall is used, for thickened pleural rind disease, according to the method used in the recently completed pemetrexed (Alimta^®) trial for MPM.

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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2023, Revista Espanola de Medicina Nuclear e Imagen Molecular
En caso de sospecha de progresión del mesotelioma pleural maligno (MPM), la imagen juega un papel importante. Nuestro objetivo es evaluar la eficacia de la PET/TC con [¹⁸F]FDG en el seguimiento de la progresión de la enfermedad, comparándola con la TC, y estimar la mediana de supervivencia global (OS, del inglés Overall Survival) según el estado de progresión en función de la TC y la PET/TC con [¹⁸F]FDG.
Se trata de un estudio observacional, retrospectivo y unicéntrico con pacientes con MPM a los que se les realizó tanto la PET/TC con [¹⁸F]FDG como la TC para controlar la progresión de la enfermedad desde marzo de 2009 hasta febrero de 2020. Se registraron las características clínicas, los hallazgos radiológicos y el estado de progresión según la TC (progresión radiológica negativa [PRN], progresión radiológica positiva [PRP]) y la PET/TC con [¹⁸F]FDG (progresión metabólica negativa [PMN], progresión metabólica positiva [PMP]). Se evaluaron las discrepancias y la concordancia entre ambos métodos. La OS se estimó mediante el método de Kaplan-Meier.
Se incluyeron un total de 56 pacientes. Había 31 (55,3%) PRN y 25 (44,7%) PRP, mientras que había 26 (46,5%) PMN y 30 (53,5%) PMP. También todos los pacientes con PRP resultaron ser PMP, sin embargo, entre los PRN, 5 pacientes (8,9% de todos los pacientes) fueron evaluados como PMP. La concordancia entre los 2 métodos en el seguimiento de la progresión de la enfermedad fue muy buena (K = 0,423; p < 0,01). La OS fue de 26 ± 2,6 meses en todos los pacientes. Las curvas de Kaplan-Meier entre PRN y PRP, y entre PMN y PMP no mostraron diferencias estadísticamente significativas (p = 0,56 y 0,25, respectivamente).
Ambos métodos son igualmente aceptables en el seguimiento de la progresión de la enfermedad en el MPM, aunque la PET/TC con [¹⁸F]FDG detectó más progresión que la TC.
In the event of suspicion of malignant pleural mesothelioma (MPM) progression, imaging plays an important role. We aimed to evaluate the efficacy of [¹⁸F]FDG PET/CT in monitoring disease progression by comparing it with CT, and estimate median overall survival (OS) according to progression status with CT and [¹⁸F]FDG PET/CT.
This was an observational, retrospective, single-institution study with MPM patients who had both [¹⁸F]FDG PET/CT and CT for monitoring disease progression from March 2009 to February 2020. Clinical features, radiological findings, and progression status according to CT [radiologic progression negative (RPN), radiologic progression positive (RPP)] and [¹⁸F]FDG PET/CT [metabolic progression negative (MPN), metabolic progression positive (MPP)] were recorded. The discrepancies and concordance between two methods were evaluated. The OS was estimated using the Kaplan–Meier method.
A total of 56 patients were included. There were thirty-one (55.3%) RPN and 25 (44.7%) RPP, while there were 26 (46.5%) MPN and 30 (53.5%) MPP. All RPP patients were also found to be MPP, however, among RPN, 5 patients (8.9% of all patients) were evaluated as MPP. The concordance between two methods in monitoring disease progression was very good (K=.423; P<.01). The OS was 26 ± 2.6 months in all patients. Kaplan-Meier curves between RPN and RPP, and between MPN and MPP did not show statistically significant differences (P=.56 and P=.25, respectively).
Both methods are equally acceptable in monitoring disease progression in MPM, even though [¹⁸F]FDG PET/CT detected more progression than CT did.
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Different subtypes of non-small cell lung cancer (NSCLC) are associated with different patterns of metastatic spread. Anatomic location of lesions in the chest may influence patterns of cancer growth and the shrinkage to therapy. Consequently, lesion location could affect apparent response rates per RECIST. We sought to explore this and develop, as needed, treatment response assessments less affected by the location.
Cases of advanced oncogene-addicted NSCLC (EGFR, ALK, and ROS1) with pre- and on-therapy imaging during initial targeted therapy were identified. Lesions located in the lung parenchyma, pleural space or intra-thoracic lymph nodes were identified and analyzed separately from each other by RECIST 1.1 (unidimensional measurements) and by a novel MAX methodology (bidimensional measurements) which takes the axis with the greatest absolute percentage change on therapy in each location as the representative measurement.
Three hundred three patients with 446 unidimensional measured lesions were included for RECIST analysis. Two hundred forty nine patients with 386 bidimensional measured lesions were included for MAX analysis, as well as the analysis comparing RECIST and MAX. Intrathoracic location significantly impacted percentage shrinkage and the response rate per RECIST. The response rates for pleural, intra-parenchymal and nodal lesions were 34.1%, 49.6%, and 68.3%, respectively (P = .0002). The MAX methodology both increased the apparent treatment effect and made it consistent between intrathoracic locations. For pleural, parenchymal and nodal lesions, the MAX calculated response rate were 83.7%, 72.2%, and 75.4%, respectively (P-value = .24).
Intrathoracic lesion location affects RECIST-based treatment effectiveness estimations. The MAX methodology neutralizes location effect when examining impact of treatment and should be explored further.
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Neoplasms of the pleura are a diverse group of benign and malignant pathologic entities that include both primary and secondary malignancies. Most neoplasms of the pleura are metastases, typically from lung cancer, although extrathoracic neoplasms such as breast and ovarian cancer have a predilection for spread to the pleura. This chapter discusses the most common primary malignant neoplasm to arise from the pleura, diffuse malignant pleural mesothelioma (MPM), with a comprehensive review of the imaging, staging evaluation, and treatment considerations for MPM.
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Treatment response assessment by imaging plays a vital role in evaluating changes in solid tumors during oncology therapeutic clinical trials. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is the reference standard imaging response criteria and provides details regarding image acquisition, image interpretation and categorical response classification. While RECIST 1.1 is applied for the majority of clinical trials in solid tumors, other criteria and modifications have been introduced when RECIST 1.1 outcomes may be incomplete. Available criteria beyond RECIST 1.1 can be explored in an algorithmic fashion dependent on imaging modality, tumor type and method of treatment. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) is available for use with PET/CT. Modifications to RECIST 1.1 can be tumor specific, including mRECIST for hepatocellular carcinoma and mesothelioma. Choi criteria for gastrointestinal stromal tumors incorporate tumor density with alterations to categorical response thresholds. Prostate Cancer Working Group 3 (PCWG3) imaging criteria combine RECIST 1.1 findings with those of bone scans. In addition, multiple response criteria have been created to address atypical imaging responses in immunotherapy.
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Malignant pleural mesothelioma is a rare tumor arising from the pleural mesothelial cells. Imaging plays a crucial role in the diagnosis, staging, and management of patients with mesothelioma. Accurate staging to stratify patients into homogeneous groups is required to evaluate the effectiveness of multimodality therapeutic regimens. CT and PET/CT are recommended for the initial staging of MPM. MRI adds value to further assess invasion of the tumor into the diaphragm, chest wall, and mediastinum. This review will discuss pearls and pitfalls in the imaging of mesothelioma with emphasis on the roles of CT, MRI, and PET/CT.
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Citation 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
Detailed guidelines pertaining to radiological assessment of malignant pleural mesothelioma are currently lacking due to the rarity of the disease, complex morphology, propensity to invade multiple planes simultaneously, and lack of specific recommendations within the radiology community about assessment, reporting, and follow-up. In March 2017, a multidisciplinary meeting of mesothelioma experts was co-sponsored by the National Cancer Institute Thoracic Malignancy Steering Committee, International Association for the Study of Lung Cancer, and the Mesothelioma Applied Research Foundation. One of the outcomes of this conference was the foundation of detailed, multidisciplinary consensus imaging and management guidelines. Here, we present the recommendations for radiologic assessment of malignant pleural mesothelioma in the setting of clinical trial enrollment. We discuss optimization of imaging parameters across modalities, standardized reporting, and response assessment within clinical trials.

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Inadequacy of the RECIST criteria for response evaluation in patients with malignant pleural mesothelioma

Abstract

Introduction

Section snippets

Patient population

Results

Discussion

Int. J. Radiat. Oncol. Biol. Phys.

Reporting results of cancer treatment

Cancer

New guidelines to evaluate the response to treatment in solid tumors

J. Natl. Cancer Inst.

Will there be resistance to the RECIST (response evaluation criteria in solid tumors)?

J. Natl. Cancer Inst.