Volumetric response classification in metastatic solid tumors on MSCT: Initial results in a whole-body setting

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Abstract

Purpose

To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously.

Materials and methods

56 consecutive patients (32 female) aged 41–82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa.

Results

Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p < 0.05, corrected). 4–8 patients’ response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements.

Conclusion

Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

Introduction

Follow up assessment of metastatic solid tumors is a frequently requested examination both in clinical radiology and imaging in oncologic randomized controlled trials (e.g. phase II). This is mostly carried out as contrast-enhanced multi-slice computed tomography (MSCT) examinations. There is limited but growing deployment of functional methods, e.g. PET-CT, CT-perfusion and parametric (e.g. diffusion weighted) MRI particularly in liver lesion imaging, although their role in response evaluation is yet unclear but promising [1], [2], [3], [4], [5]

In MSCT examinations, RECIST 1.1 [6] provides consensus guidelines regarding measurement of metastases size and evaluation of a response. Limitations of the RECIST-system include relatively high intra- and inter-observer variability in measurements and response classification [7], [8]. Volumetric analysis of metastases size has been suggested as an alternative by the RECIST council. Data from single center, single metastasis type size measurements are extensively featured in the literature [9], [10], [11], [12], [13], [14]. However, there have yet been no reports on response evaluation in more than one metastasis entity.

It is important to distinguish between size measurements and response classification. Whereas size measurement studies focus on technical parameters such as accuracy and interobserver variability, studies regarding response classification report differences in patient outcome. According to RECIST 1.1, outcome is classified on the sum of relevant lesion diameters (short axis for lymph nodes, long axis for other metastasis types). The limits for stable disease are −30% and +20% of nadir/baseline sum of diameters [6]. Studies on technical parameters are important for recommendations on what is to be regarded as stable disease and what marks progression or remission, however response classification is a clinically more relevant focus, as response classification influences decisions on therapeutic regimes and evaluation of drugs in clinical trials.

In this study, we combine examination of technical parameters and differences in tumor response classification in comparison of RECIST 1.1 and volumetric assessment.

Section snippets

Materials and methods

This is a single center retrospective analysis of 56 consecutive patients with metastatic disease. The assessment was carried out in accordance to the Declaration of Helsinki. Institutional and ethical approval was obtained and all patients gave written informed consent to retrospective analysis of their data.

Data analysis

CT-scans were reviewed by three radiologists with 8, 5 and 1.5 years of experience in RECIST respectively, blinded for patient data and readings of the other observers. Lesions of interest were selected according to RECIST 1.1 in an initial panel read. In some cases lesions smaller than required by RECIST were assessed either at baseline or follow up, providing they did fulfill size requirements at follow up as a result of disease progression, or, vice versa, at baseline as a treatment effect

Lesion sizes and patient demographics

Patient demographics are summarized in Table 1. Lesion size at baseline (n = 144) is described in detail in Table 2. Mean manually measured size of 17/144 (11.8%) lesions at baseline exceeded 35 mm, thus there was limited inclusion of very large lesions. Some lung lesions were included that were measured smaller than 10 mm at either baseline or follow up by one or more observers, providing they did fulfill RECIST 1.1 size requirements at the other time point. In detail, 21/144 (14.6%) lesions were

Response classification

According to RECIST 1.1, the limits for stable disease are −30% and +20% of nadir/baseline sum of diameters. As currently no established limits for stable disease exist in volumetric assessment, we applied RECIST criteria to volumetric evaluation as a conservative estimate, i.e. it was considered disease progression if the sum of effective diameters increased between baseline and follow up by more than 20%. There were little differences in classification between manual and volumetric

Discussion

In three common metastasis entities simultaneously, we show statistically significant smaller interobserver variability and favorable Bland–Altman limits of agreement for volumetrically as opposed to manually determined sum of relevant diameters. No significant differences were observed in agreement of response classification between manual and volumetric measurements. Therefore there is no advantage of volumetry under the same thresholds as RECIST for follow-up assessment of multi-entity

Conflict of interest

None.

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