CT Evaluation of Lymph Nodes That Merge or Split during the Course of a Clinical Trial: Limitations of RECIST 1.1

Abstract

Purpose To compare Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 with volumetric measurement in the setting of target lymph nodes that split into two or more nodes or merge into one conglomerate node. Materials and Methods In this retrospective study, target lymph nodes were evaluated on CT scans from 166 patients with different types of cancer; 158 of the scans came from The Cancer Imaging Archive. Each target node was measured using RECIST 1.1 criteria before and after merging or splitting, followed by volumetric segmentation. To compare RECIST 1.1 with volume, a single-dimension hypothetical diameter (HD) was determined from the nodal volume. The nodes were divided into three groups: (a) one-target merged (one target node merged with other nodes); (b) two-target merged (two neighboring target nodes merged); and (c) split node (a conglomerate node cleaved into smaller fragments). Bland-Altman analysis and t test were applied to compare RECIST 1.1 with HD. On the basis of the RECIST 1.1 concept, we compared response category changes between RECIST 1.1 and HD. Results The data set consisted of 30 merged nodes (19 one-target merged and 11 two-target merged) and 20 split nodes (mean age for all 50 included patients, 50 years ± 7 [standard deviation]; 38 men). RECIST 1.1, volumetric, and HD measurements indicated an increase in size in all one-target merged nodes. While volume and HD indicated an increase in size for nodes in the two-target merged group, RECIST 1.1 showed a decrease in size in all two-target merged nodes. Although volume and HD demonstrated a decrease in size of all split nodes, RECIST 1.1 indicated an increase in size in 60% (12 of 20) of the nodes. Discrepancy of the response categories between RECIST 1.1 and HD was observed in 5% (one of 19) in one-target merged, 82% (nine of 11) in two-target merged, and 55% (11 of 20) in split nodes. Conclusion RECIST 1.1 does not optimally reflect size changes when lymph nodes merge or split. Keywords: CT, Lymphatic, Tumor Response Supplemental material is available for this article. © RSNA, 2021.

Keywords: CT; Lymphatic; Tumor Response.

Figure 1:

A, Three hypothetical scenarios are shown for merging and splitting nodal lesions. Top, one-target merged (one target node [short-axis diameter ≥ 1.5 cm] merges with nearby nontarget node or nodes); middle, two-target merged (two neighboring target nodes merge with each other); and bottom, split node (a conglomerate target node splits into smaller fragments). B–D, Images show example patterns of merging in, B, one-target merged and, C, two-target merged and, D, splitting in lymph nodes that were assessed on serial CT images. These theoretical graphs show possible scenarios in which RECIST 1.1 measurements (top row) could differ from volumetric measurements (bottom row). In the one-target merging scenario (B), both volumetric measurement and RECIST 1.1 display an increase in size after merging (268 to 524 cm³ for volume and 8 to 10 cm for RECIST 1.1). In the two-target merging scenario (C), although volumetric measurement, which represents the true number of cancer cells, shows an increase in size (302 to 580 cm³), RECIST 1.1 measurement shows a decrease (12 to 10 cm). In the splitting scenario (D), the opposite can occur. While a conglomerate node gets smaller and splits into smaller fragments, the total volume shows a decrease in size (580 to 302 cm³), while RECIST 1.1 indicates an increase (10 to 12 cm). RECIST = Response Evaluation Criteria in Solid Tumors.

Figure 2:

Top images indicate percent change based on RECIST 1.1, tumor volume, and hypothetical diameter measurements for A, one-target merged, C, two-target merged, and, E, split nodes. Bottom images illustrate the percent size change of each target lesion based on RECIST 1.1 and hypothetical diameter measurement and also demonstrate the response categories of treatment for each lesion based on RECIST 1.1 definition for B, one-target merged, D, two-target merged, and, F, split nodes. RECIST 1.1 assigns four categories of response based on percent size change: complete response (the disappearance of all lesions), partial response (PR) (< 30% decrease), stable disease (SD) (≤ 30% decrease or ≤ 20% increase), and progressive disease (PD) (> 20% increase). RECIST = Response Evaluation Criteria in Solid Tumors.

Figure 3:

Bland-Altman plots show the mean difference and limit of agreement between Response Evaluation Criteria in Solid Tumors version 1.1 and hypothetical diameter method for measuring percent change in size of, A, one-target merged nodes, B, two-target merged nodes, and, C, split nodes.

Figure 4:

Two target nodules in a 52-year-old woman with ovarian cancer are shown from baseline (left) and follow-up (right). A and B, Response Evaluation Criteria in Solid Tumors version 1.1 measurement at corticomedullary phase of contrast material–enhanced CT shows tumor size reduced (3.2 to 2.4 cm, red boxes) from baseline (A) to follow-up (B). C and D, However, volumetric measurement shows an increase in size (42.10 to 78.29 cm³, red boxes) from baseline (C) to follow-up (D). B01, B05, and F06 are automated lesion annotations provided by the picture archiving and communication system. M = merged nodule.

Figure 5:

Two target nodules in a 50-year-old man with mesothelioma are shown from baseline (left) and follow-up (right). A and B, Response Evaluation Criteria in Solid Tumors version 1.1 measurement shows tumor size increased (1.7 to 1.8 cm) from baseline (A) to follow-up (B). C and D, However, volumetric measurement shows a decrease in size (7.19 to 3.09 cm³) from baseline (C) to follow-up (D). B01, B02, B09, and F06 are automated lesion annotations provided by the picture archiving and communication system. S = splitting lesion, SS = split segment.