Comparison of CT and PET-Based Assessments per Lugano Criteria in FDG-Avid Lymphoma- a Retrospective Analysis of Independent Review Assessments

Background: The Lugano classification criteria introduced in 2014 is widely used in clinical trials as well as in clinical practice for response assessment in Lymphoma. The criteria recommend a combination of disease morphology assessment using Computed Tomography (CT) and lesion metabolic activity assessment on Positron Emission Tomography (PET), with PET metabolic assessments being the driver for overall response assessment. In this study, we analyzed the alignment between assessments made using both modalities. The independent review assessments of 583 subjects with 1032 follow up timepoints from multiple Phase I to Phase-III multi-center clinical trials to determine the alignment between assessments made using both modalities.

Methods: 583 subjects with 1032 post-baseline timepoints from multiple phases I to phase-III multi-center clinical trials on lymphoma were retrospectively analyzed using the independent review data. All clinical trials used the Lugano Classification as a response assessment criteria. The variability between the PET-based metabolic assessments [Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), No Metabolic Response (NMR) and Progressive Metabolic Disease (PMD)] and CT-based morphological assessments [(Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD)] for the same timepoint was analyzed by comparing the following:

1. Timepoints where PET-based assessment was CMR, but CT based assessment was not CR and vice versa

2. Timepoints where PET-based assessment was PMD, but CT based assessment was not PD and vice versa

Results:

• 280 timepoints had CMR on PET, but only 109 of these 280 timepoints (39%) had an assessment of CR on CT (147 were PR, 23 SD, and 1 PD)

• 138 timepoints that had CR on CT but 32 (23%) were non-CMR on PET (29 were PMR, 1 NMR, and 2 PMD).

• 343 timepoints had PMD on PET and 301 of these 343 timepoints (88%) had an assessment of PD on CT (2 were CR, 28 PR, 12 SD)

• 115 timepoints had PD on CT Scan, but 10 (8%) timepoints that had PD on CT were non-PMD on PET (1 CMR, 6 PMR, and 3 NMR)

Conclusion: The results shown above suggest that PET and CT based assessments may not always be aligned. CMR on PET can be associated with residual disease on CT in about 61%, whereas a CR on CT may have associated residual metabolic activity on PET in 23% cases. This is in alignment with the Lugano criteria where PET-based metabolic activity assessment is considered a driver in lymphoma response assessment than CT. PET findings show the metabolic activity of the lesions, whereas morphological response on CT scan may be affected by underlying treatment-related effects such as fibrosis and may not always align with PET response. A PMD on PET is associated with a progression on CT scan most of the times and vice versa, but in a small number of the case, progression may not be aligned on two modalities and may need further investigation by biopsy and follow-up imaging.