Abstract 1936P
Background
In oncology trials with radiology, the baseline (BL) evaluation is critical as the selection of target lesions (TL) determines the quality of follow-up. The RECIST workgroup provided a method and recommendations for selecting TL and non-target lesions (NTL) for reporting disease evolution. However, in practice, the process of TL selection relies on the subjective opinion of radiologists and nonmalignant (NM) lesions might be mistaken as TLs. Our aim was to analyze the impact of NM lesions mistaken as TL at BL and to provide recommendations to mitigate risks in clinical trials.
Methods
Assuming that changes affect homogenously malignant lesions whereas NM lesions remain stable overtime, we simulated the change of tumor burden when a proportion of NM lesions were miss-selected as TL or NTL. As a function of the proportion of NM lesions in the tumor burden, we computed the proportional increase of malignant TL required to detect a progressive disease (PD) or a partial response (PR). We also simulated the proportional increase of malignant TL required to detect a PD after a PR. Considering Best Overall Response (BOR) and Progression Free Survival (PFS) as endpoints, we simulated the impact of selecting NM lesions as TL or NTL on clinical trial endpoints.
Results
For the measurable disease, our mathematical simulation showed that, when 1/3 of the tumor burden are NM lesions, the disease related fraction of the tumor burden should increase by more than 30% to trigger a PD or should have decreased by more than 40% to trigger a PR. To trigger a PD after a PR we showed that diseased related fraction of the tumor burden should increase by 33% respect to the 20% RECIST threshold of progression. For clinical trials, we showed that the selection of NM lesions can have a significant impact on the determination of PFS and BOR.
Conclusions
Selecting NM lesions as baseline TL can jeopardize the detection of PR or PD. In clinical trials, the impact of selecting NM lesions depends on their categorization as TL or NTL, on the proportion in tumor burden and if a PR occurred before the PD. We suggest not selecting equivocal lesions at BL for response-related endpoint (phase II trials) while selecting them as NTL for progression-related endpoint (phase III trials).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Iannessi, H. Beaumont, Y. Liu: Full/Part-time employment: Median Technologies. All other authors have declared no conflicts of interest.