Abstract
Simple SummaryImmune checkpoint inhibitors (ICI) have revolutionized cancer care. However, assessing the efficacy of these new molecules with targeted therapeutic responses may induce too much delay when using classical biomarkers derived from morphological imaging (CT). The objective of our study is to propose fast, cost-effective, convenient, and effective biomarkers using the perfusion parameters from dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of ICI early response. In a population of 63 patients with metastatic cancer eligible for immunotherapy, we demonstrate that a decrease of more than 45% in the area under the perfusion curve (AUC) between baseline and day 21 is significantly associated with better overall survival. Thus, AUC from DCE-US looks to be a promising new biomarker for the early evaluation of response to immunotherapy.Purpose: The objective of our study is to propose fast, cost-effective, convenient, and effective biomarkers using the perfusion parameters from dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of immune checkpoint inhibitors (ICI) early response. Methods: The retrospective cohort used in this study included 63 patients with metastatic cancer eligible for immunotherapy. DCE-US was performed at baseline, day 8 (D8), and day 21 (D21) after treatment onset. A tumor perfusion curve was modeled on these three dates, and change in the seven perfusion parameters was measured between baseline, D8, and D21. These perfusion parameters were studied to show the impact of their variation on the overall survival (OS). Results: After the removal of missing or suboptimal DCE-US, the Baseline-D8, the Baseline-D21, and the D8-D21 groups included 37, 53, and 33 patients, respectively. A decrease of more than 45% in the area under the perfusion curve (AUC) between baseline and D21 was significantly associated with better OS (p = 0.0114). A decrease of any amount in the AUC between D8 and D21 was also significantly associated with better OS (p = 0.0370). Conclusion: AUC from DCE-US looks to be a promising new biomarker for fast, effective, and convenient immunotherapy response evaluation.
Highlights
Immune checkpoint inhibitor (ICI) immunotherapies using monoclonal antibodies antagonizing T-cell co-inhibition receptors have been the major revolution of the last few years in anti-cancer treatment
Our study aims to determine whether perfusion parameters extracted from dynamic contrast-enhanced ultrasound can be used as biomarkers for ICI early response evaluation
In order to study the variation of perfusion due to the administration of ICI, we focused on the increase of tumor perfusion at day 8 (D8) and its decrease at day 21 (D21)
Summary
Immune checkpoint inhibitor (ICI) immunotherapies using monoclonal antibodies antagonizing T-cell co-inhibition receptors have been the major revolution of the last few years in anti-cancer treatment. By blocking the immune checkpoints used by the tumor cells to create an immunosuppressive tumor microenvironment, ICIs enhance the antitumor immune response [1]. Since the first FDA approval of an ICI (ipilimumab for the treatment of advanced melanoma both in pre-treated or chemotherapy naïve patients, in March 2011 [2]), many more therapeutic extensions and molecules have been approved [3]. The effectiveness of ICIs in metastatic cancer is no longer a question in terms of survival gain or sustainable response compared to chemotherapy. Except for melanoma and Hodgkin lymphoma, which show an excellent response rate (>50%) [4,5], only a subset of patients exhibits a good response with immunotherapy. We cite the following as examples: for advanced-stage hepatocellular carcinoma, the response rates for nivolumab and pembrolizumab were respectively 19.7% and
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