Therapy Response Imaging in Oncology by Mizuki Nishino

Author:Mizuki Nishino
Language: eng
Format: epub
ISBN: 9783030311711
Publisher: Springer International Publishing

With regard to ICB treatments in mRCC, numerous clinical trials have used and are using RECIST 1.1 to determine overall response rate and to characterize progressive disease. In the phase III study comparing nivolumab to everolimus, secondary endpoints of investigator-assessed overall response rate and progression-free survival were determined using RECIST 1.1 (Motzer et al. 2015). Of interest, patients were allowed to continue on treatment beyond RECIST PD if clinical benefit was assessed by the investigator and side effects were acceptable. Ongoing multicenter trials of ICBs combined with another ICB or another agent typically use RECIST 1.1 to characterize overall response rate and determine progression of disease on imaging. However, heterogeneous changes in tumor burden have been described in RCC patients treated with ICBs, and radiologic assessment of response in this treatment setting remains challenging (de Velasco et al. 2016). Atypical patterns have encountered, including increased before decreased tumor burden on treatment termed “pseudoprogression,” mixed changes with new lesions, and even possible “hyperprogressive” disease (Champiat et al. 2018a). Given the unique mechanism of action of these agents which block inhibitory signals of the immune system to boost T-cell response to cancer cells, it is not surprising that differences in the underlying biology yield distinct radiologic changes and toxicities in treated patients.

The differing spectrum of patterns of response and progressive disease in patients with various malignancies treated with ICB as opposed to tyrosine kinase inhibitors has been known for greater than a decade, and modified ICB class-specific imaging response criteria have been developed. The first such criteria were termed the “immune-related response criteria” (irRC), published in 2009, which aimed to capture additional response patterns in melanoma treated with ipilimumab (Wolchok et al. 2009). These criteria employ bidirectional tumor measurements and the sum product diameters of the target lesions to quantify changes in tumor burden, with thresholds of partial response and progressive disease used in the WHO criteria, specifically ≥50% decrease in tumor burden from baseline and ≥25% increase in tumor burden from the nadir, respectively. Importantly, these criteria permitted new lesions to be incorporated into the sum product diameters of the targets rather than deeming patients with new lesions as having progressive disease. Furthermore, confirmatory scans at least 4 weeks after initial response assessment scans were advised to confirm complete response, PR and PD designations, the latter in the absence of rapid clinical deterioration. Subsequently, immune-related RECIST (irRECIST) was developed, an adaptation using unidirectional measurements and PR/PD thresholds as in RECIST while maintaining elements of irRC pertaining to new lesions and confirmatory scans (Nishino et al. 2013). Subsequent iterations include immune RECIST (iRECIST) published by the RECIST working group and immune-modified RECIST (imRECIST) (Seymour et al. 2017; Hodi et al. 2018).

For the most part, despite the development of various immune-related criteria, primary endpoints in clinical trials of ICB continue to employ RECIST 1.1, including in RCC (Seymour et al. 2017). Alternative/adjunct immune-related criteria have been employed as secondary or exploratory endpoints in ongoing RCC trials at the author’s institution and others. According to the RECIST working group, RECIST 1.

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