Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy.

Purpose Treating solid tumors with cancer immunotherapy (CIT) can result in unconventional responses and overall survival (OS) benefits that are not adequately captured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. We describe immune-modified RECIST (imRECIST) criteria, designed to better capture CIT responses. Patients and Methods Atezolizumab data from clinical trials in non-small-cell lung cancer, metastatic urothelial carcinoma, renal cell carcinoma, and melanoma were evaluated. Modifications to imRECIST versus RECIST v1.1 included allowance for best overall response after progressive disease (PD) and changes in PD definitions per new lesions (NLs) and nontarget lesions. imRECIST progression-free survival (PFS) did not count initial PD as an event if the subsequent scan showed disease control. OS was evaluated using conditional landmarks in patients whose PFS differed by imRECIST versus RECIST v1.1. Results The best overall response was 1% to 2% greater, the disease control rate was 8% to 13% greater, and the median PFS was 0.5 to 1.5 months longer per imRECIST versus RECIST v1.1. Extension of imRECIST PFS versus RECIST v1.1 PFS was associated with longer or similar OS. Patterns of progression analysis revealed that patients who developed NLs without target lesion (TL) progression had a similar or shorter OS compared with patients with RECIST v1.1 TL progression. Patients infrequently experienced a spike pattern (TLs increase, then decrease) but had longer OS than patients without TL reversion. Conclusion Evaluation of PFS and patterns of response and progression revealed that allowance for TL reversion from PD per imRECIST may better identify patients with OS benefit. Progression defined by the isolated appearance of NLs, however, is not associated with longer OS. These results may inform additional modifications to radiographic criteria (including imRECIST) to better reflect efficacy with CIT agents.

Topographic effects on infrasound propagation.

Infrasound data were collected using portable arrays in a region of variable terrain elevation to quantify the effects of topography on observed signal amplitude and waveform features at distances less than 25 km from partially contained explosive sources during the Frozen Rock Experiment (FRE) in 2006. Observed infrasound signals varied in amplitude and waveform complexity, indicating propagation effects that are due in part to repeated local maxima and minima in the topography on the scale of the dominant wavelengths of the observed data. Numerical simulations using an empirically derived pressure source function combining published FRE accelerometer data and historical data from Project ESSEX, a time-domain parabolic equation model that accounted for local terrain elevation through terrain-masking, and local meteorological atmospheric profiles were able to explain some but not all of the observed signal features. Specifically, the simulations matched the timing of the observed infrasound signals but underestimated the waveform amplitude observed behind terrain features, suggesting complex scattering and absorption of energy associated with variable topography influences infrasonic energy more than previously observed.