X-ray Computed Tomography (CT) is one of the most commonly utilized anatomical imaging modalities for both research and clinical purposes. CT combines high-resolution, three-dimensional data with relatively fast acquisition to provide a solid platform for non-invasive human or specimen imaging. The primary limitation of CT is its inability to distinguish many soft tissues based on native contrast. While bone has high contrast within a CT image due to its material density from calcium phosphate, soft tissue is less dense and many are homogenous in density. This presents a challenge in distinguishing one type of soft tissue from another. A couple exceptions include the lungs as well as fat, both of which have unique densities owing to the presence of air or bulk hydrocarbons, respectively. In order to facilitate X-ray CT imaging of other structures, a range of contrast agents have been developed to selectively identify and visualize the anatomical properties of individual tissues. Most agents incorporate atoms like iodine, gold, or barium because of their ability to absorb X-rays, and thus impart contrast to a given organ system. Here we review the strategies available to visualize lung, fat, brain, kidney, liver, spleen, vasculature, gastrointestinal tract, and liver tissues of living mice using either innate contrast, or commercial injectable or ingestible agents with selective perfusion. Further, we demonstrate how each of these approaches will facilitate the non-invasive, longitudinal, in vivo imaging of pre-clinical disease models at each anatomical site.

Numerous obesity studies have coupled murine models with non-invasive methods to quantify body composition in longitudinal experiments, including X-ray computed tomography (CT) or quantitative nuclear magnetic resonance (QMR). Both microCT and QMR have been separately validated with invasive techniques of adipose tissue quantification, like post-mortem fat extraction and measurement. Here we report a head-to-head study of both protocols using oil phantoms and mouse populations to determine the parameters that best align CT data with that from QMR. First, an in vitro analysis of oil/water mixtures was used to calibrate and assess the overall accuracy of microCT vs. QMR data. Next, experiments were conducted with two cohorts of living mice (either homogenous or heterogeneous by sex, age and genetic backgrounds) to assess the microCT imaging technique for adipose tissue segmentation and quantification relative to QMR. Adipose mass values were obtained from microCT data with three different resolutions, after which the data were analyzed with different filter and segmentation settings. Strong linearity was noted between the adipose mass values obtained with microCT and QMR, with optimal parameters and scan conditions reported herein. Lean tissue (muscle, internal organs) was also segmented and quantified using the microCT method relative to the analogous QMR values. Overall, the rigorous calibration and validation of the microCT method for murine body composition, relative to QMR, ensures its validity for segmentation, quantification and visualization of both adipose and lean tissues.

Background and Aims: Immunotherapies have altered the treatment paradigm in HCC. Surrogate and modified endpoints are used to assess early success in clinical studies and guide clinical practice. We sought to determine whether surrogate endpoints and modifications to the conventional criteria for tumor response (RECIST), including modified RECIST (mRECIST) and immune-modified RECIST (imRECIST), are valid measures to predict overall survival (OS) in HCC treated with immunotherapies. Approach and Results: We performed an individual-level post hoc analysis of patients treated with atezolizumab and bevacizumab in the IMbrave150 trial (N = 279) and a cross-sectional analysis of a multicenter real-world patient cohort treated with immunotherapy (N = 328). Landmark analyses showed that objective response rates by RECIST were associated with greater OS including among Child-Pugh A and B patients and among patients treated with immunotherapies in the first- or second-line setting (IMbrave150: HR 0.24, 95% CI, 0.17–0.33; RW: HR 0.25, 95% CI, 0.15–0.43). Objective response rates by mRECIST or imRECIST were not associated with the greater predictive power of OS benefit (mRECIST: HR 0.30, 95% CI, 0.22–0.42; imRECIST: HR 0.36, 95% CI, 0.30–0.51). Progression-free survival determined by RECIST was only moderately correlated with OS, and this association was not improved using mRECIST or imRECIST. Conclusions: Our results clarify the utility of surrogate and modified endpoints in HCC treated with immunotherapies and support the use of RECIST objective response rates as an appropriate signal-finding measure for the evaluation of emerging treatments. Contrary to their intended purpose, mRECIST and imRECIST did not provide meaningful improvements in predicting OS benefits.

e23543 Background: Desmoid tumors are locally invasive mesenchymal neoplasms of fibroblastic origin arising in deep soft tissue. Despite a rare incidence of 2.4-4.3 per one million and an inability to metastasize, desmoid tumors can cause significant morbidity by invading surrounding structures, causing pain, anatomic deformities, and, in some cases, death. Due to the high post-excision recurrence rate (21-29%) and frequent spontaneous regression or stabilization (50-88%), active surveillance is the first-line treatment for desmoid tumors. Most therapeutic agents only achieve tumor stability and response rates of 10-30%. As such, a large subset of patients face disease progression without an effective therapeutic option. In this context, percutaneous cryoablation arises as a novel treatment for desmoid tumors. This retrospective chart review case series aims to describe the effectiveness of cryoablation in the treatment of desmoid tumors. Methods: We retrospectively reviewed medical records of patients with a pathologically confirmed desmoid tumor who received computed tomography (CT) guided percutaneous cryoablation at a single academic hospital between 2010 and 2021. We defined objective response rate (ORR) as the percentage of patients who have partial or complete response to cryoablation. Disease progression (PD), Stable Disease (SD), Partial Response (PR), and Complete Response (CR) were defined per mRECIST criteria. Results: We identified nine patients (8 female, mean age 33) with desmoid tumors who underwent percutaneous cryoablation. The most common tumor location was the abdominal wall (n = 5,) and the median longer axis tumor size was 9.5 cm (range: 4.5-16 cm). Seven patients received previous systemic treatments. Sorafenib (n = 6) was the most common systemic therapeutic option, followed by methotrexate/vinblastine, Adriamycin/dacarbazine, tamoxifen, nirogacestat, and sulindac. Before cryoablation, six of the seven patients receiving systematic therapies had PD; one had SD. After cryoablation, seven underwent post-cryoablation imaging. Mean time to initial post-op follow-up was 38.85 days (range: 22-60 days). Six patients achieved PR (66.67%), one patient maintained SD (11.11%), and two (22.22%) were lost to follow-up. Two patients with PR regressed to SD two and three months after initial post-cryoablation imaging, respectively, and one with SD improved to PR after eleven months. As such, ORR was 71.43% (95% CI: 0.352 to 1.08). Conclusions: Our data support cryoablation as an effective therapy for decreasing tumor burden in multi-treatment resistant desmoid tumor patients. Although larger studies are needed to assess efficacy and safety, with an ORR of over 70% and a disease control rate of over 75%, cryoablation demonstrates promising results without the toxicity of systemic therapy and thus may be an effective strategy for multi-treatment resistant desmoid tumors.

4090 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for advanced hepatocellular carcinoma (HCC). Surrogate endpoints including overall response rate (ORR) and progression-free survival (PFS) are preferred outcome measures in early-phase trials. However, ICIs can induce atypical patterns of response and progression, calling into question the validity of surrogate endpoints as predictive of overall survival (OS) benefit. We performed a post-hoc analysis of a large, randomized phase 3 clinical trial (IMbrave150) and cross-sectional analysis of a multi-institution real-world environment (RWE) to assess the OS surrogacy of ORR and PFS using Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), or immune-modified RECIST (imRECIST) in patients treated with ICIs. Methods: The IMbrave150 cohort in our analysis included 279 out of 336 patients treated with atezolizumab and bevacizumab in the intent-to-treat population. The RWE cohort included 328 patients with Child-Pugh A or B disease treated in the first or subsequent-line setting with anti-PD-1/L1 therapies. RECIST, mRECIST, and imRECIST ORR and PFS data for the IMbrave150 cohort was determined by investigators and central review, while RECIST ORR and PFS data for the RWE cohort was determined by treating providers or retrospective review. Results: In the IMbrave150 and RWE cohorts, Child-Pugh A patients treated in the first-line setting with CR/PR showed greater OS versus patients with SD/PD (IMbrave150: HR 0.16, 95% CI 0.10-0.26; RWE: HR 0.25, 95% CI 0.15-0.43). CR was associated with the greatest OS benefit, followed by PR, SD, and PD. Patients treated in the second-line setting or with Child-Pugh B disease showed that ORR was able to discriminate OS benefit but hazard ratios were closer to the null. In both cohorts, there was a positive rank correlation between RECIST PFS and OS (IMbrave150: Kendall's τ = 0.44, p < 0.001); RWE: Kendall's τ = 0.52, p < 0.001). However, only 31-46% of the variance in OS rankings was explained by PFS rankings. mRECIST PFS and imRECIST PFS showed a positive rank correlation with OS, with an explained variance of 30% and 38% for mRECIST and imRECIST, respectively. Conclusions: Our results suggest that RECIST ORR is a robust surrogate endpoint in HCC treated with ICIs. In contrast, the explained variance between RECIST PFS and OS in both the IMbrave and RWE cohorts was limited. This may reflect the impact of ICIs on response to subsequent therapies which may extend OS benefit. Although prior studies have proposed that modifications to RECIST may lead to more accurate surrogate markers, mRECIST and imRECIST ORR or PFS in HCC treated with ICIs were not associated with greater predictive performance compared to RECIST.