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The Response Evaluation in Solid Tumors (RECIST) 1.1 provides key guidance for performing imaging response assessment and defines image-based outcome metrics in oncology clinical trials, including progression free survival. In this framework, tumors identified on imaging are designated as either target lesions, non-target disease or new lesions and a structured categorical response is assigned at each imaging time point. While RECIST provides definitions for these categories, it specifically and objectively defines only the target disease. Predefined thresholds of size change provide unbiased metrics for determining objective response and disease progression of the target lesions. However, worsening of non-target disease or emergence of new lesions is given the same importance in determining disease progression despite these being qualitatively assessed and less rigorously defined. The subjective assessment of non-target and new disease contributes to reader variability, which can impact the quality of image interpretation and even the determination of progression free survival. The RECIST Working Group has made significant efforts in developing RECIST 1.1 beyond its initial publication, particularly in its application to targeted agents and immunotherapy. A review of the literature highlights that the Working Group has occasionally employed or adopted objective measures for assessing non-target and new lesions in their evaluation of RECIST-based outcome measures. Perhaps a prospective evaluation of these more objective definitions for non-target and new lesions within the framework of RECIST 1.1 might improve reader interpretation. Ideally, these changes could also better align with clinically meaningful outcome measures of patient survival or quality of life.

Purpose To investigate Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) approximations of target lesion tumor burden by comparing categorical treatment response according to conventional RECIST versus actual tumor volume measurements of RECIST target lesions. Materials and Methods This is a retrospective cohort study of individuals with metastatic renal cell carcinoma enrolled in a clinical trial (from 2003 to 2017) and includes individuals who underwent baseline and at least one follow-up chest, abdominal, and pelvic CT study and with at least one target lesion. Target lesion volume was assessed by (a) Vmodel, a spherical model of conventional RECIST 1.1, which was extrapolated from RECIST diameter, and (b) Vactual, manually contoured volume. Volumetric responses were determined by the sum of target lesion volumes (Vmodel-sum TL and Vactual-sum TL, respectively). Categorical volumetric thresholds were extrapolated from RECIST. McNemar tests were used to compare categorical volume responses. Results Target lesions were assessed at baseline (638 participants), week 9 (593 participants), and week 17 (508 participants). Vmodel-sum TL classified more participants as having progressive disease (PD), compared with Vactual-sum TL at week 9 (52 vs 31 participants) and week 17 (57 vs 39 participants), with significant overall response discordance (P < .001). At week 9, 25 (48%) of 52 participants labeled with PD by Vmodel-sum TL were classified as having stable disease by Vactual-sum TL. Conclusion A model of RECIST 1.1 based on a single diameter measurement more frequently classified PD compared with response assessment by actual measured tumor volume. Keywords: Urinary, Kidney, Metastases, Oncology, Tumor Response, Volume Analysis, Outcomes Analysis ClinicalTrials.gov registration no. NCT01865747 © RSNA, 2023 Supplemental material is available for this article.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

BackgroundTo evaluate the anatomic site(s) of initial disease progression in patients with castration resistant metastatic prostate cancer (mCRPC) in the presence or absence of pre-treatment visceral metastases while on systemic therapy.MethodsThis is a retrospective cohort study of mCRPC patients who have baseline and at least one follow up bone scan and CT chest, abdomen and pelvis (CAP). Disease progression was determined by RECIST and/or ≥ 30% increase in automated bone scan lesion area score. Kaplan-Meier plot was used to estimate the median progression free survival and log-rank tests were used to compare anatomic sites.ResultsOf 203 patients, 61 (30%) had pre-treatment visceral metastases. Patients with baseline visceral disease were 1.5 times more likely to develop disease progression (HR = 1.53; 95% CI, 1.03-2.26). Disease progression was a result of worsening bone scan disease (42% (16/38)) versus visceral (32% (12/38)) or lymph node disease (3% (1/38)) by CT or a combination thereof (23% (9/38)). Median time to progression (TTP) did not differ by anatomic location of initial progression (p = 0.86). Development of new lesions occurred in 50% of those visceral patients with soft tissue only progression and was associated with a significantly longer TTP (3.1 months (2.8-4.3 months) than those with worsening of pre-existing lesions (1.8 months (1.6-2.7 months); p = 0.04.ConclusionsPatients with pre-treatment visceral metastases in mCRPC are more likely to experience disease progression of bone disease with the initial anatomic site of progression similar to those without baseline visceral involvement.

Drug discovery and approval in oncology is mediated by the use of imaging to evaluate drug efficacy in clinical trials. Imaging is performed while patients receive therapy to evaluate their response to treatment. Response criteria, specifically Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), are standardized and can be used at different time points to classify response into the categories of complete response, partial response, stable disease, or disease progression. At the trial level, categorical responses for all patients are summated into image-based trial endpoints. These outcome measures, including objective response rate (ORR) and progression-free survival (PFS), are characteristics that can be derived from imaging and can be used as surrogates for overall survival (OS). Similar to OS, ORR and PFS describe the efficacy of a drug. U.S. Food and Drug Administration (FDA) regulatory approval requires therapies to demonstrate direct evidence of clinical benefit, such as improved OS. However, multiple programs have been created to expedite drug approval for life-threatening illnesses, including advanced cancer. ORR and PFS have been accepted by the FDA as adequate predictors of OS on which to base drug approval decisions, thus substantially shortening the time and cost of drug development (1). Use of imaging surrogate markers for drug approval has become increasingly common, accounting for more than 90% of approvals through the Accelerated Approval Program and allowing for use of many therapies which have altered the course of cancer. Keywords: Oncology, Tumor Response  RSNA, 2021.

ObjectiveMolecular testing can refine the diagnosis for the 20% of thyroid fine-needle aspiration biopsies that have indeterminate cytology. We assessed the diagnostic accuracy of molecular testing based on ultrasound risk classification.MethodsThis retrospective cohort study analyzed all thyroid nodules with indeterminate cytology at an academic US medical center (2012-2016). All indeterminate nodules underwent reflexive molecular testing with the Afirma Gene Expression Classifier (GEC). Radiologists performed blinded reviews to categorize each nodule according to the American Thyroid Association (ATA) ultrasound classification and the American College of Radiology Thyroid Imaging, Reporting and Data System. GEC results and diagnostic performance were compared across ultrasound risk categories.ResultsOf 297 nodules, histopathology confirmed malignancy in 65 (22%). Nodules by ATA classification were 8% high suspicion, 44% intermediate, and 48% low/very low suspicion. A suspicious GEC result was more likely in ATA high-suspicion nodules (81%) than in nodules of all other ATA categories (57%; P = .04). The positive predictive value (PPV) of GEC remained consistent across ultrasound categories (ATA high suspicion, 64% vs all other ATA categories, 48%; P = .39). The ATA high-suspicion category had higher specificity than a suspicious GEC result (93% vs 51%; P

PurposePseudocirrhosis has been demonstrated to mimic cirrhosis radiographically, but studies evaluating the pathophysiology and clinical features are lacking. To better understand the incidence, risk factors, clinical course, and etiology of pseudocirrhosis, we performed a retrospective analysis of consecutively treated patients with metastatic breast cancer (MBC).MethodsOf 374 patients treated for MBC from 2006 to 2012, 199 had imaging available for review. One radiologist evaluated computed tomography scans for evidence of pseudocirrhosis. Features of groups with and without pseudocirrhosis were compared by Kaplan-Meier product-limit survival estimates and log-rank tests. Wilcoxon Rank-Sum testing evaluated if patients more heavily treated were more likely to develop pseudocirrhosis. Univariate and multivariate Cox proportional hazard models investigated factors associated with mortality.ResultsPseudocirrhosis developed in 37 of 199 patients (19%). Of the patients with liver metastases, 55% developed pseudocirrhosis. Liver metastases were demonstrated in 100% of patients with pseudocirrhosis. Survival in the subset with liver metastases favored those without pseudocirrhosis, 189 versus 69 months (p = 0.01). The number of systemic regimens received were higher in patients with pseudocirrhosis (p = 0.01). Ascites was demonstrated in 68%, portal hypertension in 11%, and splenomegaly in 8% of patients with pseudocirrhosis.ConclusionsPseudocirrhosis does not occur in the absence of liver metastases, can manifest as hepatic decompensation, and appears to be associated with poorer survival amongst patients with hepatic metastases. Higher cumulative exposure to systemic therapy may be causative, instead of the previously held belief of pseudocirrhosis as an adverse effect of a particular systemic agent/class.

Background Neoadjuvant endocrine therapy presents an important downstaging option with lower toxicity than neoadjuvant chemotherapy in oestrogen receptor (ER)-positive early breast cancer. Meta-analysis of the effects of neoadjuvant endocrine therapy on surgical outcomes across randomized clinical trials (RCTs) and cohort studies has not previously been performed. Methods A systematic review and meta-analysis was performed to evaluate the effect of neoadjuvant endocrine therapy on surgical outcomes (PROSPERO (international prospective register of systematic reviews, 2020)) compared with surgery followed by adjuvant endocrine therapy. PubMed and EMBASE were searched to identify RCT and cohort studies between 1946 and 27 March 2024. Two independent reviewers manually screened the identified records and extracted the data. Risk of bias was assessed using the Cochrane Collaboration tools and random-effects meta-analysis was done with ReviewManager. Results The search identified 2390 articles eligible for screening. The review included 20 studies (12 cohort and 8 RCTs); 19 were included in the meta-analysis with a total of 6382 patients. Overall, neoadjuvant endocrine therapy was associated with a lower mastectomy rate compared with surgery first (risk ratio (RR) 0.53, 95% c.i. 0.44 to 0.64). Subgroup analysis showed similar improvement in the mastectomy rate in the neoadjuvant endocrine therapy group versus control group irrespective of study type (RCT: RR 0.58, 95% c.i. 0.50 to 0.66; cohorts: RR 0.48, 95% c.i. 0.33 to 0.70). There was no difference in the mastectomy rate by duration of neoadjuvant endocrine therapy (more than 4 months: RR 0.57, 95% c.i. 0.42 to 0.78; 4 months or less than 4 months: RR 0.52, 95% c.i. 0.43 to 0.64). Most of the studies were characterized by moderate-quality evidence with significant heterogeneity. Conclusion Neoadjuvant endocrine therapy is associated with a reduction in mastectomy rate. Given the moderate methodological quality of previous studies, further RCTs are required. Registration ID CRD42020209257 [ABSTRACT FROM AUTHOR]