Central Radiologist Research Articles

Observation and treatment of patients with progressive metastatic differentiated thyroid cancer after establishment of radioiodine refractoriness

Differentiated thyroid cancer is one of the most common malignant diseases of the endocrine system. Usually, it responds well to the standard treatment (surgery + radioiodine therapy), especially at early stages. During both treatment and dynamic observation, distant metastases are detected in 10–15 % of patients. In these cases, the patients continue treatment with radioactive iodine. If tumor cells have insufficient ability to capture and retain 131I or completely lose this ability, the effect of radioiodine therapy becomes limited and the disease progresses during therapy which leads to 5–10 % decrease in 10-year survival. The main problem in treatment of differentiated thyroid cancer is communication between radiologists in centers performing radioiodine therapy and clinical oncologists performing surgeries and observation at patient’s place of residence. For both specialists, the main goal is to identify clinical situations where early and effective treatment intervention can be beneficial without the risk of overdiagnosis and excessive treatment.The article considers common questions arising during multidisciplinary interactions with radiologists of radioiodine centers and presents concise guidelines on the observation and treatment procedures for patients with differentiated thyroid cancer.

Abstract PS05-03: MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer

Abstract Background Precise nodal staging is critical in guiding systemic and regional treatments including surgery in the management of breast cancer. Regional nodal assessment includes axillary imaging (mostly by ultrasound) and lymph node sampling. Since imaging findings suggestive of nodal metastasis are based on size and morphologic changes and not specific to tumor type, pathologic confirmation through either biopsy or removal of sentinel lymph node (SLN) remains the gold standard. Imagion is developing the MagSense® HER2 Imaging Agent (MSH2IA), an anti-human epidermal growth factor receptor 2 (HER2) conjugated with iron oxide nanoparticles, for the detection of nodal metastasis in HER2+ breast cancer patients. MSH2IA is currently being investigated in a first-in-human phase 1 study (ACTRN12621000126819) in HER2+ breast cancer patients who are diagnosed to have suspicious nodes by conventional imaging. Methods The key objectives of the phase 1 study are safety and tolerability of MSH2IA and confirmation that MSH2IA drains to the axillary lymph nodes. The study also explores MSH2IA’s ability to detect metastatic nodes when used with magnetic resonance imaging (MRI), with tumor status assessed by standard tissue histopathology. All eligible subjects receive a 22.5 mg (iron equivalent) subareolar or peritumoral injection of MSH2IA. MRI of the axilla are obtained before and 24 to 72 hours after MSH2IA injection. Core biopsy or dissection of a node suspicious by ultrasound is obtained for histopathology assessments. After completing the first cohort of 6 subjects, the protocol was amended to include the insertion of an MRI compatible clip in a node suspicious by ultrasound to localize the suspicious node for core biopsy and postdose MRI scan. Review of MRI scans and histopathology are performed in respective central laboratories. Results Thirteen participants with HER2+ breast cancer have completed the study. MSH2IA appears safe and well tolerated. The imaging agent, as administered, is detectable by MRI and pathology, confirming that MSH2IA drains to the lymph nodes via the chosen route of administration. In postdose MRI scans, study central radiologists reported distinct and differentiable MRI appearance in morphologically normal and suspicious nodes. The presence of a distinct postdose MR image appearance was confirmed by a group of independent radiologists in a separate blinded review. While normal nodes appeared with homogeneous hypointensity, morphologically suspicious nodes showed partial irregular darkening and/or speckled heterogeneous hypointensity. In evaluable subjects, histopathology of the core biopsies obtained from the clipped nodes confirmed the presence of HER2+ nodal metastasis, providing preliminary evidence for node-level concordance between MRI vs pathology observations. Safety, imaging, and pathology results from all available subjects will be presented. This phase 1 study in Australia will be closing enrollment by July 31, 2023. A phase 2 study in the United States and elsewhere is being planned with the objectives of optimizing dose, schedule, and imaging parameters for best diagnostic performance for clinical utility. Conclusion Available data from the ongoing phase 1 study show that MSH2IA appears safe and drains to the axillary lymph nodes. MSH2IA displays a distinct and differentiable MRI appearance in nodes morphologically highly suspicious for tumor, which is confirmed to be HER2+ metastasis by histopathology by node level concordance. This data provides preliminary proof of principle for the mechanism of molecularly targeted MR imaging and suggests that MSH2IA has the potential to provide tumor-specific MR imaging not currently available in conventional axillary imaging. Citation Format: Jane Fox, Shanta Velaiutham, Natalie Yang, Eddie lau, Kowsi Murugappan, Beena Kumar, Alex Laslowski, Koushik Govindarajan, Steven Reich, Stephen Thomas, Nitika Neha, Marie Zhang, Isaac Bright. MagSense® HER2, a Molecularly Targeted Magnetic Resonance Imaging Agent for the Detection of Axillary Nodal Metastasis in Subjects with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS05-03.

Artificial intelligence for assessment of vascular involvement and tumor resectability on CT in patients with pancreatic cancer

ObjectiveThis study aimed to develop and evaluate an automatic model using artificial intelligence (AI) for quantifying vascular involvement and classifying tumor resectability stage in patients with pancreatic ductal adenocarcinoma (PDAC), primarily to support radiologists in referral centers. Resectability of PDAC is determined by the degree of vascular involvement on computed tomography scans (CTs), which is associated with considerable inter-observer variability.MethodsWe developed a semisupervised machine learning segmentation model to segment the PDAC and surrounding vasculature using 613 CTs of 467 patients with pancreatic tumors and 50 control patients. After segmenting the relevant structures, our model quantifies vascular involvement by measuring the degree of the vessel wall that is in contact with the tumor using AI-segmented CTs. Based on these measurements, the model classifies the resectability stage using the Dutch Pancreatic Cancer Group criteria as either resectable, borderline resectable, or locally advanced (LA).ResultsWe evaluated the performance of the model using a test set containing 60 CTs from 60 patients, consisting of 20 resectable, 20 borderline resectable, and 20 locally advanced cases, by comparing the automated analysis obtained from the model to expert visual vascular involvement assessments. The model concurred with the radiologists on 227/300 (76%) vessels for determining vascular involvement. The model’s resectability classification agreed with the radiologists on 17/20 (85%) resectable, 16/20 (80%) for borderline resectable, and 15/20 (75%) for locally advanced cases.ConclusionsThis study demonstrates that an AI model may allow automatic quantification of vascular involvement and classification of resectability for PDAC.Relevance statementThis AI model enables automated vascular involvement quantification and resectability classification for pancreatic cancer, aiding radiologists in treatment decisions, and potentially improving patient outcomes.Key points• High inter-observer variability exists in determining vascular involvement and resectability for PDAC.• Artificial intelligence accurately quantifies vascular involvement and classifies resectability for PDAC.• Artificial intelligence can aid radiologists by automating vascular involvement and resectability assessments.Graphical

Evaluation of pre-therapeutic imaging work-up in the staging of endometrial cancer: Interest in a systematic second opinion in a cancer center

Rationale and objectivesTo evaluate the interest of a systematic second opinion in quality assessment and FIGO staging in the pretherapeutic imaging work-up. Materials and methodsA retrospective observational study was conducted on 156 patients who underwent surgery for endometrioid cancer in our institution. 42 % had their initial MRI scans performed in expert centers (University Hospital and Cancer center) and 58 % in non-expert centers. Quality assessment, concordances between initial reports, and second opinions by a junior and a senior ICL radiologist versus histopathological data were analyzed. ResultsMRI scans performed in expert centers were more complete and more likely to be rated as higher quality. The overall accuracy of T staging from initial reports vs gold standard was 0.59 (95 % CI, 0.46–0.71) in expert centers and 0.49 (95 % CI, 0.38–0.60) in non-expert centers. The overall accuracy and Kappa of a second opinion for FIGO 2009 staging from expert center and non-expert center examinations were 0.61 (95 % CI, 0.48–0.72) vs 0.50 (95 % CI, 0.39–0.60) and 0.37 vs 0.27 for junior reader and 0.62 (95 % CI, 0.49–0.74) vs 0.48 (95 % CI, 0.37–0.58) and 0.39 vs 0.24 for senior reader, respectively. There was also a significant lower confidence level of the junior radiologist in MRI FIGO staging for non-expert center examinations (p 0.003). ConclusionAccuracy in the FIGO 2009 staging and quality assessment are higher for MR examinations performed from expert centers than in non-expert centers. A systematic second opinion by radiologists in expert centers should be proposed before pre-treatment multidisciplinary consultation.

Imaging Performance of the PET Scan on a Novel Ring Gantry-Based PET/CT Linear Accelerator System in the First-in-Human Study of Biology-Guided Radiotherapy

Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality using real-time positron emission tomography (PET) to guide radiotherapy beamlets. The present study was performed with sequential cohorts of participants to evaluate the performance and safety of BgRT. Primary endpoints were previously reported. We hereby report on one of the secondary endpoints assessing a novel treatment planning machine with integrated dual kVCT/PET imaging ("novel device") performance in comparison to a third-party diagnostic PET/CT scan. This single-arm, open-label, prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (≥2cm and ≤5cm) in the lung or bone. PET imaging data were collected on the novel device and on a third-party diagnostic PET/CT performed in sequence once at the planning timepoint in Cohort I, and immediately before the last fraction among patients undergoing stereotactic radiotherapy in Cohort II. Three central read radiation oncologists (CRRO) provided an interpretation of the novel device PET scans which were compared to an agreement standard based on 3 central radiologists' review of the paired diagnostic PET/CT scan. Positive percent agreement for localization of the target tumor within the biology-tracking zone (BTZ) was the key metric because it reflects whether advancing patients to subsequent steps in the BgRT workflow based on the novel device's imaging was ultimately appropriate. In Cohort 1, 6 image comparisons were performed. The positive (%) agreement for the aggregate radiation oncologist review was 100% (5/5), reflecting that in all 5 cases where the aggregate radiation oncologists deemed the tumor to fall within the BTZ based upon the novel device PET images, the central radiologists came to the same conclusion upon review of the paired diagnostic PET/CT images. The overall (%) agreement for the aggregate radiation oncologist review was 83.3% (5/6): localization was not established on the novel device in 1 case, even though it was established on the diagnostic PET/CT. This would not pose risk in real world practice as BgRT candidacy would be aborted for tumors not visible on the novel device. In Cohort II, among the 7 image comparisons, there was 100% positive percent agreement between the aggregate CRRO and the agreement standard as the localization criteria was met in both scans for all 7 patients. This was concordant with a 100% overall percent agreement. This investigation demonstrated a 100% positive percent agreement between central review of this novel device images by radiation oncologists and central review of the accompanying third-party PET/CT images by radiologists. There were no cases where a positive localization by the aggregate CRRO was not confirmed by the third-party PET/CT standard, providing evidence against the likelihood of falsely positive localizations on the novel device that would inappropriately advance patients in the workflow.

Tumor volume and T2 hyperintensity changes from DeFi: A phase 3, randomized, controlled trial of nirogacestat in patients with desmoid tumors.

11514 Background: MRI tumor volume or T2 signal intensity changes may represent novel imaging techniques that could have a prognostic or predictive value for assessing response in desmoid tumors (DT). For example, hyperintense areas on T2-weighted images have been associated with active fibroblastic proliferation and ≥90% hyperintensity is associated with DT disease progression, whereas iso- or hypo-intense areas are associated with inactive sites of disease. In DeFi (NCT03785964), the novel gamma secretase inhibitor nirogacestat (n=70 patients) significantly improved the primary endpoint of PFS compared with placebo (n=72 patients; hazard ratio, 0.29 [95% CI, 0.15, 0.55; P<0.001]) and significantly improved the secondary endpoint of ORR per blinded, independent central review (41% vs 8%; P<0.001). Complete responses were achieved in 7% with nirogacestat and 0% with placebo. Here, we present an exploratory analysis of MRI tumor volume and T2 signal intensity changes in DeFi. Methods: Eligible adults had histologically confirmed DT that had progressed ≥20% per RECIST v1.1 within 12 months of screening. Patients were randomized 1:1 to receive nirogacestat 150 mg or placebo twice daily taken continuously in 28-day cycles. Volumetric MRI and T2 hyperintensity of the largest target tumor were evaluated at screening and every 6 cycles during the double-blind phase. MRI T2 signal intensity is represented as the ratio of hyperintensity in total tumor volume to muscle background. A blinded, independent, central radiologist reviewed all MRI scans. Results: Nirogacestat treatment led to more substantial reductions versus placebo in tumor volume and T2 hyperintensity ratio (Table). At baseline, similar proportions of patients in each arm had a T2 hyperintensity ratio ≥90% (95% vs 97%). This ratio changed from ≥90% at baseline to <90% at any time after baseline in 34% of patients in the nirogacestat arm and 15% of those on placebo. Conclusions: In DeFi, nirogacestat demonstrated substantial reduction of tumor volume and T2 hyperintensity of the largest target tumors by MRI compared with placebo in adults with DT. These results are consistent with the significant improvement in ORR achieved with nirogacestat. These data suggest that volumetric MRI and T2 hyperintensity might provide additional information in the evaluation of treatment response in DT. The prognostic or predictive value of these imaging techniques in DT should be further studied. Clinical trial information: NCT03785964 . [Table: see text]

Inter-rater agreement between radiologists using the novel CT-TDV (T3c+; tumour deposits; EMVI) system in patients with potentially curable right colon cancer.

The novel CT-TDV scoring system, identifying T3c + disease; the presence/absence of tumour deposits and EMVI has been shown to be superior in predicting prognosis when compared to the CT-TNM staging system in the evaluation of colon cancer. Reproducibility of this scoring system between specialist GI radiologists has not been assessed previously. The aim of this study was to assess the inter-rater agreement of gastrointestinal radiologists in assessing the novel pre-operative CT-TDV scoring of patients with potentially curable right-sided colon cancer. Ninety-three right colon cancer pre-operative CT scans were graded as CT TDV "good" versus TDV "poor" by four radiologists. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC) between all four readers and individual readers against the central radiologist using Cohen's κ statistic. The ICC comparing those graded as TDV "good" versus TDV "poor" for all 93 cases was 0.61 (0.51-0.70) indicating moderate reliability. Individual κ scores across the 93 cases were 0.76, 0.59 and 0.59 (p < 0.001) indicating moderate to substantial agreement. The CT TDV scoring system is reproducible amongst trained gastrointestinal radiologists in the assessment of newly diagnosed right colon cancer. This further validates the clinical utility of the CT TDV scoring system as a prognostic tool to guide the management of patients with potentially curable right colon cancer.

DOP12 Validation of radiomics features on MR enterography characterizing inflammation and fibrosis in stricturing Crohn’s disease

Abstract Background MR enterography (MRE) accurately detects Crohn’s disease (CD) strictures, yet its ability to differentiate inflammatory from fibrostenotic components within a CD stricture is limited. Artificial intelligence in cross sectional imaging, termed radiomics, is a quantitative image extraction analysis technology creating an opportunity to enhance characterization of strictures on routine MRE exams. We present a study on machine-reader evaluation of MRE to distinguish inflammation and fibrosis in CD strictures via quantitative radiomic features and compare radiomics performance to central radiologist scoring of MRE. Methods In this retrospective single center study 51 patients (n=34 for discovery; n=17 for validation) had confirmed stricturing CD (using CONSTRICT criteria) on MRE. Surgical histopathology scoring of specimens within 15 weeks of MRE exam (range 0-100, scores ≥70 =severe) was used as the reference standard for both inflammation and fibrosis. An expert abdominal radiologist blinded to clinical and histopathologic results provided a global visual analog scale (VAS, 0-100) assessment of stricture inflammation and fibrosis. 2164 3D radiomic features were extracted from the stricture regions on MRE, from which the most relevant feature subsets were identified via cross-validated machine learning analysis in the discovery cohort for differentiating between severe vs mild inflammation and fibrosis. Radiomic features and VAS scores were evaluated against pathology-defined inflammation and fibrosis in the validation cohort. Results Clinical variables including sex, age, Montreal classification and stricture type across discovery and validation groups can be found in Table 1. The median time from MRE to surgical resection was 7.1 90-15) weeks. 43% of strictures in the overall cohort were classified as severe for inflammation and 43% had severe fibrosis. Two distinct sets of radiomic features capturing textural heterogeneity (patterns, local entropy) within strictures were significantly associated with severe inflammation or severe fibrosis (p&amp;lt;0.01). For inflammation, AUC for discovery and validation were 0.69 and 0.67, respectively (Figure 1). For fibrosis, AUC for discovery and validation were 0.83 and 0.77, respectively (Figure 2). The radiologist VAS had an AUC of 0.71 for identifying inflammation and AUC 0.46 for identifying fibrosis. Combining radiomic features and radiologist VAS had no significant impact on predictor performance. Conclusion Radiomic analysis may support the identification of fibrosis, but not inflammation in stricturing CD compared to radiological visual assessment. This tool may offer a novel way to stratify patients for future anti-fibrotic therapies.

Role of Interventional Radiologists in Trauma Centers

Based on statistics available in Korea, trauma centers play a critical role in treatment of patients with trauma. Interventional radiologists in trauma centers perform various procedures, including embolization, which constitutes the basic treatment for control of hemorrhage, although interventions such as stent graft insertion may also be used. Although emergency interventional procedures have been used conventionally, rapid and effective hemorrhage control is important in patients with trauma. Therefore, it is important to accurately understand and implement the concept of damage control interventional radiology, which has gained attention in recent times, to reduce preventable trauma-induced mortality rates.

Transfer patient imaging: secondary interpretation reimbursement.

Trauma center radiologists vary widely in the degree to which they provide secondary interpretations for transferred patients' advanced imaging. A general perception of uncertainty over reimbursement for these exams often results in reluctance to provide routine overreads. The purpose of this study is to assess the difference in reimbursement rates between primary interpretations and secondary interpretations in the emergency department (ED) setting. Billing records for the three CT procedures most commonly performed in a single, major level 1 trauma center ED from January 1, 2021, to December 31, 2021, constituted the dataset. Gross charges, total receipts, and payer status were recorded for each exam, and reimbursement rates calculated. In total, 19,754 exams met the inclusion criteria. Primary interpretation was performed on 16,507 (83.6%) exams and secondary interpretation on 3247 (16.4%). For the three CPT codes examined, the average reimbursement percentage was 32.9% for primary interpretation and 43.5% for secondary interpretation. The average reimbursement percentage for commercial payers was 56.5% for primary interpretation and 65.9% for secondary interpretation. The average reimbursement percentage for Health Insurance Exchange payers was 58.5% for primary interpretation and 59.5% for secondary interpretation. The average reimbursement percentage for Medicaid was 24.7% for primary interpretation and 39.9% for secondary interpretation. The average reimbursement percentage for Medicare was 31.1% for primary interpretation and 30.2% for secondary interpretation. The average reimbursement percentage for self-paying patients was 2.3% for primary interpretation and 3.5% for secondary interpretation. Regardless of payer status, reimbursement for secondary interpretation of the three most common transfer patients' CT exams is near or greater than that of primary interpretations.

A Prospective Intervention to Reduce Burnout Among Academic Radiologists

Few studies have examined what constitutes effective interventions to reduce burnout among radiologists. We compared self-reported burnout among academic medical center radiologists before and after a series of departmental initiatives intended to increase wellbeing and professional satisfaction. This Institutional Review Board-approved, prospective study took place 2017-2019 in a tertiary academic medical center. In pre- (2017) and post-intervention (2019) periods, we administered the previously-validated Stanford Physician Wellness Survey to faculty in our 11-division radiology department. Faculty rated their burnout level across 8 domains (professional fulfillment, emotional exhaustion, interpersonal disengagement, sleep difficulties, self-compassion, negative work impact on personal relations, organizational/personal values alignment, perceived quality of supervisory leadership). Between the two surveys, departmental initiatives focusing on culture, team building, work-life balance, and personal well-being were implemented (e.g., electronic medical record training, shorter work hours). Pre- and post-survey results were compared, using Whitney-Mann U test to calculate Z scores. Faculty members rated lower professional fulfillment (Z-3.04, p=0.002), higher emotional exhaustion (Z=2.52, p=0.012), increased sleep-related impairment (Z=2.38, p=0.012), and reduced organizational/personal values alignment (Z=-4.10, p<0.0001) between the two surveys. No significant differences were identified associated with interpersonal disengagement (Z=1.82, p=0.069), self-compassion (Z=1.39, p=0.164), negative impact of work on personal relationship (Z=0.89, p=0.372) and perceived supervisory leadership quality (Z=0.07, p=0.942). Despite numerous departmental initiatives intended to improve culture, workplace efficiency, work-life balance, and personal wellness, self-reported burnout was unchanged or worsened over time.Physician and employee wellness embedded into institutional culture maybe more effective than departmental improvement initiatives.

Relationship Between Baseline Rectal Tumor Length and Magnetic Resonance Tumor Regression Grade Response to Chemoradiotherapy: A Subanalysis of the TRIGGER Feasibility Study

BackgroundIt is widely believed that small rectal tumors are more likely to have a good response to neoadjuvant treatment, which may influence the selection of patients for a ‘watch and wait’ strategy.ObjectiveThe aim of this study was to investigate whether there is a relationship between baseline tumor length on magnetic resonance imaging (MRI) and response to chemoradiotherapy.MethodThe 96 patients with locally advanced rectal cancer randomised (2:1–intervention:control) in the TRIGGER feasibility study where eligible. Baseline tumor length was defined as the maximal cranio-caudal length on baseline MRI (mm) and was recorded prospectively at study registration. Magnetic resonance tumor regression grade (mrTRG) assessment was performed on the post-chemoradiotherapy (CRT) MRI 4–6 weeks (no later than 10 weeks) post completion of CRT. This was routinely reported for patients in the intervention (mrTRG-directed management) arm and reported for the purposes of this study by the central radiologist in the control arm patients. Those with an mrTRG I/II response were defined as ‘good responders’ and those with an mrTRG III–V response were defined as ‘poor responders’.ResultsOverall, 94 patients had a post-CRT MRI performed and were included. Forty-three (46%) patients had a good response (mrTRG I/II) and 51 (54%) patients had a poor response (mrTRG III/IV). The median tumor length of good responders was 43 mm versus 50 mm (p < 0.001), with considerable overlap in tumor lengths between groups.ConclusionBaseline tumor length on MRI is not a clinically useful biomarker to predict mrTRG tumor response to CRT and therefore patient suitability for a deferral of surgery trial.

Transfer patient imaging: discordances between community and subspecialist emergency radiologists.

To determine the rate and nature of significant discordances between community and subspecialist emergency radiologists' interpretations of cross-sectional exams performed on patients transferred to our trauma center. Outside hospital CT and MRI exams performed on transfer trauma patients are routinely overread by subspecialist emergency radiologists, specifying either concordance or discordance with the interpretation by the community radiologist. We evaluated the discordant reports for clinical significance, defined as an additional finding or difference in interpretation which was likely to affect patient management. The total rate of significant discordances, rate by modality, rate by body region, and rate per patient transferred were calculated. The most common errors were identified, and the distribution of errors among individual community radiologists was examined. 9175 exams were reviewed. Significant discordances were encountered in 4.1% of exams: 3.9% for CT and 6.7% for MRI; 5.1% for head and neck exams, 3.3% for spine, 3.8% for torso, and 2.9% for extremities. The discordance rate per patient transferred was 7.7%. The most common discordances involved missing injuries to the cranio-cervical junction, missing or misinterpreting vascular injuries in the neck, and incompletely characterizing facial fractures. Discordances were evenly spread among 220 community radiologists. There is frequent discordance between community and emergency radiologists' interpretations of CT and MRI exams, leading to a change in transferred patient management. Thus, trauma center radiologists provide added value overreading these patients' exams. It is difficult to predict which patients or exams will contain discordances, justifying routine overreading of all such exams.

Radiomics Based on Contrast-Enhanced MRI in Differentiation Between Fat-Poor Angiomyolipoma and Hepatocellular Carcinoma in Noncirrhotic Liver: A Multicenter Analysis.

ObjectiveThis study aims to develop and externally validate a contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics-based model for preoperative differentiation between fat-poor angiomyolipoma (fp-AML) and hepatocellular carcinoma (HCC) in patients with noncirrhotic livers and to compare the diagnostic performance with that of two radiologists.MethodsThis retrospective study was performed with 165 patients with noncirrhotic livers from three medical centers. The dataset was divided into a training cohort (n = 99), a time-independent internal validation cohort (n = 24) from one center, and an external validation cohort (n = 42) from the remaining two centers. The volumes of interest were contoured on the arterial phase (AP) images and then registered to the venous phase (VP) and delayed phase (DP), and a total of 3,396 radiomics features were extracted from the three phases. After the joint mutual information maximization feature selection procedure, four radiomics logistic regression classifiers, including the AP model, VP model, DP model, and combined model, were built. The area under the receiver operating characteristic curve (AUC), diagnostic accuracy, sensitivity, and specificity of each radiomics model and those of two radiologists were evaluated and compared.ResultsThe AUCs of the combined model reached 0.789 (95%CI, 0.579–0.999) in the internal validation cohort and 0.730 (95%CI, 0.563–0.896) in the external validation cohort, higher than the AP model (AUCs, 0.711 and 0.638) and significantly higher than the VP model (AUCs, 0.594 and 0.610) and the DP model (AUCs, 0.547 and 0.538). The diagnostic accuracy, sensitivity, and specificity of the combined model were 0.708, 0.625, and 0.750 in the internal validation cohort and 0.619, 0.786, and 0.536 in the external validation cohort, respectively. The AUCs for the two radiologists were 0.656 and 0.594 in the internal validation cohort and 0.643 and 0.500 in the external validation cohort. The AUCs of the combined model surpassed those of the two radiologists and were significantly higher than that of the junior one in both validation cohorts.ConclusionsThe proposed radiomics model based on triple-phase CE-MRI images was proven to be useful for differentiating between fp-AML and HCC and yielded comparable or better performance than two radiologists in different centers, with different scanners and different scanning parameters.

Abstract CT233: Phase 2 clinical study to evaluate the efficacy and safety of intratumoral BO-112 in combination with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy

Abstract Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI), that acts as an agonist to toll-like receptor 3 and targets the cytosolic helicase melanoma differentiation-associated gene 5 and retinoic acid-inducible gene I. By mimicking the effect of a viral infection, it mobilizes the immune system, including activation of dendritic cells, CD8 T-cell infiltration, induction of interferons (IFNs), induction of apoptosis and enhancement of immunogenic cell death. Clinical data are available from the first-in-human study (NCT02828098) which evaluated single intratumoral (IT) BO-112 (Part 1; N = 16) and the combination of IT BO-112 with pembrolizumab or nivolumab (Part 2; N = 28). Part 2 showed an ORR of 11% and DCR of 46% in patients with multiple tumor types. Of them, 2 out of 10 (20%) patients with melanoma resistant to anti PD-1 achieved a partial response. Safety profile of BO-112, both as single agent and in combination with anti-PD-1, is manageable and currently characterized by Grade 1 fever and other flu-like symptoms. A phase 2 clinical study of IT BO-112 in combination with pembrolizumab in patients with liver metastases from colorectal or gastric/gastro-esophageal junction cancer patients is currently ongoing. Methods: Phase 2, single arm, open label study of IT BO-112 in combination with pembrolizumab in patients with advanced and/or metastatic melanoma that have progressed on anti-PD-1-containing treatment (NCT04570332). BO-112 will be administered once weekly (QW) in 1 to 8 tumor lesions, total dose 1-2 mg (depending on the number of injected lesions), for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab 200 mg will be administered Q3W. Key eligibility criteria include histologically confirmed, unresectable cutaneous or mucosal melanoma with known BRAF status. Patients must have progressed on or after treatment with an anti-PD-1/L1 mAb. At least one lesion RECIST 1.1 measurable and amenable for weekly IT injection is needed. Primary efficacy variable is ORR by RECIST 1.1, assessed by independent central radiologist (by QUIBIM Precision platform). Secondary efficacy variables include clinical activity in terms of DCR, DOR, PFS, OS, iRECIST, safety and PKs. Exploratory objectives include itRECIST and evaluation of tumor microenvironment (by Pangaea laboratory). A 1-sided alpha of 4.19% and power of 81.8% are used. A total of 40 patients will be enrolled. If less than 8 patients out of 40 have ORR, the study will not meet the statistical bar. Study was approved on 14 December in Spain; enrollment is open; two sites are active as of 18 December 2020. Nineteen sites (12 in Spain and 7 in France) are planned to be activated. Citation Format: Iván Márquez-Rodas, Miguel Fernández de Sanmamed Gutiérrez, María González Cao, Ana M. Arance, Alfonso Berrocal, Eduardo Castañon, Sofía España, Pablo Cerezuela-Fuentes, Juan F. Rodríguez-Moreno, Pilar López Criado, Juana Oramas, Luis de la Cruz Merino, Stéphane Dalle, Caroline Dutriaux, Julie Charles, Caroline Robert, Brigitte Dréno, Henri Montaudié, Philippe Saiag, Javier Sánchez-López, María Rojas, Helena Escuin-Ordinas, Vanesa Pons Sanz, Sonia Maciá, Marisol Quintero. Phase 2 clinical study to evaluate the efficacy and safety of intratumoral BO-112 in combination with pembrolizumab in patients with advanced melanoma that have progressive disease on anti-PD-1-based therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT233.

Development and Validation of a Pediatric MRI-Based Perianal Crohn Disease (PEMPAC) Index-A Report from the ImageKids Study.

As part of the prospective multicenter ImageKids study, we aimed to develop and validate the pediatric MRI-based perianal Crohn disease (PEMPAC) index. Children with Crohn disease with any clinical perianal findings underwent pelvic magnetic resonance imaging at 21 sites globally. The site radiologist and 2 central radiologists provided a radiologist global assessment (RGA) on a 100 mm visual analog scale and scored the items selected by a Delphi group of 35 international radiologists and a review of the literature. Two weighted multivariable statistical models were constructed against the RGA. Eighty children underwent 95 pelvic magnetic resonance imaging scans; 64 were used for derivation and 31 for validation. The following items were included: fistula number, location, length and T2 hyperintensity; abscesses; rectal wall involvement; and fistula branching. The last 2 items had negative beta scores and thus were excluded in a contending basic model. In the validation cohort, the full and the basic models had the same strong correlation with the RGA (r = 0.75; P < 0.01) and with the adult Van Assche index (VAI; r = 0.93 and 0.92; P < 0.001). The correlation of the VAI with the RGA was similar (r = 0.77; P < 0.01). The 2 models and the VAI had a similar ability to differentiate remission from active disease (area under the receiver operating characteristic curve, 0.91-0.94). The PEMPAC index had good responsiveness to change (area under the receiver operating characteristic curve, 0.89; 95% confidence interval, 0.69-1.00). Using a blended judgmental and mathematical approach, we developed and validated an index for quantifying the severity of perianal disease in children with CD. The adult VAI may also be used with confidence in children.

Combination of radiomic and biomarker signatures as exploratory objective in a phase II trial with intratumoral BO-112 plus pembrolizumab for advanced melanoma.

TPS9586 Background: Intratumoral immunotherapies are gaining interest in oncology, particularly in melanoma. These therapies, however, have faced some issues. For instance, standard response criteria do not accurately describe tumor burden, and responses may differ for injected/non injected lesions. Besides, target lesions may become non evaluable. Biomarkers provide interesting information for these therapies. In addition, some radiomic signatures have been associated with CD-8 infiltration. BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine (PEI) that mimics a viral infection, mobilizing the immune system and changing tumor microenvironment. Clinical data are available from a first-in-human study, which showed ORR of 11% and DCR of 46% in patients who had developed progressive disease on immunotherapy. In patients with melanoma, this ORR was 20%. A phase 2 clinical study of BO-112 with pembrolizumab in patients with liver metastases from digestive tumors is ongoing. Both studies brought up data regarding how some biomarkers are increased after a single dose of BO-112 and correlated with responses. In this phase II study in patients with pretreated melanoma (NCT04570332), we will prospectively assess CD-8 and PD-L1 by immunohistochemistry, which will be compared with multi-parametric radiologic findings and correlated with clinical benefit. In addition, retrospective DNA sequencing will be performed. This kind of exploratory analysis in intratumoral immunotherapies might be key to identify predictive and prognostic factors. Methods: Phase 2, single arm, open label study of BO-112 with pembrolizumab in patients with advanced melanoma. BO-112 is administered once weekly (QW) in 1 to 8 tumor lesions, total dose 1-2 mg (depending on the number of injected lesions), for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab 200 mg will be administered Q3W. Key eligibility criteria: advanced cutaneous or mucosal melanoma; patients must have progressed on or after treatment with an antiPD-1/L1 mAb; at least one measurable lesion amenable for weekly IT injection. Primary efficacy variable is ORR by RECIST 1.1, assessed by independent central radiologist (QUIBIM Precision platform). A 1-sided alpha of 4.19% and power of 81.8% are used. If less than 8 patients out of 40 have ORR, the study will not meet the statistical bar. Secondary endpoints include clinical activity by RECIST1.1 and iRECIST, overall survival, safety and PKs. Exploratory objectives include itRECIST and evaluation of CD-8 and PD-L1 expression by immunohistochemistry (Pangaea laboratory), which will be correlated with radiomic signatures (first order and second order) from standard-of-care computed tomography (CT) images. Enrollment is open and 1 of planned 40 patients has been enrolled. Nineteen sites are planned to participate. Clinical trial information: NCT04570332.

Recurrence at surgical margin following hepatectomy for colorectal liver metastases is not associated with R1 resection and does not impact survival

BackgroundResection margin status has traditionally been associated with tumor recurrence and oncological outcome following liver resection for colorectal liver metastases. Previous studies, however, did not address the impact of resection margin on the site of tumor recurrence and did not differentiate between true local recurrence at the resection margin and recurrence elsewhere in the liver. This study aimed to determine whether positive resection margins determine local recurrence and whether recurrence at the surgical margin influences long-term survival. MethodsClinicopathological data and oncological outcomes of patients who underwent curative resection for colorectal liver metastases between 2012 and 2017 at 2 major hepatobiliary centers (Bern, Switzerland, and Berlin, Germany) were assessed. Cross-sectional imaging following hepatectomy was reviewed by radiologists in both centers to distinguish between recurrence at the resection margin, defined as hepatic local recurrence, and intrahepatic recurrence elsewhere. The association between surgical margin status and location of tumor recurrence was evaluated, and the impact on overall survival was determined. ResultsDuring the study period, 345 consecutive patients underwent hepatectomy for colorectal liver metastases. Histologic surgical margins were positive for tumor cells (R1) in 63 patients (18%). After a median follow-up time of 34 months, tumor recurrence was identified in 154 patients (45%). Hepatic local recurrence was not detected more frequently after R1 than after R0 resection (P = .555). Hepatic local recurrence was not associated with worse overall survival (P = .436), while R1 status significantly impaired overall survival (P = .025). Additionally, overall survival was equivalent between patients with hepatic local recurrence and patients with any intrahepatic and/or extrahepatic recurrence. In patients with intrahepatic recurrence only, oncological outcomes improved if local hepatic therapy was possible (resection or ablation) in comparison to patients treated only with chemotherapy or best supportive care (3-year overall survival: 85% vs 39%; P < .0001). ConclusionThe incidence of hepatic local recurrence after hepatectomy for colorectal liver metastases is independent of R1 resection margin status. Additionally, hepatic local recurrence at the resection margin is not associated with worse overall survival compared with any other intra- or extrahepatic recurrence. Therefore, R1 status at hepatectomy seems to be a surrogate factor for advanced disease without influencing location of recurrence and thereby oncological outcome. This finding may support decision-making when extending the indication for surgery in borderline resectable colorectal liver metastases.

Self-reported Burnout: Comparison of Radiologists to Nonradiologist Peers at a Large Academic Medical Center

Relatively little data exist on factors associated with radiologists' burnout versus other medical specialties. We compared self-reported burnout among academic medical center radiologists versus nonradiologist peers to inform initiatives to increase wellbeing and professional satisfaction. In 2017, our large urban academic medical center administered the Stanford Physician Wellness Survey to faculty in fifteen clinical departments (fourteen academic, one community-based). Faculty rated burnout via Likert scale (0-no burnout; 1-occasional stress/no burnout; 2-one or more burnout symptoms; 3-persistent burnout symptoms; 4-completely burned out); burnout defined as >=2. Responses in 11 domains (professional fulfillment, emotional exhaustion, interpersonal disengagement, sleep difficulties, self-compassion, negative work impact on personal relations, perceived appreciation, control over schedule, organizational/personal values alignment, electronic health record, perceived quality of supervisory leadership) compared radiologists versus nonradiologists for association with burnout, using Whitney-Mann U test to calculate Z scores. There was no significant difference in overall self-reported burnout between radiologists and nonradiologists, nor in self-rating for emotional exhaustion, interpersonal disengagement, self-compassion, control over schedule, organizational/personal values alignment, or electronic health record experience. Radiologists had significantly lower self-rating for work happiness (Z = -2.669, p = 0.0076), finding work meaningful (Z = -2.77351, p = 0.0055), perceiving physicians as highly valued (Z = -2.5486, p = 0.0108), and believing leadership treated them with respect and dignity (Z = -3.44149, p = 0.0006). Compared to nonradiologist colleagues, radiologists were less likely to find work meaningful and more likely to feel unhappy and undervalued in the workplace and by leadership. Initiatives to increase perceived appreciation, leadership relationships, and meaningfulness of work for radiologists may reduce burnout.

Inter-rater Reliability of Sacral Ratio Measurements in Patients with Anorectal Malformations

BackgroundAnorectal malformations (ARMs) are a spectrum of congenital anomalies with varying prognosis for fecal continence. The sacral ratio (SR) is a measure of sacral development that has been proposed as a method to predict future fecal continence in children with ARM. The aim of this study was to quantify the inter-rater reliability (IRR) of SR calculations by radiologists at different institutions. Materials and methodsx-Rays in the anteroposterior (AP) and lateral planes were reviewed by a pediatric radiologist at each of six different institutions. Subsequently, images were reviewed by a single, central radiologist. The IRR was assessed by calculating Pearson correlation coefficients and intraclass correlation coefficients from linear mixed models with patient and rater-level random intercepts. ResultsImaging from 263 patients was included in the study. The mean inter-rater absolute difference in the AP SR was 0.05 (interquartile range, 0.02-0.10), and in the lateral SR was 0.16 (interquartile range, 0.06-0.25). Overall, the IRR was excellent for AP SRs (intraclass correlation coefficient [ICC], 81.5%; 95% confidence interval, 75.1%-86.0%) and poor for lateral SRs (ICC, 44.0%; 95% CI, 29.5%-59.2%). For both AP and lateral SRs, ICCs were similar when examined by the type of radiograph used for calculation, severity of the ARM, presence of sacral or spinal anomalies, and age at imaging. ConclusionsAcross radiologists, the reliability of SR calculations was excellent for the AP plane but poor for the lateral plane. These results suggest that better standardization of lateral SR measurements is needed if they are going to be used to counsel families of children with ARM.