Search

The Organ Procurement and Transplantation Network (OPTN) updated its allocation policy for liver transplantation to align with the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis of hepatocellular carcinoma (HCC). LI-RADS computed tomography/magnetic resonance imaging algorithm had achieved congruency with the American Association for the Study of Liver Diseases (AASLD) HCC Practice Guidance in 2018, and therefore, alignment of OPTN, LI-RADS, and AASLD unifies HCC diagnostic approaches. The two changes to the OPTN HCC classification are adoption of LI-RADS terminology or lexicon for HCC major imaging features as well as the modification of OPTN Class-5A through the adoption of LI-RADS-5 criteria. However, despite this significant milestone, the OPTN allocation policy may benefit from further refinements such as adoption of treatment response assessment criteria after locoregional therapy and categorization criteria for lesions with atypical imaging appearances that are not specific for HCC. In this review, we detail the changes to the OPTN HCC classification to achieve alignment with LI-RADS, discuss current limitations of the OPTN classification, and explore future directions.

Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing hepatocellular carcinoma (HCC), but risk estimates remain imprecise. We conducted a systematic review of Ovid MEDLINE, EMBASE, and Cochrane databases from inception to December 2021 to identify cohort studies examining HCC incidence among patients with LR-3 or LR-4 observations on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors of HCC were abstracted from each study, when available. Of 13 total studies, nine conducted LR-3 observation-level analyses, with the proportions of incident HCC ranging from 1.2% to 12.5% at 12 months and 4.2% to 44.4% during longer study follow-up. Among three studies with patient-level analyses, 8%-22.2% of patients with LR-3 lesions developed LR-4 observations and 11.1%-24.5% developed HCC. Among nine studies conducting LR-4 observation-level analyses, incident HCC ranged from 30.8% to 44.0% at 12 months and 30.9% to 71.0% during study follow-up; conversely, 6%-42% of observations were downgraded to LR-3 or lower. Patient-level factors associated with HCC included older age, male sex, higher alpha-fetoprotein levels, viral etiology, and prior history of HCC; observation-level factors included maximum diameter, threshold growth, T2 hyperintensity, and visibility on ultrasound. Studies were limited by small sample sizes, inclusion of patients with prior HCC, short follow-up duration, and failure to account for clustering of observations in patients or competing risks of transplantation and death. LR-3 and LR-4 observations have elevated but variable risks of HCC. Higher quality studies are necessary to identify high-risk patients who warrant close CT or MRI-based follow-up.

Our purpose was to evaluate the accuracy of LI-RADS Treatment Response Algorithm (LR-TRA) for assessing the viability of hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT), using explant pathology as the gold standard.This retrospective study included patients who underwent SBRT for locoregional treatment of HCC between 2008 and 2019 with subsequent liver transplantation. Five radiologists independently assessed all treated lesions by using the LR-TRA. Imaging and posttransplant histopathology were compared. Lesions were categorized as either completely (100%) or incompletely (100%) necrotic, and performance characteristics and predictive values for the LR-TR viable and nonviable categories were calculated for each reader. Interreader reliability was calculated using the Fleiss kappa test.A total of 40 treated lesions in 26 patients (median age, 63 years [interquartile range, 59.4-65.5]; 23 men) were included. For lesions treated with SBRT, sensitivity for incomplete tumor necrosis across readers ranged between 71% and 86%, specificity between 85% and 96%, and positive predictive value between 86% and 92%, when the LR-TR equivocal category was treated as nonviable, accounting for subject clustering. When the LR-TR equivocal category was treated as viable, sensitivity of complete tumor necrosis for lesions treated with SBRT ranged from 88% to 96%, specificity from 71% to 93%, and negative predictive value from 85% to 96%. Interreader reliability was fair (k = 0.22; 95% confidence interval, 0.13-0.33). Although a loss of arterial phase hyperenhancement (APHE) was highly correlated with pathologically nonviable tumor on explant, almost half of the patients with APHE had pathologically nonviable tumor on explant.LR-TRA v2018 performs well for predicting complete and incomplete necrosis in HCC treated with SBRT. In contrast to other locoregional therapies, the presence of APHE after SBRT does not always indicate viable tumor and suggests that observation may be an appropriate strategy for these patients.

Historically, radiation therapy was not considered in treatment of liver tumors owing to the risk of radiation-induced liver disease. However, development of highly conformed radiation treatments such as stereotactic body radiation therapy (SBRT) has increased use of radiation therapy in the liver. SBRT is indicated in treatment of primary and metastatic liver tumors with outcomes comparable to those of other local therapies, especially in treatment of hepatocellular carcinoma. After SBRT, imaging features of the tumor and surrounding background hepatic parenchyma demonstrate a predictable pattern immediately after treatment and during follow-up. The goals of SBRT are to deliver a lethal radiation dose to the targeted liver tumor and to minimize radiation dose to normal liver parenchyma and other adjacent organs. Evaluation of tumor response after SBRT centers on changes in size and enhancement; however, these changes are often delayed secondary to the underlying physiologic effects of radiation. Knowledge of the underlying pathophysiologic mechanisms of SBRT should allow better understanding of the typical imaging features in detection of tumor response and avoid misinterpretation from common pitfalls and atypical imaging findings. Imaging features of radiation-induced change in the surrounding liver parenchyma are characterized by a focal liver reaction that can potentially be mistaken for no response or recurrence of tumor. Knowledge of the pattern and chronology of this phenomenon may allay any uncertainty in assessment of tumor response. Other pitfalls related to fiducial marker placement or combination therapies are important to recognize. The authors review the basic principles of SBRT and illustrate post-SBRT imaging features of treated liver tumors and adjacent liver parenchyma with a focus on avoiding pitfalls in imaging evaluation of response.

Locoregional therapy (LRT) for hepatocellular carcinoma can be used alone or with other treatment modalities to reduce rates of progression, improve survival, or act as a bridge to cure. As the use of LRT expands, so too has the need for systems to evaluate treatment response, such as the World Health Organization and modified Response Evaluation Criteria In Solid Tumors systems and more recently, the Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA). Early validation results for LI-RADS TRA have been promising, and as research accrues, the TRA is expected to evolve in the near future.

Hepatocellular cancer (HCC) surveillance is associated with increased curative treatment and improved survival, underscoring its importance in patients with cirrhosis.

PURPOSE: To perform a systematic review and meta-analysis using individual patient data to investigate the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS) Treatment Response (TR) algorithm for detecting incomplete necrosis on pathology. METHODS: PubMed and EMBASE were searched from Jan 1, 2017 until October 14, 2020. Studies reporting diagnostic accuracy of LI-RADS TR algorithm on CT or MRI for detecting incomplete necrosis on pathology as a reference standard were included. Sensitivity and specificity were pooled using random-effects model. Subgroup analyses were performed for LRT type, and imaging modality. RESULTS: Six studies (393 patients, 534 lesions) were included. Pooled sensitivity was 0.56 (95% confidence interval [CI] 0.43–0.69) and specificity was 0.91 (95%CI 0.84–0.96). Pooled sensitivity was highest using arterial phase hyperenhancement (APHE) (0.67 [95%CI 0.51–0.81]), followed by washout (0.43 [95%CI 0.26–0.62]) and enhancement similar to pretreatment (0.24 [95%CI 0.15–0.36]). Among lesions with incomplete necrosis, 2% (95%CI 0.00–0.05) manifested as washout but no APHE; 0% (95% CI 0.00–0.02) as enhancement similar to pretreatment without both APHE and washout. Pooled sensitivity was lower after ablation than embolization (0.42 [95%CI, 0.28–0.57] vs. 0.65 [95%CI, 0.53–0.77], p=0.033). MRI and CT were comparable (p=0.783 and 0.290 for sensitivity and specificity). CONCLUSIONS: LI-RADS TR algorithm shows moderate sensitivity and high specificity for detecting incomplete necrosis after LRT. APHE is the dominant criterion, a washout contributes to small but meaningful extent, while the contribution of enhancement similar to pretreatment may be negligible. LRT type may affect performance of the algorithm.

Stereotactic body radiation therapy (SBRT) is an emerging locoregional treatment (LRT) modality used in the management of patients with hepatocellular carcinoma (HCC). The decision to treat HCC with LRT is evaluated in a multidisciplinary setting, and the specific LRT chosen depends on the treatment intent, such as bridge-to-transplant, down-staging to transplant, definitive/curative treatment, and/or palliation, as well as underlying patient clinical factors. Accurate assessment of treatment response is necessary in order to guide clinical management in these patients. Patients who undergo LRT need continuous imaging evaluation to assess treatment response and to evaluate for recurrence. Thus, an accurate understanding of expected post-SBRT imaging findings is critical to avoid misinterpreting normal post-treatment changes as local progression or viable tumor. SBRT-treated HCC demonstrates unique imaging findings that differ from HCC treated with other forms of LRT. In particular, SBRT-treated HCC can demonstrate persistent APHE and washout on short-term follow-up imaging. This brief review summarizes current evidence for the use of SBRT for HCC, including patient population, SBRT technique and procedure, tumor response assessment on contrast-enhanced cross-sectional imaging with expected findings, and pitfalls in treatment response evaluation.

Purpose Previous reports of stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) suggest unacceptably high rates of toxicity in patients with Child-Turcotte-Pugh (CTP) B liver disease. We hypothesized that an individualized adaptive treatment approach based on midtreatment liver function would maintain good local control while limiting toxicity in this population. Methods and Materials Patients with CTP-B liver disease and HCC were treated on prospective trials of individualized adaptive SBRT between 2006 and 2018. Patients underwent pre- and midtreatment liver function assessments using indocyanine green. Treatment-related toxicity was defined as a ≥2-point increase in CTP score from pretreatment within 6 months of treatment. In addition, we performed analyses with a longitudinal model to assess changes in CTP score over 12 months after SBRT. Results Eighty patients with CTP-B (median tumor size, 2.5 cm) were treated: 37 patients were CTP-B-7, 28 were CTP-B-8, and 15 were CTP-B-9. The median treatment dose was 36 Gy in 3 fractions. One-year local control was 92%. In a multivariate model controlling for tumor size, treatment dose, and baseline CTP score, higher treatment dose was associated with improved freedom from local progression (hazard ratio: 0.97; 95% confidence interval, 0.94-1.00; P = .04). Eighteen patients (24%) had a ≥2-point increase in CTP score within 6 months of SBRT. In a longitudinal model assessing changes in CTP score over 12 months after SBRT, controlling for baseline CTP and tumor size, increasing mean liver dose was associated with larger increases in CTP score (P = .04). Conclusions An individualized adaptive treatment approach allows for acceptable toxicity and effective local control in patients with HCC and CTP-B liver disease. Because increasing dose may increase both local control and toxicity, further work is needed to optimize treatment in patients with compromised liver function.

The purpose of this study is to review the recent literature analyzing the performance of Liver Imaging Reporting and Data System (LI-RADS) v2018 diagnostic and treatment response algorithm (TRA) for initial diagnosis and assessment of hepatocellular carcinoma (HCC) following locoregional therapy (LRT). LI-RADS is a comprehensive tool for assessment and reporting of observations in patients at risk of developing HCC. Since HCC is predominantly an imaging diagnosis, it is important to achieve a high sensitivity and specificity for each LR category. Therefore, a multitude of studies have been published over the recent years illustrating the diagnostic yield of both the diagnostic and treatment response algorithms. In addition, the role of abbreviated MRI for screening has also been studied recently. LI-RADS diagnostic algorithm has been validated by a number of recent studies that have provided a high diagnostic reliability for categorizing each observation, when using major as well as combination of major and ancillary features. In addition, LI-RADS TRA is being validated by the emerging literature providing promising results for treatment of HCC following ablation and nonradiation-based arterial therapies. However, further insight and in depth research is required to validate the imaging appearance of radiation-based therapies as well as utilization of ancillary features for response assessment after locoregional therapy.

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality worldwide, with rising clinical and economic burden as incidence increases. There are a multitude of evolving treatment options, including locoregional therapies which can be used alone, in combination with each other, or in combination with systemic therapy. These treatment options have shown to be effective in achieving remission, controlling tumor progression, improving disease free and overall survival in patients who cannot undergo resection and providing a bridge to transplant by debulking tumor burden to downstage patients. Following locoregional therapy (LRT), it is crucial to provide treatment response assessment to guide management and liver transplant candidacy. Therefore, Liver Imaging Reporting and Data Systems (LI-RADS) Treatment Response Algorithm (TRA) was created to provide a standardized assessment of HCC following LRT. LI-RADS TRA provides a step by step approach to evaluate each lesion independently for accurate tumor assessment. In this review, we provide an overview of different locoregional therapies for HCC, describe the expected post treatment imaging appearance following treatment, and review the LI-RADS TRA with guidance for its application in clinical practice. Unique to other publications, we will also review emerging literature supporting the use of LI-RADS for assessment of HCC treatment response after LRT.

Transitioning from radiology training to academic faculty presents many challenges. In this review, we discuss strategies to navigate this process and to facilitate success through appropriate selection of career tracks. Various modern avenues include roles as a Clinician-Educator, Clinician-Investigator, and Clinician-Administrator. Selection of the appropriate career track based on personal interests and institutional culture is critical for early and long-term career satisfaction.

Transitioning from radiology residency to academic faculty presents many challenges. In this review, we discuss the importance of introspection and mentorship to successfully navigate this process. Key points include alignment of goals with those of the institution, formation of a mentorship program, and periodic reassessment of career goals. These tips and tools can help make the transition from residency to academic faculty more seamless.

To determine the long-term natural history of size change in SBRT-treated HCC to identify an imaging biomarker to help assess treatment response. This was a retrospective cohort study of consecutive HCCs treated with SBRT from January 2008 to December 2016 with either 2 years post-treatment MRI follow-up or post-treatment resection histology. Size, major features for HCC, and mRECIST and LI-RADS v.2018 treatment response criteria were assessed at each post-treatment MRI. Local progression, distant progression, and survival were modeled with Kaplan Meier analyses. 56 HCCs met inclusion criteria. Mean baseline HCC diameter was 30 mm (range: 9–105 mm). At 3 months, 76% (N = 43) of treated HCCs decreased in size (mean reduction: 8 mm, range: 5–99 mm) and 0% (N = 0) increased in size. By 24 months, 11% (N = 5) had increased in size and were considered local progression. APHE remained in 77% (43/56) at 3 months, 38% (19/50) at 12 months, and 23% (11/47) at 24 months. mRECIST-defined viable disease was observed in 77% (43/56) at 3 months and 20% (9/47) at 24 months. LI-RADS v.2018 criteria identified viable or equivocal disease in 0% at 3 months and 10% (5/47) at 24 months. Gradual loss of APHE and slow decrease in size are normal findings in HCCs treated with SBRT, and persistent APHE does not indicate viable disease. mRECIST is not accurate in the assessment of HCC after SBRT due to an overreliance on APHE to define viable disease. Increasing mass size or new nodular APHE at the treatment site may indicate local progression.

There is a sparsity of data evaluating outcomes of patients with Liver Imaging Reporting and Data System (LI-RADS) (LR)-M lesions.To compare overall survival (OS) and progression free survival (PFS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) meeting LR-M criteria and to evaluate factors associated with prognosis.Retrospective.Patients at risk for HCC with at least one LR-M lesion with histologic diagnosis, from 8 academic centers, yielding 120 patients with 120 LR-M lesions (84 men [mean age 62 years] and 36 women [mean age 66 years]).A 1.5 and 3.0 T/3D TThe imaging categorization of each lesion as LR-M was made clinically by a single radiologist at each site and patient outcome measures were collected.OS, PFS, and potential independent predictors were evaluated by Kaplan-Meier method, log-rank test, and Cox proportional hazard model. A P value of0.05 was considered significant.A total of 120 patients with 120 LR-M lesions were included; on histology 65 were HCC and 55 were iCCA. There was similar median OS for patients with LR-M HCC compared to patients with iCCA (738 days vs. 769 days, P = 0.576). There were no significant differences between patients with HCC and iCCA in terms of sex (47:18 vs. 37:18, P = 0.549), age (63.0 ± 8.4 vs. 63.4 ± 7.8, P = 0.847), etiology of liver disease (P = 0.202), presence of cirrhosis (100% vs. 100%, P = 1.000), tumor size (4.73 ± 3.28 vs. 4.75 ± 2.58, P = 0.980), method of lesion histologic diagnosis (P = 0.646), and proportion of patients who underwent locoregional therapy (60.0% vs. 38.2%, P = 0.100) or surgery (134.8 ± 165.5 vs. 142.5 ± 205.6, P = 0.913). Using multivariable analysis, nonsurgical compared to surgical management (HR, 4.58), larger tumor size (HR, 1.19), and higher MELD score (HR, 1.12) were independently associated with worse OS.There was similar OS in patients with LR-M HCC and LR-M iCCA, suggesting that LR-M imaging features may more closely reflect patient outcomes than histology.3 TECHNICAL EFFICACY: Stage 5.

Introduction: Stereotactic body radiation therapy (SBRT) for the treatment of hepatocellular carcinoma (HCC) remains a challenge due to high rates of toxicity in patients with impaired liver function or tumors not amenable to thermal ablation. We performed a single-arm prospective phase II clinical trial utilizing a novel treatment paradigm optimizing the utility of SBRT based on the individual patient’s probability for tumor control traded off against the risk of liver injury. We hypothesized that maximizing the utility of treatment would decrease toxicity while achieving the same tumor control rate as standard therapy. Methods: Patients with Child-Pugh (CP) A to B7 disease with tumors >3.5 cm, or CP ≥ B8 with any size tumor were prospectively enrolled on an IRB approved clinical trial to undergo SBRT with baseline dose optimization and mid-treatment response adaptation. Optimization and adaptation were based on the expected utility of treatment, calculated as a weighted average of the probability of 4 combinations of toxicity and efficacy outcomes. These calculations were based on the individual patient’s baseline indocyanine green retention at 15 minutes or albumin-bilirubin score (ALBI), CP score, intended dose and fractionation, and mean liver dose with the goal of maximizing the difference between the probability of local control compared to the probability of treatment-related toxicity. Primary endpoints were rate of liver decompensation as measured by ≥2 point change in CP score within 6 months, and lesion-specific local control. Overlap weighting was used to compare patients treated on protocol with patients receiving conventional SBRT at another high-volume cancer center. Results: 56 patients with 80 tumors met inclusion criteria and had a median follow-up of 11.2 months. 44 tumors with a median size of 3.8 cm were treated in CP-A to B7 patients, while 36 tumors with a median size of 2.1 cm were treated in CP ≥ B8 patients. Optimization resulted modification of initial dose for 38% of patients. Sixty-eight percent of patients underwent mid-treatment adaptation with either omission or dose reduction of the final two treatments based on change in expected utility. The 1 year freedom from local progression was 94%. A total of 21% of patients experienced a ≥ 2 point change in CP score within 6 months. Overlap weighted analysis revealed similar local control (HR 0.69, 95% CI [0.25-1.91], p = 0.48), and overall survival (HR 1.45, 95% CI [0.69-3.0], p = 0.33), with decreased toxicity (OR 0.26, 95% CI [0.07 - 0.99], p = 0.048) compared to conventional SBRT. Conclusion: SBRT for HCC patients with large tumors or poor liver function can be optimized via an individualized, utility-based treatment paradigm which may decrease treatment-related toxicity while maintaining tumor control. Citation Format: Daniel J. Herr, Chang Wang, Mishal Mendiratta-Lala, Martha Matuszak, Charles S. Mayo, Yue Cao, Neehar Parikh, Randy Ten Hanken, Dawn Owen, Teodor Stanescu, Michael Yan, Laura A. Dawson, Matthew Schipper, Theodore S. Lawrence, Kyle C. Cuneo. A phase II study of optimized individualized adaptive radiation therapy for hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT151.

There are multiple liver-directed treatment options for hepatocellular carcinoma (HCC), which provide curative intent, help patients achieve remission, and/or provide a bridge to transplant by controlling local tumor progression and downstaging patients. After locoregional therapy (LRT), management of these patients, including liver transplant candidacy, is guided by treatment response assessment. The Liver Imaging Reporting and Data Systems (LI-RADS) treatment response algorithm (TRA) was created to provide a standardized assessment of HCC following LRT. Originally created primarily on expert opinion, subsequent literature has continued to evaluate the validity of this algorithm. In this manuscript, we review emerging literature supporting the use of LI-RADS in the assessment of HCC treatment response after LRT and highlight future updates.

Metastatic tumors interface with liver in multiple patterns, of which, the rare "sinusoidal" growth pattern can be subtle and easily overlooked on biopsy. We sought to characterize the metastasis-to-liver interface patterns of melanoma compared with other tumor types and assess the incidence of metastatic melanoma in histologically normal-appearing targeted liver lesion biopsies. Liver lesion samples from 54 melanoma patients were assessed. Nearly normal-appearing cases, defined as no obvious malignancy on routine hematoxylin and eosin stain (n=24), were stained with SOX10 and confirmed with MelanA. Tumor-to-liver interface patterns were determined in biopsies overtly positive for metastatic melanoma (n=30) versus other hepatic metastases as controls (colon, n=28; breast, n=20; pancreaticobiliary, n=20; and neuroendocrine, n=28). Of the 24 nearly normal-appearing liver biopsies from melanoma patients, 3 had subtle melanoma cells detected in sinusoids, confirmed with immunohistochemistry. Of 30 livers overtly positive for melanoma, 8 showed the sinusoidal pattern, compared with none in other metastases. In total, 11/33 (33%) cases of metastatic melanoma liver biopsies demonstrated the sinusoidal pattern. We describe 11 metastatic melanoma cases in liver with the rare sinusoidal pattern, 3 of which were subtle and easy to miss on routine hematoxylin and eosin stain. Given that sinusoidal metastasis does not elicit a tissue reaction, it is prudent for the pathologists to be aware of this pattern of metastases and have a low threshold to order immunostains for accurate diagnosis and optimal patient care.

Background: Objective radiographic assessment is crucial for accurately evaluating therapeutic efficacy and patient outcomes in oncology clinical trials. Imaging assessment workflow can be complex; can vary with institution; may burden medical oncologists, who are often inadequately trained in radiology and response criteria; and can lead to high interobserver variability and investigator bias. This article reviews the development of a tumor response assessment core (TRAC) at a comprehensive cancer center with the goal of providing standardized, objective, unbiased tumor imaging assessments, and highlights the web-based platform and overall workflow. In addition, quantitative response assessments by the medical oncologists, radiologist, and TRAC are compared in a retrospective cohort of patients to determine concordance. Patients and Methods: The TRAC workflow includes an image analyst who pre-reviews scans before review with a board-certified radiologist and then manually uploads annotated data on the proprietary TRAC web portal. Patients previously enrolled in 10 lung cancer clinical trials between January 2005 and December 2015 were identified, and the prospectively collected quantitative response assessments by the medical oncologists were compared with retrospective analysis of the same dataset by a radiologist and TRAC. Results: This study enlisted 49 consecutive patients (53% female) with a median age of 60 years (range, 29–78 years); 2 patients did not meet study criteria and were excluded. A linearly weighted kappa test for concordance for TRAC versus radiologist was substantial at 0.65 (95% CI, 0.46–0.85; standard error [SE], 0.10). The kappa value was moderate at 0.42 (95% CI, 0.20–0.64; SE, 0.11) for TRAC versus oncologists and only fair at 0.34 (95% CI, 0.12–0.55; SE, 0.11) for oncologists versus radiologist. Conclusions: Medical oncologists burdened with the task of tumor measurements in patients on clinical trials may introduce significant variability and investigator bias, with the potential to affect therapeutic response and clinical trial outcomes. Institutional imaging cores may help bridge the gap by providing unbiased and reproducible measurements and enable a leaner workflow.

The aim of the study was to identify the frequency of isolated pelvic metastasis with the goal of determining the utility of pelvic CT as a surveillance strategy in patients with resected biliary tract cancer (BTC). Study eligibility criteria included patients 18 years or older with BTC who underwent R0 or R1 surgical resection at University of Michigan between 2004 and 2018, with a minimum 6-month disease-free surveillance period. CT and MRI reports were independently graded by two radiologists as positive (organ metastasis, peritoneal carcinomatosis, or enlarged lymph nodes), equivocal (borderline lymph nodes or non-nodular ascites), or negative (absence of or benign findings) in the abdomen and pelvis separately. A 3rd blinded radiologist reviewed all positive and equivocal scans. Clinic notes were reviewed to identify new or worsening signs and symptoms that would warrant an earlier pelvic surveillance scan. A 95% binomial proportion confidence interval was used to find the probability of isolated pelvic metastasis. BTC were anatomically classified as extra-hepatic (distal and hilar) cholangiocarcinoma (38; 25%), intra-hepatic cholangiocarcinoma (57; 38%), and gallbladder cancer (56; 37%). 151 patients met eligibility criteria, of which 123 (81%) had no pelvic metastasis, 51 (34%) had localized upper abdominal metastasis, and 23 (15%) had concomitant abdominal and pelvic metastasis. Median follow-up time was 19.2 months. One (0%) subject with resected BTC (intra-hepatic) developed isolated osseous pelvic metastasis during surveillance (95% CI 0.004–0.1; p = 0.0003). 3 (2%) subjects developed isolated simple ascites (equivocal grade) without concurrent upper abdominal metastasis. Isolated pelvic metastasis is a rare occurrence during surveillance in patients with resected BTCs, and therefore, follow-up pelvic CT in absence of specific symptoms may be unnecessary.

BACKGROUND: Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis. Computational ‘radiomic’ techniques extract biomarker information from images which can be used to improve diagnosis and predict tumor biology. AIMS: We performed a systematic review of literature on radiomic features in HCC diagnosis and prognosis, with a focus on reporting metrics and methodologic standardization. METHODS: A systematic review was performed of all full-text articles published from inception through December 1, 2019. Standardized data extraction and quality assessment metrics were applied to all studies. RESULTS: A total of 54 unique studies were included for analysis. Radiomic features demonstrated good discriminatory performance to differentiate HCC from other solid lesions (c-statistics 0.66–0.95), predict microvascular invasion (c-statistic 0.76–0.92), predict early recurrence after hepatectomy (c-statistics 0.71–0.86), and predict prognosis after locoregional or systemic therapies (c-statistics 0.74–0.81). Common stratifying features for diagnostic and prognostic radiomic tools included analyses of imaging skewness, analysis of the peritumoral region, and feature extraction from the arterial imaging phase. The overall quality of the included studies was low, with common deficiencies in both internal and external validation, standardized imaging segmentation, and lack of comparison to a gold standard. CONCLUSIONS: Quantitative image analysis demonstrates promise as a non-invasive biomarker to improve HCC diagnosis and management. However, standardization of protocols and outcome measurement, sharing of algorithms and analytic methods, and external validation are necessary prior to widespread application of radiomics to HCC diagnosis and prognosis in clinical practice.

Objective and Impact Statement. This is the first longitudinal study investigating the effects of histotripsy on local tumor progression in an in vivo orthotopic, immunocompetent rat hepatocellular carcinoma (HCC) model. Introduction. Histotripsy is the first noninvasive, nonionizing, nonthermal, mechanical ablation technique using ultrasound to generate acoustic cavitation to liquefy the target tissue into acellular debris with millimeter accuracy. Previously, histotripsy has demonstrated in vivo ablation of noncancerous liver tissue. Methods. N1-S1 HCC tumors were generated in the livers of immunocompetent rats (n = 6, control; n = 15, treatment). Real-time ultrasound-guided histotripsy was applied to ablate either 100% tumor volume + up to 2mm margin (n = 9, complete treatment) or 50-75% tumor volume (n = 6, partial treatment) by delivering 1-2 cycle histotripsy pulses at 100 Hz PRF (pulse repetition frequency) with p – ≥30MPa using a custom 1MHz transducer. Rats were monitored weekly using MRI (magnetic resonance imaging) for 3 months or until tumors reached ~25mm. Results. MRI revealed effective post-histotripsy reduction of tumor burden with near-complete resorption of the ablated tumor in 14/15 (93.3%) treated rats. Histopathology showed

OBJECTIVE. The purpose of the study is to evaluate the outcomes of ultrasound (US) LI-RADS category US-3 observations detected at US performed for hepatocellular carcinoma (HCC) screening and surveillance on the basis of subsequently performed multi-phase MRI or CT or histopathology. MATERIALS AND METHODS. In this retrospective analysis, 267 patients at high risk for HCC (161 men and 106 women; mean [± SD] age, 58.6 ± 12.2 years) underwent screening liver US between January 2017 and June 2019 and were assigned US-3 observations on a prospective clinical basis using the US LI-RADS algorithm. The results of follow-up imaging studies and/or histopathology were analyzed. RESULTS. Visualization scores assigned at US were A (40.8% [109/267]), B (52.8% [141/267]), and C (6.4% [17/267]). Reasons for US-3 observations included a measurable mass of 1 cm or larger (88.8% [237/267]; mean size, 1.8 ± 1.0 cm; range, 1.0-6.9 cm), an area of parenchymal distortion of 1 cm or greater (7.9% [21/267]; mean size, 1.8 ± 0.9 cm; range, 1.0-4.0 cm), or a new venous thrombus (3.4% [9/267]). Confirmatory testing with multiphase contrast-enhanced MRI or CT or with histopathology was available for 81.6% (218/267) of patients. Causes of US-3 observations included no abnormality at MRI or CT (41.3% [90/218]), a benign lesion (32.6% [71/218]), a LI-RADS category 3 (LR-3) observation at MRI or CT (5.5% [12/218]), a LI-RADS category 4 or 5 (LR-4 or LR-5) observation at MRI or CT or identification of HCC at histopathology (18.8% [41/218]), and an LR-M (denoting probably or definitely malignant but without specific features for HCC) observation at MRI or CT or other malignancy at histopathology (1.8% [4/218]). The PPV of a US-3 observation for probable or definite HCC was 18.8%, and for any malignancy it was 20.6%. CONCLUSION. In the HCC screening population, approximately one in five US-3 observations represents probable or definite HCC at multiphase MRI or CT or HCC at histopathology. These findings support current US LI-RADS guidelines to pursue further evaluation with multiphase cross-sectional imaging for US-3 observations.

Purpose Our individualized functional response adaptive approach to liver stereotactic body radiation therapy (SBRT) with assessment of indocyanine green (ICG) retention at baseline and midtreatment to detect subclinical changes in liver function, permitting dose adjustment, has decreased toxicity while preserving efficacy. We hypothesized that assessment of the albumin-bilirubin (ALBI) score at baseline and midtreatment would allow for more practical identification of patients at risk for treatment-related toxicity (TRT). Methods and Materials Patients with hepatocellular carcinoma were treated on 3 prospective institutional review board–approved trials using baseline and midtreatment ICG to deliver individualized functional response adaptive liver SBRT. Patients received 3 or 5 fractions, with fraction 3 followed by a 1-month treatment break. TRT was a ≥2-point rise in Child-Pugh score within 6 months of SBRT. Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for assessment of TRT. Area under the receiver operating curve was used to compare predictive ability across models. Results In total, 151 patients underwent 166 treatments. Baseline Child-Pugh class and ALBI grade were A (66.9%), B (31.3%), or C (1.8%) and 1 (25.9%), 2 (65.7%), or 3 (8.4%), respectively. Thirty-five patients (20.3%) experienced TRT. On univariate analysis, baseline ALBI (OR, 1.8; 95% CI, 1.24-2.62; P = .02), baseline ICG (OR, 1.66; 95% CI, 1.17-2.35; P = .04), and change in ALBI (OR, 3.07; 95% CI, 1.29-7.32; P = .003) were associated with increased odds of TRT. ALBI-centric models performed similarly to ICG-centric models on multivariate analyses predicting toxicity (area under the receiver operating curve of 0.79 for both). In a model incorporating baseline and midtreatment change in ALBI and ICG, both ALBI values were statistically significantly associated with toxicity, whereas ICG values were not. Conclusions Incorporation of midtreatment change in ALBI in addition to baseline ALBI improves the ability to predict TRT in patients with hepatocellular carcinoma receiving SBRT. Our findings suggest that functional response adaptive treatment could be implemented in a practical manner because the ALBI score is easily obtained from standard laboratory values.

Stereotactic body radiation therapy (SBRT) is an emerging locoregional treatment (LRT) modality used in the management of patients with hepatocellular carcinoma (HCC). The decision to treat HCC with LRT is evaluated in a multidisciplinary setting, and the specific LRT chosen depends on the treatment intent, such as bridge-to-transplant, down-staging to transplant, definitive/curative treatment, and/or palliation, as well as underlying patient clinical factors. Accurate assessment of treatment response is necessary in order to guide clinical management in these patients. Patients who undergo LRT need continuous imaging evaluation to assess treatment response and to evaluate for recurrence. Thus, an accurate understanding of expected post-SBRT imaging findings is critical to avoid misinterpreting normal post-treatment changes as local progression or viable tumor. SBRT-treated HCC demonstrates unique imaging findings that differ from HCC treated with other forms of LRT. In particular, SBRT-treated HCC can demonstrate persistent APHE and washout on short-term follow-up imaging. This brief review summarizes current evidence for the use of SBRT for HCC, including patient population, SBRT technique and procedure, tumor response assessment on contrast-enhanced cross-sectional imaging with expected findings, and pitfalls in treatment response evaluation.

The imaging findings after loco regional treatment of hepatocellular carcinoma are variable based on the type of treatment used, the timing interval of imaging after treatment, and the cross-sectional modality used for treatment response assessment. Liver Imaging Reporting and Data System (LI-RADS) Treatment Response Algorithm (TRA) is a relatively new standardized method of evaluating treatment response after loco regional therapy to hepatocellular carcinoma. In this article, we provide an overview of the evolution of the treatment response algorithm, its current applicability and its outlook for the future. We will review current guidelines and discuss proposed changes to the algorithm as a means to continually improve LI-RADS TRA as an assessment tool post-loco regional treatment of hepatocellular carcinoma.

Patients with cancer have been negatively impacted during the coronavirus disease 2019 (COVID-19) pandemic, as many of these individuals may be immunosuppressed and of older age. Additionally, cancer follow-up or imaging appointments have been delayed in many clinics around the world. Postponement of routine screening exams will result in delays in new cancer diagnoses. Clinics are continuing to monitor and adapt their appointment schedules based on local outbreaks of COVID-19. Studies on COVID-19 in patients with cancer are limited, but consistently indicate that this population is at risk for more severe COVID-19 illness. Data from recent studies also suggest that pediatric patients with cancer have a lower risk of severe COVID-19 illness compared to adults. Certain features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detected by lung, brain, and gastrointestinal imaging may confound radiologists' interpretation of cancer diagnosis, staging, and treatment response. Lastly, as clinics begin to re-open for routine appointments, protocols have been put in place to reduce SARS-CoV-2 exposure to patients during their visits. This review details different perspectives on the impact of the COVID-19 pandemic on patients with cancer and on cancer imaging. Keywords: Abdomen/GI, Cardiac, Infection, Nervous-Peripheral.

BACKGROUND AND AIMS There are limited data on hepatocellular carcinoma (HCC) growth patterns, particularly in Western cohorts, despite implications for surveillance, prognosis, and treatment. Our study's aim was to quantify tumor doubling time (TDT) and identify correlates associated with indolent and rapid growth. APPROACH AND RESULTS We performed a retrospective multicenter cohort study of patients with cirrhosis diagnosed with HCC from 2008 to 2017 at six US and European health systems with two or more contrast-enhanced imaging studies performed ≥ 30 days apart prior to HCC treatment. Radiologists independently measured tumors in three dimensions to calculate TDT and specific growth rate (SGR). We used multivariable ordinal logistic regression to identify factors associated with indolent (TDT > 365 days) and rapid (TDT

Purpose The SARS-CoV-2 pandemic has drastically disrupted radiology in-person education. The purpose of this study was to assess the implementation of a virtual teaching method using available technology and its role in the continuity of education of practicing radiologists and trainees during the pandemic. Methods The authors created the Online Liver Imaging Course (OLIC) that comprised 28 online comprehensive lectures delivered in real-time and on-demand over six weeks. Radiologists and radiology trainees were asked to register to attend the live sessions. At the end of the course, we conducted a 46-question survey among registrants addressing their training level, perception of virtual conferencing, and evaluation of the course content. Results One thousand four hundred and thirty four radiologists and trainees completed interest sign up forms before the start of the course with the first webinar having the highest number of live attendees (343 people). On average, there were 89 live participants per session and 750 YouTube views per recording (as of July 9, 2020). After the end of the course, 487 attendees from 37 countries responded to the postcourse survey for an overall response rate of (33%). Approximately (63%) of participants were practicing radiologists while (37%) were either fellows or residents and rarely medical students. The overwhelming majority (97%) found the OLIC webinar series to be beneficial. Essentially all attendees felt that the webinar sessions met (43%) or exceeded (57%) their expectations. When asked about their perception of virtual conferences after attending OLIC lectures, almost all attendees (99%) enjoyed the virtual conference with a majority (61%) of the respondents who enjoyed the virtual format more than in-person conferences, while (38%) enjoyed the webinar format but preferred in-person conferences. When asked about the willingness to attend virtual webinars in the future, (84%) said that they would attend future virtual conferences even if in-person conferences resume while (15%) were unsure. Conclusion The success of the OLIC, attributed to many factors, indicates that videoconferencing technology provides an inexpensive alternative to in-person radiology conferences. The positive responses to our postcourse survey suggest that virtual education will remain to stay. Educational institutions and scientific societies should foster such models.

Background The Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm is used to assess the response of hepatocellular carcinoma (HCC) to local-regional therapy (LRT) based on enhancement patterns. The potential value of adding MRI ancillary features (AFs) needs to be investigated. Purpose To evaluate the potential application of MRI AFs in category adjustment to detect pathologic tumor viability in comparison with the LR-TR algorithm in CT and gadoxetic acid-enhanced MRI. Materials and Methods This retrospective study included patients with HCCs treated with LRT followed by surgical resection or liver transplantation between January 2014 and December 2017 who underwent both post-LRT CT and gadoxetic acid-enhanced MRI. For each treated observation, treatment response (TR) categories were assigned based on a consensus reading of three radiologists according to the LR-TR algorithm in CT and MRI and according to the MRI-modified TR algorithm in which MRI AFs were allowed for category adjustment. The diagnostic performances of CT LR-TR viable, MRI LR-TR viable, and MRI-modified TR viable categories were compared intraindividually with the McNemar test, with pathologic tumor viability used as a reference standard. Results A total of 138 patients (119 men; mean age, 58 years ± 9 [standard deviation]) with 138 treated observations (108 pathologically viable) were evaluated. The sensitivity and specificity of CT LR-TR viable and MRI LR-TR viable categories for predicting tumor viability were 73% (79 of 108 lesions; 95% confidence interval [CI]: 64%, 81%) versus 76% (82 of 108 lesions; 95% CI: 67%, 84%) and 90% (27 of 30 lesions; 95% CI: 74%, 98%) versus 83% (25 of 30 lesions; 95% CI: 65%, 94%), respectively, without differences between CT and MRI (

Imaging of primary hepatic neoplasms in patients at risk for hepatocellular carcinoma (HCC) and in patients with otherwise normal livers relies on proper multiphase image acquisition technique, with emphasis on a high-quality, late arterial phase, using either CT or MRI for accurate image interpretation. The introduction of liver imaging reporting and data system in 2011, with subsequent multiple updates, the most recent in 2018, has provided standardization of image interpretation, reporting and management recommendations for liver observations in patients at risk for HCC. This review article will emphasize key points of imaging primary liver tumors with emphasis on liver imaging reporting and data system, including strengths of this system. We will also review imaging of less common primary liver tumors such as cholangiocarcinoma and angiosarcomas. Imaging pitfall associated with primary liver malignancies will be demonstrated as well as ways to mitigate them. Finally, imaging and reporting of findings following locoregional treatment of HCC will be reviewed.

OBJECTIVE. The purpose of this article is to present strategies and guidelines that can be implemented in the performance of cross-sectional interventional procedures during the coronavirus disease (COVID-19) pandemic. CONCLUSION. Radiologists who perform cross-sectional interventional procedures can take several steps to minimize the risks to patients and radiology personnel, including screening referred patients to decide which procedures can be postponed, using appropriate personal protective equipment (PPE), minimizing the number of people involved in procedures, preserving PPE when possible, and applying proper room and equipment cleaning measures.

To determine the long-term natural history of size change in SBRT-treated HCC to identify an imaging biomarker to help assess treatment response.This was a retrospective cohort study of consecutive HCCs treated with SBRT from January 2008 to December 2016 with either 2 years post-treatment MRI follow-up or post-treatment resection histology. Size, major features for HCC, and mRECIST and LI-RADS v.2018 treatment response criteria were assessed at each post-treatment MRI. Local progression, distant progression, and survival were modeled with Kaplan Meier analyses.56 HCCs met inclusion criteria. Mean baseline HCC diameter was 30 mm (range: 9-105 mm). At 3 months, 76% (N = 43) of treated HCCs decreased in size (mean reduction: 8 mm, range: 5-99 mm) and 0% (N = 0) increased in size. By 24 months, 11% (N = 5) had increased in size and were considered local progression. APHE remained in 77% (43/56) at 3 months, 38% (19/50) at 12 months, and 23% (11/47) at 24 months. mRECIST-defined viable disease was observed in 77% (43/56) at 3 months and 20% (9/47) at 24 months. LI-RADS v.2018 criteria identified viable or equivocal disease in 0% at 3 months and 10% (5/47) at 24 months.Gradual loss of APHE and slow decrease in size are normal findings in HCCs treated with SBRT, and persistent APHE does not indicate viable disease. mRECIST is not accurate in the assessment of HCC after SBRT due to an overreliance on APHE to define viable disease. Increasing mass size or new nodular APHE at the treatment site may indicate local progression.

Purpose Intraductal papillary neoplasm of the bile duct (IPNB) is a precursor to invasive carcinoma and is a distinct pathologic diagnosis. The purpose of this study was to evaluate imaging features of IPNB on cross-sectional imaging studies with histopathologic correlation. Materials and methods In this IRB approved, HIPAA compliant retrospective observational analysis of 23 pathology proven IPNB tumors 22 imaging studies were reviewed, 14 CT and 8 MRI scans. Features evaluated in consensus by two subspecialty-trained abdominal radiologists included: presence of specific lesion/mass within the bile duct, location within the biliary tree, size, morphology, enhancement characteristics, and bile duct caliber. Results Majority of the subjects (16/18, 90%) had definite intraluminal mass, of which 7 (39%) had a polypoid mass with upstream diffuse biliary ductal dilation and 5 (28%) had a plaque-like mass with focal stricture and upstream biliary ductal dilatation. 6/18 (33%) subjects had low grade dysplasia, most commonly intestinal subtype, 7/18 (39%) subjects presented with invasive component, commonly pancreaticobiliary subtype, and 5/18 (28%) presented with high grade dysplasia. Conclusion IPNB has increased predilection for extrahepatic bile ducts, commonly presenting as either an intraluminal polypoidal mass with associated upstream biliary ductal dilation or a focal plaque like mass with associated ductal stricture at the site of the tumor.

Histotripsy has been used for tumor ablation, through controlled, non-invasive acoustic cavitation. This is the first study to evaluate the impact of partial histotripsy ablation on immune infiltration, survival outcomes, and metastasis development, in an in vivo orthotopic, immunocompetent rat HCC model (McA-RH7777). At 7–9 days post-tumor inoculation, the tumor grew to 5–10 mm, and ~50–75% tumor volume was treated by ultrasound-guided histotripsy, by delivering 1–2 cycle histotripsy pulses at 100 Hz PRF (focal peak negative pressure P– >30 MPa), using a custom 1 MHz transducer. Complete local tumor regression was observed on MRI in 9/11 histotripsy-treated rats, with no local recurrence or metastasis up to the 12-week study end point, and only a

OBJECTIVES The purpose of this study was to compare hepatic stiffness on ultrasound (US) shear wave elastography (SWE) in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation versus patients with no underlying liver disease. METHODS We performed a retrospective analysis of 4901 patients who underwent abdominal US examinations with adjunctive liver SWE between August 2014 and December 2016. Each patient was scanned supine with gentle breath holding on LOGIQ E9 (GE Healthcare, Waukesha, WI) or Epiq (Philips Healthcare, Andover, MA) US machines (3-6 MHz). Three to 10 measurements were made intercostally in the right hepatic lobe, following manufacturers' guidelines before release of the 2015 Society of Radiologists in Ultrasound consensus or the 2015 Society of Radiologists in Ultrasound consensus. The median and standard deviation of the shear wave velocity (SWV) were obtained. A 2-sample t test with the Welch approximation was used for statistical analysis. RESULTS Six patients had documented hepatic chronic GVHD or a high clinical suspicion of liver chronic GVHD. All had normal pretransplant liver function test results and no pretransplant or posttransplant hepatic infection. The control group, obtained from the same database, contained 10 patients with normal liver function test results, no abdominal pain, and no history of liver disease or conditions that may have caused liver stiffness changes. The SWVs in patients with chronic GVHD were double those in the control group (1.96 ± 0.28 versus 0.98 ± 0.27 m/s; P

Purpose To explore the use of nonradiologists as a method to efficiently reduce bias in the assessment of radiologist performance using a hepatobiliary tumor board as a case study. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant prospective quality assurance (QA) effort. Consecutive patients with CT or MR imaging reviewed at one hepatobiliary tumor board between February 2016 and October 2016 (n = 265) were included. All presentations were assigned prospective anonymous QA scores by an experienced nonradiologist hepatobiliary provider based on contemporaneous comparison of the imaging interpretation at a tumor board and the original interpretation(s): concordant, minor discordance, major discordance. Major discordance was defined as a discrepancy that may affect clinical management. Minor discordance was defined as a discrepancy unlikely to affect clinical management. All discordances and predicted management changes were retrospectively confirmed by the liver tumor program medical director. Logistic regression analyses were performed to determine what factors best predict discordant reporting. Results Approximately one-third (30% [79 of 265]) of reports were assigned a discordance, including 51 (19%) minor and 28 (11%) major discordances. The most common related to mass size (41% [32 of 79]), tumor stage and extent (24% [19 of 79]), and assigned LI-RADS v2014 score (22% [17 of 79]). One radiologist had 11.8-fold greater odds of discordance (P = .002). Nine other radiologists were similar (P = .10-.99). Radiologists presenting their own studies had 4.5-fold less odds of discordance (P = .006). Conclusions QA conducted in line with tumor board workflow can enable efficient assessment of radiologist performance. Discordant interpretations are commonly (30%) reported by nonradiologist providers.

Rationale and Objectives Women with pelvic pain or abnormal uterine bleeding may undergo diagnostic imaging. This study evaluates patient experience in transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) and explores correlations between preference and symptom severity. Materials and Methods Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant prospective study. Fifty premenopausal women with pelvic symptoms evaluated by recent TVUS and MRI and without history of gynecologic cancer or hysterectomy were included. A phone questionnaire used validated survey instruments including Uterine Fibroid Symptoms Quality of Life index, Testing Morbidities Index, and Wait Trade Off for TVUS and MRI examinations. Results Using Wait Trade Off, patients preferred TVUS over MRI (3.58 vs 2.80 weeks, 95% confidence interval [CI] −1.63, 0.12; P = .08). Summary test utility of Testing Morbidities Index for MRI was worse than for TVUS (81.64 vs 87.42, 95%CI 0.41, 11.15; P = .03). Patients reported greater embarrassment during TVUS than during MRI (P Conclusion Women with pelvic symptoms had a slight but significant preference for TVUS over MRI. Identifying specific distressing aspects of each test and patient factors contributing to negative perceptions can direct improvement in both test environment and patient preparation. Improved patient experience may increase imaging value.