Cytological diagnosis of follicular dendritic cell sarcoma with a unique pattern of D2-40 immunoexpression.

Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study.

Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study.

BACKGROUND: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. PATIENTS AND METHODS: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. FINDINGS: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. INTERPRETATION: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.

Impact of Hypoxia on Radiation-Based Therapies for Liver Cancer.

Background: Hypoxia, a state of low oxygen level within a tissue, is often present in primary and secondary liver tumors. At the molecular level, the tumor cells' response to hypoxic stress induces proteomic and genomic changes which are largely regulated by proteins called hypoxia-induced factors (HIF). These proteins have been found to drive tumor progression and cause resistance to drug- and radiation-based therapies, ultimately contributing to a tumor's poor prognosis. Several imaging modalities have been developed to visualize tissue hypoxia, providing insight into a tumor's microbiology. Methods: A systematic literature search was conducted in PubMed, EMBASE, Cochrane, and Google Scholar for all reports related to hypoxia on liver tumors. All relevant studies were summarized. Results: This review will focus on the impact of hypoxia on liver tumors and review PET-, MRI-, and SPECT-based imaging modalities that have been developed to predict and assess a tumor's response to radiation therapy, with a focus on liver cancers. Conclusion: While there are numerous studies that have evaluated the impact of hypoxia on tumor outcomes, there remains a relative paucity of data evaluating and quantifying hypoxia within the liver. Novel and developing non-invasive imaging techniques able to provide functional and physiological information on tumor hypoxia within the liver may be able to assist in the treatment planning of primary and metastatic liver lesions.

Safety and Efficacy of Concurrent Atezolizumab/Bevacizumab or Nivolumab Combination Therapy with Yttrium-90 Radioembolization of Advanced Unresectable Hepatocellular Carcinoma.

To evaluate the safety and efficacy of combining yttrium-90 radioembolization (Y90-RE) with immune checkpoint inhibitor therapy, consecutive advanced unresectable hepatocellular carcinoma (HCC) patients treated between 2016 and 2022 with atezolizumab/bevacizumab or nivolumab within three-months pre- and post-Y90-RE were retrospectively evaluated. Tumor response and treatment-related clinical/laboratory adverse events (AE) were assessed at 1 and 6 months, as well as differences in clinical and laboratory variables and median overall survival (OS) from initial treatment (whether it was Y90-RE or systemic therapy) between the two cohorts. A total of 19 patients (10 atezolizumab/bevacizumab; 9 nivolumab), comprising 84% males with median age 69 years, met the inclusion criteria. Compared to the atezolizumab/bevacizumab group, there were less males (100% vs. 67%; p = 0.02) and more ECOG ≥ 2 patients in the nivolumab group (0% vs. 33%; p = 0.02). Baseline characteristics or incidence of 6-month post-treatment any-grade AE (60% vs. 56%; p = 0.7), grade ≥ 3 AE (0% vs. 11%; p = 0.3), objective response (58% total, 60% vs. 56%; p = 0.7), and complete response (16% total; 10% vs. 22%; p = 0.8) were similar between the atezolizumab/bevacizumab and the nivolumab cohorts. Median OS was 12.9 months for the whole cohort, 16.4 months for nivolumab, and 10.7 months for atezolizumab/bevacizumab. Among patients with advanced unresectable HCC, the utilization of Y90-RE concurrently or within 90 days of nivolumab or atezolizumab/bevacizumab immunotherapy, appears to be well-tolerated and with a low incidence of severe AE.

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness, Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres.

PURPOSE: To evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (90Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Using the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after 90Y-TARE. Post procedure 90Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate. RESULTS: Between 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative 90Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative 90Y-TARE. CONCLUSIONS: Compared with glass-based ablative 90Y-TARE, resin-based ablative 90Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.

Using Deep Learning to Predict Treatment Response in Patients with Hepatocellular Carcinoma Treated with Y90 Radiation Segmentectomy.

Treatment of hepatocellular carcinoma (HCC) with Y90 radioembolization segmentectomy (Y90-RE) demonstrates a tumor dose-response threshold, where dose estimates are highly dependent on accurate SPECT/CT acquisition, registration, and reconstruction. Any error can result in distorted absorbed dose distributions and inaccurate estimates of treatment success. This study improves upon the voxel-based dosimetry model, one of the most accurate methods available clinically, by using a deep convolutional network ensemble to account for the spatially variable uptake of Y90 within a treated lesion. A retrospective analysis was conducted in patients with HCC who received Y90-RE at a single institution. Seventy-seven patients with 103 lesions met the inclusion criteria: three or fewer tumors, pre- and post treatment MRI, and no prior Y90-RE. Lesions were labeled as complete (n = 57) or incomplete response (n = 46) based on 3-month post treatment MRI and divided by medical record number into a 20% hold-out test set and 80% training set with 5-fold cross-validation. Slice-wise predictions were made from an average ensemble of models and thresholds from the highest accuracy epochs across all five folds. Lesion predictions were made by thresholding all slice predictions through the lesion. When compared to the voxel-based dosimetry model, our model had a higher F1-score (0.72 vs. 0.2), higher accuracy (0.65 vs. 0.60), and higher sensitivity (1.0 vs. 0.11) at predicting complete treatment response. This algorithm has the potential to identify patients with treatment failure who may benefit from earlier follow-up or additional treatment.

REBOA: Expanding Applications From Traumatic Hemorrhage to Obstetrics and Cardiopulmonary Resuscitation, From the AJR Special Series on Emergency Radiology.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) has emerged over the past decade as a technique to control life-threatening hemorrhage and treat hemorrhagic shock, being increasingly used to treat noncompressible traumatic torso hemorrhage. Reports during this time also support the use of a REBOA device for an expanding range of indications including nontraumatic abdominal hemorrhage, postpartum hemorrhage, placenta accreta spectrum (PAS) disorder, and cardiopulmonary resuscitation (CPR). The strongest available evidence supports REBOA as a lifesaving adjunct to definitive surgical management in trauma and as a method to help avoid hysterectomy in select patients with postpartum hemorrhage or PAS disorder. In comparison with initial descriptions of complete REBOA inflation, techniques for partial REBOA inflation have been introduced to achieve hemodynamic stability while minimizing adverse events relating to reperfusion injuries. Fluoroscopy-free REBOA has been described in various settings, including trauma, obstetrics, and out-of-hospital cardiac arrest. As the use of REBOA expands outside the trauma setting and into nontraumatic abdominal hemorrhage, obstetrics, and CPR, it is imperative for radiologists to become familiar with this technology, its proper placement, and its potential adverse sequelae.

Standard Radiation Dosimetry Models: What Interventional Radiologists Need to Know.

Thoughtful and accurate dosimetry is critical to obtain the safest and most efficacious yttrium-90 (Y90) radioembolization of primary and secondary liver cancers. Three dosimetry models are currently used in clinical practice, namely, body surface area model, medical internal radiation dose model, and the partition model. The objective of this review is to briefly outline the history behind Y90 dosimetry and the difference between the aforementioned models. When applying these three models to a single case, the differences between them are further demonstrated. Each dosimetry model in clinical practice has its own benefits and limitations. Therefore, it is incumbent upon practicing interventional radiologists to be aware of these differences to optimize treatment outcomes for their patients.

Predictors of Successful Yttrium-90 Radioembolization Bridging or Downstaging in Patients with Hepatocellular Carcinoma.

Purpose: This study aims to identify clinical and imaging prognosticators associated with the successful bridging or downstaging to liver transplantation (LT) in patients undergoing Yttrium-90 radioembolization (Y90-RE) for hepatocellular carcinoma (HCC). Methods: Retrospectively, patients with Y90-RE naïve HCC who were candidates or potential candidates for LT and underwent Y90-RE were included. Patients were then divided into favorable (maintained or achieved Milan criteria (MC) eligibility) or unfavorable (lost eligibility or unchanged MC ineligibility) cohorts based on changes to their MC eligibility after Y90-RE. Penalized logistic regression analysis was performed to identify the significant baseline prognosticators. Results: Between 2013 and 2018, 135 patients underwent Y90-RE treatment. Among the 59 (42%) patients within MC, LT eligibility was maintained in 49 (83%) and lost in 10 (17%) patients. Within the 76 (56%) patients outside MC, eligibility was achieved in 32 (42%) and unchanged in 44 (58%). Among the 81 (60%) patients with a favorable response, 16 (20%) went on to receive LT. Analysis of the baseline characteristics revealed that lower Albumin-Bilirubin score, lower Child-Pugh class, lower Barcelona Clinic Liver Cancer stage, HCC diagnosis using dynamic contrast-enhanced imaging on CT or MRI, normal/higher albumin levels, decreased severity of tumor burden, left lobe HCC disease, and absence of HBV-associated cirrhosis, baseline abdominal pain, or fatigue were all associated with a higher likelihood of bridging or downstaging to LT eligibility (p's < 0.05). Conclusion: Certain baseline clinical and tumor characteristics are associated with the successful bridging or downstaging of potential LT candidates with HCC undergoing Y90-RE.

Disproportionate Use in Minor Trauma Is Driving Emergency Department Cervical Spine Imaging: An Injury Severity Score-Based Analysis.

PURPOSE: Clinical practice guidelines intended to reduce unnecessary cervical spine imaging have yielded mixed results. We aimed to assess evolving emergency department (ED) cervical spine imaging utilization in patients with trauma by injury severity. METHODS: Using 2009 to 2018 IBM MarketScan Commercial Databases, we identified ED trauma encounters, associated cervical spine imaging, and related diagnosis codes. We classified encounters by injury severity (minor, intermediate, major) using an International Classification of Disease code-derived Injury Severity Score algorithm and studied evolving imaging utilization using multivariable Poisson regression models. RESULTS: Of all 11,346,684 ED visits for trauma, 7,753,914 (68.3%), 3,524,250 (31.1%), and 68,520 (0.6%) involved minor, intermediate, and major injuries, respectively. Overall cervical spine imaging increased 5.7% annually (incidence rate ratio [IRR] 1.057, P < .001) with radiography decreasing 2.7% annually (IRR 0.973, P < .001) and CT increasing 10.5% annually (IRR 1.105, P < .001). Radiography utilization remained unchanged for minor injuries (IRR 0.994, P = .14) but decreased for intermediate (IRR 0.928 versus minor, P < .001) and major (IRR 0.931 versus minor, P < .001) injuries. Increases in CT utilization were greatest for minor injuries (IRR 1.109, P < .001) with smaller increases in intermediate (IRR 0.960 versus minor, P < .001) and major (IRR 0.987 versus minor, P = .022) injuries. CONCLUSIONS: Recent increases in cervical spine imaging in commercially insured patients with trauma seen in the ED have been largely related to increases in CT for patients with only minor injuries, in whom imaging utilization has been historically low. Further study is necessary to assess appropriateness, implications on costs and population radiation dose, and factors influencing ordering decision making.

Improved Tumor Response in Patients on Metformin Undergoing Yttrium-90 Radioembolization Segmentectomy for Hepatocellular Carcinoma.

PURPOSE: Metformin is associated with improved outcomes after external radiation and chemotherapy but has not been studied for Y-90 radiation segmentectomy (RS). This study evaluates the effect of metformin on tumor response after Y-90 RS in patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: A retrospective analysis of patients with HCC who underwent Y-90 RS between 2014-2018 was performed. Comparisons were made between all patients taking and not taking metformin, and diabetic patients taking and not taking metformin. Tumor response was analyzed with logistic regression to compare absolute and percent change in total tumor diameter (TTD) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Overall survival (OS) was evaluated using Kaplan-Meier estimation and log-rank analysis. RESULTS: A total of 106 patients underwent 112 Y-90 RS, of which 40 were diabetic (38.8%) and 19 (18.4%) were on metformin. At baseline, the two groups of patients on metformin and not on metformin had no significant difference in age, Child-Pugh score, MELD score, ALBI grade, total tumor diameter, and size of dominant tumor. The only significant baseline difference was ECOG status. Uni- and multivariate analysis demonstrated a larger reduction in TTD and objective response by mRECIST criteria for patients undergoing Y-90 RS on metformin compared to those not on metformin. OS was similar between patients taking and not taking metformin (p = 0.912). CONCLUSION: Metformin may be associated with increased tumor response after Y-90 RS in patients with HCC. LEVEL OF EVIDENCE: III, Retrospective Study.

Tumor-to-Normal Ratio Relationship between Planning Technetium-99 Macroaggregated Albumin and Posttherapy Yttrium-90 Bremsstrahlung SPECT/CT.

PURPOSE: To quantify the relationship of the tumor-to-normal ratio (TNR) attained from the technetium-99m macroaggregated albumin (MAA) and posttreatment yttrium-90 bremsstrahlung (Y90-Brem) single-photon emission computerized tomography (SPECT)/computer tomography (CT) studies in patients with hepatocellular carcinoma (HCC) treated with glass microspheres. MATERIALS AND METHODS: Retrospectively, a total of 190 consecutive patients with HCC who underwent 204 MAA and Y90-Brem SPECT/CT for glass microsphere Y90 radiation segmentectomy (Y90-RS) or lobar treatment (Y90-RLT) between 2013 and 2018 were included. Semi-automated regions-of-interests were drawn around the targeted tumor and nontumoral liver tissue on the SPECT/CT studies. TNR values from MAA and Y90-Brem SPECT/CT were compared using paired t-tests, Pearson correlation, and median with interquartile ranges (IQR). RESULTS: The mean TNR for MAA and Y90-Brem SPECT/CT was 2.96 ± 1.86 (median, 2.64; IQR, 2.50) and 2.29 ± 1.10 (median, 2.06; IQR, 1.05), respectively (P < .0001). The mean Y90-RLT TNR was 2.88 ± 1.67 (median, 2.59; IQR, 0.83) and 2.17 ± 0.89 (median, 1.98; IQR, 0.81) for MAA and Y90-Brem SPECT/CT, respectively (P < .0001). The mean Y90-RS TNR was 3.02 ± 2.01 (median, 2.87; IQR, 3.01) and 2.39 ± 1.25 (median, 2.11; IQR, 1.28) for MAA and Y90-Brem SPECT/CT, respectively (P = .0003). TNR attained from MAA and Y90 SPECT/CT studies showed a moderate correlation in a positive linear fashion for the overall (r = 0.54; P < .001), Y90-RLT (r = 0.66, P < .001), and Y90-RS cohorts (r = 0.48, P < .001). CONCLUSIONS: The TNR attained from Y90-Brem SPECT/CT is often underestimated, positively correlated, and less variable than that attained from MAA SPECT/CT.

Evaluation of Medium-Term Efficacy of Y90 Radiation Segmentectomy vs Percutaneous Microwave Ablation in Patients with Solitary Surgically Unresectable < 4 cm Hepatocellular Carcinoma: A Propensity Score Matched Study.

OBJECTIVE: To evaluate the efficacy and safety of Y90 radiation segmentectomy (RS) vs. percutaneous microwave ablation (MWA) in patients with solitary HCC ≤ 4 cm. METHODS: From 2014 to 2017, 68 consecutive treatment naïve patients were included (34 per treatment arm). Chi-square and t-test were used to evaluate differences in baseline demographics between groups. Objective response was evaluated using mRECIST and toxicity using CTCAE. Overall survival (OS) and progression free survival (PFS) in the targeted tumor and the remainder of liver from initial treatment was calculated using Kaplan-Meier estimation. Propensity score matching was then performed with n = 24 patients matched in each group. Similar outcome analysis was then pre-formed. RESULTS: In the overall study population, both groups had similar baseline characteristics with the exception of larger lesions in the RS group. There was no difference in toxicity, objective tumor response, OS and non-target liver PFS between the MWA and RS group (p's > 0.05). In the matched cohort, the objective tumor response was 82.6% in MWA vs. 90.9%% in RS (p = 0.548). The mean OS in the MWA group (44.3 months) vs RS (59.0 months; p = 0.203). The targeted tumor mean PFS for the MWA groups was 38.6 months vs. 57.8 months in RS group (p = 0.005). There was no difference overall PFS and toxicity between the 2 matched groups. CONCLUSIONS: Our data suggest Y90 RS achieves similar tumor response and OS with a similar safety compared to MWA in the management of HCC lesions ≤ 4 cm. Additionally, targeted tumor PFS appears to be prolonged in the RS group with similar non-target liver PFS between RS and MWA group.

Associations Over Time Between Paid Medical Malpractice Claims and Imaging Utilization in the United States.

PURPOSE: The aim of this study was to explore state-level relationships between the incidence and payout amounts for medical malpractice claims and Medicare imaging utilization and spending across the United States. METHODS: Using claims data from a 5% sample of Medicare beneficiaries for 2004 to 2016, annual state population-adjusted rates of imaging utilization and spending were calculated. Using National Practitioner Data Bank files, all paid physician malpractice claims were identified, and lagged state population-adjusted rolling averages of paid claim frequencies and payout amounts were calculated. Controlling for secular trends and state fixed effects with robust standard errors clustered at the state level to account for serial autocorrelation, associations between imaging utilization and lagged paid malpractice claims were assessed using multivariate regression models. Log-log model specification was used to obtain elasticity measures. RESULTS: Between 2004 and 2016, national Medicare diagnostic imaging utilization and spending declined by 31.4% and 47.2%, respectively (from 355,057 to 243,517 examinations and from $28,591,146 to $15,099,291 per 100,000 beneficiaries). Overall national paid malpractice claims and payout amounts declined by 46.4% and 39.6%, respectively (from 4.83 to 2.59 claims and from $1,803,565 to $1,089,112 per 100,000 population). After controlling for secular trends and state fixed effects, advanced imaging utilization was positively associated with the lagged number of per capita paid malpractice claims. Each 1% increase in average paid malpractice claims was associated with a subsequent 0.20% increase in advanced imaging utilization (P = .001). CONCLUSIONS: Positive associations between paid malpractice claims and advanced Medicare imaging utilization support the contention that US physicians use medical imaging as a defensive medicine strategy.

Erratum: Yttrium-90 Radioembolization Dosimetry: What Trainees Need to Know.

[This corrects the article DOI: 10.1055/s-0040-1720954.].

Impact of blue light filtering glasses on computer vision syndrome in radiology residents: a pilot study.

Computer vision syndrome (CVS) is an umbrella term for a pattern of symptoms associated with prolonged digital screen exposure, such as eyestrain, headaches, blurred vision, and dry eyes. Commercially available blue light filtering lenses (BLFL) are advertised as improving CVS. Our pilot study evaluates the effectiveness of BLFL on reducing CVS symptoms and fatigue in a cohort of radiologists. A prospective crossover study was conducted with ten radiology residents randomized into two cohorts: one wearing BLFL first then a sham pair (non-BLFL), and the other wearing a sham pair first then BLFL, over two weeks during normal clinical work. Participants filled out a questionnaire using the validated computer vision syndrome questionnaire (CVS-Q) and the Swedish Occupational Fatigue Inventory (SOFI). The majority of symptoms [11/16 (68.8%) and 13/16 (81.3%) symptoms on the CVS-Q and SOFI, respectively] were reduced (i.e., symptoms less severe) with the BLFL compared to the sham glasses. Females rated symptoms of sleepiness and physical discomfort in the SOFI, and overall CVS-Q, as more severe. Postgraduate year (PGY)-2 residents rated all symptoms as more severe than PGY-3/4s. BLFL may ameliorate CVS symptoms. Future studies with larger sample sizes and participants of different ages are required to verify the potential of BLFL.