Safety and Feasibility of Cryoablation during Immunotherapy in Patients with Metastatic Soft Tissue Sarcoma.

PURPOSE: Patients with metastatic soft tissue sarcoma (STS) undergo a wide array of treatments, including surgery, radiation, chemotherapy, immunotherapy, and ablative therapies, to control their disease. The combination of cryoablation and immunotherapy may lead to an enhanced antitumor immune response via the abscopal effect. It is hypothesized that the combination of cryoablation and immunotherapy in patients with metastatic STS is safe and feasible. MATERIALS AND METHODS: A single-center retrospective analysis was performed on patients with metastatic STS who underwent cryoablation. Sixteen patients were treated with 27 cryoablation procedures while receiving ipilimumab and nivolumab from April 2017 to July 2020. Response Evaluation Criteria in Solid Tumors, 1.1, were used to determine the outcomes of nontarget tumors. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of the first cryoablation after initiating immunotherapy until progression or death. RESULTS: Thirty-four tumors were cryoablated, 23 of which were intentionally subtotal. The most common tumor subtype was liposarcoma (n = 4). Thirteen (81%) patients had previously demonstrated disease progression on multiple lines of chemotherapy. All tumors cryoablated with a complete intention demonstrated a complete response. Seven patients had a clinical benefit, including 1 with a complete response, 1 with a partial response, and 5 with stable disease. The median OS was 14.1 months, with a median PFS of 2.3 months (95% confidence interval, 1.8-14.3). Five patients had pneumothoraces after cryoablation, 2 of whom required chest tube placement. Eleven patients experienced adverse events related to immunotherapy, 10 of whom experienced grade 1 or 2. CONCLUSIONS: Cryoablation in patients with metastatic STS undergoing immunotherapy is feasible and safe.

Needs of Referring Providers by Practice Type: Results of a Survey at an Academic Medical Center.

OBJECTIVE. The purpose of this study was to test a published hypothetic framework of different referring provider needs for primary care, specialty care, and urgent or emergency care practitioners through questions asked in an annual survey at an academic medical center. MATERIALS AND METHODS. Seven questions regarding provider needs were included in an annual online anonymous survey of referring providers. Multiple-choice response options were provided. Differences in responses between provider types were assessed using the Mann-Whitney U test. RESULTS. The survey was sent to 3325 providers, and 514 responses were received (response rate, 15.5%). The analysis included 340 responses: 81 from primary care, 205 from specialty care, and 54 from urgent or emergency care. Results indicated that urgent or emergency care providers need examinations to be performed and interpreted more quickly, specialist providers prefer greater radiologist specialization, urgent or emergency care providers order imaging with greater frequency, primary care and urgent or emergency care providers order a greater breadth of imaging, primary care providers report greater reliance on radiologist interpretations, and all provider types highly value direct interactions with radiologists. All results were statistically significant and matched established hypotheses. CONCLUSION. Our results support the concept that referring providers tend to value different aspects of radiology services differently, according to predictable characteristics. The findings suggest that the concept of value in radiology is highly context-specific and can be evaluated, at least in part, using practice-specific referring provider assessments.

Untapped Resources: Attaining Equitable Representation for Women in IR.

PURPOSE: To investigate the current state of gender diversity among invited coordinators at the Society of Interventional Radiology (SIR) Annual Scientific Meeting and to compare the academic productivity of female interventional radiologists to that of invited male coordinators. MATERIALS AND METHODS: Faculty rosters for the SIR Annual Scientific Meetings from 2015 to 2017 were stratified by gender to quantify female representation among those asked to lead and coordinate podium sessions. To quantify academic productivity and merit, H-index, publications, and authorship by females over a 6-year period (2012-2017) were statistically compared to that of recurring male faculty. RESULTS: From 2015 to 2017, women held 7.1% (9/126), 4.3%, (8/188), and 13.7% (27/197) of the available coordinator positions for podium sessions, with no representation at the plenary sessions, and subject matter expertise was concentrated in economics and education. Academic productivity of the top quartile of published female interventional radiologists was statistically similar to that of the invited male faculty (H-index P = .722; total publications P = .689; and authorship P = .662). CONCLUSIONS: This study found that senior men dominate the SIR Annual Scientific Meeting, with few women leading or coordinating the podium sessions, despite their established academic track record.

Technical Feasibility and Clinical Effectiveness of Transjugular Intrahepatic Portosystemic Shunt Creation in Pediatric and Adolescent Patients.

PURPOSE: To examine the technical feasibility and clinical efficacy of transjugular intrahepatic portosystemic shunt (TIPS) creation in children and adolescents. MATERIALS AND METHODS: Retrospective review was performed of 59 patients (mean age 12.6 y [range, 1.5-20 y], mean weight 47.5 kg [range, 11.4-112.2 kg], mean Model for End-stage Liver Disease/Pediatric End-stage Liver Disease score 12.5 [range, 6-33]) who underwent 61 TIPS attempts at 3 tertiary children's hospitals from 2001 to 2017 for acute esophageal or gastroesophageal variceal bleeding, primary and secondary prevention of variceal bleeding, and refractory ascites. Pediatric liver disease etiologies included biliary atresia, cystic fibrosis, and ductal plate anomalies. Technical, hemodynamic, and clinical success and patency rates were reported at 1, 6, 12, and 24 months. Statistical analysis evaluated reasons for clinical failure. Kaplan-Meier analysis measured clinical success, patency, and transplant-free survival. RESULTS: Technical success was 93.4% (57/61) in 59 consecutive patients. Most common TIPS indications were treating and preventing esophageal and gastroesophageal variceal bleeding (57/59; 96.6%). Hemodynamic success was 94% (47/50). Clinical success was 80.7% (45/56). Two-year clinical success for acute variceal bleeding and ascites was 94.1% and 100%, respectively. Overall patency at 1, 6, 12, and 24 months was 98.0%, 97.8%, 94.3%, and 91.3%. Two-year transplant-free survival was 88.8%. Overall and major complication rates were 21.2% (13/61) and 8.2% (5/61), with 3 mortalities. Gradient reduction < 12 mm Hg correlated with clinical success (P < .01). CONCLUSIONS: TIPS creation in pediatric patients is technically feasible and clinically efficacious for treatment and prevention of esophageal and gastroesophageal variceal hemorrhage. High 2-year clinical success, patency, and survival rates should encourage providers to consider portosystemic shunts as a bridge to liver transplantation.

Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an Ex Vivo Swine Model.

PURPOSE: To compare the intensity of muscle contractions in irreversible electroporation (IRE) treatments when traditional IRE and high-frequency IRE (H-FIRE) waveforms are used in combination with a single applicator and distal grounding pad (A+GP) configuration. MATERIALS AND METHODS: An ex vivo in situ porcine model was used to compare muscle contractions induced by traditional monopolar IRE waveforms vs high-frequency bipolar IRE waveforms. Pulses with voltages between 200 and 5,000 V were investigated, and muscle contractions were recorded by using accelerometers placed on or near the applicators. RESULTS: H-FIRE waveforms reduced the intensity of muscle contractions in comparison with traditional monopolar IRE pulses. A high-energy burst of 2-µs alternating-polarity pulses energized for 200 µs at 4,500 V produced less intense muscle contractions than traditional IRE pulses, which were 25-100 µs in duration at 3,000 V. CONCLUSIONS: H-FIRE appears to be an effective technique to mitigate the muscle contractions associated with traditional IRE pulses. This may enable the use of voltages greater than 3,000 V necessary for the creation of large ablations in vivo.

The Role of Cone-Beam CT in Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

PURPOSE: To review available evidence for use of cone-beam CT during transcatheter arterial chemoembolization in hepatocellular carcinoma (HCC) for detection of tumor and feeding arteries. MATERIALS AND METHODS: Literature searches were conducted from inception to May 15, 2016, in PubMed (MEDLINE), Scopus, and Cochrane Central Register of Controlled Trials. Searches included "cone beam," "CBCT," "C-arm," "CACT," "cone-beam CT," "volumetric CT," "volume computed tomography," "volume CT," AND "liver," "hepatic*," "hepatoc*." Studies that involved adults with HCC specifically and treated with transcatheter arterial chemoembolization that used cone-beam CT were included. RESULTS: Inclusion criteria were met by 18 studies. Pooled sensitivity of cone-beam CT for detecting tumor was 90% (95% confidence interval [CI], 82%-95%), whereas pooled sensitivity of digital subtraction angiography (DSA) for tumor detection was 67% (95% CI, 51%-80%). Pooled sensitivity of cone-beam CT for detecting tumor feeding arteries was 93% (95% CI, 91%-95%), whereas pooled sensitivity of DSA was 55% (95% CI, 36%-74%). CONCLUSIONS: Cone-beam CT can significantly increase detection of tumors and tumor feeding arteries during transcatheter arterial chemoembolization. Cone-beam CT should be considered as an adjunct tool to DSA during transcatheter arterial chemoembolization treatments of HCC.

The Role of Dual-Phase Cone-Beam CT in Predicting Short-Term Response after Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To identify computational and qualitative features derived from dual-phase cone-beam CT that predict short-term response in patients undergoing transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 43 patients with 59 HCCs. Six features were extracted, including intensity of tumor enhancement on both phases and characteristics of the corona on the washout phase. Short-term response was evaluated by modified Response Evaluation Criteria in Solid Tumors on follow-up imaging, and extracted features were correlated to response using univariate and multivariate analyses. RESULTS: Univariate and multivariate analyses did not reveal a correlation between absolute and relative tumor enhancement characteristics on either phase with response (arterial P = .21; washout P = .40; ∆ P = .90). On multivariate analysis of qualitative characteristics, the presence of a diffuse corona was an independent predictor of incomplete response (P = .038) and decreased the odds ratio of objective response by half regardless of tumor size. CONCLUSIONS: Computational features extracted from contrast-enhanced dual-phase cone-beam CT are not prognostic of response to transarterial chemoembolization in patients with HCC. HCCs that demonstrate a diffuse, patchy corona have reduced odds of achieving complete response after transarterial chemoembolization and should be considered for additional treatment with an alternative modality.

Superselective Chemoembolization of HCC: Comparison of Short-term Safety and Efficacy between Drug-eluting LC Beads, QuadraSpheres, and Conventional Ethiodized Oil Emulsion.

PURPOSE: To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages. MATERIALS AND METHODS: From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed. RESULTS: Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found. CONCLUSION: Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance.

Production of Spherical Ablations Using Nonthermal Irreversible Electroporation: A Laboratory Investigation Using a Single Electrode and Grounding Pad.

PURPOSE: To mathematically model and test ex vivo a modified technique of irreversible electroporation (IRE) to produce large spherical ablations by using a single probe. MATERIALS AND METHODS: Computed simulations were performed by using varying voltages, electrode exposure lengths, and tissue types. A vegetable (potato) tissue model was then used to compare ablations created by conventional and high-frequency IRE protocols by using 2 probe configurations: a single probe with two collinear electrodes (2EP) or a single electrode configured with a grounding pad (P+GP). The new P+GP electrode configuration was evaluated in ex vivo liver tissue. RESULTS: The P+GP configuration produced more spherical ablation volumes than the 2EP configuration in computed simulations and tissue models. In prostate tissue, computed simulations predicted ablation volumes at 3,000 V of 1.6 cm(3) for the P+GP configurations, compared with 0.94 cm(3) for the 2EP configuration; in liver tissue, the predicted ablation volumes were 4.7 times larger than those in the prostate. Vegetable model studies verify that the P+GP configuration produces larger and more spherical ablations than those produced by the 2EP. High-frequency IRE treatment of ex vivo liver with the P+GP configuration created a 2.84 × 2.21-cm ablation zone. CONCLUSIONS: Computer modeling showed that P+GP configuration for IRE procedures yields ablations that are larger than the 2EP configuration, creating substantial ablation zones with a single electrode placement. When tested in tissue models and an ex vivo liver model, the P+GP configuration created ablation zones that appear to be of clinically relevant size and shape.

Percutaneous Cryoablation for Successful Treatment of a Persistent Urine Leak after Robotic-Assisted Partial Nephrectomy.

Urine leak after nephron-sparing surgery is a difficult and morbid situation that may delay recovery and necessitate additional hospitalization and intervention. The use of cryoablation to treat a 34-year-old woman with persistent urine leak after robotic-assisted partial nephrectomy is described. Surgery was performed to treat ureteral duplication that resulted in recurrent urinary tract infections and back pain. Cryoablation was performed with computed tomography guidance, targeting urine extravasation observed after the administration of intravenous contrast medium. Imaging performed after ablation confirmed resolution of the urine leak; renal function was preserved.

Emergent salvage direct intrahepatic portocaval shunt procedure for acute variceal hemorrhage.

PURPOSE: To review the safety and effectiveness of direct intrahepatic portocaval shunt (DIPS) creation with variceal embolization for acute variceal hemorrhage after a failed transjugular intrahepatic portosystemic shunt (TIPS) creation attempt or in patients with prohibitive anatomy. MATERIALS AND METHODS: Transjugular intrahepatic portosystemic shunt and DIPS procedures performed for variceal hemorrhage between January 2008 and July 2014 were reviewed. The default procedure was TIPS creation, with DIPS creation reserved for patients with unfavorable anatomy or who had technically unsuccessful TIPS creation. Thirteen patients underwent DIPS creation (mean age, 60 y ± 12; Child-Pugh class A/B/C, 8%/62%/30%; Model for End-stage Liver Disease score, 15 ± 5; range, 8-26) and 117 underwent TIPS creation. Four patients underwent a TIPS attempt and were converted to DIPS creation upon technical failure; 9 were treated primarily with DIPS creation because of preprocedural imaging revealing unfavorable anatomy (intrahepatic portal thrombosis, n = 2; venous distortion from prior hepatic resections, n = 2; severely angulated hepatic veins, n = 5). RESULTS: Direct intrahepatic portocaval shunt creation with variceal embolization (six gastric or esophageal; seven stomal, duodenal, or rectal) was successful in all patients; 11 also had concomitant variceal sclerotherapy. Mean DIPS procedure time was less than 2 hours. There was 1 major procedural complication. During a mean follow-up of 13.0 months ± 15.5, 1 patient developed DIPS thrombosis and recurrent hemorrhage; 1 patient underwent successful transplantation. Two deaths were observed within 30 days, neither associated with recurrent hemorrhage. CONCLUSIONS: Direct intrahepatic portocaval shunt creation appears to be a safe, expedient, and effective treatment for patients with acute variceal hemorrhage who are poor anatomic candidates for TIPS creation or who have undergone unsuccessful TIPS creation attempts.

Optimal imaging surveillance schedules after liver-directed therapy for hepatocellular carcinoma.

PURPOSE: To optimize surveillance schedules for the detection of recurrent hepatocellular carcinoma (HCC) after liver-directed therapy. MATERIALS AND METHODS: New methods have emerged that allow quantitative analysis and optimization of surveillance schedules for diseases with substantial rates of recurrence such as HCC. These methods were applied to 1,766 consecutive chemoembolization, radioembolization, and radiofrequency ablation procedures performed on 910 patients between 2006 and 2011. Computed tomography or magnetic resonance imaging performed just before repeat therapy was set as the time of "recurrence," which included residual and locally recurrent tumor as well as new liver tumors. Time-to-recurrence distribution was estimated by Kaplan-Meier method. Average diagnostic delay (time between recurrence and detection) was calculated for each proposed surveillance schedule using the time-to-recurrence distribution. An optimized surveillance schedule could then be derived to minimize the average diagnostic delay. RESULTS: Recurrence is 6.5 times more likely in the first year after treatment than in the second. Therefore, screening should be much more frequent in the first year. For eight time points in the first 2 years of follow-up, the optimal schedule is 2, 4, 6, 8, 11, 14, 18, and 24 months. This schedule reduces diagnostic delay compared with published schedules and is cost-effective. CONCLUSIONS: The calculated optimal surveillance schedules include shorter-interval follow-up when there is a higher probability of recurrence and longer-interval follow-up when there is a lower probability. Cost can be optimized for a specified acceptable diagnostic delay or diagnostic delay can be optimized within a specified acceptable cost.

Classification of hypervascular liver lesions based on hepatic artery and portal vein blood supply coefficients calculated from triphasic CT scans.

Perfusion CT of the liver typically involves scanning the liver at least 20 times, resulting in a large radiation dose. We developed and validated a simplified model of tumor blood supply that can be applied to standard triphasic scans and evaluated whether this can be used to distinguish benign and malignant liver lesions. Triphasic CTs of 46 malignant and 32 benign liver lesions were analyzed. For each phase, regions of interest were drawn in the arterially enhancing portion of each lesion, as well as the background liver, aorta, and portal vein. Hepatic artery and portal vein blood supply coefficients for each lesion were then calculated by expressing the enhancement curve of the lesion as a linear combination of the enhancement curves of the aorta and portal vein. Hepatocellular carcinoma (HCC) and hypervascular metastases, on average, both had increased hepatic artery coefficients compared to the background liver. Compared to HCC, benign lesions, on average, had either a greater hepatic artery coefficient (hemangioma) or a greater portal vein coefficient (focal nodular hyperplasia or transient hepatic attenuation difference). Hypervascularity with washout is a key diagnostic criterion for HCC, but it had a sensitivity of 72 % and specificity of 81 % for diagnosing malignancy in our diverse set of liver lesions. The sensitivity for malignancy was increased to 89 % by including enhancing lesions that were hypodense on all phases. The specificity for malignancy was increased to 97 % (p = 0.039) by also examining hepatic artery and portal vein blood supply coefficients, while maintaining a sensitivity of 76 %.

Pulmonary interstitial lymphography: A prospective trial with potential impact on stereotactic ablative radiotherapy planning for early-stage lung cancer.

This prospective feasibility trial investigated pulmonary interstitial lymphography to identify thoracic primary nodal drainage (PND). A post-hoc analysis of nodal recurrences was compared with PND for patients with early-stage lung cancer; larger studies are needed to establish correlation. Exploratory PND-inclusive stereotactic ablative radiotherapy plans were assessed for dosimetric feasibility.

ACR Appropriateness Criteria® Management of Uterine Fibroids: 2023 Update.

Uterine fibroids are the most common benign tumor in women of reproductive age and can present with symptoms including bleeding, bulk related symptoms, and infertility. Several treatment options are available for the management of uterine fibroids, including medical management, minimally invasive therapies such as uterine artery embolization and MR-guided focused ultrasound ablation, and surgical interventions ranging from laparoscopic myomectomy to open hysterectomy. Given this wide range of therapeutic interventions, it is important to understand the data supporting these interventions and to be able to apply it in different clinical settings. This document provides a summary of recent trials supporting various therapies for uterine fibroids, including recent evidence for MR-guided focused ultrasound ablation and a detailed discussion of fertility outcomes in myomectomy and uterine fibroid embolization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

From Acceptable to Superlative: Scaling a Technologist Coaching Intervention to Improve Image Quality.

OBJECTIVE: To explore factors influencing the expansion of the peer-based technologist Coaching Model Program (CMP) from its origins in mammography and ultrasound to all imaging modalities at a single tertiary academic medical center. METHODS: After success in mammography and ultrasound, efforts to expand the CMP across all Stanford Radiology modalities commenced in September 2020. From February to April 2021 as lead coaches piloted the program in these novel modalities, an implementation science team designed and conducted semistructured stakeholder interviews and took observational notes at learning collaborative meetings. Data were analyzed using inductive-deductive approaches informed by two implementation science frameworks. RESULTS: Twenty-seven interviews were collected across modalities with radiologists (n = 5), managers (n = 6), coaches (n = 11), and technologists (n = 5) and analyzed with observational notes from six learning meetings with 25 to 40 recurrent participants. The number of technologists, the complexity of examinations, or the existence of standardized auditing criteria for each modality influenced CMP adaptations. Facilitators underlying program expansion included cross-modality learning collaborative, thoughtful pairing of coach and technologist, flexibility in feedback frequency and format, radiologist engagement, and staged rollout. Barriers included lack of protected coaching time, lack of pre-existing audit criteria for some modalities, and the need for privacy of auditing and feedback data. DISCUSSION: Adaptations to each radiology modality and communication of these learnings were key to disseminating the existing CMP to new modalities across the entire department. An intermodality learning collaborative can facilitate the dissemination of evidence-based practices across modalities.

Current State of Peer Learning in Radiology: A Survey of ACR Members.

PURPOSE: Peer learning (PL) programs seek to improve upon the limitations of score-based peer review and incorporate modern approaches to improve patient care. The aim of this study was to further understand the landscape of PL among members of the ACR in the first quarter of 2022. METHODS: Members of the ACR were surveyed to evaluate the incidence, current practices, perceptions, and outcomes of PL in radiology practice. The survey was administered via e-mail to 20,850 ACR members. The demographic and practice characteristics of the 1,153 respondents (6%) were similar to those of the ACR radiologist membership and correspond to a normal distribution of the population of radiologists and can therefore be described as representative of that population. Therefore, the error range for the results from this survey is ±2.9% at a 95% confidence level. RESULTS: Among the total sample, 610 respondents (53%) currently use PL, and 334 (29%) do not. Users of PL are younger (mode age ranges, 45-54 years for users and 55-64 years for nonusers; P < .01), more likely to be female (29% vs 23%, P < .05), and more likely to practice in urban settings (52% vs 40%, P = .0002). Users of PL feel that it supports an improved culture of safety and wellness (543 of 610 [89%]) and fosters continuous improvement initiatives (523 of 610 [86%]). Users of PL are more likely than nonusers to identify learning opportunities from routine clinical practice (83% vs 50%, P < .00001), engage in programming inclusive of more team members, and implement more practice improvement projects (P < .00001). PL users' net promoter score of 65% strongly suggests that users of PL are highly likely to recommend the program to colleagues. CONCLUSIONS: Radiologists across a breadth of radiology practices are engaged in PL activities, which are perceived to align with emerging principles of improving health care and enhance culture, quality, and engagement.

Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis.

PURPOSE: Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STS), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STS. PATIENTS AND METHODS: We enrolled 30 patients with unresectable or metastatic STS to a phase II clinical trial. Patients received ipilimumab and nivolumab for four doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle. RESULTS: ctDNA was detected in at least one sample for 96% of patients. Pretreatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pretreatment to postcryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed. CONCLUSIONS: ctDNA represents a promising biomarker for monitoring response to treatment in patients with advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STS to immunotherapy.

Yttrium-90 radioembolization of renal cell carcinoma metastatic to the liver.

PURPOSE: To investigate the safety and efficacy of yttrium-90 ((90)Y) hepatic radioembolization treatment of patients with liver-dominant metastatic renal cell carcinoma (RCC) refractory to immunotherapy and targeted therapies. MATERIALS AND METHODS: Between March 2006 and December 2010, six patients with metastatic RCC underwent eight radioembolization treatments with (90)Y-labeled resin microspheres for unresectable liver-dominant metastases. All six patients had previous hepatic tumor progression despite targeted therapies or immunotherapies. All had bilobar disease and required whole-liver treatment. Clinical and biochemical toxicities were recorded, and tumor response was assessed every 2-3 months after treatment by cross-sectional imaging. RESULTS: The median dose delivered was 1.89 Gbq (range 0.41-2.03 Gbq). Grade 1 and 2 toxicities were noted in all patients, primarily fatigue. Follow-up imaging was available for five patients. In follow-up periods from 2-64 months (mean 25 months), three patients showed complete responses, and 1 patient showed a partial response by standard imaging criteria, and these patients are alive at 64 months, 55 months, 17 months, and 7 months after treatment. Two patients with rapid progression of disease died within 2 months of treatment, although hepatic malignancy or failure was not the cause of death in either patient. CONCLUSIONS: (90)Y radioembolization is a promising option for liver-dominant metastatic RCC with potential for providing long-term survival in patients refractory to or intolerant of targeted therapies.

Percutaneous cholecystostomy for acute cholecystitis: ten-year experience.

PURPOSE: To review the clinical course of patients with acute cholecystitis treated by percutaneous cholecystostomy, and to identify risk factors retrospectively that predict outcome. MATERIALS AND METHODS: A total of 106 patients diagnosed with acute cholecystitis were treated by percutaneous cholecystostomy during a 10-year period. Seventy-one (67%) presented to the emergency department (ED) specifically for acute cholecystitis, and 35 (23%) were inpatients previously admitted for other conditions. Outcomes of the two groups were compared with respect to severity of illness, leukocytosis, bile culture, liver function tests, imaging features, time intervals from onset of symptoms to medical and percutaneous intervention, and whether surgical cholecystectomy was later performed. RESULTS: Overall, 72 patients (68%) showed an improvement clinically, whereas 34 (32%) showed no improvement or a clinically worsened condition after cholecystostomy. Patients who presented to the ED primarily with acute cholecystitis fared better (84% of patients showed improvement) than inpatients (34% showed improvement; P < .0001). Gallstones were identified in 54% of patients who presented to the ED, whereas acalculous cholecystitis was more commonly diagnosed in inpatients (54%). Patients with sepsis had worse outcomes overall (P < .0001). Bacterial bile cultures were analyzed in 95% of patients and showed positive results in 52%, with no overall effect on outcome. There was no correlation between the time of onset of symptoms until antibiotic therapy or cholecystostomy in either group. Long-term outcomes for both groups were better for those who later underwent cholecystectomy (P < .0001). CONCLUSIONS: Outcomes after percutaneous cholecystostomy for acute cholecystitis are better when the disease is primary and not precipitated by concurrent illness.