Non-Contact Irreversible Electroporation in the Esophagus With a Wet Electrode Approach.

Our objective was to develop a technique for performing irreversible electroporation (IRE) of esophageal tumors while mitigating thermal damage to the healthy lumen wall. We investigated noncontact IRE using a wet electrode approach for tumor ablation in a human esophagus with finite element models for electric field distribution, joule heating, thermal flux, and metabolic heat generation. Simulation results indicated the feasibility of tumor ablation in the esophagus using an catheter mounted electrode immersed in diluted saline. The ablation size was clinically relevant, with substantially lesser thermal damage to the healthy esophageal wall when compared to IRE performed by placing a monopolar electrode directly into the tumor. Additional simulations were used to estimate ablation size and penetration during noncontact wet-electrode IRE (wIRE) in the healthy swine esophagus. A novel catheter electrode was manufactured and wIRE evaluated in seven pigs. wIRE was performed by securing the device in the esophagus and using diluted saline to isolate the electrode from the esophageal wall while providing electric contact. Computed tomography and fluoroscopy were performed post-treatment to document acute lumen patency. Animals were sacrificed within four hours following treatment for histologic analysis of the treated esophagus. The procedure was safely completed in all animals; post-treatment imaging revealed intact esophageal lumen. The ablations were visually distinct on gross pathology, demonstrating full thickness, circumferential regions of cell death (3.52 ± 0.89 mm depth). Acute histologic changes were not evident in nerves or extracellular matrix architecture within the treatment site. Catheter directed noncontact IRE is feasible for performing penetrative ablations in the esophagus while avoiding thermal damage.

Patient Radiation Doses in IR Procedures: The American College of Radiology Dose Index Registry-Fluoroscopy Pilot.

PURPOSE: To update normative data on fluoroscopy dose indices in the United States for the first time since the Radiation Doses in Interventional Radiology study in the late 1990s. MATERIALS AND METHODS: The Dose Index Registry-Fluoroscopy pilot study collected data from March 2018 through December 2019, with 50 fluoroscopes from 10 sites submitting data. Primary radiation dose indices including fluoroscopy time (FT), cumulative air kerma (Ka,r), and kerma area product (PKA) were collected for interventional radiology fluoroscopically guided interventional (FGI) procedures. Clinical facility procedure names were mapped to the American College of Radiology (ACR) common procedure lexicon. Distribution parameters including the 10th, 25th, 50th, 75th, 95th, and 99th percentiles were computed. RESULTS: Dose indices were collected for 70,377 FGI procedures, with 50,501 ultimately eligible for analysis. Distribution parameters are reported for 100 ACR Common IDs. FT in minutes, Ka,r in mGy, and PKA in Gy-cm2 are reported in this study as (n; median) for select ACR Common IDs: inferior vena cava filter insertion (1,726; FT: 2.9; Ka,r: 55.8; PKA: 14.19); inferior vena cava filter removal (464; FT: 5.7; Ka,r: 178.6; PKA: 34.73); nephrostomy placement (2,037; FT: 4.1; Ka,r: 39.2; PKA: 6.61); percutaneous biliary drainage (952; FT: 12.4; Ka,r: 160.5; PKA: 21.32); gastrostomy placement (1,643; FT: 3.2; Ka,r: 29.1; PKA: 7.29); and transjugular intrahepatic portosystemic shunt placement (327; FT: 34.8; Ka,r: 813.0; PKA: 181.47). CONCLUSIONS: The ACR DIR-Fluoro pilot has provided state-of-the-practice statistics for radiation dose indices from IR FGI procedures. These data can be used to prioritize procedures for radiation optimization, as demonstrated in this work.

Patient Radiation Doses in Interventional Radiology Procedures: Comparison of Fluoroscopy Dose Indices between the American College of Radiology Dose Index Registry-Fluoroscopy Pilot and the Radiation Doses in Interventional Radiology Study.

PURPOSE: To compare radiation dose index distributions for fluoroscopically guided interventions in interventional radiology from the American College of Radiology (ACR) Fluoroscopy Dose Index Registry (DIR-Fluoro) pilot to those from the Radiation Doses in Interventional Radiology (RAD-IR) study. MATERIALS AND METHODS: Individual and grouped ACR Common identification numbers (procedure types) from the DIR-Fluoro pilot were matched to procedure types in the RAD-IR study. Fifteen comparisons were made. Distribution parameters, including the 10th, 25th, 50th, 75th, and 95th percentiles, were compared for fluoroscopy time (FT), cumulative air kerma (Ka,r), and kerma area product (PKA). Two derived indices were computed using median dose indices. The procedure-averaged reference air kerma rate (Ka,r¯) was computed as Ka,r / FT. The procedure-averaged x-ray field size at the reference point (Ar) was computed as PKA / (Ka,r × 1,000). RESULTS: The median FT was equally likely to be higher or lower in the DIR-Fluoro pilot as it was in the RAD-IR study, whereas the maximum FT was almost twice as likely to be higher in the DIR-Fluoro pilot than it was in the RAD-IR study. The median Ka,r was lower in the DIR-Fluoro pilot for all procedures, as was median PKA. The maximum Ka,r and PKA were more often higher in the DIR-Fluoro pilot than in the RAD-IR study. Ka,r¯ followed the same pattern as Ka,r, whereas Ar was often greater in DIR-Fluoro. CONCLUSIONS: The median dose indices have decreased since the RAD-IR study. The typical Ka,r rates are lower, a result of the use of lower default dose rates. However, opportunities for quality improvement exist, including renewed focus on tight collimation of the imaging field of view.

Evaluation of an Integrated Spectroscopy and Classification Platform for Point-of-Care Core Needle Biopsy Assessment: Performance Characteristics from Ex Vivo Renal Mass Biopsies.

PURPOSE: To evaluate a transmission optical spectroscopy instrument for rapid ex vivo assessment of core needle cancer biopsies (CNBs) at the point of care. MATERIALS AND METHODS: CNBs from surgically resected renal tumors and nontumor regions were scanned on their sampling trays with a custom spectroscopy instrument. After extracting principal spectral components, machine learning was used to train logistic regression, support vector machines, and random decision forest (RF) classifiers on 80% of randomized and stratified data. The algorithms were evaluated on the remaining 20% of the data set held out during training. Binary classification (tumor/nontumor) was performed based on a decision threshold. Multinomial classification was also performed to differentiate between the subtypes of renal cell carcinoma (RCC) and account for potential confounding effects from fat, blood, and necrotic tissue. Classifiers were compared based on sensitivity, specificity, and positive predictive value (PPV) relative to a histopathologic standard. RESULTS: A total of 545 CNBs from 102 patients were analyzed, yielding 5,583 spectra after outlier exclusion. At the individual spectra level, the best performing algorithm was RF with sensitivities of 96% and 92% and specificities of 90% and 89%, for the binary and multiclass analyses, respectively. At the full CNB level, RF algorithm also showed the highest sensitivity and specificity (93% and 91%, respectively). For RCC subtypes, the highest sensitivity and PPV were attained for clear cell (93.5%) and chromophobe (98.2%) subtypes, respectively. CONCLUSIONS: Ex vivo spectroscopy imaging paired with machine learning can accurately characterize renal mass CNB at the time of tissue acquisition.

The Impact of PIK3R1 Mutations and Insulin-PI3K-Glycolytic Pathway Regulation in Prostate Cancer.

PURPOSE: Oncogenic alterations of the PI3K/AKT pathway occur in >40% of patients with metastatic castration-resistant prostate cancer, predominantly via PTEN loss. The significance of other PI3K pathway components in prostate cancer is largely unknown. EXPERIMENTAL DESIGN: Patients in this study underwent tumor sequencing using the MSK-IMPACT clinical assay to capture single-nucleotide variants, insertions, and deletions; copy-number alterations; and structural rearrangements, or were profiled through The Cancer Genome Atlas. The association between PIK3R1 alteration/expression and survival was evaluated using univariable and multivariable Cox proportional-hazards regression models. We used the siRNA-based knockdown of PIK3R1 for functional studies. FDG-PET/CT examinations were performed with a hybrid positron emission tomography (PET)/CT scanner for some prostate cancer patients in the MSK-IMPACT cohort. RESULTS: Analyzing 1,417 human prostate cancers, we found a significant enrichment of PIK3R1 alterations in metastatic cancers compared with primary cancers. PIK3R1 alterations or reduced mRNA expression tended to be associated with worse clinical outcomes in prostate cancer, particularly in primary disease, as well as in breast, gastric, and several other cancers. In prostate cancer cell lines, PIK3R1 knockdown resulted in increased cell proliferation and AKT activity, including insulin-stimulated AKT activity. In cell lines and organoids, PIK3R1 loss/mutation was associated with increased sensitivity to AKT inhibitors. PIK3R1-altered patient prostate tumors had increased uptake of the glucose analogue 18F-fluorodeoxyglucose in PET imaging, suggesting increased glycolysis. CONCLUSIONS: Our findings describe a novel genomic feature in metastatic prostate cancer and suggest that PIK3R1 alteration may be a key event for insulin-PI3K-glycolytic pathway regulation in prostate cancer.

MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study.

BACKGROUND: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer. METHODS: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting. FINDINGS: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths. INTERPRETATION: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term. FUNDING: Insightec and the National Cancer Institute.

Phase II Study of Neoadjuvant Nivolumab in Patients with Locally Advanced Clear Cell Renal Cell Carcinoma Undergoing Nephrectomy.

Immune checkpoint inhibitor therapy improves survival in patients with metastatic renal cell carcinoma (RCC) but has not been studied well preoperatively in patients with localized disease undergoing nephrectomy. We conducted a single-center study to evaluate the safety and feasibility of neoadjuvant nivolumab in patients undergoing nephrectomy for localized RCC. Eligible patients had a >20% risk of recurrence, as estimated by a preoperative nomogram. Patients received nivolumab every 2 wk for four treatments prior to surgery. The primary endpoints were feasibility, defined as completing at least three treatments without significant surgical delay, and safety, defined as the rate of surgical complications. Treatment effects were assessed by radiomics and immunohistochemistry. A total of 18 patients (11 men; median age 60 yr) with clear cell RCC were enrolled. All received at least one dose of nivolumab and proceeded to nephrectomy without delay; 16/18 patients completed all four doses. Two patients discontinued nivolumab for immune-related adverse events, and four had surgical complications as per the Clavien-Dindo classification. Integrated pathology plus radiomic analysis demonstrated an association between post-treatment immune infiltration and low entropy apparent diffusion coefficient on magnetic resonance imaging. Nivolumab prior to nephrectomy was safe and feasible, without significant surgical delays and with an expected rate of immune-related adverse events. PATIENT SUMMARY: We evaluated the outcomes for patients with localized kidney cancer who received immunotherapy prior to surgery to remove their kidney tumor. In a small group of patients who had cancer confined to the kidney, this approach appeared safe and feasible.

Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma.

PURPOSE: We report our experience with next-generation sequencing to characterize the landscape of actionable genomic alterations in renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: A query of our institutional clinical sequencing database (MSK-IMPACT) was performed that included tumor samples from 38,468 individuals across all cancer types. Somatic variations were annotated using a precision knowledge database (OncoKB) and the available clinical data stratified by level of evidence. Alterations associated with response to immune-checkpoint blockade (ICB) were analyzed separately; these included DNA mismatch repair (MMR) gene alterations, tumor mutational burden (TMB), and microsatellite instability (MSI). Data from The Cancer Genome Atlas (TCGA) consortium as well as public data from several clinical trials in metastatic RCC were used for validation purposes. Multiregional sequencing data from the TRAcking Cancer Evolution through Therapy (TRACERx) RENAL cohort were used to assess the clonality of somatic mutations. RESULTS: Of the 753 individuals with RCC identified in the MSK-IMPACT cohort, 115 showed evidence of targetable alterations, which represented a prevalence of 15.3% [95% confidence interval (CI), 12.7%-17.8%). When stratified by levels of evidence, the alterations identified corresponded to levels 2 (11.3%), 3A (5.2%), and 3B (83.5%). A low prevalence was recapitulated in the TCGA cohort at 9.1% (95% CI, 6.9%-11.2%). Copy-number variations predominated in papillary RCC tumors, largely due to amplifications in the MET gene. Notably, higher rates of actionability were found in individuals with metastatic disease (stage IV) compared with those with localized disease (OR, 2.50; 95% CI, 1.16-6.16; Fisher's P = 0.01). On the other hand, the prevalence of alterations associated with response to ICB therapy was found to be approximately 5% in both the MSK-IMPACT and TCGA cohorts and no associations with disease stage were identified (OR, 1.35; 95% CI, 0.46-5.40; P = 0.8). Finally, multiregional sequencing revealed that the vast majority of actionable mutations occurred later during tumor evolution and were only present subclonally in RCC tumors. CONCLUSIONS: RCC harbors a low prevalence of clinically actionable alterations compared with other tumors and the evidence supporting their clinical use is limited. These aberrations were found to be more common in advanced disease and seem to occur later during tumor evolution. Our study provides new insights on the role of targeted therapies for RCC and highlights the need for additional research to improve treatment selection using genomic profiling.

A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY).

PURPOSE: Prostate specific membrane antigen-targeted positron emission tomography/computerized tomography has the potential to improve the detection and localization of prostate cancer. OSPREY was a prospective trial designed to determine the diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography for detecting sites of metastatic prostate cancer. MATERIALS AND METHODS: Two patient populations underwent 18F-DCFPyL-positron emission tomography/computerized tomography. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. Cohort B enrolled patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Three blinded central readers evaluated the 18F-DCFPyL-positron emission tomography/computerized tomography. Diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography was based on imaging results compared to histopathology. In cohort A, detection of pelvic nodal disease (with specificity and sensitivity as co-primary end points) and of extrapelvic metastases were evaluated. In cohort B, sensitivity and positive predictive value for prostate cancer within biopsied lesions were evaluated. RESULTS: A total of 385 patients were enrolled. In cohort A (252 evaluable patients), 18F-DCFPyL-positron emission tomography/computerized tomography had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement; median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively. In cohort B (93 evaluable patients, median prostate specific antigen 11.3 ng/ml), median sensitivity and positive predictive value for extraprostatic lesions were 95.8% (87.8%-99.0%) and 81.9% (73.7%-90.2%), respectively. CONCLUSIONS: The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that 18F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of 18F-DCFPyL-positron emission tomography/computerized tomography to stage men with high-risk prostate cancer for nodal or distant metastases, and reliably detect sites of disease in men with suspected metastatic prostate cancer.

Anticoagulation reduces iliocaval and iliofemoral stent thrombosis in patients with cancer stented for nonthrombotic venous obstruction.

OBJECTIVE: To identify factors associated with venous stent thrombosis in patients with cancer treated for nonthrombotic iliocaval or iliofemoral venous obstruction. METHODS: We performed a retrospective review of relevant imaging and medical records from 30 consecutive patients with cancer treated at a single center who underwent venous stent placement for nonthrombotic iliocaval or iliofemoral venous obstruction between 2008 and 2018. Follow-up imaging was used to assess stent patency. Variables examined included patient demographics, cancer type, stent characteristics, anticoagulant, and antiplatelet medications and complications of treatment. RESULTS: Overall primary stent patency was 83% (25/30). The median follow-up period was 44 days (range, 3-365 days). Ten percent of patients occluded owing to in-stent thrombosis and 7% owing to tumor compression of the stent without thrombosis. Therapeutic poststent anticoagulation with enoxaparin, warfarin, or a factor Xa inhibitor was initiated in 87% of the patients. Stent thrombosis occurred in one patient in the anticoagulation group (4%) at 50 days. Stent thrombosis occurred in two patients in the nonanticoagulation group (50%), one at 9 days and the other at 91 days. Anticoagulation was found to be protective against stent thrombosis in this population (hazard ratio, 0.015; P = .011). No statistically significant associations were found among the remaining variables. One patient in the anticoagulation group experienced major bleeding (1/26 [4%]). CONCLUSIONS: Iliocaval and iliofemoral stent placement for nonthrombotic malignant venous obstruction is safe with favorable primary patency rates. Therapeutic anticoagulation is associated with less stent thrombosis in patients with cancer stented for nonthrombotic iliocaval and iliofemoral venous obstruction.

Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study.

PURPOSE: Tumor-associated macrophages correlate with increased invasiveness, growth, and immunosuppression. Activation of the colony-stimulating factor-1 receptor (CSF-1R) results in proliferation, differentiation, and migration of monocytes/macrophages. This phase I study evaluated the immunologic and clinical activity, and safety profile of CSF-1R inhibition with the mAb LY3022855. PATIENTS AND METHODS: Patients with advanced refractory metastatic breast cancer (MBC) or metastatic castration-resistant prostate cancer (mCRPC) were treated with LY3022855 intravenously in 6-week cycles in cohorts: (A) 1.25 mg/kg every 2 weeks (Q2W); (B) 1.0 mg/kg on weeks 1, 2, 4, and 5; (C) 100 mg once weekly; (D)100 mg Q2W. mCRPC patients were enrolled in cohorts A and B; patients with MBC were enrolled in all cohorts. Efficacy was assessed by RECIST and Prostate Cancer Clinical Trials Working Group 2 criteria. RESULTS: Thirty-four patients (22 MBC; 12 mCRPC) received ≥1 dose of LY3022855. At day 8, circulating CSF-1 levels increased and proinflammatory monocytes CD14DIMCD16BRIGHT decreased. Best RECIST response was stable disease in five patients with MBC (23%; duration, 82-302 days) and three patients with mCRPC (25%; duration, 50-124 days). Two patients with MBC (cohort A) had durable stable disease >9 months and a third patient with MBC had palpable reduction in a nontarget neck mass. Immune-related gene activation in tumor biopsies posttreatment was observed. Common any grade treatment-related adverse events were fatigue, decreased appetite, nausea, asymptomatic increased lipase, and creatine phosphokinase. CONCLUSIONS: LY3022855 was well tolerated and showed evidence of immune modulation. Clinically meaningful stable disease >9 months was observed in two patients with MBC.

Treatment of Chylous Ascites with Peritoneovenous Shunt (Denver Shunt) following Retroperitoneal Lymph Node Dissection in Patients with Urological Malignancies: Update of Efficacy and Predictors of Complications.

PURPOSE: We investigated the efficacy and analyzed the complication risk factors of peritoneovenous shunt in treating refractory chylous ascites following retroperitoneal lymph node dissection in patients with urological malignancies. MATERIALS AND METHODS: From April 2001 to March 2019 all patients with refractory chylous ascites after retroperitoneal lymph node dissection treated with peritoneovenous shunt were reviewed. Demographic characteristics, technical success, efficacy, patency period and complications were studied. Univariate and multivariate logistic regression analysis was performed to identify predictors of complications. RESULTS: Twenty patients were included in this study. Testicular cancer was the most common malignancy (85%). The mean number of days from surgery to detection of chylous ascites was 21 days (SD 15, range 4 to 65). Ascites permanently resolved after peritoneovenous shunt in 18 patients (90%), leading to shunt removal in 17 patients (85%) between 46 and 481 days (mean 162, SD 141). The mean serum albumin level increased 24% after shunt placement (mean 3.0±0.6 gm/dl before, 3.9±0.8 gm/dl after, p <0.05). The most common complication was occlusion (30%). Relative risk of complications increased significantly when shunt placement was more than 70 days after surgery and in patients with more than 5 paracenteses before peritoneovenous shunt placement (AR 0.71% vs 0.25%, RR 2.9, p <0.048 and AR 0.6% vs 0.125%, RR 4.8, p <0.04, respectively). CONCLUSIONS: Peritoneovenous shunt permanently treated chylous ascites in 90% of patients after retroperitoneal lymph node dissection. Peritoneovenous shunt was removed in 85% of patients. Shunt placement is an effective and safe treatment option for refractory chylous ascites. These patients might benefit from earlier intervention, after 4 to 6 weeks of conservative management as opposed to 2 to 3 months.

11C-Choline PET/CT in Recurrent Prostate Cancer: Retrospective Analysis in a Large U.S. Patient Series.

Our purpose was to evaluate the performance of 11C-choline PET/CT in detecting biochemically recurrent prostate cancer (PCa) in a large non-European cohort (in the context of emerging evidence for prostate-specific membrane antigen PET in this setting) and to map patterns of PCa recurrence. Methods: We retrospectively analyzed 11C-choline PET/CT scans from 287 patients who were enrolled in an imaging protocol based on rising prostate-specific antigen (PSA) levels (mean, 3.43 ng/mL; median, 0.94 ng/mL; range, 0.15-89.91 ng/mL) and suspected recurrent PCa. A total of 187 patients had undergone primary radical prostatectomy (RP) (79/187 had secondary radiotherapy), 30 had undergone primary radiotherapy, and 70 had a persistent PSA elevation after receiving initial treatment (69 after RP, 1 after radiotherapy). The level of suspicion for recurrence on 11C-choline PET/CT was scored (0, negative; 1, equivocal; 2, positive) by 2 readers. The correlation between 11C-choline PET/CT positivity and initial treatment, Gleason score, National Comprehensive Cancer Network stage, PSA level, PSA doubling time, PSA velocity, and time between initial treatment and PET imaging was evaluated. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria were used to map 11C-choline recurrence patterns. Results: Considering scores 1 and 2 as positives, consensus between the 2 readers deemed 66% of the 11C-choline PET/CT scans as positive. When sorted by PSA level, 45% of patients with a PSA of less than 0.5 ng/mL, 56% of patients with a PSA of 0.5-0.99 ng/mL, 70% of patients with a PSA of 1.0-1.99 ng/mL, and 90% of patients with a PSA of at least 2.0 ng/mL scored either 1 or 2 on 11C-choline PET/CT scans. When considering scores of 2 only, 11C-choline PET/CT positivity was 54% (28%, 46%, 62%, and 81%, respectively, for patients with PSA < 0.5 ng/mL, 0.5-0.99 ng/mL, 1.0-1.99 ng/mL, and ≥ 2.0 ng/mL). In multivariate analysis, only PSA level was significantly associated with scan positivity. Pattern analysis showed that pelvic lymph nodes were the most common site of recurrence, and 28% of patients had 11C-choline-positive suspected recurrences outside the initial treatment field. Conclusion:11C-choline PET/CT can detect PCa recurrence even among patients with low PSA levels when interpretation accounts for the clinical context, providing a certain pretest probability. Until prostate-specific membrane antigen agents are fully approved for PCa, choline PET/CT may provide clinical utility.

Imaging of Small Renal Masses before and after Thermal Ablation.

Thermal ablation of small renal masses is increasingly accepted as an alternative to partial nephrectomy, particularly in patients with multiple comorbidities. Many professional societies support this alternate treatment with updated guidelines. Before performing thermal ablation, it is important to stratify risk and assess technical feasibility by evaluating tumor imaging features such as size, location, and centrality. Routine postablation imaging with CT or MRI is necessary for assessment of residual or recurrent tumor, evidence of complications, or new renal masses outside the ablation zone. The normal spectrum and evolution of findings at CT and MRI include a halo appearance of the ablation zone, ablation zone contraction, and ablation zone calcifications. Tumor recurrence frequently manifests at CT or MRI as new nodular enhancement at the periphery of an expanding ablation zone, although it is normal for the ablation zone to enlarge within the first few months. Recognizing early tumor recurrence is important, as small renal masses are often easily treated with repeat ablations. Potential complications of thermal ablation include vascular injury, urine leak, ureteral stricture, nerve injury, and bowel perforation. The risk of these complications may be related to tumor size and location.©RSNA, 2019.

What Physicians and Health Organizations Should Know About Mandated Imaging Appropriate Use Criteria.

The Appropriate Use Criteria Program, enacted by the Centers for Medicare & Medicaid Services in response to the Protecting Access to Medicare Act of 2014 (PAMA), aims to reduce inappropriate and unnecessary imaging by mandating use of clinical decision support (CDS) by all providers who order advanced imaging examinations (magnetic resonance imaging; computed tomography; and nuclear medicine studies, including positron emission tomography). Beginning 1 January 2020, documentation of an interaction with a certified CDS system using approved appropriate use criteria will be required on all Medicare claims for advanced imaging in all emergency department patients and outpatients as a prerequisite for payment. The Appropriate Use Criteria Program will initially cover 8 priority clinical areas, including several (such as headache and low back pain) commonly encountered by internal medicine providers. All providers and organizations that order and provide advanced imaging must understand program requirements and their options for compliance strategies. Substantial resources and planning will be needed to comply with PAMA regulations and avoid unintended negative consequences on workflow and payments. However, robust evidence supporting the desired outcome of reducing inappropriate use of advanced imaging is lacking.

Macrophage-secreted TGF-ß1 contributes to fibroblast activation and ureteral stricture after ablation injury.

Iatrogenic injury to the healthy ureter during ureteroscope-guided ablation of malignant or nonmalignant disease can result in ureteral stricture. Transforming growth factor (TGF)-ß1-mediated scar formation is considered to underlie ureteral stricture, but the cellular sources of this cytokine and the sequelae preceding iatrogenic stricture formation are unknown. Using a swine model of ureteral injury with irreversible electroporation (IRE), we evaluated the cellular sources of TGF-ß1 and scar formation at the site of injury and examined in vitro whether the effects of TGF-ß1 could be attenuated by pirfenidone. We observed that proliferation and α-smooth muscle actin expression by fibroblasts were restricted to injured tissue and coincided with proliferation of macrophages. Collagen deposition and scarring of the ureter were associated with increased TGF-ß1 expression in both fibroblasts and macrophages. Using in vitro experiments, we demonstrated that macrophages stimulated by cells that were killed with IRE, but not LPS, secreted TGF-ß1, consistent with a wound healing phenotype. Furthermore, using 3T3 fibroblasts, we demonstrated that stimulation with paracrine TGF-ß1 is necessary and sufficient to promote differentiation of fibroblasts and increase collagen secretion. In vitro, we also showed that treatment with pirfenidone, which modulates TGF-ß1 activity, limits proliferation and TGF-ß1 secretion in macrophages and scar formation-related activity by fibroblasts. In conclusion, we identified wound healing-related macrophages to be an important source of TGF-ß1 in the injured ureter, which may be a paracrine source of TGF-ß1 driving scar formation by fibroblasts, resulting in stricture formation.

Utility of Core Biopsy Specimen to Identify Histologic Subtype and Predict Outcome for Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma histologic subtype is an important indicator of patient outcomes, so preoperative knowledge of subtype may be helpful to guide surgical planning. We evaluated the sensitivity and prognostic efficacy of specimens from computed tomography-guided core needle biopsies to predict histologic subtype and patient outcome after surgery. METHODS: We retrospectively identified 221 patients with lung adenocarcinoma who underwent computed tomography-guided lung biopsy and subsequent surgical resection. Concordance, accuracy, specificity, and sensitivity of histologic subtypes from core biopsy specimens were compared with surgically resected specimens. Tumor characteristics and biopsy procedural factors were analyzed to determine impact on diagnostic sensitivity. Histologic subtype based on biopsy specimen, clinical, tumor, and treatment variables were also examined in relation to time to progression. RESULTS: Overall concordance of biopsy samples with the predominant subtype from surgical specimens was 77%. Specificity (sensitivity) of detecting a nonaggressive and aggressive subtype were 86% (93%) and 95% (48%), respectively. Length of core specimen and percentage subtype composition in the surgically resected specimen were correlated with improved sensitivity but to a lesser extent with aggressive subtypes. Presence of an aggressive subtype in biopsy specimens was an independent predictor of progression after surgery (subdistribution hazard ratio, 2.51; 95% confidence interval, 1.28-4.94; p = 0.0075). CONCLUSIONS: Specimens from computed tomography-guided core biopsies can predict lung adenocarcinoma progression after surgical resection. Future prospective studies should address the role of core biopsy in preoperative planning.

Volumetric 3D assessment of ablation zones after thermal ablation of colorectal liver metastases to improve prediction of local tumor progression.

PURPOSE: The goal of this study was to develop and evaluate a volumetric three-dimensional (3D) approach to improve the accuracy of ablation margin assessment following thermal ablation of hepatic tumors. METHODS: The 3D margin assessment technique was developed to generate the new 3D assessment metrics: volumes of insufficient coverage (VICs) measuring volume of tissue at risk post-ablation. VICs were computed for the tumor and tumor plus theoretical 5- and 10-mm margins. The diagnostic accuracy of the 3D assessment to predict 2-year local tumor progression (LTP) was compared to that of manual 2D assessment using retrospective analysis of a patient cohort that has previously been reported as a part of an outcome-centered study. Eighty-six consecutive patients with 108 colorectal cancer liver metastases treated with radiofrequency ablation (2002-2012) were used for evaluation. The 2-year LTP discrimination power was assessed using receiver operating characteristic area under the curve (AUC) analysis. RESULTS: A 3D assessment of margins was successfully completed for 93 out of 108 tumors. The minimum margin size measured using the 3D method had higher discrimination power compared with the 2D method, with an AUC value of 0.893 vs. 0.790 (p = 0.01). The new 5-mm VIC metric had the highest 2-year LTP discrimination power with an AUC value of 0.923 (p = 0.004). CONCLUSIONS: Volumetric semi-automated 3D assessment of the ablation zone in the liver is feasible and can improve accuracy of 2-year LTP prediction following thermal ablation of hepatic tumors. KEY POINTS: • More accurate prediction of local tumor progression risk using volumetric 3D ablation zone assessment can help improve the efficacy of image-guided percutaneous thermal ablation of hepatic tumors. • The accuracy of evaluation of ablation zone margins after thermal ablation of colorectal liver metastases can be improved using a volumetric 3D semi-automated assessment approach and the volume of insufficient coverage assessment metric. • The new 5-mm volume-of-insufficient-coverage metric, indicating the volume of tumor plus 5-mm margin that remained untreated, had the highest 2-year local tumor progression discrimination power.

Autologous Blood Patch Injection versus Hydrogel Plug in CT-guided Lung Biopsy: A Prospective Randomized Trial.

Purpose To compare the effect of autologous blood patch injection (ABPI) with that of a hydrogel plug on the rate of pneumothorax at CT-guided percutaneous lung biopsy. Materials and Methods In this prospective randomized controlled trial ( https://ClinicalTrials.gov , NCT02224924), a noninferiority design was used for ABPI, with a 10% noninferiority margin when compared with the hydrogel plug, with the primary outcome of pneumothorax rate within 2 hours of biopsy. A type I error rate of 0.05 and 90% power were specified with a target study population of 552 participants (276 in each arm). From October 2014 to February 2017, all potential study participants referred for CT-guided lung biopsy (n = 2052) were assessed for enrollment. Results The data safety monitoring board recommended the trial be closed to accrual after an interim analysis met prespecified criteria for early stopping based on noninferiority. The final study group consisted of 453 participants who were randomly assigned to the ABPI (n = 226) or hydrogel plug (n = 227) arms. Of these, 407 underwent lung biopsy. Pneumothorax rates within 2 hours of biopsy were 21% (42 of 199) and 29% (60 of 208); chest tube rates were 9% (18 of 199) and 13% (27 of 208); and delayed pneumothorax rates within 2 weeks after biopsy were 1.4% (three of 199) and 1.5% (three of 208) in the ABPI and hydrogel plug arms, respectively. Conclusion Autologous blood patch injection is noninferior to a hydrogel plug regarding the rate of pneumothorax after CT-guided percutaneous lung biopsy. © RSNA, 2018 Online supplemental material is available for this article.