Percutaneous Cryoablation of Plasmacytomas: Oncologic Effectiveness and Adverse Events.

PURPOSE: To evaluate the oncologic outcomes and adverse events associated with cryoablation of plasmacytomas. MATERIALS AND METHODS: Retrospective review of an institutional percutaneous ablation database showed that 43 patients underwent 46 percutaneous cryoablation procedures for treatment of 44 plasmacytomas between May 2004 and March 2021. The treatment of 25 (25 of 44, 56.8%) tumors was augmented with bone consolidation/cementoplasty. The median patient age was 64 years (interquartile range [IQR], 54-69), and 30 of 43 (69.8%) patients were men. The median maximum plasmacytoma diameter was 5.0 cm (IQR, 3.1-7.0). Thirty of 44 (68.2%) tumors were periacetabular, vertebral, or located in the iliac wing. Twenty-nine of 44 (65.9%) cryoablated plasmacytomas were recurrent tumors after prior external beam radiation therapy (EBRT). Survival analyses were performed using the Kaplan-Meier method. Adverse events were graded using Society of Interventional Radiology criteria. RESULTS: The 5-year estimated local tumor recurrence-free survival was 85.3% (95% CI, 74.1%-98.1%), the 5-year estimated new plasmacytoma-free survival was 49.9% (95% CI, 33.9%-73.4%), and the 5-year estimated overall survival was 70.4% (95% CI, 56.9%-87.1%). Nine of 46 (19.6%) major adverse events occurred in 8 patients, including 3 of 46 (6.5%) new or progressive pathologic fractures at the ablation site requiring surgical intervention, 3 of 46 (6.5%) nerve injuries, 1 of 46 (2.2%) avascular necrosis and femoral head collapse, 1 of 46 (2.2%) septic arthritis, and 1 of 46 (2.2%) acute renal failure caused by rhabdomyolysis. CONCLUSIONS: Percutaneous cryoablation is a viable treatment option for patients with plasmacytomas, including those with recurrent plasmacytomas after EBRT. Postcryoablation adverse events are relatively common.

Musculoskeletal Interventional Oncology: A Contemporary Review.

Musculoskeletal interventional oncology is an emerging field that addresses the limitations of conventional therapies for bone and soft-tissue tumors. The field's growth has been driven by evolving treatment paradigms, expanding society guidelines, mounting supportive literature, technologic advances, and cross-specialty collaboration with medical, surgical, and radiation oncology. Safe, effective, and durable pain palliation, local control, and stabilization of musculoskeletal tumors are increasingly achieved through an expanding array of contemporary minimally invasive percutaneous image-guided treatments, including ablation, osteoplasty, vertebral augmentation (with or without mechanical reinforcement via implants), osseous consolidation via percutaneous screw fixation (with or without osteoplasty), tumor embolization, and neurolysis. These interventions may be used for curative or palliative indications and can be readily combined with systemic therapies. Therapeutic approaches include the combination of different interventional oncology techniques as well as the sequential application of such techniques with other local treatments, including surgery or radiation. This article reviews the current practice of interventional oncology treatments for the management of patients with bone and soft-tissue tumors with a focus on emerging technologies and techniques.

Radiofrequency Ablation of Benign and Malignant Thyroid Nodules.

Thyroid nodule treatment has significantly evolved over recent years with attempts to individualize treatment on the basis of the cause of the nodule and patient performance status. The risks and complications associated with surgery and radioactive iodine have promoted interest in additional therapies such as radiofrequency ablation (RFA). RFA creates an electrical current through a target tissue (thyroid nodule) with resultant tissue heating causing coagulative necrosis. National and international groups are beginning to recognize the role of RFA as a viable therapeutic option in the treatment of thyroid nodules. Based on numerous guidelines, RFA is indicated in the treatment of symptomatic benign nodules and autonomously functioning nodules when surgery is refused or when the patient would not tolerate surgery. The treatment of thyroid malignancy with RFA is controversial, with some groups advocating for its use in the treatment of small papillary thyroid cancers in specific scenarios. The most important aspect of RFA is the preprocedural workup and adequate patient selection. Procedural technique varies among centers. However, RFA is typically performed as a single-day-admission outpatient procedure. Methods such as hydrodissection and a moving shot technique are employed to ensure adequate coverage of the nodule without overtreating the peripheries and damaging sensitive structures. As a result, the procedure is well tolerated, and major complications such as recurrent laryngeal nerve injury and nodule rupture are very rare. In the proper patient cohort, thyroid RFA offers an efficacious and safe option in the management of thyroid nodules. An invited commentary by Filippiadis and Vrachliotis is available online. ©RSNA, 2022.

Innovative Fetal Therapy for a Giant Congenital Pulmonary Airway Malformation with Hydrops.

INTRODUCTION: Congenital pulmonary airway malformations (CPAMs) complicated by hydrops portend significant morbidity and mortality, with fetal survival estimates less than 10%. CASE PRESENTATION: We report successful use of ultrasound-guided radiofrequency ablation at 21-week gestation in a hydropic fetus with CPAM, with subsequent resolution of hydrops. Thirty-two-week MRI noted persistent mediastinal shift, and US at 36 weeks and 5 days noted polyhydramnios. Maternal gestational hypertension prompted delivery at 37 weeks, with a cesarean section performed after a failed trial of labor. The infant required CPAP at 100% and weaned to 21%. Tachypnea persisted, and chest CT on day of life 2 demonstrated multiple large cysts in the right lower lobe with anterior pneumothorax. On day of life 3, she successfully underwent a thoracoscopic right lower lobectomy. Adhesions to the chest wall and rib abnormalities were noted. She was extubated to CPAP at the conclusion of the procedure. She was able to wean to 21% on POD2 and transitioned to oral feeds. Her chest tube was removed with resultant ex vacuo pneumothorax noted. She remained asymptomatic and was discharged home on room air POD11. Pathology confirmed a type 1 CPAM. CONCLUSION: In utero radiofrequency ablation may be an adjunct to the management of large CPAM.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Musculoskeletal Oncologic Interventions: Proceedings from the Society of Interventional Radiology and Society of Interventional Oncology Research Consensus Panel.

Musculoskeletal interventions are increasingly used with palliative and curative intent in the multidisciplinary treatment of oncology patients with bone and soft-tissue tumors. There is an unmet need for high-quality evidence to guide broader application and adoption of minimally invasive interventional technologies to treat these patients. Therefore, the Society of Interventional Radiology Foundation and the Society of Interventional Oncology collaborated to convene a research consensus panel to prioritize a research agenda addressing the gaps in the current evidence. This article summarizes the panel's proceedings and recommendations for future basic science and clinical investigation to chart the course for interventional oncology within the musculoskeletal system. Key questions that emerged addressed the effectiveness of ablation within specific patient populations, the effect of combination of ablation with radiotherapy and/or immunotherapy, and the potential of standardization of techniques, including modeling and monitoring, to improve the consistency and predictability of treatment outcomes.

Phase 1 trial of Vismodegib and Erlotinib combination in metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Interplay between the Hedgehog (HH) and epidermal growth factor receptor (EGFR) pathways modulating the outcome of their signaling activity have been reported in various cancers including pancreatic ductal adenocarcinoma (PDAC). Therefore, simultaneous targeting of these pathways may be clinically beneficial. This Phase I study combined HH and EGFR inhibition in metastatic PDAC patients. METHODS: Combined effects of HH and EGFR inhibition using Vismodegib and Erlotinib with or without gemcitabine in metastatic solid tumors were assessed by CT. Another cohort of patients with metastatic PDAC was evaluated by FDG-PET and tumor biopsies-derived biomarkers. RESULTS: Treatment was well tolerated with the maximum tolerated dose cohort experiencing no grade 4 toxicities though 25% experienced grade 3 adverse effects. Recommended phase II dose of Vismodegib and Erlotinib were each 150 mg daily. No tumor responses were observed although 16 patients achieved stable disease for 2-7 cycles. Paired biopsy analysis before and after first cycle of therapy in PDAC patients showed reduced GLI1 mRNA, phospho-GLI1 and associated HH target genes in all cases. However, only half of the cases showed reduced levels of desmoplasia or changes in fibroblast markers. Most patients had decreased phospho-EGFR levels. CONCLUSIONS: Vismodegib and Erlotinib combination was well-tolerated although overall outcome in patients with metastatic PDAC was not significantly impacted by combination treatment. Biomarker analysis suggests direct targets inhibition without significantly affecting the stromal compartment. These findings conflict with pre-clinical mouse models, and thus warrant further investigation into how upstream inhibition of these pathways is circumvented in PDAC.

Drivers of the Decision to Biopsy and Follow-Up of Small Suspicious Thyroid Nodules.

OBJECTIVE: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center. METHODS: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied. RESULTS: We identified 141 nodules in 129 patients: mean age 58.1±14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5-188.7]), radiology recommendation for biopsy (OR 2.6 [1.8-3.9]) and radiology report of the nodule as "suspicious" (OR 2.1 [1.4-3.2]). Patient's age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations. CONCLUSION: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules. ABBREVIATIONS: ATA = American Thyroid Association; OR = odds ratio.

Systematic optimization of ultrasound grayscale imaging presets and its application in abdominal scanning.

PURPOSE: Ultrasound grayscale imaging preset optimization has often been qualitative and dependent upon vendor application specialists. This study aimed to propose a systematic approach for grayscale imaging preset optimization and apply the approach in a clinical abdominal scan setting. METHODS: A six-step approach was detailed including identification of clinical task, adjustment of basic parameters, fine-tuning of advanced parameters, image performance metrics confirmation, clinical evaluation and data analysis, and implementation of new presets and monitoring of clinical usage. Its application in an abdominal scanning task was described for each step with phantoms, volunteers, and software tools. RESULTS: Clinical image data analytics facilitated the understanding of the imaging task, relevant transducers, and target characteristics, in addition to specific requests from radiologists. Quantitative measurements were made on global image contrast and gray map function. In addition, clinically relevant phantoms and volunteer scans without and with acoustic distortion layers were involved to determine the new presets. Furthermore, phantom signal to noise ratio study and clinical evaluation using volunteers with different body habitus were utilized to confirm the superiority of the new presets. Quantitative clinical usage monitoring demonstrated successful implementation of the new presets. CONCLUSIONS: A systematic approach for grayscale imaging preset optimization has been proposed and successfully applied for a specific clinical task. This approach was designed to be generalizable and relatively flexible, which would facilitate movement away from previous qualitative and subjective approaches.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group. Postablation tumor growth was monitored up to 7 days. Tumor volumes were compared for drug or ablation groups by using two-way analysis of variance. N1S1 HCC cells pretreated with BEZ235 or control and subjected to moderate heat stress (45°C for 10 minutes) or control (37°C for 10 minutes) were analyzed by using mass spectrometry. Protein interaction networks were derived from protein expression analysis software, and cellular function activation state (Z-score) and fold-change in AKT phosphorylation were calculated.ResultsThere was a 37%-75% reduction in HCC tumor volume by day 7 after ablation in the BEZ235 plus ablation group (713 mm3 ± 417) compared with vehicle plus sham (1559 mm3 ± 552), vehicle plus ablation (1041 mm3 ± 591), and BEZ235 plus sham (1108 mm3 ± 523) groups (P < .001, P = .04, and P = .005, respectively). PI3K/mTOR inhibition prevented moderate heat stress-induced AKT signaling (Z-score, -0.2; P < .001) and isoform-specific AKT phosphorylation compared with the vehicle plus heat stress group. PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by White in this issue.

Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling.

Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group). Experiments were repeated with rats randomly assigned to receive either the adjuvant phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor (NVP-BEZ235) or the vehicle control. Heat-stressed HCC cells and hepatocytes were analyzed by using microarray or quantitative real-time polymerase chain reaction analysis for growth factor expression (three or more experiments). Groups were compared by using one- or two-way analysis of variance, and post hoc pairwise comparison was performed with the Dunnett test. Results There were more non-heat-stressed HCC cells when cells were cocultured with cells subjected to moderate but not physiologic or severe heat stress (P < .001 for both). Local intrahepatic N1S1 tumors were larger at day 18 in the 3W×60s (mean, 3102 mm3 ± 463 [standard error]; P = .004) and 3W×90s (mean, 3538 mm3 ± 667; P < .001) groups than in the sham group (mean, 1363 mm3 ± 361) but not in distant intrahepatic tumors (P = .31). Adjuvant BEZ235 resulted in smaller N1S1 tumors in the BEZ235 and laser thermal ablation group than in the vehicle control and laser thermal ablation group (mean, 1731 mm3 ± 1457 vs 3844 mm3 ± 2400, P < .001). Moderate heat stress induced expression of growth factors in HCC cells and hepatocytes, including heparin-binding growth factor, fibroblast growth factor 21, and nerve growth factor (range, 2.9-66.9-fold; P < .05). Conclusion Moderate heat stress and laser thermal ablation induce hepatocellular carcinoma growth, which is prevented with adjuvant PI3K/mTOR/protein kinase B inhibition.

A Comparison of Bleeding Complications in Patients Undergoing Percutaneous Renal Cryoablation Using Cryoprobes with and without Heat-Based Track Ablation.

PURPOSE: To determine if the use of heat-based track ablation with new-generation cryoprobes is associated with decreased renal cryoablation bleeding complications. MATERIALS AND METHODS: Eighty-nine patients who underwent percutaneous cryoablation for treatment of a solitary renal mass with the use of cryoprobes with track ablation (CwTA) from October 29, 2015, to May 18, 2017, were compared with a propensity score-matched control group of 178 patients who underwent treatment with the use of cryoprobes without track ablation (Cw/oTA) from January 5, 2012, to October 28, 2015. Bleeding complications were assessed with the use of the Clavien-Dindo classification system and compared between the matched patient groups by means of conditional logistic regression, both univariately and in a multivariate model to adjust for imbalanced covariates. Change in patient hemoglobin was evaluated as a secondary measure of periprocedural bleeding. RESULTS: Seven of the 89 patients (7.9%) who underwent percutaneous renal cryoablation with the use of CwTA developed major (grade ≥3) bleeding complications, versus 13 of the 178 patients (7.3%) treated with the use of Cw/oTA. Conditional logistic regression analysis adjusted for potential confounders showed that major, minor, and overall bleeding complications were not associated with the type of cryoprobes used for treatment (P values .727, .370, and .733, respectively). There was also no significant difference in postprocedural change in hemoglobin for patients treated with the use of CwTA compared with Cw/oTA (P = .909). Furthermore, total duration of track ablation in patients with bleeding complications (mean 169 seconds, SD 68, range 60-240) was not significantly different than in patients without bleeding complications (mean 171 seconds, SD 86, range 30-360; P = .940). CONCLUSIONS: The use of cryoprobes with heat-based track ablation did not decrease the incidence of bleeding complications after renal cryoablation compared with procedures performed without track ablation.

Percutaneous Cryoablation of Solitary, Sporadic Renal Cell Carcinoma: Outcome Analysis Based on Clear-Cell versus Papillary Subtypes.

PURPOSE: To evaluate treatment outcomes with percutaneous cryoablation (PCA) based on renal cell carcinoma (RCC) histology. METHODS AND MATERIALS: Patients treated with PCA for a solitary, sporadic stage T1a RCC from 2003 to 2016 were identified from a single institution's renal ablation registry. Patients with multiple tumors, history of RCC, or genetic syndromes associated with RCC (n = 60); no specific RCC subtype determined from core biopsy (n = 66); RCC subtype other than clear-cell or papillary (n = 7); or less than 3 mo of follow-up imaging (n = 5) were excluded. In total, 173 patients met study inclusion criteria. Oncologic outcomes, clinical outcomes, and complications were evaluated based on tumor subtype. RESULTS: Of the 173 patients who underwent PCA for a stage T1a RCC, 130 (75%) had clear-cell RCC (ccRCC) and 43 (25%) had papillary RCC (pRCC). Median tumor size was 2.9 cm (range, 1.3-4.0 cm). Technically successful cryoablation was achieved in all 173 patients. Local tumor recurrence developed in 6 patients with ccRCC (4.6%), new renal tumors developed in 1 patient (0.8%), and metastatic RCC developed in 1 patient (0.8%) who also had local tumor recurrence. No patients with pRCC showed local tumor recurrence, new renal tumors, or metastatic disease. The 5-year disease-free survival rate in patients with ccRCC was 88%, compared with 100% in patients with pRCC (P = .48). Nine patients (5.2%), all with ccRCC, experienced major complications (P = .11). CONCLUSIONS: Percutaneous ablation is a viable treatment option for patients with clinical stage T1a pRCC and ccRCC. Percutaneous ablation may be a very favorable treatment strategy particularly for pRCC.

Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies.

The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress (n ≥ 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W × 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression (n ≥ 6 per group). Serum was collected from patients undergoing thermal ablation for HCC (n = 16) at baseline, 3-6, and 18-24 h postablation and analyzed for VGF expression. Data were analyzed using ordinary or repeated-measures one-way analysis of variance and post hoc pairwise comparison with Dunnett's test. Moderate heat stress induced time-dependent VGF mRNA (3- to 15-fold; p < 0.04) and protein expression and secretion (3.1- to 3.3-fold; p < 0.05). Thermal ablation induced VGF expression at the hepatic ablation margin at 1 and 3 days postablation but not remote from the ablation zone or distant intrahepatic lobe. There was no detectable serum VGF following hepatic thermal ablation in rats and no increase in serum VGF following HCC thermal ablation in patients at 3-6 and 18-24 h postablation compared to baseline (0.71- and 0.63-fold; p = 0.27 and p = 0.16, respectively). Moderate heat stress induces expression and secretion of VGF in HCC cells and hepatocytes in vitro, and thermal ablation induces local intrahepatic but not distant intrahepatic or systemic VGF expression in vivo.

Heat stress induced, ligand-independent MET and EGFR signalling in hepatocellular carcinoma.

PURPOSE: The aims of the present study were 2-fold: first, to test the hypothesis that heat stress induces MET and EGFR signalling in hepatocellular carcinoma (HCC) cells and inhibition of this signalling decreases HCC clonogenic survival; and second, to identify signalling pathways associated with heat stress induced MET signalling. MATERIALS AND METHODS: MET+ and EGFR+ HCC cells were pre-treated with inhibitors to MET, EGFR, PI3K/mTOR or vehicle and subjected to heat stress or control ± HGF or EGF growth factors and assessed by colony formation assay, Western blotting and/or quantitative mass spectrometry. IACUC approved partial laser thermal or sham ablation was performed on orthotopic N1S1 and AS30D HCC tumours and liver/tumour assessed for phospho-MET and phospho-EGFR immunostaining. RESULTS: Heat-stress induced rapid MET and EGFR phosphorylation that is distinct from HGF or EGF in HCC cells and thermal ablation induced MET but not EGFR phosphorylation at the HCC tumour ablation margin. Inhibition of the MET and EGFR blocked both heat stress and growth factor induced MET and EGFR phosphorylation and inhibition of MET decreased HCC clonogenic survival following heat stress. Pathway analysis of quantitative phosphoproteomic data identified downstream pathways associated with heat stress induced MET signalling including AKT, ERK, Stat3 and JNK. However, inhibition of heat stress induced MET signalling did not block AKT signalling. CONCLUSIONS: Heat-stress induced MET and EGFR signalling is distinct from growth factor mediated signalling in HCC cells and MET inhibition enhances heat stress induced HCC cell killing via a PI3K/AKT/mTOR-independent mechanism.

Development of a robust MRI fiducial system for automated fusion of MR-US abdominal images.

We present the development of a two-component magnetic resonance (MR) fiducial system, that is, a fiducial marker device combined with an auto-segmentation algorithm, designed to be paired with existing ultrasound probe tracking and image fusion technology to automatically fuse MR and ultrasound (US) images. The fiducial device consisted of four ~6.4 mL cylindrical wells filled with 1 g/L copper sulfate solution. The algorithm was designed to automatically segment the device in clinical abdominal MR images. The algorithm's detection rate and repeatability were investigated through a phantom study and in human volunteers. The detection rate was 100% in all phantom and human images. The center-of-mass of the fiducial device was robustly identified with maximum variations of 2.9 mm in position and 0.9° in angular orientation. In volunteer images, average differences between algorithm-measured inter-marker spacings and actual separation distances were 0.53 ± 0.36 mm. "Proof-of-concept" automatic MR-US fusions were conducted with sets of images from both a phantom and volunteer using a commercial prototype system, which was built based on the above findings. Image fusion accuracy was measured to be within 5 mm for breath-hold scanning. These results demonstrate the capability of this approach to automatically fuse US and MR images acquired across a wide range of clinical abdominal pulse sequences.

Retrospective Review of Percutaneous Image-Guided Ablation of Oligometastatic Prostate Cancer: A Single-Institution Experience.

PURPOSE: To retrospectively review and report the efficacy and safety of percutaneous image-guided ablation (cryoablation or radiofrequency ablation) in the treatment of oligometastatic prostate cancer. MATERIALS AND METHODS: An institutional registry was retrospectively reviewed and revealed 16 patients with oligometastatic prostate cancer (median age, 67 y; range, 50-86 y) who underwent percutaneous image-guided ablation to treat 18 metastatic sites. A subgroup of 7 patients with 8 metastases were androgen-deprivation therapy (ADT)-naïve and underwent ablation to delay initiation of ADT. Local tumor control, progression-free survival (PFS), ADT-free survival, and procedural complications were analyzed. RESULTS: Local tumor control was achieved in 15 of 18 metastases (83%) at a median follow-up of 27 months (range, 5-56 mo). Local tumor recurrence was found in 3 of 18 metastases (17%), with a median time to local recurrence of 3.5 months (range, 3-38 mo). Estimated PFS rates at 12 and 24 months were 56% (95% confidence interval [CI], 30%-76%) and 43% (95% CI, 19%-65%), respectively. In the 7 ADT-naïve patients, local tumor control was achieved in all metastases, and the median ADT-free survival period was 29 months. There were no major procedural complications. CONCLUSIONS: In this cohort of patients with oligometastatic prostate cancer, percutaneous image-guided ablation was feasible and well tolerated and achieved acceptable local tumor control rates. Percutaneous ablation may be of particular utility in patients who wish to delay initiation of ADT.

Outcomes of Ultrasound-Guided Thrombin Injection of Nongroin Arterial Pseudoaneurysms.

PURPOSE: To evaluate success and complication rates of percutaneous ultrasound-guided thrombin injection of nongroin pseudoaneurysms (PSAs). MATERIALS AND METHODS: Retrospective review of a prospectively maintained institutional database yielded 39 cases of arterial PSAs occurring at nongroin sites that were treated with percutaneous ultrasound-guided thrombin injection between 2000 and 2016 (average patient age 69.2 y ± 14.0). Of PSAs, 74.4% (29/39) arose in the upper extremities, and 92.3% (36/39) were iatrogenic. The brachial artery was the most commonly affected vessel (51.3% [20/39]), and arterial access was the most common cause (56.4% [22/39]). Average overall PSA size was 2.4 cm (range, 0.5-7.2 cm); average amount of thrombin injected was 320 IU (range, 50-2,000 IU). Technical success was defined as absence of flow within the PSA immediately after thrombin injection. Treatment success was defined as sustained thrombosis on follow-up imaging obtained at 1-3 days after treatment. RESULTS: Technical and treatment success rates of thrombin injections were 100% (39/39) and 84.8% (28/33), respectively. Longer term follow-up imaging (average 71 d; range, 12-201 d) was available for 7 of the treatment successes with 100% (7/7) showing sustained thrombosis. Comparing treatment successes and failures, there was no significant difference in average PSA size (2.3 cm vs 2.0 cm, P = .51) or average amount of thrombin injected (360 IU vs 180 IU, P = .14). There were no complications. CONCLUSIONS: Ultrasound-guided thrombin injection is a safe, efficacious treatment option for PSAs arising in nongroin locations.

Ablation of Musculoskeletal Metastases.

OBJECTIVE: The purpose of this article is to summarize the evidence supporting thermal ablation of musculoskeletal metastases on the basis of clinical application and to describe an approach to percutaneous ablative treatment, including patient workup, procedural strategy and techniques, and postablation follow-up. CONCLUSION: Percutaneous ablation of musculoskeletal metastases may result in significant pain palliation, prevention of morbidity from skeletal-related events, and local tumor control. This minimally invasive approach has unique advantages compared with surgery or radiation therapy.

Utility of PET/CT After Cryoablation for Early Identification of Local Tumor Progression in Osseous Metastatic Disease.

OBJECTIVE: The purpose of this study is to evaluate the utility of combined PET/CT for the detection of early local tumor progression after cryoablation of bone metastases. MATERIALS AND METHODS: A retrospective single-institution review revealed 61 consecutive patients with 80 separate bone metastases treated with cryoablation who were evaluated with a preablation PET/CT and at least two postablation PET/CT examinations between September 2007 and July 2015. Patients were excluded if they had local therapy or pathologic fracture after ablation. The patients were grouped according to postcryoablation disease status (i.e., local tumor progression or not) and PET radiotracer (i.e., 11C-choline or 18F-FDG) used. The maximum standardized uptake value (SUVmax) ratio (i.e., ratio of SUVmax to blood pool) was calculated within each osseous metastasis before and after cryoablation, and these were then compared between groups. RESULTS: Of the 61 patients and 80 ablations performed, 32 patients were imaged with FDG PET/CT and 29 were imaged with 11C-choline PET/CT. Twenty-three patients imaged with FDG and 13 patients imaged with 11C-choline had evidence of local tumor progression on all postablation PET/CT examinations. The SUVmax ratio was significantly higher in patients with local tumor progression on the first and most remote postcryoablation PET/CT examinations for both FDG and 11C-choline (p < 0.001 in all cases). There was no significant difference in the postablation systemic therapy between the groups with and without local tumor progression. CONCLUSION: Increased SUVmax ratio in patients after cryoablation for osseous metastatic disease should raise concern about local tumor progression independently of time after ablation.