Regorafenib in patients with advanced Ewing sarcoma: results of a non-comparative, randomised, double-blind, placebo-controlled, multicentre Phase II study.

BACKGROUND: The REGOBONE multi-cohort study explored the efficacy and safety of regorafenib for patients with advanced bone sarcomas; this report details the Ewing sarcoma (ES) cohort. METHODS: Patients with relapsed ES progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progression. The primary endpoint was the progression-free rate at 8 weeks. With one-sided α of 0.05, and 80% power, at least 14/24 progression-free patients at 8 weeks were needed for success. RESULTS: From September 2014 to November 2019, 41 patients were accrued. 36 patients were evaluable for efficacy: 23 on regorafenib and 13 on placebo. Thirteen patients (56%; one-sided 95% CI [37.5%-[)) were progression-free at 8 weeks on regorafenib vs. 1 (7.7%; 95% CI [0.4%-[) on placebo. Median PFS was 11.4 weeks on regorafenib, and 3.9 weeks on placebo. Ten placebo patients crossed over to receive regorafenib after progression. The most common grade ≥3 regorafenib-related adverse events were pain (22%), asthenia (17%), thrombocytopenia (13%) and diarrhoea (13%). CONCLUSION: Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy.

Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children.

BACKGROUND AND PURPOSE: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. METHODS: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. RESULTS: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8-13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%-99.1%) and 79.0% (95% CI, 54.4%-94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912-1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. CONCLUSIONS: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: 3618210420, 2217698.

Rectal Artery Embolization for Hemorrhoidal Disease: Anatomy, Evaluation, and Treatment Techniques.

Chronic hemorrhoidal disease is a common anorectal condition that leads to hemorrhoidal hyperplasia, which affects millions of people worldwide and is a significant medical and socioeconomic issue. Rectal bleeding is one of the main chronic symptoms. Recurrent rectal bleeding can alter an individual's quality of life and, more rarely, cause anemia. Pain is less common, occurring only in the event of complications such as congestive exacerbation, external hemorrhoidal thrombosis, or fissures. The most standard treatment involves dietary and hygiene measures, use of phlebotonic drugs, and nonsurgical treatment such as infrared photocoagulation or elastic band ligation. Excisional treatments such as hemorrhoidectomy and hemorrhoidopexy are the reference standards for treatment of hemorrhoidal disease. Embolization of the rectal arteries (ie, emborrhoid) has recently emerged as an effective treatment option, with few reported adverse effects, minimal blood loss, and a same-day hospital procedure. Hemorrhoid embolization is performed by using femoral or radial access. The inferior mesenteric artery and then the superior rectal arteries are catheterized with a microcatheter. Embolization can be performed by using different agents. Studies have shown improvement in symptoms and high technical success rates after treatment. The basic principles of hemorrhoid embolization that must be understood to achieve effective treatment, including those related to patient evaluation, the arterial anatomy, basic embolization, and published results, are reviewed. An invited commentary by Thompson and Kelley is available online. ©RSNA, 2022.

Progression of adenomyosis magnetic resonance imaging features under ulipristal acetate for symptomatic fibroids.

RESEARCH QUESTION: What is the evolution of adenomyosis on magnetic resonance imaging (MRI) after a 3-month treatment course of daily 5 mg doses of ulipristal acetate (UPA) for symptomatic fibroids? DESIGN: A monocentric prospective pilot study on patients who underwent a 3-month treatment course of UPA for symptomatic fibroids between January 2014 and December 2017. Patients underwent pelvic MRI shortly before (pre-MRI) and after treatment (post-MRI). The diagnosis of adenomyosis on MRI was defined by the observation of intramyometrial cysts and/or haemorrhagic foci within these cystic cavities and/or a thickening of the junctional zone >12 mm. The progression of adenomyosis was defined by the presence of at least one of the aforementioned criteria of adenomyosis on the pre-MRI and by at least one of the following on the post-MRI: (i) increased thickness of the junctional zone ≥20% and/or (ii) increased number of intramyometrial cysts. The appearance of adenomyosis was defined by the absence of the aforementioned criteria of adenomyosis on the pre-MRI and the presence of at least one of these criteria on the post-MRI. RESULTS: Seventy-two patients were included. The MRI features of adenomyosis progressed for 12 of 15 patients (80.0%) for whom adenomyosis was identified on the pre-MRI. An appearance of adenomyosis was identified after treatment for 15 of 57 patients (26.3%) for whom adenomyosis was not identified on the pre-MRI. CONCLUSIONS: A 3-month treatment course of daily 5 mg doses of UPA could provoke a short-term progression or an emergence of typical adenomyosis intramyometrial cysts on MRI examinations.

Safety and Efficacy of Peripheral Embolization with EASYX Liquid Embolic Agent: A Multicenter Prospective Study.

PURPOSE: To evaluate the clinical safety and efficacy of EASYX, a new nonadhesive precipitating liquid embolic agent based on a polyvinyl alcohol ether polymer labeled with iodine molecules, for peripheral embolization. MATERIALS AND METHODS: This open-label prospective multicenter study was conducted on 50 consecutive patients treated with embolization using EASYX in 3 academic hospitals from April 2018 to July 2019. Indications for embolization were symptomatic varicocele (n = 15), type II endoleak (n = 8), acute hemorrhage (n = 16), portal vein embolization (PVE; n = 9), or angiomyolipoma (AML; n = 2). Patient characteristics, technical and clinical success rates, pain at injection, and satisfaction of the interventional radiologists were assessed. Follow-up imaging was performed using ultrasound for varicoceles (at 1 month) and computed tomography (CT) for the other indications (at 3 or 6 months). RESULTS: The immediate technical success rate was 98%. The clinical success rates were 100% for acute hemorrhage and type II endoleaks, 89% for PVE, 86% for varicoceles, and 50% for AMLs. Patients who underwent PVE showed significant hypertrophy of the future liver remnant at follow-up (P < .001), and 55.6% of patients proceeded to hepatectomy. The absence of artifacts on imaging allowed improved monitoring of the aneurysmal sac in patients with type II endoleaks. The satisfaction rate of the interventional radiologists was >90% for 5 of 7 items. CONCLUSIONS: EASYX as a novel copolymer liquid embolic agent was safe and efficient for peripheral embolization. The absence of tantalum allowed reduced CT artifacts on imaging follow-up, which was especially useful in patients with type II endoleaks.

Catheter-Directed Hemorrhoidal Dearterialization Technique for the Management of Hemorrhoids: A Meta-Analysis of the Clinical Evidence.

PURPOSE: To assess the efficacy and safety of a catheter-directed hemorrhoidal dearterialization technique for the management of hemorrhoidal bleeding. MATERIALS AND METHODS: A systematic review and meta-analysis of pubmed, cochrane, and scopus databases was conducted according to the preferred reporting items for systematic reviews and meta-Analysis (PRISMA) guidelines. Clinical studies reporting on catheter-directed hemorrhoidal dearterialization for rectal bleeding were analyzed. RESULTS: Fourteen studies (n = 362) were identified. The mean maximum follow-up duration was 12.1 months (SD, 7.31; range, 1-28; median, 12), and the mean length of hospital stay was 1.5 days (SD, 1.1; range, 0-2.5). The mean technical success was 97.8% (SD, 3.5), and the mean clinical success was 78.9% (SD, 10.5). A statistically significant reduction in the french bleeding score before and after embolization was noted (P = .004). In subgroup analysis, when the coils-only group was compared with the coils and particles group, the average rebleeding rate was 21.5% (n = 111; SD, 18.2; range, 0%-44%) versus 10.05% (N = 108; SD, 4.8; range, 5%-15.7%), respectively (P < .0001). No bowel ischemia/necrosis or anorectal complications were reported. CONCLUSIONS: The current preliminary clinical evidence suggests that catheter-directed hemorrhoidal dearterialization is an effective and safe procedure for the treatment of hemorrhoidal bleeding. The standardization of the technique and the generation of higher level evidence will be required to compare this minimally invasive procedure with more invasive surgical options for patients with grades I-III hemorrhoids and chronic bleeding.

Description of morphological evolution of lung tumors treated by percutaneous radiofrequency ablation: long term follow-up of 100 lesions with chest CT.

PURPOSE: Radiofrequency ablation (RFA) is a safe and effective minimally invasive treatment for pulmonary tumors. Patterns on chest computed tomography (CT) after RFA are classified into five types; however, the follow-up has not been fully described. The objectives of this study were to describe (1) the CT pattern 3 years after RFA and (2) its evolution over 7 years. MATERIALS AND METHODS: Lesions treated with RFA between 2009 and 2017 and with ≥3 years of follow-up CT data were included. Lesions with local recurrences were excluded from the study. The morphology of the ablation zone was classified as nodular, fibrotic, atelectatic, cavitary, and disappeared. Other initial anatomical parameters were recorded. Kruskal-Wallis or Chi-square tests were used to compare the groups. RESULTS: One hundred lung RFA scars were included, and a retrospective longitudinal study was performed. Three years after RFA, nodular, fibrotic, atelectatic, and cavitary scars, and disappearance were observed in 49%, 36%, 5%, 3%, and 6% of the scars, respectively. Evolution over 7 years showed that the fibrosis, atelectasis, and disappearance remained stable over time, whereas 28% of nodular scars evolved into fibrotic scars. Additionally, 45% of cavitary scars evolved into nodular scars. Pleural contact was associated with disappearance, and the use of a 20-mm needle was associated with atelectasis. CONCLUSION: Follow-up after RFA showed that fibrosis, disappearance, and atelectasis remained stable over time. Nodular scars could evolve into fibrotic scars, and cavitary scars could evolve into nodular scars.

Percutaneous lung and liver CT-guided ablation on swine model using microwave ablation to determine ablation size for clinical practice.

PURPOSE: Microwave ablation (MWA) provides an effective treatment of lung and liver tumors but suffers from a lack of reproducibility of ablation size among currently available technologies. In-vitro evaluations are far removed from clinical practices because of uninfused tissue. This study is in-vivo preclinical testing of a new MWA system on swine lungs and liver. MATERIALS AND METHODS: All ablations were performed under CT guidance and multiple algorithms were tested with a power of 50, 75, and 100 W for durations of 3, 5, 8, 10, and 15 min. A 3 D-evaluation of the ablation zone was carried out using enhanced-CT. The sphericity index, coefficients of variation, and energy efficiency (which corresponds to the volume yield according to the power supplied) were calculated. RESULTS: Fifty liver and 48 lung ablations were performed in 17 swine. The sphericity index varies from 0.50 to 0.80 for liver ablations and from 0.40 to 0.69 for lung ablations. The coefficient of variation was below 15% for 4/5 and 4/8 protocols for lung and liver ablations, respectively. The energy efficiency seems to decrease with the duration of the ablation from 0.60 × 10-3 cm3/J (75 W, 3 min) to 0.26 × 10-3 cm3/J (100 W, 15 min) in the liver and from 0.57 × 10-3 cm3/J (50 W, 10 min) to 0.42 × 10-3 cm3/J (100 W, 12 min) in the lungs. CONCLUSION: A shorter treatment time provides the best energy efficiency, and the best reproducibility is obtained for a 10 min treatment duration. The system tested provides an interesting reproducibility in both lung and liver measurements. Our results may help interventional radiologists in the optimal selection of treatment parameters.

Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study.

BACKGROUND: Regorafenib has proven activity in patients with pretreated gastrointestinal stromal tumours and colorectal and hepatocellular carcinoma. We designed REGOBONE to assess the efficacy and safety of regorafenib for patients with progressive metastatic osteosarcoma and other bone sarcomas. This trial comprised four parallel independent cohorts: osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. In this Article, we report the results of the osteosarcoma cohort. METHODS: In this non-comparative, double-blind, placebo-controlled, phase 2 trial, patients aged 10 years or older with histologically confirmed osteosarcoma whose disease had progressed after treatment with one to two previous lines of chemotherapy for metastatic disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly assigned (2:1) to receive either oral regorafenib (160 mg/day, for 21 of 28 days) or matching placebo. Patients in both groups also received best supportive care. Randomisation was done using a web-based system and was stratified (permuted block) by age at inclusion (<18 vs ≥18 years old). Investigators and patients were masked to treatment allocation. Patients in the placebo group, after centrally confirmed progressive disease, could cross over to receive regorafenib. The primary endpoint was the proportion of patients without disease progression at 8 weeks. Analyses were done by modified intention to treat (ie, patients without any major entry criteria violation who initiated masked study drug treatment were included). All participants who received at least one dose of study drug were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT02389244, and the results presented here are the final analysis of the osteosarcoma cohort (others cohorts are ongoing). FINDINGS: Between Oct 10, 2014, and April 4, 2017, 43 adult patients were enrolled from 13 French comprehensive cancer centres. All patients received at least one dose of assigned treatment and were evaluable for safety; five patients were excluded for major protocol violations (two in the placebo group and three in the regorafenib group), leaving 38 patients who were evaluable for efficacy (12 in the placebo group and 26 in the regorafenib group). 17 of 26 patients (65%; one-sided 95% CI 47%) in the regorafenib group were non-progressive at 8 weeks compared with no patients in the placebo group. Ten patients in the placebo group crossed over to receive open-label regorafenib after centrally confirmed disease progression. 13 treatment-related serious adverse events occurred in seven (24%) of 29 patients in the regorafenib group versus none of 14 patients in the placebo group. The most common grade 3 or worse treatment-related adverse events during the double-blind period of treatment included hypertension (in seven [24%] of 29 patients in the regorafenib group vs none in the placebo group), hand-foot skin reaction (three [10%] vs none), fatigue (three [10%] vs one [3%]), hypophosphataemia (three [10%] vs none), and chest pain (three [10%] vs none). No treatment-related deaths occurred. INTERPRETATION: Regorafenib demonstrated clinically meaningful antitumour activity in adult patients with recurrent, progressive, metastatic osteosarcoma after failure of conventional chemotherapy, with a positive effect on delaying disease progression. Regorafenib should be further evaluated in the setting of advanced disease as well as potentially earlier in the disease course for patients at high risk of relapse. Regorafenib might have an important therapeutic role as an agent complementary to standard cytotoxic chemotherapy in the therapeutic armamentarium against osteosarcoma. FUNDING: Bayer HealthCare.

Predictors of uterine fibroid volume reduction under ulipristal acetate: a prospective MRI study.

RESEARCH QUESTION: Can patient and/or uterine fibroid characteristics predict the volume reduction of fibroids under ulipristal acetate (UPA) treatment? DESIGN: This was a monocentric observational prospective cohort study of women with symptomatic fibroids who were willing to undergo surgery after a 3-month treatment of daily 5 mg doses of UPA. Patients underwent magnetic resonance imaging before and after treatment, and the volumes of the three largest fibroids were assessed. The reduction in volume was assessed qualitatively: fibroids decreasing in volume were considered to be 'responsive' to treatment, and fibroids that were stable or increased in volume were considered to be 'non-responsive'. Comparisons were made of patient (age and body mass index) and fibroid (initial volume, number and location) characteristics between fibroids that were responsive and non-responsive to UPA treatment. RESULTS: Fifty-three women were included in the final analysis and 116 fibroids were measured. The initial number and initial volume of the fibroids were statistically associated with the response to UPA treatment (adjusted odds ratio [OR] 0.645, 95% confidence interval [CI] 0.461-0.903, P = 0.0115 for number of fibroids, and adjusted OR 1.447, 95% CI 1.063-1.970, P = 0.0195 for initial volume, with a log-linear relationship). Submucosal fibroids had a higher response rate to treatment (i.e. a decrease in volume) than intramural fibroids (21/25 [84.0%] versus 15/28 [53.6%]; P = 0.0490; adjusted OR 4.478, 95% CI 1.007-19.918). CONCLUSIONS: The location, initial volume and number of fibroids may allow prediction of the outcome of a single 3-month treatment course of daily 5 mg doses of UPA in terms of reduction in volume before surgery.

Short-term outcomes after major hepatic resection in patients with cirrhosis: a 75-case unicentric western experience.

BACKGROUND: The benefit of performing major hepatic resection (MHR) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial because of its high risk of posthepatectomy liver failure (PHLF). This study was conducted to assess the risk of MHR for HCC in patients with cirrhosis. METHODS: Patients with Child-Pugh A or B cirrhosis and HCC who underwent MHR from January 2000 to June 2014 were retrospectively identified. Risk factors for postoperative morbidity and mortality using univariate and multivariate analyses were evaluated. RESULTS: Seventy patients with Child-Pugh A (93%) and 5 (7%) with Child-Pugh B cirrhosis underwent MHR for HCC. Thirteen (17%) had Barcelona Clinic Liver Cancer (BCLC) stage A, 39 (50%) had BCLC B, and 23 (32%) had BCLC C disease. A perioperative blood transfusion was performed in 18 patients (24%). Ninety-day postoperative mortality was 9% (n=7). Major complications occurred in 16 patients (21%), including PHLF in 9 patients (12%). A multivariate analysis showed that perioperative blood transfusion was the main independent factor associated with mortality (OR= 6.5) and major morbidity (OR=10). CONCLUSION: In selected patients with HCC and cirrhosis, MHR is feasible and has acceptable mortality, but careful perioperative management and limiting blood loss are required.

Portal vein stenosis preconditioning of living donor liver in swine: early mechanisms of liver regeneration and gain of hepatic functional mass.

To reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as an effective preconditioning method to induce cell proliferation in the contralateral lobe without downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours after preconditioning and investigate the changes in liver volume and function. Fourteen pigs were used this study. Five pigs were used to study the genetic, cellular and molecular mechanisms set up in the early hours following the establishment of our preconditioning. The remaining nine pigs were equally divided into three groups: sham-operated animals, 20% LPV stenosis, and 100% LPV stenosis. Volumetric scanning and 99 mTc-Mebrofenin hepatobiliary scintigraphy were performed before preconditioning and 14 days after to study morphological and functional changes in the liver. We demonstrated that liver regeneration triggered by 20% LPV stenosis in the contralateral lobe involves TNF-α, IL-6, and inducible nitric oxide synthase 2 by means of STAT3 and hepatocyte growth factor. We confirmed that our preconditioning was responsible for an increase in the total liver volume. Finally, we demonstrated that this volumetric gain was associated with an increase in hepatic functional capacity. NEW & NOTEWORTHY We describe a new preconditioning method for major hepatectomy that is applicable to hepatectomy for donation. We identified 20% left portal vein stenosis as effective preconditioning that is capable of inducing cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. In this study, we report the pathways involved in the first hours following preconditioning, and we confirm that 20% left portal vein stenosis is responsible for an increase in the functional capacity and total liver volume in a porcine model.

Embolization of the Superior Rectal Arteries for Hemorrhoidal Disease: Prospective Results in 25 Patients.

PURPOSE: To evaluate efficacy and safety of superior rectal artery embolization of hemorrhoidal disease as a first-line invasive treatment. MATERIALS AND METHODS: This prospective study was conducted between 2014 and 2015 on 25 consecutive patients (16 men and 9 women with a mean age of 53 y [range, 30-76 y]) with grade II-III hemorrhoids refractory to medical treatment. A transfemoral superselective superior rectal artery branch embolization was performed using 2- and 3-mm diameter microcoils. Over the following 12 months, clinical outcomes were evaluated using the French bleeding score, Goligher prolapse score, visual analog scale (VAS) score for pain, quality-of-life score. The primary endpoint was relief of symptoms by 12 months based on a 2-point minimum improvement on VAS score and bleeding score. RESULTS: At 12 months after embolization, clinical success was obtained in 18 patients (72%), 8 of whom had 2 embolizations. VAS score decreased from 4.6 to 2.3 (P < .01), and bleeding score decreased from 5.5 to 2.3 (P < .01). Quality-of-life and prolapse scores also showed improvement (P < .05), and no patients experienced any early or late complications. Complete clinical failure was observed in 7 patients. After coil embolization, the collateral supply to the hemorrhoidal cushions was significantly related to any recurrence (P = .001). CONCLUSIONS: Hemorrhoidal artery coil embolization was found to be a safe and effective treatment for grade II-III hemorrhoids.

Outcomes of Pulmonary Artery Embolization and Stent Graft Placement for the Treatment of Hemoptysis Caused by Lung Tumors.

PURPOSE: To evaluate the safety and efficacy of endovascular management of pulmonary artery lesions caused by lung tumors. MATERIALS AND METHODS: Nineteen patients (15 men, 4 women; average age: 60.3 years, range, 51-86 years) treated for massive or recurrent hemoptysis with transarterial pulmonary artery embolization between 2010 and 2016 were included in this multicenter, retrospective study. Inclusion criteria were: patients with lung cancer and at least 1 episode of hemoptysis with a pulmonary artery lesion detected by computed tomography (CT) angiography or after failed bronchial artery embolization. No patient undergoing pulmonary embolization for a lung tumor was excluded. Technical success, clinical success, and complications were recorded. The survival curve was estimated using the Kaplan-Meier method RESULTS: Mean follow-up was 188.1 days (range, 0-1440 days). Primary and assisted technical success rates were 73.7% (14/19) and 84.2% (16/19), respectively. Two patients died during the procedure due to massive hemoptysis and cardiac arrest, and 1 patient was treated with surgery. All patients with technical success achieved clinical success without further bleeding. No complications were noted, and no pulmonary infarction was detected on CT scan during follow-up. Survival rates after embolization at 1 and 3 months were 67% (95% confidence interval [CI]: 40%-90%) and 46% (95% CI: 23%-80%), respectively, with 36.8% (n = 7) of the patients still alive at the end of the study. CONCLUSIONS: Embolization is an effective and safe treatment of lung tumors with pulmonary arterial bleeding.

Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.

BACKGROUND: Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma. METHODS: SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2-5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. FINDINGS: Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9-33·6) in the SIRT group and 28·1 months (20·0-35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7-9·9) in the SIRT group versus 9·9 months (8·7-11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94-1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. INTERPRETATION: In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. FUNDING: Sirtex Medical Inc.

Patient dose in interventional radiology: a multicentre study of the most frequent procedures in France.

OBJECTIVES: A national retrospective survey on patient doses was performed by the French Society of Medical physicists to assess reference levels (RLs) in interventional radiology as required by the European Directive 2013/59/Euratom. METHODS: Fifteen interventional procedures in neuroradiology, vascular radiology and osteoarticular procedures were analysed. Kerma area product (KAP), fluoroscopy time (FT), reference air kerma and number of images were recorded for 10 to 30 patients per procedure. RLs were calculated as the 3rd quartiles of the distributions. RESULTS: Results on 4600 procedures from 36 departments confirmed the large variability in patient dose for the same procedure. RLs were proposed for the four dosimetric estimators and the 15 procedures. RLs in terms of KAP and FT were 90 Gm.cm2 and 11 mins for cerebral angiography, 35 Gy.cm2 and 16 mins for biliary drainage, 75 Gy.cm2 and 6 mins for lower limbs arteriography and 70 Gy.cm2 and 11 mins for vertebroplasty. For these four procedures, RLs were defined according to the complexity of the procedure. For all the procedures, the results were lower than most of those already published. CONCLUSIONS: This study reports RLs in interventional radiology based on a national survey. Continual evolution of practices and technologies requires regular updates of RLs. KEY POINTS: • Delivered dose in interventional radiology depends on procedure, practice and patient. • National RLs are proposed for 15 interventional procedures. • Reference levels (RLs) are useful to benchmark practices and optimize protocols. • RLs are proposed for kerma area product, air kerma, fluoroscopy time and number of images. • RLs should be adapted to the procedure complexity and updated regularly.

Role of dual-energy computed tomography in detecting early recurrences of lung tumours treated with radiofrequency ablation.

PURPOSE: Detecting a recurrence after lung radiofrequency ablation (RFA) is based on a group of arguments that include CT, positron emission tomography (PET-CT) at 3 months and clinical patient follow-up. There is no one examination that is absolutely reliable. Recurrences are diagnosed tardily, when the cancers are locally extended, or when the patients are metastatic. The purpose of this article is to investigate the utility of dual-energy computed tomography (DECT) in order to assess therapeutic responses to RFA for lung neoplasia. MATERIALS AND METHODS: This institutional review board-approved study enroled 70 patients with lung tumours who underwent DECT after RFA. All patients provided a written informed consent for the study. RESULTS: The study included 70 consecutive patients, and 191 DECT measures were performed. We collected the enhancement values of all scars without establishing a prior threshold of positivity. The optimal threshold value areas appeared to be located between 20 and 35 Hounsfield unit (HU) with sensitivity between 70% and 82%; specificity between 72% and 90%; a negative predictive value (NPV) between 96% and 97% and a diagnostic accuracy index between 73% and 87%. At the one month follow-up, 53 nodules were analysed with DECT and four nodules had recurred, all of which were detected by DECT. The sensitivity, which was calculated at 100%, was excellent; the NPV was at 100% (CI: 91.62, 100) and the specificity was at 85.71% (CI: 73.33, 92.9). The diagnostic accuracy index was 86.79% (CI: 75.16, 93.45) and the average DECT acquisitions dosimetry was 106 mGy.cm (33mGy.cm 245mGy.cm). CONCLUSION: DECT could be a conceivable alternative for detecting early recurrence after lung RFA. Key points After lung RFA, a PET CT has a high rate of false positives in the initial phase; The study of enhancement in the follow-up of lung lesions treated with RFA, and especially by DECT, can be relevant; Dual Energy CT has a good efficiency for a threshold between 20 and 35 HU, especially in the first month after RFA; DECT could be a conceivable alternative for detecting early recurrence.

Persistent pathways after lung radiofrequency ablation as a risk factor of drain placement.

PURPOSE: The risk factors of pneumothorax after lung radiofrequency (RF) ablation are long known. The objective was to demonstrate that the visualisation of an aeric RF path after the needle withdrawal was predictive of pneumothorax occurrence and chest tube placement. MATERIALS AND METHODS: A total of 70 patients were retrospectively included in this study. For each patient, we determined the pneumothorax risk factors (age, gender, previous surgery, emphysema, lesion size, distance between pleura and lesion), visualisation of a RF track, length and thickness, presence of pneumothorax, volume, chest tube placement, duration of drainage and hospital stay. RESULTS: Among 70 patients included retrospectively, 26 needed a chest tube placement (37%). Considering the group with path visualisation (37 patients, group A) and the patients without path visualisation (group B), the 2 groups were comparable for pneumothorax risk factors. Considering the patients who needed a chest drain, the visualisation of the path was significatively more important (23 cases, 88.4%) (p< 10-3) than in the group without (8 patients, 31.8%). Multivariate analyses were significant in the three analyses after adjustments on the risk factors for the occurrence of pneumothorax. Incidence of drains was significantly more (p < 10-3) important in group A (23 drainages 62%) than in group B (4 drainages or 12%). The length and thickness of the tracks were not predictable of drain placement. CONCLUSIONS: Besides the well-known risk factors of severe pneumothorax after lung RFA, the simple visualisation of an aeric path just after the RF needle withdrawal is significantly associated with chest tube placement and can be considered as a risk factor as itself.

Pathological effects of lung radiofrequency ablation that contribute to pneumothorax, using a porcine model.

OBJECTIVES: The incidence of pneumothorax is 7 times higher after lung radiofrequency ablation (RFA) than after lung biopsy. The reasons for such a difference have never been objectified. The histopathologic changes in lung tissue are well-studied and established for RF in the ablation zone. However, it has not been previously described what the nature of thermal injury might be along the shaft of the RF electrode as it traverses through normal lung tissue to reach the ablation zone. The purpose of this study was to determine the changes occurring around the RF needle along the pathway between the ablated zone and the pleura. MATERIAL AND METHODS: In 3 anaesthetised and ventilated swine, 6 RFA procedures (right and left lungs) were performed using a 14-gauge unipolar multi-tined retractable 3 cm radiofrequency LeVeen probe with a coaxial introducer positioned under CT fluoroscopic guidance. In compliance with literature guidelines, we implemented a gradually increasing thermo-ablation protocol using a RF generator. Helical CT images were acquired pre- and post-RFA procedure to detect and evaluate pneumothorax. Four percutaneous 19-gauge lung biopsies were also performed on the fourth swine under CT guidance. Swine were sacrificed for lung ex vivo examinations, scanning electron microscopy (SEM) and pathological analysis. RESULTS: Three severe (over 50 ml) pneumothorax were detected after RFA. In each one of them, pathological examination revealed a fistulous tract between ablation zone and pleura. No fistulous tract was observed after biopsies. In the 3 cases of severe pneumothorax, the tract was wide open and clearly visible on post procedure CT images and SEM examinations. The RFA tract differed from the needle biopsy tract. The histological changes that are usually found in the ablated zone were observed in the RFA tract's wall and were related to thermal lesions. These modifications caused the creation of a coagulated pulmonary parenchyma rim between the thermo-ablation zone and the pleural space. The structural properties of the damage can explain why the RFA tract is remains patent after needle withdrawal. CONCLUSION: Our study demonstrates for the first time that the changes around the RF needle are the same as in the ablated zone. The damage could create fistulous tracts along the needle path between thermo-ablation zone and pleural space. These fistulas could certainly be responsible for severe pneumothorax that occurs in many patients treated with lung RFA.