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Supplementary Data from Imatinib Mesylate as a Preoperative Therapy in Dermatofibrosarcoma: Results of a Multicenter Phase II Study on 25 Patients

Aims: The treatment of dermatofibrosarcoma protuberans (DFSP) involves wide local excision with frequent need for reconstructive surgery. A t(17;22) translocation resulting in COL1A1-PDGFB fusion is present in >95% of cases. Certain patient observations and a report on nine patients suggest that imatinib mesylate, targeting platelet-derived growth factor receptor β, has clinical potential in DFSP. The primary aim of this phase II multicenter study was to define the percentage of clinical responders (Response Evaluation Criteria in Solid Tumors) to a 2-month preoperative daily administration of 600 mg of imatinib mesylate before wide local excision. The secondary aims were to determine tolerance, objective response from imaging results (ultrasound and magnetic resonance imaging), and pathologic responses observed in sequential tissue specimens.Patients and Methods: A two-stage flexible design was used with interim analysis after the recruitment of six patients. Twenty-five adults suffering from primary or recurrent DFSP were included from July 2004 to May 2006.Results: The COL1A1-PDGFB fusion gene was detected in 21 out of 25 patients following fluorescence in situ hybridization analysis (two cases were noninformative). A clinical response was achieved in nine (36%) patients (95% confidence interval, 18.9-57.5). The median relative tumoral decrease was 20.0% (range, −12.5 to 100). Apart from expected grade 1 or 2 side effects, we observed one grade 3 neutropenia, one grade 3 maculopapular rash, and one grade 4 transient transaminitis.Conclusion: Our results support the use of imatinib in a neoadjuvant setting in nonresectable DFSP, or when surgery is difficult or mutilating. These results will be useful for setting hypotheses in the evaluation of new drugs to treat primary or secondary resistance to imatinib. Clin Cancer Res; 16(12); 3288–95. ©2010 AACR.

Objective: To evaluate the impact of age on the zonal anatomy of the prostate by MRI using morphometric and textural analysis. Methods: A total of 154 men (mean age: 63 years) who underwent MRI due to a high prostate-specific antigen (PSA) level were included retrospectively. At each MRI examination the following variables were measured: overall dimensions of the prostate (whole gland (WG), transitional zone (TZ), and peripheral zone (PZ)), and thickness of the anterior fibromuscular stroma (AFMS) and the periprostatic venous plexus (PPVP) on T2 weighted images. Identical regions of interest (ROIs) were delineated on the apparent diffusion coefficient (ADC) map on the anterior (horn) and posterior part of the PZ. Textural (TexRAD®) parameter differences between TZ and PZ ROIs on T2 weighted images were analyzed by linear regression. Results were correlated with age (distributed into five decades from 22 to 89 years). Results: Age was positively correlated with PSA level and glandular volumes (WG, TZ, and TZ/WG ratio; p < 0.0001) and was negatively correlated with AFSM and PPVP thickness (p < 0.0001). There was a positive correlation between ADC values of the PZ and age (p = 0.003) and between entropy of the TZ and PZ and age (p < 0.001). Conclusion: Gradual variations in morphologic and textural features of the prostate were observed with age, mainly due to the increase in TZ volume while PZ volume tended to decrease. These modifications resulted in textural changes mainly at the expense of entropy. Advances in knowledge: Entropy could be relevant for studying the process of aging of the prostate.

Background Inter-individual variations of non-glomerular filtration rate (GFR) determinants of serum creatinine, such as muscle mass, account for the imperfect performance of estimated GFR (eGFR) equations. We aimed to develop an equation based on creatinine and total lumbar muscle cross-sectional area measured by unenhanced computed tomography scan at the third lumbar vertebra. Methods The muscle mass–based eGFR (MMB-eGFR) equation was developed in 118 kidney donor candidates (iohexol clearance) using linear regression. Validation cohorts included 114 healthy subjects from another center (51Cr-EDTA clearance, validation population 1), 55 patients with chronic diseases (iohexol, validation population 2), and 60 patients with highly discordant creatinine and cystatin C–based eGFR, thus presumed to have atypical non-GFR determinants of creatinine (51Cr-EDTA, validation population 3). Mean bias was the mean difference between eGFR and measured GFR, precision the standard deviation (SD) of the bias, and accuracy the percentage of eGFR values falling within 20% and 30% of measured GFR. Results In validation population 1, performance of MMB-eGFR was not different from those of CKD-EPICr2009 and CKD-EPICr2021. In validation population 2, MMB-eGFR was unbiased and displayed better precision than CKD-EPICr2009, CKD-EPICr2021 and EKFC (SD of the biases: 13.1 vs 16.5, 16.8 and 15.9 mL/min/1.73 m2). In validation population 3, MMB-eGFR had better precision and accuracy {accuracy within 30%: 75.0% [95% confidence interval (CI) 64.0–86.0] vs 51.5% (95% CI 39.0–64.3) for CKD-EPICr2009, 43.3% (95% CI 31.0–55.9) for CKD-EPICr2021, and 53.3% (95% CI 40.7–66.0) for EKFC}. Difference in bias between Black and white subjects was −2.1 mL/min/1.73 m2 (95% CI −7.2 to 3.0), vs −8.4 mL/min/1.73 m2 (95% CI −13.2 to −3.6) for CKD-EPICr2021. Conclusion MMB-eGFR displayed better performances than equations based on demographics, and could be applied to subjects of various ethnic backgrounds.

Objectives To evaluate the use of pre-cryoablation biopsy for small renal masses (SRMs) and the effects of increasing uptake on histological results of treated SRMs. Methods From 2015 to 2019, patients with sporadic T1N0M0 SRMs undergoing percutaneous, laparoscopic, or open cryoablation from 14 European institutions within the European Registry for Renal Cryoablation (EuRECA) were included for the retrospective analysis. Univariate and multivariate logistic models were used to evaluate the trends, histological results, and the factors influencing use of pre-cryoablation biopsy. Results In total, 871 patients (median (IQR) age, 69 (14), 298 women) undergoing cryoablation were evaluated. The use of pre-cryoablation biopsy has significantly increased from 42% (65/156) in 2015 to 72% (88/122) in 2019 (p < 0.001). Patients treated for a benign histology are significantly more likely to have presented later in the trend, where pre-cryoablation biopsy is more prevalent (OR: 0.64, 95% CI 0.51–0.81, p < 0.001). Patients treated for undiagnosed histology are also significantly less likely to have presented in 2018 compared to 2016 (OR 0.31, 95% CI 0.10–0.97, p = 0.044). Patients aged 70+ are less likely to be biopsies pre-cryoablation (p < 0.05). R.E.N.A.L. nephrometry score of 10+ and a Charlson Comorbidity Index > 1 are factors associated with lower likelihood to not have received a pre-cryoablation biopsy (p < 0.05). Conclusion An increased use of pre-cryoablation biopsy was observed and cryoablation patients treated with a benign histology are more likely to have presented in periods where pre-cryoablation biopsy is not as prevalent. Comparative studies are needed to draw definitive conclusions on the effect of pre-cryoablation biopsy on SRM treatments. Key Points • The use of biopsy pre-ablation session has increased significantly from 42% of all patients in 2015 to 74% in 2019. • Patients are less likely to be treated for a benign tumour if they presented later in the trend, where pre-cryoablation biopsy is more prevalent, compared to later in the trend (OR 0.64, 95% CI 0.51–0.81, p < 0.001). • Patients with comorbidities or a complex tumour (R.E.N.A.L. nephrometry score > 10) are less likely to not undergo biopsy as a separate session to cryoablation.

Background: to report the safety of outpatient prostatic artery embolization (PAE) after a significant learning curve. Methods: a retrospective bi-institutional study was conducted between June 2018 and April 2022 on 311 consecutive patients, with a mean age of 69 years ± 9.8 (47–102), treated by outpatient PAE. Indications included lower urinary tract symptoms, acute urinary retention, and hematuria. When needed, 3D-imaging and/or coil protection of extra-prostatic supplies were performed to avoid non-target embolization. Adverse events were monitored at 1-, 6-, and 12-month follow-ups. Results: bilateral PAE was achieved in 305/311 (98.1%). Mean dose area product/fluoroscopy times were 16,408.3 ± 12,078.9 (2959–81,608) μGy.m2/36.3 ± 1.7 (11–97) minutes. Coil protection was performed on 67/311 (21.5%) patients in 78 vesical, penile, or rectal supplies. Embolization-related adverse events varied between 0 and 2.6%, access-site adverse events between 0 and 18%, and were all minor. There was no major event. Conclusion: outpatient PAE performed after achieving a significant learning curve may lead to a decreased and low rate of adverse events. Experience in arterial anatomy and coil protection may play a role in safety, but the necessity of the latter in some patterns may need confirmation by additional studies in randomized designs.

Background: to evaluate the safety and feasibility of a shorter time to hemostasis applied to outpatient transradial (TR) Prostatic Artery Embolization (PAE). Methods: a retrospective bi-institutional study was conducted between July 2018 and April 2022 on 300 patients treated by outpatient TR PAE. Indications included lower urinary tract symptoms, acute urinary retention, and hematuria. Mean patient height was 176 ± 6.3 (158–192) cm. The primary endpoint was safety of a 45 min deflation protocol for hemostasis. The secondary endpoint was the feasibility of PAE using TR access. Results: technical success was 98.7% (296/300). There was one failure due to patient height. Mean DAP/fluoroscopy times were 16,225 ± 12,126.3 (2959–81,608) μGy·m2/35 ± 14.7 (11–97) min, and mean time to discharge was 80 ± 6 (75–90) min. All access site and embolization-related adverse events were minor. Mild hematoma occurred in 10% (30/300), radial artery occlusion (RAO) in 10/300 (3.3%) cases, and history of smoking was a predictor for RAO. There was no major event. Conclusion: the safety of TR PAE using a 45 min time to hemostasis was confirmed, and TR PAE is feasible in most cases. Radial artery occlusion was still observed and may be favored by smoking.

To establish national reference levels (RLs) in interventional procedures under CT guidance as required by the 2013/59/Euratom European Directive. Seventeen categories of interventional procedures in thoracic, abdominopelvic, and osteoarticular specialties (percutaneous infiltration, vertebroplasty, biopsy, drainage, tumor destruction) were analyzed. Total dose length product (DLP), number of helical acquisitions (NH), and total DLP for helical, sequential, or fluoroscopic acquisitions were recorded for 10 to 20 patients per procedure at each center. RLs were calculated as the 3rd quartiles of the distributions and target values for optimization process (TVOs) as the median. RLs and TVOs were compared with previously published studies. Results on 5001 procedures from 49 centers confirmed the great variability in patient dose for the same category of procedures. RLs were proposed for the DLPs and NHs in the seventeen categories. RLs in terms of DLP and NH were 375 mGy.cm and 2 NH for spinal or peri-spinal infiltration, 1630 mGy.cm and 3 NH for vertebroplasty, 845 mGy.cm and 4 NH for biopsy, 1950 mGy.cm and 8 NH for destruction of tumors, and 1090 mGy.cm and 5 NH for drainage. DLP and NH increased with the complexity of procedures. This study was the first nationwide multicentric survey to propose RLs for interventional procedures under CT guidance. Heterogeneity of practice in centers were found with different levels of patient doses for the same procedure. The proposed RLs will allow imaging departments to benchmark their practice with others and optimize their protocols. • National reference levels are proposed for 17 categories of interventional procedures under CT guidance. • Reference levels are useful for benchmarking practices and optimizing protocols. • Reference levels are proposed for dose length product and the number of helical acquisitions.

Chimeric Antigen Receptor T cells (CAR-T) are an outbreaking treatment option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common specific toxicities, while severe neutropenia and infections are often observed as well. From March 2020, early G-CSF prophylaxis at day (D) two post-infusion was systematically proposed. We then compared patients treated before that date who did not receive G-CSF or who received late (after D5) G-CSF as control group. Patients administered with early G-CSF had similar duration of grade 4 neutropenia but significantly decreased incidence of febrile neutropenia (58% versus 81%, p = 0.018). Similar rate of toxicities was observed, including overall and grade 3-4 CRS (p = 0.93 and p = 0.28, respectively), and overall and grade 3-4 ICANS (p = 0.62 and p = 0.88, respectively). We observed no difference in the quality of CAR T-cells expansion (p = 0.79, %Cmax), nor in response rate (best ORR, 57.6% vs 61.8%, p = 0.93), nor survival even in a group of patients adjusted by a propensity score. In conclusion, early G-CSF administration was safe and effective in reducing febrile neutropenia without impact on toxicities nor on anti-lymphoma activity of CAR-T.

The original version of this article, published on 02 May 2020, unfortunately contained a mistake.

PURPOSE: To train and assess the performance of a deep learning–based network designed to detect, localize, and characterize focal liver lesions (FLLs) in the liver parenchyma on abdominal US images. MATERIALS AND METHODS: In this retrospective, multicenter, institutional review board–approved study, two object detectors, Faster region-based convolutional neural network (Faster R-CNN) and Detection Transformer (DETR), were fine-tuned on a dataset of 1026 patients (n = 2551 B-mode abdominal US images obtained between 2014 and 2018). Performance of the networks was analyzed on a test set of 48 additional patients (n = 155 B-mode abdominal US images obtained in 2019) and compared with the performance of three caregivers (one nonexpert and two experts) blinded to the clinical history. The sign test was used to compare accuracy, specificity, sensitivity, and positive predictive value among all raters. RESULTS: DETR achieved a specificity of 90% (95% CI: 75, 100) and a sensitivity of 97% (95% CI: 97, 97) for the detection of FLLs. The performance of DETR met or exceeded that of the three caregivers for this task. DETR correctly localized 80% of the lesions, and it achieved a specificity of 81% (95% CI: 67, 91) and a sensitivity of 82% (95% CI: 62, 100) for FLL characterization (benign vs malignant) among lesions localized by all raters. The performance of DETR met or exceeded that of two experts and Faster R-CNN for these tasks. CONCLUSION: DETR demonstrated high specificity for detection, localization, and characterization of FLLs on abdominal US images. Supplemental material is available for this article. RSNA, 2022 Keywords: Computer-aided Diagnosis (CAD), Ultrasound, Abdomen/GI, Liver, Tissue Characterization, Supervised Learning, Transfer Learning, Convolutional Neural Network (CNN)

Background: Local recurrence after radiation therapy for prostate cancer is a major clinical issue. Various local treatments are available with mitigated functional and oncological outcomes. The aim of the present study was to evaluate perioperative and oncological results of salvage cryotherapy (CT) as treatment of local recurrence of prostate cancer. Methods: We retrospectively reviewed all patients treated with hemi-prostatic salvage CT for local recurrence of prostate cancer in 1 academic hospital between November 2011 and April 2019. Local recurrence was defined according to the Phoenix criteria (prostate-specific antigen [PSA] nadir + 2 ng/mL), associated with a prostatic MRI target lesion and confirmed by biopsy. Perioperative and functional complications were collected. Cox regression was conducted to assess factors associated with time to initiation of androgen deprivation therapy (ADT). Statistical analyses were conducted using R Studio. Results: A total of 29 patients were treated with an average follow-up of 37.6 months. Median age at CT was 77 years. Median PSA before CT was 5.1 ng/mL (min-max: 2.74–18). 17.2% of patients displayed a high D’Amico risk group. Median hospital stay was 1.4 days. Four patients (13.8%) experienced postoperative acute urinary retention. Nineteen patients (65.5%) experienced late functional complications (3 erectile dysfunctions, 3 stress incontinence, and 13 urinary frequency). Fourteen patients displayed recurrence after salvage treatment (48.2%). Median time to introduction of ADT was 15.1 months. ADT-free survival at 1 and 2 years was, respectively, 74% and 61%. In multivariate analysis, ISUP score 4 and PSA nadir Conclusions: Salvage focal CT may delay the use of ADT in locally recurrent prostate cancer after RT and offers an alternative for eligible patients. The technique was feasible with acceptable perioperative morbidity and acceptable midterm oncological outcome.

International audience; Ultrasound (US) images usually contain identifying information outside the ultrasound fan area and manual annotations placed by the sonographers during exams. For those images to be exploitable in a Deep Learning framework, one needs to first delineate the border of the fan which delimits the ultrasound fan area and then remove other annotations inside. We propose a parametric probabilistic approach for the first task. We make use of this method to generate a training data set with segmentation masks of the region of interest (ROI) and train a U-Net to perform the same task in a supervised way, thus considerably reducing computational time of the method, one hundred and sixty times faster. These images are then processed with existing inpainting methods to remove annotations present inside the fan area. To the best of our knowledge, this is the first parametric approach to quickly detect the fan in an ultrasound image without any other information than the image itself.

OBJECTIVES To compare the oncological outcomes of percutaneous cryoablation (PCA) vs robot-assisted partial nephrectomy (RAPN) for the treatment of T1 renal tumours. PATIENTS AND METHODS We conducted a retrospective study in all patients treated by RAPN or PCA for malignant renal tumours in one of four centres between 2009 and 2016. Tumours were paired one by one using radiological tumour stage and RENAL nephrometry score (package matchit, R software version 3.2.2). Malignancy was confirmed by biopsy for all patients in the PCA group. Patient characteristics before and after matching and oncological results were compared between the two groups. Cox regression, adjusted for age, treatment type, histological type and margins, was used to identify factors associated with time to local recurrence. Positive margins were defined histologically in the RAPN group and radiologically in the PCA group. RESULTS A total of 647 patients were identified; 470 underwent RAPN and 177 underwent PCA. After matching, there was no significant difference between the two groups (RAPN, n = 177; PCA, n = 177) with regard to tumour stage, RENAL nephrometry score, tumour size (27.6 vs 25.9 mm; P = 0.07) and gender ratio. Patients in the PCA group remained significantly older (69.9 vs 59.8 years; P < 0.001). The absolute recurrence rate was 2.8% in the RAPN group vs 8.4% in the PCA group (P = 0.03). The 5-year recurrence-free survival rate was 85% in the PCA group vs 95% in the RAPN group (log-rank P = 0.02). In multivariate analysis, the presence of positive margins and the type of treatment were the two factors significantly associated with local recurrence (P < 0.001 and P = 0.046, respectively). CONCLUSION The local recurrence rate after PCA was significantly higher than after RAPN for T1 renal tumours. Incomplete treatment was the main criterion associated with recurrence. The recurrence rate may have been overestimated in the PCA group because of closer radiological follow-up in these patients.

The purpose of this study is to describe the management and outcome of critically ill cancer patients with Superior Vena Cava Syndrome (SVCS). All cancer patients admitted to the medical intensive care unit (ICU) of the Saint-Louis University Hospital for a SVCS between January 2004 and December 2016 were included. Of the 50 patients included in the study, obstruction of the superior vena cava was partial in two-thirds of the cases and complete in one-third. Pleural effusion was reported in two-thirds of the patients, pulmonary atelectasis in 16 (32%), and pulmonary embolism in five (10%). Computed tomography of the chest showed upper airway compression in 18 (36%) cases, while echocardiography revealed 22 (44%) pericardial effusions. The causes of SVCS were diagnosed one (0–3) day after ICU admission, using interventional radiology procedures in 70% of the cases. Thirty (60%) patients had hematological malignancies, and 20 (40%) had solid tumors. Fifteen (30%) patients required invasive mechanical ventilation, seven (14%) received vasopressors, and renal replacement therapy was implemented in three (6%). ICU, in-hospital, and 6-month mortality rates were 20, 26, and 48%, respectively. The cause of SVCS was the only factor independently associated with day 180 mortality by multivariate analysis. Patients with hematological malignancies had a lower mortality than those with solid tumors (27 versus 80%) (odds ratio 0.12, 95% confidence interval (0.02–0.60), p

Objectives In Luxembourg, the frequency of CT and MRI examinations per inhabitant is among the highest in Europe. A national audit was conducted to evaluate the appropriateness of CT and MRI examinations according to the national referral guidelines for medical imaging. Methods Three hundred and eighty-eight CT and 330 MRI requests corresponding to already performed examinations were provided by all radiology departments in Luxembourg. Four external radiologists evaluated the clinical elements for justification present in each request. They consensually assessed the appropriateness of each requested examination with regard to the national referral guidelines and their clinical experience. Results The appropriateness rate (AR) was higher for MRI requests than for CT requests (79% vs. 61%; p

Rationale and Objectives The study aimed to evaluate the performances of two iterative reconstruction (IR) algorithms and of filtered back projection (FBP) when using reduced-dose chest computed tomography (RDCT) compared to standard-of-care CT. Materials and Methods An institutional review board approval was obtained. Thirty-six patients with hematologic malignancies referred for a control chest CT of a known lung disease were prospectively enrolled. Patients underwent standard-of-care scan reconstructed with hybrid IR, followed by an RDCT reconstructed with FBP, hybrid IR, and iterative model reconstruction. Objective and subjective quality measurements, lesion detectability, and evolution assessment on RDCT were recorded. Results For RDCT, the CTDIvol (volumetric computed tomography dose index) was 0.43 mGy⋅cm for all patients, and the median [interquartile range] effective dose was 0.22 mSv [0.22–0.24]; corresponding measurements for standard-of-care scan were 3.4 mGy [3.1–3.9] and 1.8 mSv [1.6–2.0]. Noise significantly decreased from FBP to hybrid IR and from hybrid IR to iterative model reconstruction on RDCT, whereas lesion conspicuity and diagnostic confidence increased. Accurate evolution assessment was obtained in all cases with IR. Emphysema identification was higher with iterative model reconstruction. Conclusion Although iterative model reconstruction offered better diagnostic confidence and emphysema detection, both IR algorithms allowed an accurate evolution assessment with an effective dose of 0.22 mSv.

International audience; Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease treated with anti-CD20-based immuno-chemotherapy (R-CHOP). We identified that low levels of GAPDH predict a poor response to R-CHOP treatment. Importantly, we demonstrated that GAPDH(low) lymphomas use OxPhos metabolism and rely on mTORC1 signaling and glutaminolysis. Consistently, disruptors of OxPhos metabolism(phenformin) or glutaminolysis (L-asparaginase) induce cytotoxic responses in GAPDH(low) B cells and improve GAPDH(low) B cell-lymphoma-bearing mice survival, while they are low or not efficient on GAPDH(high) B cell lymphomas. Ultimately, we selected four GAPDH(low) DLBCL patients, who were refractory to all anti-CD20-based therapies, and targeted DLBCL metabolism-using L-asparaginase (K), mTOR inhibitor (T), and metformin (M) (called KTM therapy). Three out of the four patients presented a complete response upon one cycle of KTM. These findings establish that the GAPDH expression level predicts DLBCL patients' response to R-CHOP treatment and their sensitivity to specific metabolic inhibitors.

Background Proper usage of renal tumor biopsy (RTB) remains to be determined in the setting of renal tumors diagnosis, particularly in the elderly population. The aim of the study was to evaluate the perioperative and pathological results of RTB in a population of patients over 75 and to compare the performance of the procedure to their younger counterparts. Material and methods Systematic RTB were prospectively performed in a single center between 2009 and 2012. Patients’ and tumor characteristics, operative and pathological results were collected. Data were compared between patients under and over 75 years old. Particular attention was paid to influence of RTB on treatment decision-making. Results A total of 180 patients were included (137 patients 75 years). Size of tumor, clinical stage, radiological aspect and RENAL score were not statistically different between patients under or over 75 years. No difference was observed between the 2 groups regarding complication rate (2.9% vs. 0%, respectively, P = 0.625). One hundred fifty-seven patients (87.2%) had a positive diagnosis at first RTB, with no difference between the 2 groups regarding histology (P = 0.942). After biopsy, only 73.1% of patients 75 years had concordance between radiological and histological findings (P = 0.919). Treatment decision was challenged after RTB in 21.8% of patients 75 years. Conclusions RTB was as safe and accurate in the eldest population, as it is in the general population, and should be performed routinely considering its influence on patient management strategy.

To investigate the diagnostic value of ultrasound-guided core needle biopsy (US-CNB) in suspected cases of lymph node metastasis from cutaneous melanoma. All patients with cutaneous melanoma followed in Saint-Louis Hospital between 2006 and 2010 who underwent US-CNB for suspicion of melanoma lymph node metastasis were reviewed retrospectively. Histopathological results of US-CNB samples were classified as melanoma, other malignancy, suspicious, inadequate, or benign. The diagnostic accuracy of US-CNB was assessed by comparison with two reference standards: histopathological examination of the radical lymph node dissection or, when this was not available, clinical and radiological follow-up. The data from 72 US-CNB were analyzed. Forty-four melanomas, 22 benign, three other malignancies, three inadequate samples, and no inconclusive specimens were diagnosed. Seventy-one US-CNB results were confirmed (98.6%). US-CNB achieved high sensitivity, specificity, and positive predictive value (respectively, 97.9, 100, and 100%). No adverse events were reported after the procedure. US-CNB provided a mean tissue volume of 16.7 mm per lymphadenopathy. US-CNB has diagnostic value similar to that of fine-needle aspiration cytology. It represents a reliable alternative method in melanoma lymph node metastasis to avoid surgery in patients who will not benefit from it. US-CNB provides relatively large samples of tissue suitable for comprehensive genomic analyses currently needed for research and personalized care of melanoma patients.

The risk of central nervous system (CNS) dissemination in mantle cell lymphoma (MCL) is low and occurs late in the course of the disease. However, prognosis in such cases remains extremely poor despite high-dose antimetabolite chemotherapy. Among novel drugs used to treat relapsing MCL patients, ibrutinib, an oral inhibitor of Bruton tyrosine kinase, shows great promise. Here we report the clinical observation of 3 MCL patients with symptomatic CNS relapse treated with single-agent ibrutinib. All 3 patients had dramatic and rapid responses with almost immediate recovery from symptoms. We also confirmed that ibrutinib crosses the blood-brain barrier with parallel pharmacokinetic analyses in plasma and cerebrospinal fluid using a validated LC-MS/MS method. All responses were ongoing after 2 months to 1 year of follow-up.

PURPOSE Mediastinal masses of various origins can be encountered on imaging in symptomatic or asymptomatic patients. We aimed to evaluate the diagnostic yield and complication rate of computed tomography (CT)-guided mediastinal core needle biopsies in a large population of patients presenting with mediastinal masses and to identify the factors that could influence these results. MATERIALS AND METHODS In total, 293 consecutive CT-guided mediastinal biopsies, performed in 285 patients with equivocal masses at a single center from 2006 to 2011, were included. Lesion characteristics, technical biopsy parameters, final diagnoses, diagnostic yields (number of biopsies that yielded a complete diagnosis divided by the total number of biopsies), and complication rates were recorded. RESULTS Malignant diagnoses, including lymphoproliferative disorders (N=151, 53%) and lung cancers (N=54, 19%), were established in 233 cases (82%). Benign lesions were found in 52 procedures (18%), including sarcoidosis (N=19, 7%) and infections (N=17, 6%). The overall diagnostic yield was 87% and was lower for lymphoma residual masses (57%) than for initial diagnosis or relapses of known disease (90%). Complications occurred in 21 patients (7%), but only 2 patients (0.7%) required hospitalization for >12 hours. Neither the diagnostic yield nor the complication rate was influenced by the target characteristics or by technical parameters. CONCLUSIONS CT-guided core needle biopsy of equivocal mediastinal masses is a minimally invasive procedure that is effective and safe, even in cases of small targets or targets in challenging locations.

The aim of this study was to evaluate the feasibility of cryoablation of renal tumours without sedation. We prospectively evaluated 149 computed tomography-guided renal cryoablation procedures that were performed at our institution between 2009 and 2013. The patients received only 1 g of IV paracetamol prior to the procedure; intraprocedural, local anaesthesia was administered. We recorded the date and duration of the procedure, size and location of the tumour, number of cryoneedles used, need for dissection with saline or carbon dioxide and intraprocedural degree of pain, which was scored using an established visual analogue pain score (VAS) (0–10). Multivariate analysis was used to identify the associations between the recorded parameters and VAS. An interventional radiologist and a technician could perform all procedures without the help of anaesthesiologists and with adequate analgesia. The pain level ranged from 0 to 8 (mean, 2.0). It did not correlate with the tumour size or with the number of cryoneedles. It was significantly greater when the ice ball involved renal cavities (p = .0033) and when carbon dioxide was used for dissection (p

To evaluate the accuracy of the apparent diffusion coefficient (ADC) provided by diffusion-weighted imaging (DWI) in predicting the response to neoadjuvant chemotherapy (NACT) at baseline in patients according to their breast tumour phenotypes. This retrospective study was approved by our institutional review board. One hundred eighteen consecutive women with locally advanced breast cancer who had undergone NACT followed by breast surgery were included. DWI was performed at 1.5 T less than 2 weeks before NACT. We studied the correlation between pretreatment ADC and response in pathology after surgery according to immunohistochemical features and intrinsic subtypes (luminal A, luminal B, HER2-enriched, and triple-negative tumours). After surgery, the pathologist recognized 24 complete responders (CRps) and 94 non-complete responders (NCRps). No difference was identified between the pretreatment ADCs of the CRp and NCRp patients. There were differences in pretreatment ADCs among the luminal A (1.001 ± 0.143 × 10−3 mm2/s), luminal B (0.983 ± 0.150 × 10−3 mm2/s), HER2-enriched (1.132 ± 0.216 × 10−3 mm2/s), and triple-negative (1.168 ± 0.245 × 10−3 mm2/s; P = 0.0003) tumour subtypes. In triple-negative tumours, the pretreatment ADC was higher in NCRp (1.060 ± 0.143 × 10−3 mm2/s) than in CRp patients (1.227 ± 0.271 × 10−3 mm2/s; P = 0.047). Pretreatment ADC can predict the response of breast cancer to NACT if tumour subtypes are considered. Key Points • Apparent diffusion coefficient helps clinicians to assess patients with breast cancer. • Pretreatment ADC is related to tumour grade and hormone receptor status. • Pretreatment ADC is lower in luminal A and B than in triple-negative tumours. • Pretreatment ADC is higher in complete than in non-complete responders to neoadjuvant chemotherapy.

The aim of this study was to evaluate the safety profile of gadoterate meglumine from clinical trials, postmarketing observational studies, and pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 25 years of clinical use and over 50 million administered doses.Assessment of the safety of gadoterate meglumine through processing and review of all safety data was collected after magnetic resonance imaging procedures. All ADRs originated from 3 major sources: (1) a clinical study database including 50 phase I to IV studies involving 2822 patients, (2) a safety database including 8 postmarketing safety studies (PMSs) involving 151,050 patients, and (3) a pharmacovigilance database compiling safety experience following over 50 million doses administered between March 1989 and September 2015.Among the 2822 patients receiving gadoterate meglumine in the clinical trials, 241 (8.5%) experienced 405 postinjection adverse events (AEs), considered related to the contrast agent for 113 patients (4.0%). Serious AEs were reported for 27 patients (1.0%) and assessed as related to gadoterate meglumine for 2 patients (0.07%). None of the PMS studies showed evidence of unexpected safety issues, with a very low rate of AEs (1%). Postmarketing safety experience with over 50 million doses of gadoterate meglumine prescribed for 25 years of approved use worldwide compiled spontaneous reports for 3797 patients who experienced 8397 ADRs, yielding a very low reported incidence of ADRs of 0.007% of patients. There was no single-agent case of confirmed nephrogenic systemic fibrosis with gadoterate meglumine either from clinical development programs or from postmarketing experience.Based on clinical trials, postmarketing observational studies and pharmacovigilance data, a very low incidence of ADRs was reported with gadoterate meglumine, which has no impact on its favourable benefit-risk ratio.

Thyroid surgery is common, but complications may occur. High-intensity focused ultrasound (HIFU) is a minimally invasive alternative to surgery. We hypothesized that an optimized HIFU device could be safe and effective for ablating benign thyroid nodules without affecting neighboring structures.In this open, single-center feasibility study, 25 patients were treated with HIFU with real-time ultrasound imaging 2 weeks before a scheduled thyroidectomy for multinodular goiter. Thyroid ultrasonography imaging, thyroid function, were evaluated before and after treatment. Adverse events were carefully recorded. Each patient received HIFU for one thyroid nodule, solid or mixed, with mean diameter ≥8 mm, and no suspicion of malignancy. The HIFU device was progressively adjusted with stepwise testing. The energy level for ablation ranged from 35 to 94 J/pulse for different groups of patients. One pathologist examined all removed thyroids.Three patients discontinued treatment due to pain or skin microblister. Among the remaining 22 patients, 16 showed significant changes by ultrasound. Macroscopic and histological examinations showed that all lesions were confined to the targeted nodule without affecting neighboring structures. At pathological analysis, the extent of nodule destruction ranged from 2% to 80%. Five out of 22 patients had over 20% pathological lesions unmistakably attributed to HIFU. Seventeen cases had putative lesions including nonspecific necrosis, hemorrhage, nodule detachment, cavitations, and cysts. Among these 17 cases, 12 had both ultrasound changes and cavitation at histology that may be expected for an HIFU effect. In the last three patients ablated at the highest energy level, significant ultrasound changes and complete coagulative necrosis were observed in 80%, 78%, and 58% of the targeted area, respectively. There were no major complications of ablation.This study showed the potential efficacy of HIFU for human thyroid nodule ablation. Lesions were clearly visible by histology and ultrasound after high energy treatments, and safety and tolerability were good. We identified a power threshold for optimal necrosis of the target thyroid tissue. Further studies are ongoing to assess nodule changes at longer follow-up times.

Summary Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin–bleomycin–vinblastine–dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide–etoposide–oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m2 days 1–3), etoposide (150 mg/m2 days 1–3) and oxaliplatin (130 mg/m2 day 1). Patients

Diffuse large B-cell lymphoma is the most common and one of the most aggressive lymphomas in adults. The standard, R-CHOP-based treatment needs improvement. There has been recent interest in anti-angiogenic therapy, but its cellular effects in lymphoma are little known. In five aggressive B-cell lymphoma patients, we analyzed the microvessel and lymphoma cell changes after Aflibercept, an angiogenic inhibitor. Under ultrasonography, we performed two biopsies, one before any treatment and one two hours after Aflibercept, before R-CHOP. Using ultrasonography, immuno-histochemistry, double immuno-fluorescent staining, and electron microscopy, we compared the early changes induced by Aflibercept to the early changes induced by R-CHOP in three control patients. We identified microvessel damage in the five patients treated with Aflibercept but not in the three patients treated with R-CHOP. Two hours after Aflibercept, microvessel damage was focal, with severely damaged microvessel sections close to normal ones in the same area; different stages of microvessel damage were concomitantly found, with an increase in relative necrosis area in three cases. There was no difference in necrosis or relative microvessel area after R-CHOP. For lymphoma cells, the two biotherapies induced similar changes, with increase in apoptosis but not in proliferation. We identified focal microvascular damage, necrosis, and apoptosis of lymphoma cells in aggressive B-cell lymphoma as soon as 2 h after Aflibercept. This suggests that there is more than one mechanism associated with the early effect of anti-angiogenic therapy in lymphoma.

Until recently, only nuclear medicine techniques allowed combining whole-body anatomical and functional information. Now, diffusion-weighted imaging seeks to compete with these techniques in the field of oncology, providing assessment of tumour spread, characterizing lesions and evaluating therapeutic response. The first issue has been widely evaluated since the first published whole-body diffusion-weighted images looking like scintigraphy. Optimal background suppression and diffusion weighting highlighted tumours with restricted diffusion. For the two latter issues, ADC seems to represent the key element; it should allow differentiation between benign and malignant tissue, and active from inactive lesions after treatment. This is of paramount importance for the monitoring of lymphomas treated with chemotherapy alone, or for solid tumors treated by neoadjuvant therapies. However, imaging protocols still differ between studies, and there is considerable overlap in ADC values between healthy and neoplastic tissues. Despite this difficulty to identify a clinically reliable threshold for malignancy, there is no doubt that ADC will represent as a reliable biomarker in the future for some malignancies, and lymphomas represent a helpful model for this purpose.

Resume L’incidence du cancer du rein est en constante augmentation, touchant notamment les petites tumeurs decouvertes fortuitement, qui representent aujourd’hui plus de 59 % des cas, avec une proportion de patients âges de plus de 65 ans qui a double en 30 ans. L’histoire naturelle des tumeurs de moins de 4 cm est tres variable. La question se pose d’un traitement radical ou d’une simple surveillance chez les patients les plus fragiles de par leur âge ou leurs comorbidites. Les traitements mini-invasifs comme la radiofrequence permettent de traiter les tumeurs de rein avec une morbi-mortalite faible et des resultats oncologiques satisfaisants.

Revised guidelines for the staging and response criteria of Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL) were recently published to include the expanding role of positron emission tomography/computed tomography (PET/CT) using 18F-fluoro-2-deoxyglucose. Here, we discuss the new guidelines and the need for standardized PET acquisition and interpretation in HL and NHL. We also discuss how the role for CT is evolving in the process of making treatment decisions and provide insight on how best to standardize the use of PET/CT for making therapeutic choices.

OBJECTIVE. We describe a coaxial introducer provided with an additional blunt-tip stylet that allows safe access to difficult-to-reach lymph nodes in the chest, abdomen, and pelvis under CT control.CONCLUSION. Once the thoracic, abdominal, or pelvic wall is crossed by the introducer fitted with the sharp-tip stylet, the blunt-tip stylet replaces the sharp stylet for further progression in the fat toward the target. The soft-tip stylet carries a smaller risk of inadvertent perforation displacing vital structures.

Because of its cellular uptake pattern, ferumoxtran-10 may be potentially useful for the imaging of a variety of diseases (eg, atheroma, multiple sclerosis, stroke, renal graft rejection, glomerulonephritis and brain tumors, in addition to differentiation of metastatic and nonmetastatic lymph nodes). The aim of this article is to present a comprehensive review of the safety and tolerability of ferumoxtran-10 as reported during clinical development of the compound as an ultrasmall superparamagnetic iron oxide contrast agent for use in magnetic resonance imaging.The safety profile of ferumoxtran-10 was assessed using pooled data from 37 phase I to III clinical studies in 1777 adults (1663 received the contrast agent [1527 patients and 136 healthy volunteers], 75 received placebo, and 39 patients were enrolled but did not receive study medication).At least one adverse event was reported in 23.2% of patients who received ferumoxtran-10. Adverse events were of mild-to-moderate severity in 86.3% of patients in the ferumoxtran-10 group. At least 1 event considered by the investigator to be related to study treatment was reported in 18.2% of patients in the ferumoxtran-10 group. The most commonly reported treatment-related adverse events were back pain, pruritus, headache, and urticaria. A total of 44 patients (2.6%) in the ferumoxtran-10 group reported 76 serious adverse event (SAE). Only 7 SAEs (0.42%) were considered to be treatment-related (anaphylactic shock, chest pain, dyspnea, skin rash, oxygen saturation decreased, and 2 cases of hypotension). There were 12 deaths, only one of which (anaphylactic shock) was considered to be related to ferumoxtran-10 which was administered by bolus injection of undiluted product, a mode of administration that is no longer recommended. Results in high-risk groups of patients including the elderly and those with hepatic, renal or cardiovascular disease seemed to show no cause for special clinical concern in these groups.Clinical experience to date therefore shows ferumoxtran-10 to be a well tolerated contrast agent.

OBJECTIVE—To characterize insulin action in Africans with ketosis-prone diabetes (KPD) during remission. RESEARCH DESIGN AND METHODS—At Saint-Louis Hospital, Paris, France, 15 African patients with KPD with an average 10.5-month insulin-free near-normoglycemic remission period (mean A1C 6.2%) were compared with 17 control subjects matched for age, sex, BMI, and geographical origin. Insulin stimulation of glucose disposal, and insulin suppression of endogenous glucose production (EGP) and nonesterified fatty acids (NEFAs), was studied using a 200-min two-step (10 mU · m−2 body surface · min−1 and 80 mU · m−2 · min −1 insulin infusion rates) euglycemic clamp with [6,6-2H2]glucose as the tracer. Early-phase insulin secretion was determined during an oral glucose tolerance test. RESULTS—The total glucose disposal was reduced in patients compared with control subjects (7.5 ± 0.8 [mean ± SE] vs. 10.5 ± 0.9 mg · kg−1 · min−1; P = 0.018). EGP rate was higher in patients than control subjects at baseline (4.0 ± 0.3 vs. 3.0 ± 0.1 mg · kg−1 · min−1; P = 0.001) and after 200-min insulin infusion (10 mU · m−2 · min−1: 1.6 ± 0.2 vs. 0.6 ± 0.1, P = 0.004; 80 mU · m−2 · min−1: 0.3 ± 0.1 vs. 0 mg · kg−1 · min−1, P = 0.007). Basal plasma NEFA concentrations were also higher in patients (1,936.7 ± 161.4 vs. 1,230.0 ± 174.1 μmol/l; P = 0.002) and remained higher after 100-min 10 mU · m−2 · min−1 insulin infusion (706.6 ± 96.5 vs. 381.6 ± 55.9 μmol/l; P = 0.015). CONCLUSIONS—The triad hepatic, adipose tissue, and skeletal muscle insulin resistance is observed in patients with KPD during near-normoglycemic remission, suggesting that KPD is a form of type 2 diabetes.

Purpose The aim of this study was to assess the value of combining MRI and 18F-fluorocholine (FCH) PET/CT for patients with a biochemical relapse (BR) after prostate radiotherapy or brachytherapy. Patients and Methods All patients with a BR (BR definition: nadir prostate-specific antigen, +2 ng/mL) had a multiparametric MRI and FCH PET/CT if there was no clinical sign of relapse. Identification of the relapse was considered positive if both imaging techniques were concordant or in case of pathological relapse confirmation. Results Sixty-five consecutive patients were analyzed. Initial treatment was external beam radiation therapy (EBRT; n = 40), surgery followed by EBRT (n = 11), or brachytherapy (n = 14). Gleason score was 6 in 23 patients, 7 in 35 patients, and 8 to 10 in 7 patients. Median prostate-specific antigen value at the time of relapse was 7.6 ng/mL. Determination of relapse location was identified in 46 patients (70.7%). Relapses were only local in 24 patients (37%), nodal in 16 (24.6%), and distant in 9 (14%). In 4 cases, MRI showed a local relapse not seen by FCH PET/CT. Among the 24 patients with an isolated local relapse, 13 underwent a confirmatory biopsy and 9 were positive. At the end, only 7 patients (11%) could have a salvage local treatment: cryotherapy of the prostate in 6 cases and 1 nodal EBRT. Conclusions In case of BR after radiotherapy or brachytherapy, combining MRI and FCH PET/CT could identify the site of relapse in 70% of patients. This could facilitate the selection of the patients for local salvage treatment.

To present a new compartmental analysis model developed to simultaneously measure tissue perfusion and capillary permeability in a tumor using MRI and a macromolecular contrast medium. Rhadomyosarcomas were implanted subcutaneously in 20 rats and studied by 1.5-T MRI using a fast gradient echo sequence (2D fast SPGR TR/TE/alpha 13 ms/1.2 ms/60 degrees ) after injection of a macromolecular contrast medium. The left ventricle and tumor signal intensities were converted into concentrations and modeled using compartmental analysis, yielding tumor perfusion F, distribution volume Vdistribution, volume transfer constant Ktrans, rate constant of influx kpe, and initial extraction (fraction) E. Tumor perfusion was F=43+/-29 ml.min-1.100 g-1. The permeability study allowed the measurement of kpe=0.37+/-0.12 min-1 and Ktrans=0.01+/-0.0031 min-1. The blood volume could be assimilated to the distribution volume (Vdistribution=2.9+/-1.01%) since the capillary leakage was small. The simultaneous assessment of perfusion and permeability allowed quantification of the initial extraction (fraction) E=2.34+/-1.05%. Quantification of both tumor perfusion and capillary leakage is feasible using MRI using a macromolecular blood pool agent. The method should improve tumor characterization.

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty-two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication.

To test, by using an electrotransfer protocol for the transfection of skeletal muscle with naked plasmid complementary DNA, whether in vivo magnetic resonance (MR) imaging can help delineate either the spatial extent of the electric field when contrast agent is injected intraperitoneally or the transfection area when contrast agent is injected locally.Three groups of five mice each were examined at 4 T. Gadopentetate dimeglumine was injected intraperitoneally before electroporation in group 1 and after electroporation in group 2. In group 3, gadopentetate dimeglumine was coinjected in situ with plasmid pCMV-beta Gal in the gastrocnemius muscle before electroporation. MR imaging and muscle preparation for histologic examination were performed 3 days later. On T1-weighted images, increase of muscle signal intensity was determined in regions of interest (ROIs) of treated legs and compared with contralateral ROIs. Comparison of signal intensity increase between groups 1 and 2 was performed with Kruskal-Wallis test.In groups 1 and 3, T1-weighted images of treated muscle showed zones of strongly increased signal intensity. In corresponding ROIs of groups 1, 2, and 3, the mean T1-weighted signal intensity increase at day 3 was 1.64 +/- 0.20 (SD), 1.16 +/- 0.06, and 1.58 +/- 0.17, respectively. The difference between groups 1 and 2 (ie, gadopentetate dimeglumine injected before and after electrotransfer) was significant (P.001) both without and with correction for T2 variation (1.47 +/- 0.19 and 1.04 +/- 0.09, respectively). In group 3, after in situ coinjection of gadopentetate dimeglumine and plasmid, the area of increased signal intensity revealed at ex vivo MR imaging of the muscle showed a reasonable concordance with the transfected area revealed with beta-galactosidase on histologic sections.In vivo and ex vivo results indicate that atraumatic visualization of the permeabilized and transfected area is possible.

Renal-cell carcinomas (RCC) are often resistant to conventional cytotoxic agents. Xenograft models are used for in vivo preclinical studies and drug development. The validity of these studies is highly dependent on the phenotypic and genotypic stability of the models. Here we assessed the stability of six aggressive human RCC xenografted in nude/NMRI mice. We compared the initial samples (P0), first (P1) and fifth (P5) passages for the following criteria: histopathology, immunohistochemistry for CK7, CD10, vimentin and p53, DNA allelic profiles using 10 microsatellites and CGH-array. Next we evaluated the response to sunitinib in primary RCC and corresponding xenografted RCC. We observed a good overall stability between primary RCC and corresponding xenografted RCC at P1 and P5 regarding histopathology and immunohistochemistry except for cytokeratin 7 (one case) and p53 (one case) expression. Out of 44 groups with fully available microsatellite data (at P0, P1 and P5), 66% (29 groups) showed no difference from P0 to P5 while 34% (15 groups) showed new or lost alleles. Using CGH-array, overall genomic alterations at P5 were not different from those of initial RCC. The xenografted RCC had identical response to sunitinib therapy compared to the initial human RCC from which they derive. These xenograft models of aggressive human RCC are clinically relevant, showing a good histological and molecular stability and are suitable for studies of basic biology and response to therapy.