[Extensive transfixing skin necrosis after breast biopsy under local anesthesia: About four cases]. / Nécrose cutanée étendue transfixiante après biopsie mammaire sous anesthésie locale : rapport de quatre cas.

INTRODUCTION: Local anesthetics with adrenaline are widely used in routine practice and have long proven their benefits and safety. The rare complications due to their use mainly concern immuno-allergic and vascular mechanisms. DESCRIPTION: In this article, we present four similar cases of early transfixing skin necrosis occurring after radioguided breast biopsy under local anesthesia using epinephrine local anesthetics in the context of a diagnostic approach to breast cancer. DISCUSSION: Although the literature is comforting about the use of local anesthetics, even on the extremities, severe skin complications continue to be reported sporadically. The analysis and understanding of these phenomena would allow, in the long run, to avoid them and to reduce their importance. CONCLUSION: The occurrence of skin necrosis after breast biopsy under radiographic control is rare and seems to be related to the local anesthetic procedure. Although similar cases have been reported in the literature, it does not seem possible today to conclude on the exact physiopathology of these complications. A better knowledge of the pathophysiology of these complications would help to avoid their occurrence in the future.

Efficacy and safety of crizotinib in ALK-positive systemic anaplastic large-cell lymphoma in children, adolescents, and adult patients: results of the French AcSé-crizotinib trial.

BACKGROUND: The French phase II AcSé-crizotinib trial aimed to evaluate the safety and efficacy of crizotinib in patients with ALK, ROS1, and MET-driven malignancies, including ALK-positive anaplastic large-cell lymphoma (ALK+ ALCL). METHODS: ALK+ ALCL patients 12 months or older with measurable disease and no standard care options available received crizotinib twice daily at 165 mg/m2 in children and adolescents and 250 mg in adults. The primary end-point was the response rate at 8 weeks. RESULTS: Twenty-eight patients were enroled between February 2014 and March 2018. Three patients who were not treated were excluded from the analysis. The median age was 19 years. The median previous line of chemotherapy was two. In the 24 patients with an evaluable response, the response rate at 8 weeks was 67% (95% CI: 47-82%). All patients discontinued crizotinib after a median treatment duration of 3.7 months: eight for progression, two for adverse events (AEs) related to prior treatments, and 15 by choice, including six for allogeneic stem-cell transplantation. The median follow-up was 45 months. Nine patients experienced an event: eight relapses (seven after crizotinib discontinuation and one after dose reduction), and one died in complete remission. The median duration of response was 43.3 months (95% CI: 8.3-not reached). The 3-year progression-free and overall survival rates were 40% (95% CI: 23-59%) and 63% (95% CI: 43-79%). Grade 3 or 4 treatment-related AEs occurred in 32% of patients. CONCLUSION: Crizotinib shows efficacy and an acceptable safety profile in ALK+ ALCL relapsed/refractory patients. However, a large proportion of patients experience a relapse after crizotinib discontinuation. Future studies will assess if prolonged ALK inhibitor exposure has curative potential without consolidation.

Sequence analyses of relapsed or refractory diffuse large B-cell lymphomas unravel three genetic subgroups of patients and the GNA13 mutant as poor prognostic biomarker, results of LNH-EP1 study.

Advances in molecular profiling of newly diagnosed diffuse large B-cell lymphoma (DLBCL) have recently refine genetic subgroups. Genetic subgroups remain undetermined at the time of relapse or refractory (RR) disease. This study aims to decipher genetic subgroups and search for prognostic molecular biomarkers in patients with RR-DLBCL. From 2015 to 2021, targeted next-generation sequencing analyses of germline-matched tumor samples and fresh tissue from RR-DLBCL patients were performed. Unsupervised clustering of somatic mutations was performed and correlations with patient outcome were sought. A number of 120 patients with RR-DLBCL were included in LNH-EP1 study and a molecular tumor landscape was successfully analyzed in 87% of patients (104/120 tumor samples). The median age was 67.5 years (range 27.4-87.4), median number of previous treatments was 2 (range 1-9). The most frequently mutated genes were TP53 (n = 53 mutations; 42% of samples), CREBBP (n = 39; 32%), BCL2 (n = 86; 31%), KMT2D (n = 39; 28%) and PIM1 (n = 54; 22%). Unsupervised clustering separated three genetic subgroups entitled BST (enriched in BCL2, SOCS1, and TNFRSF14 mutations); TKS (enriched in TP53, KMT2D, and STAT6 mutations); and PCM (enriched in PIM1, CD79B, and MYD88 mutations). Median overall survival (OS) was 11.0 (95% confidence interval [CI]: 8.1-12.6) months. OS was not significantly different between the three genetic subgroups. GNA13 mutant was significantly associated with an increased risk of death (hazard ratio: 6.6 [95% CI: 2.1-20.6]; p = .0011) and shorter OS (p = .0340). At the time of relapse or refractory disease, three genetic subgroups of DLBCL patients were delineated, which could help advance precision molecular medicine programs.

Outcomes of Transplant-Eligible Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Salvage Chemotherapy: The Gustave Roussy Experience.

INTRODUCTION: After failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients. PATIENTS AND METHODS: This retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen. RESULTS: Forty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88). CONCLUSION: Second-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.

A new automated method to evaluate 2D mammographic breast density according to BI-RADS® Atlas Fifth Edition recommendations.

OBJECTIVES: Radiologists' visual assessment of breast mammographic density (BMD) is subject to inter-observer variability. We aimed to develop and validate a new automated software tool mimicking expert radiologists' consensus assessments of 2D BMD, as per BI-RADS V recommendations. METHODS: The software algorithm was developed using a concept of Manhattan distance to compare a patient's mammographic image to reference mammograms with an assigned BMD category. Reference databases were built from a total of 2289 pairs (cranio-caudal and medio-lateral oblique views) of 2D full-field digital mammography (FFDM). Each image was independently assessed for BMD by a consensus of radiologists specialized in breast imaging. A validation set of additional 800 image pairs was evaluated for BMD both by the software and seven blinded radiologists specialized in breast imaging. The median score was used for consensus. Software reproducibility was assessed using FFDM image pairs from 214 patients in the validation set to compare BMD assessment between left and right breasts. RESULTS: The software showed a substantial agreement with the radiologists' consensus (unweighted κ = 0.68, 95% CI 0.64-0.72) when considering the four breast density categories, and an almost perfect agreement (unweighted κ = 0.84, 95% CI 0.80-0.88) when considering clinically significant non-dense (A-B) and dense (C-D) categories. Correlation between left and right breasts was high (rs = 0.87; 95% CI 0.84-0.90). CONCLUSIONS: BMD assessment by the software was strongly correlated to radiologists' consensus assessments of BMD. Its performance should be compared to other methods, and its clinical utility evaluated in a risk assessment model. KEY POINTS: • A new software tool assesses breast density in a standardized way. • The tool mimics radiologists' clinical assessment of breast density. • It may be incorporated in a breast cancer risk assessment model.

Patient-assisted compression helps for image quality reduction dose and improves patient experience in mammography.

We evaluated the impact of patient-assisted compression (PAC) on image quality, dose, workflow and patient experience of mammography. Patients aged 40-90 years coming for bilateral mammography were included prospectively in the study. After positioning each breast, the technologist performed the compression and exposure of the first breast, initiated the compression of the other until 3 daN and then let the patient complete the compression using a remote control device. Image quality, compression force, breast thickness, average glandular dose and pain value for each breast were assessed for PAC and technologist compression (TC). The compression level was significantly higher with PAC than TC for both craniocaudal (CC; median difference 2.0 daN, p < 0.0001) and mediolateral oblique (MLO) views (median difference 1.5 daN, p < 0.0001). Breast thickness was reduced with PAC (CC, median difference -1.90 cm, p = 0.02), as well as glandular dose (CC, median difference -0.03, p = 0.02). The image quality was rated equivalent for both modes in 85% (85/100) of cases, superior for PAC in 10% (10/100) of cases and inferior in 5% (5/100) of cases. There was no significant difference in discomfort or pain felt between PAC and TC modes. Seventy-four percent of patients reported that the self-compressing device would facilitate their reattendance. PAC may be a suitable technique for mammography examinations, providing an equivalent image quality to TC. Moreover, as the breast compression level is increased, PAC may help reduce breast thickness, hence glandular dose. The fact that patients have control over the procedure may change their perception of mammography and improve uptake and compliance.

Helping patients make informed decisions. Two-year evaluation of the Gustave Roussy prostate cancer multidisciplinary clinic.

OBJECTIVES: The initial treatment decision for newly diagnosed non-metastatic prostate cancer is complex. Multiple valid approaches exist, without a clear and absolute consensus for every clinical scenario, and therefore specialist opinions may vary. Multidisciplinary consultations focusing on shared decision-making aim to provide an apposite tool for the initial treatment decision. We have evaluated the first two years of activity of the Gustave Roussy Prostate Cancer Multidisciplinary Clinic (PCMC), dedicated to the initial decision-making for non-metastatic prostate cancer. METHODS: PCMC consists of two consecutive specialist consultations with a urological surgeon and a radiation oncologist, followed by a dedicated Tumor Board discussion. A study questionnaire was addressed to all PCMC patients via postal mail. Medical notes and questionnaire responses of 195 eligible patients were analyzed. RESULTS: The questionnaire response rate was 69% (134 patients). Complete satisfaction rate was high (114 of 118 responders, 97%). Patients were offered new treatment options in 55% of cases, and felt better informed in 98% (122 of 125 responders). The double consultation was considered useful (124 of 129 responders, 96%). Reported feeling of active participation was significantly elevated (117 of 131 responders, 89%), while 46% of patients (57 of 125) modified their decision on the management of their prostate cancer following their PCMC consultation. CONCLUSIONS: The experience of a multidisciplinary consultation in the initial management of non-metastatic prostate cancer renders high patient satisfaction, improves their appreciation of feeling better informed, promotes active participation and shared decision-making and strongly influences their final decision.

[Hodgkin lymphoma: Current and future therapeutic strategies]. / Le lymphome de Hodgkin : stratégies thérapeutiques actuelles et futures.

Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups. More recently, several groups have tried to develop treatment strategies adapted to the response to chemotherapy, evaluated by interim PET/CT scan. However to date, the combined treatment with chemotherapy followed by radiation therapy remains a standard in most of the above-diaphragmatic localized forms. Immune checkpoint inhibitors, and especially anti-PD1 antibodies, have shown dramatic results in some serious forms of relapsed or refractory HL, with limited toxicity, and may contribute in the future to reduce the toxicities of treatments.

Three-dimensional computed tomography angiography reconstruction of the origin of the uterine artery and its clinical significance.

PURPOSE: In women, the uterine artery is the main branch of the internal iliac artery, vascularizing most of the uterus. Knowledge of its origin and variations is essential during extensive gynaecological surgery and interventional radiological procedures. We aimed to investigate its origin and explore its anatomical variations by three-dimensional (3D) reconstructed computed tomography (CT) angiography. METHODS: This was a retrospective, monocentric observational study involving CT scans of the abdomen and lower limbs of women < 50 years old with 3D reconstructed CT images of the internal and external iliac arterial axes. RESULTS: Between 01 January 2014 and 31 December 2015, among 986 cases of CT scans performed in women, for all indications, 3D reconstructed images for 43 women could be analysed. The uterine artery originated from a common trunk with the umbilical artery in 62.7% of cases, from a direct branch of the internal iliac artery in 25.6% of cases, directly from the superior gluteal artery in 9.3% of cases and from the internal pudendal artery in 2.3%. CONCLUSIONS: Three-dimensional(3D) reconstructed CT angiography can detect the point of origin of the uterine artery. Therefore, it can be used as a mapping tool of the pelvic arterial tree. Our study corroborates data from the literature that the uterine artery most often originates from a common trunk with the umbilical artery. However, surgeons and intervention radiologists must be aware of the variability of its origin to facilitate the safety of the patients during procedures.

A retrospective, matched paired analysis comparing bendamustine containing BeEAM versus BEAM conditioning regimen: results from a single center experience.

The combination of carmustine, etoposide, aracytin, and melphalan(BEAM) conditioning regimen in autologous stem-cell transplantation (ASCT) is widely used in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. It is also an option in patients with very-high risk aggressive NHL in first complete remission (CR). Recently, a phase Ib-II feasibility study using bendamustine replacing carmustine (BCNU) was reported. We report herein a safety and efficacy analysis of bendamustine-EAM (BeEAM) with a control BEAM counterpart paired cohort (1/2). One hundred and two patients were analyzed. Overall survival (OS) and progression-free survival (PFS) were not reached and seemed to be comparable between both groups. However, grade III or greater diarrhea was significantly higher in BeEAM patients (44 vs. 15%, p = .002). The median number of days with fever >38 °C was significantly higher in BeEAM group (5.5 vs. 2, p < .001). This case-control study suggests that BeEAM followed by ASCT using bendamustine at 100 mg/m2/d is effective but has a different toxicity profile than the BEAM regimen.

Improving digital breast tomosynthesis reading time: A pilot multi-reader, multi-case study using concurrent Computer-Aided Detection (CAD).

PURPOSE: Evaluate concurrent Computer-Aided Detection (CAD) with Digital Breast Tomosynthesis (DBT) to determine impact on radiologist performance and reading time. MATERIALS AND METHODS: The CAD system detects and extracts suspicious masses, architectural distortions and asymmetries from DBT planes that are blended into corresponding synthetic images to form CAD-enhanced synthetic images. Review of CAD-enhanced images and navigation to corresponding planes to confirm or dismiss potential lesions allows radiologists to more quickly review DBT planes. A retrospective, crossover study with and without CAD was conducted with six radiologists who read an enriched sample of 80 DBT cases including 23 malignant lesions in 21 women. Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) compared the readings with and without CAD to determine the effect of CAD on overall interpretation performance. Sensitivity, specificity, recall rate and reading time were also assessed. Multi-reader, multi-case (MRMC) methods accounting for correlation and requiring correct lesion localization were used to analyze all endpoints. AUCs were based on a 0-100% probability of malignancy (POM) score. Sensitivity and specificity were based on BI-RADS scores, where 3 or higher was positive. RESULTS: Average AUC across readers without CAD was 0.854 (range: 0.785-0.891, 95% confidence interval (CI): 0.769,0.939) and 0.850 (range: 0.746-0.905, 95% CI: 0.751,0.949) with CAD (95% CI for difference: -0.046,0.039), demonstrating non-inferiority of AUC. Average reduction in reading time with CAD was 23.5% (95% CI: 7.0-37.0% improvement), from an average 48.2 (95% CI: 39.1,59.6) seconds without CAD to 39.1 (95% CI: 26.2,54.5) seconds with CAD. Per-patient sensitivity was the same with and without CAD (0.865; 95% CI for difference: -0.070,0.070), and there was a small 0.022 improvement (95% CI for difference: -0.046,0.089) in per-lesion sensitivity from 0.790 without CAD to 0.812 with CAD. A slight reduction in specificity with a -0.014 difference (95% CI for difference: -0.079,0.050) and a small 0.025 increase (95% CI for difference: -0.036,0.087) in recall rate in non-cancer cases were observed with CAD. CONCLUSIONS: Concurrent CAD resulted in faster reading time with non-inferiority of radiologist interpretation performance. Radiologist sensitivity, specificity and recall rate were similar with and without CAD.

Are we reproducible in measurement of NET liver metastasis?

Accurate measurement of well-differentiated neuroendocrine tumours (NET) liver metastases is critical to determine tumour slope and to assess treatment efficacy. Our objectives were to determine which CT or MRI sequence is the most reproducible to measure NET liver metastases and to assess the percentage of variability of measurements. Intra and inter-observer variability were studied on triphasic abdominal CT or liver MRI in 22 and 32 NET patients respectively. Patients were treatment-naïve or under somatostatin analogues. A maximum of 5 liver target lesions per patient was defined and three radiologists measured them on each sequence. Reproducibility were analysed by calculating the relative variation (RV) as defined by RECIST criteria. We analysed 1656 target measurements for CT and 3384 for MRI. Intra-observers RV were better than inter-observers. T2 for MRI and portal-phase for CT were associated with the lowest measurement variability. The MRI sequence offering the best intra and inter-observer reproducibility is the T2W-sequence. MRI allows more reproducible measurement than CT (inter-observer RV <20% in 96.8% for MRI and 81% for CT). Our study demonstrates intermediate to high imaging reproducibility of liver metastases measurements in NET patients. Non-enhanced MRI should be preferred to triphasic-CT for follow-up, assessment of treatment and trials.

Poor predictive value of positive interim FDG-PET/CT in primary mediastinal large B-cell lymphoma.

PURPOSE: Though commonly used to assess response to therapy, the prognostic value of interim FDG-PET/CT in Primary Mediastinal Large B-cell Lymphoma (PMBCL) is unclear. METHODS: We conducted a retrospective study on 36 consecutive patients treated at our institution for a PMBCL between 2006 and 2014. All patients with a positive interim FDG-PET/CT had undergone histological restaging consisting either in a surgical debulking of the residual lesion (15 patients) or a CT-guided core needle biopsy (two patients). All FDG-PET/CT were secondarily reviewed according to the more recent Deauville criteria. RESULTS: Interim FDG-PET/CT was considered positive in 17/36 patients using visual evaluation. Among these patients, 14 had a Deauville score of 4. Histological restaging was negative in all but one case, showing inflammation and/or fibrosis. After a median follow-up of 48.5 months, a total of five patients have relapsed, two patients in the positive FDG-PET/CT group, and three patients in the negative FDG-PET/CT group, respectively. CONCLUSIONS: These data indicate that a positive interim FDG-PET/CT does not reflect persistence of active disease in the vast majority of PMBCL cases. The relapse rate appears similar regardless of interim FDG-PET/CT results and interpretation criteria. This suggests that interim FDG-PET/CT has a poor positive predictive value, thus kt should be used with caution in PMBCL.

Not All Patients with a Pancreatic Neuroendocrine Tumour Will Benefit from All Approved or Recommended Therapeutic Options: A Real-Life Retrospective Study.

BACKGROUND: At least nine therapeutic options are recommended or approved for pancreatic neuroendocrine tumour (pNET). The primary endpoint of this study was to determine the number of therapeutic lines given before death. Secondary endpoints were to determine toxic events as a function of number of therapeutic lines and of time. METHODS: Patients with pNET treated between 1998 and 2010 at our centre were characterised. All therapeutic lines were recorded as well as tumour- or toxic-related deaths. Persistent treatment-related toxicity (PTRT) was defined as: chronic kidney disease, anaemia, thrombocytopenia, neutropenia, severe liver failure, cardiac failure and recurrent sepsis, precluding at least one other therapeutic option or second cancers. RESULTS: Ninety-two patients were analysed. The median follow-up was 7 years. The 1-, 2- and 5-year overall survival rates were 90, 81 and 51%, respectively. After 3 and 5 therapeutic lines, 23 and 50% of patients had died, respectively. After 3 and 5 lines, the frequency of toxic events was 8 and 24%, respectively. Overall, 17 toxic events were observed including 6 treatment-related deaths and 11 PTRT. After 1, 2 and 5 years of treatment, the frequency of toxic events was 6, 9 and 16%, respectively. CONCLUSION: Tumour- and toxic-related deaths as well as PTRT may preclude access to all therapeutic options in patients with pNET. Optimised risk benefit sequence should be investigated.

Blue Lymphangitis of the Breast after Breast Cancer: Case Report.

Carcinomatous lymphangitis accounts for 5% of all skin metastases, but blue lymphangitis of the breast has never been described. We report a case of blue lymphangitis of the breast in a patient 11 years after treatment for ipsilateral breast cancer that was in full remission. Breast examination and imaging showed no other abnormalities. Skin biopsy revealed a carcinomatous-pigmented infiltration corresponding to melanoma metastasis, which helped highlight a primitive right flank injury. This case report emphasizes that a full body exam should always be performed with unusual presentation of breast cancer and reiterates the indispensable place of histology before any diagnosis.

The challenge of rapid diagnosis in oncology: Diagnostic accuracy and cost analysis of a large-scale one-stop breast clinic.

PURPOSE: Rapid diagnosis is a key issue in modern oncology, for which one-stop breast clinics are a model. We aimed to assess the diagnosis accuracy and procedure costs of a large-scale one-stop breast clinic. PATIENTS AND METHODS: A total of 10,602 individuals with suspect breast lesions attended the Gustave Roussy's regional one-stop breast clinic between 2004 and 2012. The multidisciplinary clinic uses multimodal imaging together with ultrasonography-guided fine needle aspiration for masses and ultrasonography-guided and stereotactic biopsies as needed. Diagnostic accuracy was assessed by comparing one-stop diagnosis to the consolidated diagnosis obtained after surgery or biopsy or long-term monitoring. The medical cost per patient of the care pathway was assessed from patient-level data collected prospectively. RESULTS: Sixty-nine percent of the patients had masses, while 31% had micro-calcifications or other non-mass lesions. In 75% of the cases (87% of masses), an exact diagnosis could be given on the same day. In the base-case analysis (i.e. considering only benign and malignant lesions at one-stop and at consolidated diagnoses), the sensitivity of the one-stop clinic was 98.4%, specificity 99.8%, positive and negative predictive values 99.7% and 99.0%. In the sensitivity analysis (reclassification of suspect, atypical and undetermined lesions), diagnostic sensitivity varied from 90.3% to 98.5% and specificity varied from 94.3% to 99.8%. The mean medical cost per patient of one-stop diagnostic procedure was €420. CONCLUSIONS: One-stop breast clinic can provide timely and cost-efficient delivery of highly accurate diagnoses and serve as models of care for multiple settings, including rapid screening-linked diagnosis.

Variability and errors when applying the BIRADS mammography classification.

To standardize mammographic reporting, the American College of Radiology mammography developed the Breast Imaging Reporting and Data System (BIRADS) lexicon. However, wide variability is observed in practice in the application of the BIRADS terminology and this leads to classification errors. This review analyses the reasons for variations in BIRADS mammography, describes the types of errors made by readers with illustrated examples, and details BIRADS category 3 which is the most difficult category to use in practice.