Contrast media for hysterosalpingography: systematic search and review providing new guidelines by the Contrast Media Safety Committee of the European Society of Urogenital Radiology.

OBJECTIVES: Hysterosalpingography (HSG) is widely used for evaluating the fallopian tubes; however, controversies regarding the use of water- or oil-based iodine-based contrast media (CM) remain. The aim of this work was (1) to discuss reported pregnancy rates related to the CM type used, (2) to validate the used CM in published literature, (3) to discuss possible complications and side effects of CM in HSG, and (4) to develop guidelines on the use of oil-based CM in HSG. METHODS: A systematic literature search was conducted for original RCT studies or review/meta-analyses on using water-based and oil-based CM in HSG with fertility outcomes and complications. Nine randomized controlled trials (RCTs) and 10 reviews/meta-analyses were analyzed. Grading of the literature was performed based on the Oxford Centre for Evidence-Based Medicine (OCEBM) 2011 classification. RESULTS: An approximately 10% higher pregnancy rate is reported for oil-based CM. Side effects are rare, but oil-based CM have potentially more side effects on the maternal thyroid function and the peritoneum. CONCLUSIONS: 1. HSG with oil-based CM gives approximately 10% higher pregnancy rates. 2. External validity is limited, as in five of nine RCTs, the CM used is no longer on the market. 3. Oil-based CM have potentially more side effects on the maternal thyroid function and on the peritoneum. 4. Guideline: Maternal thyroid function should be tested before HSG with oil-based CM and monitored for 6 months after. CLINICAL RELEVANCE STATEMENT: Oil-based CM is associated with an approximately 10% higher chance of pregnancy compared to water-based CM after HSG. Although side effects are rare, higher iodine concentration and slower clearance of oil-based CM may induce maternal thyroid function disturbance and peritoneal inflammation and granuloma formation. KEY POINTS: • It is unknown which type of contrast medium, oil-based or water-based, is the optimal for HSG. • Oil-based contrast media give a 10% higher chance of pregnancy after HSG, compared to water-based contrast media. • From the safety perspective, oil-based CM can cause thyroid dysfunction and an intra-abdominal inflammatory response in the patient.

Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial.

BACKGROUND: The aim of this trial was to investigate the addition of the anti-SLAMF7 monoclonal antibody elotuzumab to lenalidomide, bortezomib, and dexamethasone (RVd) in induction and consolidation therapy as well as to lenalidomide maintenance treatment in transplant-eligible patients with newly diagnosed multiple myeloma. METHODS: GMMG-HD6 was a phase 3, randomised trial conducted at 43 main trial sites and 26 associated trial sites throughout Germany. Adult patients (aged 18-70 years) with previously untreated, symptomatic multiple myeloma, and a WHO performance status of 0-3, with 3 being allowed only if caused by myeloma disease and not by comorbid conditions, were randomly assigned 1:1:1:1 to four treatment groups. Induction therapy consisted of four 21-day cycles of RVd (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 4, 8, and 11]; and dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, 12, and 15 for cycles 1-2) or, RVd induction plus elotuzumab (10 mg/kg intravenously on days 1, 8, and 15 for cycles 1-2, and on days 1 and 11 for cycles 3-4; E-RVd). Autologous haematopoietic stem-cell transplantation was followed by two 21-day cycles of either RVd consolidation (lenalidomide 25 mg orally on days 1-14; bortezomib 1·3 mg/m2 subcutaneously on days 1, 8, and 15; and dexamethasone 20 mg orally on days 1, 2, 8, 9, 15, and 16) or elotuzumab plus RVd consolidation (with elotuzumab 10 mg/kg intravenously on days 1, 8, and 15) followed by maintenance with either lenalidomide (10 mg orally on days 1-28 for cycles 1-3; thereafter, up to 15 mg orally on days 1-28; RVd/R or E-RVd/R group) or lenalidomide plus elotuzumab (10 mg/kg intravenously on days 1 and 15 for cycles 1-6, and on day 1 for cycles 7-26; RVd/E-R or E-RVd/E-R group) for 2 years. The primary endpoint was progression-free survival analysed in a modified intention-to-treat (ITT) population. Safety was analysed in all patients who received at least one dose of trial medication. This trial is registered with ClinicalTrials.gov, NCT02495922, and is completed. FINDINGS: Between June 29, 2015, and on Sept 11, 2017, 564 patients were included in the trial. The modified ITT population comprised 559 (243 [43%] females and 316 [57%] males) patients and the safety population 555 patients. After a median follow-up of 49·8 months (IQR 43·7-55·5), there was no difference in progression-free survival between the four treatment groups (adjusted log-rank p value, p=0·86), and 3-year progression-free survival rates were 69% (95% CI 61-77), 69% (61-76), 66% (58-74), and 67% (59-75) for patients treated with RVd/R, RVd/E-R, E-RVd/R, and E-RVd/E-R, respectively. Infections (grade 3 or worse) were the most frequently observed adverse event in all treatment groups (28 [20%] of 137 for RVd/R; 32 [23%] of 138 for RVd/E-R; 35 [25%] of 138 for E-RVd/R; and 48 [34%] of 142 for E-RVd/E-R). Serious adverse events (grade 3 or worse) were observed in 68 (48%) of 142 participants in the E-RVd/E-R group, 53 (39%) of 137 in the RVd/R, 53 (38%) of 138 in the RVd/E-R, and 50 (36%) of 138 in the E-RVd/R (36%) group. There were nine treatment-related deaths during the study. Two deaths (one sepsis and one toxic colitis) in the RVd/R group were considered lenalidomide-related. One death in the RVd/E-R group due to meningoencephalitis was considered lenalidomide and elotuzumab-related. Four deaths (one pulmonary embolism, one septic shock, one atypical pneumonia, and one cardiovascular failure) in the E-RVd/R group and two deaths (one sepsis and one pneumonia and pulmonary fibrosis) in the E-RVd/E-R group were considered related to lenalidomide or elotuzumab, or both. INTERPRETATION: Addition of elotuzumab to RVd induction or consolidation and lenalidomide maintenance in patients with transplant-eligible newly diagnosed multiple myeloma did not provide clinical benefit. Elotuzumab-containing therapies might be reserved for patients with relapsed or refractory multiple myeloma. FUNDING: Bristol Myers Squibb/Celgene and Chugai.

Factors Impacting Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: A Combined Analysis of the Prospective CIRT Studies.

PURPOSE: Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However, optimising the timing of TARE in relation to systemic therapies and patient selection remains challenging. We report here on the effectiveness, safety, and prognostic factors associated with TARE for ICC in a combined analysis of the prospective observational CIRT studies (NCT02305459 and NCT03256994). METHODS: A combined analysis of 174 unresectable ICC patients enrolled between 2015 and 2020 was performed. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every follow-up visit. Log-rank tests and a multivariable Cox proportional hazard model were used to identify prognostic factors. RESULTS: Patients receiving a first-line strategy of TARE in addition to any systemic treatment had a median OS and PFS of 32.5 months and 11.3 months. Patients selected for first-line TARE alone showed a median OS and PFS of 16.2 months and 7.4 months, whereas TARE as 2nd or further treatment-line resulted in a median OS and PFS of 12 and 9.3 months (p = 0.0028), and 5.1 and 3.5 months (p = 0.0012), respectively. Partition model dosimetry was an independent predictor for better OS (HR 0.59 [95% CI 0.37-0.94], p = 0.0259). No extrahepatic disease, no ascites, and < 6.1 months from diagnosis to treatment were independent predictors for longer PFS. CONCLUSION: This combined analysis indicates that in unresectable ICC, TARE in combination with any systemic treatment is a promising treatment option. LEVEL OF EVIDENCE: level 3, Prospective observational.

Waiting times between examinations with intravascularly administered contrast media: a review of contrast media pharmacokinetics and updated ESUR Contrast Media Safety Committee guidelines.

The pharmacokinetics of contrast media (CM) will determine how long safe waiting intervals between successive CT or MRI examinations should be. The Contrast Media Safety Committee has reviewed the data on pharmacokinetics of contrast media to suggest safe waiting intervals between successive contrast-enhanced imaging studies in relation to the renal function of the patient. CLINICAL RELEVANCE STATEMENT: Consider a waiting time between elective contrast-enhanced CT and (coronary) angiography with successive iodine-based contrast media administrations in patients with normal renal function (eGFR > 60 mL/min/1.73 m2) of optimally 12 h (near complete clearance of the previously administered iodine-based contrast media) and minimally 4 h (if clinical indication requires rapid follow-up). KEY POINTS: • Pharmacokinetics of contrast media will guide safe waiting times between successive administrations. • Safe waiting times increase with increasing renal insufficiency. • Iodine-based contrast media influence MRI signal intensities and gadolinium-based contrast agents influence CT attenuation.

A prospective observational study of real-world treatment and outcome in secondary CNS lymphoma.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) confers a dismal prognosis and treatment advances are constrained by the lack of prospective studies and real-world treatment evidence. METHODS: Patients with SCNSL of all entities were included at first diagnosis and patient characteristics, treatment data, and outcomes were prospectively collected in the Secondary CNS Lymphoma Registry (SCNSL-R) (NCT05114330). FINDINGS: 279 patients from 47 institutions were enrolled from 2011 to 2022 and 243 patients (median age: 66 years; range: 23-86) were available for analysis. Of those, 49 (20 %) patients presented with synchronous (cohort I) and 194 (80 %) with metachronous SCNSL (cohort II). The predominant histology was diffuse large B-cell lymphoma (DLBCL, 68 %). Median overall survival (OS) from diagnosis of CNS involvement was 17·2 months (95 % CI 12-27·5), with longer OS in cohort I (60·6 months, 95 % CI 45·5-not estimable (NE)) than cohort II (11·4 months, 95 % CI 7·8-17·7, log-rank test p < 0.0001). Predominant induction regimens included R-CHOP/high-dose MTX (cohort I) and high-dose MTX/cytarabine (cohort II). Rituximab was used in 166 (68 %) of B-cell lymphoma. Undergoing consolidating high-dose therapy and autologous hematopoietic stem cell transplantation (HDT-ASCT) in partial response (PR) or better was associated with longer OS (HR adjusted 0·47 (95 % CI 0·25-0·89), p = 0·0197). INTERPRETATION: This study is the largest prospective cohort of SCNSL patients providing a comprehensive overview of an international real-world treatment landscape and outcomes. Prognosis was better in patients with SCNSL involvement at initial diagnosis (cohort I) and consolidating HDT-ASCT was associated with favorable outcome in patients with PR or better.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences.

Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients.

Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligible NDMM patients treated in 2005-2020 with novel agent-based triplet/quadruplet IT. Primary endpoints were severe infections, death, or a combination of both. Patients were divided in a training (n = 1333) and three validation cohorts (n = 2367). During IT, 11.8%, 1.8%, and 12.5% of patients in the training cohort experienced severe infections, death, or both, respectively. Four major, baseline risk factors for severe infection/death were identified: low platelet count (<150/nL), ISS III, higher WHO performance status (>1), and age (>60 years). A risk score (1 risk factor=1 point) stratified patients in low (39.5%; 0 points), intermediate (41.9%; 1 point), and high (18.6%; ≥2 points) risk. The risk for severe infection/death increased from 7.7% vs. 11.5% vs. 23.3% in the low- vs. intermediate- vs. high-risk groups (p < 0.001). The risk score was independently validated in three trials incorporating quadruplet IT with an anti-CD38 antibody. Our analyses established a robust and easy-to-use score to identify NDMM patients at risk of severe infection/death, covering the latest quadruplet induction therapies. Trial registrations: HOVON-65/GMMG-HD4: EudraCT No. 2004-000944-26. GMMG-MM5: EudraCT No. 2010-019173-16. GMMG-HD6: NCT02495922. EMN02/HOVON-95: NCT01208766. GMMG-HD7: NCT03617731.

Safe use of contrast media in myasthenia gravis: systematic review and updated European Society of Urogenital Radiology Contrast Media Safety Committee guidelines.

OBJECTIVES: It is uncertain whether modern iodine-based or gadolinium-based contrast media (CM) administration can lead to increased symptoms in patients with myasthenia gravis. METHODS: A systematic search in Medline was conducted for studies describing the symptomatology of myasthenia gravis patients before and after receiving intravenous (IV) CM and having a matched control group of myasthenia gravis patients who did not receive IV CM. RESULTS: Three retrospective studies were selected with a total of 374 myasthenia gravis patients who received iodine-based CM and a total of 313 myasthenia gravis patients who underwent unenhanced CT and served as controls. Pooling of the data from the three retrospective studies showed that in 23 of 374 patients, increased symptoms after iodine-based CM administration were described (6.1%). Increased symptomatology also occurred in 11 of 313 patients after unenhanced CT (3.5%). When looking more deeply into the data of the three studies, conflicting results were found, as two articles did not find any relationship between CM and myasthenia gravis symptoms. The remaining study only found a significant increase in symptomatology within 1 day after CT scanning: seven patients (6.3%) in the contrast-enhanced CT group and one patient (0.6%) in the unenhanced CT group (p = 0.01). CONCLUSIONS: There is limited evidence on the relationship between CM and myasthenia gravis symptoms. In the vast majority of myasthenia gravis patients, CM are safe. Probably, in less than 5% of the patients, iodine-based CM administration may lead to increased severity of the symptoms within the first 24 h after administration. CLINICAL RELEVANCE STATEMENT: Be aware that intravenous administration of iodine-based contrast media can lead to an increase of symptoms in patients with myasthenia gravis within the first 24 h. This can probably happen in less than 5% of the patients. KEY POINTS: • It is unclear whether modern contrast media can lead to increased symptoms in myasthenia gravis patients after intravenous administration. • There seems to be a small risk of increased myasthenia gravis symptoms within 24 h after intravenous administration of iodine-based contrast media, probably in less than 5% of the administrations. • Gadolinium-based contrast media are safe for patients with myasthenia gravis.

Analytical interference of intravascular contrast agents with clinical laboratory tests: a joint guideline by the ESUR Contrast Media Safety Committee and the Preanalytical Phase Working Group of the EFLM Science Committee.

The Contrast Media Safety Committee of the European Society of Urogenital Radiology has, together with the Preanalytical Phase Working Group of the EFLM Science Committee, reviewed the literature and updated its recommendations to increase awareness and provide insight into these interferences. CLINICAL RELEVANCE STATEMENT: Contrast Media may interfere with clinical laboratory tests. Awareness of potential interference may prevent unwanted misdiagnosis. KEY POINTS: • Contrast Media may interfere with clinical laboratory tests; therefore awareness of potential interference may prevent unwanted misdiagnosis. • Clinical Laboratory tests should be performed prior to radiological imaging with contrast media or alternatively, blood or urine collection should be delayed, depending on kidney function.

General condition and comorbidity of long-term survivors of adult acute lymphoblastic leukemia.

Cure rates in adult acute lymphoblastic leukemia (ALL) improved using pediatric-based chemotherapy and stem cell transplantation (SCT). However, limited data on the health condition of cured adults are available whereas pediatric data cannot be transferred. The GMALL analyzed the health status in survivors of adult ALL retrospectively. Physicians answered a questionnaire on general condition (Eastern Cooperative Oncology Group [ECOG] status) and comorbidity or syndrome occurrence observed after treatment. Five hundred and thirty-eight patients with a median age of 29 (range, 15-64) years at diagnosis were analyzed, median follow-up was 7 (range, 3-24) years. Thirty-one percent had received SCT. ECOG status was 0-1 in 94%, 34% had not developed significant comorbidities. Most frequent comorbidities involved the neurologic system (27%), endocrine system (20%), skin (18%), graft-versus-host-disease (15%), cardiac system (13%), fatigue (13%). SCT impacted ECOG status and comorbidity occurrence significantly. ECOG 0-1 was observed in 86% of SCT and 98% of non-SCT patients (P<0.0001); comorbidity was observed in 87% and 57% respectively (P<0.0001). Our analysis elucidates the spectrum of comorbidities in cured adult ALL patients, with higher risk for transplanted patients, providing stimulations for the design of adequate aftercare programs. Overall, a large proportion of non-SCT patients achieved unrestricted general condition. The data provide a reference for new patient-centered endpoints in future trials.

Work and Training Conditions of German Residents and Young Radiologists in Interventional Radiology - A Nationwide Survey.

With the increasing need for minimally invasive procedures based on lower complication rates, higher patient acceptance, and technical developments, there is a growing focus on the sound interventional training of young radiologists. This survey aimed to analyze the current situation in interventional radiology (IR) training in Germany to detect shortcomings and identify areas for improvement.From November 1-30, 2020, an online questionnaire was distributed to representative radiological associations and societies with the request to forward it to radiology residents and radiologists < 40 years. The 44 questions covered six distinct areas from personal working conditions to the characterization of the IR department, training conditions, role of women in IR, and attendance at congresses/external training.A total of 330 participants completed the questionnaire. 77 % of participants expressed a high interest in IR, and 47 % could even imagine subspecializing in interventional radiology. Most institutions provided the necessary learning conditions and infrastructure. The rate of overall satisfaction with IR training conditions was 45 % (vs. a dissatisfaction rate of 39 %). However, females showed a lower satisfaction rate with their training environment than male participants (28 % vs. 51 %; P = 0.06). Positive correlations with work satisfaction were found for the presence and duration of the IR rotation, the number of partly independently/mentored performed interventions, and structured feedback. Moreover, the need for a structured training curriculum was expressed by 67 % of participants.Radiological residents and young radiologists expressed a high interest in interventional radiology, and they rate the infrastructure of German hospitals regarding IR as sufficient. However, they expressed the need for consistent IR rotations and better-structured resident and postgraduate education (curricula & interviews).Interest in interventional radiology among radiological residents and young radiologists in Germany is high, but satisfaction with interventional radiology training leaves room for improvement. The most frequently mentioned aspects that can improve IR training were · organized rotations of at least 6 months. · structured curriculums with face-to-face feedback. · structured guidance by senior interventionists during procedures. CITATION FORMAT: · Sieren M, Katoh M, Mahnken AH et al. Work and Training Conditions of German Residents and Young Radiologists in Interventional Radiology - A Nationwide Survey. Fortschr Röntgenstr 2022; 194: 1346 - 1357.

Nationwide Provision of Radiologically-guided Interventional Measures for the Supportive Treatment of Tumor Diseases in Germany - An Analysis of the DeGIR Registry Data. / Flächendeckende Versorgung mit radiologisch-interventionellen supportiven Maßnahmen bei Tumorerkrankungen und anderen Erkrankungen (DeGIR-Modul C) in Deutschland ­ Eine Analyse der DeGIR-Registerdaten.

PURPOSE: In addition to direct oncologic therapy, interventional radiology plays an important supportive role in oncologic therapy primarily guided by other disciplines. These supporting measures include diagnostic punctures, drainages, biliary interventions, central venous access including port implantations, osteoplasties, pain therapies etc.). This study investigated the extent to which these radiologically guided supportive measures are available in Germany. MATERIAL AND METHODS: All interventional procedures documented in the DeGIR-registry (excluding transhepatic portosystemic shunts) of the years 2018 and 2019 were recorded (DeGIR-module C). A breakdown of the documented interventions was performed based on federal states as well as 40 individual regions (administrative districts and former administrative districts). RESULTS: A total of 136,328 procedures were recorded at 216 centers in DeGIR Module C in 2018 and 2019. On average, 389 cases were documented per hospital in 2018 and 394 cases in 2019; the increase per hospital from 2019 is not statistically significant but is relevant in the aggregate when new participating centers are included, with an overall increase of 10 % (6,554 more cases than the previous year). Normalized to one million inhabitants, an average of 781 procedures took place across Germany in 2018 and 860 in 2019. Districts with no registered procedures are not found for Module C.Indications for Module C interventions were mostly interdisciplinary in 2018 and 2019. In this context, the quality of outcome was very high; for the procedures drain placement, marking and biopsy the technical success was 99 %, while the complication rate was lower than 1 %. CONCLUSION: The structural analysis of this work concludes that in Germany there is good nationwide availability of radiologically guided supportive measures in oncological therapy. Accordingly, the training situation for prospective interventional radiologists is good, as the distribution to centers with high experience is excellent. In addition, the overall outcome quality of radiology-guided interventions is very high. KEY POINTS: · In Germany, there is good nationwide coverage of radiologically guided supportive interventions in oncological therapy.. · The training situation for prospective interventional radiologists is good, as the distribution to centers with high experience is excellent.. · The overall outcome quality of radiology-guided interventions is very high.. CITATION FORMAT: · Nadjiri J, Schachtner B, Bücker A et al. Nationwide Provision of Radiologically-guided Interventional Measures for the Supportive Treatment of Tumor Diseases in Germany - An Analysis of the DeGIR Registry Data. Fortschr Röntgenstr 2022; 194: 993 - 1002.