Добірка наукової літератури з теми "330.322.54 (043)"

AbstractAimIt is unclear whether body mass index (BMI) is a useful measurement for examining prostate motion. Patient’s subcutaneous adipose tissue thickness (SAT) and weight has been shown to correlate with prostate shifts in the left/right direction. We sought to analyse the relationship between BMI and interfraction prostate movement in order to determine planning target volume (PTV) margins based on patient BMI.Materials and methodsIn all, 38 prostate cancer patients with three implanted gold fiducial markers in their prostate were recruited. Height, mass and SAT were measured, and the extent of interfraction prostate movement in the left/right, superior/inferior and anterior/posterior directions was recorded during each daily fiducial marker-based image-guided radiotherapy treatment. Mean corrective shift in each direction for each patient, along with BMI values, were calculated.ResultsThe median BMI value was 28·4 kg/m2 (range 21·4–44·7). Pearson’s product-moment correlation analysis showed no significant relationship between BMI, mass or SAT and the extent of prostate movement in any direction. Linear regression analysis also showed no relationship between any of the patient variables and the extent of prostate movement in any direction (BMI: R2=0·006 (ρ=0·65), 0·002 (ρ=0·80) and 0·001 (ρ=0·86); mass: R2=0·001 (ρ=0·87), 0·010 (ρ=0·54) and 0·000 (ρ=0·99); SAT: R2=0·012 (ρ=0·51), 0·013 (ρ=0·50) and 0·047 (ρ=0·19) for shifts in the X, Y and Z axis, respectively). Patients were grouped according to BMI, as BMI<30 (n=25, 65·8%) and BMI≥30 (n=13, 34·2%). A two-tailed t-test showed no significant difference between the mean prostate shifts for the two groups in any direction (ρ=0·320, 0·839 and 0·325 for shifts in the X, Y and Z axis, respectively).FindingsBMI is not a useful parameter for determining individualised PTV margins. Gold fiducial marker insertion should be used as standard to improve treatment accuracy.

Background:Bimekizumab (BKZ), a monoclonal antibody that selectively neutralises interleukin (IL)-17A and IL-17F, is a potential therapeutic option in ankylosing spondylitis (AS).Objectives:To report 48-week (wk) patient-reported outcomes (PROs) in patients (pts) with AS treated with BKZ in a phase 2b dose-ranging study (BE-AGILE;NCT02963506).Methods:Pts with active AS (Bath AS Disease Activity Index [BASDAI] ≥4; spinal pain ≥4 [0–10]), fulfilling modified New York criteria (central reading), and inadequate response/intolerance to NSAIDs were randomised according to the study design (Figure 1). PROs included spinal pain, fatigue (BASDAI Q1), morning stiffness (mean of BASDAI Q5 + 6), Bath AS Functional Index (BASFI), Medical Outcomes Study (MOS) Sleep Problems Index II and AS Quality of Life questionnaire (ASQoL). Efficacy is reported for pts initially randomised to placebo (PBO) or BKZ 160/320 mg every 4 weeks (Q4W); treatment-emergent adverse events (TEAEs) are reported for pts who received ≥1 dose of study drug (Safety Set).Results:Of 303 pts, 181 were randomised to PBO or BKZ 160/320 Q4W mg at Wk 0; 179/181 completed Wk 12 and 161/181 completed Wk 48. At Wk 12, improvements in pain, fatigue, morning stiffness, BASFI, sleep and ASQoL were greater in BKZ pts vs PBO pts. Responses were further improved or maintained to Wk 48, with no meaningful differences between BKZ 160 mg and 320 mg (Table 1). Serious TEAEs occurred in 13/303 (4.3%) pts (Table 2), which included 2 major adverse cardiac events considered not related to study drug. Oral candidiasis occurred in 16 (5.3%) pts.Table 1.PRO efficacy endpoints to Week 48 (multiple imputation)Mean (SD)WkPBO – BKZ 160 mg(n=24)PBO – BKZ 320 mg(n=36)BKZ 160 mg(n=58)BKZ 320 mg(n=61)Spinal pain06.9 (1.4)7.0 (1.9)6.6 (2.0)7.3 (1.5)CfB12-1.5 (1.6)-0.7 (1.7)-2.6 (2.2)-3.6 (2.4)48-3.7 (2.0)-3.7 (2.6)-3.8 (2.4)-4.7 (2.1)Fatigue06.4 (1.7)6.8 (1.6)6.4 (1.7)6.4 (1.9)CfB12-0.7 (2.5)-1.0 (1.7)-2.1 (2.2)-2.1 (2.5)48-2.7 (2.2)-2.8 (2.4)-3.1 (2.1)-3.3 (2.4)Morning stiffness06.9 (1.7)6.7 (2.0)6.5 (1.8)6.6 (2.1)CfB12-1.5 (1.7)-1.1 (1.5)-2.8 (2.0)-3.4 (2.7)48-3.9 (2.2)-3.6 (2.4)-3.9 (2.2)-4.4 (2.4)BASFI05.8 (1.8)5.5 (2.2)5.5 (2.2)5.9 (2.0)CfB12-1.0 (2.1)-0.3 (1.7)-1.7 (1.8)-2.2 (2.0)48-2.9 (2.2)-2.4 (2.2)-2.5 (2.0)-2.9 (2.2)MOS Sleep Problems Index II045.5 (8.1)45.3 (7.9)46.9 (7.5)47.2 (9.4)CfB122.1 (8.3)1.8 (6.8)5.6 (6.7)6.8 (7.5)487.6 (8.7)8.0 (9.1)6.5 (6.1)8.0 (7.9)ASQoL08.4 (4.7)9.2 (4.7)8.4 (4.3)8.7 (4.3)CfB12-1.3 (5.5)-1.3 (3.7)-3.5 (4.3)-4.6 (4.8)48-4.2 (5.6)-5.3 (5.6)-4.9 (4.1)-5.4 (4.8)CfB: change from baselineTable 2.Overview of TEAEs to Week 48 (Safety Set; N=303)n (%)BKZ 160 mg(n=149)BKZ 320 mg(n=150)All BKZ [a](N=303)Any TEAE103 (69.1)122 (81.3)235 (77.6)Drug-related TEAEs48 (32.2)54 (36.0)110 (36.3)Serious TEAEs5 (3.4)6 (4.0)13 (4.3)Discontinuations due to TEAEs7 (4.7)10 (6.7)20 (6.6)[a] Includes TEAEs for 16 and 64 mg BKZConclusion:Pts with active AS demonstrated rapid and sustained improvements in PROs, sleep and quality of life over 48 wks of BKZ treatment. BKZ was generally well tolerated with no unexpected safety findings versus previous studies.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Lianne S. Gensler Grant/research support from: Pfizer, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, GSK, Novartis, UCB, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Mary Katherine Farmer Employee of: UCB Pharma, Dominique Baeten Employee of: UCB Pharma, Nadine Goldammer Employee of: UCB Pharma, Jason Coarse Employee of: UCB Pharma, Marga Oortgiesen Employee of: UCB Pharma, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma

Abstract Background: Intracranial hemorrhage (ICH) is a serious complication of warfarin therapy. Plasma infusion is the current standard of care in the US, even though most guidelines recommend prothrombin complex concentrate (PCC) as the preferred therapy; PCC has several advantages over plasma including no ABO blood type requirement, no lengthy thawing and infusion process, and a very small volume of virally inactivated pure vitamin K-dependent factors (VKDF) content that causes neither volume overload nor TRALI. Ideal PCC should contain adequate amounts of all VKDF (4-factor). As our group reported at the 2006 ASH meeting, PCC currently available in the USA have a very low FVII content (hence called a 3-factor PCC), often resulting in an incomplete correction of supratherapeutic INR. PCC is, therefore, often supplemented with 1–2 units of plasma to provide FVII; however, many elderly patients on warfarin do not tolerate an additional fluid volume and there is an urgency to correct coagulopathy in ICH. Recombinant FVIIa (rFVIIa) has been used to reverse warfarin effect with variable success. An experimental model has shown that rFVIIa corrects PT/INR in vitro but fails to correct bleeding because it does not address FII and X deficiencies critical for thrombin generation in vivo when compared with PCC. Therefore, we developed a trauma coumadin protocol (TCP) for urgent warfarin reversal for ICH, which includes both PCC and a low dose rFVIIa. Methods: TCP was approved by the Blood Utilization Review Committee of the Parkland Memorial Hospital and consists of administration of 4000 IU PCC (Profilnine, Grifols) and 1.2 mg rFVIIa; 5 mg intravenous Vit K1 is also administered daily for 3 days. PCC contains FII no more than 150 units, FX no more than100 units, and FVII no more than 35 units for each 100 units of FIX. Pre- and post-TCP VKDF were measured when possible (Table 2). We compared 19 patients treated with TCP with a 12 patient-non-TCP control group (warfarin-ICH) treated either with plasma alone (n=3) or plasma plus PCC (n=9). We will also compare (software delay) the 2 groups for extension of hematoma volume; the radiologist will be blinded to the therapy. Results: The TCP group included 12 females and 7 males aged 46–87 years (median 64). The control group included 4 females and 8 males aged 53–89 years (median 73). TCP patients had significantly faster as well as complete correction of PT/INR as compared to the controls. (Table-1). Post-TCP CT scans showed stable hematomas. 1/19 TCP patients with pituitary adenoma had pre-TCP INR of 7.2 and post-TCP INR of 0.9. He developed thrombotic stroke and acute myocardial infarction 2 days later; he was discharged home. The patient received 2.4 mg of rFVIIa because initially the dose of rVIIa was stratified based on INR (1.2 mg for INR 5.0 or less and 2.4 mg for INR greater than 5.0). . Examination of post-treatment FVII levels (Table-2) led us to modify TCP rFVIIa dose to a 1.2 mg, irrespective of INR. Conclusion: TCP rapidly and effectively corrects warfarin-associated coagulopathy in patients with ICH. Because thrombotic complications remain a concern, 4-factor PCC should further be evaluated. Table 1. Test results Time relative to TCP treatment TCP group n=19 Control group n=12 p value INR Mean ± SD (range) Pre 3.1±2.0 (1.4–5.1) 3.2 ±1.6 (1.4–7.2) 0.991 Post 1.1±0.3 (0.9–2.0) 1.4 ±0.3 (0.9–2.0) 0.003 PT Mean ± SD (range) Pre 28.1±17.3 (13.5–65.1) 28.9±14.0 (13.7–62.6) 0.887 Post 10.7±2.2 (9.3–18.1) 13.8±2.8 (9.3–18.3) 0.002 PTT Mean ± SD (range) Pre 36.0±10.3 (21.8–59.8) 38.2 ±11.5 (25.4–60.6) 0.591 Post 24.7±4.2 (19.5–32.2) 27.8±4.5 (22.8–30.9) 0.058 Time from TCP to INR correction (min) Mean ± SD (range) 145.4±107 (22–329) 267±76 (83–697) 0.023 Median 111 240 Table 2. Test results INR PT PTT FII FVII FIX FX Pretreatment Mean ± SD (range) 3.3±2.0 (1.5–7.4) 29.6±17.3 (14.4.–65.1) 35.7±9.9 (30.1–54.7) 54±41 (6–117) 23 ±12 (6–37) 57 ±28 (17–96) 44 ±30 (5–74) Posttreatment Mean ± SD (range) 1.1±0.4 (0.9–2.0) 11.0±3.0 (9.4–18.1) 25.9±4.1 (19.5–32.2) 148±84 (27–323) 394±141 (114–600) 97±22 (58–130) 144±54 (89–268)

323 Background: In 2012 the ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit of mCRPC patients treated with Ra-223 over placebo. To date clinical outcomes of Ra-223 treatment in a non-study population have not been prospectively evaluated. Methods: The ROTOR registry aimed to include 300 patients in 20 Dutch hospitals prior to Ra-223 treatment at the physician’s discretion. Clinical parameters collected included: positioning of Ra-223, Adverse Events (AE’s; CTCAE v4.03), Skeletal Related Events (SRE) and survival data. SRE was defined as radiotherapy to a bone metastasis, a new pathological fracture, spinal cord compression and/or bone surgery. Progression-Free Survival (PFS) was defined as survival until radiological or clinical progression, subsequent treatment or death. Results: Between April 2014 and September 2017, 305 patients were included of whom 300 were evaluable. The mean age of patients was 72.6 (range 46.3-91.5) years, 255 (85%) had ≥ 6 bone metastases and 197 (65.5%) were pretreated with taxanes and/or abiraterone or enzalutamide (214 (71.3%)). Two-hundred and ninety (96.7%) patients were treated with Ra-223. Twenty-nine (9.7%), 104 (34.7%), 96 (32%) and 66 (22%) patients received Ra-223 as a first, second, third, ≥ fourth mCRPC treatment line, respectively. Patients received an average of 4.6 (SD 1.8) cycles of Ra-223, while 140 (46.7%) completed all six cycles. After a median follow-up of 13.2 months, PFS was 5.1 (CI 4.5-5.8) months and OS 15.2 (CI 12.8-17.6) months. Eighty-two (27.3%) patients were hospitalized during Ra-223 treatment (Serious AE). Grade ≥ 3 anemia, neutropenia and thrombocytopenia was found in 54 (18.0%), 8 (2.7%) and 11 (3.7%) patients, respectively. Other frequent AE’s (all grades) were nausea (90 (30%)), diarrhea (83 (27.7%)) and fatigue (178 (59.3%)). SREs were observed in 46 (15.3%) patients; 22 (7.3%) received radiotherapy, 6 (2%) developed pathologic fractures, 17 (5.6%) spinal cord compression and 1 (0.3%) received bone surgery during Ra-223 therapy. Conclusions: The non-study ROTOR population had characteristics, all grade AEs and OS comparable with the treatment arm of ALSYMPCA. Clinical trial information: NCT03223597.

We tested the validity and reliability of the BioSpace InBody 320, Omron and Bod-eComm body composition devices in men and women (n 254; 21–80 years) and boys and girls (n 117; 10–17 years). We analysed percentage body fat (%BF) and compared the results with dual-energy X-ray absorptiometry (DEXA) in adults and compared the results of the InBody with underwater weighing (UW) in children. All body composition devices were correlated (r 0·54–0·97; P ≤ 0·010) to DEXA except the Bod-eComm in women aged 71–80 years (r 0·54; P = 0·106). In girls, the InBody %BF was correlated with UW (r 0·79; P ≤ 0·010); however, a more moderate correlation (r 0·69; P ≤ 0·010) existed in boys. Bland–Altman plots indicated that all body composition devices underestimated %BF in adults (1·0–4·8 %) and overestimated %BF in children (0·3–2·3 %). Lastly, independent t tests revealed that the mean %BF assessed by the Bod-eComm in women (aged 51–60 and 71–80 years) and in the Omron (age 18–35 years) were significantly different compared with DEXA (P ≤ 0·010). In men, the Omron (aged 18–35 years), and the InBody (aged 36–50 years) were significantly different compared with DEXA (P = 0·025; P = 0·040 respectively). In addition, independent t tests indicated that the InBody mean %BF in girls aged 10–17 years was significantly different from UW (P = 0·001). Pearson's correlation analyses demonstrated that the Bod-eComm (men and women) and Omron (women) had significant mean differences compared with the reference criterion; therefore, the %BF output from these two devices should be interpreted with caution. The repeatability of each body composition device was supported by small CV ( < 3·0 %).

Background:Bimekizumab (BKZ), a monoclonal antibody that selectively inhibits interleukin (IL)-17A and IL-17F, has demonstrated clinical efficacy and safety in patients with ankylosing spondylitis (AS) treated over a period up to 96 weeks.1,2Objectives:To report 3-year interim safety and efficacy of BKZ in patients with active AS from a phase 2b dose-ranging study (BE AGILE; NCT02963506) and its ongoing open-label extension (OLE; NCT03355573).Methods:BE AGILE study design has been described previously.1 Patients treated with BKZ 160 mg or 320 mg every 4 weeks (Q4W) at Week 48 in BE AGILE were eligible for OLE entry. All OLE patients received BKZ 160 mg Q4W. Treatment-emergent adverse events (TEAEs) are reported for the BE AGILE safety set (patients who received ≥1 dose of BKZ on study entry) for total exposure to BKZ across BE AGILE and the OLE. Efficacy outcomes are reported for the OLE full analysis set (patients who entered the OLE and had ≥1 dose of BKZ and ≥1 valid efficacy variable measurement in the OLE), and include: ASAS40, ASAS20, ASAS PR, ASDAS, ASDAS-CII, ASDAS-MI, ASDAS-ID (<1.3) and ASDAS <2.1. Data are reported as imputed (multiple imputation [MI] based on the missing at random assumption, or non-responder imputation [NRI]) and as observed case (OC).Results:262/303 (86%) patients randomised at BE AGILE study baseline completed Week 48 on BKZ 160 mg or 320 mg. At Week 48, 255/262 (97%) patients entered the OLE (full analysis set: 254); 219 patients had an efficacy assessment at Week 156. Over the 156 weeks, the exposure-adjusted incidence rate (EAIR) per 100 patient-years (PY) of TEAEs was 143.5, with an EAIR of 5.8 for serious TEAEs, 1.3 for serious infections, and 3.8 for Candida infections (Table 1). All Candida infections were mild or moderate; none were systemic or led to study discontinuation. Over 156 weeks, the EAIR of inflammatory bowel disease (1.2), anterior uveitis (0.8), and injection site reactions (0.5) remained low. Efficacy demonstrated at Week 48 in BE AGILE was maintained or improved up to Week 156 (Figure 1). Mean ASDAS improved from 3.9 at BE AGILE baseline to 2.0 and 1.8 at Weeks 48 and 156 respectively (by MI). At Week 156 in the NRI analyses, ASAS40 and ASAS PR were achieved by 62.6% (OC: 72.6%) and 32.7% (OC: 37.9%) patients respectively. ASDAS-ID and ASDAS <2.1 responder rates (NRI) were maintained or continued to increase from Week 48, and by Week 156, responses were achieved by 28.0% (OC: 33.0%) and 57.1% (OC: 67.4%) patients respectively. ASDAS-MI responder rates (NRI) continued to increase from 44.9% at Week 48 to 46.5% at Week 156 (OC: 52.9%).Table 1.Safety for total exposure to BKZ across BE AGILE and the OLEBE AGILEWeeks 0–48BE AGILE + OLEWeeks 0–156n (%) [EAIR/100 PY]BKZ 160 mg(n=149;114.2 PY)BKZ 320 mg(n=150;119.6 PY)All BKZ(N=303;261.3 PY)All BKZ(N=303;781.0 PY)Any TEAE103 (69.1) [168.7]122 (81.3) [221.1]235 (77.6) [186.2]280 (92.4) [143.5]Serious TEAEs5 (3.4) [4.4]6 (4.0) [5.1]13 (4.3) [5.1]43 (14.2) [5.8]Key TEAEs of special monitoringSerious infections3 (2.0) [2.7]1 (0.7) [0.8]4 (1.3) [1.5]10 (3.3) [1.3]Candida infections10 (6.7) [9.1]9 (6.0) [7.9]19 (6.3) [7.5]28 (9.2) [3.8]Inflammatory bowel disease1 (0.7) [0.9]2 (1.3) [1.7]4 (1.3) [1.5]9 (3.0) [1.2]Anterior uveitis1 (0.7) [0.9]1 (0.7) [0.8]2 (0.7) [0.8]6 (2.0) [0.8]Study discontinuations due to TEAEs7 (4.7)10 (6.7)20 (6.6)38 (12.5)Drug-related TEAEs48 (32.2)54 (36.0)110 (36.3)149 (49.2)Deaths1 (0.7)01 (0.3)2 (0.7)TEAEs are reported for the BE AGILE safety set for total exposure to BKZ across BE AGILE and the OLE. There was one death in BE AGILE (cardiac arrest) and one in the OLE (road traffic accident); neither was considered treatment-related.Conclusion:The safety profile of BKZ in patients with AS was in line with previous observations.1.2 Patients treated with BKZ demonstrated sustained and consistent efficacy over 156 weeks.References:[1]van der Heijde D. Ann Rheum Dis 2020;79:595–604; 2. Baraliakos X. Arthritis Rheumatol 2020;72 (suppl 10).Acknowledgements:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, Employee of: Director of Imaging Rheumatology, Atul Deodhar Speakers bureau: Janssen, Novartis, Pfizer, Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB Pharma, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, GSK, Novartis, Pfizer, UCB Pharma, Grant/research support from: Pfizer, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Eli Lilly, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Biocad, Eli Lilly, Gilead, GSK, MSD, Novartis, Pfizer, Samsung Bioepis, UCB Pharma, Grant/research support from: AbbVie, MSD, Novartis, Pfizer, Alan Kivitz Shareholder of: Pfizer, Novartis, Speakers bureau: Amgen, Eli Lilly, Pfizer, Novartis, Consultant of: Novartis, UCB Pharma, Maxime Dougados Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, Novartis, Pfizer, UCB Pharma, Natasha de Peyrecave Employee of: UCB Pharma, Marga Oortgiesen Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, UCB Pharma

ObjectiveTo elucidate current epidemiological, clinical profiles, and treatment of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome.MethodsWe conducted a nationwide survey in 2015 using an established epidemiologic method. Data processing sheets were sent to all neurology and hematology specialist departments throughout Japan to identify patients with POEMS who were seen between April 2012 and March 2015.ResultsThe estimated number of patients with POEMS was 392 (95% confidence interval [CI] 320–464), and the prevalence was 0.3 per 100,000. Detailed clinical profiles were available for 167 patients. Median age at onset was 54 years (range, 21–84 years), and the ratio of male to female was 1.5. All patients showed polyneuropathy; 89% had monoclonal plasma cell proliferation; and 84% had elevated vascular endothelial growth factor level in whom pretreatment serum or plasma was available (n = 87). Other common features were skin changes (84%), edema/effusion (81%), and organomegaly (76%). A total of 160 patients were treated with any of the following: radiation, corticosteroids, melphalan, thalidomide, lenalidomide, bortezomib, or autologous stem cell transplantation. Primary therapeutic options were thalidomide (n = 86) and autologous stem cell transplantation (n = 71). Thirty-nine patients (24%) were initially treated with corticosteroid alone. The 10-year overall survival was 93% (95% CI 86%–96%).DiscussionThis study showed current epidemiologic and clinical status of POEMS syndrome in Japan. A quarter of patients were still inadequately treated with corticosteroid alone, whereas either autologous stem cell transplantation or immunomodulatory drugs improved the prognosis.

Abstract Background: Congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) causes cortisol insufficiency and androgen excess. A phase 2 trial of crinecerfont, a CRF1 receptor antagonist, in 18 adults with 21OHD showed prominent decreases in ACTH, 17-hydroxyprogesterone, and androstenedione (A4), and in women, testosterone (T), after 14 days of treatment. In men with 21OHD, T derives from both adrenals and testes; in poor disease control, A4/T ratio is elevated due to disproportionately increased adrenal A4 production and decreased testicular T production. We sought to determine the impact of crinecerfont on both adrenal and gonadal androgen production in men with 21OHD in this phase 2 trial. Methods: A4 and T data were analyzed for 7 men who completed 1 or more of 4 oral dosing regimens: Cohort 1, 50 mg QHS, n=4; Cohort 2, 100 mg QHS, n=2; Cohort 3, 100 mg QPM, n=5; and Cohort 4, 100 mg BID, n=3 (14 total treatment periods). Mean 0600-1000 4-hour morning window (M4hMW) and mean 24-hour (M24h) A4, T, and A4/T ratios were analyzed from serial serum samples at baseline and on day 15. Results: Dose-dependent reductions in M4hMW A4 were observed [median (range)] in men, consistent with previously presented data in all subjects:Cohort 1: -21% (-84 to -12%);Cohort 2: -37% (-51% to -23%);Cohort 3: -43% (-85% to +140%);Cohort 4: -62% (-90% to -33%). In contrast, M4hMW T showed inconsistent changes [median (range)]: Cohort 1: +18% (-40% to +82%);Cohort 2: -4% (-4.3% to -3.8%);Cohort 3: +9% (-11 to +24%);Cohort 4: +9% (-3% to +27%). Thus, M4hMW A4/T ratios decreased with dose. Values at baseline, on day 15, and percent changes [median (range)] were, respectively:Cohort 1: 0.9 (0.3–2.6), 0.6 (0.1–2.1), -26% (-91% to +23%);Cohort 2: 5.0 (4.8–5.2), 3.3 (2.5–4.2), -35% (-49% to -20%);Cohort 3: 0.6 (0.1–6.9), 0.3 (0.1–2.7), -54% (-85% to +178%);Cohort 4: 3.9 (0.6–5.9), 0.4 (0.3–2.1), -65% (-92% to -31%). M24h A4/T ratios similarly declined in all cohorts. Values at baseline, on day 15, and percent changes [median (range)] were, respectively:Cohort 1: 1.0 (0.3–2.3), 0.4 (0.1–1.9), -33% (-92% to +2%);Cohort 2: 4.3 (3.8–4.9), 2.7 (2.4–3.0), -36% (-51% to -22%);Cohort 3: 0.5 (0.1–4.7), 0.4 (0.1–2.4), -59% (-78% to +310%);Cohort 4: 3.2 (0.4–4.1), 0.4 (0.3–1.7), -58% (-89% to -31%). Conclusions: Following crinecerfont therapy, A4 and A4/T decreased in a dose-dependent manner in men with 21OHD. In contrast to reductions in T observed in women with 21OHD, T did not change consistently and rose in some men. Preserved T values despite marked A4 reductions suggests testicular T production increased during crinecerfont therapy, perhaps due to release of gonadotropin suppression from adrenal-derived androgens. Long term studies are needed to determine if crinecerfont treatment improves additional measures of testicular function in men with 21OHD. Reference: RJ Auchus, et al. J Endocr Soc 2020;4(Suppl 1):OR25-03.

116 Background: Multiple barriers exist in providing quality palliative care to low-income patients with cancer. Such disparities may negatively influence effective management of symptoms including pain. Our objective was to compare referral patterns and characteristics (level of symptom distress) of uninsured vs insured patients. Methods: We reviewed randomly selected charts of 100 Indigent (IND) and 100 Medicaid (MC) patients and compared them with a random sample of 300 patients with insurance (INS) referred during the same time period (1/2010 to 12/2014) to our SCC. Data was collected for date of registration at the cancer center, diagnosis of Advanced Cancer (ACD), first visit to the SCC (PC1), symptom assessment (Edmonton Symptom Assessment Scale-ESAS) at PC1. We excluded self-pay patients. Results: Results for IND, MC and INS (n = 481) respectively are as follows: Mean (SD) Age in yrs. was 50 (12), 48 (11) and 63 (13); p < 0.001. Percentage of non-white was 44%, 51% and 19.5%; p < 0.001. Percentage of unmarried patients was 64%, 68% and 33%; p < 0.001. Mean (SD) ESAS score at PC1 for pain was 5.6 (3.2), 6.7 (2.5), 4.9 (3.2); p < 0.001. Percentage of patients on opioids upon referral was 86%, 62%, and 54%; p < 0.001. Mean (SD) for referral time in months from ACD to PC1 was 8.7 (SD 10.4), 12.3 (SD 18.1) and 12 (SD 19.9) p = 0.31; for no. of encounters with SC per month were 0.46 (0.45), 0.41 (0.46) and 0.3 (0.55); p = 0.01; for survival in months (PC1 to last contact) was 6.4 (5.8), 5.6 (6.4) & 6 (7.22) p = 0.77. Conclusions: Uninsured patients had significantly higher levels of pain, were more frequently on opioids, younger, non-white and not married. They also required a larger number of SCC encounters. Insurance status did not impact timing of SCC referral or SCC follow ups at our cancer center.

Background: Deep inferior epigastric perforator and muscle sparing transverse rectus abdominis muscle flaps are commonly used flaps for autologous breast reconstruction. CT-angiography allows to analyse the perforator course preoperatively. Our aim was to compare the different aspects of perforator anatomy in the most detailed study. Methods: CT-angiographies of 300 female patients with autologous breast reconstruction of 10 years were analysed regarding the anatomy of the deep inferior epigastric artery and every perforator. Results: Overall, 2260 perforators were included. We identified correlations regarding the DIEA branching point and number of perforators and their intramuscular course. The largest perforator emerged more often from the medial branch of the DIEA than the smaller perforators (70% (416/595) vs. 54% (878/1634), p < 0.001) and more often had a direct connection to the SIEV (large 67% (401/595) vs. small 39% (634/1634), p < 0.01). Medial row perforators were larger than the laterals (lateral 1.44 mm ± 0.43 (n = 941) vs. medial 1.58 mm ± 0.52 (n = 1304) (p < 0.001)). The larger and more medial the perforator, the more likely it was connected to the SIEV: perforators with direct connection to the SIEV had a diameter of 1.65 mm ± 0.53 (n = 1050), perforators with indirect connection had a diameter of 1.43 ± 0.43 (n = 1028), perforators without connection had a diameter of 1.31 mm ± 0.37 (n = 169) (p < 0.001). Medial perforators were more often directly connected to the SIEV than lateral perforators (medial 56% (723/1302) vs. lateral 35% (327/941), p < 0.001). A lateral perforator more often had a short intramuscular course than medial perforators (69% (554/800) vs. 45% (474/1055), p < 0.001), which was also more often observed in the case of a small perforator and a caudal exit of the rectus sheath. Conclusion: The largest perforator emerges more often from the medial branch of the DIEA and frequently has a direct connection to the SIEV, making medial row perforators ideal for DIEP flap transplantation.