Dataset Information

Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

ABSTRACT: Purpose: Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondary effectiveness outcomes, will be published later. Overall, CIRT-FR is aiming to support French authorities in the decision making on reimbursement considerations for this treatment.

Methods: Data on patients enrolled in CIRT-FR from August 2017 to October 2019 were analysed. The interim analysis describes clinical practice, baseline characteristics, safety (adverse events according to CTCTAE 4.03) and quality of life (according to EORTC QLQ C30 and HCC module) aspects after TARE.

Results: This cohort included 200 patients with hepatocellular carcinoma (114), metastatic colorectal cancer (mCRC; 38) and intrahepatic cholangiocarcinoma (33) amongst others (15). TARE was predominantly assigned as a palliative treatment (79%). 12% of patients experienced at least one adverse event in the 30 days following treatment; 30-day mortality was 1%. Overall, global health score remained stable between baseline (66.7%), treatment (62.5%) and the first follow-up (66.7%).

Conclusion: This interim analysis demonstrates that data regarding safety and quality of life generated by randomised-controlled trials is reflected when assessing the real-world application of TARE.

Trial registration: Clinical Trials.gov NCT03256994.

SUBMITTER: Loffroy R

PROVIDER: S-EPMC7728633 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

Loffroy Romaric R Ronot Maxime M Greget Michel M Bouvier Antoine A Mastier Charles C Sengel Christian C Tselikas Lambros L Arnold Dirk D Maleux Geert G Pelage Jean-Pierre JP Pellerin Olivier O Peynircioglu Bora B Sangro Bruno B Schaefer Niklaus N Urdániz María M Kaufmann Nathalie N Bilbao José Ignacio JI Helmberger Thomas T Vilgrain Valérie V

Cardiovascular and interventional radiology 20200925 1

<h4>Purpose</h4>Radioembolization has emerged as a treatment modality for patients with primary and secondary liver tumours. This observational study CIRT-FR (CIRSE Registry for SIR-Spheres Therapy in France) aims to evaluate real-life clinical practice on all patients treated with transarterial radioembolization (TARE) using SIR-Spheres yttrium-90 resin microspheres in France. In this interim analysis, safety and quality of life data are presented. Final results of the study, including secondar ...[more]

PMID: 32975600

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Project description:Transarterial radioembolization (TARE) effectively treats unresectable primary and metastatic liver tumors through intra-arterial injection of Yttrium-90 (90 Y) beta particle emitting microspheres which implant around the tumor. Current dosimetry models are highly simplistic and there is a large need for an image-based dosimetry post-TARE, which would improve treatment safety and efficacy. Current post-TARE imaging is 90 Y bremsstrahlung SPECT/CT and we study the use of these images for dosimetry. Retrospective image review of ten patients having a Philips HealthcareTM SPECT/CT following TARE SIR-Spheres® implantation. Emission series with attenuation correction were resampled to 3 mm resolution and used to create image-based dose distributions. Dose distributions and analysis were performed in MIM Software SurePlanTM utilizing SurePlanTM Local Deposition Method (LDM) and a dose convolution method (WFBH). We sought to implement a patient-specific background subtraction prior to dose calculation to make these noisy bremsstrahlung SPECT images suitable for post-TARE dosimetry. On average the percentage of mean background counts to maximum count in the image across all patients was 9.4 ± 4.9% (maximum = 7.6%, minimum = 2.3%). Absolute dose increased and profile line width decreased as background subtraction value increased. The average value of the LDM and WFBH dose methods was statistically the same. As background subtraction value increased, the DVH curves become unrealistic and distorted. Background subtraction on bremsstrahlung SPECT image has a large effect on post-TARE dosimetry. The background contour defined provides a systematic estimate to the activity background that accounts for the scanner and patient conditions at the time of the image study and is easily implemented using commercially available software. Using the mean count in the background contour as a subtraction across the entire image gave the most realistic dose distributions. This methodology is independent of microsphere and software manufacturer allowing for use with any available products or tools.

Project description:BACKGROUND:NTRK1, NTRK2 and NTRK3 gene fusions (NTRK gene fusions) occur in a range of adult cancers. Larotrectinib is a potent and highly selective ATP-competitive inhibitor of TRK kinases and has demonstrated activity in patients with tumours harbouring NTRK gene fusions. PATIENTS AND METHODS:This multi-centre, phase I dose escalation study enrolled adults with metastatic solid tumours, regardless of NTRK gene fusion status. Key inclusion criteria included evaluable and/or measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Larotrectinib was administered orally once or twice daily, on a continuous 28-day schedule, in increasing dose levels according to a standard 3?+?3 dose escalation scheme. The primary end point was the safety of larotrectinib, including dose-limiting toxicity. RESULTS:Seventy patients (8 with tumours with NTRK gene fusions; 62 with tumours without a documented NTRK gene fusion) were enrolled to 6 dose cohorts. There were four dose-limiting toxicities; none led to study drug discontinuation. The maximum tolerated dose was not reached. Larotrectinib-related adverse events were predominantly grade 1; none were grade 4 or 5. The most common grade 3 larotrectinib-related adverse event was anaemia [4 (6%) of 70 patients]. A dose of 100?mg twice daily was recommended for phase II studies based on tolerability and antitumour activity. In patients with evaluable TRK fusion cancer, the objective response rate by independent review was 100% (eight of the eight patients). Eight (12%) of the 67 assessable patients overall had an objective response by investigator assessment. Median duration of response was not reached. Larotrectinib had limited activity in tumours with NTRK mutations or amplifications. Pharmacokinetic analysis showed exposure was generally proportional to administered dose. CONCLUSIONS:Larotrectinib was well tolerated, demonstrated activity in all patients with tumours harbouring NTRK gene fusions, and represents a new treatment option for such patients. CLINCALTRIALS.GOV NUMBER:NCT02122913.

Project description:BackgroundHysterectomy is the most common major gynaecological procedure. The aim of this study was to study vaginal, sexual and urinary symptoms following total abdominal hysterectomy (TAH), non-descent vaginal hysterectomy (NDVH) and total laparoscopic hysterectomy (TLH) in a low resource setting.MethodsA multi-centre randomized controlled trial (RCT) was conducted in two public sector hospitals in Sri Lanka. Participants were patients requiring hysterectomy for non-malignant uterine causes. Exclusion criteria were uterus> 14 weeks, previous pelvic surgery, medical illnesses which contraindicated laparoscopic surgery, and those requiring incontinence surgery or pelvic floor surgery.Vaginal, sexual function and urinary symptoms were assessed by the validated translations of ICIQ-VS and ICIQ-FLUTS questionnaires. Post-operative improvement (pre-operative - post-operative) was assessed.ResultsThere was an improvement (median (IQ1-IQ3) in vaginal symptoms [TAH 6(2-8) vs 4(0-8), p < 0.001; NDVH 6(4-8.5) vs 5(0-8), p < 0.001; TLH 4(2-10.5) vs 4(0-10), p < 0.001], urinary flow symptoms [TAH 2(1-4) vs 1 (0-3), p < 0.001; NDVH 3 (2-5) vs 2 (0.5-4), p < 0.001; TLH 1(1-4) vs 1(0-3), p < 0.05], urinary voiding symptoms [TAH 0(0-0) vs 0(0-0), p = 0.20; NDVH 0(0-1) vs 0(0-0.8), p < 0.05; TLH 0(0-0) vs 0(0-0), p < 0.05] and urinary incontinence symptoms [TAH 0(0-2) vs 0(0-2), p = 0.06; NDVH 0(0-3) vs 0(0-3), p < 0.001; TLH 0(0-3) vs 0(0-2), p < 0.05] at 1-year (TAH n = 47, NDVH n = 45, TLH n = 47). There was an improvement in sexual symptoms only in the TLH group [TAH 0(0-11.5) vs 0(0-14), p = 0.08); NDVH 0(0-0) vs 0(0-0), p = 0.46; TLH 0(0-0) vs 0(0-4), p < 0.05].There was no significant difference among the three different routes in terms of vaginal symptoms score [TAH 2 (0-2), NDVH 0 (0-2), TLH 0 (0-2), p = 0.33], sexual symptoms [TAH 0 (0-0), NDVH 0 (0-0), TLH 0 (0-0), p = 0.52], urinary flow symptoms [TAH 0 (0-1), NDVH 0 (0-1), TLH 0 (0-2), p = 0.56], urinary voiding symptoms [TAH 0 (0-0), NDVH 0 (0-0), TLH 0 (0-0), p = 0.64] and urinary incontinence symptoms [TAH 0 (0-0), NDVH 0 (0-1), TLH 0 (0-1), p = 0.35] at 1-year.ConclusionsThere was a post-operative improvement in vaginal symptoms and urinary symptoms in all three groups. There was no significant difference in pelvic organ symptoms between the three routes; TAH, NDVH and TLH.Trial registrationSri Lanka clinical trials registry, SLCTR/2016/020 and the International Clinical Trials Registry Platform, U1111-1194-8422, on 26 July 2016. Available from: http://slctr.lk/trials/515.

Project description:Objective: To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. Methods: In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. Results: Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline. Conclusion: Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology.

Project description:Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8-86.8) vs. 40.2 Gy (12.5-83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

Project description:BackgroundThe fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP) is a promising new artemisinin-based combination therapy (ACT). We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda.Methods and findingsIn total 3,547 patients were enrolled: 1,814 patients (32% children under five years) received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28-63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; ORs (95%CI) 2.74 (2.13 to 3.51) and 3.11 (2.31 to 4.18), respectively. DP treatment resulted in a rapid clearance of fever and parasitaemia. The PCR genotype corrected efficacy at Day 28 of DP assessed by survival analysis was 98.7% (95%CI 97.6-99.8). DP was superior to the comparator drugs in protecting against both P.falciparum recurrence and recrudescence (P = 0.001, weighted by site). There was no difference between DP and MAS3 in treating P. vivax co-infections and in suppressing the first relapse (median interval to P. vivax recurrence: 6 weeks). Children under 5 y were at higher risk of recurrence for both infections. The proportion of patients developing gametocytaemia (P = 0.002, weighted by site) and the subsequent gametocyte carriage rates were higher with DP (11/1000 person gametocyte week, PGW) than MAS3 (6/1000 PGW, P = 0.001, weighted by site).ConclusionsDP proved a safe, well tolerated, and highly effective treatment of P.falciparum malaria in Asia and Africa, but the effect on gametocyte carriage was inferior to that of MAS3.

Dataset Information

Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

Publications

Short-term Safety and Quality of Life Outcomes Following Radioembolization in Primary and Secondary Liver Tumours: a Multi-centre Analysis of 200 Patients in France.

Similar Datasets

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