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Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma. SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2–5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9–33·6) in the SIRT group and 28·1 months (20·0–35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7–9·9) in the SIRT group versus 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94–1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. Sirtex Medical Inc.

Background: This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens. Methods: Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9–2.2). Results: Of 50 eligible patients, 38 (76%) had received ⩾4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25–50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1–2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0–18.3); 2-year survival was 19.6%. Conclusion: Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC.

PurposeRadioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality.MethodsWe retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy.ResultsThe Progression-Free Survival and Overall Survival (OS) were 7.6 months [95% Confidence Interval (CI): 4.6–10.6] and 16.4 months [95% CI: 7.8–25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11–0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11–4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9 months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4 months, log-rank p = 0.019).ConclusionOur results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly.

PurposeA multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres.MethodsA steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%–79%, no agreement ≤ 49%).ResultsForty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100–120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement).ConclusionPractitioners are encouraged to work towards adoption of these recommendations.

Abstract PurposeIn light of recently published clinical reports and trials, the TheraSphere Global Dosimetry Steering Committee (DSC) reconvened to review new data and to update previously published clinical and dosimetric recommendations for the treatment of hepatocellular carcinoma (HCC).MethodsThe TheraSphere Global DSC is comprised of health care providers across multiple disciplines involved in the treatment of HCC with yttrium-90 (Y-90) glass microsphere–based transarterial radioembolization (TARE). Literature published between January 2019 and September 2021 was reviewed, discussed, and adjudicated by the Delphi method. Recommendations included in this updated document incorporate both the results of the literature review and the expert opinion and experience of members of the committee.ResultsCommittee discussion and consensus led to the expansion of recommendations to apply to five common clinical scenarios in patients with HCC to support more individualized efficacious treatment with Y-90 glass microspheres. Existing clinical scenarios were updated to reflect recent developments in dosimetry approaches and broader treatment paradigms evolving for patients presenting with HCC.ConclusionUpdated consensus recommendations are provided to guide clinical and dosimetric approaches for the use of Y-90 glass microsphere TARE in HCC, accounting for disease presentation, tumor biology, and treatment intent.

Yttrium fluoride (YF3) and yttrium oxide (Y2O3) protective coatings prepared using an atmospheric plasma spraying technique were used to investigate the relationship between surface erosion behaviors and their nanoparticle generation under high-density plasma (1012–1013 cm−3) etching. As examined by transmission electron microscopy, the Y2O3 and YF3 coatings become oxyfluorinated after exposure to the plasma, wherein the yttrium oxyfluoride film formation was observed on the surface with a thickness of 5.2 and 6.8 nm, respectively. The difference in the oxyfluorination of Y2O3 and YF3 coatings could be attributed to Y–F and Y–O bonding energies. X-ray photoelectron spectroscopy analyses revealed that a strongly fluorinated bonding (Y–F bond) was obtained on the etched surface of the YF3 coating. Scanning electron microscopy and energy dispersive X-ray diffraction analysis revealed that the nanoparticles on the 12-inch wafer are composed of etchant gases and Y2O3. These results indicate that the YF3 coating is a more erosion-resistant material, resulting in fewer contamination particles compared with the Y2O3 coating.

We show how a quantum state in a microwave cavity mode can be transferred to and stored in a phononic mode via an intermediate magnon mode in a magnomechanical system. For this we consider a ferrimagnetic yttrium iron garnet (YIG) sphere inserted in a microwave cavity, where the microwave and magnon modes are coupled via a magnetic-dipole interaction and the magnon and phonon modes in the YIG sphere are coupled via magnetostrictive forces. By modulating the cavity and magnon detunings and the driving of the magnon mode in time, a stimulated Raman adiabatic passage-like coherent transfer becomes possible between the cavity mode and the phonon mode. The phononic mode can be used to store the photonic quantum state for long periods as it possesses lower damping than the photonic and magnon modes. Thus our proposed scheme offers a possibility of using magnomechanical systems as quantum memory for photonic quantum information.

The observation of the spin Nernst effect in platinum thin film is reported. This and the spin Hall effects are found to be of similar magnitude. The observation of the spin Hall effect 1 , 2 , 3 triggered intense research on pure spin current transport 4 . With the spin Hall effect 1 , 2 , 5 , 6 , the spin Seebeck effect 7 , 8 , 9 and the spin Peltier effect 10 , 11 already observed, our picture of pure spin current transport is almost complete. The only missing piece is the spin Nernst (–Ettingshausen) effect, which so far has been discussed only on theoretical grounds 12 , 13 , 14 , 15 . Here, we report the observation of the spin Nernst effect. By applying a longitudinal temperature gradient, we generate a pure transverse spin current in a Pt thin film. For readout, we exploit the magnetization-orientation-dependent spin transfer to an adjacent yttrium iron garnet layer, converting the spin Nernst current in Pt into a controlled change of the longitudinal and transverse thermopower voltage. Our experiments show that the spin Nernst and the spin Hall effect in Pt are of comparable magnitude, but differ in sign, as corroborated by first-principles calculations.

The spin chemical potential characterizes the tendency of spins to diffuse. Probing this quantity could provide insight into materials such as magnetic insulators and spin liquids and aid optimization of spintronic devices. Here we introduce single-spin magnetometry as a generic platform for nonperturbative, nanoscale characterization of spin chemical potentials. We experimentally realize this platform using diamond nitrogen-vacancy centers and use it to investigate magnons in a magnetic insulator, finding that the magnon chemical potential can be controlled by driving the system’s ferromagnetic resonance. We introduce a symmetry-based two-fluid theory describing the underlying magnon processes, measure the local thermomagnonic torque, and illustrate the detection sensitivity using electrically controlled spin injection. Our results pave the way for nanoscale control and imaging of spin transport in mesoscopic systems.

Background Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10 , overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo bio-distribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111 In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90 Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90 Y-OTSA-101 for radionuclide therapy. Results From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111 In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90 Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111 In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90 Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90 Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration The study was registered on the NCT01469975 website with a registration code NCT01469975 on November the third, 2011.