Stereotactic Body Radiotherapy Combined With Lenvatinib With or Without PD-1 Inhibitors as Initial Treatment for Unresectable Hepatocellular Carcinoma.

PURPOSE: The aim of this study was to compare the clinical benefit and safety of the triple combination of stereotactic body radiotherapy (SBRT), lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors with the dual combination of SBRT and lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC). METHODS AND MATERIALS: Patients with uHCC who received SBRT in combination with lenvatinib and PD-1 inhibitors or SBRT in combination with lenvatinib alone as first-line treatment from October 2018 to July 2022 were reviewed in this study. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were intrahepatic PFS, extrahepatic PFS, and objective remission rate. In addition, safety profiles were assessed by analyzing treatment-related adverse events between the two groups to assess safety profiles. RESULTS: In total, 214 patients with uHCC who received combination therapy were included in this retrospective study. Among them, 146 patients received triple combination therapy of SBRT, lenvatinib, and PD-1 inhibitors (SBRT-L-P group), and 68 patients received dual therapy of SBRT and lenvatinib (SBRT-L group). The median OS times of the 2 groups were 31.2 months and 17.4 months, respectively (P < .001). The median PFS time was significantly longer in the SBRT-L-P group than in the SBRT-L group (15.6 months vs 8.8 months, P < .001). Additionally, the median intrahepatic PFS (17.5 vs 9.9 months, P < .001) and extrahepatic PFS (20.9 vs 11.6 months, P < .001) were significantly longer in the SBRT-L-P group than in the SBRT-L group. The objective remission rate in the SBRT-L-P group was higher than in the SBRT-L group (63.0 vs 39.7%, P = .002). The incidence and severity of treatment-related adverse events in the SBRT-L-P group were comparable to those in the SBRT-L group. CONCLUSION: The use of both lenvatinib and PD-1 inhibitors with SBRT in patients with uHCC was associated with improved overall survival compared with lenvatinib and SBRT alone with a manageable safety profile.

Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study.

BACKGROUND AND OBJECTIVES: Patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombosis (PVTT) are presently lacking effective treatment options. We aimed to compare the efficacy and safety of lenvatinib with or without SBRT for HCC with PVTT. MATERIALS AND METHODS: This retrospective analysis included 37 patients treated with lenvatinib in combination with SBRT and 77 patients treated with lenvatinib alone from August 2018 to August 2021. Overall survival (OS), progression-free survival (PFS), intrahepatic PFS (IHPFS) and objective remission rate (ORR) were compared between the two groups, while adverse events (AEs) was analyzed between the two groups to assess safety profiles. RESULTS: Median OS, PFS and IHPFS were significantly prolonged in the combination treatment group compared with the single treatment group (median OS, 19.3 vs. 11.2 months, p < 0.001; median PFS: 10.3 vs. 5.3 months, p < 0.001; median IHPFS, 10.7 vs. 5.3 months, p < 0.001). Moreover, a higher ORR (56.8% vs. 20.8%, P < 0.001) were observed in the lenvatinib combined with SBRT group. In subgroup analyses of Vp1-2 and Vp3-4 group, median OS, PFS and IHPFS were also significantly longer in the lenvatinib combined with SBRT group than those in the lenvatinib alone group. AEs in the combined therapy group were mostly manageable and the incidence was not statistically significant compared to the monotherapy group. CONCLUSION: Lenvatinib plus SBRT had a significantly better survival benefit than lenvatinib monotherapy in the treatment of HCC patients with PVTT and was well tolerated.

Comparison of stereotactic body radiotherapy with and without lenvatinib for advanced hepatocellular carcinoma: a propensity score analysis.

PURPOSE: Lack of evidence on the benefit of stereotactic body radiotherapy (SBRT) in combination with lenvatinib for advanced hepatocellular carcinoma (HCC). Our research compared the efficacy and safety of SBRT plus lenvatinib versus SBRT alone in clinical practice for the treatment of advanced HCC. METHODS: Propensity score matching (PSM) analysis was used to reduce selection bias. Overall survival (OS), progression-free survival (PFS), intrahepatic PFS (IHPFS), and objective response rate (ORR) were compared between the two groups. Additionally, safety profiles were also evaluated in the two groups. RESULTS: After PSM, 35 patients from each group were selected and the date was compared. Compared with the SBRT alone group, the median OS, PFS, and IHPFS were significantly prolonged in SBRT plus lenvatinib group (median OS 16.8 vs. 11.0 months, pOS = 0.043; median PFS 9.1 vs. 3.7 months, pPFS < 0.001; median IHPFS 9.5 vs. 4.2 months, pIHPFS = 0.004). The 6- and 12-month OS rates were 91.4% and 68.6% in the combined therapy group and 82.9% and 48.6% in the monotherapy group, respectively. The 6- and 12-month PFS rates were 68.6% and 34.3% in the combined therapy group and 31.4% and 8.6% in the monotherapy group, respectively. Furthermore, a higher ORR was observed in SBRT plus lenvatinib group (54.29% vs. 22.86%, p = 0.007). Subgroup analysis of patients with macroscopic vascular invasion (MVI) also had similar results. Moreover, most adverse events (AEs) were mild-to-moderate and manageable in the SBRT plus lenvatinib group. CONCLUSION: SBRT plus lenvatinib is expected to significantly improve OS, PFS, IHPFS, and ORR for patients with advanced HCC when compared to SBRT alone, with manageable adverse effects.

Recent advances in high- ß N experiments and magnetohydrodynamic instabilities with hybrid scenarios in the HL-2A Tokamak.

Over the past several years, high- ß N experiments have been carried out on HL-2A. The high- ß N is realized using double transport barriers (DTBs) with hybrid scenarios. A stationary high- ß N ( > 2 ) scenario was obtained by pure neutral-beam injection (NBI) heating. Transient high performance was also achieved, corresponding to ß N ≥ 3 , n e / n e G ∼ 0.6 , H 98 ∼ 1.5 , f b s ∼ 30 % , q 95 ∼ 4.0 , and G ∼ 0.4 . The high- ß N scenario was successfully modeled using integrated simulation codes, that is, the one modeling framework for integrated tasks (OMFIT). In high- ß N plasmas, magnetohydrodynamic (MHD) instabilities are abundant, including low-frequency global MHD oscillation with n = 1, high-frequency coherent mode (HCM) at the edge, and neoclassical tearing mode (NTM) and Alfvénic modes in the core. In some high- ß N discharges, it is observed that the NTMs with m / n = 3 / 2 limit the growth of the plasma energy and decrease ß N . The low-n global MHD oscillation is consistent with the coupling of destabilized internal (m/n = 1/1) and external (m/n = 3/1 or 4/1) modes, and plays a crucial role in triggering the onset of ELMs. Achieving high- ß N on HL-2A suggests that core-edge interplay is key to the plasma confinement enhancement mechanism. Experiments to enhance ß N will contribute to future plasma operation, such as international thermonuclear experimental reactor .

Control system of neoclassical tearing modes in real time on HL-2A tokamak.

The stability and performance of tokamak plasmas are routinely limited by various magneto-hydrodynamic instabilities, such as neoclassical tearing modes (NTMs). This paper presents a rather simple method to control the NTMs in real time (RT) on a tokamak, including the control principle of a feedback approach for RT suppression and stabilization for the NTMs. The control system combines Mirnov, electron cyclotron emission, and soft X-ray diagnostics used for determining the NTM positions. A methodology for fast detection of 2/1 or 3/2 NTM positions with 129 × 129 grid reconstruction is elucidated. The forty poloidal angles for steering the electron cyclotron resonance heating (ECRH)/electron cyclotron current drive launcher are used to establish the alignment of antenna mirrors with the center of the NTM and to ensure launcher emission intersecting with the rational surface of a magnetic island. Pilot experiments demonstrate the RT control capability to trace the conventional tearing modes (CTMs) in the HL-2A tokamak. The 2/1 CTMs have been suppressed or stabilized by the ECRH power deposition on site or with the steerable launcher.

Development of a real time magnetic island identification system for HL-2A tokamak.

A novel real time magnetic island identification system for HL-2A is introduced. The identification method is based on the measurement of Mirnov probes and the equilibrium flux constructed by the equilibrium fit (EFIT) code. The system consists of an analog front board and a digital processing board connected by a shield cable. Four octal-channel analog-to-digital convertors are utilized for 100 KHz simultaneous sampling of all the probes, and the applications of PCI extensions for Instrumentation platform and reflective memory allow the system to receive EFIT results simultaneously. A high performance field programmable gate array (FPGA) is used to realize the real time identification algorithm. Based on the parallel and pipeline processing of the FPGA, the magnetic island structure can be identified with a cycle time of 3 ms during experiments.

Development of a low-drift integrator system on the HL-2A tokamak.

In this work, we developed a new integrator system with low-drift and small integration time constant less than 1 ms, which applies to the weak signals from magnetic measurements. This integrator system is designed on the basis of the analog drift compensation and the real-time digital correction of residual drift. The analog drift compensation is achieved by the subtraction between two integrators and the digital correction method is available due to the stability of integral drift in short time scale. The algorithm of the residual drift calculation and correction is implemented by the field programmable gate array. The integral drift can be well compensated within 10 mV/10 s at RC = 0.5 ms and meet the requirements of magnetic diagnostic on HL-2A.