The role of radiotherapy in patients with refractory Hodgkin’s lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

Background:Approximately 10%–30%of patients with Hodgkin’s lymphoma(HL)experience relapse or refractory(R/R)disease after first-line standard therapy.Brentuximab vedotin(BV)and immune checkpoint inhibitors(ICIs)have important roles in the salvage treatment of R/R HL.However,subsequent treatment for HL refractory to BV and/or ICI treatment is challenging.Methods:We retrospectively analyzed patients in two institutions who had R/R HL,experienced BV or ICI treatment failure,and received radiotherapy(RT)thereafter.The overall response rate(ORR),duration of response(DOR),progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Overall,19 patients were enrolled.First-line systemic therapy comprised doxorubicin,bleomycin,vinblastine,and dacarbazine(ABVD,84.2%);AVD plus ICIs(10.5%);and bleomycin,etoposide,doxorubicin,cyclophosphamide,vincristine,procarbazine,and prednisone(BEACOPP,5.3%).After first-line therapy,15(78.9%)and four patients(21.1%)had refractory disease and relapsed,respectively.After R/R HL diagnosis,six(31.6%),two(10.5%),and 11(57.9%)patients received BV and ICIs concurrently,BV monotherapy,and ICI monotherapy,respectively.All patients received intensity-modulated RT(n=12,63.2%)or volumetric modulated arc therapy(VMAT;n=7,36.8%).The ORR as well as the complete response(CR)rate was 100%;the median DOR to RT was 17.2 months(range,7.9–46.7 months).Two patients showed progression outside the radiation field;one patient had extensive in-field,out-of-field,nodal,and extranodal relapse.With a median follow-up time of 16.2 months(range,9.2–23.2 months),the 1-year PFS and OS were 84.4%and 100%,respectively.PFS was associated with extranodal involvement(P=0.019)and gross tumor volume(P=0.044).All patients tolerated RT well without adverse events of grade≥3.Conclusion:RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Development of CAR T cell therapy targeting glypican-3 in liver cancer

Objective:Glypican-3(GPC3)is a promising therapeutic target in hepatocellular carcinoma(HCC).We have generated the HN3 and h YP7 antibodies that recognize the N-lobe and C-lobe of GPC3,respectively.Here,we engineered human T cells that express GPC3-specific chimeric antigen receptors(CARs)and evaluated their potential for the treatment of HCC.

A 3D convolutional neural network model with multiple outputs for simultaneously estimating the reactive transport parameters of sandstone from its CT images

Porosity,tortuosity,specific surface area(SSA),and permeability are four key parameters of reactive transport modeling in sandstone,which are important for understanding solute transport and geochemical reaction pro-cesses in sandstone aquifers.These four parameters reflect the characteristics of pore structure of sandstone from different perspectives,and the traditional empirical formulas cannot make accurate predictions of them due to their complexity and heterogeneity.In this paper,eleven types of sandstone CT images were firstly segmented into numerous subsample images,the porosity,tortuosity,SSA,and permeability of the subsamples were calculated,and the dataset was established.The 3D convolutional neural network(CNN)models were subse-quently established and trained to predict the key reactive transport parameters based on subsample CT images of sandstones.The results demonstrated that the 3D CNN model with multiple outputs exhibited excellent prediction ability for the four parameters compared to the traditional empirical formulas.In particular,for the prediction of tortuosity and permeability,the 3D CNN model with multiple outputs even showed slightly better prediction ability than its single-output variant model.Additionally,it demonstrated good generalization per-formance on sandstone CT images not included in the training dataset.The study showed that the 3D CNN model with multiple outputs has the advantages of simplifying operation and saving computational resources,which has the prospect of popularization and application.

Temperature-dependent structural changes of[Bmim]FeCl4 magnetic ionic liquid characterized by an in-situ X-ray absorption fine structure

The temperature-dependent structural changes in 1-butyl-3-methylimidazolium tetrafluoride([Bmim]FeCl4)magnetic ionic liquid(MIL)were investigated by using in-situ X-ray absorption fine structure(XAFS)combined with Raman spectroscopy and DFT calculations.XAFS re sults revealed that the coordination number and bond length of Fe-Cl in the anion of[Bmim]FeCl4 MIL decreased with increments in temperature.These results directly reflected the dissociation of tetrahedral structure[FeCl4]^-,and the formation of bridge-chain[Fe2 Cl5]^+,and[FeCl2]^+species in the anion of[Bmim]FeCl4 MIL.These behaviors indicated that[FeCl4]^-dissociation was endothermic,and was promoted by increased temperature.The results obtained through XAFS were in agreement with those obtained through Raman spectroscopy and DFT calculations.

Structural analysis of [Bmim]_2CuCl_4 ionic liquids in the presence of water and ethanol by XAFS technique

The structure of [Bmim]2CuCl4 ionic liquids （Bmim： 1-butyl-3-methylimidazolium） with different ratios of H2O and C2H5OH was investigated using X-ray absorption fine structure （XAFS） technique. In this study, XAFS was employed to directly probe the conformational variations of copper ions in [Bmim]2CuCl4 with the addition of either water or ethanol. XAFS analysis confirmed that the structure of ionic liquids gradually transformed from tetrahedral to octahedral configuration with the increase in ratio of H2O. Our results also showed that water molecules coordinated with the copper ions of [Bmim]2CuCl4, leading to the conformational change in ionic liquids. However, the XAFS spectra of [Bmim]zCuCIa/C2H5OH indicated no coordination of anhydrous ethanol with the copper ions of [Bmim]2CuC14. The structure of [Bmim]2CuCl4 ionic liquids is maintained as the tetrahedral configuration in presence of ethanol. Therefore, anhydrous ethanol causes little variation in the structure of ionic liquids and it is a good solvent for the dilution of ionic liquids.