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.

Strong support effect induced by MXene for the synthesis of metal sulfides nanosheet arrays with sulfur vacancies towards selective CO_(2)-to-CO photoreduction

Selective CO_(2)-to-CO photoreduction is under intensive research and requires photocatalysts with tuned microstructures to accelerate the reaction kinetics.Here,we report CuInS_(2)nanosheet arrays with sulfur vacancies(VS)grown on the two-dimensional(2D)support of Ti_(3)C_(2)T_(x)MXene for CO_(2)-to-CO photoreduction.Our results reveal that the use of Ti_(3)C_(2)T_(x)induces strong support effect,which causes the hierarchical nanosheet arrays growth of CuInS_(2)and simultaneously leads to charge transfer from CuInS_(2)to Ti_(3)C_(2)T_(x)support,resulting in VSformed in CuInS_(2).The strong support effect based on Ti_(3)C_(2)T_(x)is proven to be applicable to prepare a series of different metal indium sulfide arrays with VS.CuInS_(2)nanosheet arrays with VSsupported on Ti_(3)C_(2)T_(x)benefit the photocatalytic selective reduction of CO_(2)to CO,manifesting a remarkable over 14.8-fold activity enhancement compared with pure CuInS_(2).The experimental and computational investigations pinpoint that VSof CuInS_(2)resulting from the support effect of Ti_(3)C_(2)T_(x)lowers the barrier of the rate-limiting step of^(*)COOH→^(*)OH+^(*)CO,which is the key to the photoactivity enhancement.This work demonstrates MXene support effects and offers an effective approach to regulate the atomic microstructure of metal sulfides toward enhancing photocatalytic performance.

Solvation structure design for stabilizing MXene in transition metal ion solutions

Although MXene has attracted great interest in diverse fields,it is susceptible to oxidation in water(H_(2)O)with transition metal ions such as Co^(2+),Fe^(2+),and Cu^(2+),which is pronounced at high temperatures.This impedes the preparation of MXene-based composites and their functional applications.Here,this study revealed that Co^(2+)increases the maximum and average atomic charge of H in H_(2)O to improve the reactivity of H_(2)O,which leads to the fact that Co^(2+)catalyzes the oxidation of Ti_(3)C_(2)T_(x)MXene.Furthermore,the addition of N,Ndimethyl formamide(DMF)reduces theH_(2)Oactivity and improves the oxidation stability of Ti_(3)C_(2)T_(x)in the presence of Co^(2+)via preferentially forming coordination bonds with Co^(2+).This strategy is also effective in enhancing the oxidation tolerance of Ti_(3)C_(2)T_(x)to Fe^(2+)in H_(2)O.Moreover,it is feasible to enhance the oxidation stability of Ti2CTx MXene in H_(2)O with the existence of Co^(2+).By virtue of these,the CoO/Ti_(3)C_(2)T_(x)composite was successfully prepared without obvious Ti_(3)C_(2)T_(x)oxidation,which is desirable to harness the advantages of Ti_(3)C_(2)T_(x)as the complementary component for lithium-ion batteries.This work provides a straightforward paradigm to enhance the oxidation resistance of MXene in H_(2)O in the presence of transition metal ions and at high temperatures,which opens a new vista to use MXene for target applications.