Hyaluronic Acid-RGD Peptide Conjugated Mesoporous Silica-coated Gold Nanorods for Cancer Dual-targeted Chemo-photothermal Therapy

A multifunctional drug delivery system（GNRs@mSiO_2-HA-RGD） was developed by conjugating targeting ligand hyaluronic acid（HA） and RGD with mesoporous silica-coated gold nanorods（GNRs@mSiO_2） for dual-targeted chemo-photothermal therapy. The physiochemical properties of the prepared nanoparticles were characterized by FTIR, UV-vis spectra, and ~1H NMR. Doxorubicin hydrochloride（DOX）, an anticancer drug, was used as the model drug to investigate the drug loading, in vitro drug release profiles and cytotoxicity. The experimental results show that DOX-GNRs@mSiO_2-HA-RGD is synthesized with a mean diameter of 116 nm and a sufficient load capacity of about 19.8%. It also has p H-enzyme sensitive and NIRtriggered drug release manner. Cellular uptake indicates that DOX-GNRs@mSiO_2-HA-RGD exhibits a higher cellular uptake via CD44 receptor and integrin receptor mediated endocytosis compared with the GNRs@mSiO_2 modified with one receptor or no receptor. In comparison with chemotherapy or photothermal therapy alone, DOX-GNRs@mSiO_2-HA-RGD displayes the synergistic effects and achieves a higher therapeutic efficacy. It can be expected that DOX-GNRs@mSiO_2-HA-RGD is a potential dual-targeted chemo-photothermal therapeutic platform for effective cancer treatment.

Silicon dioxide-protection boosting the peroxidase-like activity of Fe single-atom catalyst for combining chemo-photothermal therapy

Carbon-based single-atom catalysts(SACs)have been widely studied in the field of biomedicine due to their excellent catalytic performance.However,carbon-based SACs usually aggregate during pyrolysis,which leads to the reduction of catalytic activity.Here,we describe a method to improve the monodispersion of SACs using silicon dioxide as a protective layer.The decoration of silicon dioxide serves as a buffer layer for individual nanoparticles,which is not destroyed during the pyrolysis process,ensuring the single-particle dispersion of the nanoparticles after etching.This approach increased the hydroxyl groups on the surface of Fe-SAC(Fe-SAC-SE)and improved its water solubility,resulting in a four times enhancement of the peroxidase(POD)-like activity of Fe-SAC-SE(58.4 U/mg)than that of non-protected SACs(13.9 U/mg).The SiO_(2)-protection approach could also improve the catalytic activities of SACs with other metals such as Mn,Co,Ni,and Cu,indicating its generality for SACs preparation.Taking advantage of the high POD-like activity,photothermal properties,and large specific surface area of Fe-SAC-SE,we constructed a synergistic therapeutic system(Fe-SAC-SE@DOX@PEG)for combining the photothermal therapy,catalytic therapy,and chemotherapy.It was verified that the photothermal properties of Fe-SAC-SE@DOX@PEG could effectively improve its POD-like activity,exhibiting excellent tumor-killing performance at the cellular level.This work may provide a general approach to improve the performances of SACs for disease therapy and diagnosis.

Self-assembly nanomicelle-microneedle patches with enhanced tumor penetration for superior chemo-photothermal therapy

Nanomedicine with high specificity has been a promising tool for cancer diagnosis and therapy.However,the successful application of nanoparticle-based superficial cancer therapy is severely hindered by restricted deep tumor tissue accumulation and penetration.Herein,a self-assembly nanomicelle dissolving microneedle(DMN)patch according to the“nano in micro”strategy was conducted to co-deliver a first-line chemotherapeutic agent paclitaxel(PTX),and a photosensitizer IR780(PTX/IR780-NMs@DMNs)for chemo-photothermal synergetic melanoma therapy.Upon direct insertion into the tumor site,DMNs created a regular and multipoint three-dimensional drug depot to maximize the tumor accumulation.Accompanied by the DMN dissolution,the composition of the needle matrixes self-assembled into nanomicelles,which could efficiently penetrate deep tumor tissue.Upon laser irradiation,the nanomicelles could not only ablate tumor cells directly by photothermal conversion but also trigger PTX release to induce tumor cell apoptosis.In vivo results showed that compared with intravenous injection,IR780 delivered by PTX/IR780-NMs@DMNs was almost completely accumulated at the tumor site.The antitumor results revealed that the PTX/IR780-NMs@DMNs could effectively eliminate tumors with an 88%curable rate without any damage to normal tissues.This work provides a versatile and generalizable framework for designing self-assembly DMN-mediated combination therapy to fight against superficial cancer.

NIR-triggered drug delivery system based on phospholipid coated ordered mesoporous carbon for synergistic chemo-photothermal therapy of cancer cells

Chemo-photothermal treatment is one of the most efficient strategies for cancer therapy.However,traditional drug carriers without near-infrared absorption capacity need to be loaded with materials behaving photothermal properties,as it results in complicated synthesis process,inefficient photothermal effects and hindered NIR-mediated drug release.Herein we report a facile synthesis of a polyethylene glycol(PEG)linked liposome(PEG-liposomes)coated doxorubicin(DOX)-loaded ordered mesoporous carbon(OMC)nanocomponents(PEG-LIP@OMC/DOX)by simply sonicating DOX and OMC in PEG-liposomes suspensions.The as-obtained PEG-LIP@OMC/DOX exhibits a nanoscale size(600±15 nm),a negative surface potential(-36.70 mV),high drug loading(131.590 mg/g OMC),and excellent photothermal properties.The PEG-LIP@OMC/DOX can deliver loaded DOX to human MCF-7 breast cancer cells(MCF-7)and the cell toxicity viability shows that DOX unloaded PEG-LIP@OMC has no cytotoxicity,confirming the PEG-LIP@OMC itself has excellent biocompatibility.The NIR-triggered release studies demonstrate that this NIR-responsive drug delivery system enables on-demand drug release.Furthermore,cell viability results using human MCF-7 cells demonstrated that the combination of NIR-based hyperthermal therapy and triggered chemothe rapy can provide higher therapeutic efficacy than re spective monothe rapies.With these excellent features,we believe that this phospholipid coating based multifunctional delivery system strategy should promote the application of OMC in nanomedical applications.

Gold nanorods/tetrahedral DNA composites for chemo-photothermal therapy

Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency.Herein,we constructed a nanocomposite based on gold nanorods(GNRs)and drug-loaded tetrahedral DNA nanostructures(TDN)for chemophotothermal combinational therapy.Anti-tumor drug doxorubicin(DOX)was loaded via the insertion within GC base pairs of TDN.The aptamer AS1411 was attached to the apex of TDN(ATDN)to target tumor cells.The DOX-loaded DNA tetrahedron(ATDN-DOX)was compressed by the GNRs coated with PEI(GNRs@ATDN-DOX)to realize the photothermal function and lysosome escape.GNRs under the illumination of 808nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer.The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN.The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape.The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.

Coordination-responsive drug release inside gold nanorod @ metal-organic framework core-shell nanostructures for near-infrared-induced synergistic chemo-photothermal therapy

Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 （ZIF-8）, a typical metal-organic framework （MOF）, is coated onto single gold nanorod （AuNR） core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared （NIR） light. Impressivel）~ high doxorubicin hydrochloride （DOX） loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.

Doxorubicin-Ioaded Fe3O4@MoS2-PEG-2DG nanocubes as a theranostic platform for magnetic resonance imaging- guided chemo-photothermal therapy of breast cancer

Molybdenum disulfide （MoS2）, a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging （MRI）-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes （IOMS NCs） via the integration of MoS2 （MS） film onto iron oxide （IO） nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose （2-DG）, a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs （IOMS-PEG-2DG NCs） acted as drug-carriers for doxorubicin （DOX）, which could be easily loaded within the NCs. The obtained IOMS-PEG（DOX）-2DG NCs exhibited a 3？2 relaxivity coefficient of 48.86 （mM）^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG（DOX）-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.

2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy

An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation,tumor progression and metastasis.This makes iron metabolism an attractive therapeutic target.Unfortunately,current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities.We report here a dual-therapeutic prodrug,DOXjade,that allows for iron chelation chemo-photothermal cancer therapy.This prodrug takes advantage of the clinically approved iron chelator deferasirox(ExJade®)and the topoisomerase 2 inhibitor,doxorubicin(DOX).Loading DOXjade onto ultrathin 2D Ti_(3)C_(2) MXene nanosheets produces a construct,Ti_(3)C_(2)-PVP@DOXjade,that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites,while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%.Antitumor mechanistic investigations reveal that upon activation,Ti_(3)C_(2)-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor(TfR).A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo.The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Mesoporous PtPd nanoparticles for ligand-mediated and imaging-guided chemo-photothermal therapy of breast cancer

The synergistic therapy of chemotherapy and photothermal therapy(PTT)has been reported as a promising antitumor strategy.To achieve effective combination therapy,developing more suitable candidate nanomaterials with optimal photothermal property and high chemical drug loading capacity is very necessary.Herein,a bimetallic PtPd nanoparticle was synthesized with the merits of excellent photothermal effect and mesoporous structure for doxorubicin(DOX)loading.We further designed PtPd-ethylene glycol(PEG)-folic acid(FA)-doxorubicin(DOX)nanoparticle for chemo-photothermal therapy of MCF-7 tumor with folic acid engineering to achieve active targeting.Moreover,excellent photoacoustic(PA)imaging of PtPd-PEG-FA-DOX nanoparticles facilitated the precise in vivo tracking and further evaluation of nanoparticles’targeting effect.The in vitro and in vivo results both demonstrated PtPd-PEG-FA-DOX nanoparticles serve as a safe and promising system for effective treatment of MCF-7 tumor.

A pH-responsive biomimetic drug delivery nanosystem for targeted chemo-photothermal therapy of tumors

Smart drug delivery nanosystem is significant for tumor treatments due to its possibility of temporally,spatially,and dose-controlled release.However,the therapeutic efficacy of drug delivery nanosystem is often compromised in cancer treatment as the enrichment of therapeutic agents in the reticuloendothelial system.Herein,doxorubicin(DOX)loaded biomimetic drug delivery nanosystem with macrophage cell membrane(MCM)camouflaged,MnFe_(2)O_(4)-DOX-MCM nanocube(NC),is developed for cancer treatment with tumor targeting,pH-stimuli drug release,and chemo-photothermal therapeutic effects.The nanosystem shows the capability of immune escape and enhanced cellular uptake of cancer cells due to the MCM decoration.Acid-labile bond between the MnFe2O4 NCs and DOX remains stable at physiological condition and release drugs immediately in response to the endo-/lysosome pH stimuli.Meanwhile,the photothermal effect of the nanosystem destroys tumor tissue,which further promotes chemotherapeutic efficacy.In vivo results demonstrate the tumor homing ability and produce a notable synergistic therapeutic effect of the NCs.Thus,biomimetic pH-responsive drug delivery nanosystem,MnFe_(2)O_(4)-DOX-MCM NCs,is an effective nanoplatform,which might be potential application for cancer synergistic treatment.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.

The Role of Music Therapy in Supporting Intellectually Disabled Youth in Senegal

Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Dual-Fields Rotational Total Skin Electron Therapy: Investigation and Implementation

Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. Methods and Materials: The DFR-TSET combined the Stanford 6-field and McGill rotational methods. Dual 6 MeV electron beams in high dose total skin electron mode were used for DFR-TSET on a commercial linac. Beam profiles and dosimetric properties were measured using solid phantoms. The dose rate at expanded source-to-surface distance (SSD) was a combination of static rate and rotational rate. In vivo dosimetry of patient skin was performed on patients’ skin using film, metal oxide semiconductor field-effect transistors (MOSFET), and optically stimulated luminescent dosimeters (OSLD). Results: Dual field rotational total skin electron therapy exhibited good (≤±10%) uniformity in the beam profiles in the vertical direction at an extended SSD of 332 cm with a gantry angulation of ±20˚ deviated from the horizontal direction. In-vivo measurements confirmed acceptable uniformity of the patients’ total body surfaces and revealed anatomically self-blocked or shielded areas where underdosing occurred. Conclusions: The clinical implementation of DFR-TSET effectively utilizes the special mode on a linac. This technique provides short beam-on times, uniform dose distribution, large treatment field, and reduced dose of x-ray contamination to the patients. In-vivo measurements indicate satisfactory delivery and dose uniformity of the prescribed dose. Electron boost fields are recommended at normal SSDs to address underdosed areas.