Autonomous VR Exposure Therapy for Anxiety Disorders Using Conversational AI—Ethical and Technical Implications and Preliminary Results

The need for psychotherapy is very high and the lack of care causes a lot of suffering and high costs. This paper presents an interdisciplinary approach to creating an AI-guided exposure therapy for fear of heights in virtual reality (VR). First, ethical principles for the use of conversational AI in psychotherapy were translated into technical requirements and made measurable. Based on this, an autonomous virtual reality exposure therapy was iteratively developed with a therapist. The feasibility and implementation of the ethical principles were tested with a patient. The patient was very satisfied with the VR setup. The AI therapist was also rated positively, although there is still room for improvement regarding conversational skills. Overall, the paper shows how AI can contribute responsibly to improving the psycho-therapeutic supply. It also provides guidelines that make ethical principles tangible and measurable for developers.

Relationship between primary caregivers’social support function,anxiety,and depression after interventional therapy for acute myocardial infarction patients

BACKGROUND An acute myocardial infarction(AMI)is often treated with direct coronary intervention and requires home-based rehabilitation.Caregivers of patients with AMI need adequate social support to maintain high-quality care;however,their social support function is low,and relevant indicators for intervention must be identified.AIM To analyze the correlation between social support for primary caregivers,their anxiety,and depression,when caring for patients with AMI after interventional therapy.METHODS Using convenience sampling,we selected 300 primary caregivers of patients with AMI who had undergone interventional therapy.The Social Support Rating Scale(SSRS),Self-Rating Anxiety Scale(SAS),and Self-Rating Depression Scale(SDS)were used to assess the primary caregivers.A Pearson’s correlation analysis was used to analyze the correlations between the SSRS,SAS,and SDS,and a multiple logistic regression analysis was used to analyze the factors influencing the low social support function of primary caregivers.The receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the predictive ability of the SAS and SDS for low social support function in primary caregivers.RESULTS Considering the norm among Chinese people,AMI caregivers’objective support,subjective support,support utilization,and SSRS scores were lower,while their SAS and SDS scores were higher.The SSRS scores of female caregivers were higher than those of the male caregivers(t=2.123,P=0.035).The Pearson correlation analysis showed that objective support,subjective support,support utilization,and SSRS total scores were significantly correlated with both SAS(r=-0.414,-0.460,-0.416,-0.535)and SDS scores(r=-0.463,-0.379,-0.349,-0.472).Among the 300 AMI caregivers,56 cases(18.67%)had a low level of support function(SSRS≤22 points).Logistic regression model analysis showed that SAS and SDS were independent risk factors for low social support function of AMI caregivers,regardless of adjustment for other variables(P<0.05).SAS and SDS predicted that the AUC of AMI caregivers with low support function was 0.84,sensitivity was 67.9 and 71.4,and specificity was 84.0 and 70.9,respectively.CONCLUSION The social support function of the primary caregiver of patients with AMI after interventional therapy was lower and negatively correlated with anxiety and depression in the primary caregiver.

Significance of music therapy in treating depression and anxiety disorders among people with cancer

Globally,cancer cases and mortality have recently escalated and have attracted global concern.The clinical diagnosis and manifestation of cancer can result in significant mental health issues like depression and anxiety disorders.The tendency of people with cancer to suffer from psychological disorders such as anxiety and depression is usually high.A significant number of deaths related to cancer may likely not be from the killer disease but from psychological disorders associated with the illness.The utilization of music as a remedial approach to healing mental disorders cannot be overstated.Thus,identifying the impacts of music therapy in dealing with depression and anxiety disorders among people with cancer is relevant,as the majority of methods used in treating cancer have some side effects which may trigger psychological disorders in cancer patients.Ultimately,this study explored the significance of music therapy in treating depression and anxiety disorders among people with cancer.To achieve the aim of this study,the authors employed a narrative literature review to investigate the significance of music therapy in addressing depression and anxiety disorders among people with cancer.The type of literature review employed in this study is to provide an understanding of the selected research papers.The review found that music therapy significantly reduces depression and anxiety disorders among breast cancer,lung cancer,prostate cancer,and colorectal cancer patients.It is needful for healthcare providers to incorporate music therapy interventions while treating people with cancer.This will help reduce cancer deaths resulting from psychological disorders rather than the killer disease,cancer.However,the standardized procedures and evaluation criteria for applying music-based intervention strategies in oncology medicine still need to be further established and improved.

ShotBlocker versus cryotherapy for reducing pain and anxiety associated with subcutaneous injection

Objective:To determine and compare the abilities of Shot Blocker and cryotherapy for reducing pain and anxiety associated with subcutaneous injections.Subcutaneous injection has been used excessively for continuous,low-dose administration of drugs.Considering that these drugs may require prolonged administration,new devices and methods of injection are needed to decrease pain and anxiety associated with repeated drug injections.Methods:A quasi-experimental study design on a purposive sample of 54 patients comprised of both sexes has been utilized.The subjects were divided into 2 equal groups(group 1,Shot Blocker;group 2,cryotherapy),and 3 tools were used,namely the sociodemographic and medical data sheet,Verbal Descriptor Scale for measuring pain,and Beck Anxiety Inventory.Results:A significant reduction in pain and anxiety mean scores was observed after using cryotherapy and Shot Blocker techniques during subcutaneous injection.In addition,the Shot Blocker group exhibited significantly lower pain and anxiety mean scores compared with the cryotherapy group.Conclusions:Our findings revealed that Shot Blocker and cryotherapy were effective non-pharmacological methods for reducing pain and anxiety levels associated with repeated subcutaneous injections.

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.

Meta analysis on the effectiveness of auricular therapy combined with modern medicine in the treatment of depression/anxiety disorders in maintenance hemodialysis patients

Objective:We used meta-analysis to explore the clinical efficacy of auricular point therapy combined with modern medicine in improving depression/anxiety in maintenance hemodialysis patients.Methods:We searched CNKI,Wanfang,Weipu,CBM,The Cochrane Library,PubMed,Web of Science,Embase through computer to build a randomized controlled trials of auricular therapy combined with modern medicine in the treatment of depression/anxiety disorders in China and abroad since 2022.Two evaluators independently screened the studies,extracted and cross-checked the key data in the studies independently after determining the included studies,and then evaluated the quality of the studies respectively.Finally,we used RevMan 5.3 platform for statistical processing of data.Results:This meta-analysis included a total of 12 clinical randomized controlled trials,including a total of 899 patients.The results showed that the observation group was more effective in reducing the scores of Hamilton Anxiety Scale,self rating Anxiety Scale,self rating Depression Scale,Pittsburgh sleep quality index score of maintenance hemodialysis patients.In addition,there was no statistical difference between the observation group and the control group in improving the total clinical effective rate.Conclusion:The observation group has a more obvious effect on the improvement of anxiety or depression in maintenance hemodialysis patients.However,due to the limitation of the quantity and quality of the included studies,the real efficacy of auricular therapy combined with modern medicine in improving anxiety or depression disorder after maintenance hemodialysis still needs to be supported by more carefully designed and standardized multi-center,large-sample clinical studies.

Design of a Biomedical Device to Reduce Anxiety Experienced by Patients Diagnosed with Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease that occurs due to loss of nerve cells that produce dopamine in the brain, affecting approximately 4 million people worldwide. PD patients often feel an increase in anxiety levels daily. While there are medications/exercises to help relieve anxiety, there are limited methods to reduce anxiety without the help of a caretaker. As a result, MEDIC Foundation, a non-profit organization in British Columbia, Canada, is designing an automated system that consists of a wristband and an application which uses vi-bration therapy to help reduce anxiety of PD patients. Literature reviews were conducted to document the project’s needs. Phase I of the project focused on de-veloping a prototype for the application and phase II on developing the wrist-band. The team developed prototypes of a wristband that automatically applies vibration near the median nerve as the heart rate variability (HRV) deviates away from the normal threshold of the user, and an application that displays real-time heart rate variability signals as well as provides for relaxation. The development of the prototype is still in early progress. By creating this automated system, we aim to provide a solution to senior PD patients to relieve anxiety independently. .

Risk and Protective Factors Associated with Depression and Anxiety among Pregnant Women during the COVID-19 Pandemic

Background: The coronavirus disease (COVID-19) pandemic has impacted perinatal women’s mental health. However, protective factors associated with depression among pregnant Japanese women during the pandemic have not been reported. Purpose: The present study investigated the risk and protective factors associated with depression and anxiety among pregnant women during the COVID-19 pandemic. Methods: An online questionnaire was administered to 157 pregnant women between October 2022 and May 2023 at two general hospitals in Japan. The Japanese versions of the Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7) were used to assess symptoms of depression and anxiety. The χ2 test or Fisher’s exact test and multivariate logistic regression model were used to examine factors associated with depression and anxiety among pregnant women. Results: Overall, 47.1% and 35.7% of the pregnant women reported depressive and anxiety symptoms, respectively. A “history of mental illness” was a risk factor for depression and anxiety among pregnant women during the COVID-19 pandemic. Additionally, unmarried status was a risk factor for anxiety among pregnant women, whereas outdoor and indoor exercises were protective factors against depression and anxiety, respectively. Conclusions: Exercise may have protected pregnant women from depression and anxiety during the COVID-19 pandemic. Encouraging exercise may help maintain the mental health of pregnant women who do not have exercise restrictions.

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.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

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.

A Study on the Correlation between Salivary Cortisol Content and Anxiety and Depression in Pregnant and Postpartum Women

Objective: To analyze the correlation between salivary cortisol content and anxiety and depression in pregnant and postpartum women. Method: 300 pregnant and postpartum women who were admitted from January 2021 to December 2021 were selected as the research subjects. They were all tested with the Hamilton Anxiety Scale (HAMA) and the Edinburgh Postnatal Depression Scale (EPDS). 40 pregnant women with anxiety and depression were selected as the observation group, and 50 normal pregnant women were selected as the control group, adopting logistic regression analysis to investigate the correlation between salivary cortisol and postpartum anxiety and depression during pregnancy. Result: The salivary cortisol levels in the observation group were significantly higher than those in the control group before bedtime, after waking up the next day, 15 minutes after waking up, 30 minutes after waking up, 60 minutes after waking up, and 1 hour before lunch (p < 0.05). Maternal depression and anxiety were not related to age, weight, gestational age, negative events, or history of adverse pregnancy and childbirth (p > 0.05). Maternal depression and anxiety are closely related to salivary cortisol levels and educational background (p Conclusion: There is a close correlation between anxiety and depression and an increase in cortisol levels, suggesting that the salivary cortisol awakening response during pregnancy has a predictive effect on the occurrence of postpartum depression.

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.

Anxiety Mouse Model Constructed by Single Intraperitoneal Injection of m-Chlorophenpiperazine

Anxiety disorder is a common mental disorder. It is necessary to establish a rapid, stable and specific anxiety model to provide a theoretical basis for further research on the pathogenesis of anxiety and drug development. A single intraperitoneal injection of m-chlorophenylpipera-zine (mCPP) (1, 2, 4 mg/kg) was given to male ICR mice to establish an anxiety model, and the effects of mCPP on anxiety behavior, pain, athletic ability, passive avoidance response ability and depressive behavior of male ICR mice were evaluated. A single intraperitoneal injection of mCPP shortened the time in open arms and decreased the percentage of time in open arms of mice in the elevated plus-maze test. mCPP also shortened center zone distance and reduced the number of entries to the central zone in the open field test. Moreover, mCPP reduced head-dip counts and increased the head-dip latency of mice in the hole-board test. After being administrated with a single intraperitoneal injection of mCPP for 24h, the mice showed no significant difference in the entry into the light side and the percentage of time in the light side of the light-dark box test. A single intraperitoneal injection of mCPP had no effects on tail flick latency, rotating time, number of errors and the step-down latency, the immobility time of mice in the tail-flick test, rotarod test, step-down test and TST respectively. In conclusion, we established a rapid and stable anxiety mouse model by single intraperitoneal injection of mCPP.

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.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

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.