Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients:

Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.

Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines

Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960 s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclinesin the adjuvant setting for patients with breast cancer. We consulted Pub Med, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review.

All-trans Retinoic Acid,Arsenic Trioxide,and Anthracycline-based Chemotherapy Improves Outcome in Newly Diagnosed Acute Promyelocytic Leukemia Regardless of FLT3-ITD Mutation Status

All-trans retinoic acid(ATRA)and pre-upfront arsenic trioxide(ATO)have revolutionized the therapy of acute promyelocytic leukemia(APL).However,internal tandem duplication of FMS-like tyrosine kinase 3(FLT3-ITD)mutations is associated with increased risk of relapse.The aim of this study was to analyze the prognostic impact of FLT3-ITD on APL patients who received remission induction with ATRA,idarubicin(IDA)and/or ATO,followed by ATRA plus ATO along with anthracycline,as consolidation therapy.A total of 72 patients newly diagnosed with APL were included in this study.83.3%of the patients achieved complete remission(CR)after induction therapy.FLT3-ITD mutations were detected in 16(22.2%)patients and closely related to bcr-3 PML-RARa transcript(P<0.001).The 5-year overall survival(OS)rate was 100%in both FLT3-ITDposltlve and FLT3-ITD^(negatlve)groups,and there was no significant difference in 5-year event-free survival(EFS)between the two groups(78.3%vs.83.3%,P=0.85).ATRA plus ATO and anthracycline-based chemotherapy achieved great outcome in newly diagnosed APL regardless of the FLT3-ITD mutation status.

Risk Factors Associated with Anthracycline Induced Cardiac Dysfunction in Pediatric Patients

Anthracyclines (i.e., doxorubicin, daunorubicin) have significant impact on outcome in many pediatric chemotherapy protocols and therefore remain the mainstay of treatment. The objective of this study was to identify the risk factors for anthracycline induced cardiac dysfunction in pediatric patients. Multiple logistic regression model was applied to assess the risk factors for development of cardiac dysfunction. 110 pediatric oncology patients were available for final analysis. 75 (66%) children were males and mean age was 74 ± 44 months. ALL (n = 70, 64%) was the most common primary diagnosis followed by lymphoma (n = 19;17%) and AML (n = 12, 11%). Daunorubicin alone or in combination with doxorubicin was used in (n = 94, 85%) patients and cumulative dose n = 95;86%) children. 24 (22%) children received radiation therapy as per protocol and sepsis were observed in 47 (43%) cases. Post anthracycline, 15 (14%) children had cardiac dysfunction within a month;out of them 10/15 (67%) had isolated diastolic dysfunction, while 28 (25%) developed dysfunction within a year. 19 (17%) had pericardial effusion. 11 expired and out of them, 7 had significant cardiac dysfunction. Cumulative dose > 300 mg/m2 (p p = 0.009;AOR 3.5) and sepsis (p = 0.002;AOR 2.6) were found to be independent risk factors associated anthracycline induced cardiac dysfunction. At univariant level use of daunorubicin alone or in combination therapy (p p 0.048, OR 9.7) were also found statistically significant. In conclusion anthracycline induced cardiac dysfunction is mostly related to cumulative dose > 300 mg/m2, use of Daunorubicin alone or in combination with doxorubicin, mode of delivery, radiation therapy and sepsis. Regular long term follow-up with cardiologist is the key point for early diagnosis and therapy for a long term survival.

Intrinsic Wave Velocity Propagation:A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients

Objective Anthracycline chemotherapeutic agents have significant cardiotoxicity.The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular(LV)myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation(IVP),and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment.Methods A total of 68 newly diagnosed breast cancer patients,who were treated with anthracycline-based chemotherapy,were analyzed.Transthoracic echocardiography was performed at baseline(T0),and after 1,2,3,4 and 8 chemotherapeutic cycles(T1,T2,T3,T4 and T5,respectively).Then,the IVP,LV strain parameters[global longitudinal strain(GLS),longitudinal peak strain rate at systole(LSRs),longitudinal peak strain rate at early diastole(LSRe),longitudinal peak strain rate at late diastole(LSRa),and the E/LSRe ratio],and conventional echocardiographic parameters were obtained and further analyzed.A relative reduction of>15%in GLS was considered a marker of early LV subclinical dysfunction.Results Compared to the T0 stage,IVP significantly increased at the T1 stage.However,there were no significant changes in GLS,LSRs,or LSRe between the T0 and T1 stages.These parameters significantly decreased from the T2 stage.LSRa started to significantly decrease at the T5 stage,and the E/LSRe ratio started to significantly increase at the T3 stage(all P<0.05).At the T0 stage,IVP(AUC=0.752,P<0.001)had a good predictive value for LV subclinical dysfunction after chemotherapy.Conclusions IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.

Luminol-potassium permanganate chemiluminescence system for the determination of three anthracycline antibiotics

Objective To establish a flow-injection chemiluminescence method for the determination of doxorubicin,epirubicin and mitoxantrone and study its reaction mechanism.Methods In alkaline medium,chemiluminescence of luminol-potassium permanganate system could be inhibited obviously by anthracycline antibiotics.Combined with flow-injection technique,a new chemiluminescence method for determining the anthracycline antibiotics was set up.The chemiluminescence mechanism of the luminol-potassium permanganate system was also discussed.Results Under optimal conditions,the good linear ranges of doxorubicin,epirubicin and mitoxantrone were 5.0×10-9-1.0×10-6g/mL,1.0×10-9-1.0×10-5g/mL and 3×10-9-1.0×10-6g/mL,respectively.The detection limits of doxorubicin,epirubicin and mitoxantrone were 3.0×10-9g/mL,5.0×10-8g/mL and 2.0×10-9g/mL,respectively.During eleven repeated inter-day and intra-day precision tests of 1.0×10-6g/mL samples,the relative standard deviations corresponded to reference values of 3.0%,2.8% and 2.1%.Conclusion The developed method is sensitive,accurate,rapid and of low cost.It can be applied to determine doxorubicin hydrochloride,epirubicin hydrochloride and mitoxantrone hydrochloride in injection preparations.

Effect of traditional Chinese medicine on anthracycline-induced cardiotoxicity in animal models:A systematic review and metaanalysis

Objective:To evaluate the effect of traditional Chinese medicine(TCM)on anthracycline-induced cardiotoxicity(AIC)in animal models.Methods:Separate systematic searches for preclinical studies were performed in the PubMed,EMBASE,Web of Science,Chinese National Knowledge Infrastructure,Chinese Biomedical Database,Chinese Scientific Journal Database,and Wanfang Data from inception to August 2019.The primary outcomes were echocardiography,serum assays for myocardial enzymograms,histological assessments,and electrocardiograms.The secondary outcomes mainly included body weight and safety evaluations.The protocol is registered on PROSPERO(CRD42019145819).RevMan(V.5.3)was used for meta-analysis.Results:We identified 10 studies from 9 international scientific publications describing the efficacy of TCM on AIC animal models.All the included studies reported that,compared with animal model without any intervention,TCM significantly improved ventricular function,cardiac biomarkers,electrocardiograph results,and cardiac fibrosis.Improved survival rates and body mass indices were also observed with TCM.We further pooled the available data from four studies(63 animals)for the meta-analysis and the results showed that,compared with models without any intervention,TCM significantly increased the ejection fraction by 14.13%(95%CI,9.96e18.29)and fraction shortening by 8.66%(95%CI,6.05 e11.26).Creatine kinase-MB(SMD=2.49,95%CI:-3.12 to-1.85)and lactate dehydrogenase(SMD=-2.78,95%CI:-3.45 to-2.12)were also significantly decreased by TCM.Conclusions:TCM is effective in improving AIC in animal models and has tremendous potential to be translated to treat AIC in clinical practice.Additionally,the systematic review and meta-analysis of animal experiments may be valuable in enhancing and guiding animal experiments and promoting the transformation of the results.

ISOLATION AND STRUCTURE DETERMINATION OF XF-1,A NEW ANTHRACYCLINE ANTIBIOTIC

A new Mutactimycin group antibiotic(XF-1)was isolated from the mycelium of Streptomyces sp.80-115 and its structure has been determined on the basis of its spectroscopical and chemical properties. XF-1 showed active against some Gram positive bacteria.

Anthracycline-induced cardiotoxicity:A case report and review of literature

BACKGROUND Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment.The use of anthracycline is limited by dose-dependent cardiotoxicity,which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure.Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents,there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity(AIC).CASE SUMMARY A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70%determined by transthoracic and dobutamine stress echocardiogram.She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery,and received a total of 450 mg/m2 doxorubicin at the end of her treatment course.She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms.Approximately two months after her last chemotherapy,the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure.Echocardiogram showed an ejection fraction of 5%-10%with severe biventricular failure.Despite attempts to optimize cardiac function,the patient’s hemodynamic status continued to decline,and resuscitation was not successful on the seventh day of hospitalization.The autopsy showed no evidence of osteosarcoma,and the likely cause of death was cardiac failure with the evidence of pulmonary congestion,liver congestion,and multiple body cavity effusions.CONCLUSION We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo.Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice.We have reviewed literature and recent advances in the prediction and prevention of AIC.Although risk factors currently identified can help stratify patients who need closer monitoring,there are limitations to our current understanding and further research is needed in this field.

A 29-year-old pregnant woman with a history of anthracycline-induced clinical heart failure

The number of women with heart disease who reach childbearing age in a good functional state increases continuously as advances in diagnosis and treatment improve overall health and prognosis. The cardiologist’s role is to give the woman an estimate of both maternal and fetal risk to allow her to make an informed decision about embarking on a pregnancy, and to provide appropriate antenatal care. There are only a few data about the natural history of anthracycline-induced cardiomyopathy during preg- nancy;we report our experience of a 29-year- old pregnant woman with a history of anthracycline-induced clinical heart failure.

Capecitabine combined with weekly docetaxel in Chinese patients 〉65 years with anthracycline-resistant metastatic breast cancer

Background There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer （MBC） in older Chinese patients. Methods MBC patients aged 〉65 years pretreated with 1-5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m^2 twice daily, days 1-14, plus docetaxel 30 mg/m^2 on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles （median 4, range 2-8） and were evaluable for efficacy. Results The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia （12%）, alopecia （7%）, grade 3 nausea and vomiting （2%） and grade 3 nail toxicity （2%）. Conclusions Capecitabine 825 mg/m^2 twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women 〉65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.

Detection of Subclinical Anthracyclines＇ Cardiotoxicity in Children with Solid Tumor

Background： Cardiotoxicity is one of the most serious chronic complications ofanthracyclines therapy. Assessment of the left ventricular ejection fraction （LVEF） fails to detect subtle cardiac dysfunction of left ventricular （LV）. This study aimed to detect and evaluate new parameters of subclinical anthracyclines＇ cardiotoxicity in children with solid tumor. Methods： A detailed echocardiographic examination was performed in 36 children with hepatoblastoma or rhabdomyosarcoma after receiving anthracyclines＇ chemotherapy and 36 healthy controls from January 2015 to December 2016. The LVEF, ratio of early diastolic peak velocity of transmitral flow （E） and septal diastolic e＇ mitral annular peak velocity （e＇）, tricuspid annular plane systolic excursion （TAPSE）, and LV global longitudinal strain （GLS） were evaluated using M-mode, tissue Doppler imaging （TDI）, and two-dimensional speckle tracking echocardiography （2D-STE）, respectively. Echocardiographic parameters were compared between patient group and healthy controls. All patients were divided into two subgroups based on their anthracyclines＇ cumulative dosage （〈300 mg/m^2 subgroup and ≥300 mg/m^2 subgroup）. Results： All patients had no presentation of heart failure and LVEF within normal range （65.7 ± 5.1%）. Compared with healthy controls, the mean E/e＇ increased significantly （7.9 ±0.7 vs. 10.2 ± 3.5, t = 3.72, P 〈 0.01 ）, mean TAPSE decreased significantly （ 17.2 ± 1.3 mm vs. 14.2 ± 3.0 mm, t = -4.03, P 〈 0.01）, and mean LV GLS decreased significantly （-22.2% ± 1.9% vs. -17.9% ± 2.9%, t = -5.58, P 〈 0.01） in patient group. Compared with subgroup with anthracyclines＇ cumulative dosage 〈 300 mg/m^2, mean LV GLS decreased significantly （- 18.7 ＋ 2.7% vs. - 16.5 ~ 2. 1%, t = 2.15, P = 0.04）, the mean E/e＇ increased significantly （9.1 ±1.5 vs. 11.5 ± 4.9, t = -2.17, P = 0.04）, and mean TAPSE decreased significantly （14.2±2.1 mm vs. 12.5±2.2 mm, t = -2.82, P = 0.02） in subgroup with anthracyclines＇ cumulative dosage 〉300 mg/m^2. Conclusions： LV GLS is helpful in the early detection of subclinical LV dysfunction using 2D-STE. E/e＇ and TAPSE are other sensitive parameters in detecting subclinical cardiac dysfunction of both ventricles by TD1. These parameters show significant change with different anthracyclines＇ cumulative dosage, so cumulative dosage should be controlled in clinical treatment.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines:A Systematic Review and Meta-Analysis

Objective:To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.Methods:Randomized controlled trials(RCTs)were identified by searching China National Knowledge Infrastructure(CNKI),Wanfang Database,Chinese Biomedical Literature Database(CBM),Pub Med,Cochrane Library,and Embase Databases from the inceptions until December 2020.The Cochrane Handbook was used to evaluate the risk of bias in the included studies.Data analysis was conducted using Rev Man 5.3 software.Results:Totally 19 RCTs with 2,331 participants were included in this review.Results showed that in improving arrhythmia(13 RCTs,n=1,877,RR=0.37,95%CI 0.25 to 0.52,P<0.00001),the treatment group was superior to the control group.In terms of reducing left ventricular end-diastolic diameter(LVEDD,2 RCTs,n=128,MD=-0.79,95%CI-0.93 to-0.65,P<0.00001)and left ventricular end systolic diameter(LVESD,2 RCTs,n=128,MD=-0.58,95%CI-0.82 to-0.35,P<0.00001),the treatment group was also better than the control group.In reducing myocardial enzymes such as creatine kinase(CK)[(3 RCTs,n=256,SMD=-0.80,95%CI-1.16 to-0.44,P<0.0001),(2 RCTs,n=126,SMD=-0.62,95%CI-0.98 to-0.26,P=0.0007)],the treatment group was superior to the control group.Conclusion:Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines.However,in the future,it is still necessary to conduct high-quality RCTs to verify its efficacy.

Genetic polymorphisms of autophagy-related gene 5 (ATG5) rs473543 predict different disease-free survivals of triple-negative breast cancer patients receiving anthracycline- and/or taxane-based adjuvant chemotherapy

Background:Autophagy plays a crucial role in chemotherapy resistance of triple-negative breast cancer(TNBC).Hence,autophagy-related gene 5(ATG5),an essential molecule involved in autophagy regulation,is presumably associated with recurrence of TNBC.This study was aimed to investigate the potential influence of single-nucleotide polymorphisms in ATG5 on the disease-free survival(DFS)of early-stage TNBC patients treated with anthracycline-and/or taxane-based chemotherapy.Methods:We genotyped ATG5 SNP rs473543 in a cohort of 316 TNBC patients treated with anthracycline-and/or taxane-based chemotherapy using the sequenom’s MassARRAY system.Kaplan-Meier survival analysis and Cox proportional hazard regression analysis were used to analyze the association between ATG5 rs473543 genotypes and the clinical outcome of TNBC patients.Results:Three genotypes,AA,GA,and GG,were detected in the rs473543 of ATG5 gene.The distribution of ATG5 rs473543 genotypes was significantly different between patients with and without recurrence(P=0.024).Kaplan-Meier survival analysis showed that patients carrying A allele of ATG5 rs473543 had an increased risk of recurrence and shorter DFS compared with those carrying the variant genotype GG in rs473543(P=0.034).In addition,after adjust-ing for clinical factors,multivariate Cox regression analyses revealed that the AA/GA genotype of rs473543 was an independent predictor for DFS(hazard risk[HR],1.73;95%confidence interval[CI],1.04-2.87;P=0.034).In addition,DFS was shorter in node-negative patients with the presence of A allele(AA/GA)than in those with the absence of A allele(P=0.027).Conclusion:ATG5 rs473543 genotypes may serve as a potential marker for predicting recurrence of early-stage TNBC patients who received anthracycline-and/or taxane-based regimens as adjuvant chemotherapy.

Potential role of pemetrexed in metastatic breast cancer patients pre-treated with anthracycline or taxane

Objectives: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. Methods: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were‘‘pemetrexed’’ or‘‘LY231514’’ or“Alimta”,“metastatic breast cancer”, and“advanced breast cancer”. Results: There were 15 studies (n ? 1002) meeting our criteria for evaluation. Eight single-agent trials (n ? 551) and seven using combinations with other agents (n ? 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8%to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. Conclusion: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Com-munications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Burden of chronic diseases among sarcoma survivors treated with anthracycline chemotherapy:results from an observational study

Aim:Cardiovascular disease is a leading cause of mortality among long-term cancer survivors treated with large total doses of doxorubicin.An increase in coronary artery disease(CAD)among childhood cancer survivors by age 45 has been observed and is driven by primarily anthracycline chemotherapy and to a lesser extent chest radiation that includes the heart in the radiation field.The risk factors and associated chronic diseases(hypertension,etc.)are well known for CAD and can be often prevented or treated,thus reducing the risk of CAD in these patients.We piloted a risk-based survivorship clinic in an academic medical center to characterize the distribution of risk factors for CAD and improve the quality of life in a population of sarcoma survivors treated with doxorubicin.Methods:We followed a prospective cohort of sixty-one survivors of bone and soft tissue sarcoma treated with doxorubicin chemotherapy(>400 mg/m2)and at least 2 years post-therapy attending the sarcoma survivorship clinic.We collected clinical,demographic data,and patient reported outcomes via PROMIS questionnaires annually.Results:We demonstrated a high burden of chronic diseases in this population.Among six chronic conditions that are known risk factors for CAD(hypertension,diabetes,obesity,chronic inflammation,kidney disease and dyslipidemia),more than one-fourth(26%,16/61)of patients had three or more of these risk factors at baseline visit,and 49%(30/61)had two or more.Conclusion:The results of this pilot study support the presence of modifiable CAD risk factors in this population of sarcoma survivors.Evidence-based guidelines for high-risk survivors of rare cancers are needed.

Non-anthracycline chemotherapy associated with a poor outcome in elderly Egyptian patients with diffuse large B-cell non-Hodgkin lymphoma

Aim:Rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone(CHOP)is the standard treatment for patients with diffuse large B-cell non-Hodgkin lymphoma(DLBCNHL).Nevertheless,anthracyclines are contraindicated for some patients,e.g.cardiac dysfunction,severe hepatic dysfunction,jaundice.Thus,this study assessed the effectiveness of non-anthracycline chemotherapy regimen cyclophosphamide,vincristine,and prednisone(CVP)in elderly DLBCNHL patients vs.the standard CHOP.Methods:This retrospective study included 418 DLBCNHL patients diagnosed between 2003 and 2006 and followed until March 2014.During this period of time,rituximab was not available for all patients,particularly for patients older than 60 years.Results:CHOP and CVP were administered to 351(84%)and 67(16%)patients,respectively.Older age and comorbidities,particularly cardiovascular and diabetes mellitus,were independent determinants for not receiving CHOP.Patients received more courses of CHOP treatment than that of CVP(6 vs.3 courses;P<0.001)and developed more toxicities(48.4%vs.23.9%;P<0.001),particularly fatigue,alopecia,and gastrointestinal tract toxicities.Complete response rate was higher in CHOP than in CVP(69.9%vs.29.9%;P<0.001).Moreover,early death was significantly higher in CVP group of patients than in CHOP(43.3%vs.8.6%;P<0.001).After a median follow-up of 71 months,the median overall survival(OS)and event-free survival(EFS)were signifi cantly better in CHOP than in CVP(49.5 vs.3.7 months and 32.2 vs.3.5 months;P<0.001 for both,respectively).Older age,poor age-adjusted International Prognostic Index scores,not receiving CHOP or consolidative radiotherapy were independent predictors of poor OS and EFS.Conclusion:Use of the CVP regime to treat DLBCNHL patients who were unfit to the standard CHOP treatment was associated with lower remission rates and poorer EFS and OS in this group of patients.

The magnitude of benefit from adding taxanes to anthracyclines in the adjuvant settings of breast cancer:discussion of large trials and meta-analyses

The taxanes family of chemotherapy,which includes paclitaxel and docetaxel,has been incorporated in the adjuvant breast cancer treatments since 1990s.Sequential and concurrent use of taxanes was investigated with anthracyclines in many adjuvant early breast cancer randomized clinical trials.Results from taxanes trials showed inconsistent benefits.However,several meta-analyses showed significant survival benefit of adding taxanes.In this review article,data were collected and summarized from eleven large randomized trials and three meta-analyses to show and discuss the magnitude of benefit of taxanes-anthracyclines combination compared to anthracyclines only adjuvant regimens in early breast cancer.This article aims at providing the oncologists with a well-organized,inclusive and updated evidence.

Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

Real-time three-dimensional echocardiography predicts cardiotoxicity induced by postoperative chemotherapy in breast cancer patients

BACKGROUND The anthracycline chemotherapeutic drugs are cardiotoxic.Studies have found some indicators related to cardiotoxicity.However,there is currently no accurate indicator that can predict cardiac toxicity early.AIM To explore the diagnostic value of real-time three-dimensional echocardiography(RT3DE)in predicting cardiac toxicity in breast cancer patients undergoing chemotherapy.METHODS Female breast cancer patients who underwent radical mastectomy and postoperative chemotherapy at the Affiliated Hanzhou First People’s Hospital,Zhejiang University School of Medicine were recruited.All patients were routinely administered with chemotherapy for four cycles(T1-T4)after surgery.Two-dimensional(2D)echocardiography,RT3DE,and serological examinations were performed after each cycle of chemotherapy.Patients were divided into a toxic group and a non-toxic group based on whether patients hadΔleft ventricular ejection fraction>10%after one year of chemotherapy.Repeated measurement analysis of variance was used to compare the changes in 2D echocardiographic indicators,serological indicators,and RT3DE indicators before independent predictive indicators for cardiac toxicity in postoperative chemotherapy patients.Receiver operating characteristics(ROC)curve analysis was performed to analyze the diagnostic value of potential indicators in the diagnosis of cardiotoxicity.RESULTS A total of 107 female breast cancer patients were included in the study.T4 maximum peak velocity in early diastole(E peak)/mitral annulus lateral tissue Doppler(e'peak)(E/e'),serological indicators[T4 cardiac troponin I(cTnI)and T4 pro-brain natriuretic peptide(Pro-BNP)],T3 minimum left atrial volume(LAV),T4 LAVmin,T3 LAV before the start of the P wave(LAVprep),and T4 LAVprep in the toxicity group were significantly higher than those in the nontoxic group.Multivariate logistic regression found that T4 cTnI,T4 Pro-BNP,T3 LAVmin,T4 LAVmin,T3 LAVprep,and T4 LAVprep had potential predictive value for cardiac toxicity(P<0.05).ROC results showed that T4 LAVmin had the highest accuracy for diagnosing cardiac toxicity[area under the curve(AUC)=0.947;sensitivity=78.57%;specificity=94.62%],followed by T4 LAVprep(AUC=0.899;sensitivity=100%;specificity=66.67%).The accuracies of LAVprep and LAVprep in predicting cardiac toxicity were higher than those of T3 LAVmin and T3 LAVprep.CONCLUSION RT3DE of left atrial volume can be used to predict the cardiotoxicity caused by chemotherapy,and it is expected to guide the clinical adjustment of dose and schedule in time.