Anthracycline Chemotherapy Research Articles

Effects of anthracycline chemotherapy and Kuan-Sin-Yin on the spectral indices of arterial pulse waveforms in breast cancer patients.

The vascular structure and function are potentially useful biomarkers for tumor detection. Treatment with chemotherapeutic agents may impair vascular function and increase the risk of cardiovascular disease. This study aimed to use noninvasive pulse waveform measurements to identify differences in the frequency-domain indices of the pulse waveform in breast-cancer patients following anthracycline chemotherapy between with (Group KSY) and without (Group NKSY) receiving Kuan-Sin-Yin (KSY) treatment.Radial blood pressure waveform (BPW) signals were measured noninvasively for 3 minutes in 31 patients, and the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires were administered. The following pulse indices were calculated for 10 harmonics: the amplitude proportion and its coefficient of variation, and the phase angle and its standard deviation.The changes in spectral BPW indices were more prominent in Group NKSY than in Group KSY, especially for the decreases in BPW variability indices. Scores on the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires suggested that the quality of life following chemotherapy was better in Group KSY.The identified decreases in pulse variability indices could be related to the greater impairment of regulatory activities in Group NKSY. The present findings may be meaningful in developing techniques with advantages such as being noninvasive and time-saving to evaluate the blood supply and physiological conditions following chemotherapy or other treatment strategies in cancer patients.

Value of Echocardiography and Cardiac Magnetic resonance in assessing left ventricular function in breast and gastric cancer patients after Anthracycline Chemotherapy

BackgroundEchocardiography (ECHO) and cardiac magnetic resonance imaging (MRI) are used to observe changes in the left ventricular structure in patients with breast and gastric cancer after 6 cycles of chemotherapy. Based on the observed values, we aimed to evaluate the cardiotoxicity of anthracyclines in cancer patients and to analyze the consistency of the two examination methods in assessing left ventricular function after chemotherapy.MethodsFrom January 2020 to January 2022, the data of 80 patients with malignant tumors who received anthracycline chemotherapy (breast cancer, n = 40; gastric cancer, n = 40) and 40 healthy volunteers (Control group) were retrospectively collected. Serum high-sensitivity cardiac troponin T (hs-cTnT) levels were detected by an automatic immunoassay analyzer. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were measured by cardiac MRI and 2-dimensional ECHO using the biplane Simpson’s method.ResultsCompared with baseline values, serum high-sensitivity cardiac troponin T (hs-cTnT) levels were significantly increased in patients with breast cancer and gastric cancer after 6 cycles of chemotherapy (P < 0.05). In addition, LVEDV, LVESV and LVEF measured with MRI were higher than those detected by ECHO in cancer patients after 6 cycles of chemotherapy (P < 0.05). And the Bland-Altman plot analysis showed that LVEDV, LVESV and LVEF measured by the two examination methods were in good agreement.ConclusionBreast and gastric cancer patients exhibited elevated levels of hs-cTnT after 6 cycles of chemotherapy, indicating potential cardiotoxicity. Additionally, cardiac MRI and 2-dimensional ECHO showed good agreement in assessing left ventricular function, with ECHO tending to underestimate volume measurements compared to MRI.

Potential Biomarker of Acute Anthracycline-induced Cardiotoxicity Among Children With Acute Lymphoblastic Leukemia: Cardiac Adriamycin-responsive Protein.

This study aimed to investigate whether serum cardiac adriamycin-responsive protein (CARP) can serve as a sensitive and specific biomarker of anthracyclines (ANT)-induced cardiotoxicity. Fifty-five children with acute lymphoblastic leukemia were recruited. Before and after the administration of ANT, serum levels of CARP, high-sensitivity troponin T, creatine kinase-MB, and electrocardiogram were measured. Postchemotherapeutic clinical manifestations of cardiotoxicity were also investigated. Adverse cardiac events (ACEs) were graded according to the Common Terminology Criteria for Adverse Events 4.0. Then, the CARP expression was statistically analyzed among different groups. The receiver operating characteristic curve was used to evaluate the efficacy of CARP in predicting acute ANT-induced cardiotoxicity. After ANT chemotherapy, the serum CARP concentration increased in the non-ACEs group but decreased in the ACEs group ( P < 0.05). In addition, not only the serum CARP levels (△CARP) was negatively correlated with the grade of ACEs (R=-0.754, P < 0.0001) but also the extent of QT interval corrected (QTc) prolongation (△QTc; R=-0.5592, P < 0.01). The area under the receiver operating characteristic curve of CARP was 90.94% ( P < 0.0001), and the sensitivity and specificity were 88.64% and 91.67%, respectively, all of which are superior to △high-sensitivity troponin T, △creatine kinase-MB, and △QTc. In conclusion, serum CARP could serve as a novel sensitive and specific biomarker of acute ANT-induced cardiotoxicity, which is negatively associated with ACE grade.

Subsequent female breast cancer risk associated with anthracycline chemotherapy for childhood cancer

Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m−2: 1.24, 95% confidence interval (CI): 1.18–1.31), with more than twofold increased risk for survivors treated with ≥200 mg m−2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200–299 mg m−2, HR: 2.33 for 300–399 mg m−2 and HR: 2.78 for ≥400 mg m−2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59–6.63). For patients treated with or without chest irradiation, HRs per 100 mg m−2 of doxorubicin were 1.11 (95% CI: 1.02–1.21) and 1.26 (95% CI: 1.17–1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m−2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.

The Association of Metformin With Heart Failure in Patients With Diabetes Mellitus Receiving Anthracycline Chemotherapy

BackgroundThe prevention of heart failure (HF) is an important issue in patients treated with anthracyclines. Metformin, widely used to treat diabetes mellitus (DM), protects from anthracycline-induced cardiotoxicity in vitro and in animal models. ObjectivesThe aim of our study was to test the association of metformin with the occurrence of symptomatic HF in patients with DM receiving anthracyclines. MethodsA total of 561 patients with DM received new anthracycline therapy between 2008 and 2021 in a tertiary care center; propensity score matching was used to compare patients with or without metformin treatment. The primary outcome was new onset symptomatic HF occurring within 1 year of the initiation of anthracyclines. ResultsA total of 315 patients (65 ± 11 years of age, 33.7% male) were included. Patients with and without metformin were well matched for age, sex, type of cancer, medications, and cardiovascular risk factors. Six patients treated with metformin and 17 matched patients developed HF within 1 year of anthracycline initiation. The incidence of HF in patients treated with metformin was lower than patients without metformin within 1 year after anthracyclines (cumulative incidence: 3.6% vs 10.5%; P = 0.022; HR: 0.35; 95% CI: 0.14-0.90; P = 0.029). The use of metformin (HR: 0.71; 95% CI: 0.50-1.00; P = 0.049), was also associated with lower mortality. ConclusionsThe use of metformin was associated with a lower incidence of HF and overall mortality in patients with DM receiving anthracyclines. Our findings should be further confirmed by randomized control trials.

Topoisomerase IIα immunoexpression in feline mammary carcinomas: A correlation with Ki67 immunoexpression and the mitotic count

The aim of the study was to compare the immunohistochemical expression of topoisomerase IIα protein (Topo IIα) with Ki67 expression and mitotic count in feline mammary carcinomas (FMCs). Topo IIα is considered as a proliferation indicator as well as a molecular target of anthracycline chemotherapy. The studied material included 70 FMCs from female cats treated with mastectomy. Primary mouse monoclonal antibodies directed against Topo IIα and Ki67 were used in immunohistochemical reactions. The number of mitotic figures was counted at 400× magnification in a field of 2.37 mm2. Immunohistochemical reaction for Topo IIα occurred in cell nuclei. The Topo IIα index ranged from 6.12% to 54.60% and was positively correlated with the values of the Ki67 index (r = 0.7193) and the mitotic count (r = 0. 2858). This indicates the potential possibility of use of the immunohistochemical expression of Topo IIα to assess the rate of proliferation in FMCs. The wide range of expression of Topo IIα in individual tumorus found in the conducted studies allows us to hypothesize that its assessment could be used as a predictive marker in chemotherapy of FMCs with the use of anthracyclines. However, this requires confirmation in clinical trials.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178. This study is listed on cinicaltrials.gov with identifier NCT05118178.

Abstract P2147: Inhibition Of Cdk7 Attenuates Doxorubicin Cardiotoxicity And Enhances Anticancer Efficacy

Background: The anthracycline family of anticancer agents such as doxorubicin (DOX) can induce apoptotic death of cardiomyocytes and cause cardiotoxicity. We previously reported that DOX-induced apoptosis is accompanied by cardiomyocyte cell cycle-reentry. Cell cycle progression requires cyclin-dependent kinase 7 (CDK7)-mediated activation of downstream cell cycle CDKs. This study aims to determine whether CDK7 can be targeted for cardioprotection during anthracycline chemotherapy. Methods and Results: DOX exposure induced CDK7 activation in mouse heart and isolated cardiomyocytes. Cardiac-specific ablation of Cdk7 attenuated DOX-induced cardiac dysfunction and fibrosis. Treatment with the covalent CDK7 inhibitor THZ1 also protected against DOX-induced cardiomyopathy and apoptosis. DOX induced activation of the proapoptotic CDK2-FOXO1-Bim axis in a CDK7-dependent manner. In response to DOX, endogenous CDK7 directly bound and phosphorylated CDK2 at Thr160 in cardiomyocytes, leading to full CDK2 kinase activation. Importantly, inhibition of CDK7 further suppressed tumor growth when used together with DOX in an immunocompetent mouse model of breast cancer. Conclusions: Activation of CDK7 is necessary for DOX-induced cardiomyocyte apoptosis and cardiomyopathy. Our findings uncover a novel proapoptotic role for CDK7 in cardiomyocytes. Moreover, this study suggests that inhibition of CDK7 attenuates DOX-induced cardiotoxicity, but augments the anticancer efficacy of DOX. Therefore, combined administration of CDK7 inhibitor and DOX may exhibit diminished cardiotoxicity but superior anticancer activity.

Chemotherapy induced right ventricular cardiomyopathy; a systematic review and meta-analysis.

Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact of chemotherapeutic agents on the integrity and function of the right ventricle (RV). The current metanalysis compared pre- chemotherapy versus post- chemotherapy RV parameters measured on 2D echocardiography in patients receiving anthracycline and/or trastuzumab across all breast cancer patients. A systematic search across PubMed, EMBASE and Cochrane databases were performed from inception of the databases until November 2021 for relevant studies. We used the inverse variance method with a random effect model and DerSimonian and Laird method of Tau2 generation to calculate mean difference [MD] with 95% confidence interval [CI]. The analysis was carried out using RevMan Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Fifteen studies, constituting total of 644 patients, met the inclusion criteria, with most studies having a follow up period of less than 12 months from initiation of chemotherapy. Anthracycline and/or Trastuzumab chemotherapy resulted in a statistically significant reduction in right ventricular ejection fraction (RVEF) at follow-up [MD: 2.70, 95% CI: 0.27 to 5.13, P-value- 0.03, I2- 71%, χ2 P-value < 0.05]. Treatment with Anthracycline and/or Trastuzumab chemotherapy resulted in a significant reduction in RV fractional area change (RVFAC) at follow-up [MD: 3.74, 95% CI: 1.33 to 6.15, P-value < 0.01, I2- 68%, χ2 P-value < 0.05]. RV free wall longitudinal strain (RVFWLS) was lower at baseline, while LVEF was significantly reduced at follow-up [MD: -1.00, 95% CI: -1.86 to -0.15, P-value < 0.05, I2- 0%, χ2 P-value-0.40], [MD: 4.04, 95% CI: 2.08 to 6.01, P-value < 0.01, I2- 91%, χ2 P-value < 0.05], respectively. However, treatment with Anthracycline and/or Trastuzumab chemotherapy had no statistically significant effect on Tricuspid annular plane systolic excursion (TAPSE) at follow-up [MD: 0.53, 95% CI: -0.11 to 1.17, P-value-0.11, I2- 98%, χ2 P-value < 0.05]. Chemotherapy with anthracyclines and trastuzumab negatively affects right ventricular function leading to decline in RVEF, RVFAC, RVFWLS and LVEF.

TITAN Trial: A Randomized Controlled Trial of a Cardiac Rehabilitation Care Model in Breast Cancer

BackgroundCardiac rehabilitation (CR) modeled care is recommended for patients with breast cancer to mitigate risk of cardiotoxicity. However, the cardiovascular impact of CR-modeled interventions has not been studied. ObjectivesThe purpose of this study was to evaluate if a multidisciplinary model of CR reduces cardiotoxicity and improves cardiovascular risk in patients undergoing breast cancer treatment. MethodsWe randomly assigned patients with stage I to III breast cancer scheduled to receive anthracycline and/or trastuzumab-based chemotherapy to the CR intervention (n = 37) or usual care (n = 37). The intervention included guideline-directed management of cardiovascular risk factors, dietary counselling, and supervised exercise for 52 weeks. Cardiac magnetic resonance imaging, cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, and serum biomarkers were acquired at baseline and 52 weeks. ResultsThere was no difference in the primary outcome, left ventricular ejection fraction (LVEF), between groups at 52 weeks (61% ± 6%). Other markers of cardiotoxicity, including high-sensitivity troponin I and brain natriuretic peptide, were similar between groups. However, total cholesterol (5.2 ± 0.8 mmol/L to 4.7 ± 0.8 mmol/L, P = 0.002) and low-density lipoprotein (3.0 ± 0.7 mmol/L to 2.4 ± 0.7 mmol/L, P < 0.001) decreased in the intervention group at 52 weeks and were unchanged in usual care. In all patients, adverse cardiac and metabolic changes occurred over 52 weeks including reductions in LVEF, left ventricular mass, high-density lipoprotein, lean body mass, insulin-like growth factor-1, as well as increased triglycerides, whole-body and truncal fat mass (all P < 0.050). ConclusionsThe CR-modeled intervention had no effect on LVEF or biomarkers of cardiotoxicity. Future lifestyle intervention trials in patients with breast cancer should consider targeting other risk factors associated with incident cardiovascular disease. (Multidisciplinary Team IntervenTion in CArdio-ONcology [TITAN Study] [TITAN]; NCT01621659)

Anthracyclines versus No Anthracyclines in the Neoadjuvant Strategy for HER2+ Breast Cancer: Real-World Evidence.

Deescalation strategies omitting anthracyclines (AC) have been explored in early human epidermal growth factor receptor 2-positive breast cancer (HER2+ EBC), showing similar efficacy regarding pathological complete response (pCR) and long-term outcomes as AC-containing regimens. The standard treatment for this tumor subtype is based on chemotherapy and dual HER2 blockade with trastuzumab and pertuzumab, with AC-containing regimens remaining a frequent option for these patients, even in non-high-risk cases. The primary aim of this study was to assess and compare the effectiveness of neoadjuvant regimens with and without AC used in the treatment of HER2+ EBC in the clinical practice according to the pCR achieved with each. This retrospective multicentric study included patients with HER2+ EBC from Portuguese, Spanish, and Chilean hospitals (January 2018-December 2021). Patients receiving neoadjuvant therapy (NAT) with dual HER2 blockade (trastuzumab and pertuzumab), followed by surgery, were included. Statistical analysis used chi-squared/Fisher's exact test for associations, multivariate logistic regression for pCR, and Kaplan-Meier method for event-free survival (EFS). IBM SPSS Statistics 29.0 analyzed the data. The study included 371 patients from eight hospitals. Among them, 237 received sequential AC and taxane-based chemotherapy with 4 cycles of trastuzumab and pertuzumab, while 134 received 6 cycles of TCHP (docetaxel, carboplatinum, trastuzumab, and pertuzumab). The average age of the patients was 52.8 years and 52.7 years, respectively. Omitting AC from the neoadjuvant approach did not preclude achieving pCR [p=0.246, 95% confidence interval (CI) 0.235-0.257] and was safe regardless of patient characteristics. Relapse rates were 6.8% (16 patients) in the AC group and 4.5% (6 patients) in the TCHP group. Over a median follow-up of 2.9 years, the estimated 3-year EFS was 92.5% in the AC group and 95.4% in the TCHP group (hazard ratio 0.602, 95% CI 0.234-1.547, p=0.292, favoring TCHP). This study reports real-world evidence showing similar pCR and EFS outcomes with treatment regimens with and without AC and raises awareness of possible overtreatment and long-term toxicity in some patients with HER2+ EBC with the use of AC.

Peficitinib ameliorates doxorubicin-induced cardiotoxicity by suppressing cellular senescence and enhances its antitumor activity

Irreversible cardiotoxicity limits the clinical applications of doxorubicin (DOX). Cardiotoxicity can be detected early using clinical assessment; however, effective preventive measures are still lacking. Peficitinib (ASP015K), a JAK (Janus kinase) inhibitor, is a potent anti-inflammatory agent in autoimmune diseases. Nevertheless, little research has been conducted on anti-ageing and anti-tumour therapies. In this study, we investigated whether ASP015K could attenuate DOX-induced cardiotoxicity through its anti-ageing effects and whether it would affect the tumour treatment effect of DOX by establishing senescence, acute heart injury, and xenograft models. We observed that ASP015K could antagonise the senescence induced by various factors, including hydrogen peroxide and DOX. In addition, ASP015K treatment significantly alleviated cardiac function damage, histopathological deterioration, myocardial fibrosis, and oxidative damage in acute injury mouse models. ASP015K enhanced the sensitivity of tumour cells to DOX therapy and significantly slowed down the tumour growth rate and tumour volume in the xenograft mouse model. Therefore, ASP015K is expected to be developed as a potential cardioprotective agent to prevent or reduce the cardiotoxic side effects of anthracyclines in chemotherapy.

Reasons for and time to seeking healthcare in cardiac clinics by women with a history of successfully treated breast cancer

Background: Various methods of breast cancer treatment are potentially cardiotoxic: anthracycline chemotherapy, HER2-targeted therapy, and radiation therapy to the left side of the chest. In clinical practice, cardiologists deal with a wide range of complications caused by the mentioned methods.Objective: To analyze the reasons for and timing of seeking healthcare in cardiac clinics by women with a history of successfully treated breast cancer.Methods: Our single-center retrospective observational study included 125 women (mean age at the time of seeking healthcare was 68.1 ± 8.6 years).Results: Patients with a history of radiation therapy had higher peak velocity (P = .015) and peak gradient (P = .017) across the aortic valve. As part of their examination and treatment 71 patients underwent coronary angiography. Of them, 21 patients (29.6%) had coronary artery stenting, and 23 patients (32.4%) underwent coronary artery bypass grafting. Forty-two patients (33.6%) underwent heart valve replacement: aortic valve replacement in 92.9% of the cases (n = 39) and mitral valve replacement in 7.1% of the cases (n = 3). We found a strong negative correlation between the age at the time of radiation therapy and the time to onset of valvular heart disease (r = −0.748; P = .000004) and an average negative correlation between the age and the time to surgical treatment (r = −0.695; P = .00003).Conclusion: We studied the main reasons for seeking healthcare in cardiac clinics by women with a history of breast cancer, analyzed cardiac operations in terms of antitumor therapy types, and found a strong correlation between the age at the time of antitumor therapy and the time to onset of valvular heart disease, as well as the time to cardiac surgery. Received 20 November 2022. Revised 21 May 2023. Accepted 31 May 2023. Funding: The study was supported by Ministry of Science and Higher Education of Russian Federation (No. 075-15-2022-301). Conflict of interest: The authors declare no conflict of interest. Contribution of the authors: The authors contributed equally to this article.

Primary care utilization and cardiovascular screening in adult-aged survivors of childhood cancer: A report from the childhood cancer survivor study (CCSS).

e22020 Background: Among the half million survivors of childhood cancer in the US, cardiovascular disease (CVD) is the leading non-cancer cause of premature death. Adult survivors of childhood cancer are largely managed by community-based primary care providers (PCPs), and healthcare utilization patterns related to CVD screening and survivorship care are not well-described. Methods: Within the CCSS cohort, we conducted a randomized intervention trial (NCT03104543) focused on improving CVD risk factor control among survivors at increased risk for CVD due to prior chest radiotherapy and/or anthracycline chemotherapy. Using medical records from participants’ PCPs over the 2 years preceding trial enrollment, we ascertained the numbers of PCP and specialist visits, CVD conditions (i.e., hypertension, dyslipidemia, diabetes) and screening (i.e., blood pressure, lipid, diabetes testing, and cardiac testing [ECG, echocardiogram, or other imaging completed or planned]). We also abstracted acknowledgement of participants’ cancer history, cardiotoxic treatment exposures, or a survivorship care plan (SCP). Multivariable logistic regression assessed characteristics associated with having cardiac testing, retaining covariates associated with p &lt; 0.10 in univariate testing. Results: Of 347 enrolled participants, 293 (84%) had evaluable data (median age 40y, range 22–65; 49% female; 87% non-Hispanic White; mean 31y since childhood cancer). In the prior 2y, 81% of participants had a documented PCP office visit (median 3 visits [IQR 2–5]), 22% had a subspecialty visit (4% saw cardiology), and 16% had no visits. The prevalence of blood pressure, lipid, and diabetes screening was 82%, 57%, and 63%, respectively; 29% had cardiac testing done or planned, including 22% with echocardiography. Only 68% of participants had records referencing a history of cancer. PCP documentation of prior cardiotoxic exposures was low compared with known exposures: radiotherapy (35% vs 69%; p &lt; 0.001), anthracycline chemotherapy (9% vs 76%; p = 0.017); only 12% had any documentation noting an increased risk for CVD. Few participants’ records referenced a need for cancer-related late effects surveillance (38%), and even fewer referenced an SCP (5%). In multivariable analysis, independent predictors of cardiac testing included documentation of increased CVD risk (Odds Ratio [OR] 11.61, 95% CI 3.31–40.67), presence of a late effects surveillance plan (OR 3.71, 95% CI 1.62–8.48), and existing CVD conditions (modeled as 0, 1, or 2+ conditions; OR 2.21, 95% CI 1.41–3.47, for each additional level). Conclusions: Adult survivors of childhood cancer at increased risk of CVD had low rates of cardiac testing and documentation of risk in PCP medical records. Increasing participant and PCP awareness of CVD risks and late effects surveillance recommendations may improve screening.

Efficacy of paxman scalp cooling system at lower temperatures for prevention of anthracycline associated chemotherapy induced alopecia.

12108 Background: Chemotherapy induced alopecia (CIA) significantly impairs QoL. Scalp cooling devices typically used at -5°C decrease CIA. However, there is still room to improve efficacy with anthracycline therapy. This prospective study was performed to evaluate the safety, tolerability, and efficacy of the Paxman Scalp Cooling System (PSCS)® when used at cooler temperatures of -7.5°C and -10°C. Methods: Patients with stage I-III breast cancer receiving anthracycline chemotherapy at Memorial Sloan Kettering Cancer Center from 12/23/2019 – 10/12/2022 were enrolled on this IRB-approved study. They were evaluated for hair loss at baseline, weeks 4, 8 (primary endpoint), end of treatment, and 24 weeks post treatment using clinical photography and trichoscopy, which measures hair width and count. Degree of hair loss was graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4. Successful hair preservation is indicated by alopecia grades 0 and 1. Results: 34 patients (mean age 44) used the PSCS at cooler temperatures with no DLTs. 7 patients received scalp cooling at -7.5°C and 27 patients at -10°C. 19 women (55.9%) were included in the final analysis; 7 patients withdrew or were taken off study prior to the primary endpoint and 8 patients did not successfully complete photographic or trichoscopic follow-up assessments. At the baseline visit, 95% of patients had grade 0 alopecia (n = 18) and 5.3% had grade 1 alopecia (n = 1). At week 8 (primary endpoint) 53% of patients had grade 1 alopecia and 47% had grade 2 alopecia. At completion of therapy, 7% of patients had grade 0 alopecia, 36% had grade 1 alopecia, 7% are pending and 50% had grade 2 alopecia. At 24 weeks post treatment completion, 23% of patients had grade 0 alopecia (n = 3), 31% had grade 1 alopecia (n = 4), and 46% of patients are pending results (n = 6). At baseline, the average hair count was 149.0 per cm2 (n = 19) and the average hair width was 68.9μm (n = 19). At week 4 and 8, there was a -27% and -8.9% change in hair count and -8.6% and -9.3 percent change in hair width (n = 18) respectively. By end of treatment, percent change was -37.8 and -11.6 for hair count and hair width, respectively (n = 14). At 24 weeks post treatment completion, both the average hair count and hair width for patients were higher compared to their baseline (hair count = 242 per cm2 and hair width = 70.7μm (n = 13; 6 patients pending). Conclusions: Overall, use of the PSCS for successful hair preservation is effective, safe, and tolerable at lower temperatures for patients being treated with anthracycline chemotherapy. 43% of patients had hair preservation at the completion of the study. At 24 weeks post treatment, the average hair count and width was higher than the values at baseline indicating thicker, full hair regrowth. None of the patients displayed grade 2 alopecia at 24 weeks post treatment, allowing patients to avoid the use of a wig to hide resulting CIA. Clinical trial information: NCT04180579 .

A phase ll study on the neoadjuvant treatment of resectable high-risk soft tissue sarcoma with anlotinib and doxorubicin.

e23542 Background: Anthracycline and ifosfomide-based chemotherapy is the main neoadjuvant treatment option for resectable high-risk STS with severe myelosuppression and other side effects. Anlotinib has been approved as second-line treatment for most of advanced STS by the Chinese agency. This study was conducted to evaluate the efficacy and safety of anlotinib in combination with doxorubicin in the neoadjuvant treatment of patients with resectable high-risk STS to reduce the toxicity of chemotherapy. Methods: This is a single-center, prospective study. Eligible patients were those ≥18years old, ECOG performance state of 0-1, with histologically confirmed locally resectable high-risk STS. All patients received a preoperative combination of anlotinib (12mg once daily, on for 2 weeks, off for 1 week) and doxorubicin (75mg /m2, IV, D1-2, every 3 weeks) .The combination treatment was repeated 2 to 3 cycles before operation. The primary endpoint was objective response rate (ORR), and the second endpoints were Disease control rate (DCR), and side effects. Results: Between December 2020 and December 2022, 13 patients were evaluated, including 4 synovial sarcoma, 3 undifferentiated sarcoma, 3 spindle cell sarcoma, 2 liposarcoma, 1 angiosarcoma. The median age was 35 years. 1 patients (7.69%) achieved a confirmed partial response (PR) and 7 (53.85%) had stable disease (SD). The ORR and DCR were 7.69% and 61.54% respectively. All patients underwent marginal or extensive excision of the tumor and none underwent amputation. Most of Treatment-related adverse events included neutropenia 5 (38.46%), hypothyroidism 3 (23.08%), anemia 2(15.38%). Three patients experienced grade 3 or 4 adverse events, neutropenia (1/13, 7.69%) and tumor hemorrhage (2/13, 15.38%). No wound complications such as infection, delayed healing or haematoma occurred. Conclusions: This study suggested that the combination of anlotinib and doxorubicin might be a option for neoadjuvant therapy for patients with resectable high-risk STS due to the anti-tumor activity and acceptable toxicity.

Trastuzumab-induced cardiotoxicity in breast cancer patients: A meta-analysis and review of the literature (2012-2022).

e24101 Background: Breast cancer (BC) is the most common type of cancer diagnosed, and 10-15% of BC patients develop a HER2-positive disease with a poor prognosis. In a previous meta-analysis of NCCTG N9831 and NSABP B-31 trials, treatment of early-stage HER2-positive BC patients with Trastuzumab and chemotherapeutic drugs improved overall survival by 37%. Trastuzumab-induced cardiotoxicity (TIC) is characterized by cardiac dysfunction, including decreased left ventricular ejection fraction (LVEF) and heart failure. Per package inserts, the incidence of TIC is 4-6 times higher than the control. An important risk factor for TIC is the administration of concomitant anthracycline chemotherapy. Several studies have reported that this treatment combination can significantly reduce LVEF compared to Trastuzumab alone. In this study, we compiled recent randomized controlled trials (RCTs) and clinical trial data to evaluate the incidence of cardiotoxicity in Trastuzumab-treated BC and study management guidelines specifically directed for TIC. This will help reduce the morbidity and mortality in these patients. Methods: Our search included PubMed, EMBASE, Web of Science, and Cochrane Library articles from July 2012 through July 2022. RCTs and clinical trials that used Trastuzumab as a therapy and reported its cardiotoxic effects were included. A random-effects model was utilized with Review Manager, and a P value &lt; 0.05 was considered significant. The entire analysis of treatment and control groups had various guideline-directed chemotherapies, including anthracycline-based regimens. Results: Our initial search yielded 26 results. After a full literature review by two independent reviewers, we selected four studies that included 1481 patients with cardiotoxicity data in the treatment and control groups. The analysis pooled from clinical trials showed that the odds of cardiotoxicity (specifically LVEF reduction) in patients treated with Trastuzumab were about seven times higher than the control group (OR 6.78, 95% CI 2.85-16.09, p-value &lt; 0.0001). The guidelines recommend withholding Trastuzumab for ≥ 16% absolute decrease in LVEF from pre-treatment values or an LVEF value below normal institutional limits and ≥ 10% absolute decrease in LVEF from pretreatment values. The safety of continuation or resumption of Trastuzumab in patients with TIC has not been studied, and there are no standardized management guidelines. Conclusions: We conclude in our study that the odds of TIC are increased by almost seven times compared to chemotherapy alone. In addition to just regular monitoring of these patients with history, physical examination, and determination of LVEF by echocardiogram or MUGA scan per protocol, there is a need to formulate guidelines for continuation or resumption of Trastuzumab in patients with TIC.

Left Ventricle Size Correlates with Peak Exercise Capacity in Pediatric Cancer Survivors Exposed to Anthracycline Chemotherapy

Cancer survivors exposed to anthracycline chemotherapy are at risk for developing cardiomyopathy, which may have delayed clinical manifestation. In a retrospective cross-sectional study, we evaluated the utility of cardiopulmonary exercise testing (CPET) for detecting early cardiac disease in 35 pediatric cancer survivors by examining the associations between peak exercise capacity (measured via percent predicted peak VO2) and resting left ventricular (LV) function on echocardiography and cardiac magnetic resonance imaging (cMRI). We additionally assessed the relationships between LV size on resting echocardiography or cMRI and percent predicted peak VO2 since LV growth arrest can occur in anthracycline-exposed patients prior to changes in LV systolic function. We found reduced exercise capacity in this cohort, with low percent predicted peak VO2 (62%, IQR: 53–75%). While most patients in our pediatric cohort had normal LV systolic function, we observed associations between percent predicted peak VO2 and echocardiographic and cMRI measures of LV size. These findings indicate that CPET may be more sensitive in manifesting early anthracycline-induced cardiomyopathy than echocardiography in pediatric cancer survivors. Our study also highlights the importance of assessing LV size in addition to function in pediatric cancer survivors exposed to anthracyclines.

C9 THE EFFECT OF ANTHRACYCLINE CHEMOTHERAPY ON PEAK LEFT ATRIAL LONGITUDINAL STRAIN: A METANALYSIS

Abstract Background Currently there is a limited number of studies reporting atrial function, evaluated by peak left atrial longitudinal strain (PALS), among patients undergoing anthracycline chemotherapy. Objective We investigated this issue through a meta–analysis of echocardiography studies that reported data on: A) PALS before and after anthracycline chemotherapy and B) PALS in patients who have previously received anthracycline chemotherapy versus controls. Methods The PubMed, OVID–MEDLINE and Cochrane library databases were systematically analysed to search articles and abstracts published from inception to 29th December 2022. Studies were identified by using Me–SH terms and crossing the following terms: “left atrial strain”, AND “cardiotoxicity”, “anthracycline”, “anthracycline cardiotoxicity” and “echocardiography”. Results The meta–analysis included a total of 967 patients from 10 studies. A) The metanalysis of six studies evaluating PALS before and after anthracycline chemotherapy in a total of 343 patients showed a significant PALS worsening after anthracycline (30,05±2,5 vs 26,8±3,1) with standard mean difference (SMD) being –0,27±0,06, p &amp;lt; 0.0001. Figure 1 panel A. B) Five studies evaluated PALS in 359 patients who have previously received anthracycline chemotherapy versus 356 controls. Compared with controls, PALS was significantly worse in the pooled anthracycline group (34,63±1,8 vs 37,64±2,7) with SMD being –0.35 ± 0,08, p &amp;lt; 0.0001. Figure 1 panel B. Conclusions Our metanalysis suggests a detrimental effect of anthracycline chemotherapy on atrial function evaluated by PALS.

Renin-angiotensin System Antagonists and Beta-blockers in Prevention of Anthracycline Cardiotoxicity: a Systematic Review and Meta-analysis.

The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).