Trióxido de arsénico en pacientes con leucemia promielocítica aguda en recaída / Trióxido de arsénico em pacientes com leucemia promielocítica aguda recuperável

INTRODUCCIÓN: Cuadro clínico: La leucemia promielocítica aguda (LPA) representa el 5% a 20% de los casos de leucemia mieloide aguda (LMA) (1,2); sin embargo, entre pacientes de origen latino se ha reportado una frecuencia de 38%. En Perú, a pesar de que no se tienen reportes de la frecuencia de la leucemia promielocítica aguda (LPA), en un estudio realizado entre el año 1996 y 2008 en el Hospital Nacional Edgardo Rebagliati Martins se observó que el 52% y 38% de los pacientes con LPA se encontraban entre los grupos etarios de 16 - 40 años y 41 - 60 años, respectivamente (3). En pacientes con LPA sin tratamiento la mediana de sobrevida es menor a un mes, debido al sangrado descontrolado (4). Sin embargo, con los avances recientes en las terapias, la sobrevida ha mejorado y la mayoría de los pacientes alcanza la remisión completa y se mantiene. El tratamiento de la LPA comprende tres etapas: remisión o inducción, consolidación y mantenimiento. Del total de pacientes con LPA tratados con ácido trans-retinoico (ATRA) más quimioterapia con antraciclinas, el 10 % al 20% sufre una recaída. El objetivo de tratamiento de este grupo de pacientes es alcanzar la remisión molecular, con planes de proseguir con quimioterap

Assessment of Left Ventricular Diastolic Function in Patients with Diffuse Large B-cell Lymphoma after Anthracycline Chemotherapy by using Vector Flow Mapping.

BACKGROUND: Patients with diffuse large B-cell lymphoma (DLBCL) often experience a poor prognosis due to cardiac damage induced by anthracycline chemotherapy, with left ventricular diastolic dysfunction manifesting early. Vector Flow Mapping (VFM) is a novel technology, and its effectiveness in detecting left ventricular diastolic dysfunction following anthracycline chemotherapy remains unverified. OBJECTS: This study evaluates left ventricular diastolic function in DLBCL patients after anthracycline chemotherapy using vector flow mapping (VFM). MATERIALS AND METHODS: We prospectively enrolled 54 DLBCL patients who had undergone anthracycline chemotherapy (receiving a minimum of 4 cycles) as the case group and 54 age- and sex-matched individuals as controls. VFM assessments were conducted in the case group pre-chemotherapy (T0), post-4 chemotherapy cycles (T4), and in the control group. Measurements included basal, middle, and apical segment energy loss (ELb, ELm, ELa) and intraventricular pressure differences (IVPDb, IVPDm, IVPDa) across four diastolic phases: isovolumic relaxation (D1), rapid filling (D2), slow filling (D3), and atrial contraction (D4). RESULTS: When comparing parameters between the control and case groups at T0, no significant differences were observed in general data, conventional ultrasound parameters, and VFM parameters (all P > 0.05). From T0 to T4, ELa significantly increased throughout the diastole cycle (all P < 0.05); ELm increased only during D4 (all P < 0.05); and ELb increased during D1, D2, and D4 (all P < 0.05). All IVPD measurements (IVPDa, IVPDm, IVPDb) increased during D1 and D4 (all P < 0.05) but decreased during D2 and D3 (all P < 0.05). Significant positive correlations were identified between ELa-D4, IVPDa-D4, and parameters A, e', E/e,' and LAVI (all r > 0.5, all P < 0.001). Negative correlations were noted with E/A for ELa- D4 IVPDa-D4 (all r < -0.5, all P < 0.001). Positive correlations were observed for IVPDa-D1, IVPDa-D2 with E, E/e', and LAVI (0.3

Clinical outcomes of adjuvant taxane plus anthracycline versus taxane-based chemotherapy regimens in older adults with node-positive, triple-negative breast cancer: A SEER-Medicare study.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer associated with an aggressive clinical course. Adjuvant chemotherapy reduces the risk of recurrence and improves survival in patients with node-positive TNBC. The benefit of anthracycline plus taxane (ATAX) regimens compared with non-anthracycline-containing, taxane-based regimens (TAX) in older women with node-positive TNBC is not well characterised. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1106 women with node-positive TNBC diagnosed at age 66 years and older between 2010 and 2015. We compared patient clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs). Kaplan-Meier survival curves were generated to estimate 3-year overall survival (OS) and cancer-specific survival (CSS). Cox proportional hazard models were used to analyse OS and CSS while controlling for patient and tumour characteristics. RESULTS: Of the 1106 patients in our cohort, 767 (69.3%) received adjuvant chemotherapy with ATAX (364/767, 47.5%), TAX (297/767, 39%) or other regimens (106/767, 13.8%). Independent predictors of which patients were more likely to receive ATAX versus TAX included more extensive nodal involvement (≥4), age, marital/partner status and non-cardiac comorbidities. There was a statistically significant improvement in 3-year CSS (81.8% versus 71.4%) and OS (70.7% versus 51.3%) with the use of any chemotherapy in our cohort (P < 0.01). Three-year CSS and OS for patients who received ATAX versus TAX were similar at 82.8% versus 83.7% (P = 0.80) and 74.2% versus 72.7% (P = 0.79), respectively. There was a trend towards improved CSS and OS in patients with four or more positive lymph nodes who received ATAX versus TAX (hazard ratio 0.66, 95% CI: 0.36-1.23, P = 0.19 and hazard ratio 0.68, 95% CI: 0.41-1.14, P = 0.14, respectively). CONCLUSION: Among older women with node-positive TNBC, a majority of patients received adjuvant chemotherapy, which was associated with an improvement in CSS and OS. When compared with TAX chemotherapy, there was a trend towards better outcomes with ATAX for patients with ≥4 nodes.

Association of Preexisting Heart Failure With Outcomes in Older Patients With Diffuse Large B-Cell Lymphoma.

Importance: Anthracycline-containing regimens are highly effective for diffuse large B-cell lymphoma (DLBCL); however, patients with preexisting heart failure (HF) may be less likely to receive anthracyclines and may be at higher risk of lymphoma mortality. Objective: To assess the prevalence of preexisting HF in older patients with DLBCL and its association with treatment patterns and outcomes. Design, Setting, and Participants: This longitudinal cohort study used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare registry from 1999 to 2016. The SEER registry is a system of population-based cancer registries, capturing more than 25% of the US population. Linkage to Medicare offers additional information from billing claims. This study included individuals 65 years and older with newly diagnosed DLBCL from 2000 to 2015 with Medicare Part A or B continuously in the year prior to lymphoma diagnosis. Data were analyzed from September 2020 to December 2022. Exposures: Preexisting HF in the year prior to DLBCL diagnosis ascertained from billing codes required one of the following: (1) 1 primary inpatient discharge diagnosis, (2) 2 outpatient diagnoses, (3) 3 secondary inpatient discharge diagnoses, (4) 3 emergency department diagnoses, or (5) 2 secondary inpatient discharge diagnoses plus 1 outpatient diagnosis. Main Outcomes and Measures: The primary outcome was anthracycline-based treatment. The secondary outcomes were (1) cardioprotective medications and (2) cause-specific mortality. The associations between preexisting HF and cancer treatment were estimated using multivariable logistic regression. The associations between preexisting HF and cause-specific mortality were evaluated using cause-specific Cox proportional hazards models with adjustment for comorbidities and cancer treatment. Results: Of 30 728 included patients with DLBCL, 15 474 (50.4%) were female, and the mean (SD) age was 77.8 (7.2) years. Preexisting HF at lymphoma diagnosis was present in 4266 patients (13.9%). Patients with preexisting HF were less likely to be treated with an anthracycline (odds ratio, 0.55; 95% CI, 0.49-0.61). Among patients with preexisting HF who received an anthracycline, dexrazoxane or liposomal doxorubicin were used in 78 of 1119 patients (7.0%). One-year lymphoma mortality was 41.8% (95% CI, 40.5-43.2) with preexisting HF and 29.6% (95% CI, 29.0%-30.1%) without preexisting HF. Preexisting HF was associated with higher lymphoma mortality in models adjusting for baseline and time-varying treatment factors (hazard ratio, 1.24; 95% CI, 1.18-1.31). Conclusions and Relevance: In this study, preexisting HF in patients with newly diagnosed DLBCL was common and was associated with lower use of anthracyclines and lower use of any chemotherapy. Trials are needed for this high-risk population.

Functional status and therapy for older adults with diffuse large B-cell lymphoma in nursing homes: A population-based study.

OBJECTIVES: To characterize the prevalence of functional and cognitive impairments, and associations between impairments and treatment among older patients with diffuse large B cell lymphoma (DLBCL) receiving nursing home (NH) care. METHODS: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify beneficiaries diagnosed with DLBCL 2011-2015 who received care in a NH within -120 ~ +30 days of diagnosis. Multivariable logistic regression was used to compare receipt of chemoimmunotherapy (including multi-agent, anthracycline-containing regimens), 30-day mortality, and hospitalization between NH and community-dwelling patients, estimating odds ratios (OR) and 95% confidence interval (CI). We also examined overall survival (OS). Among NH patients, we examined receipt of chemoimmunotherapy based on functional and cognitive impairment. RESULTS: Of the eligible 649 NH patients (median age: 82 years), 45% received chemoimmunotherapy; among the recipients, 47% received multi-agent, anthracycline-containing regimens. Compared with community-dwelling patients, those in a NH were less likely to receive chemoimmunotherapy (OR: 0.34, 95%CI: 0.29-0.41), had higher 30-day mortality (OR: 2.00, 95%CI: 1.43-2.78) and hospitalization (OR: 1.51, 95%CI: 1.18-1.93), and poorer OS (hazard ratio: 1.36, 95%CI: 1.11-1.65). NH patients with severe functional (61%) or any cognitive impairment (48%) were less likely to receive chemoimmunotherapy. CONCLUSIONS: High rates of functional and cognitive impairment and low rates of chemoimmunotherapy were observed among NH residents diagnosed with DLBCL. Further research is needed to better understand the potential role of novel and alternative treatment strategies and patient preferences for treatment to optimize clinical care and outcomes in this high-risk population.

Assessment of Global Cardiac Function Using AutoSTRAIN Automatic Strain Quantitative Technology in Patients With Breast Cancer Undergoing Anthracycline-Based Chemotherapy.

In patients with breast cancer undergoing anthracycline-based chemotherapy, we investigated the deformational parameters of the left ventricle, right ventricle and left atrium, as well as the relationship between these parameters. Ninety-five patients with breast cancer who were treated with anthracycline-based chemotherapy were enrolled. The control group included 116 healthy female volunteers. Parameters including left ventricular global longitudinal strain (LV-GLS); right ventricular free wall longitudinal strain (RVFWSL) and global longitudinal strain (RV4CSL); and peak strain of the left atrium during LV systole (LASR), early LV diastole (LASCD) and late LV diastole (LASCT) were analyzed by speckle tacking echocardiography. LV-GLS, LASR, LASCD, RVFWSL and RV4CSL in the chemotherapy group decreased significantly by 15.6%, 13.8%, 19.8%, 21.8% and 13.2% (p < 0.05), respectively, when compared with the control group. LASCT was slightly increased in the chemotherapy group but the increase was not statistically significant (p > 0.05). Formulas for the influencing factors of LV-GLS were LV-GLS = -18.73738541 + 0.13961 × LVIDd + 0.09672 × LASCD + 0.18113 × RVFWSL in the control group and LV-GLS = -8.026302253 + 0.20811 × LASCD + 0.11084 × LASCT + 0.12153 × RVFWSL in the chemotherapy group. Both LV contraction and RV contraction were impaired after the completion of anthracycline-based therapy, and RVFWSL may be superior to LV-GLS in assessing cardiotoxicity. LA reserve and channel function were significantly reduced, while pump function was slightly increased. Compared with the results among healthy people, the influencing factor of LV-GLS varied after anthracycline treatment, and LA function had a greater impact on LV-GLS.

Evaluating anthracycline + taxane versus taxane-based chemotherapy in older women with node-negative triple-negative breast cancer: a SEER-Medicare study.

PURPOSE: Adjuvant chemotherapy reduces recurrence in early-stage triple-negative breast cancer (TNBC). However, data are lacking evaluating anthracycline + taxane (ATAX) versus taxane-based (TAX) chemotherapy in older women with node-negative TNBC, as they are often excluded from trials. The purpose of this study was to evaluate the effect of adjuvant ATAX versus TAX on cancer-specific (CSS) and overall survival (OS) in older patients with node-negative TNBC. PATIENTS AND METHODS: Using the SEER-Medicare database, we selected patients aged ≥ 66 years diagnosed with Stage T1-4N0M0 TNBC between 2010 and 2015 (N = 3348). Kaplan-Meier survival curves and adjusted Cox proportional hazards models were used to estimate 3-year OS and CSS. Multivariant Cox regression analysis was used to identify independent factors associated with use of ATAX compared to TAX. RESULTS: Approximately half (N = 1679) of patients identified received chemotherapy and of these, 58.6% (N = 984) received TAX, 25.0% (N = 420) received ATAX, and 16.4% (N = 275) received another regimen. Three-year CSS and OS was improved with any adjuvant chemotherapy from 88.9 to 92.2% (p = 0.0018) for CSS and 77.2% to 88.6% for OS (p < 0.0001). In contrast, treatment with ATAX compared to TAX was associated with inferior 3-year CSS and OS. Three-year CSS was 93.7% with TAX compared to 89.8% (p = 0.048) for ATAX and OS was 91.0% for TAX and 86.4% for ATAX (p = 0.032). CONCLUSION: While adjuvant chemotherapy was associated with improved clinical outcomes, the administration of ATAX compared to TAX was associated with inferior 3-year OS and CSS in older women with node-negative TNBC. The use of adjuvant ATAX should be considered carefully in this patient population.

Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)-Positive Breast Cancer.

Importance: The neoadjuvant treatment options for ERBB2-positive (also known as HER2-positive) breast cancer are associated with different rates of pathologic complete response (pCR). The KATHERINE trial showed that adjuvant trastuzumab emtansine (T-DM1) can reduce recurrence in patients with residual disease compared with patients treated with trastuzumab; however, T-DM1 and other ERBB2-targeted agents are costly, and understanding the costs and health consequences of various combinations of neoadjuvant followed by adjuvant treatments in the United States is needed. Objective: To examine the costs and disease outcomes associated with selection of various neoadjuvant followed by adjuvant treatment strategies for patients with ERBB2-positive breast cancer. Design, Setting, and Participants: In this economic evaluation, a decision-analytic model was developed to evaluate various neoadjuvant followed by adjuvant treatment strategies for women with ERBB2-positive breast cancer from a health care payer perspective in the United States. The model was informed by the KATHERINE trial, other clinical trials with different regimens from the KATHERINE trial, the Flatiron Health Database, McKesson Corporation data, and other evidence in the published literature. Starting trial median age for KATHERINE patients was 49 years (range, 24-79 years in T-DM1 arm and 23-80 years in trastuzumab arm). The model simulated patients receiving 5 different neoadjuvant followed by adjuvant treatment strategies. Data analyses were performed from March 2019 to August 2020. Exposure: There were 4 neoadjuvant regimens: (1) HP: trastuzumab (H) plus pertuzumab (P), (2) THP: paclitaxel (T) plus H plus P, (3) DDAC-THP: dose-dense anthracycline/cyclophosphamide (DDAC) plus THP, (4) TCHP: docetaxel (T) plus carboplatin (C) plus HP. All patients with pCR, regardless of neoadjuvant regimen, received adjuvant H. Patients with residual disease received different adjuvant therapies depending on the neoadjuvant regimen according to the 5 following strategies: (1) neoadjuvant DDAC-THP followed by adjuvant H, (2) neoadjuvant DDAC-THP followed by adjuvant T-DM1, (3) neoadjuvant THP followed by adjuvant DDAC plus T-DM1, (4) neoadjuvant HP followed by adjuvant DDAC/THP plus T-DM1, or (5) neoadjuvant TCHP followed by adjuvant T-DM1. Main Outcomes and Measures: Lifetime costs in 2020 US dollars and quality-adjusted life-years (QALYs) were estimated for each treatment strategy, and incremental cost-effectiveness ratios were estimated. A strategy was classified as dominated if it was associated with fewer QALYs at higher costs than the alternative. Results: In the base-case analysis, costs ranged from $415 833 (strategy 3) to $518 859 (strategy 4), and QALYs ranged from 9.67 (strategy 1) to 10.73 (strategy 3). Strategy 3 was associated with the highest health benefits (10.73 QALYs) and lowest costs ($415 833) and dominated all other strategies. Probabilistic analysis confirmed that this strategy had the highest probability of cost-effectiveness (>70% at willingness-to-pay thresholds of $0-200,000/QALY) and was associated with the highest net benefit. Conclusions and Relevance: These results suggest that neoadjuvant THP followed by adjuvant H for patients with pCR or followed by adjuvant DDAC plus T-DM1 for patients with residual disease was associated with the highest health benefits and lowest costs for women with ERBB2-positive breast cancer compared with other treatment strategies considered.

Assessment of Doxorubicin and Pembrolizumab in Patients With Advanced Anthracycline-Naive Sarcoma: A Phase 1/2 Nonrandomized Clinical Trial.

IMPORTANCE: Anthracycline-based therapy is standard first-line treatment for most patients with advanced and metastatic sarcomas. Although multiple trials have attempted to show improved outcomes in patients with soft-tissue sarcoma over doxorubicin monotherapy, each has fallen short of demonstrating improved outcomes. OBJECTIVE: To evaluate the safety and efficacy of doxorubicin in combination with pembrolizumab in patients with advanced, anthracycline-naive sarcomas. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized clinical trial used a 2-stage phase 2 design and was performed at a single, academic sarcoma specialty center. Patients were adults with good performance status and end-organ function. Patients with all sarcoma subtypes were allowed to enroll with the exception of osteosarcoma, Ewing sarcoma, and alveolar and embryonal rhabdomyosarcoma. INTERVENTIONS: Two dose levels of doxorubicin (45 and 75 mg/m2) were tested for safety in combination with pembrolizumab. MAIN OUTCOMES AND MEASURES: Objective response rate (ORR) was the primary end point. Overall survival (OS) and progression-free survival (PFS) were secondary end points. Correlative studies included immunohistochemistry, gene expression, and serum cytokines. RESULTS: A total of 37 patients (22 men; 15 women) were treated in the combined phase 1/2 trial. The median (range) patient age was 58.4 (25-80) years. The most common histologic subtype was leiomyosarcoma (11 patients). Doxorubicin plus pembrolizumab was well tolerated without significant unexpected toxic effects. The ORR was 13% for phase 2 patients and 19% overall. Median PFS was 8.1 (95% CI, 7.6-10.8) months. Median OS was 27.6 (95% CI, 18.7-not reached) months at the time of this analysis. Two of 3 patients with undifferentiated pleomorphic sarcoma and 2 of 4 patients with dedifferentiated liposarcoma had durable partial responses. Tumor-infiltrating lymphocytes were present in 21% of evaluable tumors and associated with inferior PFS (log-rank P = .03). No dose-limiting toxic effects were observed. CONCLUSIONS AND RELEVANCE: In this nonrandomized clinical trial, doxorubicin plus pembrolizumab was well tolerated. Although the primary end point for ORR was not reached, the PFS and OS observed compared favorably with prior published studies. Further studies are warranted, especially those focusing on undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02888665.

Magnetic resonance imaging assessment of chemotherapy-related adipocytic maturation in myxoid/round cell liposarcomas: specificity and prognostic value.

OBJECTIVE: To investigate the specificity, clinical implication and prognostic value of MRI adipocytic maturation (MAM) in myxoid/round cells liposarcomas (MRC-LPS) treated with neoadjuvant chemotherapy (NAC). METHODS: Of the 89 patients diagnosed with MRC-LPS at our sarcoma reference center between 2008 and 2018, 28 were included as they were treated with NAC, surgery and radiotherapy. All patients underwent contrast-enhanced MRIs at baseline and late evaluation. A control cohort of 13 high-grade pleomorphic and dedifferentiated LPS with same inclusion criteria was used to evaluate the specificity of MAM in MRC-LPS. Two radiologists analyzed the occurrence of MAM, changes in the tumor architecture, shape and surrounding tissues during NAC. Pathological features of tumor samples were reviewed and correlated with MRI. Metastatic relapse-free survival was estimated with Kaplan-Meier curves and Cox models. Associations between prognostic T1-based delta-radiomics features and MAM were investigated with Student t-test. RESULTS: MAM was more frequent in MRC-LPS (p = 0.045) and not specific of any type of chemotherapy (p = 0.7). Regarding MRC-LPS, 14 out of 28 patients (50%) demonstrated MAM. Eight patients showed metastatic relapses. MAM was not associated with metastatic relapse-free survival (p = 0.9). MAM correlated strongly with the percentage of histological adipocytic differentiation on surgical specimen (p < 0.001), which still expressed the tumor marker NY-ESO-1. None of the prognostic T1-based delta-radiomics features was associated with MAM. CONCLUSION: MAM seems a neutral event during NAC. ADVANCES IN KNOWLEDGE: MAM predominated in MRC-LPS and was not specific of a type of chemotherapy. Occurrence of MAM was not associated with better patients' metastasis free survival.

Prognostic Value of Cardiac Biomarkers Assessment in Combination with Myocardial 2D Strain Echocardiography for Early Detection of Anthracycline-Related Cardiac Toxicity.

BACKGROUND: Anthracyclines, a widely used chemotherapy agent with a definite survival improvement, can result in cardiac toxicity presenting with HF (heart failure). OBJECTIVE: We aim to assess the predictive value of cardiac biomarkers assessment in combination with myocardial two-dimensional strain echocardiography for early detection of cardiac toxicity in patients who underwent Anthracycline-based chemotherapy. METHODS: Fifty-two consecutive adult patients scheduled to undergo the first course of Anthracycline-based chemotherapy were subjected to the study. All the patients underwent highly sensitive 2D echocardiographic evaluation before the treatment, 4 and 12 weeks after completion of first-course chemotherapy. Longitudinal and segmental strains were measured. Serum levels of High-sensitive cardiac troponin I (hscTn-I) and N-terminal-pro-BNP (NT-proBNP) were also assessed before the initiation and 3 weeks after completion of first-course chemotherapy. RESULTS: Fifteen patients (28.8%) revealed a decrease in LVEF (Left Ventricular Ejection Fraction) throughout the evaluations, while just 5 patients met the criteria of cardiac toxicity (9.6%). AUC for Global Longitudinal Strain (GLS) ROC curve at 4 weeks of follow-up was calculated to be 0.968. Inferoseptal Systolic Longitudinal Strain (SLS) had the highest AUC value (AUC: 0.934) among different wall SLS. LVESD (Left Ventricular End-Systolic Diameter) at first and second evaluation could predict the risk of cardiac toxicity among LVESD, LVEDD (Left Ventricular End Diastolic Diameter) and LVEDV (Left Ventricular End-Diastolic Volume). Among cardiac biomarkers, hscTnI had higher sensitivity, while NT-proBNP had higher specificity for cardiac toxicity. CONCLUSION: This study has shown that hs-cTnI with good sensitivity can predict cardiac toxicity in Anthracycline-based chemotherapy receiver. The use of strain with speckle echocardiography method has a prognostic value; however, both longitudinal and segmental strain should be assessed. Lateral and inferoseptal SLS (Segmental Longitudinal Strain) are specific markers of cardiac toxicity in the course of anthracycline-related cardiac toxicity.

Echocardiographic Assessment of Cardiac Function in Pediatric Survivors of Anthracycline-Treated Childhood Cancer.

BACKGROUND: Anthracycline-induced cardiotoxicity is a major cause of morbidity and mortality in childhood cancer survivors (CCSs). Echocardiographic myocardial strain imaging is recommended in adult patients with cancer, but its role in pediatric CCSs has not been well established. Aims of this study were to determine the prevalence of abnormalities in left ventricular strain in pediatric CCSs, to compare strain with other echocardiographic measurements and blood biomarkers, and to explore risk factors for reduced strain. METHODS: CCSs ≥3 years from their last anthracycline treatment were enrolled in this multicenter study and underwent a standardized functional echocardiogram and biomarker collection. Regression analysis was used to identify factors associated with longitudinal strain (LS). RESULTS: Five hundred forty-six pediatric CCSs were compared with 134 healthy controls. Abnormal left ventricular ejection fraction (<50%) and mean LS (Z score, <-2) was found in 0.8% and 7.7% of the CCSs, respectively. LS was significantly lower in CCSs than in controls, but the absolute difference was small (0.7%). Lower LS in CCSs was associated with older current age and higher body surface area. Sex, cumulative anthracycline dose, radiotherapy, and biomarkers were not independently associated with LS. Circumferential strain, diastolic parameters, and biomarkers were not significantly different in pediatric CCSs. CONCLUSIONS: Global systolic function and LS are only mildly reduced in pediatric CCSs, and most LS values are within normal range. This makes single LS measurements of limited added value in identifying CCSs at risk for cardiac dysfunction. The utility of strain imaging in the long-term follow-up of CCS remains to be demonstrated.

Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy.

BACKGROUND: There is a lack of consensus to guide which breast cancer patients require left ventricular function assessment (LVEF) prior to anthracycline therapy; the cost-effectiveness of screening this patient population has not been previously evaluated. METHODS: We performed a retrospective analysis of the Yale Nuclear Cardiology Database, including 702 patients with baseline equilibrium radionuclide angiography (ERNA) scan prior to anthracycline and/or trastuzumab therapy. We sought to examine associations between abnormal baseline LVEF and potential cardiac risk factors. Additionally, we designed a Markov model to determine the incremental cost-effectiveness ratio (ICER) of ERNA screening for women aged 55 with stage I-III breast cancer from a payer perspective over a lifetime horizon. RESULTS: An abnormal LVEF was observed in 2% (n = 14) of patients. There were no significant associations on multivariate analysis performed on self-reported risk factors. Our analysis showed LVEF screening is cost-effective with ICER of $45,473 per QALY gained. For a willingness-to-pay threshold of $100,000/ QALY, LVEF screening had an 81.9% probability of being cost-effective. Under the same threshold, screening was cost-effective for non-anthracycline cardiotoxicity risk of RR ≤ 0.58, as compared to anthracycline regimens. CONCLUSIONS: Age, preexisting cardiac risk factors and coronary artery disease did not predict a baseline abnormal LVEF. While the prevalence of an abnormal baseline LVEF is low in patients with breast cancer, our results suggest that cardiac screening prior to anthracycline is cost-effective.

Congestive heart failure in older adults diagnosed with follicular lymphoma: A population-based study.

BACKGROUND: To the authors' knowledge, there is limited information regarding the long-term risk of congestive heart failure (CHF) among patients with follicular lymphoma, a prevalent non-Hodgkin lymphoma diagnosis among those aged >65 years, especially within the context of therapeutic exposures and preexisting comorbidities. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data from 1999 through 2013, the authors identified 6109 patients with follicular lymphoma who were diagnosed at age ≥66 years between January 1, 2000 and December 31, 2011, and a frequency-matched Medicare noncancer sample. Subdistribution hazards models assessed risks associated with new-onset CHF through December 31, 2013. Propensity score-matched models examined CHF risk in patients receiving anthracyclines when compared with matched noncancer controls. RESULTS: When compared with matched controls, patients with follicular lymphoma receiving anthracyclines at ages 66 to 75 years had a 1.7-fold (95% confidence interval, 1.4-fold to 2.1-fold) higher risk of new-onset CHF; patients diagnosed at age >75 years did not differ from noncancer controls with regard to CHF risk. Preexisting hypertension was associated with a 1.7-fold and 1.35-fold, respectively, increased hazard of CHF for each age group, independent of anthracycline exposure. Preexisting diabetes was associated with 1.5-fold increased hazard of CHF only in those patients aged 66 to 75 years. Patients with new-onset CHF had a 18% lower 10-year survival compared with those without CHF. CONCLUSIONS: Patients with follicular lymphoma who were exposed to anthracyclines between the ages of 66 years and 75 years were found to be at an increased risk of new-onset CHF; preexisting hypertension and diabetes appeared to increase this risk. The findings of the current study support and inform the risk-based follow-up of vulnerable populations.

Subclinical anthracycline-induced cardiotoxicity in long-term follow-up of asymptomatic childhood cancer survivors: Assessment by speckle tracking echocardiography.

OBJECTIVE: Survivors of childhood cancer treated with anthracyclines carry the risk for developing late-onset cardiotoxicity. The purpose of this study was to evaluate left ventricular (LV) function in this patient group and compare it with healthy controls by means of conventional and speckle tracking echocardiography (STE) after exposure to chemotherapy. MATERIAL AND METHODS: Conventional and STE were performed in 45 childhood cancer survivors (mean age 11 ± 4.6; 26 male) treated with anthracyclines (median cumulative dosage 240 mg/m2 ; range, 100-460) and compared with age, gender and body surface area matched healthy controls. Follow-up period after chemotherapy was 21.9 ± 17.8 months. Blood samples were taken from survivors and controls to determine brain natriuretic peptide (BNP). RESULTS: Following anthracycline exposure, pediatric cancer survivors had lower longitudinal, radial anteroseptal, and radial anterior strain values compared to controls (P < .05). The calculated global longitudinal and global radial strain values were lower compared to the control group (P < .05). Both groups had normal ejection fraction (EF) and fractional shortening (FS). Brain natriuretic peptide (BNP) levels of both groups were in the normal range. CONCLUSION: Despite normal EF and FS, children exposed to anthracycline therapy may have late-onset subtle changes of LV strain values measured by STE. Whether these changes of strain can predict future risk of developing heart failure needs to be explored in further studies.

Role of anthracycline and comprehensive geriatric assessment for elderly patients with diffuse large B-cell lymphoma.

Survival outcome for elderly patients with newly diagnosed diffuse large B-cell lymphoma remains suboptimal in the rituximab era. In this systematic review, we summarize available evidence relevant to the inclusion of anthracycline in upfront chemoimmunotherapy for these elderly patients and highlight the need of prospective clinical trials. With limited prospective data, we find that pretreatment comprehensive geriatric assessment accurately predicts survival and treatment-related toxicities, suggesting its potential role in guiding overall treatment decision-making.

Modern Management of Anthracycline-Induced Cardiotoxicity in Lymphoma Patients: Low Occurrence of Cardiotoxicity with Comprehensive Assessment and Tailored Substitution by Nonpegylated Liposomal Doxorubicin.

BACKGROUND: Anthracyclines (AC) are still undeniable drugs in lymphoma treatment, despite occasionally causing cardiotoxicity. Liposomal AC may reduce cardiotoxicity while retaining clinical efficacy; also, biomarker monitoring during chemotherapy allows early detection of cardiac damage, enabling strategies to prevent left ventricular ejection fraction (LVEF) deterioration. MATERIALS AND METHODS: We conducted a prospective observational trial in a real-life population of lymphoma patients, combining advanced echocardiography and biomarkers (Troponin I [TnI]) for early detection of cardiotoxicity; we applied a prespecified policy to minimize cardiotoxicity, selecting patients with higher baseline risk to replace doxorubicin with nonpegylated liposomal doxorubicin (NPLD) and starting cardioprotective treatment when subclinical cardiotoxicity was detected. RESULTS: Ninety-nine patients received ≥1 cycle of chemotherapy (39 with NPLD): 38 (NPLD = 34) were older than 65 years. At baseline, the NPLD subgroup had more cardiovascular risk factors and comorbidities than the doxorubicin subgroup. After treatment, echocardiographic parameters did not worsen in the NPLD subgroup; significant LVEF reduction occurred in two patients treated with doxorubicin. Over treatment course, TnI rises increased linearly in the doxorubicin subgroup but modestly in the NPLD subgroup. At doxorubicin doses >200 mg/m2 the difference was statistically significant, with more TnI rises in the doxorubicin subgroup. NPLD-treated patients did not experience higher rates of grade 3-4 adverse events. Within the diffuse large B-cell lymphomas category, we observed similar rates of complete and overall responses between doxorubicin- and NPLD-treated patients. CONCLUSION: A comprehensive strategy to prevent, detect, and treat cardiotoxicity allows an optimal management of the lymphoma with low incidence of cardiac complications. The Oncologist 2017;22:422-431 IMPLICATIONS FOR PRACTICE: Despite the recent advances of targeted therapy in cancer, old cytotoxic drugs such as anthracyclines (AC) still play a fundamental role in the treatment of many lymphoma patients. We tested and validated in a real-life setting a personalized approach to prevent, detect, and treat AC-induced cardiotoxicity; biomarker monitoring was accomplished by Troponin I measurements before and after chemotherapy infusions, allowing detection of early subclinical cardiotoxicity, which was preemptively treated with cardio-protectants (beta blockers and angiotensin-converting-enzyme inhibitors). A telemedicine system allowed interdisciplinary management of the patients with an expert cardiologist. Furthermore, tailored use of liposomal AC following a prespecified policy appeared to prevent the excess cardiotoxicity expected in high-risk patients.

Impact of persistent left ventricular regional wall motion abnormalities in childhood cancer survivors after anthracycline therapy: Assessment of global left ventricular myocardial performance by 3D speckle-tracking echocardiography.

AIMS: To identify left ventricular (LV) mechanical impairment by 3D speckle-tracking echocardiography (3DSTE) in long-term childhood cancer survivors after anthracycline therapy with or without persistent LV regional diastolic wall motion abnormalities (WMA) and a preserved LV ejection fraction (EF >53%). METHODS AND RESULTS: Thirty-two patients (median: 14.6 years) and 12 age-matched controls were studied. The patients were divided into two groups according to the existence of WMA: Group 1 (with WMA: n=14), Group 2 (without WMA: n=18). 3DSTE was performed to assess LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), global area strain (GAS), LV torsion, LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV). LV systolic dyssynchrony index (SDI) was calculated as the percentage of the standard deviation of time to peak strain of the 16 segments divided by the RR interval. There was no significant difference in LVEDV, LVESV, GLS, torsion, or SDI derived from LS, CS, or AS among the 3 groups. In contrast, there were significant differences in GRS, GCS, and GAS, and SDI derived from RS among the 3 groups. Compared with group 2, group 1 had significantly reduced GRS (p<0.001), GCS (p<0.01), GAS (p<0.01), and greater SDI derived from GRS (p<0.01). Moreover, the existence of WMA was correlated with GRS (p<0.001), SDI derived from GRS (p<0.001), and LVEF (p=0.036). Multiple linear regression analysis identified GRS as a significant determinant of the existence of WMA (ß=0.751, p=0.001). CONCLUSION: Childhood cancer survivors with persistent LV regional WMA show a reduced LV myocardial performance compared with those without WMA, despite a preserved LVEF.

Assessment of global longitudinal strain at low-dose anthracycline-based chemotherapy, for the prediction of subsequent cardiotoxicity.

AIMS: We sought to assess whether global longitudinal strain (GLS) measured early during treatment with anthracyclines (at a cumulative dose of 150 mg/m2) can predict subsequent alterations in left ventricular ejection fraction. METHODS AND RESULTS: Eighty-six patients with Hodgkin's disease, non-Hodgkin's lymphoma, or acute leukaemia and receiving anthracyclines were prospectively included. Patients underwent complete echocardiography on four occasions: baseline (V1); after reaching a cumulative dose of 150 mg/m2 (V2); end of treatment (V3); and 1 year follow-up (V4). Six patients developed cardiotoxicity, defined as a decrease in left ventricular ejection fraction of >10 percentage points, to a value <53%, at V4. GLS measured at V1 and V2 was significantly lower in the cardiotoxicity group vs. the controls (P = 0.042 and P = 0.01, respectively). Compared with GLS at V1, GLS obtained at V2 provided incremental predictive information and appeared to be the strongest predictor of cardiotoxicity (area under the receiver-operating-characteristic curve, 0.82). At a threshold of -17.45% for GLS measured at V2, the sensitivity and specificity of detecting cardiotoxicity were 67% (95% confidence interval 33-100) and 97% (95% confidence interval 94-100), respectively. CONCLUSION: GLS greater than -17.45%, obtained after 150 mg/m2 of anthracycline therapy, is an independent predictor of future anthracycline-induced cardiotoxicity. These findings should encourage physicians to perform echocardiography earlier during treatment with anthracyclines.

Assessment of late anthracycline-induced cardiotoxicity by 123I-mIBG cardiac scintigraphy in patients treated during childhood and adolescence.

PURPOSE: The goal of this study was to evaluate late cardiotoxic effects of anthracyclines (ATC) by evaluating cardiac sympathetic activity in a cohort of asymptomatic patients previously treated with ATC for childhood cancers. METHODS: We studied 89 asymptomatic patients previously treated with ATC with a normal echocardiogram (49 men and 40 women) and a control group of 40 healthy individuals (26 men and 14 women). Both groups underwent planar myocardial 123I-meta-iodobenzylguanidine scintigraphy (123I-mIBG). From these images, the early and late heart-to-mediastinum (H/M) ratio and washout rate (WR) were assessed. RESULTS: The mean survival at the time of the 123I-mIBG scintigraphy was 5.3 ± 3.4 years. Patients treated with ATC had a lower but clinical normal left ventricular ejection fraction (LVEF) compared to controls (60.44 ± 6.5 vs 64.1 ± 6.0%, P < 0.01). Both the late H/M ratio and WR were not able to discriminate ATC treated patients from controls. The cumulative ATC dose was the only independent predictor of the LVEF, explaining approximately 12% of the variation in LVEF (P = 0.01). CONCLUSIONS: Although the pathophysiology behind ATC cardiotoxicity is most likely multifactorial, myocardial sympathetic activity is not associated with a reduction in LVEF 5-years after completion of chemotherapy.