BACKGROUND: Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline.
METHODS: We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety.
RESULTS: A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044).
CONCLUSIONS: Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.

Objectives: Several studies have indicated that dietary interventions may offer protection against the development of cardiac damage in the case of anthracycline-induced cardiomyopathy (AIC). The goal of this study was to assess whether an evidence-based cardioprotective diet can be effective in preventing AIC in patients with breast cancer. Design: Randomized, open-label, controlled trial. The study period was set for 18 weeks, and the data were analyzed by generalized estimating equation modeling and one-way repeated measures analysis of variance. Setting/Location: Shahid Rajaie Hospital affiliated (Tehran, Iran). Subjects: Fifty anthracycline-treated patients with breast cancer. Interventions: Patients were randomized to receive either a 2-hour training in evidence-based cardio-protective diet or Carvedilol 6.25 mg bid. Outcome Measures: The primary outcome was the number of patients with abnormal left ventricular ejection fraction (LVEF) after 18 weeks. Results: At week 18, 12 (48%) out of 25 participants in the cardioprotective diet group had abnormal LVEF in comparison with 21 (84%) out of 25 in the carvedilol group (p = 0.007). Also, 2 (8%) out of 25 in the cardioprotective diet group compared with 7 (28%) out of 25 participants in the carvedilol group had abnormal global longitudinal strain (p = 0.066). The diet group showed significant improvements in the quality-of-life dimensions named \"health change\" and \"general health\" compared with the carvedilol group using the Short Form-36 Health Survey questionnaire. Conclusions: This study suggests that an evidence-based cardioprotective diet can contribute to the prevention of AIC. Although current treatments for AIC can be effective, further research is mandatory for more options.

UNASSIGNED: Chemotherapy with anthracyclines can cause cardiotoxicity, possibly leading to stopping treatment in some cancer patients. In cardio-oncology research, preventing and minimizing anthracycline-induced cardiotoxicity (AIC) is a hot issue. For the treatment of AIC, calycosin (CA), an isoflavone component in astragali radix (AR), has become a research focus. However, the elaborate mechanisms of calycosin treating AIC remain to be unrevealed.
UNASSIGNED: To explore the effects of CA on AIC through multiple dimensions concerning network pharmacology, molecular docking, and experimental evaluations.
UNASSIGNED: The study evaluated calycosin\'s potential targets and mechanisms for treating AIC using network pharmacology and molecular docking. The candidate genes/targets of CA and AIC were screened using the online-available database. Protein-protein interactions (PPI) between the common targets were constructed using the STRING platform, and the results were then visualized using Cytoscape. Molecular docking was used to evaluate the strength of the binding force between CA and the common targets. The possible pharmacological mechanisms of CA were explained by pathway enrichment and GSEA. Subsequently, the candidate targets were identified in vitro experiments.
UNASSIGNED: Network pharmacology effectively discovered the CA\'s multitarget intervention in AIC, including TNF, ABCC1, TOP2A, ABCB1, and XDH. CA binds to the ATP-binding cassette subfamily B member 1(ABCB1) had the highest binding energy (-7.5 kcal/mol) according to the molecular docking analysis and was selected and visualized for subsequent analysis. In vitro experiments showed that ABCB1 exhibited significant time-curve changes under different doses of doxorubicin (DOX) compared with DMSO control experiments. The anti-AIC pharmacological mechanism of CA were revealed by highlighting the biological processes of oxidative stress (OR) and inflammation.
UNASSIGNED: We employed a practicable bioinformatics method to connect network and molecular docking to determine the calycosin\'s therapeutic mechanism against AIC and identified some bioinformatics results in in vitro experiments. The results presented show that CA may represent an encouraging treatment for AIC.

UNASSIGNED: Acute myeloid leukemia (AML) is the most common form of leukemia among adults in Japan. This study aimed to understand the treatment patterns, health care resource utilization, and costs of FMS-like tyrosine kinase 3 mutation-positive (FLT3m+) AML patients in Japan.
UNASSIGNED: A retrospective cohort study of Japanese FLT3m + AML patients was conducted using data extracted from a national hospital-based claims database provided by Medical Data Vision Co. Ltd. (MDV; Tokyo, Japan). Patients were identified from the MDV database between April 2008 and April 2021 inclusive.
UNASSIGNED: A total of 360 patients were included in this study. The study results suggest that cytarabine + anthracyclines was the most common first-line (1 L) treatment, accounting for 41.3% of the patients. FLT3 inhibitors (FLT3i) was the most common treatment across the study period (95.7%). The mean age of patients was 62.4 years, and most were 65 years or older. The median overall survival (OS) after initiating FLT3i treatment was 394 days. The median treatment duration of FLT3i was 88.5 days, while it was 66.0 days for patients treated with FLT3i within 60 days after hematopoietic stem cell transplantation (HSCT). The overall mean monthly total treatment cost was JPY 2,009,531.7/per patient per month (PPPM) (USD 17,967.9/PPPM).
UNASSIGNED: The study found specific treatment patterns, trends and features in patients with FLT3m + AML. FLT3i was the most prescribed treatment across the study period and the overall median OS after initiating FLT3i treatment was over 1 year. The findings of this study could be helpful for clinicians to optimize treatment strategies for FLT3m + AML in Japan.

BACKGROUND: Anthracycline-based chemotherapy has improved the prognosis of various malignancies, but increases the long-term risk of heart failure (HF). Identification of patients at risk prior to treatment initiation is warranted. Therefore, the aim of this study was to evaluate if a familial predisposition to HF increases the risk of anthracycline related HF.
METHODS: Using nationwide Danish registries, all patients treated with anthracycline from 2004 to 16 were identified. The primary outcome was long-term HF risk. First-degree relatives were identified in the Danish Family Registry and exposure was defined as a first-degree biological relative with prior HF. Risk of HF was evaluated in a cumulative incidence function and the association in a multivariable Cox regression model.
RESULTS: A total of 11,651 patients (median age 49.1 years (IQR: 43.6-53.7), 12.2% male) were included after exclusion of 46 with preanthracycline HF. Median follow-up was 3.8 years (IQR 1.9-6.4). In the group with a first-degree relative with HF (n = 1,608) 35 patients (2.2%) were diagnosed with HF vs 133 (1.3%) in the group without a first-degree relative with HF (n = 10,043), corresponding to incidence rates per 1,000 patient-years of 5.2 (CI:3.8-7.3) vs 3.0 (CI:2.5-3.5). The cumulative incidence of HF after 10 years was higher in the first-degree relative group (3.2% vs 2.0%, P = .004); adjusted hazard ratio 1.53 (CI:1.05-2.23, P = .03).
CONCLUSIONS: In this nationwide register-based study having a first-degree relative with HF was associated with increased risk of anthracycline related HF, suggesting that attention towards family predisposition may be warranted when estimating the risk of anthracycline related cardiotoxicity.

UNASSIGNED: Anthracycline cardiotoxicity is a concern in survivors of childhood cancers. Recent evidence suggests that remote ischemic conditioning (RIC) may offer myocardial protection.
UNASSIGNED: This randomized sham-controlled single-blind study tested the hypothesis that RIC may reduce myocardial injury in pediatric cancer patients receiving anthracycline chemotherapy.
UNASSIGNED: We performed a phase 2 sham-controlled single-blind randomized controlled trial to determine the impact of RIC on myocardial injury in pediatric cancer patients receiving anthracycline-based chemotherapy. Patients were randomized to receive RIC (3 cycles of 5-minute inflation of a blood pressure cuff placed over 1 limb to 15 mm Hg above systolic pressure) or sham intervention. The intervention was applied within 60 minutes before initiation of the first dose and before up to 4 cycles of anthracycline therapy. The primary outcome was the plasma high-sensitivity cardiac troponin T (hs-cTnT) level. The secondary outcome measures included echocardiographic indexes of left ventricular systolic and diastolic function and the occurrence of cardiovascular events.
UNASSIGNED: A total of 68 children 10.9 ± 3.9 years of age were randomized to receive RIC (n = 34) or sham (n = 34) intervention. Plasma levels of hs-cTnT showed a progressive increase across time points in the RIC (P < 0.001) and sham (P < 0.001) groups. At each of the time points, there were no significant differences in hs-cTnT levels or LV tissue Doppler and strain parameters between the 2 groups (all P > 0.05). None of the patients developed heart failure or cardiac arrhythmias.
UNASSIGNED: RIC did not exhibit cardioprotective effects in childhood cancer patients receiving anthracycline-based chemotherapy. (Remote Ischaemic Preconditioning in Childhood Cancer [RIPC]; NCT03166813).

UNASSIGNED: The cardiotoxic effects of doxorubicin, trastuzumab, and other anticancer agents are well known, but molecular genetic testing is lacking for the early identification of patients at risk for therapy-related cardiac toxicity.
UNASSIGNED: Using the Agena Bioscience MassARRAY system, we genotyped TRPC6 rs77679196, BRINP1 rs62568637, LDB2 rs55756123, RAB22A rs707557, intergenic rs4305714, LINC01060 rs7698718, and CBR3 rs1056892 (V244M) (previously associated with either doxorubicin or trastuzumab-related cardiotoxicity in the NCCTG N9831 trial of anthracycline-based chemotherapy ± trastuzumab) in 993 patients with HER2+ early breast cancer from the NSABP B-31 trial of adjuvant anthracycline-based chemotherapy ± trastuzumab. Association analyses were performed with outcomes of congestive heart failure (N = 29) and maximum decline in left ventricular ejection fraction (LVEF) using logistic and linear regression models, respectively, under an additive model with age, baseline LVEF, and previous use of hypertensive medications as covariates.
UNASSIGNED: Associations of maximum decline in LVEF in the NCCTG N9831 patients did not replicate in the NSABP B-31 patients. However, TRPC6 rs77679196 and CBR3 rs1056892 were significantly associated with congestive heart failure, p < 0.05, with stronger associations observed in patients treated with chemotherapy only (no trastuzumab) or in the combined analysis of all patients relative to those patients treated with chemotherapy + trastuzumab.
UNASSIGNED: TRPC6 rs77679196 and CBR3 rs1056892 (V244M) are associated with doxorubicin-induced cardiac events in both NCCTG N9831 and NSABP B-31. Other variants previously associated with trastuzumab-related decline in LVEF failed to replicate between these studies.

This study aimed to evaluate the changes in the left ventricular (LV) myocardial work (MW) in breast cancer patients following chemotherapy by left ventricular pressure-strain loop (LVPSL).A total of 50 patients with newly breast cancer undergoing postoperative adjuvant chemotherapy containing anthracycline were selected. Echocardiography was performed before the treatment (T0), the second (T2) and fourth (T4) cycles of chemotherapy, and 3 (P3 m) and 6 (P6 m) months after the end of chemotherapy. The standard dynamic images of the required sections were collected. After off-line analysis, the routine, global myocardial strain, and global MW parameters were obtained, and the average regional MW index (RMWI) and regional MW efficiency (RMWE) at three levels of LV were calculated.Compared with those at T0 and T2, the global work index (GWI), global constructive work (GCW), global work efficiency (GWE), and global longitudinal strain (GLS) gradually decreased and global wasted work (GWW) gradually increased at T4, P0, and P6 m. The mean RMWI and RMWE of the three levels of LV exhibited a gradually decreasing trend at T4, P0, and P6 m compared with those at T0 and T2. The GWI, GCW, GWE, mean RMWI, and RMWE (basal, medial, and apical) were negatively correlated with the GLS (r = -0.76, -0.66, -0.67, -0.76, -0.77, -0.66, -0.67, -0.59, and -0.61, respectively), whereas the GWW was positively correlated with the GLS (r = 0.55).The mean RMWI and RMWE are effective parameters to reflect the cardiotoxicity of LV, and LVPSL has certain value in the evaluation of the left ventricular myocardial work (LVMW) during anthracycline treatment and follow-up in breast cancer patients.

UNASSIGNED: In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial.
UNASSIGNED: Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group.
UNASSIGNED: The CSBrS-012 study (2010-2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC.
UNASSIGNED: A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran-Mantel-Haenszel test.
UNASSIGNED: A total of 2507 patients were enrolled: the anthracycline group (n = 1581, 63%) and the nonanthracycline group (n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65-2.43); p < 0.001). In the subsequent subgroup analysis, substantial differences in pCR rates between the anthracycline and nonanthracycline groups were detected in the nontargeted [OR = 1.91, 95% CI (1.13-3.23); p = 0.015] and dual-HER2-targeted populations [OR = 0.55, 95% CI (0.33-0.92); p = 0.021) before PSM, whereas differences vanished after PSM. The pCR rates between the anthracycline and nonanthracycline groups did not differ for the single target population, either before or after PSM.
UNASSIGNED: In the presence of trastuzumab and/or pertuzumab, the pCR rate of patients with HER2-positive breast cancer receiving anthracycline was not superior to that of patients receiving nonanthracycline. Thus, our study further provides clinical evidence for exempting anthracycline treatment in HER2-positive breast cancer in the era of targeted therapy.

There is no standard front-line therapy for older patients with classical Hodgkin lymphoma (cHL). We analyzed the clinical presentation and front-line management of older Australian patients with cHL and explored factors associated with unplanned hospital admission and survival.
Patients aged ≥ 61 years and diagnosed between 2011 and 2020, were retrospectively identified through the Lymphoma and Related Diseases Registry (LaRDR) and Australasian Lymphoma Alliance (ALA) institutional databases. Descriptive statistics and Kaplan-Meier survival analyses were performed using STATA-v17.
195 patients were identified, 72 from LaRDR,123 from ALA. Median age of the combined cohort was 72 years (range 61-93); 56.4% male, 35.3% had stage I-II, bulk present in 9.2%, 33.9% had extra-nodal disease and 48.2% had B-symptoms. Chemotherapy was commenced in 91.3% of patients, with an anthracycline-based regimen used in 81%. Median number of cycles given for stage I-II was 2 and for stage III-IV was 6. Radiotherapy was administered in 26.2% of patients. A complete remission to front-line chemotherapy was achieved in 60.7% of patients. During front-line therapy in the ALA cohort, 89 unplanned hospitalizations occurred in 58 patients, with infection accounting for 59.6% of admissions. Treatment-related mortality was 5.2%. Only performance status and anthracycline use correlated with unplanned hospitalizations. Estimated 2-year progression free survival was 63.7% and 2-year overall survival was 71.2%. Anthracycline use and younger age were independently associated with improved survival.
The management of older patients with cHL in Australia is diverse but aligns with international data. Anthracycline-based therapy improved survival but resulted in frequent unplanned hospitalizations.