Garzón-Dangond, Juan Manuel

e20761 Background: The prognostic role of serial circulating tumor DNA (ctDNA) dynamics during osimertinib treatment has been described mainly in Asian and European populations; however, it remains poorly defined in Hispanic patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC). Our aim was to determine whether serial plasma EGFR testing identifies patients at high risk of early mortality. Methods: This multicenter, retrospective study included 64 Hispanic patients with stage IIIB–IV EGFR-mutant NSCLC treated with first-line osimertinib between 2018 and 2023. Tumor tissue genotyping was performed using hybrid-capture next-generation sequencing. Plasma EGFR mutations were assessed at baseline, week 8, and week 24. Overall survival (OS) and progression-free survival (PFS) were analyzed using Cox models adjusted for p53 status, RAF-pathway alterations, and metastatic burden. Results: The cohort had a median age of 61 years, with 65.6% of patients being female and 56.2% being never-smokers. Sensitizing EGFR mutations consisted mainly of exon 19 deletion (59.4%) and L858R (39.1%). Relevant co-mutations were identified in TP53 (29.7%) and RAF-pathway genes (6.2%). Plasma ctDNA remained positive in 42.2% of patients at week 8 and 22.0% at week 24. Week-8 ctDNA persistence was strongly associated with an inferior OS (HR 9.36, 95% CI 3.80–23.03, p < 0.001) after multivariable adjustment. Week-24 positivity also predicted worse OS (HR 3.34, 95% CI 1.13–9.89, p = 0.02). ctDNA status at week 8 or 24 was not significantly associated with PFS. Patients with TP53 or RAF pathway mutations demonstrated higher rates of molecular persistence. Conclusions: In Hispanic patients receiving Osimertinib, ctDNA positivity at 8-24 weeks is able to identify patients with poor survival outcomes. ctDNA monitoring may provide an early, non-invasive biomarker to guide treatment intensification and trial enrollment in EGFR-mutant NSCLC.

Abstract Background Global longitudinal strain (GLS) by 2D speckle tracking echocardiography (2D-STE) has been widely utilized to detect early underlying systolic myocardial dysfunction in patients with normal ejection fraction (EF). Reduced GLS is observed in patients with hypertrophic and amyloid cardiomyopathies. However, the impact of chronic kidney disease (CKD) on GLS remains underexplored. CKD patients present with multiple cardiovascular comorbidities, increased left ventricular mass index (LVMI), and altered cardiac remodeling which is a dynamic and adaptive physiological response. Left ventricular (LV) remodeling is classified based on relative wall thickness (RWT ≤ or &gt; 0.42) and LVMI (≤ or &gt; 88 g/m² for women and ≤ or &gt; 102 g/m² for men) into four distinct categories: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). Purpose To assess and describe the LV-GLS values (SD) in male and female patients with CKD across different remodeling patterns and compare them to controls without comorbidities Methods A retrospective echocardiographic analysis was conducted on patients evaluated from 01/01/2008 to 12/31/2018. A total of 546 CKD patients and 1041 controls were identified and matched in a ≈2:1 ratio by age, gender, and cardiac geometry. ANOVA and Tukey-Kramer analysis compared GLS across groups, with data distributions visualized via box plots. P-values &lt;0.05 were considered significant. Results The mean age of CKD patients and controls was 63.3 (SD 12.7) and 63.1 (SD 12.6) years, respectively. Overall, GLS values in CKD patients were comparable to controls, with significant differences in select subgroups. In females with eccentric hypertrophy, GLS was lower in CKD stage V vs. controls (-16.2 ± 2.5 vs. -20.7 ± 2.3, p &lt; 0.05), CKD stage III (-16.2 ± 2.5 vs. -19.5 ± 2.4, p &lt; 0.05), and CKD stage IV (-16.2 ± 2.5 vs. -20.2 ± 2.4, p &lt; 0.05) (Table 1). Across CKD stages, GLS trended toward the lower limit of normality, particularly in advanced CKD. In males with normal geometry, GLS values for controls and CKD stages I, II, III, IV and V were -20.3 ± 1.9, -19.1 ± 2.3, -19.4 ± 2.7, -19.5 ± 2.8, -19.8 ± 3.6, and -17.7 ± 2.7 (Figure 1a). In females, corresponding values were -21.0 ± 2.2, -19.9 ± 2.7, -20.2 ± 2.0, -20.8 ± 2.5, -20.2 ± 3.4, and -18.8 ± 3.4, respectively (Figure 1b). Conclusion GLS values in CKD patients were largely comparable to controls for both genders. However, those with CKD V exhibited GLS values near the lower limit of normality, particularly in eccentric hypertrophy. These findings suggest that in this group of patients there is subclinical myocardial dysfunction, warranting further investigation. The values reported may serve as reference points for GLS assessment in CKD patients.

Abstract Introduction Anthracyclines (ACs) have been identified as cardiotoxic drugs. They are associated with contractile dysfunction of the heart, which can manifest as heart failure. However, differentiating between HFrEF (left ventricular ejection fractions [LVEF] ≤40%) or HFpEF (LVEF &gt;40%) has been overlooked. Purpose Using a retrospective cohort of patients with breast cancer (BC), Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and controls from the Rochester Epidemiology Project, we evaluated the association of ACs use with risk of HFrEF and/or HFpEF. Methods 797 subjects with BC, HL or NHL diagnosed from 1988 to 2010 were identified, 658 treated with ACs (ACs group) and 139 not treated with ACs (no-ACs group). Controls (n=1526) were subjects without cancer. The median (Q1, Q3) follow up was 11.5 years (7.4, 16.7). Cox proportional hazards regression was used to compare the risk of HFpEF and HFrEF in the three cohorts, adjustment for sex, CV comorbidities (type 2 diabetes [T2D], hypertension [HTN] and dyslipidemia), radiotherapy (RT), and ACs cumulative dose was performed. Results Baseline characteristics are shown in table 1. HFpEF occurred in 29/1526 subjects in the control group, 3/139 in the no-ACs group and in 14/658 in the ACs group. Compared to the control group, there was not an increased risk of developing HFpEF in the no-ACs group (HR 1.67, CI 95%: 0.5 – 5.53, p = 0.39) or in the ACs group (HR 1.83, CI 95%: 0.95 – 3.52, p = 0.06) (Figure 1). Compared with no-ACs group, the ACs group had a similar risk of developing HFpEF (HR 1.09, CI 95%: 0.3 – 3.87, p = 0.88). RT was associated with a lower risk of HFpEF (HR 0.21, CI 95%: 0.06 – 0.75, p = 0.01). In the multivariable analysis, T2D (HR 6.91, CI 95%: 3.07-15.56, p = &lt;0.0001) was associated with higher risk of HFpEF. A cumulative dose of ACs &gt; 250 mg/m2 was not associated with increased risk of HFpEF. HFrEF occurred in 25/1526 subjects in the control group, in 4/139 in the no-ACs group and in 31/658 in the ACs group. Compared to the control group, the ACs group had a significant increase in the risk of HFrEF (HR 4.77, CI 95%: 2.76 – 8.22, p &lt; 0.0001), the no-ACs group did not (HR 2.81, CI 95%: 0.97 – 8.12, p = 0.055) (figure 2). RT was associated with lower risk of HFrEF (HR 0.29, CI 95%: 0.13 – 0.65, p = 0.002). In the multivariable analysis, ACs (HR 4.23, CI 95%: 2.4-7.47, p = &lt; 0.0001) being male (HR 2.45, CI 95%: 1.43 – 4.15, p &lt; 0.0001), smoking history (HR 2, CI 95%: 1.16 – 3.44, p &lt; 0.01), and HTN (HR 3.23, CI 95%: 1.9 – 5.61, p &lt; 0.0001), were associated with higher risk of HFrEF. A cumulative dose of ACs &gt; 250 mg/m2 was not associated with increased risk of HFrEF. Conclusion To our knowledge this is the first study to differentiate between HFpEF and HFrEF in this cohort. ACs were not associated with increased risk of HFpEF. However, ACs were associated with increased risk of HFrEF, but not with a specific dose. These results should be validated in other population cohorts.

Abstract Background Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts. Purpose We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population. Methods Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method. Results 696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=&lt;0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=&lt;0.01]. In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1). Conclusion DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.