Cerhan, James R.

Abstract Background The diagnosis of cardiotoxicity (CT) related to cancer therapy has gained significance due to its impact on morbidity and mortality. The 2022 cardio-oncology European Society of Cardiology (ESC) Guidelines defined CT as symptomatic if a patient has clinical heart failure or asymptomatic based on changes in the ejection fraction (EF) or global longitudinal strain (GLS). The role of right ventricular parameters, such as tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall strain (RVFWS), in predicting CT is unknown. AIM Evaluate if TAPSE and RVFWS can predict the development of CT in lymphoma patients treated with anthracyclines. Methods For this prospective observational study, Hodgkin & non-Hodgkin lymphoma patients (n=222) treated with anthracyclines were recruited from 2013 to 2021 and were followed for one year. Echocardiographic variables TAPSE and RVFWS were measured at baseline(T0), during treatment(T1), and up to 1 year after chemotherapy completion(T2). CT was defined according to the ESC guidelines excluding GLS changes. We performed: Kruskal-Wallis test to find differences at baseline values, logistic regression to evaluate the association of TAPSE and RVFWS with CT, area under the curve (AUC) of the receiving operator characteristic (ROC) to measure the discriminative test ability and two sample proportion test to calculate the negative predictive value (NPV). A p-value <0.05 was considered significant. Results 222 patients were enrolled and 23 developed CT: 4.5% (n=10) at T1 and 6.2% (n=13) at T2. The median of RVFWS at T0 was significantly different in patients who developed CT compared to those who did not at T1 (CT-22% vs. no CT-27% p=0.04) and T2 (CT -23%, no CT -26.5% p=0.03). RVFW values at T0 were associated with CT at T1 (OR, 1.281 95% CI,1.09-1.52 p=0.002) and T2 (OR 1.23 95% CI,1.07-1.44 p=0.003). At T0 RVFWS cutoff value of -24% had an AUC of 0.85 for the prediction of CT at T1, with a sensitivity of 83% and specificity of 76% (p=0.03). At T0, RVFWS cutoff of -25% had an AUC of 0.80 for the prediction of CT at T2, with a sensitivity of 75% and specificity of 60%, (p=0.04). RVFWS absolute values >26% at T0 and T1 had an NPV of 100% for the development of CT in T1 and T2. The median TAPSE at T0 was significantly different in patients who developed CT at T1 compared to those who did not (CT patients 18.7 mm vs no CT patients 23.6 mm p=0.04). TAPSE values at T0 were associated with CT development at T1 but not at T2 OR 0.76 (95% CI,0.66-0.87 p=<0.001). At T0, TAPSE cutoff of 21.6 mm had an AUC of 0.77 for the prediction of CT at T1, with a sensitivity of 77% and specificity of 70% (p=0.03). Conclusions Baseline absolute RVFWS values <24% and <25% were associated with CT at T1 and T2, respectively. Values >26% had an excellent NPV for the development of CT. Baseline TAPSE values <21.6 were associated with CT at T1. These parameters should be evaluated in other cancer populations.TAPSE and RVFWS association with CTRVFWS and TAPSE at T0 to predict CT

Abstract Extranodal marginal zone lymphoma (EMZL) has a very indolent course, and the validation of surrogate markers could accelerate novel therapies. Although prognostic markers do exist, no surrogate markers have been validated in EMZL. We hypothesized that time to complete response within 24 months (TTCR24) and complete response (CR) at 24 months (CR24) could be valid surrogate markers of progression-free survival (PFS). The International Extranodal Lymphoma Study Group 19 phase 3 trial showed the advantage of double therapy (rituximab + chlorambucil) over single therapy (rituximab or chlorambucil) on PFS. We used 2 recently published single-trial approaches to assess whether TTCR24 and CR24 were good surrogate markers of 8-year PFS (8y-PFS). Among the 401 patients, 264 (66%) reached a CR in the first 24 months, of which 222 (84%) remained in CR at month 24. The cumulative incidence of CR over time was significantly higher in patients under double therapy (hazard ratio, 1.75; P < .001). The double therapy arm was associated with a higher CR24 rate, a shorter TTCR24, and a longer 8y-PFS. The estimated proportion of treatment effect on 8y-PFS explained by TTCR24 was 95% (95% confidence interval [CI], 0.27-1.87). CR24 was also a strong surrogate marker because it mediated 90% (95% CI, 0.51-2.22) of the treatment effect on PFS and its natural indirect effect was significant throughout the follow-up. We found that TTCR24 predicted 95% and that CR24 mediated 90% of the treatment effect on long-term PFS. Therefore, TTCR24 and CR24 could be used in clinical trials as informative and valid early indicators of treatment effect on PFS. This trial was registered at www.clinicaltrials.gov as #NCT00210353.

Objective: Evaluate the effects of ketamine versus propofol when used for induction of anesthesia in elderly, high-risk cardiac surgical patients on postoperative complications including cognitive dysfunction, delirium, and acute kidney injury. Methods: Prospective, randomized study performed at a tertiary medical center. A total of 52 patients aged ≥70 and older presenting for complex cardiac surgery were randomized to receive either ketamine or propofol for induction of anesthesia. Patients underwent a battery of cognitive testing preoperatively and postoperatively and the incidence of delirium and acute kidney injury were measured. Norepinephrine (NEE) equivalents following induction were assessed for each group. Results: A total of 49 patients were included, 25 in the ketamine group and 24 in the propofol group with 3 patients excluded from the analysis. No difference was found between groups in either postoperative cognitive dysfunction or delirium incidence. Acute kidney injury occurred in 6 (24%) patients in the ketamine group in 12 (50%) patients in the propofol group, but the difference did not meet statistical significance (P = 0.08; Relative Risk = 2.1, 95% CI 0.9–4.7). NEE equivalents were lower in the ketamine group, 9.6 ± 22.2 versus 32.7 ± 46.0, P < 0.03. Conclusions: The use of ketamine versus propofol for induction of anesthesia did not impact the incidence of postoperative cognitive dysfunction or delirium. Twice as many patients in the propofol group developed acute kidney injury, although not reaching statistical significance and warranting further investigation. In elderly, high-risk patients, ketamine was associated with a significantly reduced need for vasopressor support following induction.

Introduction: patients exposed to chest, breast or mediastinal RT, may present with accelerated atherosclerosis and CAD due to diffuse micro and macrovascular fibrosis. However, CAD risk has not been well established in a community-based study. Aims: Describe CAD risk in patients treated with chemotherapy with and without RT and evaluate the cumulative incidence of CAD (coronary revascularization, MI and abnormal stress test and coronary angiogram). Methods: From 1985-2010, we identified 744 patients with a new diagnosis of breast cancer or lymphoma, using the Rochester Epidemiology Project (REP) who received chemotherapy with or without RT. CAD risk was assessed by a proportional hazards model for time to event. RT was treated as a time dependent co-variable, with index date being chemotherapy start date, significance was considered as a p<.05. Characteristics were evaluated by a multivariable Cox model to consider RT and time censoring. Results: 744 patients treated with chemotherapy were identified, of these 488 (65.6%) had breast cancer, 256 (34.4%) lymphoma, and 367 (49%) also received RT. The mean total RT dose was 5.5 ± 1.2 (Gy) for those that had CAD and 5.4 (Gy) ± 1.1 for non-CAD patients, p=0.4. The cumulative incidence of CAD events (accounting for death as a competing risk) at 5 and 10 years of follow-up was 1.9% (CI 1.14-3.2) and 3.06% (CI 2.01-4.7), respectively p<.05 figure1. Baseline differences between those receiving RT or not, were not significant for DM and HTN; however, males and ages 70-79 were less likely to receive RT, table1. In a multivariable model, there was no difference in the CAD outcomes between those with and without RT, HR= 1.21 [0.48-3.06] p=.69, after adjusting for age, gender, DM, and HTN and those <49 y/o had a lower risk of CAD. Table2 Conclusion: In this REP retrospective cohort study, the risk of developing a CAD event was similar between chemotherapy plus RT and chemotherapy only regimens, even after considering gender, age, HTN and DM.