Thesis etd-05252020-184320 |
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Thesis type
Tesi di specializzazione (4 anni)
Author
PETRICCIUOLO, SERENA
URN
etd-05252020-184320
Thesis title
Biohumoral and echocardiographic parameters in the prediction of cardiovascular events or cardiotoxicity after cancer treatment with immune checkpoint inhibitors
Department
PATOLOGIA CHIRURGICA, MEDICA, MOLECOLARE E DELL'AREA CRITICA
Course of study
MALATTIE DELL'APPARATO CARDIOVASCOLARE
Supervisors
relatore Prof. Pedrinelli, Roberto
relatore Prof. De Caterina, Raffaele
correlatore Dott.ssa Delle Donne, Maria Grazia
relatore Prof. De Caterina, Raffaele
correlatore Dott.ssa Delle Donne, Maria Grazia
Keywords
- cancer
- cardiac troponin T
- chemotherapy
- echocardiography
- global longitudinal strain
- immune checkpoint inhibitors
Graduation session start date
19/06/2020
Availability
Full
Summary
Background and Aims: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment, but have been associated with immune-related adverse events (irAEs). Early diagnosis of irAEs is important to enact early treatment. We aimed at analyzing the prognostic role of high-sensitivity cardiac troponin T (TnT-hs) and echocardiographic parameters, including 2D global longitudinal strain (GLS), in irAEs.
Methods and Results: We prospectively studied 30 lung cancer patients, 23 men (76%), median age 68 (95% CI 58-73 years), before and after ICI therapies. Patients underwent a baseline and an 80-day (95% CI 65-107) follow-up examination, after an average 5 cycles of chemotherapy. At baseline, all patients had normal ejection fraction [57.2% (54.2-59.35)] and GLS [17.5 (15.9-19.5%)]. Median TnT-hs values across a first ICI cycle were 11 (8-19.5) and 14 (8.75-25.25) ng/L, respectively. Three (10%) patients died, and two (6%) had pericardial disease. Such major adverse CV events at follow-up all occurred in patients with baseline TnT-hs ≥14 ng/L - upper normal reference limit (p=0.01 vs patients with baseline TnT-hs<14 ng/L). TnT-hs values at baseline ≥14 ng/L were also associated with a higher (p=0.006) risk of ESC guidelines-defined cardiotoxicity. We found no correlation between basal TnT-hs values and changes in GLS (p=0.171); or between pre-/post-cycle changes in TnT-hs and changes in GLS (p=0.568). At receiver-operator curve (ROC) analysis, a TnT-hs value ≥14 ng/L was the best cut-off predicting all-cause mortality (AUC 0.807, sensitivity=100%, specificity=69%), CV events (AUC 0.865; sensitivity=100%, specificity=61%) and cardiotoxicity (AUC 0.739; sensitivity=80%, specificity=67%).
Conclusions: In early cancer treatment with ICI, baseline TnT-hs ≥14 ng/L, but not pre-/post ICI TnT-hs changes or changes in echocardiographic parameters, including GLS, predicts CV events and cardiotoxicity.
Methods and Results: We prospectively studied 30 lung cancer patients, 23 men (76%), median age 68 (95% CI 58-73 years), before and after ICI therapies. Patients underwent a baseline and an 80-day (95% CI 65-107) follow-up examination, after an average 5 cycles of chemotherapy. At baseline, all patients had normal ejection fraction [57.2% (54.2-59.35)] and GLS [17.5 (15.9-19.5%)]. Median TnT-hs values across a first ICI cycle were 11 (8-19.5) and 14 (8.75-25.25) ng/L, respectively. Three (10%) patients died, and two (6%) had pericardial disease. Such major adverse CV events at follow-up all occurred in patients with baseline TnT-hs ≥14 ng/L - upper normal reference limit (p=0.01 vs patients with baseline TnT-hs<14 ng/L). TnT-hs values at baseline ≥14 ng/L were also associated with a higher (p=0.006) risk of ESC guidelines-defined cardiotoxicity. We found no correlation between basal TnT-hs values and changes in GLS (p=0.171); or between pre-/post-cycle changes in TnT-hs and changes in GLS (p=0.568). At receiver-operator curve (ROC) analysis, a TnT-hs value ≥14 ng/L was the best cut-off predicting all-cause mortality (AUC 0.807, sensitivity=100%, specificity=69%), CV events (AUC 0.865; sensitivity=100%, specificity=61%) and cardiotoxicity (AUC 0.739; sensitivity=80%, specificity=67%).
Conclusions: In early cancer treatment with ICI, baseline TnT-hs ≥14 ng/L, but not pre-/post ICI TnT-hs changes or changes in echocardiographic parameters, including GLS, predicts CV events and cardiotoxicity.
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