INCIDENCE OF CHEMOTHERAPY INDUCED LEFT VENTRICULAR
DYSFUNCTION VARIES DEPENDING ON THE DEFINITION
Amy Erica Lin1, Maria Michalowska1, Ciril Khorolsky1, Philippe L. Bedard2, Eitan Amir2, Mark
Iwanochko3, Paaladinesh Thavendiranathan1
1
Division of Cardiology, Peter Munk Cardiac Center, Ted Rogers Program in Cardiotoxicity Prevention,
Toronto General Hospital, University Health Network, University of Toronto, 585 University Avenue,
Toronto, Ontario, Canada M5G 2N2
2
Division of Medical Oncology and Hematology, Princess Margaret Cancer Center, University Health
Network, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5T 2M9
3
Division of Cardiology, Toronto Western Hospital, University Health Network, 399 Bathurst Street,
Toronto, Ontario, Canada M5T 2S8
!
Author contact : Amy Erica Lin, [email protected]
Character count : title 86 + body 1416 + table 496 = 1998 total
!
Background
Several different definitions of chemotherapy induced cardiotoxicity (CTOX) exist. We sought to assess the
differences in the incidence of CTOX in women with HER2+ breast cancer who received cancer treatment
with different commonly used definitions.
Methods
Consecutive women with stage I-III HER2+ breast cancer treated at the Princess Margaret Hospital
(Toronto) between 2006 and 2013 were retrospectively identified. All patients received trastuzumab.
Patients were included if a pre-therapy MUGA scan with ≥3 subsequent follow-up scans were available.
Based on published criteria and guidelines, 4 CTOX definitions were studied. χ2 test was used to compare
groups.
Results
326 women were included (age 52±12 yrs). There was a significant difference in the incidence of CTOX
between the 4 definitions, p=0.0003 (Table). The highest incidence was with the Cardiac Review and
Evaluation Committee (CREC) criterion (23%, definition 2) while the lowest was with the oldest criterion
(12%, definition 4) that is still commonly used. There was no significant difference (p=0.08) in the
incidence between the CREC criteria and the new criterion (proposed by the American Society of
Echocardiography (ASE). However the incidence was significantly higher with both these criteria compared
to definition 4 (p=0.04 and 0.0002 respectively).
Conclusions
The incidence of CTOX differs significantly between existing definitions and the varied use may result in
CTOX being missed or over diagnosed. The best criterion for CTOX is unknown. Studies focused on longterm outcomes based on the various criteria are needed to establish the optimal CTOX criterion.
!
!
HF!Symptoms!
Asymptomatic!
Symptomatic!(%)!
(%)!
37!(64.9)!
20!(35.1)!
CTOX!Definition!
CTOX,!n!(%)!
Days!to!CTOX!(%)!
1:!>10%!to!<!53%1!
2:!≥10%!to!≤!55%!
without!symptoms!
OR!≥5%!drop!to!
≤55%!with!
symptoms2!
57!(17.5)!
315!±!259!
75!(23)!
322!±!284!
54!(72)!
21!(28)!
3:!any!decline!of!
LVEF!by!≥15%3!
4:!≥10%!to!≤50%4!
76!(23.3)!
292!±!211!
65!(85.5)!
11!(14.5)!
39!(12.0)!
304!±!207!
22!(56.4)!
17!(43.6)!
!
1!
New!criterion!suggested!by!ASE!(Plana!et!al,!JASE,!2014)!
!CREC!criterion!(Seidman!et!al,!J!Clin!Oncol!2002)!
3!!
Based!on!early!MUGA!work!!
4
!The!oldest!CTOX!definition!and!commonly!used!by!oncologists!(Schwartz!et!al,!Am!J!Medicine,!1987)!!
2