TY - JOUR
T1 - Cardiac Function Modifies the Impact of Heart Base Dose on Survival
T2 - A Voxel-Wise Analysis of Patients With Lung Cancer From the PET-Plan Trial
AU - Craddock, Matthew
AU - Nestle, Ursula
AU - Koenig, Jochem
AU - Schimek-Jasch, Tanja
AU - Kremp, Stephanie
AU - Lenz, Stefan
AU - Banfill, Kathryn
AU - Davey, Angela
AU - Price, Gareth
AU - Salem, Ahmed
AU - Faivre-Finn, Corinne
AU - van Herk, Marcel
AU - McWilliam, Alan
N1 - Funding Information: Mr. Craddock, Dr. McWilliam, Dr. Price, and Dr. Faivre-Finn are supported by Cancer Research UK by means of funding to the Cancer Research Manchester Centre [C147/A25254]. Drs. Faivre-Finn, McWilliam, and van Herk are also supported by the National Institute for Health and Care Research Manchester Biomedical Research Centre . Dr. Price is also supported by Cancer Research UK RadNet Manchester (C1994/A28701). Publisher Copyright: © 2022 International Association for the Study of Lung Cancer
PY - 2023/1
Y1 - 2023/1
N2 - Introduction: Heart dose has emerged as an independent predictor of overall survival in patients with NSCLC treated with radiotherapy. Several studies have identified the base of the heart as a region of enhanced dose sensitivity and a potential target for cardiac sparing. We present a dosimetric analysis of overall survival in the multicenter, randomized PET-Plan trial (NCT00697333) and for the first time include left ventricular ejection fraction (EF) at baseline as a metric of cardiac function. Methods: A total of 205 patients with inoperable stage II or III NSCLC treated with 60 to 72 Gy in 2 Gy fractions were included in this study. A voxel-wise image-based data mining methodology was used to identify anatomical regions where higher dose was significantly associated with worse overall survival. Univariable and multivariable Cox proportional hazards models tested the association of survival with dose to the identified region, established prognostic factors, and baseline cardiac function. Results: A total of 172 patients remained after processing and censoring for follow-up. At 2-years posttreatment, a highly significant region was identified within the base of the heart (p < 0.005), centered on the origin of the left coronary artery and the region of the atrioventricular node. In multivariable analysis, the number of positron emission tomography–positive nodes (p = 0.02, hazard ratio = 1.13, 95% confidence interval: 1.02–1.25) and mean dose to the cardiac subregion (p = 0.02, hazard ratio = 1.11 Gy−1, 95% confidence interval: 1.02–1.21) were significantly associated with overall survival. There was a significant interaction between EF and region dose (p = 0.04) for survival, with contrast plots revealing a larger effect of region dose on survival in patients with lower EF values. Conclusions: This work validates previous image-based data mining studies by revealing a strong association between dose to the base of the heart and overall survival. For the first time, an interaction between baseline cardiac health and heart base dose was identified, potentially suggesting preexisting cardiac dysfunction exacerbates the impact of heart dose on survival.
AB - Introduction: Heart dose has emerged as an independent predictor of overall survival in patients with NSCLC treated with radiotherapy. Several studies have identified the base of the heart as a region of enhanced dose sensitivity and a potential target for cardiac sparing. We present a dosimetric analysis of overall survival in the multicenter, randomized PET-Plan trial (NCT00697333) and for the first time include left ventricular ejection fraction (EF) at baseline as a metric of cardiac function. Methods: A total of 205 patients with inoperable stage II or III NSCLC treated with 60 to 72 Gy in 2 Gy fractions were included in this study. A voxel-wise image-based data mining methodology was used to identify anatomical regions where higher dose was significantly associated with worse overall survival. Univariable and multivariable Cox proportional hazards models tested the association of survival with dose to the identified region, established prognostic factors, and baseline cardiac function. Results: A total of 172 patients remained after processing and censoring for follow-up. At 2-years posttreatment, a highly significant region was identified within the base of the heart (p < 0.005), centered on the origin of the left coronary artery and the region of the atrioventricular node. In multivariable analysis, the number of positron emission tomography–positive nodes (p = 0.02, hazard ratio = 1.13, 95% confidence interval: 1.02–1.25) and mean dose to the cardiac subregion (p = 0.02, hazard ratio = 1.11 Gy−1, 95% confidence interval: 1.02–1.21) were significantly associated with overall survival. There was a significant interaction between EF and region dose (p = 0.04) for survival, with contrast plots revealing a larger effect of region dose on survival in patients with lower EF values. Conclusions: This work validates previous image-based data mining studies by revealing a strong association between dose to the base of the heart and overall survival. For the first time, an interaction between baseline cardiac health and heart base dose was identified, potentially suggesting preexisting cardiac dysfunction exacerbates the impact of heart dose on survival.
KW - Cardiac toxicity
KW - Ejection fraction
KW - Heart
KW - Non–small cell
UR - http://www.scopus.com/inward/record.url?scp=85140776492&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtho.2022.09.004
DO - https://doi.org/10.1016/j.jtho.2022.09.004
M3 - Article
C2 - 36130693
SN - 1556-0864
VL - 18
SP - 57
EP - 66
JO - Journal of thoracic oncology
JF - Journal of thoracic oncology
IS - 1
ER -