TITLE:
Impact of Cardiac Dose on Overall Survival in Lung Stereotactic Body Radiotherapy (SBRT) Compared to Conventionally Fractionated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)
AUTHORS:
Justin D. Anderson, Jiuyun Hu, Jing Li, Steven E. Schild, Mirek Fatyga
KEYWORDS:
Lung Cancer, Lung SBRT, Cardiac Toxicity, Lung Radiation Therapy, Non-Small Cell Lung Cancer
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.12 No.7,
July
15,
2021
ABSTRACT: Purpose: To examine possible association between heart irradiation and Overall
Survival (OS) in lung SBRT patients and to compare observed associations with
cardiac toxicity models previously derived in LA-NSCLC patient studies. Materials
and Methods: 197 Patients treated with lung SBRT at Mayo Clinic Arizona
were selected for this IRB-approved study. Multivariate Cox model with Akaike Information Criterion
(AIC) was used to select patient specific
covariates associated with OS. Heart dosimetry was represented by VD indices, which is a percentage of volume exposed to dose D or greater. Multivariate
Cox models with patient specific covariates and single VD index per model was used to find a range of doses which were predictive
for OS. A digital subdivision of the heart was further used to determine the spatial distribution of doses which were predictive for OS. A coarse
subdivision divided heart into 4 segments, while the fine subdivision divided heart into 64 segments. Knowledge constrained
Fused Lasso operator was used to derive a more complete model which correlated
heart dosimetry with OS. Results of statistical analysis were compared to
predictions of a model of cardiac toxicity in LA-NSCLC patients. Results: Higher
age (p V2Gy in the right-inferior segment (HR = 1.012/1%, p =
0.02), and V1Gy in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in
the right-inferior segment of the heart was also associated with reduced OS (HR
= 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed
that approximately 25% of heart volume in the inferior part of the heart (15/64
segments), when irradiated to doses in the 1 Gy - 5 Gy range,
were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived
model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of
OS due to heart irradiation in lung SBRT patients, because of relatively low
doses to the heart in most lung SBRT patients. Conclusions: Doses lower
than 5 Gy in the inferior segments of the heart may be associated with reduced
overall survival in patients treated for lung lesions with SBRT. Stage and
histology of the disease, as well as patients’ age, were also associated with
overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients
and lung SBRT patients suggest different etiology of cardiac toxicity in the
two groups.