The dose of radiation delivered during non small-cell lung cancer (NSCLC) treatment influenced cardiac and mortality outcomes in patients who did not have coronary heart disease (CHD) at the time of treatment although somewhat paradoxically, it did not affect patients with CHD nearly as much, a retrospective analysis has shown.
In a cohort of 701 NSCLC patients, a dose of V15 Gy to the left anterior descending (LAD) coronary artery greater than or equal to 10% was associated with almost a 14-fold greater risk of major acute coronary events (MACE) at an adjusted hazard ratio (HR) of 13.9 (95% CI, 1.23-157.2; P=0.03), Katelyn Atkins, MD, PhD, Cedars-Sinai Medical Center, Los Angeles, California and colleagues reported in JAMA Oncology.
Moreover, the same dose to the same cardiac structure was associated with a 58% increased risk in all-cause mortality at an adjusted HR of 1.58 (95% CI, 1.09-2.29; P=0.02), the authors added.
“Radiation exposure of arterial vessels alters the natural history of coronary artery disease by inducing inflammation that subsequently triggers accelerated progression if the disease,” Atkins and colleagues explained and added,”Our study suggests that LAD coronary artery V15 Gy greater than or equal to 10% is an independent factor associated with MACE and all-cause mortality in patients with NSCLC.”
The analysis included patients who were treated with 3-D conformal radiotherapy or intensity-modulated radiotherapy techniques between December 2001 and January 2014. The median age was 65 years (interquartile range, (IQR), 57-73 years) and almost two-thirds of patients at 64.1% were at high CHD risk according to Framingham criteria. The median follow-up was 20.4 months (IQR, 8.2-44.6 months) and 47.8 months (IQR, 31.6-75.4) months in patients who were still alive at the time of study analysis.
The one year cumulative incidence of MACE was 3.9% (95% CI, 2.6-5.5%) with a median time to first MACE of 20.6 months (IQR, 8.8-43.3 months), the investigators noted. Specifically, among patients without CHD, a dose of V15 Gy greater than or equal to 10% to the LAD increased the risk of MACE by almost 25-fold at a HR of 24.8 (95% CI, 3.49-176.4; P=0.001) compared to those who received V15 Gy dose of less than 10%.
In the same group of patients, the estimated rate of MACE at one year was 4.9% (95% CI, 2.6-8.3%) compared with 0% for those who received LAD V15 Gy of less than 10%.
“By contrast, among patients with CHD…there was not a statistically significant increase in the risk of MACE with LAD coronary artery V15 Gy greater than or equal to 10% vs less than 10%,” Atkins and colleagues wrote. Indeed, only a left ventricle dose of V15 Gy greater than or equal to 1% was associated with increased risk of MACE among patients with—and without—CHD, with MACE estimates at one year of 5% versus 0.4% for in those without CHD compared to those treated with less than 1% (P<0.001).
Estimated MACE rates for patients with CHD were 8.4% versus 4.1% for those treated with V15 Gy of 1% or greater compared with less than 1% (P0.046), the authors noted. Again among patients with CHD, “there was no statistically significant increase in the risk of all-cause mortality with the LAD coronary artery V15 Gy greater than or equal to 10% vs less than 10%,” the authors stressed.
Among patients without CHD, a left circumflex coronary artery V15 Gy greater than or equal to 14%; a left ventricle V15 Gy greater than or equal to 1%, and a mean total coronary arteries dose greater than or equal to 7 Gy conferred a 5% absolute increase in 1-year MACE estimates, as the authors also noted.
In the same group of non-CHD patients, all-cause mortality at 2 years was increased to 51.2% among those who received a LAD coronary artery dose of V15 Gy greater than or equal to 10% compared with 42.2% for those who received less than 10% (P=0.009) while all-cause mortality at 2 years was again higher at 53.2% in the same group of patients who received a mean total coronary artery dose of greater than or equal to 7 Gy compared with 40% for those who received a smaller mean total coronary artery dose (P=0.01).
Only left ventricle V15 Gy greater than or equal to 1% conferred an increased risk of MACE among patients with CHD, the authors stressed.
“Given the shared risk profiles between CHD and cancer and the high prevalence of CHD among patients with NSCLC, careful assessment of preexisting cardiac risk is necessary because optimal cardiac dose constraints may differ based on preexisting cardiac status,” the authors wrote. They authors also recommended that clinicians titrate cardiac and left coronary artery radiation doses to as low as is reasonably allowable while achieving safe lung dose-volume exposure and maintaining tumor coverage.
Commenting on the findings, Carmen Bergon, MD, PHD, Washington University School of Medicine, St. Louis, Missouri, and colleagues noted that competing risks of severe cardiac events in patients with NSCLC have become more important as newer treatments, notably immunotherapy, have led to improvements in overall survival.
“The study by Atkins and colleagues…brings us closer to improved personalization of radiation therapy to minimize long-term risks in patients with lung cancer,” the editorialists noted.
However, even though the goal of radiation planning is to keep the heart dose as low as reasonably possible, “for lung cancer, there is the added challenge of balancing lung doses and heart doses to provide acceptably low likelihoods of severe toxicities,” they cautioned. “[K]nowledge of more sensitive cardiac substructures may allow further sparing of that region during radiation planning, resulting in reduction of adverse effects.”
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The risk of both MACE and all-cause mortality was increased in NSCLC patients without coronary heart disease who received a LAD dose of V15 Gy greater than or equal to 10% during treatment for their lung cancer.
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Among patients with coronary heart disease, the risk of MACE with the same LAD dose of V15 Gy greater than or equal to 10% was not significantly different compared to patients who received a V15 dose of less than 10%.
Pam Harrison, Contributing Writer, BreakingMED™
Atkins had no conflicts of interest to disclose.
Bergon reported receiving grants from Innovation Pathways.
Cat ID: 914
Topic ID: 74,914,730,914,24,192,65,925
