Observational study makes the case for early cardio-oncology consult
For non-small cell lung cancer (NSCLC) patients, more radiation to the heart adds to early mortality and cardiovascular morbidity, especially for those with preexisting heart problems, a retrospective cohort study found.
Increasing radiation dose delivered to the heart was linked with a significantly greater risk of all-cause mortality (adjusted HR 1.02/Gy; P=0.007) and major adverse cardiovascular events (adjusted HR 1.05/Gy; P<0.001) during a median follow-up of 20.4 months, reported Raymond Mak, MD, of Brigham and Women's Hospital in Boston, and colleagues in the Journal of the American College of Cardiology.
The risk was especially high for patients with pre-existing coronary heart disease (CHD), with a 3.58-fold greater risk of a major adverse cardiac event (MACE) than seen among those without CHD (P<0.001).
The findings reinforce the known elevated cardiovascular risk for NSCLC patients but deepen the understanding of the "incremental risk of cardiac radiation dose exposure as a potentially modifiable risk factor," the researchers wrote.
This should have the effect of "substantially affecting national guidelines on radiotherapy planning and providing a shared framework among radiation oncologists, primary care physicians, and cardiologists to increase recognition and treatment of cardiovascular events and inform post-radiotherapy cardiac risk prevention strategies," they added.
"The take-home clinical recommendation is that we need to get early involvement from cardiologists for these patients that are at highest risk of developing a heart attack or other major complication after radiation therapy," Mak told MedPage Today.
These careful, detailed findings form a solid base to build an evidence-based cardiovascular approach to lung cancer patients, and potentially any patient, being treated with chest radiation, noted Guilherme Oliveira, MD, MBA, of the Case Western Reserve University School of Medicine in Cleveland, in an accompanying editorial.
This patient population should be tested for CHD, he recommended. If found, mean heart dose should be kept to a minimum, as no dose is completely safe; if not found, the Framingham Risk Score should still be calculated and addressed, and the mean heart dose kept under 10 Gy, Oliveira wrote.
In the study, a mean heart dose of at least 10 Gy was related to a significantly greater risk of death in CHD-negative patients (HR 1.34, P=0.014). This threshold didn't appear meaningful in those with CHD (HR 0.94, P=0.66), which Oliveira interpreted as "any dose can augment the risk disproportionately."
"Most importantly, the authors teach us that adverse events occur very early -- within 1 and 2 years of exposure -- definitively laying to rest the notion that radiation to the heart has predominantly delayed effects," he wrote.
"The message is clear: in this day and age, no cancer patient undergoing chest radiation should fail to see a cardio-oncologist," Oliveira concluded.
Mak's group evaluated 748 consecutive, locally-advanced NSCLC patients receiving thoracic radiotherapy using intensity-modulated or conventional radiotherapy techniques but not stereotactic body radiotherapy.
Among them, 268 had preexisting CHD based on, as Oliveira noted, having "painstakingly combed all charts to determine the presence or absence of previous coronary heart disease (CHD) by interrogating notes, laboratory results, electrocardiograms, stress tests, coronary angiograms, and computed tomography scans."
Just over 71% of patients died and 10.3% had at least one MACE after a median follow-up of 20.4 months. The cohort had a mean age of 65 years and was 49.2% female.
Over 32% of patients developed at least one grade 3 or worse adverse event. Again, this risk was higher with a history of CHD (41.8% vs 26.3% without CHD).
Cox and Fine and Gray regressions were used to pinpoint predictors of all-cause mortality and major adverse cardiac events, adjusting for cardiovascular prognostic factors, like pre-existing CHD and lung cancer prognostic factors.
Limitations of the study include its retrospective nature and the heterogeneous therapy regimens. Also, "retrospective assessment may in fact underestimate true cardiac risk, particularly in patients with limited follow-up due to competing risks or medical care received locally and incompletely captured despite in-depth medical record review," the researchers emphasized.
"Prospective studies are needed to assess the effect of combined cardiac risk stratification, cardiac radiation dose reduction techniques, and post-radiotherapy preventive care on survival and quality of life in patients with lung cancer," the researchers wrote.
Mak disclosed relationships with AstraZeneca and NewRT.
Journal of the American College of Cardiology
Source Reference: Atkins KM, et al "Cardiac radiation dose, cardiac disease, and mortality in patients with lung cancer" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2019.03.500.
Journal of the American College of Cardiology
Source Reference: Oliveira GH "The raveled risk of radiation revealed" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2019.04.011.
Read the original article on Medpage Today: Lung Cancer Survival Suffers With Each Gray of Radiation to the Heart