Contemporary Studies Dispute Findings of Radiation-Induced Cardiotoxicity  


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At the 2013 Breast Cancer Symposium, studies suggested that with current radiotherapy techniques the mean radiation doses to the heart are much lower—and thus radiotherapy is presumably much safer—than findings suggested by an article published in The New England Journal of Medicine last spring.1

Mean Heart Doses Lower Than Reported

Geraldine M. Jacobson, MD, MPH, and colleagues from West Virginia University, Morgantown, reviewed the treatment plans of 78 patients (86 breasts) treated in 2012/2013, which were computed tomography–based, field-in-field forward planning with heart blocking .2 Patients received hypofractionation (16 x 2.66 Gy, no boost) or standard fractionation (46.8–50.4 Gy +/– 10 Gy boost) radiotherapy.

They found the average mean heart doses were 1.45 Gy for the left breast and 0.70 for the right.  Averages were 1.16 Gy and 0.48 Gy, respectively, under hypofractionation and 1.60 Gy and 0.84 Gy, respectively, under standard fractionation. Mean heart doses for the left vs right breasts were significantly different (P = .002), and breast doses and mean heart doses were significantly correlated (P = .026), Dr. Jacobson reported.

“Mean heart dose in patients treated at our institution with heart avoidance and three-dimensional [3D] field-in-field treatment planning is much lower than the published reports of patients treated prior to 2001—1.06 Gy vs 4.9 Gy,” she noted.

David E. Wazer, MD, Radiation Oncologist-in-Chief at Tufts Medical Center, Boston, discussed the paper at the meeting and commented, “These findings undermine the credibility of the NEJM paper as to its relevance in current practice. The investigators showed that using contemporary planning, left and right breast mean heart doses are all less than 25% of the values reported in that paper.”

A second study presented at the meeting examined heart exposure in 100 patients treated with 3D conformal radiotherapy for left-sided breast cancer and also found mean doses to be lower (2.89 Gy) than those reported by Darby et al (4.9 Gy), and that the median volume of heart exposed to doses higher than 5 Gy is also low (17%).3

“This is not to say that radiation oncologists are not concerned about the heart, or that there is not a real potential for injury,” he said.

Studies Shows No Increased Risk of Heart Disease

Also reported at the Breast Cancer Symposium was a large population-based study from the Netherlands, which showed that women who received radiotherapy for ductal carcinoma in situ (DCIS) had no increased risk of cardiovascular disease compared to the general population or to patients with DCIS treated with surgery alone.4

Naomi B. Boekel, MSc, of Netherlands Cancer Institute, Amsterdam, described 10,468 women treated between 1989 and 2004, of whom 28% received radiotherapy. After a median follow-up of 10 years, the diagnosis of cardiovascular disease was similar between patients receiving surgery alone (9%) or surgery plus radiotherapy (8%), and between patients who received left- sided radiotherapy (7%) vs right-sided (8%).

“This is a powerful paper with a large cohort and remarkably detailed data,” Dr. Wazer noted. “Its one weakness is that follow-up was just 10 years, but it’s a fantastically valuable dataset that we hope will be reanalyzed after 5 more years.”

A recent paper from Europe used strain rate imaging (a sensitive echocardiographic technique that evaluates wall motion) and revealed that if the left ventricle is included in the incident beam path, wall motion abnormalities can be detected shortly after radiotherapy is delivered, and they persist for at least 14 months.5

Results from a study led by Lori J. Pierce, MD, of the University of Michigan, were “more reassuring,” he continued. The study compared single-photon emission CT myocardial perfusion scans pre- and post-treatment and quantified doses to the heart and coronary arteries.6 Radiotherapy was not associated with any clinically significant defects.

“They used sophisticated 3D treatment planning and kept the heart out of the incident, ie, primary beam. The average mean dose to the heart was relatively high (2.82 Gy) but it was being delivered in very low doses on a daily basis. No correlation was found for low doses delivered to cardiac structures and perfusion, the summed stress defects scores or ejection fraction. They saw no clinically significant defects after radiotherapy, and this is reassuring. If we are meticulous with our treatment planning, we can have a positive effect with respect to cardiac injury,” Dr. Wazer concluded. ■

Disclosure: Drs. Jacobson, Wazer, and Boekel reported no potential conflicts of interest.

References

1. Darby SC, Ewertz M, McGale P, et al: Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368:987-998, 2013.

2. Jacobson GM, Wen S, Zhang J, et al: Mean radiation dose to the heart in patients with breast cancer. 2013 Breast Cancer Symposium. Abstract 56. Presented September 7, 2013.

3. Lonardi F, Gioga G, Coeli M, et al: Heart exposure in 100 consecutive, unselected patients treated with adjuvant 3D conformal radiotherapy for left-sided breast cancer. 2013 Breast Cancer Symposium. Abstract 103. Presented September 8, 2013.

4. Boekel NB, Schaapveld M, Gietema JA, et al: Cardiovascular morbidity and mortality in patients treated for ductal carcinoma in situ of the breast. 2013 Breast Cancer Symposium. Abstract 58. Presented September 7, 2013. 

5. Erven K, Florian A, Slagmolen P, et al: Subclinical cardiotoxicity detected by strain rate imaging up to 14 months after breast radiation therapy. Int J Radiat Oncol Biol Phys 85:1172-1178, 2013.

6. Chung E, Corbett JR, Moran JM, et al: Is there a dose-response relationship for heart disease with low-dose radiation therapy? Int J Radiat Oncol Biol Phys 85:959-964, 2013.


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