Nick Mulcahy

October 07, 2011

October 7, 2011 (Miami Beach, Florida) — Radiation to the whole breast for early breast cancer does not place women at increased risk for long-term pulmonary toxicity, compared with mastectomy, according to a new study presented here at the American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting.

The study also found that patients with radiation-induced pneumonitis at the time of treatment were not at increased risk for pulmonary complications 25 years later.

This is study's "most important finding" — that "acute pneumonitis did not predict the development of late fibrosis," said Phillip Devlin, MD, from the Dana-Farber/Brigham and Women's Cancer Center in Boston, Massachusetts, who was not involved in the work.

These data come from a trial that dates back to a time when breast-conservation therapy (lumpectomy plus radiation) was still a controversial approach to treatment.

In that trial, 247 patients with stage I to II breast cancer were randomized to modified radical mastectomy or breast-conservation therapy (45 to 48.6 Gy whole breast, 15 to 20 Gy boost), and treated from 1979 to 1987 at the National Cancer Institute (NCI) in Bethesda, Maryland.

Twenty-five years later, 102 patients were still alive and 61 participated in the new study. These women, all of whom are now elderly, returned to the NCI campus for 2 days of diagnostic imaging and pulmonary function testing.

"This study demonstrates no difference in either radiographic evidence of pulmonary fibrosis or pulmonary symptomatology," the researchers conclude. The lead author was Nicole Simone, MD, assistant professor of radiation oncology at the Kimmel Cancer Center of Thomas Jefferson University in Philadelphia, Pennsylvania.

The 2 treatment approaches to early breast cancer have "largely equivalent pulmonary toxicity," write Dr. Simone and colleagues.

Symptomatic pneumonitis within 1 year of treatment was higher with breast-conservation therapy (n = 31) than with mastectomy (n = 30) (16.7% vs 0.0%; P = .02). However, 25 years later, patients with pneumonitis were not significantly more likely to develop late fibrosis (mean lung zone score, 0.57 vs 0.37; P = .54) or pulmonary function test (PFT) abnormalities (mean PFT diffusion defect, 1.25 vs 0.83; P = .95).

"I think it's fabulous," said Dr. Devlin, who is secretary/treasurer of ASTRO, about the pneumonitis/fibrosis findings. Pulmonary toxicity is "very, very much a concern" with radiotherapy, he said, adding that these are the "longest-term data known."

"One of the downsides to whole-breast radiation is pneumonitis and fibrosis developing on the right side of the body and coronary artery disease developing on the left side," Dr. Devlin explained in an interview with Medscape Medical News.

There was more fibrosis among the women who received radiation, Dr. Simone pointed out. The mean number of lung zones with any fibrosis did not significantly differ by treatment (2.2 vs 1.5; P = .18), but the mean score of the worst lung zone for each patient was higher with breast-conservation therapy (0.93 vs 0.58; P = .03).

Nevertheless, "there was no functional change," said Dr. Simone about the 2 groups. She was referring to that fact that PFT measures were similar in the breast-conservation and mastectomy groups, including total lung capacity (100.0% vs 103.8%; P = .39) and diffusion defect (0.89 vs 0.83; P = .80).

"Radiation patients did not have lower DLCO values [diffusing capacity of the lung for carbon monoxide] or increased diffusion defects, which are historically noted abnormalities after radiation," the authors explain.

However, the forced expiratory volume in 1 s/forced vital capacity ratio was lower in the breast-conservation groups than in the mastectomy group (72.1% vs 76.0%; = .04), they report.

Survival Curves Separating at 25 Years

This study was the brainchild of Dr. Simone, who got to know some of the study participants while working as a resident rotating through the Washington, DC–metro area federal healthcare institutions (Walter Reed Hospital, Navy Hospital, and NCI).

The survival curves for the NCI participants have begun to separate at 25 years, Dr. Simone told Medscape Medical News. The mastectomy patients are suddenly showing a survival benefit. Dr. Simone and colleagues wondered if late pulmonary and cardiac toxicities related to radiotherapy might be to blame.

This led to the follow-up study being launched.

In all, 61 women underwent a detailed history and exam, posteroanterior and lateral chest x-ray, thoracic computed tomography, and PFTs. A radiologist blinded to patient history evaluated imaging and scored each lung zone using validated fibrosis severity scales (3 zones per lung; on a scale of 0 to 3 [none, mild, moderate to severe]). A blinded pulmonologist classified PFT defects by severity (on a scale of 0 to 3).

The authors note that the risks of developing fibrosis, based on imaging and PFT abnormalities, did not differ by age, chemotherapy use (node-positive patients received chemotherapy at the time of initial treatment), side of breast primary, development of ipsilateral recurrence or contralateral cancer, or history of smoking, asthma, or interstitial lung disease (P > 0.05 for all).

The team has yet to present their findings on the cardiotoxicities from the study, but Dr. Simone gave a hint: "The same does not hold true." Still, in the words of Dr. Devlin, these data on pulmonary function are "reassuring."

Dr. Simone agreed. The "potential pulmonary toxicity" of radiotherapy is "something that gives women [with breast cancer] pause, especially young patients," she said.

The authors have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting: Abstract 11. Presented October 3, 2011.

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