SABCS: Study links APBI to higher complication rates

Accelerated partial-breast irradiation (APBI) brachytherapy is associated with higher rates of late mastectomies, postoperative complications, and radiation-related toxicities compared with traditional whole-breast irradiation, according to a study presented at the San Antonio Breast Cancer Symposium (SABCS).

Researchers from MD Anderson Cancer Center at the University of Texas examined the effectiveness and toxicity outcomes in older Medicare patients treated with APBI brachytherapy versus whole-breast irradiation, which has long been the standard of care for breast cancer radiation therapy.

Criticism of the study surfaced almost immediately among attendees at the symposium. One critique was that the study is based on an analysis of Medicare billing codes rather than actual clinical outcomes. However, in spite of the criticism, most radiation therapy specialists contacted by AuntMinnie.com believe that APBI should still be administered within the context of a clinical trial, rather than made more widely available.

Rising use of APBI

Breast brachytherapy involves inserting a catheter containing a radioactive source, and it is performed twice daily for a duration of five to seven days. The procedure offers a faster cycle of treatment for patients with breast cancer, as conventional whole-breast radiation therapy requires daily treatments for up to seven weeks.

APBI procedure volume has been rising rapidly since the first device was cleared in the U.S. in 2002. APBI brachytherapy treatments have increased from less than 1% in 2000 to 13% of patients undergoing treatment in 2007, according to Dr. Benjamin D. Smith, an assistant professor of radiation oncology at MD Anderson and lead author of the study, who presented at the meeting.

Smith and colleagues examined Medicare claims of women older than 66 years of age who had been diagnosed with incident-invasive breast cancer between 2000 and 2007. This cohort of 130,535 women underwent breast-conservation surgery followed by radiotherapy.

The MD Anderson researchers analyzed the effectiveness of the radiation therapy, infectious and noninfectious postoperative complications, and complications following radiotherapy treatment, including breast pain, rib fractures, and/or fat necrosis.

They determined that women who elected to have the APBI treatment had a twofold increased risk of having a subsequent mastectomy. In addition, 4% of these patients underwent a subsequent mastectomy, compared with 2.2% who had conventional whole-breast irradiation.

Along with the higher incidence of post-treatment mastectomy, patients who had breast brachytherapy procedures had a higher incidence of acute and late toxicities. Sixteen percent of breast brachytherapy patients experienced infectious complications, compared with 10% of conventionally treated patients. The rate for noninfectious complications was 16% and 8%, respectively.

With the exception of pneumonitis, the five-year cumulative incidence of postradiation complications was also higher with APBI.

Complication rates of APBI versus whole-breast radiation therapy
APBI brachytherapy Whole-breast irradiation
Breast pain 14.9% 11.7%
Fat necrosis 9.1% 3.7%
Pneumonitis 0.1% 0.8%
Rib fracture 4.2% 3.6%

Smith said that he was shocked by the results.

"I think that our results are very plausible and consistent with the literature," he said. "However, I did not expect that we would find a difference in outcomes between brachytherapy and whole-breast irradiation using this claims-based approach. Such an approach has never been used before to evaluate breast brachytherapy."

Study co-author Dr. Grace Smith, PhD, a postdoctoral fellow and radiation oncology resident, said that these data underscore the importance of waiting for mature data from randomized clinical trials before breast brachytherapy is widely adopted. National randomized trials comparing APBI brachytherapy to conventional whole-breast irradiation are ongoing; two have been completed.

MD Anderson will continue to offer APBI brachytherapy to patients in ongoing institutional and multi-institutional clinical protocols, according to Dr. Thomas Buchholz, professor and head of the division of radiation oncology.

Radiation oncologists comment

But other radiation oncologists who are familiar with APBI were skeptical of the study. These include Dr. Frank Vicini, a radiation oncologist with Michigan Healthcare Professionals, who has been regularly publishing outcomes data from a matched set of 199 patients treated with APBI and 199 patients who received conventional treatment.

"First of all, it's important to recognize that this is not a clinical study," he said. "It is an analysis of billing codes. This analysis summarizes what medical charges were recorded by nonphysicians."

Billing codes were used as surrogates for clinical outcomes, he pointed out, and there was no way to verify the accuracy of the charges. This is a concern because a lot of peer-reviewed literature has shown that Medicare patient charges can be fraught with error.

"All this study tells us is that when billing codes are analyzed, there appear to be differences in outcomes based upon billing code surrogates for clinical outcomes. You can't turn something nonclinical into clinical," Vicini emphasized. "Unfortunately, there is no way to go back and validate that the billing codes are accurate. Although the authors acknowledge the flaws in their study, these are not trivial. In my opinion, they are huge."

It's not unheard of for a lumpectomy to be incorrectly coded and charged as a claim for payment as a mastectomy, Vicini said. He also referenced published data -- in addition to his own -- that contradicts Smith and colleagues' findings that patients treated with APBI have higher incidences of toxicities and postradiation complications. The data from the trial he is heading indicate that toxicities and complications are not greater and that the local recurrence rate is comparable.

"How can a billing code analysis trump the data of phase III clinical trials?" Vicini asked. "It is unheard of."

Dr. Peter Beitsch, a breast oncology surgeon affiliated with the Dallas Surgical Group, also expressed concern about the quality of the data. The study reported a higher hospitalization rate for APBI patients (9.6%) compared to whole-breast-irradiated patients (5.7%), he noted, yet he does not know one breast surgeon who has had an APBI-treated patient admitted to a hospital.

"Large retrospective databases can provide interesting data, although it all depends on the quality of data entered and how it is subsequently explored," Beitsch said. "The [Surveillance, Epidemiology, and End Results (SEER)]-Medicare database is a large repository of mainly medical claims data with little information on patients, their actual cancer, and other clinical data."

The MD Anderson study will not alter his discussions with or the treatment of his patients, Beitsch said. "I have talked with several MD Anderson surgeons who also are not altering their discussions and treatments," he said.

Dr. Bruce Haffty, chairman of the department of radiation oncology at the University of Medicine and Dentistry of New Jersey, did not discount the study, but he said there are limitations to its interpretation based on the inherent biases associated with its design and its retrospective nature.

He pointed out that each group may have population differences, which could contribute to the differences in outcomes, including mastectomy rates.

"The study demonstrates the importance of the data that will be coming out from the ongoing randomized trials comparing partial-breast irradiation to conventional whole-breast irradiation," Haffty said. "It also demonstrates the importance of adherence to a cautious approach in the selection of patients for partial-breast irradiation outside of a clinical trial."

The study will not change his current approach to patients, Haffty said. As a strong believer in putting most patients in a clinical trial when appropriate, he will continue to recommend enrollment in an APBI trial. For patients who want to be considered for APBI outside of a clinical trial, he will continue to use the American Society for Radiation Oncology (ASTRO) consensus panel guidelines for "suitable" patients.

Dr. Lori Pierce, professor of radiation oncology at the University of Michigan, said the study is noteworthy because it underscores the importance of studying APBI in a systematic way in clinical trials. Pierce only recommends APBI treatment for patients willing to enroll in a clinical trial.

"The study highlights potential complications and outcomes in a very large patient cohort," she said.

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