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Accelerated Partial Breast Irradiation: More Data Needed, Researchers Say

Charles Bankhead

Despite showing promise as a potential alternative to whole breast irradiation, accelerated partial breast irradiation (APBI) requires further clinical evaluation to address unresolved issues, particularly those related to patient selection, panelists generally agreed during a discussion at the American Society of Therapeutic Radiology and Oncology (ASTRO).

"We have favorable 10-year results from institutions that have extensive clinical experience," said Robert R. Kuske Jr., M.D., professor of human oncology at the University of Wisconsin in Madison. "We have documented satisfaction of patients and referring physicians. We have shown that brachytherapy can be done in multiple institutions with quality control. We have momentum toward a national phase III randomized trial that will compare 6 weeks of external beam radiation therapy with 4 to 5 days of accelerated partial breast irradiation."

The volume of data notwithstanding, he continued, future acceptance of APBI depends on "data, data, and more data. It is very important to avoid catastrophes."

The lone dissenting voice on the panel came from a Michigan radiation oncologist whose institution has the most extensive clinical experience in terms of follow-up. But even the dissent was qualified.

"I believe there is sufficient data to support clinical use of partial breast irradiation in appropriately selected patients, with application of well-tested fractionation schedules, extreme attention to high-quality radiation therapy, delivery, and reproducibility," said Frank Vicini, M.D., a radiation oncologist at William Beaumont Hospital in Royal Oak, Mich.

"That does not mean that I do not support investigational studies," he added. "Every patient treated with partial breast irradiation at our institution is still on an investigational study. Nevertheless, I believe the body of data support the use in selected patients."

Kuske sees APBI as a potential solution to the problem of suboptimal therapy in breast cancer patients who receive breast-conserving treatment. Noting that only about half of patients with early-stage breast cancer undergo breast conservation, Kuske said that omission of radiation therapy from conservative therapy represents a particularly ominous problem. "There is no data whatsoever to support not offering breast irradiation as part of breast conservation therapy," said Kuske. "We have to ask whether partial breast irradiation might decrease the proportion of women who are receiving suboptimal therapy as part of breast conservation."

APBI has evolved in several directions, but a common feature is a substantial reduction in the 6- to 7-week time period required for conventional external beam whole-breast irradiation. APBI approaches include 4 to 5 days of interstitial brachytherapy, 4 to 5 days of balloon-delivered intracavitary brachytherapy, 4 to 5 days of conformal or intensity-modulated partial breast irradiation, and single-dose intraoperative radiation therapy, the latter of which is under investigation in Europe, said Kuske. Of the various techniques, interstitial brachytherapy has the greatest clinical experience, he added.

Appropriate patient selection remains a key issue in the clinical application of APBI. Generally accepted criteria include patients who are older than age 45, have tumors smaller than 3 cm, infiltrating ductal carcinoma, and no evidence of multicentric disease, said Douglas Arthur, M.D., assistant professor of radiation oncology at Virginia Commonwealth University in Richmond. Additionally, microscopically negative surgical margins are "a must," Arthur said, and selection criteria also include negative axillary nodes and no extensive intraductal component (EIC-negative).

Arthur argued that so-called whole-breast irradiation does not in fact cover the entire breast.

"Anyone who has done CT simulations knows that we don’t cover the whole breast, and there is no data I am aware of that says we have to cover the whole breast," he said. "I would propose that the target is the partial breast, not the whole breast and that the appropriate target is 1 to 2 cm around the lumpectomy cavity. That’s dependent on the surgical resection and appropriate pathologic assessment of the tissue."

His proposal notwithstanding, Arthur acknowledged that the precise amount of the breast tissue that requires radiation coverage has not been determined. Another unresolved issue relates to assessment of the homogeneity of the radiation dose. Currently available methods for calculating homogeneity are inadequate, said Arthur.

Reviewing available clinical data on APBI, Vicini noted that 199 patients have received breast brachytherapy at his institution since 1993, including high-dose and low-dose regimens. Median follow-up is 5 years, and a substantial number of the patients have been followed for 6 to 8 years. In that time five local recurrences have been documented. The 5-year actuarial recurrence rate for the entire cohort has been 1.2%.

Vicini compared the APBI cohort with 1,503 patients who received external beam radiation therapy. The groups were matched for histology, margin status, nodes, age, tumor size, receptor status, and tamoxifen use. The 5-year actuarial rate of recurrence was low in both groups, and the rates of in-breast recurrence locally or elsewhere in the breast did not differ between them.

One criticism of APBI is that use of the technique could lead to unnecessary treatment. Vicini noted that data from 11 randomized trials have failed to identify any subset of patients that do not require radiation therapy after lumpectomy. Moreover, the trials have provided no evidence of decreased overall survival in patients receiving APBI, except for a subset analysis of one Italian study, he added. Extensive data analyses also have failed to show differences in rates of recurrence locally or elsewhere in the breast.

Offering a critical overview of the current status of APBI, Abram Recht, M.D., said patient selection is the biggest problem among unresolved issues. Other unknowns relate to optimal dose volume, dose fractionation, and total radiation dose.

"What are the tradeoffs?" asked Recht, associate professor Harvard Medical School and the Joint Center for Radiation Therapy in Boston. "What are the relative advantages and disadvantages of different radiation modalities? How do you integrate partial breast irradiation with chemotherapy? If partial breast irradiation doesn’t work or if the patient develops another primary elsewhere in the breast, can we still salvage the breast? What is the impact of partial breast irradiation on overall survival? We don’t know the answers to any of these questions."

Available data also show that breast cancer patients attach considerable importance to even minor differences in outcome, he added.

"To prove that partial breast irradiation is equivalent to standard whole-breast irradiation will require hundreds or thousands of patients with long follow-up to show whether there are small but meaningful differences in outcome," said Recht. "We don’t necessarily need randomized trials, but this does raise a major problem related to how we introduce new technology."

"This is an exciting approach that will allow more patients to undergo breast-conserving therapy more quickly at lower cost with less risk of long-term complications," Recht added. "I believe all aspects of partial breast irradiation should be systematically investigated. Until more data are available, I think this is best performed as part of investigational studies. One has to inform patients that partial breast irradiation is not a routine standard of care."


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