The results of a study presented at the San Antonio Breast Cancer Symposium (SABCS) prompted enough controversy to warrant a statement from 3 major medical societies and an expert panel teleconference on December 14, 2011 to discuss the analysis of data presented by the MD Anderson Cancer Center physicians.
The study, "Partial Breast Brachytherapy is Associated With Inferior Effectiveness and Increased Toxicity Compared to Whole Breast Irradiation in Older Patients," was a retrospective analysis of Medicare patients comparing safety and effectiveness of accelerated partial breast brachytherapy (APBI) compared to whole-breast irradiation (WBI). Since the presentation at SABCS, major medical societies, including the American Society for Therapeutic Radiology and Oncology (ASTRO), the American Society of Breast Surgeons (ASBS), and the American Brachytherapy Society (ABS) have come out with statements expressing their concerns of the results.
"The report was based upon a review of Medicare claims data and, as such, is subject to limits in interpretation due to its retrospective nature and the inherent selection bias that exists in any study of this design. From prior analyses, we know that Medicare claims data are severely limited when it comes to extracting critically important details such as the general medical condition of the patient, the extent of the tumor, and many other important prognostic factors," according to the official ABS statement. ABS went on to highlight the difficulty to obtain critical history of treatment details through Medicare records.
Although there are still questions about APBI compared to WBI, prospective clinical trials are the only way to compare the two treatments, according to the ABS statement. Of note, the Medicare patients in this current analysis were mostly treated with a less-advanced form of APBI; the study does not take into account the current advances with this treatment.
Background on the Study and APBI
The study presented in San Antonio was a retrospective study analyzing Medicare records of female patients who had received an earlier form of APBI. The results showed that 2.2% of patients undergoing WBI had a mastectomy, compared to 4% of patients who underwent an APBI. The presenters claimed that this increase is small but statistically significant and noted slightly higher toxicities in the partial irradiation cohort. The study showed that the overall survival was the same in both groups.
APBI therapy only exposes the affected cancerous tissue to radiation treatment and shortens the treatment from a span of several weeks to 4 or 5 days. Previous to 1991 when APBI was started at the Ochsner Clinic, WBI had been used for decades, delivered daily for a total of 5–8 weeks for early-stage breast cancer patients.
According to Dr. Robert Kuske of the Arizona Breast Cancer Specialists Center, APBI has been one of the most studied treatments for breast cancer in the last 20 years. Studies have shown that APBI results in decreased treatment time and decreases the exposure of a patient’s healthy tissue to radiation. Dr. Kuske emphasized that there are currently seven important prospective ongoing trials that are comparing APBI to WBI. Dr. Kuske is a coprincipal investigator of one of these trials, the NASBP-B-39 study, comparing 5-day accelerated APBI to 6-week WBI.
Expert Panel Discussion
The panelists agreed that the retrospective analysis has limited utility and an inherent flaw in its design. The use of mastectomy rates as a valid surrogate for recurrence rate is not justified, according to the breast cancer panelists.
"We do know that women received more chemotherapy in the whole-breast irradiation group of patients. This by itself could account for the small 1.8% difference in mastectomy rates between the two groups," Dr. Kuske stated during the teleconference. He also pointed out that data on the aggressiveness of tumors among the Medicare patients is not available and further confounds the results. Other factors such as diabetes, obesity, smoking history, and BRCA mutation status, which can all impact mastectomy rates, were missing from the analysis, as well as details about types of systemic treatments patients underwent.
Dr. Peter Beitsch, a coprincipal Investigator of the American Society of Breast Surgeons’ MammoSite Registry added that the Surveillance Epidemiology and End Results (SEER) database used in the Medicare study does not have good data on local, regional, or distal recurrence. "The Medicare claims SEER database certainly has its place in research, but in general, it is fraught with data entry inaccuracies."
Dr. Beitsch attempted to distill factual data of the study that both the "lay and the medical press has latched on to," as he described it. The Registry has had 1,440 patients, and more than 16 papers on the safety and efficacy, comparable to WBI, have been published.
"Unequivocally, accelerated partial breast irradiation is a safe and effective form of treating the breast after appropriately performed lumpectomy in patients over age somewhere between 45 and 50 with early-stage invasive breast cancer," said Dr. Beitsch during the call yesterday.
Dr. Beitsch pointed out that the higher hospitalization rate for APBI patients compared to WBI patients was puzzling as he has never had either an APBI or WBI admitted to the hospital for complications from the procedure. He pointed out that older, more sick patients generally receive APBI, which could explain the higher hospitalization rate.
"To state that partial breast irradiation based on this database is less effective is false and misleading. The survival rate’s the same, and there's no report whatsoever about what the actual recurrence rate was in the breast," Dr. Kuske concluded.
The major lesson to be learned is that there is a major difference between statistical significance and clinical relevance. A study can have a statistically significant result, yet it could be neither biologically nor patient-outcome relevant. In this case, a difference of 1.8% in mastectomy rates is not likely to make a difference for a patient-treatment decision in the clinic.