Presenter: D.R. McHaffie Presenter's Affiliation: Presenter's Affiliation: Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI Type of Session: Scientific
Over the past several years, patients are increasingly being offered accelerated partial-breast irradiation (APBI) as an alternative to whole breast radiation therapy for the adjuvant treatment of ductal carcinoma in situ (DCIS) or early-stage invasive breast cancer.
APBI allows for a decreased treatment duration and decreased radiation to uninvolved portions of the breast and adjacent organs. Studies with limited follow-up have demonstrated low local recurrence rates and excellent cosmetic results with APBI.
Several multicenter, randomized clinical trials have been initiated to compare the effectiveness and safety of APBI with whole breast radiation therapy. Despite the lack of mature clinical trial data with long-term patient follow-up, APBI is increasingly being used outside the framework of a clinical trial
Despite this, few data have been generated that can aid in determining which patients can safely be treated with APBI and which patients would be better served with whole breast radiation therapy. As a result, the American Society for Radiation Oncology (ASTRO) initiated a Task Force of experts in the field of breast cancer to develop a consensus statement pertaining to patient selection criteria for the use of APBI in patients not enrolled on a clinical trial. The recently published guidelines generated from this Task Force defined a group of patients for which caution should be used when treating patients with APBI off of a clinical trial [Smith BD, et al. Int J Radiat Oncol Biol Phys. 2009;74(4):987-1001.].
This study reviews the outcomes of patients treated with APBI that were defined as higher risk patients according to the ASTRO cautionary criteria.
Materials and Methods
Between March 2001 and June 2006, a total of 322 consecutive patients were treated with APBI at the University of Wisconsin. Of this group, 136 patients were identified as having met the ASTRO cautionary criteria.
Patients in the higher risk cohort met cautionary criteria based on age 50-59 years (63.2%), having pure DCIS (23.5%), an extensive intraductal component (12.5%), tumor size 2.1 cm to 3.0 cm (9.6%), estrogen receptor negative malignancy (8.1%), lobular histology (7.4%), or surgical resection margins <2 mm (7.4%). Additionally, 27.9% of patients possessed multiple cautionary factors.
All patients were treated with high-dose-rate brachytherapy to a total dose of 32 Gy to 34 Gy in eight to 10 fractions administered twice daily over four to five days. Administration was done via a multicatheter technique (93.4%) or via MammoSite® balloon (6.6%).
With a median follow-up of 60 months (range 1.3 months to 92.4 months), five patients experienced in-breast tumor recurrences. Of these, three were local recurrences and two were locoregional recurrences. Among patients with a recurrence, two were successfully salvaged with mastectomy and have no evidence of disease at last follow-up and two are deceased. All five patients with in-breast tumor recurrences failed between 24 months and 50 months following therapy. The 6-year actuarial local control rate in this study was 95.2% ± 4.1%.
Including contralateral events, the 6-year disease-free survival rate was 89.6%. The 6-year cause-specific survival and overall survival rates were 97.6% and 95.3%, respectively. There were no ipsilateral failures among 32 patients with DCIS, with an actuarial local recurrence rate of 0%. This percentage was not significantly different that the 6.1% local recurrence rate for patients with invasive disease (p = 0.24).
Among 104 patients with Stage I or II invasive carcinoma, the actuarial local recurrence rate for patients considered cautionary by virtue of age alone was 0%, compared with 12.7% of those deemed cautionary due to histopathologic or surgical factors (p = 0.018). Local recurrences were observed in one of 17 patients with an extensive intraductal component, two of 11 with estrogen receptor negative status tumors, one of 10 with margins <2 mm, two of 10 with lobular histology, and two of 13 with a tumor size between 2.1 cm and 3.0 cm.
Although locoregional recurrences remained low at 6 years for the entire cohort, our experience suggests that patients with an extensive intraductal component, estrogen receptor negative status tumors, close surgical margins, lobular histology, and tumor size 2.1 cm to 3.0 cm should be approached with caution until prospective, randomized data become available given the higher rate of local recurrence within this group.
In the absence of these surgical or histopathologic cautionary factors, however, those aged 50–59 years do not appear to be at significant risk of local recurrence, indicating potential suitability for treatment with APBI.
The absence of ipsilateral breast tumor recurrences observed among those with DCIS also supports the use of APBI in this cohort of patients.
Even for patients with higher risk features, as defined by the ASTRO cautionary criteria, the ipsilateral breast local recurrence in this study population was low. However, among the total patient population treated with APBI at the University of Wisconsin, the authors did not report how the ipsilateral breast local recurrence rate compares for the 136 patients with cautionary criteria and the remaining 186 patients treated with APBI. A significance difference among patients with cautionary features and patients with suitable features, if it exists, would clearly have been worth mentioning by the authors.
The increased rate of local recurrence for patients considered cautionary by virtue of age versus those deemed cautionary due to histopathologic or surgical factors (0.0% vs. 12.7%, p = 0.018) may be due to patient with certain histopathologic or surgical factors having more aggressive tumors. Previously published data have demonstrated that patients with close or positive surgical margins, estrogen receptor negative status tumors, or larger primary tumors are more likely to experience an ipsilateral breast recurrence following adjuvant therapy with whole breast irradiation. While a similar effect may being occurring in this patient population following APBI, the increased rate of recurrence in this subgroup may be occurring due to lack of radiation to the entire breast that may help to control microscopic occult ipsilateral disease.
Previously published phase III trials and meta-analyses have demonstrated that patients at a younger age at the time of breast conserving therapy with whole breast radiation therapy are more like to suffer from an ipsilateral breast tumor recurrence. This relationship would be expected to hold true for patients treated with APBI. This study, however, did not demonstrate any recurrences in patients aged 50 to 59 years without other adverse risk factors. This suggests that these patients may be good candidates for APBI, but additional study with longer follow-up is indicated.
No in-breast recurrences were observed among patients with DCIS, also indicating that these patients are good candidates for APBI. Although the American Brachytherapy Society (ABS) has recommended criteria for patient selection for APBI to include only patients with invasive ductal adenocarcinoma tumors, the American Society of Breast Surgeons (ASBS) also recommends APBI for patients with DCIS tumors ≤3 cm. As only 32 patients in this study had a diagnosis of DCIS, no definitive conclusions can be made regarding the utility of APBI in this patient population.
Of note, the ASTRO cautionary criteria did not include an assessment of Her-2 status. Previous data has demonstrated an increased risk of recurrence in patients with Her-2 positive disease. As not all patients in this study underwent Her-2 assessment, no conclusions can be made regarding the efficacy of APBI among patients with Her-2 positive disease.
Confirmatory randomized studies will be needed before concluding that APBI is an acceptable substitute for whole breast external beam radiation therapy for patients undergoing breast conservation therapy, particularly among patients with higher risk features. The National Surgical Adjuvant Breast and Bowel Project and the RTOG (NSABP B-39/RTOG 0413) phase III trial comparing whole breast radiation therapy to APBI should help to determine the role for APBI. Higher risk patients, including those age <50 years, or those with estrogen receptor-negative tumors or axillary lymph node metastasis, are currently being enrolled on that trial.
While patients with cautionary and unsuitable risk factors should ideally be treated with APBI only on a clinical trial, long-term follow-up of clinical trials or retrospective assessments of patients with these higher risk features is essential to determine the efficacy and utility of APBI in this patient population. Longer follow-up of this patient cohort would be a welcomed addition to the existing medical literature that could aid practitioners interested in treating higher risk patients with APBI.
Ultimately, this study affirms the use of APBI in higher risk patients meeting the ASTRO cautionary criteria. However, as long-term follow-up of this patient population is lacking, such higher risk patients who desire to be treated with APBI should be treated on a clinical trial.
Aug 27, 2012 - Accelerated partial breast irradiation yields five-year clinical outcomes and patterns of failure similar to those achieved with whole breast irradiation, with excellent three-year survival for women who develop an ipsilateral breast tumor recurrence, according to a study published in the Sept. 1 issue of Cancer.