Authors: P.L. Dorn, H. Al-Hallaq, M. Goldberg, Y. Hassan, N. Jaskowiak, G. Newstead, S.J. Chmura.
For several decades, whole breast irradiation (WBI) has been used after breast conserving surgery as a means of reducing risk of ipsilateral breast tumor recurrence.
The efficacy of whole breast irradiation has been demonstrated in multiple randomized controlled trials and meta-analyses with follow-up intervals in excess of twenty years (Clarke et al. Lancet, 2005).
In recent years, a growing interest in accelerated partial breast irradiation (APBI) has emerged.
Potential advantages of APBI include increased convenience with shortened treatment courses, as well as a potential reduction in radiation dose to a portion of the affected breast and other surrounding organs.
However, potential disadvantages of APBI include the possibility for occult disease to be missed during APBI as well as a concern that APBI may be associated with inferior long-term breast cosmesis.
ASTRO has also previously published consensus guidelines regarding selection of appropriate patients for APBI (Smith et al. IJROBP, 2009).
The ASTRO consensus guidelines have stated that suitable patients for APBI include patients who meet the following criteria:
Age ≥ 60 years
Tumor size ≤ 2.0 cm that is unicentric, removed with negative margins > 2mm, Estrogen receptor positive, and without evidence of LVSI
Patients must have no evidence of Lymph node metastases as assessed by Sentinel Lymph Node Biopsy.
APBI is not recommended for patients with DCIS or for patients who have received Neoadjuvant chemotherapy outside of the context of a clinical trial.
Treatment for early-stage breast cancer with APBI is currently under further investigation in a multi-institutional randomized controlled trial, NSABP B-39, which compares WBI to APBI for women with early stage favorable breast cancers.
MRI of the breast has been studied by several groups for the purposes of screening women with high risk of breast cancer, planning potential therapies, and assessing disease response to therapy.
Previously published retrospective data supports the use of MRI in addition to standard imaging (mammogram and ultrasound) in the pre-operative assessment of potential APBI candidates.( Al-Hallaq Cancer 2008)
MRI is not required and its use was not recorded for patients who are enrolled on NSABP B-39. The use of MRI is also not defined within the previously published ASTRO consensus guidelines for the use of APBI.
Therefore the authors undertook a prospective study to further evaluate the utility of MRI in determining candidacy for APBI.
The authors' institutional policy dictates that all women with newly diagnosed breast carcinoma undergo pre-operative bilateral breast MRI (1.5 Tesla) in addition to mammogram and/or ultrasound.
All outside imaging was either repeated or reviewed at by a breast radiologist at the authors' institution.
Beginning in June of 2009, all imaging and surgical pathology were reviewed in a multidisciplinary setting by radiologists, surgeons, pathologists and radiation oncologists in order to determine candidacy for APBI according to the entry criteria of the NSABP B-39 .
All patients were initially prospectively screened for potential APBI based on ASTRO consensus guidelines, without the use of MRI data.
In patients eligible for APBI, the authors then prospectively documented whether MRI identified additional lesions in the same quadrant (multifocal), different quadrant (multicentric), or contralateral breast.
Suspicious findings on MRI were biopsied in order to confirm pathology.
The authors then recorded whether MRI findings prompted a change in the eligibility for APBI.
Prospectively collected data was verified by retrospective review of all patient records.
Univariate analysis was performed to examine clinical factors associated with MRI identification of additional disease.
Between June 2009 through October 2010, 486 cases were screened in a multidisciplinary conference for potential APBI.
Characteristics of the Study Cohort
The median age was 56 (range, 26-86).
Median tumor size of index lesion was 1.3 cm (Range 0.5 cm – 3.0 cm)
Amongst eligible patients:
71% had invasive ductal carcinoma
20% had ductal carcinoma in situ
9% had invasive lobular carcinoma
91 patients (18.7 %) were then deemed eligible for APBI based on mammogram, ultrasound, and pathology data alone.
Patients eligible for APBI were then stratified by ASTRO Risk Criteria:
11% were categorized as having Suitable Risk
53.8% were categorized as Cautionary Risk
35.1% were categorized as Unsuitable Risk
Among the 91 eligible patients, MRI indentified additional suspicious lesions in 32 patients (35.1%).
8 of these patients were felt to require no further work-up after additional imaging with ultrasound or mammogram
24 of these patients were felt to require biopsy with a total of 27 distinct suspicious lesions identified.
Pathology from 10/27 (37%) lesions biopsied demonstrated malignancy in 10 total patients.
The false-positive rate of MRI was 63%, and the positive predictive value was 33.3%.
Thus a total of 10/91 patients (11.0 %) were found to have additional foci of disease identified by MRI rendering them ineligible for APBI.
Multifocal disease was found in 9/91 patients (9.9%)
Contralateral disease was confirmed in 1 of 91 (1.1%).
Univariate analysis found that pre-menopausal status (25% vs. 7.1%, p = 0.03), age < 50 (23.1% vs. 6.2 %, p = 0.02), clinical tumor size ≥ 2 cm (25% vs. 7.5%), and lobular histology (28.6% vs. 10%, p= 0.12) were all associated with greater likelihood of MRI identification of additional disease.
These prospective results appear consistent with previous retrospective findings that MRI identifies additional disease in a clinically significant percentage of patients.
MRI identified additional suspicious lesions in approximately 1 in 3 patients, prompted a biopsy in approximately 1 in 4 patients, and resulted in a change in eligibility for APBI in approximately 1 in 10 patients.
Treatment of these patients with limited radiation fields would result in under-treatment of the tumor and could potentially compromise disease control.
MRI may be more likely to identify additional disease in patients with pre-menopausal status, age < 50, tumor size ≥ 2 cm, and potentially lobular histology.
The impact of MRI on disease outcomes for these patients remains unknown. It is unclear if the additional lesions identified would have been excised or included within PTV margins of PBI treatment.
MRI should be increasingly considered as part of the standard work-up for women who are otherwise candidates for APBI.
MRI may help refine criteria for selecting patients for PBI especially those with high risk features.
APBI is a new treatment technique after breast conserving surgery that currently remains under investigation, and may ultimately provide a more convenient treatment option for carefully selected patients compared to traditional WBI.
One of the potential major problems with APBI is that there is a possibility for occult foci of disease to go untreated using this treatment technique.
The addition of MRI to the pre-treatment work-up for potential APBI candidates may help to identify patients with additional foci of disease that is otherwise not identified using other imaging techniques such as ultrasound or mammography.
This study was a well conducted prospective analysis examining the use of MRI as a tool to help select appropriate patients for APBI.
The authors found that the use of MRI identified 11.0 % of patients who had additional foci of disease that was previously unknown, making those patients ineligible for APBI.
Thus the use of MRI identified a substantial number of patients who were inappropriate for APBI.
A limitation of the study findings is the high false positive rate of MRI (63%) which led to additional negative biopsies in a considerable number of patients.
Should MRI become part of the standard work-up of APBI candidates, the potential convenience of APBI may be counterbalanced by the need for additional biopsies and the toxicities and resultant anxieties associated with additional tests.
Further analyses and follow-up from these results may help to elucidate whether the use of MRI in selection of patients for APBI results in a meaningful improvement in clinical outcomes.