Partial Breast Irradiation as an Alternative to Whole Breast Radiation


Partial Breast Irradiation Techniques PBI can be carried out with four principally different techniques: interstitial brachytherapy with multiple catheters, intracavitary brachytherapy (Mammosite system, Cytyc, Marlborough, MA), intraoperative radiotherapy and external 3D conformal radiotherapy. Each of these techniques has unique advantages and limitations and is in a different stage of development and acceptance.


Interstitial brachytherapy with catheters is the PBI technique with the longest reported period of follow-up.16


In this approach, catheters are


placed at 1–1.5cm intervals through the breast tissue surrounding the lumpectomy cavity. The number of catheters is determined by the shape and the size of the target. Interstitial brachytherapy has been used with all possible dose rates, including low- and high-dose rates. This technique permits individual conformation of the irradiated volume precisely adapted to the anatomical conditions.17


approach results in significant heterogeneity of dose delivered,18–20 target coverage might be inferior to other PBI techniques20 dose might be elevated.21


trial. A meta-analysis33 of three completed randomised studies28–30


been recently published while the fourth study32 completion of the meta-analysis and was not included.


has was presented after the


The earliest phase III randomised trial on APBI was conducted from 1982 to 1987 at the Christie Hospital in Manchester.29,34


Overall, 713 patients


However, this the


and the skin


Intracavitary brachytherapy (MammoSite) has been developed to be a less operator-dependent procedure compared with interstitial brachytherapy. The MammoSite is a balloon catheter, which consists of a double-lumen catheter with an inflatable balloon at the distal tip. The balloon is inserted in the lumpectomy cavity, either during or following breast-conserving treatment, and is then filled with saline and contrast material such that the surrounding tissue is stretched tightly around it. Treatment is delivered immediately in the lumpectomy cavity using a high-dose source, which is inserted into the centre of the balloon. The method is simple, with a short learning curve.22


Conversely, the


Moreover, catheters can be a source of discomfort and potentially promote bleeding, infections and late damage such as fibrosis and telangiectasia.


Additionally, the distance between the balloon and the skin appears to be the most important factor for achieving optimal cosmetic results.23,24


Intraoperative radiotherapy (IORT) consists of single-fraction treatment targeted at the tumour bed during the surgical procedure, immediately after the removal of the tumour mass. Two modalities of IORT have been described using either electron, as developed in Milan,25


or photon


beams (based on ‘soft’ X-rays of 50kV) developed by the University College of London.26


As this irradiation is performed during the same


surgical procedure, there is no need for future hospitalisation and transportation of patients. Moreover, the application of a high-dose precisely targeted to a limited volume can be performed while sparing the surrounding tissues.17


The major flaw of this technique is the lack of


definite pathological data regarding resection margins, histological features and axillary nodal status at the time of radiation therapy.


A recent consensus statement from the American Society for Radiation Oncology (ASTRO) concluded that there are insufficient clinical and dosimetric data to determine the optimal technique for APBI delivery.16


Current Randomised Evidence


To date, five randomised trials have been published comparing PBI and WBRT in patients with early breast cancer. Four of them28–30,32


reported


data on locoregional recurrences and overall survival, while the fifth study31


EUROPEAN ONCOLOGY was a preliminary acute toxicity analysis of an ongoing randomised


A preliminary analysis of an Italian study including 259 patients who were randomised to receive either WBRT or APBI demonstrated that APBI has a very low acute skin toxicity.31


A meta-analysis of the three above-mentioned phase III randomised controlled studies comparing partial breast irradiation with whole breast-radiation therapy was recently presented.33


A total of 1,140


patients were included: 575 were randomised to whole breast irradiation and 565 to limited-field or PBI. The meta-analysis revealed no statistically significant difference between the partial and whole breast radiation arms associated with death (odds ratio [OR] 0.912, 95% confidence interval [CI] 0.674–1.234; p=0.550), distant metastasis


19


limitations of the technique are that the target volume is standardised without allowing individual conformation and the therapeutic range is only 10mm.17


with breast tumours less than 4cm and negative lymph nodes were randomised, after BCS, to receive either WBRT (40Gy in 15 fractions in 21 days) or limited field irradiation only to the tumour bed (40–42.5Gy in 10 fractions in 10 days). In this study, the limited field irradiation was significantly associated with higher local and regional recurrences, while there were no differences in terms of overall survival and distant metastases between the two treatment arms. These disappointing results should be interpreted with caution due to the old radiation technique used in the study, the poor quality control, the inadequate axillary and systemic management and the incomplete pathological examination.35


In addition, a single field size was used for all patients in the limited-field arm irrespective of the tumour dimensions or other characteristics, which could have resulted in several instances of ‘geographical miss’. The lack of appropriate patient selection criteria was highlighted when the results were analysed according to the type of primary tumour and it was found that limited-field radiotherapy was inadequate only for patients with infiltrating lobular cancers or cancers with an extensive intra-ductal component.


The second study was performed during 1986–1990 by the Yorkshire Breast Cancer Group.30


In this study, 174 patients, irrespective of nodal


status, were randomised to receive either WBRT or irradiation only in the tumour bed. In this study, a higher risk of locoregional recurrences was demonstrated. However, there were uncertainties on target-volume definition, the irradiation technology used was inadequate, more patients in the tumour-bed-only irradiation arm had axillary node positive disease and the study did not reach its target on participants due to a low accrual rate.


The first well-designed randomised phase III trial was performed by the National Institute of Oncology in Hungary.28,36,37


In this study, 258 patients


with T1, N0–1mi, grade 1–2, non-lobular breast cancer undergoing BCS were randomised to either WBRT or APBI (high-dose-rate interstitial brachytherapy or limited-field electron-beam radiotherapy). At the median follow-up of 60 months there were no significant differences in locoregional recurrences or overall survival. Regarding toxicity, there were no significant differences between the two treatment arms in terms of incidence of fat necrosis and late radiation side effects.37 WBRT.37


Patients with APBI had a better cosmetic result compared with


The Hungarian study is the only randomised trial that analysed the cosmetic results and the late side-effects of APBI.


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