Partial breast irradiation: why and how

Introduction

Successful treatment of early breast cancer, with high cure rates and excellent cosmetic results, is a reality that has been achieved in the past 25 years due in part to the use of post-tumorectomy whole breast radiotherapy [1]. The EORTC randomized trial questioned the need for radiation boost to the post-tumorectomy surgical bed, with an evident age-related local control effect [2]. Furthermore, examination of the topography of breast cancer recurrences after breast conservation, whether or not a radiotherapy treatment component was included, revealed that recurrences developed in the operative area in 90% of cases [1]. These factors have stimulated emerging interest in exploring partial breast irradiation (PBI) in early breast cancer. Intraoperative radiation therapy (IORT) is an appropiate technical alternative to delivering PBI, together with high dose rate brachytherapy and/or external irradiation precision techniques (3DCRT, IMRT).

Method

IORT implies delivery of a high, single dose of radiation to a limited intrasurgical anatomic area. In the case of post-tumorectomy early breast cancer, the target volume is the tumor bed, maintaining a safety margin in depth (thickness of tissue to be treated) and laterally. Dosimetrically, electrons and high dose rate brachytherapy are well suited to these requirements. Intrabeam (soft X-rays at 50 kV), mammosite 3DCRT and IMRT are alternative technologies that have been adopted into clinical radiotherapy practice and have theoretically favourable dose-gradient effects. Target size, normal tissues included in the radiation fields, and operative/treatment time are variables that differ for each individual patient. The optimal PBI dose is under investigation based upon radiobiological dose-effects models. An efficient therapeutic index in IORT trials has been identified, with boost doses in the range 10–12.5 Gy (maximum 15 Gy). For IORT single radiation component, clinical information is scarce [3, 4].

Clínical trials

Limited institutional experience and pilot studies are available in the literature describing results with IORT as a boost, hypofractionated HDRB, or external irradiation. There are two ongoing randomized trials that have been recruiting patients since 2000 using Intrabeam system (active in UK, Europe, USA and Australia) and Novac-7 (electrons; Milan). Both trials are exploring single doses around 20 Gy. In 2005 a multi-institutional randomized trial including PBI HDR brachytherapy was initiated. Selection criteria for inclusion are strict in these trials, and a highly selected group of breast cancer patients with good prognosis are apparently being investigated. An extensive review of clinical research considerations, radiobiological implications, pathology and surgical methodological requirements, physics specifications, and summary of the available literature was recently published after a group expert meeting to define the state of the art and science of PBI, including all available techniques [5].

Discussion

Recent randomized trials have questioned the need for systematic use of whole breast irradiation after lumpectomy in the context of selection by age, tumor size, or tamoxifen treatment [6]. While the data in PBI consolidate and mature, there is solid evidence to support moderation in clinical practice modification. Professor Bartelink [7] has summarized arguments to question the potential contribution of PBI, in particular IORT, to change clínical practice in the treatment of early breast cancer. The most relevant issues to be addressed, for an sceptical or conservative opinion regarding PBI, are as follows:

• 1. The omission of external beam irradiation without validated tools for selection of patients according to biological risk might compromise local control and survival.

• 2. The biological effects (both in tumor control and normal tissue toxicity) of a high single radiation dose, as is used in IORT, or altered fractionation as is used in other PBI techniques trials are speculative, with a significant risk for unpredictable late damage to normal tissue.

• 3. Target volume definition and dosimetric characteristics of the two ongoing randomized clinical trials have major methodological and technical differences, which will make local results uncomparable.

Some additional topics will be introduced for discussion in the presentation, such as influence of PBI in the radiotherapy management of metastatic axia, modification of scales for cosmetic assessment, treatment planning availability, dosimetric disturbances with the use of shielding material, and opportunities for prospective testing of biological predictive factors on tolerance of normal tissues.

The mentioned arguments seem valid and should be influential in the scientific development of PBI for breast cancer. Experts in PBI and precision radiotherapy for human cancer have been particularly meticulous in analyzing local effects and topography of recurrences. If PBI successfully contributes to the treatment of breast cancer, then surgeons and radiation oncologists should be open minded and change their clinical practice. Health authorities should facilitate the appropiate technology to ensure that this particular population breast cancer patients receives quality treatment.