Accelerated partial breast irradiation: Current controversies, techniques and results.

The main advantage of the sole brachytherapy in the organ conserving treatment of breast cancer is the potential to improve the quality of life for patients. We have now enough clinical data demonstrating comparable long-term data – the same local control rates, survival rates and minimal side effects in comparison with conventional whole breast radiotherapy. Of course, also the quality assurance is critical here – suboptimal quality assurance in the brachytherapy technique and/or target definition leads to unsatisfactory results.
For partial breast irradiation different treatment techniques can be used: 1. Multicatheter system (typically HDR fractionated 8 x 4 Gy or PDR-brachytherapy 50 Gy/0.6 Gy/h), 2. Balloon technique (typically HDR-brachytherapy fractionated 8 x 4 Gy or 10 x 3.4 Gy), 3. Single-fraction intraoperative radiation therapy (IORT) either with IORT dedicated accelerator as in ELIOT Milano Study (single fraction 21 Gy) or with low energy x-ray machine (50 kV single fraction 5 Gy), 4. Partial-breast external beam intensity modulated radiotherapy (IMRT typically fractionated 10 x 3.4 Gy or 5 x 6 Gy). Each technique has advantages and disadvantages.
With the multicatheter system the main advantages are that the tumour parameters (inclusion criteria) are exactly known at the time of implantation, and that the target volume coverage is not limited in form and volume. Further advantages of the multicatheter system are, that it has very good reproducibility and the fact that the treatment planning is simple and reliable. Considered as possible disadvantages are more puncture sites (> 10) and an individually long learning curve. The majority of the published multicatheter system APBI-studies found local control rates between 92.3% and 100% with median follow-up periods between 2 and 6.3 years. Reviewing literature it seems obvious, that acute and late toxicity is clearly related to the prescribed total dose as well as the implant volume, and that in our opinion the implant volume of the reference isodose may exceed 200 ccm only in exceptional cases. As late toxicity of this method often discussed is the incidence of fat necrosis. Some series have reported high incidences by up to 27% of patients with sole multicatheter brachytherapy and significant association with implant volume. Here it is important to stress, that the fat necrosis may not be overestimated. Asymptomatic fat necrosis may be observed in up to 1/3 of irradiated patients indepedently from type of radiation and even without radiation (calcified suture, coarse calcification owing to necrosis) and the need of a surgical intervention is very rare.
With the balloon system the advantages are: a short learning curve treatment planning is simple and reliable in any centre with a HDR remote-afterloader good reproducibility and only one puncture site. The main disadvantages of the balloon system are, that despite some progress the target volume coverage in comparison with the multicatheter system is very limited in form and volume, and that the tumour parameters (inclusion criteria) are not exactly known at the time of implantation. The probability of acute and may be also late toxicity is similar as using multicatheter system and related to the prescribed total dose and to the implant volume. Though with regard to very limited variability of isodose form the risk of side effects can be increased, in particular if the critical distance to the skin in not respected. The incidence of the side effects of balloon system as erythema, catheter site drainage, pain breast, breast edema or seroma between 11% and 57% seems to be higher than using multicatheter system. To compare definitely the late toxicities of both systems is up-to-date not possible, because the incidence of late complications is a function of time and the follow-up data of balloon system are still to short.
Single fraction intraoperative radiation therapy (IORT, single dose 21 Gy) with an IORT dedicated accelerator with different electron energies 3,5,7,9 and 12 MeV and collimators allows good target volume coverage with sufficient dose. Disadvantage is that the tumour parameters are not exactly known at the time of irradiation and that the availability of this expensive system is limited and requires special radiation protected surgery rooms.
Single fraction IORT with 50 kV x-ray machine and single fraction of 5 Gy (Intrabeam) has from our point of view only disadvantages: beside typical disadvantages of IORT – the tumour parameters are not exactly known at the time of irradiation, the dose distribution produced in this low-energy x-ray machine is extremely limited in form and volume and allows only insufficient 5 Gy single fraction in 1 cm tissue depth (with 20 Gy in 1 mm and only 1 Gy in 27 mm). In our opinion this concept is questionably.
Partial-breast external beam intensity modulated radiotherapy (IMRT) has the same advantages as the multicatheter system – the tumour parameters (inclusion criteria) are exactly known at the time of irradiation and the target volume coverage is not limited in form and volume. The problem is of course the daily patient/breast fixation, in comparison to brachytherapy techniques high integral dose in the neighbourhood of the target volume and only limited experiences are available up to now.

Conclusion:

1. Up to now it is not possible to say which method is the best. The multicatheter system, PBI-IMRT and IORT with dedicated accelerator are very flexible and make it possible to cover any form of target, but the balloon system is easy to handle. For IORT with 50 kV x-ray machine only feasibility results are available and the concept with Dref=5 Gy is questionable.
   
2. All methods have similar acute side effects.
   
3. The differences are due to the probability of (serious) late side effects and in the need of skill and experience.
   
4. To date the long term result are available only for the multicatheter system – excellent local control, minimal side effects, excellent cosmesis.
   
5. Only the results of the Phase III studies will give us an answer, which system will be the best.