Intraoperative radiotherapy of the breast - really a valide option or “only” comfortable

Intraoperative radiotherapy (IORT) of the breast is an innovative treatment option for early breast cancer and has rapidly entered clinical practice in the last years. There are several indications using a breast IORT. Generally accepted because of excellent long-term results is the intraoperative tumorbed boost followed by an external whole breast irradiation (WBI) (1,2). Considering that most in-breast tumor recurrences are seen in or near to the initial tumor site (3-7) partial breast irradiation (PBI) as the sole radiotherapy treatment modality is of large interest. Different PBI techniques, such as an IORT with electrons or 50 kV X-rays (Intrabeam^©), the interstitial multicatheter or balloncatheter (Mammosite^©) brachytherapy or also the 3D conformal external beam radiotherapy are in clinical use [overview in (8,9)], whereby no superiority could be shown for one of them.

However, up to now no data of randomized clinical trials with an adequate follow-up comparing the PBI with the standard WBI are available. First results of the TARGIT-trial, published by Vaidya et al., reporting an equal local relapse rate using either WBI or IORT et al. seems to be promising (10). But because of the short follow-up of 24.6 months the data must be interpreted as preliminary. Definitively, a valid statement concerning the local tumor control after PBI can at earliest given after a follow-up of 10 years, especially because of the more subsequent appearances of recurrences elsewhere in the breast compared to tumorbed recurrences (11,12).

One of the most frequently mentioned arguments preferring the breast IORT is the shortening of the total radiation treatment time by one to two weeks performing an IORT boost or to one day performing a PBI contributing to the patient comfort. Among this the assessment of radiation-related quality-of-life (QoL) aspects plays an important role. Welzel et al. (13) evaluated this issue based on a single-center subgroup of 87 patients enrolled into the randomized trial TARGIT-A (10). Furthermore, the results were compared to two control groups outside the TARGIT-A trial.

The patients of the TARGIT-A trial treated with IORT alone had significantly fewer breast symptoms and a trend to less general pain and arm symptoms compared to patients receiving IORT and WBI. Furthermore, patients treated with IORT alone showed a significantly better radiation-related QoL than those treated with external beam radiotherapy as assessed by restrictions in daily activities, general pain, breast and arm symptoms. No relevant differences could be observed between TARGIT-patients receiving IORT and EBRT and (non-randomized) patients receiving an IORT-boost or percutaneous boost.

One main limitation of the study was mentioned by the authors themself. The data were collected based on patients participating in a randomized trial but the analysis itself was performed cross-sectional designed. Therefore, the results do not allow conclusions regarding causality but they can strongly advert to aspects associated with self-reported QoL. Another problem is, analogously to the tumor control data published by Vaidya et al. (10), the short follow-up of 32 months. It is known, that the development of side effects associated with breast irradiation like fibrosis is an ongoing process and continues beyond 3 years (14-16).

It should be noted that, because of the different physical characteristics and especially the minor dose homogeneity of the Intrabeam-system (17) the data are only applicable to the Linac-based IORT with electrons of limited extend.

Concluding, comparing different treatment techniques for breast irradiation the “IORT alone” approach seems to be superior according to QoL aspects. The data published by Welzel et al. are very interesting and will enforce the discussion around the PBI.

Acknowledgements

Disclosure: The author declares no conflict of interest.

References

1. Sedlmayer F, Fastner G, Merz F, et al. IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: results of an ISIORT pooled analysis. Strahlenther Onkol 2007;183:32-4. [PubMed]
2. Wenz F, Welzel G, Blank E, et al. Intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage X-rays: the first 5 years of experience with a novel approach. Int J Radiat Oncol Biol Phys 2010;77:1309-14. [PubMed]
3. Bartelink H, Horiot JC, Poortmans P, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med 2001;345:1378-87. [PubMed]
4. Clarke DH, Lê MG, Sarrazin D, et al. Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: experience of the Institut Gustave-Roussy. Int J Radiat Oncol Biol Phys 1985;11:137-45. [PubMed]
5. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233-41. [PubMed]
6. Morrow M. Rational local therapy for breast cancer. N Engl J Med 2002;347:1270-1. [PubMed]
7. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227-32. [PubMed]
8. Njeh CF, Saunders MW, Langton CM. Accelerated Partial Breast Irradiation (APBI): A review of available techniques. Radiat Oncol 2010;5:90. [PubMed]
9. Sauer G, Strnad V, Kurzeder C, et al. Partial breast irradiation after breast-conserving surgery. Strahlenther Onkol 2005;181:1-8. [PubMed]
10. Vaidya JS, Joseph DJ, Tobias JS, et al. Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet 2010;376:91-102. [PubMed]
11. Freedman GM, Anderson PR, Hanlon AL, et al. Pattern of local recurrence after conservative surgery and whole-breast irradiation. Int J Radiat Oncol Biol Phys 2005;61:1328-36. [PubMed]
12. Gujral DM, Sumo G, Owen JR, et al. Ipsilateral breast tumor relapse: local recurrence versus new primary tumor and the effect of whole-breast radiotherapy on the rate of new primaries. Int J Radiat Oncol Biol Phys 2011;79:19-25. [PubMed]
13. Welzel G, Boch A, Sperk E, et al. Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. Radiat Oncol 2013;8:9. [PubMed]
14. Immink JM, Putter H, Bartelink H, et al. Long-term cosmetic changes after breast-conserving treatment of patients with stage I-II breast cancer and included in the EORTC ‘boost versus no boost’ trial. Ann Oncol 2012;23:2591-8. [PubMed]
15. Lemanski C, Azria D, Thezenas S, et al. Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results. Int J Radiat Oncol Biol Phys 2006;64:1410-5. [PubMed]
16. Poortmans PM, Collette L, Horiot JC, et al. Impact of the boost dose of 10 Gy versus 26 Gy in patients with early stage breast cancer after a microscopically incomplete lumpectomy: 10-year results of the randomised EORTC boost trial. Radiother Oncol 2009;90:80-5. [PubMed]
17. Nairz O, Deutschmann H, Kopp M, et al. A dosimetric comparison of IORT techniques in limited-stage breast cancer. Strahlenther Onkol 2006;182:342-8. [PubMed]