Breast Cancer


(OR 0.740, 95% CI 0.506–1.082; p=0.120) or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278–7.202; p=0.560). APBI therapy resulted in a statistically significantly higher risk for developing local recurrences (pooled OR 2.150, 95% CI 1.396–3.312; p=0.001] and axillary recurrences (pooled OR 3.430, 95% CI 2.058–5.715; p


as discussed above.


Nevertheless, the limited available randomised data (only three eligible trials), the variety of the PBI techniques used, the poor methodological quality of the two included trials29,30 follow-up (five years) in two trials28,30


and the relatively shorter median compared with the median time


needed in order to demonstrate the impact on mortality (seven to eight years)38


are considerable limitations of the meta-analysis.


Recently, the results of the Targeted Intraoperative Radiotherapy (TARGIT-A) trial,32


a large international randomised controlled trial of targeted IORT versus WBRT for breast cancer, were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2010.32


In


this study, 2,232 patients were randomised to receive either intraoperative targeted radiotherapy or whole breast external beam radiotherapy. With targeted radiation technique the surface of the tumour bed typically received 20Gy that attenuated to 5–7Gy at 1cm depth. The study presents data in terms of local recurrences and toxicity with a median follow-up of four years. There were six local recurrences in the IORT group and five in the external beam radiotherapy group, with no difference between the two arms. In terms of frequency of complications and major toxicities, no differences were observed between the two arms, while radiotherapy-related toxicities were significantly lower in targeted radiotherapy arm. This study represents the largest randomised trial on this topic and provides additional randomised evidence about the safety of PBI and the potential benefits from the use of this technique in women with early breast cancer.


Data from these trials are expected to provide level I evidence about the application of PBI in clinical practice.


1. Veronesi U, et al., N Engl J Med, 2002;16:1227–32. 2. Fisher B, et al., N Engl J Med, 2002;347:1233–41. 3. Bartelink H, et al., N Engl J Med, 2001;345:1378–87. 4. Kurtz JM, et al., Cancer, 1989;63:1912–17. 5. Malmstrom P, et al., Eur J Cancer, 2003;39:1690–97. 6. Veronesi U, et al., Ann Oncol, 2001;12:997–1003. 7. Clark RM, et al., J Natl Cancer Inst, 1996;88:1659–64. 8. Fisher ER, et al., Semin Surg Oncol, 1992;8:161–6. 9. Vicini FA, et al., Int J Radiat Oncol Biol Phys, 2004;60:722–30. 10. Fowble B, et al., Int J Radiat Oncol Biol Phys, 1990;19:833–42. 11. Athas WF, et al., J Natl Cancer Inst, 2000;92:269–71. 12. Nattinger AB, J Natl Cancer Inst, 2001;93:1344–6. 13. Lazovich DA, JAMA, 1991;266:3433–8. 14. Mikeljevic JS, et al., Br J Cancer, 2004;90:1343–8. 15. Sher DJ, et al., Int J Radiat Oncology Biol Phys, 2009;74:440–46. 16. Smith BD, et al., Int J Radiat Oncol Biol Phys, 2009;74: 987–1001.


17. Sauer R, et al., Cancer, 2007;110:1187–94. 18. Dickler A, et al., Brachytherapy, 2007;6:164–8. 19. Bovi J, et al., Radiother Oncol, 2007;84:226–32. 20. Weed DW, et al., Brachytherapy, 2005;4:121-129


Currently, six ongoing phase III randomised trials in the US and Europe are testing APBI (with all available techniques) against WBRT after BCS.39–44


Concerns Regarding Partial Breast Irradiation Besides the above-mentioned theoretical advantages of APBI, there are also data from studies that raise concerns in terms of the rationale for this new technology. The data from clinical45,46


and histopathological47


studies show that a considerable proportion of local recurrences after BCS occurred away from the primary tumour. Several studies have attempted to identify the pattern of ipsilateral breast tumour relapse after conservative surgery; however, the results are contradictory and not easily comparable, since the definition of same-site relapse has no generally accepted criteria and the extension of surgery varies. This means that a local recurrence close to the surgical cavity after a quadrantectomy corresponds to breast recurrence elsewhere if a lumpectomy had been performed.48


Another concern is raised from


detailed histopathological analysis of the entire specimen after mastectomy47,49,50


and magnetic resonance imaging51 studies suggesting


that multifocal-same-quadrant or multicentric-other-quadrant foci are relatively common in patients with early-stage breast cancer. The extent of the disease in these patients cannot be encompassed using partial breast irradiation techniques. The clinical significance of multifocal and multicentric foci are uncertain;49


however, the reason these foci did not


reach clinical significance may be that patients who suffer from the first local recurrence, which in the vast majority of cases occurs close to primary tumour, undergo mastectomy before a tumour focus becomes clinically apparent. Finally, evidence suggests that rates of ipsilateral recurrence away from the primary site after BCS and WBRT are lower than new breast cancer in the controlateral cancer.46,52


Even if


radiotherapy seems to increase the development of new primary cancer in the controlateral breast,53


these data suggest that WBRT could have a


protective effect on other areas of the breast. Conclusion


PBI is a new technology that offers potential advantages compared with WBRT. The most valid concern regarding PBI as a new treatment modality in oncology is its oncological safety. Although limited, current randomised evidence supports that this new technology is a safe treatment modality as it does not seem to jeopardise survival compared with standard WBRT. Nevertheless, this radiation-delivering technique is unlikely to replace WBRT as the ‘gold standard’ treatment for all early breast cancer patients. Ongoing large phase III randomised trials will identify the subgroups of patients who will benefit from PBI. Until then, PBI methods remain investigational and should be performed only in patients enrolled in controlled clinical trials. n


21. Perera F, et al., Int J Radiat Oncol Biol Phys, 2005;62:1283–90. 22. Gittleman M, et al., Int J Radiat Oncol Biol Phys, 2003;57: 365–6.


23. Bensaleh S, et al., Acta Oncol, 2008;22:1–8. 24. Benitez PR, et al., Am J Surg, 2007;194:456–62. 25. Veronesi U, et al., Arch Surg, 2003;138:1253–6. 26. Vaidya JS, et al., Lancet Oncol, 2004;5:165–73. 27. Khan AJ, et al., Brachytherapy, 2006;5:183–8. 28. Polgar C, et al., Int J Radiat Oncol Biol Phys, 2004;60:1173–81. 29. Ribeiro GG, et al., Clin Oncol, 1993;5:278–83. 30. Dodwell DJ, et al., Clin Oncol, 2005;17:618–22. 31. Livi L, et al., Int J Radiat Oncol Biol Phys, 2010;77(2):509–15. 32. Vaidya JS, et al., Lancet, 2010;376:91–102. 33. Valachis A, et al., Breast J, 2010;16:245–51. 34. Ribeiro GG, et al., Clin Oncol, 1990;2:27–34. 35. Formenti SC, et al., Int J Radiat Oncol Biol Phys, 2004;60: 493–504.


36. Polgar C, et al., J Surg Oncol, 2002;80:121–8. 37. Lovey K, et al., Int J Radiat Oncol Biol Phys, 2007;69:724–31. 38. Rothenberg BM, et al., Technology Evaluation Center Assessment Program, 2007;22(4).


39. Orecchia R, et al., Breast, 2003;12:483–90. 40. Polgar C, et al., Semin Radiat Oncol, 2005;15:116–22. 41. NSABP B-39, Clin Adv Hematol Oncol, 2006;4:719–21. 42.


OCOG. Ontario Clinical Oncology Group (OCOG), Canadian Institutes of Health Research (CIHR), Canadian Breast Cancer Research Alliance. RAPID: Randomized Trial of Accelerated Partial Breast Irradiation; 2008. Available at: clinicaltrials.gov/ct2/show/NCT00282035.


43. Available at: groups.eortc.be/radio/res/irma/synopsis_ trial_irma1.pdf


44. Coles C, Yarnold J, Clin Oncol (R Coll Radiol), 2006;18:587–90. 45. Smith TE, et al., Int J Radiat Oncol Biol Phys, 2000;48:1281–9. 46. Freedman GM, et al., Int J Radiat Oncol Biol Phys, 2005;61: 1328–36.


47. Holland R, et al., Cancer, 1985;56:979–90. 48. Offersen BV, et al., Radiother Oncol, 2009;90:1–13. 49. Vaidya JS, et al., Br J Cancer, 1996;74:820–24. 50. Faverly DRG, et al., Cancer, 2001;91:647–59. 51. Schnall M, Magn Reson Imaging Clin N Am, 2006;1:379–81. 52. Mannino M, Yarnold J, Radiother Oncol, 2009;91:16–22. 53. Clarke M, et al., Lancet, 2005;366:2087–2106.


20


EUROPEAN ONCOLOGY


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