방사선종양학과 - 혈액종양내과 Joint Conference 경희의료원 방사선종양학과 R4 공 문 규

RT target and fractionation schedule in usual clinical practice –Target: whole breast –Dose fractionation: total 45-50Gy with daily 1.8-2Gy ± tumor bed boost 최근 방사선치료의 큰 흐름은 hypofractionation 인데, breast cancer 에서도 hypofractionation 이 가능할까 ? 대부분의 cancer 는 primary tumor 또는 surgical bed 에 margin 을 추가해서 치료하는데, breast cancer 는 꼭 whole breast 를 치료해야 하나 ?

Introduction Most widely used fractionation regimen in breast cancer RT –Total 45-50Gy with 1.8-2Gy daily fraction ± surgical bed boost New fractionation regimen interested in recent years –Hypofractionation for whole breast irradiation(WBI) –Accelerated partial breast irradiation(APBI)

Hypofractionation for Whole Breast Irradiation

Trials of Hypofractionation Versus Conventional WBI 3 randomized trials that have compared hypofractionation with conventional fractionation for WBI(whole breast irradiation) ⇒ Ontario Clinical Oncology Group(OCOG) trial. J Natl Cancer Inst 2002;94: OCOG trial. N Engl J Med 2010;362: ⇒ UK standardization of breast radiotherapy(START) trial A. Lancet Oncol 2008;9: ⇒ START trial B. Lancet 2008;371:

Rates of pneumonitis, symptomatic lung fibrosis, rib fracture, ischemic heart disease –Very low in all trials –No differences between arms in all trials Trials of Hypofractionation Versus Conventional WBI

Use of Hypofractionation in Clinical Practice Subgroup analyses from OCOG trial –Reported that hypofractionation was less effective for patients with high-grade tumors Haviland et al. N Engl J Med 2010;362:1843 –Meta-analysis performed in response to upper results –Could not find any detrimental effect of hypofractionation for high-grade disease In summary… –It seems reasonable to treat high-grade tumors with hypofractionation

Major consideration in hypofractionation –The treatment of the regional nodes Galecki et al. Acta Oncol 2006;45: Johansson et al. Int J Radiat Oncol Biol Phys 2000;48: Olsen et al. Int J Radiat Oncol Biol Phys 1993;26:43-49 –Reported risk of brachial plexopathy in hypofractionated RT Use of Hypofractionation in Clinical Practice

START A trial –Only 1 case of brachial plexopathy in 41.6Gy group START B trial –No brachial plexopathy In summary… –Maybe relatively safe, but need to wait for more data and longer follow-up before using hypofractionation for regional LNs RT Use of Hypofractionation in Clinical Practice

In conclusion, the results of these studies have confirmed that hypofractionation for WBI(whole breast irradiation) is safe and effective Reasonable regimens for hypofractionation –Total 42.5Gy with daily 2.66Gy over 3 weeks –Total 41.6Gy with daily 3.2Gy over 5 weeks –Total 40Gy with daily 2.67Gy over 3 weeks Use of Hypofractionation in Clinical Practice

Partial-Breast Irradiation

Biological Rationale Vicini et al. Int J Radiat Oncol Biol Phys 2004;60: Ohtake et al. Cancer 1995;76:32-45 Imamura et al. Breast Cancer Res Treat 1985;62: –Provided evidences that the extension of tumor for most patients is limited to within 1cm from the primary lesion

Fisher et al. N Engl J Med 2002;347: Veronesi et al. Ann Oncol 2001;12: Liljegren et al. J Clin Oncol 1999;17: –Lumpectomy + WBI vs lumpectomy only –Reported anatomic location of in-breast failures –“Elsewhere failure” occurred less than 4%, with equal frequency in both group Biological Rationale Lumpectomy cavity 로부터 1cm 이상 벗어난 부위에서 발 생한 recurrence

Hypofractionated Partial-Breast Irradiation Techniques/Data 4 principal methods to deliver APBI (accelerated partial breast irradiation) –Multicatheter interstitial brachytherapy (MIB) –Balloon-based brachytherapy (MammoSite) –External beam RT (EBRT) –Intraoperative radiotherapy (IORT)

1. MIB Technique

There are no large phase Ⅲ randomized trials with long-term follow-up

2. Balloon-Based Brachytherapy (MammoSite)

There are no large phase Ⅲ randomized trials with long-term follow-up

3. External Beam RT (EBRT) Recently, most commonly used technique Target definition –CTV: tumor bed + 1~1.5cm –PTV: CTV + 0.5~1cm Dose prescription –Total dose 38.5Gy with 3.85Gy/fraction twice daily

There are no large phase Ⅲ randomized trials with long-term follow-up

4. Intraoperative Radiotherapy (IORT) Single fraction dose(20Gy) delivered to the lumpectomy site at the time of surgery To protect the thoracic wall, an aluminum-lead disk is placed between breast tissue and pectoralis muscle Not commonly used in these days –Unknown long-term side effects of single high dose radiation –Limited availability

Conclusions

Two important contributions in breast cancer radiotherapy in recent years –Whole breast hypofractionated radiotherapy –Accelerated partial breast irradiation (APBI) Whole breast hypofractionated radiotherapy –All randomized trials shown similar outcomes compared with conventional fractionation Accelerate partial breast irradiation (APBI) –Multiple single- and multi-institutional data have been published good results –Long-term results of large phase Ⅲ trials are still pending

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