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Five year outcomes of hypofractionated simultaneous integrated boost irradiation in breast conserving therapy; patterns of recurrence
benefit of PMRT or RNI. In this study, patients undergo breast-conserving surgery or mastectomy with sentinel node biopsy after neoadjuvant systemic therapy. Those with sentinel node-negative disease are randomized to receive PMRT or no PMRT (or RNI vs no RNI in the setting of breast conservation), and those with sentinel node-positive disease are randomized to receive PMRT (or RNI in the setting of breast conservation) or PMRT (or RNI in the setting of breast conservation) plus completion axillary dissection. Enrollment in these clinical trials should be strongly considered for all patients who fit these criteria, and in
time, if these important trials are able to accrue well, we will have critically needed randomized data to guide us in decisions regarding PMRT in this setting.
Five year outcomes of hypofractionated simultaneous integrated boost irradiation in breast conserving therapy; patterns of recurrence
fractionation schedule for breastconserving therapy in patients with breast cancer. With modern, sophisticated treatment planning software, an SIB can now easily be planned. In the past, concern would have been expressed with regard to safety in terms of cosmetic outcomes (breast fibrosis, shrinkage, edema, and telangiectasia) with the 2.3 Gy per fraction used in the SIB in this study. However, 2 randomized studies (a Canadian1 trial and the UK Standardisation of Breast Radiotherapy [START] Trial B2) comparing hypofractionated whole-breast radiotherapy (delivering 2.65 Gy/fraction and 2.67 Gy/fraction, respectively, to the whole breast) with standard-fractionation whole-breast radiotherapy (2 Gy/fraction) have reported 10-year outcomes suggesting that cosmesis after hypofractionated whole-breast irradiation is at least as good as that after whole-breast irradiation with standard fractionation. The SIB boost study presents a 5-year
Bantema-Joppe EJ, Vredeveld EJ, de Bock GH, et al (Univ of Groningen, The Netherlands) Radiother Oncol 108:269-272, 2013
In 2005, we introduced hypofractionated 3-dimensional conformal radiotherapy with a simultaneous integrated boost (3D-CRT-SIB) technique after breast conserving surgery. In a consecutive series of 752 consecutive female invasive breast cancer patients (stages I-III) the 5-year actuarial rate for local control was 98.9%. This new technique gives excellent 5-year local control. This article by Bantema-Joppe and colleagues presents a thoughtprovoking radiotherapy technique and
J. L. Wright, MD
References 1. McGuire SE, Gonzalez-Angulo AM, Huang EH, et al. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2007;68:1004-1009.
2. Huang EH, Tucker SL, Strom EA, et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol. 2004;22: 4691-4699. 3. Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012;30:3960-3966.
actuarial local control rate of 98.9%. The Canadian study reported a 10year local recurrence rate of 6.2% in the hypofractionated arm, with no boost delivered. The UK START Trial B reported a 3.8% local relapse rate at 10 years in the 40-Gy hypofractionated arm, with 43% of patients receiving a boost. Certainly, the treatment planning with the hypofractionated SIB technique reported by Bantema-Joppe and colleagues is intriguing. But with the publication of the Canadian trial and the UK START Trial B in which whole-breast radiotherapy was completed in 3-4 weeks, the question now is whether a 5.5week (28-fraction) treatment schedule would be indicated in most cases. E. S. Bloom, MD
References 1. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
169
The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up
hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010; 362:513-520. 2. Haviland JS, Owen JR, Dewar JA, et al; START Trialists’ Group.
IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: Long term results of an ISIORT pooled analysis Fastner G, Sedlmayer F, Merz F, et al (Paracelsus Med Univ, Salzburg, Austria; et al) Radiother Oncol 108:279-286, 2013
Purpose.dLinac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy. Material and Methods.dUntil 10/ 2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10 Gy was applied (90% reference isodose), preceding WBI with 50e54 Gy (single doses 1.7e2 Gy). Results.dAt a median follow up of 72.4 months (0.8e239), only 16 inbreast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5e 151 months after primary treatment. In multivariate analysis only grade 3
170
reached significance (p ¼ 0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients <40 years; 40e 49 years; 50e59 years and $60 years, respectively. Conclusion.dIn all risk subgroups, a 10 Gy IOERT boost prior to WBI provided outstanding local control rates, comparing favourably to all trials with similar length of follow up. The use of an additional dose of radiation to the lumpectomy bed in patients with invasive breast cancer receiving BCT followed by WBI has been shown in several prospective randomized trials1,2 to further reduce the risk of ipsilateral breast tumor recurrence (IBTR). In parallel, contemporary treatment (including systemic therapy), surgical techniques, and attention to surgical margins have translated into improvements in locoregional control over time.3 In keeping with this trend, Fastner and colleagues reported that the use of high-dose IOERT to the tumor bed in patients receiving contemporary treatment resulted in a very low risk of locoregional recurrence. With all-time low rates of IBTR now being reported, the parameters associated with IBTR and, secondarily, cosmesis and cost of care continue to be refined. A recent consensus guideline4 from the Society of Surgical Oncology and the American Society for Radiation Oncology for patients
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
results of two randomised controlled trials. Lancet Oncol. 2013;14:1086-1094.
with stage I or II invasive breast cancer receiving BCT and WBI reported that cumulative data supported the definition of an adequate margin as “no ink on tumor.” Adherence to this definition should reduce the number of patients requiring reexcision and thereby reduce cost and potentially improve long-term cosmesis. Cumulative data also suggest that a radiation boost at standard fractionation does not nullify the increased risk of IBTR associated with a positive margin.4 An intraoperative single-fraction boost is interesting in this context because it has the advantage of decreasing geographic misses that may occur after wound closure, thus increasing convenience, reducing cost, and theoretically increasing the biological effect in eliminating microscopic residual disease.5 However, persistent questions surrounding this approach remain unanswered. Does the delivery of a single high dose of radiation, as with stereotactic body radiation therapy, result in better local control than a boost delivered with standard fractionation, as suggested by this study? Recent data suggest an a/b ratio for breast cancer in the range of 3.8-4.6 Gy.6,7 Several single-institution studies of boosts delivered in 1 high-dose fraction either with intraoperative electrons or brachytherapy suggest results comparable to historical outcomes from boosts delivered with fractionated external beam radiation therapy5,8; however, prospective randomized data
time, if these important trials are able to accrue well, we will have critically needed randomized data to guide us in decisions regarding PMRT in this setting.
Five year outcomes of hypofractionated simultaneous integrated boost irradiation in breast conserving therapy; patterns of recurrence
fractionation schedule for breastconserving therapy in patients with breast cancer. With modern, sophisticated treatment planning software, an SIB can now easily be planned. In the past, concern would have been expressed with regard to safety in terms of cosmetic outcomes (breast fibrosis, shrinkage, edema, and telangiectasia) with the 2.3 Gy per fraction used in the SIB in this study. However, 2 randomized studies (a Canadian1 trial and the UK Standardisation of Breast Radiotherapy [START] Trial B2) comparing hypofractionated whole-breast radiotherapy (delivering 2.65 Gy/fraction and 2.67 Gy/fraction, respectively, to the whole breast) with standard-fractionation whole-breast radiotherapy (2 Gy/fraction) have reported 10-year outcomes suggesting that cosmesis after hypofractionated whole-breast irradiation is at least as good as that after whole-breast irradiation with standard fractionation. The SIB boost study presents a 5-year
Bantema-Joppe EJ, Vredeveld EJ, de Bock GH, et al (Univ of Groningen, The Netherlands) Radiother Oncol 108:269-272, 2013
In 2005, we introduced hypofractionated 3-dimensional conformal radiotherapy with a simultaneous integrated boost (3D-CRT-SIB) technique after breast conserving surgery. In a consecutive series of 752 consecutive female invasive breast cancer patients (stages I-III) the 5-year actuarial rate for local control was 98.9%. This new technique gives excellent 5-year local control. This article by Bantema-Joppe and colleagues presents a thoughtprovoking radiotherapy technique and
J. L. Wright, MD
References 1. McGuire SE, Gonzalez-Angulo AM, Huang EH, et al. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int J Radiat Oncol Biol Phys. 2007;68:1004-1009.
2. Huang EH, Tucker SL, Strom EA, et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol. 2004;22: 4691-4699. 3. Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012;30:3960-3966.
actuarial local control rate of 98.9%. The Canadian study reported a 10year local recurrence rate of 6.2% in the hypofractionated arm, with no boost delivered. The UK START Trial B reported a 3.8% local relapse rate at 10 years in the 40-Gy hypofractionated arm, with 43% of patients receiving a boost. Certainly, the treatment planning with the hypofractionated SIB technique reported by Bantema-Joppe and colleagues is intriguing. But with the publication of the Canadian trial and the UK START Trial B in which whole-breast radiotherapy was completed in 3-4 weeks, the question now is whether a 5.5week (28-fraction) treatment schedule would be indicated in most cases. E. S. Bloom, MD
References 1. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
169
The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up
hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010; 362:513-520. 2. Haviland JS, Owen JR, Dewar JA, et al; START Trialists’ Group.
IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: Long term results of an ISIORT pooled analysis Fastner G, Sedlmayer F, Merz F, et al (Paracelsus Med Univ, Salzburg, Austria; et al) Radiother Oncol 108:279-286, 2013
Purpose.dLinac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy. Material and Methods.dUntil 10/ 2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10 Gy was applied (90% reference isodose), preceding WBI with 50e54 Gy (single doses 1.7e2 Gy). Results.dAt a median follow up of 72.4 months (0.8e239), only 16 inbreast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5e 151 months after primary treatment. In multivariate analysis only grade 3
170
reached significance (p ¼ 0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients <40 years; 40e 49 years; 50e59 years and $60 years, respectively. Conclusion.dIn all risk subgroups, a 10 Gy IOERT boost prior to WBI provided outstanding local control rates, comparing favourably to all trials with similar length of follow up. The use of an additional dose of radiation to the lumpectomy bed in patients with invasive breast cancer receiving BCT followed by WBI has been shown in several prospective randomized trials1,2 to further reduce the risk of ipsilateral breast tumor recurrence (IBTR). In parallel, contemporary treatment (including systemic therapy), surgical techniques, and attention to surgical margins have translated into improvements in locoregional control over time.3 In keeping with this trend, Fastner and colleagues reported that the use of high-dose IOERT to the tumor bed in patients receiving contemporary treatment resulted in a very low risk of locoregional recurrence. With all-time low rates of IBTR now being reported, the parameters associated with IBTR and, secondarily, cosmesis and cost of care continue to be refined. A recent consensus guideline4 from the Society of Surgical Oncology and the American Society for Radiation Oncology for patients
Breast Diseases: A Year BookÒ Quarterly Vol 25 No 2 2014
results of two randomised controlled trials. Lancet Oncol. 2013;14:1086-1094.
with stage I or II invasive breast cancer receiving BCT and WBI reported that cumulative data supported the definition of an adequate margin as “no ink on tumor.” Adherence to this definition should reduce the number of patients requiring reexcision and thereby reduce cost and potentially improve long-term cosmesis. Cumulative data also suggest that a radiation boost at standard fractionation does not nullify the increased risk of IBTR associated with a positive margin.4 An intraoperative single-fraction boost is interesting in this context because it has the advantage of decreasing geographic misses that may occur after wound closure, thus increasing convenience, reducing cost, and theoretically increasing the biological effect in eliminating microscopic residual disease.5 However, persistent questions surrounding this approach remain unanswered. Does the delivery of a single high dose of radiation, as with stereotactic body radiation therapy, result in better local control than a boost delivered with standard fractionation, as suggested by this study? Recent data suggest an a/b ratio for breast cancer in the range of 3.8-4.6 Gy.6,7 Several single-institution studies of boosts delivered in 1 high-dose fraction either with intraoperative electrons or brachytherapy suggest results comparable to historical outcomes from boosts delivered with fractionated external beam radiation therapy5,8; however, prospective randomized data