Original Article
Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer
N Engl J Med 2010; 362:513-520February 11, 2010
- Abstract
Background
The optimal fractionation schedule for whole-breast irradiation after breast-conserving surgery is unknown.
Methods
We conducted a study to determine whether a hypofractionated 3-week schedule of whole-breast irradiation is as effective as a 5-week schedule. Women with invasive breast cancer who had undergone breast-conserving surgery and in whom resection margins were clear and axillary lymph nodes were negative were randomly assigned to receive whole-breast irradiation either at a standard dose of 50.0 Gy in 25 fractions over a period of 35 days (the control group) or at a dose of 42.5 Gy in 16 fractions over a period of 22 days (the hypofractionated-radiation group).
Results
The risk of local recurrence at 10 years was 6.7% among the 612 women assigned to standard irradiation as compared with 6.2% among the 622 women assigned to the hypofractionated regimen (absolute difference, 0.5 percentage points; 95% confidence interval [CI], −2.5 to 3.5). At 10 years, 71.3% of women in the control group as compared with 69.8% of the women in the hypofractionated-radiation group had a good or excellent cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, −6.9 to 9.8).
Conclusions
Ten years after treatment, accelerated, hypofractionated whole-breast irradiation was not inferior to standard radiation treatment in women who had undergone breast-conserving surgery for invasive breast cancer with clear surgical margins and negative axillary nodes. (ClinicalTrials.gov number, NCT00156052.)
Media in This Article
Figure 1
Outcomes in Patients with Breast Cancer Who Received a Hypofractionated Regimen of Radiation Therapy as Compared with Patients Who Received the Standard Regimen.Figure 2
Hazard Ratios for Ipsilateral Recurrence of Breast Cancer in Subgroups of Patients.Article Activity
- Article
In women with breast cancer who undergo breast-conserving surgery, whole-breast irradiation reduces the risk of local recurrence and can prevent the need for mastectomy.1-4 An update of a meta-analysis conducted by the Early Breast Cancer Trialists' Collaborative Group showed that breast irradiation after breast-conserving surgery reduces mortality from breast cancer.5 However, up to 30% of women in North America who undergo breast-conserving surgery do not undergo breast irradiation, in part because of the inconvenience of the therapy and its cost.6
In the original trials that evaluated whole-breast irradiation after breast-conserving surgery, 50.0 Gy of radiation was commonly given in 25 fractions over a period of 5 weeks in daily fractions of 2.0 Gy.1,2 Radiobiologic models suggest that a larger daily dose (hypofractionation) given over a shorter time (accelerated therapy) might be just as effective7; this regimen may also be more convenient for patients and less resource-intensive than the standard schedule. Low rates of local recurrence and limited radiation-induced morbidity have been reported with such approaches.8-10 Schedules used in these studies ranged from 40.0 to 44.0 Gy given in 15 to 16 fractions over a 3-week period, with daily fractions of 2.5 to 2.7 Gy.
In 2002, we reported the 5-year results of a randomized trial in which whole-breast irradiation at a dose of 50.0 Gy given in 25 fractions over a period of 35 days was compared with accelerated, hypofractionated whole-breast irradiation, at a dose of 42.5 Gy given in 16 fractions over a period of 22 days, after breast-conserving surgery in women with axillary lymph node–negative breast cancer.11 Local recurrence rates were 3% and cosmetic outcomes, which reflect radiation-related morbidity, were similar in both groups. Toxic effects of radiation, in particular toxicity related to large doses per fraction, can increase over time12,13; this raised concerns that inhibited the universal adoption of the hypofractionated approach.14,15 In this article, we describe the results of our trial at a median follow-up of 12 years.
Methods
Patients
Details of the study design have been described elsewhere.11 Briefly, the participants had invasive carcinoma of the breast with negative axillary nodes and were treated by means of breast-conserving surgery and axillary dissection. Exclusion criteria were invasive disease or ductal carcinoma in situ involving the margins of excision, tumors that were larger than 5 cm in diameter, and a breast width of more than 25 cm at the posterior border of the medial and lateral tangential beams, which could increase the heterogeneity of the radiation dose to the breast.
The participating centers were the Cancer Care Ontario cancer centers in Hamilton, Toronto, Ottawa, Sudbury, London, Windsor, Kingston, and Thunder Bay; Princess Margaret Hospital in Toronto; and Montreal General Hospital in Montreal. The study protocol was approved by the institutional review board of each participating center, and all patients provided written informed consent. All authors contributed to the design, data collection, and interpretation of the analysis. All authors vouch for the accuracy and completeness of the reported data.
Treatment Regimens
Randomization was performed centrally through the Ontario Clinical Oncology Group coordinating center in Hamilton, Ontario. Patients were stratified according to age (<50 years or ≥50 years), tumor size (≤2 cm or >2 cm), systematic adjuvant therapy (tamoxifen, any chemotherapy, or no therapy), and center. A computer-generated randomization schedule assigned patients to standard whole-breast irradiation at a dose of 50 Gy given in 25 fractions over a period of 35 days (the control group) or accelerated, hypofractionated whole-breast irradiation at a dose of 42.5 Gy given in 16 fractions over a period of 22 days (the hypofractionated-radiation group). Radiation was delivered by means of two opposed tangential fields, with treatment provided daily from Monday through Friday. No attempt was made to treat the axilla or the supraclavicular or internal mammary nodes, and boost irradiation of the tumor bed was not used.
Follow-up and Outcomes
After completion of radiation therapy, patients were seen every 6 months for 5 years and then yearly. At each visit, a history was taken, and physical examination was performed. If a participant was unable to attend a scheduled follow-up visit, the family doctor was contacted regarding recurrence, new cancer, or death. Mammography was performed 6 months after radiation therapy and then yearly. Late toxic effects of radiation were assessed 3, 5, and 10 years after randomization. Cosmetic outcomes were assessed at baseline and at these same subsequent time points.
The primary outcome was any local recurrence of invasive cancer in the treated breast. Secondary outcomes were a distant (including regional) recurrence of breast cancer; second cancers, including contralateral breast cancer; breast cosmesis; late toxic effects of radiation; and death. The cause of death (cancer, a cardiac-related cause, or another cause) was also evaluated as a possible indicator of radiation-associated morbidity. Two physicians independently adjudicated the cause of death with supporting documentation. If there was disagreement in attribution, a third physician reviewed the case.
Radiation-related toxic effects were assessed by a clinical-trials nurse with the use of the Late Radiation Morbidity Scoring Scheme, developed by the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (EORTC).16 The treatment assignment was not concealed from the clinical-trials nurse. Effects of radiation therapy on skin and subcutaneous tissue were graded on a scale of 0 to 4 (with 0 indicating no toxic effects and grade 4 indicating skin ulceration or soft-tissue necrosis). A trained clinical-trials nurse assessed the cosmetic outcome using the EORTC cosmetic rating system.17 Nurses compared the treated breast with the untreated breast and graded a number of characteristics, including the size and shape of the breast and the location of the areola and nipple, telangiectasia, and the global cosmetic result. Characteristics were graded on a scale of 0 to 3 (with 0 indicating no difference between the treated and untreated breasts or an excellent result and grade 3 indicating a large difference or a poor result). We report only the global cosmetic outcome. Cosmesis and toxic effects were not evaluated after recurrence or a second cancer.
Statistical Analysis
The study was designed to assess the noninferiority of the hypofractionated regimen relative to the standard schedule for radiation therapy. The rate of local recurrence at 5 years in the control group was assumed to be 7%. On the basis of the results of an earlier trial in which the rate of local recurrence at 5 years was 8% with the use of breast irradiation as compared with 30% with no further treatment3 (absolute difference, 22 percentage points; 99% confidence interval [CI], 15 to 29), we accepted a maximum loss of efficacy of 5 percentage points in the hypofractionated-radiation group. This noninferiority margin was determined through consultation with radiation oncologists. The sample size for the trial, 600 patients per group, was based on these assumptions and a power of 80% with a one-sided alpha level of 5%. The first analysis, performed at 69 months, showed relatively low event rates, and a second analysis was planned when all patients had completed a 10-year assessment.
Analysis of the primary end point was performed according to the intention-to-treat principle. The time to local recurrence was defined as the number of days from randomization to local recurrence as a first event. Data were censored at the time of distant recurrence, last contact, or death, whichever occurred first. Overall survival was defined as the time to death from any cause. Rates of local recurrence and overall survival were determined according to the Kaplan–Meier method. The difference in the 10-year local-recurrence rates (the rate in the control group minus the rate in the hypofractionated-radiation group) was calculated with a two-sided 95% confidence interval (a one-sided 97.5% confidence interval) by means of the Greenwood formula. The noninferiority hypothesis was tested with the use of a z-test offset by the noninferiority margin. We used the log-rank test to compare overall survival in the two groups, and we used Cox proportional-hazards models to evaluate the consistency of treatment effects by testing for interactions between the treatment group and subgroups of interest. For the subgroup analysis, tumor size was dichotomized as smaller than 2 cm or 2 cm or larger.
Results of the scales used to measure skin and subcutaneous toxic effects were dichotomized and described as the proportion of patients with no toxic effects versus the proportion with toxic effects of any grade. For cosmesis, we report the percentage of patients with one of four levels of cosmesis, and the results were also dichotomized as the proportion of patients with an excellent or a good result versus the proportion with a fair or poor result. Groups were compared with the use of 95% confidence intervals for the difference between proportions. Repeated-measures logistic-regression models were used to investigate the effect of treatment, time from randomization, and baseline variables on the cosmetic outcome. Results of unplanned and sensitivity analyses and the effect of censoring are included in the Supplementary Appendix, available with the full text of this article at NEJM.org.
Results
Study Participants
Between April 1993 and September 1996, a total of 1234 patients underwent randomization, with 612 assigned to the control group and 622 to the hypofractionated-radiation group. The two groups were similar at baseline: 24.7% of the women were younger than 50 years of age; 31.3% had tumors that were 2 cm or larger in diameter; 26.1% had estrogen-receptor–negative disease and 18.8% had high-grade disease; 41.8% received adjuvant tamoxifen, and 10.9% had received adjuvant systemic therapy, most commonly cyclophosphamide, methotrexate, and fluorouracil. Twenty-one patients (12 in the control group and 9 in the hypofractionated-radiation group) did not receive the specified radiation regimen (1.7%). All 1234 patients were included in the efficacy analysis; 98 (7.9%) were lost to follow-up. For the toxicity analysis, 873 patients were evaluated at 5 years and 455 patients were evaluated at 10 years.
Local Recurrence
Local invasive recurrence of breast cancer was the first event in 83 patients (42 patients in the control group and 41 patients in the hypofractionated-radiation group). The cumulative incidence of local recurrence was similar in the two groups (Figure 1AFigure 1
Outcomes in Patients with Breast Cancer Who Received a Hypofractionated Regimen of Radiation Therapy as Compared with Patients Who Received the Standard Regimen.). At 10 years, the cumulative incidence of local recurrence was 6.7% in the control group as compared with 6.2% in the hypofractionated-radiation group (absolute difference, 0.5 percentage points; 95% CI, −2.5 to 3.5); that is, we have 97.5% confidence that the hypofractionated regimen is no worse than the control regimen by 2.5 percentage points. The test of the null hypothesis that the accelerated regimen would be worse than the standard treatment (by >5 percentage points) was rejected in favor of noninferiority (P<0.001). In addition to the 83 invasive recurrences, there were 13 cases of noninvasive local recurrences (i.e., ductal carcinoma in situ): 6 cases in the control group and 7 in the hypofractionated-radiation group. At 10 years, the cumulative incidence of invasive or noninvasive local recurrence was 7.5% in the control group as compared with 7.4% in the hypofractionated-radiation group (absolute difference, 0.1 percentage points; 95% CI, −3.1 to 3.3). A subgroup analysis showed that the treatment effect was similar regardless of the patient's age, tumor size, estrogen-receptor status, or use or nonuse of systemic therapy (Figure 2Figure 2Hazard Ratios for Ipsilateral Recurrence of Breast Cancer in Subgroups of Patients.). The hypofractionated regimen appeared to be less effective in patients with high-grade tumors; in this subgroup, the cumulative incidence of local recurrence at 10 years was 4.7% in the control group as compared with 15.6% in the hypofractionated-radiation group (absolute difference, −10.9 percentage points, 95% CI, −19.1 to −2.8; test for interaction, P=0.01).Mortality
There were 248 deaths (126 in the control group and 122 in the hypofractionated-radiation group). The probability of survival over time was similar in the two groups (P=0.79) (Figure 1B). At 10 years, the probability of survival was 84.4% in the control group as compared with 84.6% in the hypofractionated-radiation group (absolute difference, −0.2 percentage points; 95% CI, −4.3 to 4.0). In the control group of 612 patients, 82 deaths were related to cancer (13.4%), 9 were related to cardiac disease (1.5%), and 35 were due to other causes (5.7%). In the hypofractionated-radiation group of 622 patients, 82 deaths were related to cancer (13.2%), 12 were related to cardiac disease (1.9%), and 28 were due to other causes (4.5%). No significant differences were detected between the groups (P=0.56).
Toxic Effects of Radiation and Cosmetic Outcome
Table 1Table 1
Late Toxic Effects of Radiation, Assessed According to the RTOG–EORTC Late Radiation Morbidity Scoring Scheme. shows the percentage of patients with toxic effects of irradiation of the skin and subcutaneous tissue 5 and 10 years after randomization. Neither grade 4 skin ulceration nor soft-tissue necrosis was observed. Although the incidence of late toxic effects of radiation did increase over the follow-up period, at 10 years, the proportion of women with grade 3 radiation-associated morbidity was 4% or less. At 10 years, there were no skin toxic effects in 70.5% of women in the control group as compared with 66.8% of women in the hypofractionated-radiation group (absolute difference, 3.7 percentage points; 95% CI, −4.9 to 12.1). There were no toxic effects in subcutaneous tissue in 45.3% of women in the control group as compared with 48.1% of women in the hypofractionated-radiation group (absolute difference, −2.8 percentage points; 95% CI, −11.7 to 6.5).Table 2Table 2
Global Cosmetic Outcome, Assessed According to the EORTC Scale. shows the cosmetic outcome at baseline, 5 years, and 10 years. Although the global cosmetic outcome worsened over time, no significant differences were observed between the groups at any time. At 10 years, 71.3% of women in the control group as compared with 69.8% of women in the hypofractionated-radiation group, had an excellent or good cosmetic outcome (absolute difference, 1.5 percentage points; 95% CI, −6.9 to 9.8). The repeated-measures logistic-regression analysis suggested that the cosmetic outcome was affected by the time from randomization as well as by the patient's age and tumor size, but there was no interaction with treatment (Table 3Table 3
Predictors of an Excellent or Good EORTC Global Cosmetic Rating.).Discussion
Our goal was to determine whether whole-breast irradiation after breast-conserving surgery could be safe and effective when administered in a larger dose per fraction and in a shorter period of time than in the standard schedule. The 5-year results of our trial reported previously showed no significant differences in efficacy or toxicity between the radiation regimens.11 Nevertheless, because radiation-related microvascular damage increases over time, there was concern that late toxic effects of radiation associated with the hypofractionated regimen could develop.14,18
At a median follow-up of 12 years, the risk of local recurrence at 10 years was low in both groups, and the results with the hypofractionated regimen were not inferior to the results with standard, longer treatment. In an exploratory subgroup analysis, hypofractionation appeared to be less effective for high-grade tumors than for lower-grade tumors. The result of this analysis could be a chance finding, but it may instead reflect a different inherent radiation sensitivity of high-grade tumors or biologic subtypes of breast cancer that are associated with high-grade tumors.19
In the long term, radiation therapy may cause skin telangiectasia and fibrosis of subcutaneous tissue, leading to loss of volume and retraction of the breast, all of which can adversely affect the cosmetic outcome. We did see a worsening of the cosmetic outcome over time, which coincided with the increase in toxic effects of irradiation of the skin and subcutaneous tissue. However, we saw no increase in toxic effects in women who received accelerated, hypofractionated radiation therapy as compared with those who received the standard regimen. Although older age and large tumor size were associated with a worse cosmetic outcome, the outcomes of the hypofractionated regimen were similar to those of the standard regimen.
Whole-breast irradiation, particularly on the left side, has been associated with a slightly increased risk of death attributable to coronary artery disease.20 This late effect is not usual until 10 years or more after radiation therapy. In our trial, we observed no significant difference in overall survival between the two treatment groups, and at a median follow-up of 12 years, few cardiac-related deaths were observed and no increase occurred in patients who received the hypofractionated regimen.
Recently, 5-year results were reported from two trials: the UK Standardisation of Breast Radiotherapy (START) Trial A, which compared each of two schedules of hypofractionation given over 5 weeks with conventional whole-breast irradiation, and START Trial B, which compared a hypofractionation schedule given over 3 weeks with conventional treatment (Current Controlled Trials number for both trials, ISRCTN59368779).21,22 Although both trials had limited follow-up, the results were consistent with those of our trial.
The potential limitations of our study should be noted. The trial was restricted to women who had node-negative, invasive breast cancer with clear margins of excision after lumpectomy. Although we did include patients with microinvasive breast cancer and women in whom a component of the breast cancer was ductal carcinoma in situ, it is not entirely clear whether our results can be extrapolated to women with ductal carcinoma in situ only. We did not include women with node-positive breast cancer, and for this reason our results are not applicable to patients for whom nodal irradiation is planned. Women with large breasts were also not included, and few women received adjuvant chemotherapy. Such patients can be at increased risk for an adverse cosmetic outcome with standard radiotherapy, so it is unclear whether hypofractionation would lead to an outcome that would be any worse than that with standard treatment. We did not use boost irradiation, because at the time the study was initiated, the efficacy of boost irradiation had not been demonstrated and we wanted to avoid the confounding effect that boost irradiation could have on local recurrence or breast cosmesis. Since the completion of our trial, the results of other trials, providing support for the use of boost irradiation, have been published.23,24 Boost irradiation was permitted in both START trials, and adjuvant chemotherapy was used more widely than in our trial. To date, no increase in toxic effects in these trials has been reported.
In conclusion, our long-term results provide support for the use of accelerated, hypofractionated, whole-breast irradiation in selected women with node-negative breast cancer after breast-conserving surgery. For women with breast cancer who are similar to the patients in this trial, an abbreviated course of radiation therapy should be more convenient and less costly than standard treatment, and its availability as a treatment option may lead to an increase in the number of women who receive breast irradiation after breast-conserving surgery.
Supported by grants from the Canadian Breast Cancer Research Alliance and the Canadian Cancer Society (through the National Cancer Institute of Canada).
Financial and other disclosures provided by the authors are available with the full text of this article at NEJM.org.
Source Information
From McMaster University and Juravinski Cancer Centre, Hamilton, ON (T.J.W., M.N.L., J.A.J., S.P., H.L.); Odette Cancer Centre (J-P.P., R.M.) and Princess Margaret Hospital (A.F.) — both in Toronto; Cancer Centre of Southeastern Ontario, Kingston (W.S.); Ottawa Regional Cancer Centre, Ottawa (L.G.); Northeastern Regional Cancer Centre, Sudbury, ON (J.B.); London Regional Cancer Centre, London, ON (F.P.); Windsor Regional Cancer Centre, Windsor, ON (K.S.); Northwestern Regional Cancer Centre, Thunder Bay, ON (S.G.); and McGill University and Montreal General Hospital, Montreal (C.F.) — all in Canada.
Address reprint requests to Dr. Whelan at the Juravinski Cancer Centre, 699 Concession St., Hamilton, ON L8V 5C2, Canada, or at tim.whelan@jcc.hhsc.ca.
- References
References
1
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;347:1233-1241
Full Text | Web of Science | Medline2
Veronesi U ,Luini A ,Del Vecchio M , et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med 1993;328:1587-1591
Full Text | Web of Science | Medline3
Clark RM ,Whelan T ,Levine M , et al. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. J Natl Cancer Inst 1996;88:1659-1664
CrossRef | Web of Science | Medline4
Forrest AP ,Stewart HJ ,Everington D , et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet 1996;348:708-713
CrossRef | Web of Science | Medline5
Clarke M ,Collins R ,Darby S , et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366:2087-2106
Web of Science | Medline6
Virnig B ,Habermann E ,Al-Raie W , et al. Increased use of breast-conserving surgery: preferred treatment or failure to provide adequate local therapy? Breast Cancer Res Treat 2007;106:Suppl 1:S188-S188
Web of Science7
Fowler JF . The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989;62:679-694
CrossRef | Web of Science | Medline8
Ash DV ,Benson EA ,Sainsbury JR ,Round C ,Head C . Seven-year follow-up on 334 patients treated by breast conserving surgery and short course radical postoperative radiotherapy: a report of the Yorkshire Breast Cancer Group. Clin Oncol (R Coll Radiol) 1995;7:93-96
CrossRef | Medline9
Olivotto IA ,Weir LM ,Kim-Sing C , et al. Late cosmetic results of short fractionation for breast conservation. Radiother Oncol 1996;41:7-13
Web of Science | Medline10
Shelley W ,Brundage M ,Hayter C ,Paszat L ,Zhou S ,Mackillop W . A shorter fractionation schedule for postlumpectomy breast cancer patients. Int J Radiat Oncol Biol Phys 2000;47:1219-1228
CrossRef | Web of Science | Medline11
Whelan T ,MacKenzie R ,Julian J , et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 2002;94:1143-1150
CrossRef | Web of Science | Medline12
Curran D ,van Dongen JP ,Aaronson NK , et al. Quality of life of early-stage breast cancer patients treated with radical mastectomy or breast-conserving procedures: results of EORTC trial 10801. Eur J Cancer 1998;34:307-314
CrossRef | Web of Science | Medline13
Powell S ,Cooke J ,Parsons C . Radiation-induced brachial plexus injury: follow-up of two different fractionation schedules. Radiother Oncol 1990;18:213-220
CrossRef | Web of Science | Medline14
Harris J . Notes on the Ontario Trial in the context of breast-conserving therapy for early-stage breast cancer. J Clin Oncol 2000;18:Suppl:43S-44S
Web of Science | Medline15
Sartor CI ,Tepper JE . Is less more? Lessons in radiation schedules in breast cancer. J Natl Cancer Inst 2002;94:1114-1115
CrossRef | Web of Science | Medline16
Winchester DP ,Cox JD . Standards for breast-conservation treatment. CA Cancer J Clin 1992;42:134-162
CrossRef | Web of Science | Medline17
Aaronson NK ,Bartelink H ,van Dongen JA ,van Dam FS . Evaluation of breast conserving therapy: clinical, methodological and psychosocial perspectives. Eur J Surg Oncol 1988;14:133-140
Web of Science | Medline18
Dewar JA ,Benhamou S ,Benhamou E , et al. Cosmetic results following lumpectomy, axillary dissection and radiotherapy for small breast cancers. Radiother Oncol 1988;12:273-280
CrossRef | Web of Science | Medline19
Sorlie T ,Perou CM ,Tibshirani R , et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869-10874
CrossRef | Web of Science | Medline20
Taylor CW ,McGale P ,Darby SC . Cardiac risks of breast-cancer radiotherapy: a contemporary view. Clin Oncol (R Coll Radiol) 2006;18:236-246
CrossRef | Web of Science | Medline21
START Trialists' Group,
Bentzen SM ,Agrawal RK , et al. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol 2008;9:331-341
CrossRef | Web of Science | Medline22
START Trialists' Group,
Bentzen SM ,Agrawal RK , et al. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet 2008;371:1098-1107
CrossRef | Web of Science | Medline23
Bartelink H ,Horiot JC ,Poortmans P , et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10822 trial. J Clin Oncol 2007;25:3259-3265
CrossRef | Web of Science | Medline24
Romestaing P ,Lehingue Y ,Carrie C , et al. Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized trial in Lyon, France. J Clin Oncol 1997;15:963-968
Web of Science | Medline
- Citing Articles (71)
Citing Articles
1
Matthew E. Hardee, Shahzad Raza, Stewart J. Becker, Gabor Jozsef, Stella C. Lymberis, Tsivia Hochman, Judith D. Goldberg, Keith J. DeWyngaert, Silvia C. Formenti. (2012) Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique. International Journal of Radiation Oncology*Biology*Physics 82:3, e415-e423
CrossRef2
David J. Hoopes, David Kaziska, Patrick Chapin, Daniel Weed, Benjamin D. Smith, E. Ronald Hale, Peter A. Johnstone. (2012) Patient Preferences and Physician Practice Patterns Regarding Breast Radiotherapy. International Journal of Radiation Oncology*Biology*Physics 82:2, 674-681
CrossRef3
Scott V. Bratman, Daniel S. Kapp, Kathleen C. Horst. (2012) Evolving trends in the initial locoregional management of male breast cancer. The Breast
CrossRef4
Philip Wong, Christine Lambert, Ramanakumar V. Agnihotram, Marc David, Marie Duclos, Carolyn R. Freeman. (2012) Ductal Carcinoma in Situ—The Influence of the Radiotherapy Boost on Local Control. International Journal of Radiation Oncology*Biology*Physics 82:2, e153-e158
CrossRef5
Gillian C. Barnett, Jennifer S. Wilkinson, Anne M. Moody, Charles B. Wilson, Nicola Twyman, Gordon C. Wishart, Neil G. Burnet, Charlotte E. Coles. (2012) Randomized Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy for Early Breast Cancer: Interim Results at 2 Years. International Journal of Radiation Oncology*Biology*Physics 82:2, 715-723
CrossRef6
Gary M. Freedman. (2012) Hypofractionated Radiation Therapy in the Treatment of Early-Stage Breast Cancer. Current Oncology Reports 14:1, 12-19
CrossRef7
Benjamin Rosenbluth. (2012) The Use of Radiation Therapy in the Geriatric Population. Clinics in Geriatric Medicine 28:1, 105-114
CrossRef8
Manjeet Chadha, Dan Vongtama, Patricia Friedmann, Celina Parris, Susan K. Boolbol, Rudolph Woode, Louis B. Harrison. (2012) Comparative Acute Toxicity from Whole Breast Irradiation Using 3-Week Accelerated Schedule With Concomitant Boost and the 6.5-Week Conventional Schedule With Sequential Boost for Early-Stage Breast Cancer. Clinical Breast Cancer 12:1, 57-62
CrossRef9
John Ng, Igor Shuryak, Yanguang Xu, K.S. Clifford Chao, David J. Brenner, Ryan J. Burri. (2012) Predicting the Risk of Secondary Lung Malignancies Associated with Whole-Breast Radiation Therapy. International Journal of Radiation Oncology*Biology*Physics
CrossRef10
Amy Yuen Meei Teh, Lorraine Walsh, Thomas G. Purdie, Allen Mosseri, Wei Xu, Wilfred Levin, C. Anne Koch, Anthony Fyles, Fei-Fei Liu, B.C. John Cho. (2012) Concomitant intensity modulated boost during whole breast hypofractionated radiotherapy – A feasibility and toxicity study. Radiotherapy and Oncology 102:1, 89-95
CrossRef11
Coen W. Hurkmans, Ingrid Dijckmans, Miranda Reijnen, Jorien van der Leer, Corine van Vliet-Vroegindeweij, Maurice van der Sangen. (2012) Adaptive radiation therapy for breast IMRT-simultaneously integrated boost: Three-year clinical experience. Radiotherapy and Oncology
CrossRef12
Christopher F. Njeh, Mark W. Saunders, Christian M. Langton. (2012) Accelerated partial breast irradiation using external beam conformal radiation therapy: A review. Critical Reviews in Oncology/Hematology 81:1, 1-20
CrossRef13
Csaba Polgár, Tibor Major, János Fodor. (2012) Korszerű sugárkezelés emlőmegtartó műtét után. Orvosi Hetilap 153:2, 45-55
CrossRef14
Renee Royak-Schaler, Colleen Pelser, Patricia Langenberg, Jennifer Hayes, Lisa Gardner, Kim Nesbitt, Wendla Citron, Cynthia L. Drogula, Diane Dwyer. (2012) Characteristics Associated with the Initiation of Radiation Therapy after Breast-Conserving Surgery among African American and White Women Diagnosed with Early-Stage Breast Cancer in Maryland, 2000–2006. Annals of Epidemiology 22:1, 28-36
CrossRef15
C. Bourgier, S. Heymann, P. Vielh, D. Azria. (2012) Implications radiobiologiques de la classification moléculaire des cancers du sein : présent ou avenir ?. Cancer/Radiothérapie
CrossRef16
Pietro Sanpaolo, Viviana Barbieri, Domenico Genovesi, Vincenzo Fusco, Giampiero Ausili Cèfaro. (2011) Biologically effective dose and breast cancer conservative treatment: is duration of radiation therapy really important?. Breast Cancer Research and Treatment
CrossRef17
P. Auberdiac, C. Chargari, L. Cartier, A. Mélis, N. Malkoun, C. Chauleur, J.-P. Jacquin, G. de Laroche, N. Magné. (2011) Hormonoradiothérapie exclusive dans la prise en charge du cancer du sein de la personne âgée : cas clinique et revue de la littérature des schémas hypofractionnés. Cancer/Radiothérapie 15:8, 723-727
CrossRef18
Jonathan Fong, Emil D. Kurniawan, Allison K. Rose, Arlene Mou, John P. Collins, Julie A. Miller, G. Bruce Mann. (2011) Outcomes of Screening-Detected Ductal Carcinoma In Situ Treated with Wide Excision Alone. Annals of Surgical Oncology 18:13, 3778-3784
CrossRef19
Tanya S. Berrang, Ivo Olivotto, Do-Hoon Kim, Alan Nichol, B.C. John Cho, Islam G. Mohamed, Tarnjit Parhar, J.R. Wright, Pauline Truong, Scott Tyldesley, Jonathan Sussman, Elaine Wai, Tim Whelan. (2011) Three-Year Outcomes of a Canadian Multicenter Study of Accelerated Partial Breast Irradiation Using Conformal Radiation Therapy. International Journal of Radiation Oncology*Biology*Physics 81:5, 1220-1227
CrossRef20
S. Chatterjee, I. Mallick, R. Achari. (2011) Hypofractionation in Breast Cancer: Is it Fair to Generalise the Data?. Clinical Oncology
CrossRef21
Michele Avanzo, Joseph Stancanello, Marco Trovò, Rajesh Jena, Mario Roncadin, Mauro G. Trovò, Elvira Capra. (2011) Complication probability model for subcutaneous fibrosis based on published data of partial and whole breast irradiation. Physica Medica
CrossRef22
Domenico Cante, Maria Rosa La Porta, Valeria Casanova-Borca, Piera Sciacero, Giuseppe Girelli, Massimo Pasquino, Pierfrancesco Franco, Franca Ozzello. (2011) Accelerated Hypofractionated Adjuvant Whole Breast Radiotherapy with Concomitant Photon Boost after Conserving Surgery for Early Stage Breast Cancer: A Prospective Evaluation on 463 Patients. The Breast Journal 17:6, 586-593
CrossRef23
Jayant S. Vaidya, Michael Baum, Jeffrey S. Tobias, Frederik Wenz, Samuele Massarut, Mohammed Keshtgar, Basil Hilaris, Christobel Saunders, Norman R. Williams, Chris Brew-Graves, Tammy Corica, Mario Roncadin, Uta Kraus-Tiefenbacher, Marc Sütterlin, Max Bulsara, David Joseph. (2011) Long-Term Results of Targeted Intraoperative Radiotherapy (Targit) Boost During Breast-Conserving Surgery. International Journal of Radiation Oncology*Biology*Physics 81:4, 1091-1097
CrossRef24
Jonathan D. Schoenfeld, Jay R. Harris. (2011) Abbreviated course of radiotherapy (RT) for breast cancer. The Breast 20, S116-S127
CrossRef25
Paige L. Dorn, Kimberly S. Corbin, Hania Al-Hallaq, Yasmin Hasan, Steven J. Chmura. (2011) Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients. International Journal of Radiation Oncology*Biology*Physics
CrossRef26
B. Cutuli, A. Fourquet. (2011) Irradiation hypofractionnée dans le cancer du sein : pour ou contre ?. Cancer/Radiothérapie 15:6-7, 445-449
CrossRef27
S. Aebi, T. Davidson, G. Gruber, F. Cardoso, . (2011) Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 22:Supplement 6, vi12-vi24
CrossRef28
Benjamin D. Smith, Soren M. Bentzen, Candace R. Correa, Carol A. Hahn, Patricia H. Hardenbergh, Geoffrey S. Ibbott, Beryl McCormick, Julie R. McQueen, Lori J. Pierce, Simon N. Powell, Abram Recht, Alphonse G. Taghian, Frank A. Vicini, Julia R. White, Bruce G. Haffty. (2011) Fractionation for Whole Breast Irradiation: An American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline. International Journal of Radiation Oncology*Biology*Physics 81:1, 59-68
CrossRef29
Jennifer R. Bellon, Eleanor E. R. Harris, Douglas W. Arthur, Lisa Bailey, Lisa Carey, Sharad Goyal, Michele Y. Halyard, Kathleen C. Horst, Meena S. Moran, Shannon M. MacDonald, Bruce G. Haffty. (2011) ACR Appropriateness Criteria® Conservative surgery and Radiation - Stage I and II Breast Carcinoma. The Breast Journal 17:5, 448-455
CrossRef30
J.-P. Pignol, E. Rakovitch, J. Zeppieri, W. Hanna. (2011) Accuracy and Completeness of Pathology Reporting — Impact on Partial Breast Irradiation Eligibility. Clinical Oncology
CrossRef31
Thomas A. Buchholz, Kelly K. Hunt. (2011) Breast Conservation Therapy in the 21st Century. The Breast Journal 17:5, 445-447
CrossRef32
Birgitte Offersen, Inger Højris, Marie Overgaard. (2011) Radiation-induced heart morbidity after adjuvant radiotherapy of early breast cancer – Is it still an issue?. Radiotherapy and Oncology 100:2, 157-159
CrossRef33
A. Goldhirsch, W. C. Wood, A. S. Coates, R. D. Gelber, B. Thurlimann, H.- J. Senn, . (2011) Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Annals of Oncology 22:8, 1736-1747
CrossRef34
Y. Belkacémi, A. Fourquet, B. Cutuli, C. Bourgier, M. Hery, G. Ganem, H. Marsiglia, M. Namer, J. Gligorov, D. Azria. (2011) Radiotherapy for invasive breast cancer: Guidelines for clinical practice from the French expert review board of Nice/Saint-Paul de Vence. Critical Reviews in Oncology/Hematology 79:2, 91-102
CrossRef35
Andrea M. Abbott, Elizabeth B. Habermann, Todd M. Tuttle. (2011) Trends in the use of implantable accelerated partial breast irradiation therapy for early stage breast cancer in the United States. Cancer 117:15, 3305-3310
CrossRef36
A Ring, M Reed, R Leonard, I Kunkler, H Muss, H Wildiers, L Fallowfield, A Jones, R Coleman. (2011) The treatment of early breast cancer in women over the age of 70. British Journal of Cancer 105:2, 189-193
CrossRef37
J. Ben Wilkinson, Alvaro A. Martinez, Peter Y. Chen, Mihai I. Ghilezan, Michelle F. Wallace, Inga S. Grills, Chirag S. Shah, Christina K. Mitchell, Evelyn Sebastian, Amy S. Limbacher, Pamela R. Benitez, Eric A. Brown, Frank A. Vicini. (2011) Four-year results using balloon-based brachytherapy to deliver accelerated partial breast irradiation with a 2-day dose fractionation schedule. Brachytherapy
CrossRef38
Janice A Lyons, Charles Woods, Nicholas Galanopoulos, Paula Silverman. (2011) Emerging radiation techniques for early-stage breast cancer after breast-conserving surgery. Future Oncology 7:7, 915-925
CrossRef39
Erik van Werkhoven, Guus Hart, Harm van Tinteren, Paula Elkhuizen, Laurence Collette, Philip Poortmans, Harry Bartelink. (2011) Nomogram to predict ipsilateral breast relapse based on pathology review from the EORTC 22881-10882 boost versus no boost trial. Radiotherapy and Oncology 100:1, 101-107
CrossRef40
(2011) First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiotherapy and Oncology 100:1, 93-100
CrossRef41
E.C. Ko, K. Forsythe, M. Buckstein, J. Kao, B.S. Rosenstein. (2011) Radiobiological rationale and clinical implications of hypofractionated radiation therapy. Cancer/Radiothérapie 15:3, 221-229
CrossRef42
Brian D. Kavanagh, Moyed Miften, Rachel A. Rabinovitch. (2011) Advances in Treatment Techniques. The Cancer Journal 17:3, 177-181
CrossRef43
Baldassarre Stea, Lisa J. Hazard, Victor J. Gonzalez, Russell Hamilton. (2011) The role of radiation therapy in the control of locoregional and metastatic cancer. Journal of Surgical Oncology 103:6, 627-638
CrossRef44
Christopher Herbert, Alan Nichol, Ivo Olivotto, Lorna Weir, Ryan Woods, Caroline Speers, Pauline Truong, Scott Tyldesley. (2011) The Impact of Hypofractionated Whole Breast Radiotherapy on Local Relapse in Patients with Grade 3 Early Breast Cancer: A Population-based Cohort Study. International Journal of Radiation Oncology*Biology*Physics
CrossRef45
Todd M. Tuttle, Natasha M. Rueth, Andrea Abbott, Beth A. Virnig. (2011) Trends in the local treatment of breast cancer: Should we be worried?. Journal of Surgical Oncology 103:4, 313-316
CrossRef46
Susan A McCloskey, Steve P Lee, Michael L Steinberg. (2011) Roles and types of radiation in breast cancer treatment: early breast cancer, locoregionally advanced, and metastatic disease. Current Opinion in Obstetrics and Gynecology 23:1, 51-57
CrossRef47
Todd M. Tuttle, Stephanie Jarosek, Elizabeth B. Habermann, Doug Yee, Jianling Yuan, Beth A. Virnig. (2011) Omission of radiation therapy after breast-conserving surgery in the United States. Cancern/a-n/a
CrossRef48
Ronald M. Witteles. (2011) Radiation Therapy for Breast Cancer. Journal of the American College of Cardiology 57:4, 453-454
CrossRef49
Navita Somaiah, John Yarnold. (2011) Overview of Hypofractionation in Breast Radiotherapy. Breast Diseases: A Year Book Quarterly 22:4, 346-349
CrossRef50
D. Ali, R. Le Scodan. (2011) Treatment of the primary tumor in breast cancer patients with synchronous metastases. Annals of Oncology 22:1, 9-16
CrossRef51
Sophia M. Edwards-Bennett, Candace R. Correa, Eleanor E. Harris. (2011) Optimization of Adjuvant Radiation in Breast Conservation Therapy: Can We Minimize without Compromise?. International Journal of Breast Cancer 2011, 1-6
CrossRef52
Elaine S. Wai, Mary L. Lesperance, Cheryl S. Alexander, Pauline T. Truong, Matthew Culp, Patricia Moccia, Jennifer F. Lindquist, Ivo A. Olivotto. (2011) Effect of radiotherapy boost and hypofractionation on outcomes in ductal carcinoma in situ. Cancer 117:1, 54-62
CrossRef53
P.L. Dorn, S.J. Chmura. (2011) Effect of Radiotherapy Boost and Hypofractionation on Outcomes in Ductal Carcinoma In Situ. Breast Diseases: A Year Book Quarterly 22:3, 278-279
CrossRef54
Atif J. Khan, Roger G. Dale, Douglas W. Arthur, Bruce G. Haffty, Dorin A. Todor, Frank A. Vicini. (2011) Ultrashort courses of adjuvant breast radiotherapy. Cancern/a-n/a
CrossRef55
Paola Pinnarò, Stefano Arcangeli, Carolina Giordano, Giorgio Arcangeli, Fabrizio Impiombato, Valentina Pinzi, Giuseppe Iaccarino, Antonella Soriani, Valeria Landoni, Lidia Strigari. (2011) Toxicity and cosmesis outcomes after single fraction partial breast irradiation in early stage breast cancer. Radiation Oncology 6:1, 155
CrossRef56
Susan Hoover, Elizabeth Bloom, Sunil Patel. (2011) Review of Breast Conservation Therapy: Then and Now. ISRN Oncology 2011, 1-13
CrossRef57
Melissa L James, Margot Lehman, Phil N Hider, Mark Jeffery, Brigid E Hickey, Daniel P Francis, Brigid E Hickey. 2010. Fraction size in radiation treatment for breast conservation in early breast cancer. .
CrossRef58
John Yarnold, Joanne Haviland. (2010) Hypofractionated Adjuvant Whole Breast Radiotherapy: Progress and Prospects. Acta Oncologica 49:8, 1288-1292
CrossRef59
Umberto Veronesi, Roberto Orecchia, Alberto Luini, Viviana Galimberti, Stefano Zurrida, Mattia Intra, Paolo Veronesi, Paolo Arnone, Maria Cristina Leonardi, Mario Ciocca, Roberta Lazzari, Pietro Caldarella, Nicole Rotmensz, Claudia Sangalli, Daniele Sances, Patrick Maisonneuve. (2010) Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Research and Treatment 124:1, 141-151
CrossRef60
Judy C. Boughey, Elizabeth A. Mittendorf, Lawrence J. Solin, J. Michael Dixon, Todd M. Tuttle, Peter D. Beitsch, Hiram S. Cody, A. Marilyn Leitch, Lisa A. Newman. (2010) Controversies in Breast Surgery. Annals of Surgical Oncology 17:S3, 230-232
CrossRef61
Simon Powell. (2010) Radiotherapy for Breast Cancer in the 21st Century. The Breast Journal 16, S34-S38
CrossRef62
(2010) Scientific Surgery. British Journal of Surgery 97:8, 1313-1313
CrossRef63
A. Ginot, J. Doyen, J.-M. Hannoun-Lévi, A. Courdi. (2010) Dose de tolérance des tissus sains : la peau et les phanères. Cancer/Radiothérapie 14:4-5, 379-385
CrossRef64
Deborah Williamson, Robert Dinniwell, Sharon Fung, Melania Pintilie, Susan J. Done, Anthony W. Fyles. (2010) Local control with conventional and hypofractionated adjuvant radiotherapy after breast-conserving surgery for ductal carcinoma in-situ. Radiotherapy and Oncology 95:3, 317-320
CrossRef65
Caroline L. Holloway, Valerie Panet-Raymond, Ivo Olivotto. (2010) Hypofractionation should be the new ‘standard’ for radiation therapy after breast conserving surgery. The Breast 19:3, 163-167
CrossRef66
Bruce G. Haffty. (2010) Radiotherapy: Hypofractionation for breast cancer—clinical implications. Nature Reviews Clinical Oncology 7:6, 304-306
CrossRef67
(2010) Hypofractionated Radiotherapy for Breast Cancer. New England Journal of Medicine 362:19, 1843-1844
Full Text68
B.G. Haffty. (2010) Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer. Breast Diseases: A Year Book Quarterly 21:3, 267-268
CrossRef69
Megan E. Daly, Kathleen C. Horst. (2010) Locoregional Management of Breast Cancer in Women Younger Than 40. Breast Diseases: A Year Book Quarterly 21:3, 207-210
CrossRef70
L.W. Cuttino. (2010) Feasibility Trial of Partial Breast Irradiation With Concurrent Dose-Dense Doxorubicin and Cyclophosphamide in Early-Stage Breast Cancer. Breast Diseases: A Year Book Quarterly 21:3, 274-275
CrossRef71
J.L. Wright, C. Takita. (2010) Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with 90Y-labeled biotin. Breast Diseases: A Year Book Quarterly 21:4, 371-372
CrossRef
- Letters
