Conventional Whole-breast Irradiation Research Articles

Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial

We previously confirmed the non-inferiority of accelerated partial breast irradiation (APBI) with interstitial brachytherapy in terms of local control and overall survival compared with whole-breast irradiation for patients with early-stage breast cancer who underwent breast-conserving surgery in a phase 3 randomised trial. Here, we present the 5-year late side-effects and cosmetic results of the trial. We did this randomised, controlled, phase 3 trial at 16 centres in seven European countries. Women aged 40 years or older with stage 0-IIA breast cancer who underwent breast-conserving surgery with microscopically clear resection margins of at least 2 mm were randomly assigned 1:1, via an online interface, to receive either whole-breast irradiation of 50 Gy with a tumour-bed boost of 10 Gy or APBI with interstitial brachytherapy. Randomisation was stratified by study centre, menopausal status, and tumour type (invasive carcinoma vs ductal carcinoma in situ), with a block size of ten, according to an automated dynamic algorithm. Patients and investigators were not masked to treatment allocation. The primary endpoint of our initial analysis was ipsilateral local recurrence; here, we report the secondary endpoints of late side-effects and cosmesis. We analysed physician-scored late toxicities and patient-scored and physician-scored cosmetic results from the date of breast-conserving surgery to the date of onset of event. Analysis was done according to treatment received (as-treated population). This trial is registered with ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, we randomly assigned 1328 women to receive either whole-breast irradiation (n=673) or APBI with interstitial brachytherapy (n=655); 1184 patients comprised the as-treated population (551 in the whole-breast irradiation group and 633 in the APBI group). At a median follow-up of 6·6 years (IQR 5·8-7·6), no patients had any grade 4 toxities, and three (<1%) of 484 patients in the APBI group and seven (2%) of 393 in the whole-breast irradiation group had grade 3 late skin toxicity (p=0·16). No patients in the APBI group and two (<1%) in the whole-breast irradiation group developed grade 3 late subcutaneous tissue toxicity (p=0·10). The cumulative incidence of any late side-effect of grade 2 or worse at 5 years was 27·0% (95% CI 23·0-30·9) in the whole-breast irradiation group versus 23·3% (19·9-26·8) in the APBI group (p=0·12). The cumulative incidence of grade 2-3 late skin toxicity at 5 years was 10·7% (95% CI 8·0-13·4) in the whole-breast irradiation group versus 6·9% (4·8-9·0) in the APBI group (difference -3·8%, 95% CI -7·2 to 0·4; p=0·020). The cumulative risk of grade 2-3 late subcutaneous tissue side-effects at 5 years was 9·7% (95% CI 7·1-12·3) in the whole-breast irradiation group versus 12·0% (9·4-14·7) in the APBI group (difference 2·4%; 95% CI -1·4 to 6·1; p=0·28). The cumulative incidence of grade 2-3 breast pain was 11·9% (95% CI 9·0-14·7) after whole-breast irradiation versus 8·4% (6·1-10·6) after APBI (difference -3·5%; 95% CI -7·1 to 0·1; p=0·074). At 5 years' follow-up, according to the patients' view, 413 (91%) of 454 patients had excellent to good cosmetic results in the whole-breast irradiation group versus 498 (92%) of 541 patients in the APBI group (p=0·62); when judged by the physicians, 408 (90%) of 454 patients and 503 (93%) of 542 patients, respectively, had excellent to good cosmetic results (p=0·12). No treatment-related deaths occurred, but six (15%) of 41 patients (three in each group) died from breast cancer, and 35 (85%) deaths (21 in the whole-breast irradiation group and 14 in the APBI group) were unrelated. 5-year toxicity profiles and cosmetic results were similar in patients treated with breast-conserving surgery followed by either APBI with interstitial brachytherapy or conventional whole-breast irradiation, with significantly fewer grade 2-3 late skin side-effects after APBI with interstitial brachytherapy. These findings provide further clinical evidence for the routine use of interstitial multicatheter brachytherapy-based APBI in the treatment of patients with low-risk breast cancer who opt for breast conservation. German Cancer Aid.

Patterns of Radiation Therapy Boost Administration in 356,160 Breast Cancer Patients Treated With Hypofractionated Versus Conventional Whole-Breast Irradiation

Patterns of Radiation Therapy Boost Administration in 356,160 Breast Cancer Patients Treated With Hypofractionated Versus Conventional Whole-Breast Irradiation

Partial breast irradiation for early breast cancer.

Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). To determine whether PBI/APBI is equivalent to or better than conventional or hypo-fractionated WBRT after breast-conserving therapy for early-stage breast cancer. We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions. Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis. We included seven RCTs and studied 7586 women of the 8955 enrolled.Local recurrence-free survival appeared worse for women receiving PBI/APBI compared to WBRT (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.11 to 2.35; six studies, 6820 participants, low-quality evidence). Cosmesis (physician-reported) appeared worse with PBI/APBI (odds ratio (OR) 1.51, 95% CI 1.17 to 1.95, five studies, 1720 participants, low-quality evidence). Overall survival did not differ with PBI/APBI (HR 0.90, 95% CI 0.74 to 1.09, five studies, 6718 participants, high-quality evidence).Late radiation toxicity (subcutaneous fibrosis) appeared worse with PBI/APBI (OR 6.58, 95% CI 3.08 to 14.06, one study, 766 participants, moderate-quality evidence). Acute skin toxicity appeared reduced with PBI/APBI (OR 0.04, 95% CI 0.02 to 0.09, two studies, 608 participants). Telangiectasia (OR 26.56, 95% CI 3.59 to 196.51, 1 study, 766 participants) and radiological fat necrosis (OR 1.58, 95% CI 1.02 to 2.43, three studies, 1319 participants) appeared worse with PBI/APBI. Late skin toxicity (OR 0.21, 95% CI 0.01 to 4.39, two studies, 608 participants) and breast pain (OR 2.17, 95% CI 0.56 to 8.44, one study, 766 participants) appeared not to differ with PBI/APBI.'Elsewhere primaries' (new primaries in the ipsilateral breast) appeared more frequent with PBI/APBI (OR 3.97, 95% CI 1.51 to 10.41, three studies, 3009 participants).We found no clear evidence of a difference for the comparison of PBI/APBI with WBRT for the outcomes of: cause-specific survival (HR 1.08, 95% CI 0.73 to 1.58, five studies, 6718 participants, moderate-quality evidence), distant metastasis-free survival (HR 0.94, 95% CI 0.65 to 1.37, four studies, 3267 participants, moderate-quality evidence), relapse-free survival (HR 1.36, 95% CI 0.88 to 2.09, three studies, 3811 participants), loco-regional recurrence-free survival (HR 1.80, 95% CI 1.00 to 3.25, two studies, 3553 participants) or mastectomy rates (OR 1.20, 95% CI 0.77 to 1.87, three studies, 4817 participants, low-quality evidence). Compliance was met: more than 90% of the women in all studies received the RT they were assigned to receive. We found no data for the outcomes of costs, quality of life or consumer preference. It appeared that local recurrence and 'elsewhere primaries' (new primaries in the ipsilateral breast) are increased with PBI/APBI (the difference was small), but we found no evidence of detriment to other oncological outcomes. It appeared that cosmetic outcomes and some late effects were worse with PBI/APBI but its use was associated with less acute skin toxicity. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.

Abstract S5-03: Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: 5-year survival results of a phase 3 randomized trial

Abstract Background. Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity modulated radiotherapy (IMRT) had theoretical advantage of further increase in dose conformity compared to 3D technique, with more normal tissue sparing. We present the results of a randomized equivalence trial comparing local recurrence and survival of APBI using IMRT technique to conventional WBI in early stage BC. Methods. This study was performed at the University of Florence (Florence, Italy). Women aged more than 40 years affected by early breast cancer, with a maximum tumor diameter of 25 mm, suitable for breast-conserving surgery, were randomly assigned in a 1:1 ratio to receive either external whole-breast irradiation (WBI) or APBI using IMRT technique. Patients in the APBI arm received a total dose of 30 Gy in 5 fractions to the tumor bed. Those in the WBI arm received 50 Gy in 25 fractions, followed by a boost of 10 Gy in 5 fractions. For this equivalence trial the prespecified equivalence margin was local recurrence of 5% in the APBI arm. The primary endpoint was occurrence of ipsilateral breast tumor recurrences (IBTR); overall survival (OS) and treatment toxicity were secondary endpoints. Treatment tolerance was assessed using the acute and late radiation morbidity scoring scheme from Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Cosmetic outcome was scored on the Harvard Breast Cosmesis scale. This trial is registered with ClinicalTrials.gov, number NCT02104895. Results. 520 patients were randomized (260 to external WBI and 260 to APBI with IMRT) between 2005 and 2013. At a median follow-up of 5 years (range 0.6-9.0), we recorded 6 IBTR: 3 sited in the quadrant index (true recurrence) and 6 in other quadrants. The mean time to IBRT was 2.9 years (range 1-4). The 5-year IBTR rate was 1.5% (3 cases) in the APBI group (95% CI 0.1-3.0), within the prespecified equivalence threshold of 5%, in comparison to that of WBI group (1.4%; 95% CI 0-2.8). No statistically significant difference emerged between two groups (log rank test p=0.86). OS at 5 years did not significantly differ between the groups (p=0.057). We identified 8 deaths (5-year event rate: 2.1%; 95% CI 0.9-3.3), 7 in the WBI group and only 1 in the APBI group. The 5-year overall survival was 96.6% for the WBI group and 99.4% for APBI group. Concerning acute adverse events, APBI group showed a statistically significant better safety considering any grade of skin toxicity (p=0.0001). No grade 3 toxicity was observed for APBI group. Concerning late side effects, only two cases (0.8%) experienced grade 2 toxicity in WBI group (skin fibrosis). In both treatment groups the cosmetic result was rated as excellent/good for more than 90% of patients. Overall, APBI group showed better outcome to WBI group (p=0.045). Conclusions. To our knowledge this is the first randomized study using IMRT technique for APBI delivery. No statistical difference in terms of IBTR was shown between the two arms. APBI showed a significant better acute and late toxicity profile compared to WBI. Citation Format: Lorenzo Livi, Icro Meattini, Livia Marrazzo, Stefania Pallotta, Gabriele Simontacchi, Calogero Saieva, Vieri Scotti, Carla De Luca Cardillo, Paolo Bastiani, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi. Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: 5-year survival results of a phase 3 randomized trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S5-03.

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial

BackgroundAccelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. MethodsThis study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. FindingsA total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0years (Interquartile Range (IQR) 3.4–7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1–3.0) and in the WBI group (three cases; 95% CI 0.0–2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). InterpretationTo our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile.

Radiographic findings after treatment with balloon brachytherapy accelerated partial breast irradiation.

The use of accelerated partial breast irradiation (APBI) following breast-conserving surgery is rapidly gaining popularity as an alternative to whole-breast irradiation (WBI) in selected patients with early-stage breast cancer. Although data on the long-term effectiveness and safety of APBI accelerated partial breast irradiation are still being gathered, the shorter treatment course and narrowed radiation target of APBI accelerated partial breast irradiation provide an attractive alternative for carefully selected patients. These patients include those with relatively small tumors (≤3 cm), negative or close margins, and negative sentinel lymph nodes. Possible long-term complications include telangiectasia and the development of a palpable mass at the lumpectomy site. Mammographic findings in patients who have undergone APBI accelerated partial breast irradiation are distinct from those in patients who have undergone conventional WBI whole-breast irradiation . The most common post-APBI accelerated partial breast irradiation radiographic findings include formation of seromas at the lumpectomy site, focal parenchymal changes such as increased trabeculation and parenchymal distortion, fat necrosis, and skin changes such as thickening or retraction. Given the continued evolution of breast cancer treatment, it is important that radiologists have a comprehensive understanding of APBI accelerated partial breast irradiation in terms of rationale, patient selection criteria, common postprocedural radiographic findings (and how they differ from post-WBI whole-breast irradiation findings), and advantages and potential complications.

Uptake and Costs of Hypofractionated vs Conventional Whole Breast Irradiation After Breast Conserving Surgery in the United States, 2008–2013

Based on randomized evidence, expert guidelines in 2011 endorsed shorter, hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients. To examine the uptake and costs of hypofractionated WBI among commercially insured patients in the United States. Retrospective, observational cohort study, using administrative claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013, we classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n = 8924) included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement. Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks of treatment). Use of hypofractionated and conventional WBI, total and radiotherapy-related health care expenditures, and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment, age, comorbid disease, prior chemotherapy, axillary lymph node involvement, intensity-modulated radiotherapy, practice setting, and other contextual variables. Hypofractionated WBI increased from 10.6% (95% CI, 8.8%-12.5%) in 2008 to 34.5% (95% CI, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% CI, 6.0%-10.2%) in 2008 to 21.2% (95% CI, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were $28,747 for hypofractionated and $31,641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; 95% CI, $1610-$4234; P < .001) and $64,273 for hypofractionated and $72,860 for conventional WBI in the hypofractionation-permitted cohort (difference, $8587; 95% CI, $5316-$12,017; P < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBI in either cohort. Hypofractionated WBI after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However, only 34.5% of patients with hypofractionation-endorsed and 21.2% with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013.

Partial breast irradiation for early breast cancer.

Breast conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiation therapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed (partial breast irradiation: PBI) sometimes with a shortened treatment duration (accelerated partial breast irradiation: APBI). To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for early-stage breast cancer. We searched the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11 April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we searched the International Standard Randomised Controlled Trial Number Register, the World Health Organization's International Clinical Trials Registry Platform (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22 April 2014). We searched for grey literature: Open Grey (23 April 2014), reference lists of articles, a number of conference proceedings and published abstracts, and did not apply any language restrictions. Randomised controlled trials (RCTs) without confounding and evaluating conservative surgery plus PBI/APBI versus conservative surgery plus whole breast RT. We included both published and unpublished trials. Three review authors (ML, DF and BH) performed data extraction and resolved any disagreements through discussion. We entered data into Review Manager for analysis. BH and ML assessed trials, graded the methodological quality using Cochrane's Risk of Bias tool and resolved any disagreements through discussion. We included four RCTs that had 2253 women. Two older trials examined RT techniques which do not reflect current practice and one trial had a short follow-up. We downgraded the quality of the evidence for our key outcomes due to risk of bias. Taken together with other GRADE recommendations, the quality of evidence for our outcomes was very low to low. For the comparison of partial breast irradiation/accelerated breast irradiation (PBI/APBI) with whole breast irradiation (WBRT), local recurrence-free survival appeared worse (Hazard Ratio (HR) 1.74, 95% confidence interval (CI) 1.23 to 2.45; three trials, 1140 participants, very low quality evidence). Cosmesis appeared improved with PBI/APBI in a single trial (OR 0.40, 95% CI 0.23 to 0.72; one trial, 241 participants, very low quality evidence), but late toxicity (telangiectasia OR 4.41, 95% CI 3.21 to 6.05; very low quality evidence, 708 participants) and subcutaneous fibrosis (OR 4.27, 95% CI 3.04 to 6.01; one trial, 710 participants, very low quality evidence) appeared increased in another trial. We found no clear evidence of a difference for the comparison of PBI/APBI versus WBRT for the outcomes of: overall survival (HR 0.99, 95% CI 0.83 to 1.18; three trials, 1140 participants, very low quality evidence), cause-specific survival (HR 0.95, 95% CI 0.74 to 1.22; two trials, 966 participants, low evidence quality), distant metastasis-free survival (HR 1.02, 95% CI 0.81 to 1.28; 1140 participants, low quality evidence), subsequent mastectomy rate (OR 0.20, 95% CI 0.01 to 4.21; 258 participants, low quality evidence) and relapse-free survival (HR 0.99, 95% CI 0.53 to 1.85; 258 participants, low quality evidence). We found no data for the outcomes of acute toxicity, new ipsilateral breast primaries, costs, quality of life or consumer preference. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.

Intraoperative radiotherapy with electrons (ELIOT) for early breast cancer: the European Institute of Oncology experience

Partial breast irradiation (PBI) as an alternative to whole breast irradiation (WBI) is an attractive approach tested in several phase II and a few phase III studies, using different modalities of irradiation. Intraoperative radiotherapy (RT) with electrons allows the reduction of a whole course of WBI to a single session during surgery. The European Institute of Oncology (Milan, Italy) conducted a series of investigations aimed proving the safety and the effectiveness of intraoperative RT as a full dose PBI. The single dose of 21 Gy was calculated to be theoretically equivalent to a full course of conventional WBI. This ultimate form of hypofractionation carried some concern regarding the long-term impact on breast parenchyma. Phase I and II studies and a number of off- protocol patients have shown feasibility and good short-term results in both disease control and cosmesis. The results of the ELIOT randomized phase III trial comparing intraoperative RT to conventional WBI are discussed in the context of a worldwide scenario including other four randomized studies and one metanalysis, so far. From the analysis of the available data, the adequate patient selection emerges as mandatory to make intraoperative RT and other PBI modalities a reasonable alternative to conventional WBI. Further investigations are required to fully understand the weight of clinical and histologic variables classically associated with increased risk of local recurrence. In addition, the role of molecular classification in the pattern of recurrence after PBI will be more and more predominant.

Efficacy and Safety of Accelerated Partial Breast Irradiation after Breast-conserving Surgery: A Meta-analysis of Published Comparative Studies

To compare the treatment outcomes between accelerated partial breast irradiation (APBI) and conventional whole-breast irradiation (WBI) and to explore the efficacy and safety of APBI as an adjuvant treatment for early-stage breast cancer who received breast-conserving therapy. Eligible studies were identified on Medline, Embase, and the Cochrane Library updated to July 10, 2012. Comparative studies were considered for inclusion. Analyses were carried out using Stata software. Eleven comparative studies with a total of 7,097 patients were included. The meta-analysis showed that there were no statistically significant differences between group APBI and group WBI associated with the supraclavicular failure, distant metastasis, overall survival, and disease-free survival, while local recurrence (LR) and axillary failure (AF) increased in group APBI. The sensitivity analysis indicated that both the LR and AF were not statistically significant difference between the two groups. In the subgroup analysis, LR was statistically significantly higher in group APBI for patients with the age <60, large tumor size, and unknown margin status. APBI is a safe treatment modality and could become a potential option for the delivery of adjuvant radiation therapy in patients receiving breast-conserving therapy, especially for the suitable group that was classified by the American Society of Radiation Oncology Consensus Panel.

Abstract P5-14-09: Brachytherapy, 3-dimentional conformal radiotherapy, and intensity modulated radiotherapy for breast cancer patients undergoing breast conservation: Effectiveness and guideline concordance

Abstract Background: There has been a rapid increase in the use of new radiation techniques for postlumpectomy radiation, including partial breast irradiation via brachytherapy (APBI-b), 3-dimentional conformal radiotherapy (3D-CRT), and intensity modulated radiotherapy (IMRT) techniques. However, it is unknown if these new radiation techniques provide survival benefit equivalent to external beam whole-breast irradiation (WBI) in patients undergoing breast conservation. Additionally, compliance with the 2009 ASTRO guidelines for partial breast radiation has not been examined in a contemporary cohort of patients. Method: From the National Cancer Database, we identified 718,392 women diagnosed with AJCC stage 0-III breast cancer between 2003 and 2010, who underwent breast conserving surgery. Patients were classified into suitable, cautionary, or unsuitable for APBI-b according to ASTRO guidelines. Cox proportional hazard models were used to examine the effectiveness of the new irradiation modalities on overall survival in all eligible patients and within each ASTRO category. Results: Overall, 37,363 patients (6.4%) underwent APBI-b, 40,767 (5.7%) underwent IMRT, 45,721 (6.4%) underwent 3D-CRT, 421,497 (58.7%) underwent conventional WBI. The utilization of the three new radiation techniques increased over the study period, and 31.3% of all patients treated with radiotherapy after lumpectomy actually used one of the three new methods in 2010. Overall, 35% of patients receiving APBI-b fell in the suitable category, 47% in the cautionary category, and 18% in the unsuitable category. After publication of the ASTRO guideline, the proportion of patients receiving APBI-b in the suitable category has increased from 34% in 2008 to 40% in 2010. After a median follow up of 46 months, 52,099 patients died. In invasive breast cancer patients, we found patients undergoing APBI-b had a 38% reduction in the risk of death, compared to patients without radiotherapy (hazard ratio, HR = 0.62, 95% CI: 0.57-0.66, p&amp;lt;0.001) after adjusting for age, tumor stage, tumor grade, hormone receptor status, race/ethnicity, insurance, and other clinical, pathologic, and facility factors. The adjusted HR was 0.63 (95% CI: 0.59-0.67, p&amp;lt;0.001) for IMRT, 0.60 (95% CI: 0.57-0.64, p&amp;lt;0.001) for 3D-CRT, and 0.62 (95% CI: 0.60-0.64, p&amp;lt;0.001) for conventional WBI. The effectiveness of the four radiation modalities was similar (p = 0.84). In the ASTRO suitable category, the HR of APBI-b was 0.70 (95% CI: 0.63-0.79), which is similar to the effect of APBI-b in the cautionary category (HR = 0.64, 95% CI: 0.56-0.73). Conclusions: In a large cohort of women with early stage breast cancer, radiotherapy using three new techniques (APBI-b, IMRT, and 3D-CRT) was found to be as effective in reducing mortality as conventional whole breast irradiation. Although this is promising, long-term follow-up studies and randomized clinical trials are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-09.

Five-Year Outcomes, Cosmesis, and Toxicity With 3-Dimensional Conformal External Beam Radiation Therapy to Deliver Accelerated Partial Breast Irradiation

To report the interim results from a study comparing the efficacy, toxicity, and cosmesis of breast-conserving treatment with accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy (3D-CRT). 102 patients with early-stage breast cancer who underwent breast-conserving surgery were randomized to receive either WBI (n=51) or APBI (n=51). In the WBI arm, 48 Gy was delivered to the whole breast in daily fractions of 2 Gy, with or without additional 10 Gy to the tumor bed. In the APBI arm, patients received 37.5 Gy in 3.75 Gy per fraction delivered twice daily. Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria. Skin elasticity was measured using a dedicated device (Multi-Skin-Test-Center MC-750-B2, CKelectronic-GmbH). Cosmetic results were assessed by the physician and the patients as good/excellent, regular, or poor. The median follow-up time was 5 years. No local recurrences were observed. No significant differences in survival rates were found. APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI (P<.01). Late skin toxicity was no worse than grade 2 in either group, without significant differences between the 2 groups. In the ipsilateral breast, the areas that received the highest doses (ie, the boost or quadrant) showed the greatest loss of elasticity. WBI resulted in a greater loss of elasticity in the high-dose area compared with APBI (P<.05). Physician assessment showed that >75% of patients in the APBI arm had excellent or good cosmesis, and these outcomes appear to be stable over time. The percentage of patients with excellent/good cosmetic results was similar in both groups. APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI.

Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial

Background and purposeTo report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI). Patients and methodsBetween 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1–2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50Gy WBI (n=130) or PBI (n=128). The latter consisted of either 7×5.2Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n=88) or 50Gy electron beam (EB) irradiation (n=40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results. ResultsAfter a median follow up of 10.2years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p=0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p<0.01). ConclusionsPartial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI.

Abstract PD04-02: Accelerated hypofractionated versus conventional whole breast radiotherapy for localised left-sided breast cancer: the effect on long-term cardiac morbidity

Abstract PURPOSE: Equivalent long-term outcomes have been demonstrated between conventional whole breast radiotherapy (CWBRT) and accelerated hypofractionated whole breast radiotherapy (AWBRT) for early-stage breast cancer. However, there is ongoing concern regarding the long-term risk of cardiac injury with AWBRT in women with left-sided breast cancer. The primary goal of this population-based study was to determine whether there was an increase in cardiac morbidity with AWBRT versus CWBRT based on hospital administrative data. MATERIALS AND METHODS: Between 1990 and 1998, 2706 women, aged less than 80 years with left-sided early-stage breast cancer were treated with post-operative radiotherapy (RT) to the breast or chest wall alone. Baseline patient, tumour and treatment factors were recorded in a provincial outcomes database, linked to hospital administrative databases and de-identified. Data from hospitalization records two years prior to RT were used to identify baseline cardiac risk factors (including hypertension (HTN), diabetes, hypercholesterolemia and prior cardiac events) and other comorbidities. There was a policy of using CWBRT for women with breast and chest wall radiotherapy planning separations of &amp;gt;23cm, so a propensity-score model was developed to balance cardiac and breast cancer risk factors between women who received AWBRT (42.5–44 Gy/16 fractions) versus CWBRT (45–50 Gy/25 fractions). The first event of a hospital admission for cardiac causes after RT was determined from hospitalization records. Cumulative incidence of cardiac morbidity was estimated at 10 years after RT for AWBRT versus CWBRT groups. Gray's test was used to test for differences in the cumulative incidence curves between the AWBRT and CWBRT groups. RESULTS: The median follow-up [range] was 13.2 [10–28] years. 485 women were treated with CWBRT and 2221 women were treated with AWBRT. The CWBRT group had a higher prevalence of diabetes, with a trend towards higher prevalence of HTN and other cardiac risk factors. Age, year of diagnosis, stage, grade, ER status, hormone and chemotherapy use were not statistically different between the RT groups. There was no statistically significant difference at 10 years in the incidence rate (as measured by first hospitalisation for cardiac morbidity) between the RT groups. The 10-year cumulative incidence of these hospitalization events for cardiac morbidity (95% CI) was 20.8% (19.1–22.5) with AWBRT and 22.1% (18.5–25.9) with CWBRT. This difference was not significant between raw unadjusted values (p = 0.07) or after propensity score adjustment with Gray's test (p = 0.2). Differences were also not statistically different at 15 years follow-up. These values are comparable with published long-term cardiac morbidity rates with CWBRT. Mortality due to cardiac cause was not statistically different between the two groups at 15 years follow-up. CONCLUSION: Hospitalization for a primary or contributing cardiac cause at 15 years follow-up was not significantly different between women with left-sided early-stage breast cancer treated with AWBRT versus CWBRT even after correcting for pretreatment cardiac risk factors and events. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD04-02.

Brachytherapy for Breast Cancer: Maybe Not So Good

Brachytherapy uses an implanted radioactive source to deliver radiation therapy. The upsides of brachytherapy after lumpectomy include shorter duration than the typical 6 to 8 week course of conventional whole-breast irradiation (WBI), and more-limited exposure of normal breast tissue to radiation. Although some data suggest that brachytherapy compares favorably with WBI in efficacy and adverse events, most reports have included small numbers of participants and …

Dosimetric evaluation of 3Dconformal acceleratedpartial-breast irradiation vs. whole-breast irradiation: A comparative study

Background:Conventional early breast cancer treatment consists of lumpectomy followed by whole-breast irradiation (WBI) therapy. Accelerated partial-breast irradiation (APBI) is also an approach to post-lumpectomy radiation for early breast cancer.Aim:The purpose of this study is to compare two different external-beam APBI techniques using three-dimensional (3D) conformal radiation therapy (3DCRT), with conventional whole-breast irradiation based on the radiation conformity index, dose homogeneity index, and dose to organs at risk.Materials and Methods:WBI treatment plans were compared with two different 3DCRT APBI plans for each of 15 patients (8 with right sided lesions, 7 with left sided lesions). The first APBI plan (APBI 1) used two small coplanar fields conformed to the planning target volume (PTV) using multileaf collimators (MLCs) and wedges, while the other APBI plan (APBI 2) used three non-coplanar fields conformed to the PTV using MLCs and wedges.Results:Both the APBI techniques improved the conformity index significantly over whole-breast tangents while maintaining dose homogeneity and not causing significant increase in dose to organs at risk.Conclusion:Both the 3DCRT APBI techniques are technically feasible and dosimetrically appealing,with better target coverage and relative sparing of normal critical organs

Clinical Treatment Planning Using a Non-invasive Image-Guided Conical Breast Brachytherapy Applicator

Purpose: AccuBoost applicators are designed to deliver whole breast irradiation (WBI) boost dose in a non-invasive manner instead of conventional WBI electron boost. In order to irradiate the target volume while providing additional dose sparing to critical structures like the skin, the current round applicator design has been augmented through addition of an internally-truncated cone shield. Brachytherapy dose distributions for the new cone applicator were simulated using model Monte Carlo (MC) methods for radiation transport and a conventional treatment planning system (TPS), and the dose distributions compared to the unmodified round applicator.

The less than whole breast radiotherapy approach

The addition of conventional whole breast irradiation (WBI) to breast conserving surgery (BCS) reduces the risk of early breast cancer recurrence and leads to a statistically and clinically significant improvement in overall survival. However, the long duration of conventional WBI regimens negatively impacts on quality of life. This has led investigators to evaluate an alternative approach of delivering radiation to a limited volume of tissue around the tumour cavity only (partial breast irradiation) and delivering a larger than standard dose of radiation with each treatment (accelerated partial breast irradiation, APBI). This approach may be achieved by a number of techniques: interstitial brachytherapy, intracavitary brachytherapy using the Mammosite device, intraoperative techniques using electrons or low-energy photons, external beam radiotherapy or permanent seed implant. This articles will review the rationale for the less that whole breast radiotherapy approach and describe the techniques by which it can be achieved and the results obtained to date. Finally, the 7 prospective randomised controlled trials of conventional WBI versus APBI which are open and currently recruiting patients will be discussed.

Local control with conventional and hypofractionated adjuvant radiotherapy after breast-conserving surgery for ductal carcinoma in-situ

Purpose Adjuvant whole breast radiotherapy (WBRT) for ductal carcinoma in situ (DCIS) improves local control, however an optimal dose fractionation remains undefined. WBRT following breast-conserving surgery for invasive breast cancer demonstrates equivalent efficacy and morbidity for conventional and hypofractionated treatment. Our group policy allowed for the use of both schedules, therefore we compared local control in women with DCIS following breast-conserving surgery. Patients and methods Two hundred and sixty-six patients treated between January 1999 and December 2004 with conventional (50 Gy in 25 fractions) or hypofractionated (42.4 Gy in 16 fractions or 40 Gy/16 + 12.5 Gy boost) WBRT after breast-conserving surgery for DCIS were retrospectively reviewed. Median follow-up was 3.76 years (range 0.1–8.9 years). Results One hundred and four patients (39%) were treated with conventional and 162 (61%) with hypofractionated WBRT. The median age was 56.7 years (range 32.2–83.8 years), and prognostic features were well matched in both groups, apart from a small increase in tumour size in the conventional arm (1.75 vs. 2.12 cm, p = 0.05). Actuarial risk of recurrence at 4 years was 7% with hypofractionated WBRT and 6% with the conventional schedule ( p = 0.9). Univariate analysis showed an increased risk of recurrence with high nuclear grade tumours (11% at 4 years for grade 3 vs. 4% for grade 1/2, p = 0.029). Conclusions Hypofractionated adjuvant WBRT following breast-conserving surgery for DCIS has comparable local control to a conventional radiation schedule. Hypofractionated WBRT is more convenient for patients, has equivalent morbidity and should be considered in this patient group.

Patient Preferences and Physician Practice Patterns Regarding Breast Radiotherapy

Patient Preferences and Physician Practice Patterns Regarding Breast Radiotherapy