Accelerated Partial Breast Irradiation Group Research Articles

Adjuvant Hypofractionated Whole Breast Irradiation (WBI) vs. Accelerated Partial Breast Irradiation (APBI) in Postmenopausal Women with Early Stage Breast Cancer: 5Years Update of the HYPAB Trial

Therapeutical strategies in breast cancer are continuously updating. Recent researches assessed the possibility of irradiating only the surgical bed in selected patients (Partial Breast Irradiation, PBI). In 2014 we designed a study to evaluate toxicity and cosmesis of APBI using Volumetric Modulated Arc Therapy-Rapid Arc compared with hypofractionated whole breast irradiation (WBI). We present here the 5-years updated data. HYPAB was a single-institution randomized trial that recruited 172 patients from 2015 to 2018. Patients underwent conserving surgery and were randomized to either adjuvant WBI (40.5Gy/15 fractions with simultaneous boost to 48 Gy to tumoral bed) or APBI (30Gy/5 fractions), both delivered with VMAT-RA technique. Clinical evaluation was performed during the first visit, once a week during radiotherapy and during follow up. Cosmesis was assessed using the Harvard Scale for Breast Cosmesis. At the time of the analysis 161 patients were eligible, 53% in the WBI and 47% in the APBI group, with a median follow-up of 67 months. Most common late skin toxicities were G1 fibrosis (32%) and oedema (28%) and were higher in the WBI group; no G3 toxicities were observed. Cosmesis was rated poor in only 6 cases. 147 patients had no evidence of disease at the last follow-up, and no patients died of the disease. Mature results confirm the safety and efficacy of APBI in selected early stage breast cancer patients. Late toxicity is improved in the APBI arm at the cost of a slight increase in local relapse. Further studies are ongoing to better elucidate the use of APBI as a de-escalation approach.

Prospective Cohort Study to Evaluate Toxicity and Cosmesis between Interstitial APBI and Ultra-Hypo-Fractionated Whole Breast Irradiation in Patients with Early Breast Cancer

Both interstitial multi-catheter brachytherapy based accelerated partial breast irradiation (APBI) and ultra-hypo-fractionated whole breast irradiation (WBI) with 5 fractions can complete treatment in a short time and result in lower treatment-related costs. Although data are available on their toxicity compared with conventional and hypo-fractionated regimens, there are few data directly comparing these two techniques. This prospective cohort study enrolled early breast cancer patients with negative ink margin, T1 or T2 stage, and tumor size of 3 cm or less, with 0 to 3 positive lymph nodes after adequate axillary dissection or negative sentinel lymph node biopsy (N0-1), regardless of receptor status (ER, PR, HER2neu). Of the total 31 patients, 15 received APBI with multi-catheter interstitial brachytherapy (35 Gy in10 fractions over 5 days with a minimum interval of 6 hours between fractions) and 16 patients received WBI (27 Gy in 5 fractions over 5 days) with either 3DCRT or VMAT technique. Acute toxicity was assessed using the RTOG toxicity grading and breast cosmesis was assessed using the Harvard breast cosmesis score. Toxicity and cosmesis were assessed immediately after treatment, after one month, and after three months of treatment. Results were compared between groups using the Mann Whitney U test. All patients completed a 3-month follow-up after completion of treatment. There was no statistically significant difference between the 2 groups in terms of highest grade toxicity (p = 0.97) and acute toxicity immediately after RT (p = 1.0) and after 1 month of RT (p = 0.91). However, at 3 months, more patients in the WBI group had a residual skin reaction than in the APBI group (p = 0.03). There was no statistically significant difference in breast cosmesis scores at any time point. 53.3%, 6.6% had grade 1 and 2 skin toxicities respectively immediately after RT in the APBI group and 62.5% of patients had grade 1 skin toxicity in WBI group. After 1 month 26.6%, 26.6% & 13.3% patients had grade 2, grade 1 and grade 3 toxicities respectively. In the WBI group, at 1 month, 50%, 18.7% and 12.5% patients had grade 1, 3 and 2 skin toxicities respectively. At 3 months, 42.8% and 7.1% of patients in the APBI group had grade 1 and grade 2 toxicities, respectively. In the WBI group, 78.5% and 7.1% of patients had grade 1 and 2 skin toxicities respectively. In this study, no difference in acute toxicity or breast cosmesis was demonstrated between APBI-based interstitial brachytherapy and ultra-hypo-fractionated WBI. Since both regimens can be administered within 5 days, the decision between them is challenging for both physicians and patients. This study can be considered hypothesis-generating and used for further planning of equivalence or noninferiority studies.

Second Conservative Treatment for Local Recurrence Breast Cancer: A GEC-ESTRO Oncological Outcome and Prognostic Factor Analysis

For second ipsilateral breast tumor event (2nd IBTE), second conservative treatment (2nd CT) combining lumpectomy plus accelerated partial breast reirradiation (APBrI) represents a curative option. The aim of this study was to analyze oncological prognostic factors for patients with a 2nd IBTE treated with 2nd CT. An analysis of clinical practices was conducted across 7 academic hospitals/cancer centers in 6 European countries based on the GEC-ESTRO database. Patients presenting a 2nd IBTE occurring after conservative surgery (lumpectomy+axillary evaluation) and irradiation performed for the primary tumor underwent a 2nd CT with brachytherapy-based APBrI. The main outcome was 5-year cumulative incidence (CI) rate of second local relapse. All analyzed patients were classified according to risk groups for Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) accelerated partial breast irradiation (APBI) and molecular classification and time interval between first and second breast surgery (TIS1S2). Finally, we combined GEC-ESTRO APBI, molecular, and TIS1S2 risk groups, leading to the definition of a new score (named TAM: score based on the combination of time interval [T] between first and second surgery and APBI [A] and molecular [M] classifications) specifically designed for 2nd IBTE oncological outcome analysis. From July 1994 to January 2021, a total of 508 patients received a 2nd CT. At the time of 2nd IBTE, median age was 64.6 years (range, 56.2-72.6). With a median follow-up of 60.9 months (56.2-72.6), the 5-year second local relapse CI rate was 4% (95% confidence interval [95% CI], 2%-6%). The 5-year distant metastasis disease CI rate was 7% (95% CI, 4%-10%). Five-year disease-free and overall survival rates were 89% (95% CI, 86%-93%) and 91% (95% CI, 88%-94%), respectively. In multivariate analysis, TAM score was an independent prognostic factor for all the oncological items (P < .001) except disease-specific survival (P=.07) and overall survival (P=.09). The grade ≥3 late toxicity rate was 12.1%. This analysis of 2nd CT combining lumpectomy with APBrI for 2nd IBTE confirmed the excellent oncological results obtained after 2nd CT. Furthermore, the GEC-ESTRO TAM score appears to be an important prognostic factor, assisting patients and physicians in the decision-making process.

Cosmetic Outcome and Toxicity After Stereotactic Accelerated Partial Breast Irradiation in Early Breast Cancer: A Prospective Observational Cohort Study

The aim of this work was to prospectively evaluate the toxicity and cosmetic outcomes of 5-fraction, stereotactic, accelerated partial breast irradiation (APBI). This prospective observational cohort study enrolled women who underwent APBI for invasive carcinoma or carcinoma in situ of the breast. APBI was delivered using a CyberKnife M6 robotic radiosurgery system at 30 Gy in 5 nonconsecutive, once-daily fractions. Women undergoing whole breast irradiation (WBI) were also enrolled for comparison. Patient-reported and physician-assessed adverse events were recorded. Breast fibrosis was measured using a tissue compliance meter, and breast cosmesis was assessed using BCCT.core (an automatic, computer-based software). Outcomes were collected until 24 months posttreatment according to the study protocol. In total, 204 patients (APBI, n=103; WBI, n=101) were enrolled. Regarding patient-reported outcomes, the APBI group reported significantly less skin dryness (6.9% vs 18.3%; P=.015), radiation skin reaction (9.9% vs 23.5%; P=.010), and breast hardness (8.0% vs 20.4%; P=.011) at 6 months than the WBI group. On physician assessment, the APBI group had significantly less dermatitis at 12 months (1.0% vs 7.2%; P=.027) than the WBI group. Any severe toxicities after APBI were rare in patient-reported outcomes (score ≥3, 3.0%) and physician assessments (grade ≥3, 2.0%). In the uninvolved quadrants, measured fibrosis in the APBI group was significantly lower than that in the WBI group at 6 (P=.001) and 12 (P=.029) months but not at 24 months. In the involved quadrant, measured fibrosis in the APBI group was not significantly different from that in the WBI group at any time. Cosmetic outcomes in the APBI group were mostly excellent or good (77.6%) at 24 months, and there was no significant cosmetic detriment from the baseline. Stereotactic APBI was associated with less fibrosis in the uninvolved breast quadrants than WBI. Patients showed minimal toxicity and no detrimental effects on cosmesis after APBI.

Accelerated Partial Breast Irradiation vs. Intraoperative Radiation Therapy for Early-Stage Breast Cancer and Ductal Carcinoma In Situ

<h3>Purpose/Objective(s)</h3> Accelerated partial breast irradiation (APBI) delivered with intensity modulated radiation therapy (IMRT) over 5 fractions represents an attractive and convenient method of delivering adjuvant radiation therapy without compromising oncologic or aesthetic outcomes. Intraoperative radiation therapy (IORT) is another method of delivering radiation therapy to the lumpectomy cavity. Initial results reported in clinical trials utilizing IORT were encouraging; however, with longer follow up, higher rates of local recurrence have been observed in contrast to APBI. We report the outcomes of a large cohort of patients treated with 5 fraction APBI and IORT at our institution after undergoing breast conservation surgery (BCS) for stage 0-IIA breast cancer. <h3>Materials/Methods</h3> We performed a retrospective review of 482 patients with stage I-IIA stage breast cancer and ductal carcinoma in situ (DCIS) treated with lumpectomy and APBI at our institution. In total, 267 patients in our cohort received IMRT from December of 2015 to May of 2021 while 215 patients received IORT from October of 2011 to May of 2019. All patients in the IMRT group received 30 Gy in 5 fractions. All patients in the IORT group received 20 Gy in 1 fraction prescribed to the applicator surface delivered at the time of surgery without additional radiation. Kaplan-Meier analysis was used to estimate locoregional control (LRC) and overall survival (OS) among the 2 groups. <h3>Results</h3> Mean age at diagnosis of the patients was 67 years in the IMRT group and 71 years in the IORT cohort. The IMRT group included 220 patients with Stage I breast cancer (82%), 4 patients with Stage IIA breast cancer (1%), and 43 (16%) patients with DCIS. The IORT group had 198 (92%) with stage I breast cancer, 12 patients (6%) had Stage IIA breast cancer, and 5 patients (2%) had DCIS. After a median follow up of 16 months in the APBI group, only 1 (0.4%) patient experienced a local recurrence, and no patients experienced a regional or distant recurrence. After a median follow up of 55 months in the IORT group, 12 patients (5.6%) experienced a local recurrence, 1 patient (0.5%) experienced a nodal recurrence, and 4 patients (1.9%) experienced a distant recurrence. There was no significant statistical difference in hormonal therapy receipt between both groups (75.3% vs 76.7%, p=0.64). There was no significant difference in 2-year LRC between the APBI and the IORT groups (98.9% in the APBI group vs. 99% in the IORT group, p=0.32). There were no differences in 2-year OS between the two groups (99.6% vs 98.5%, p=0.33). The 5-year LRC was 92.7% in the IORT group. <h3>Conclusion</h3> In a large institutional series of patients with Stage 0-IIA breast cancer treated with BCS followed by 5 fraction APBI or IORT, despite having low risk features and high rates of endocrine therapy use, IORT was associated with high rates of locoregional recurrence of approximately 7% at 5 years. Longer term follow up is needed for comparative effectiveness observations between the two groups.

The comparison of transforming growth factor beta-1 serum levels in early-stage breast cancer patients treated with external beam whole breast irradiation plus boost versus interstitial brachytherapy accelerated partial breast irradiation

PURPOSETransforming growth factor beta-1 (TGF-β1) is a profibrotic cytokine used as an early biomarker to develop radiation-induced fibrosis (RIF). This study aimed to compare TGF-β1 serum levels in early-stage breast cancer patients treated with whole-breast radiation therapy (WBRT) plus boost versus accelerated partial breast irradiation (APBI) using multicatheter interstitial brachytherapy. METHODS AND MATERIALSThis clinical trial study was conducted on 20 women with early-stage breast cancer after breast-conserving surgery candidate for adjuvant radiotherapy in Golestan hospital, Ahvaz, in 2021. In one group APBI with high-dose-rate brachytherapy (n = 10), the other group WBRT with external beam radiation plus boost (n = 10) was performed. Serum level of TGF-β1 was evaluated before radiotherapy, immediately after the end of radiotherapy and three months after the end of radiotherapy by Enzyme-linked immunosorbent assay technique (ELISA). ResultsMedian serum TGF-β1 level before radiotherapy was not significantly different between the two groups (p = 0.971). In both APBI and WBRT groups, serum TGF-β1 levels significantly decreased immediately after radiotherapy compared to before treatment (p = 0.005 and p = 0.007, respectively); But three months after radiotherapy, serum TGF-β1 levels increased significantly in the WBRT group (40.50 to 77.41 pg/mL; p = 0.017), while no significant change was observed in the APBI group (24.75 to 30.50 pg/mL; p = 0.332). ConclusionSHigher TGF-β1 values in the WBRT group after radiotherapy can be used as an early and vital biomarker in this treatment, and this data may corroborate links between TGF-beta1 and fibrosis and fibrosis rates between APBI and WBRT; It also shows the preference for using the brachytherapy technique in this group of patients. However, due to the small number of samples, definitive conclusions require further prospective studies.

The Acute and Late Toxicities of MRI-Guided External Beam Partial Breast Irradiation Delivered Using a Once-per-Day Regimen

<h3>Purpose/Objective(s)</h3> The use of external beam accelerated partial breast irradiation (APBI) using a twice-per-day regimen has raised concerns about increase rates of late toxicities. We compared toxicity outcomes of external beam APBI using a once-per-day regimen and accelerated hypofractionated whole breast irradiation (AWBI) in patients with early-stage breast cancer. <h3>Materials/Methods</h3> This was a single-institution, retrospective cohort study. Patients aged ≥50 years with pTisN0 or pT1N0 breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included. APBI was delivered at 38.5 Gy in 10 fractions once daily using magnetic resonance imaging (MRI)-guided radiotherapy only to patients who were strictly "suitable", according to the ASTRO-APBI guidelines. AWBI was delivered at 40.5–43.2 Gy in 15 or 16 fractions with or without a boost. <h3>Results</h3> Between October 2015 and December 2018, 173 and 300 patients underwent APBI and AWBI, respectively. At a median follow-up of 34.9 months (range 7.1 to 55.4 months), the 3-year recurrence-free survival rates of the APBI and AWBI groups were both 99.2% (<i>P</i> = 0.63). Acute toxicities were less frequent in the APBI than AWBI group (grade 1: 95 [54.9%] vs. 233 [77.7%] patients; grade 2: 7 [4.0%] vs. 44 [14.7%] patients; no grade ≥3 toxicities were observed in either group, <i>P</i> < 0.001). Late toxicities were less common in the APBI than AWBI group (grade 1: 112 [64.7%] vs. 197 [65.7%] patients; grade 2: 9 [5.2%] vs. 64 [21.3%] patients; grade 3: 0 vs. 5 [1.7%] patients, <i>P</i> < 0.001). Multivariate analysis showed that APBI was significantly associated with fewer late toxicities of grade ≥2 compared with AWBI (odds ratio 4.17, <i>P</i> = 0.006). <h3>Conclusion</h3> Once-per-day APBI using MRI-guided radiotherapy afforded excellent locoregional control and fewer toxicities compared with AWBI. This scheme could be an attractive alternative to AWBI in patients who meet the ASTRO-APBI guidelines.

The Acute and Late Toxicities of MRI-Guided External Beam Partial Breast Irradiation Delivered Using a Once-Per-Day Regimen.

Background and PurposeThe use of external beam accelerated partial breast irradiation (APBI) using a twice-per-day regimen has raised concerns about increase rates of late toxicities. We compared toxicity outcomes of external beam APBI using a once-per-day regimen and accelerated hypofractionated whole breast irradiation (AWBI) in patients with early-stage breast cancer.Materials and MethodsThis was a single-institution, retrospective cohort study. Patients aged ≥50 years with pTisN0 or pT1N0 breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included. APBI was delivered at 38.5 Gy in 10 fractions once daily using magnetic resonance imaging (MRI)-guided radiotherapy only to patients who were strictly “suitable”, according to the ASTRO-APBI guidelines. AWBI was delivered at 40.5–43.2 Gy in 15 or 16 fractions with or without a boost.ResultsBetween October 2015 and December 2018, 173 and 300 patients underwent APBI and AWBI, respectively. At a median follow-up of 34.9 months (range 7.1 to 55.4 months), the 3-year recurrence-free survival rates of the APBI and AWBI groups were both 99.2% (p=0.63). Acute toxicities were less frequent in the APBI than AWBI group (grade 1: 95 [54.9%] vs. 233 [77.7%] patients; grade 2: 7 [4.0%] vs. 44 [14.7%] patients; no grade ≥3 toxicities were observed in either group, p<0.001). Late toxicities were less common in the APBI than AWBI group (grade 1: 112 [64.7%] vs. 197 [65.7%] patients; grade 2: 9 [5.2%] vs. 64 [21.3%] patients; grade 3: 0 vs. 5 [1.7%] patients, p<0.001). Multivariate analysis showed that APBI was significantly associated with fewer late toxicities of grade ≥2 compared with AWBI (odds ratio 4.17, p=0.006).ConclusionOnce-per-day APBI afforded excellent locoregional control and fewer toxicities compared with AWBI. This scheme could be an attractive alternative to AWBI in patients who meet the ASTRO-APBI guidelines.

Abstract PS15-19: Preoperative selection of patients with early-stage invasive breast cancer for intraoperative radiation therapy (IORT): A single-institution experience

Abstract Purpose/Objective: Intraoperative radiation therapy (IORT) is a form of accelerated partial breast irradiation (APBI) delivered at the time of lumpectomy for early-stage breast cancer. Upfront selection of patients based on favorable preoperative characteristics is important to achieve good outcomes. Here we present our single-institution experience in the management of invasive breast cancer with IORT. We focused on the classification of patient suitability for IORT by the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines using preoperative and postoperative clinicopathologic factors, as well as treatment outcomes and recurrences. Materials/Methods: We reviewed our institutional prospective registry database (AAAJ8512) to identify patients with biopsy-proven invasive breast cancer treated with breast IORT between 9/2013 and 4/2020 using the Zeiss Intrabeam™. Patients received a single dose of 20Gy delivered to the lumpectomy cavity surface at the time of planned surgery. We excluded patients from analysis with prior radiation to the breast, or triple negative disease at initial diagnosis. We reviewed preoperative and postoperative clinicopathologic factors to determine each patient’s ASTRO APBI suitability (suitable, cautionary or unsuitable) based on the 2017 consensus guidelines. Results: 237 patients were treated with IORT for early stage breast cancer. Median age was 67 years (range 44-94 years). Median extent of disease by conventional imaging was 1.0 cm (range 0 - 3.0cm). 51/103 (49.5%) patients with heterogeneously or extremely dense breasts underwent a MRI preoperatively. Based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable according ASTRO APBI guidelines, 46 (19.4%) cautionary and no patients were unsuitable. APBI group suitability changed in 95 (40.1%) patients based on final pathology from the time of lumpectomy, summarized in Table 1. 17 (7.2%) patients underwent re-excision for close or positive margins. 39 (16.5%) patients received additional adjuvant whole breast radiotherapy including 10/18 (56%) of unsuitable patients. Of 212 (89.5%) patients who initiated hormone therapy (HT), 191 (80.6%) were compliant at last follow up. Median follow-up for all patients was 38.2 months (0.4 - 74.5). Five (2.1%) patients experienced ipsilateral breast tumor recurrence, 1 (0.4%) patient experienced new contralateral breast cancer, and 2 (1.6%) patients experienced distant recurrence with the median time to event of 27.8 months (range 6.3-50.4). Of the 5 patients with ipsilateral breast tumor recurrence, 2 (0.8%) were true local recurrences &amp;lt;2cm from the initial lumpectomy bed with the same histology as initial tumor, both cases were cautionary risk and one declined HT, 3 (1.3%) were new breast primaries occurring &amp;gt;2cm from lumpectomy bed with a different histology. Conclusion: Breast IORT is an attractive cost-effective option for women with early stage breast cancer, and our 3-year true local recurrence rate is 0.8%. Optimal patient selection is key based on preoperative characteristics. Patients who become unsuitable or cautionary for APBI based on final pathology should be considered for additional adjuvant therapy. Table 1ReasonASTRO APBI Pre-Op Suitability#SizeER (-)AgeT2ILCSuitable191Cautionary46114101122Unsuitable0ASTRO APBI Post-Op Suitability Change#SizeClose MarginsPositive MarginsLVIMultifocalILCEICSuitable to Cautionary7792023211124Suitable to Unsuitable12111Cautionary to Unsuitable624Abbreviations: ER = Estrogen Receptor; ILC = Invasive Lobular Carcinoma; LVI = Lymphovascular Invasion; EIC = Extensive Intraductal Component Citation Format: Andrea M Brown, Christine Chin, Eileen Connolly, Roshni Rao, Bret Taback, Lisa Wiechmann. Preoperative selection of patients with early-stage invasive breast cancer for intraoperative radiation therapy (IORT): A single-institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-19.

Comparison Between Accelerated Partial Breast Irradiation and Whole Breast Irradiation: APBI IMRT Florence Retrospective Analysis of Subjective, Objective and Patient-reported Cosmetic Outcomes

Accelerated partial breast irradiation (APBI) represents a valid alternative to whole breast irradiation (WBI) in selected low risk patients with early stage breast cancer. The long-term analysis of the APBI-IMRT Florence randomized phase 3 trial showed no significant difference in terms of both local and distant disease control and survival outcomes. Acute/late toxicity and cosmesis evaluations were significantly in favor of the APBI arm. The aim of this analysis is to compare the agreement between objective and subjective patient-reported outcome measures (PROMs) of cosmesis assessment. From June 2019 to January 2020, 95 women previously enrolled in the APBI-IMRT Florence trial accepted to undergo photographic assessment. Late skin toxicity was assessed following the RTOG/EORTC late Radiation Morbidity Scoring questionnaire. Digital photographs were assessed (objective method) using the BCCT.core software v.31 (Breast Cancer Conservative Treatment. Cosmetic Results). Breast cosmetic outcomes scored both by physician and patient (subjective methods) were recorded using the Harvard Breast Cosmesis Grading Scale. At median follow up of 11 years (IQR 10.5-11.6 years), we evaluated 95 patients (51 APBI, 44 WBI). Late skin toxicity rates (any grade) were significantly in favor of the APBI group of patients (36.4% vs 6%; p = 0.0003). Also, cosmetic assessment was significantly in favor of the APBI group both evaluated by physician (excellent-good [EG] 98% vs 90%, p<0.0001; fair-poor [FP] 2% vs 10%, p = 0.0455) and patient (EG 86% vs 70%, p<0.0001; FP 14% vs 30%, p<0.0001). The BCCT.core cosmetic assessment showed significantly improved outcomes in the APBI group (EG 65% vs FP 35%) as compared to WBI group (EG 52% vs FP 48%; p = 0.0001). We observed a good agreement between BCCT.core objective evaluation and both patients (p = 0.19) and physicians PROMs (p = 0.17). Patients treated with APBI showed significant improved late toxicity and cosmetic outcomes. There is a significative agreement between patients/physician PROMs and BCCT.core. This score has proven to be a feasible tool in breast cancer clinical practice.

Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial

Whole-breast irradiation after breast-conserving surgery for patients with early-stage breast cancer decreases ipsilateral breast-tumour recurrence (IBTR), yielding comparable results to mastectomy. It is unknown whether accelerated partial breast irradiation (APBI) to only the tumour-bearing quadrant, which shortens treatment duration, is equally effective. In our trial, we investigated whether APBI provides equivalent local tumour control after lumpectomy compared with whole-breast irradiation. We did this randomised, phase 3, equivalence trial (NSABP B-39/RTOG 0413) in 154 clinical centres in the USA, Canada, Ireland, and Israel. Adult women (>18 years) with early-stage (0, I, or II; no evidence of distant metastases, but up to three axillary nodes could be positive) breast cancer (tumour size ≤3 cm; including all histologies and multifocal breast cancers), who had had lumpectomy with negative (ie, no detectable cancer cells) surgical margins, were randomly assigned (1:1) using a biased-coin-based minimisation algorithm to receive either whole-breast irradiation (whole-breast irradiation group) or APBI (APBI group). Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with or without a supplemental boost to the tumour bed, and APBI was delivered as 34 Gy of brachytherapy or 38·5 Gy of external bream radiation therapy in 10 fractions, over 5 treatment days within an 8-day period. Randomisation was stratified by disease stage, menopausal status, hormone-receptor status, and intention to receive chemotherapy. Patients, investigators, and statisticians could not be masked to treatment allocation. The primary outcome of invasive and non-invasive IBTR as a first recurrence was analysed in the intention-to-treat population, excluding those patients who were lost to follow-up, with an equivalency test on the basis of a 50% margin increase in the hazard ratio (90% CI for the observed HR between 0·667 and 1·5 for equivalence) and a Cox proportional hazard model. Survival was assessed by intention to treat, and sensitivity analyses were done in the per-protocol population. This trial is registered with ClinicalTrials.gov, NCT00103181. Between March 21, 2005, and April 16, 2013, 4216 women were enrolled. 2109 were assigned to the whole-breast irradiation group and 2107 were assigned to the APBI group. 70 patients from the whole-breast irradiation group and 14 from the APBI group withdrew consent or were lost to follow-up at this stage, so 2039 and 2093 patients respectively were available for survival analysis. Further, three and four patients respectively were lost to clinical follow-up (ie, survival status was assessed by phone but no physical examination was done), leaving 2036 patients in the whole-breast irradiation group and 2089 in the APBI group evaluable for the primary outcome. At a median follow-up of 10·2 years (IQR 7·5-11·5), 90 (4%) of 2089 women eligible for the primary outcome in the APBI group and 71 (3%) of 2036 women in the whole-breast irradiation group had an IBTR (HR 1·22, 90% CI 0·94-1·58). The 10-year cumulative incidence of IBTR was 4·6% (95% CI 3·7-5·7) in the APBI group versus 3·9% (3·1-5·0) in the whole-breast irradiation group. 44 (2%) of 2039 patients in the whole-breast irradiation group and 49 (2%) of 2093 patients in the APBI group died from recurring breast cancer. There were no treatment-related deaths. Second cancers and treatment-related toxicities were similar between the two groups. 2020 patients in the whole-breast irradiation group and 2089 in APBI group had available data on adverse events. The highest toxicity grade reported was: grade 1 in 845 (40%), grade 2 in 921 (44%), and grade 3 in 201 (10%) patients in the APBI group, compared with grade 1 in 626 (31%), grade 2 in 1193 (59%), and grade 3 in 143 (7%) in the whole-breast irradiation group. APBI did not meet the criteria for equivalence to whole-breast irradiation in controlling IBTR for breast-conserving therapy. Our trial had broad eligibility criteria, leading to a large, heterogeneous pool of patients and sufficient power to detect treatment equivalence, but was not designed to test equivalence in patient subgroups or outcomes from different APBI techniques. For patients with early-stage breast cancer, our findings support whole-breast irradiation following lumpectomy; however, with an absolute difference of less than 1% in the 10-year cumulative incidence of IBTR, APBI might be an acceptable alternative for some women. National Cancer Institute, US Department of Health and Human Services.

External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial

Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

APBI (Accelerated Partial-Breast Irradiation) Versus WBI (Whole-Breast Irradiation) Delivered with the Same Dose Fractionation: A Propensity Score Matched Analysis of Two Prospective Studied Cohorts

The recent updates of the RAPID and RTOG 0413 trials have led to renewed interest in the question of APBI versus WBI outcomes. On the other hand, IMPORT-LOW, which was the only APBI randomized study strictly testing treatment volume without the confounding effect of dose-time factors, reported non-inferiority of APBI with fewer late toxicities. In this study, we report our institutional experience comparing two matched prospective cohorts of breast cancer patients treated with the same dose-fractionation using APBI or WBI. Two phase II trials using the same dose fractionation of 4995 cGy in 15 fractions enrolled early stage breast cancer patients at our institution between 2008 and 2017; one utilizing APBI and the other utilizing WBI. A total of 184 patients were enrolled in both trials (34 on the APBI and 150 on the WBI). Patients who received regional nodal irradiation or who were treated prone on the WBI trial were excluded. We then performed a propensity score 1:1 match between the two cohorts using age, histology, breast volume, and seroma volume. Outcomes of interest included loco-regional control, acute and late toxicity, and cosmesis. Cosmesis was scored using the Harvard Cosmesis Scale; toxicities were recorded using CTCAE version 4.03. A total of 68 patients were matched. All patients had T1-T2, N0 disease with negative margins. Median follow up was 62.5 months [6-96] for the WBI patients versus 92.5 months [23-119] for the APBI patients. Median time to final cosmetic evaluation was 24.5 months [6-67] in the WBI cohort versus 90 months [9-119] in the APBI cohort. In accordance with the propensity score match, breast size mean (1400 cc vs 1600 cc; p =0.15), seroma size mean (37 cc vs 49 cc, p=0.27) and mean age (58 vs 60, p=0.17) were similar in the two groups. Ipsilateral breast recurrence rates were similar between the two groups (2/34, 5.9%) in the APBI versus (3/34, 8.8%) in the WBI, p= 1.0. In the WBI group, 1 patient had distant metastasis 6 years after treatment and 1 patient had a contralateral breast recurrence (CBR). In the APBI group, 4 patients had CBR. At final cosmetic evaluation, 91.2% in each cohort had excellent/good cosmesis, 5.9% in each cohort had fair cosmesis and 2.9% (1 patient in each cohort) had poor cosmesis, p = 0.92. In the WBI cohort, 11/34 patients had grade 2 or 3 acute toxicities (32.4%) versus 2/34 in the APBI group (5.9%), p= 0.01. In the WBI cohort, 12/34 patients had grade 2 or 3 late toxicities (35.3%) versus 7 in the APBI group (20.6%), p= 0.28. Clinical outcomes, toxicity profiles and cosmetic results were similar in patients treated with APBI or WBI, with significantly fewer grade 2–3 acute side effects after APBI. Our results are in agreement with the IMPORT-LOW outcomes and suggest that with similar fractionation schemes APBI and whole breast are associated with similar outcomes.

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial

Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. German Cancer Aid.

Catheter-Based Accelerated Partial Breast Brachytherapy Results in Excellent Patient-Reported Quality of Life

Accelerated partial breast irradiation (APBI) and whole breast radiotherapy (WBR) are treatment options for early stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving APBI or WBR. 197 chronologically matched patients (pts) with low risk, early stage breast cancer were treated with either APBI or WBR between October 2012 and May 2015. The Linear Analog 10-point Scales (LASA), Breast Cancer Treatment Outcome Scale (BCTOS), and Harvard Breast Cosmesis Scale (HBCS) were used to assess overall quality of life (LASA), pain (LASA, BCTOS), fatigue (LASA), perceived aesthetic and functional status (BCTOS, LASA), and breast cosmesis (BCTOS, HBCS). Comparisons of PROs between treatment groups were performed using Fisher exact test, chi-square, Wilcoxon rank-sum, and regression methods. Survey compliance was 66% (64 APBI and 67 WBR pts). Median follow-up was 13.3 months, with a mean interval between the last fraction and survey completion of 15.4 v 14.2 months (p=0.58), for the APBI and WBR groups, respectively. The majority of respondents had grade 1-2 (86%), T1 (92%), and N0 (93%) in-situ or invasive ductal carcinoma. Pts treated with WBR were more likely to be younger (median 65 v 69 yrs, p=0.02), have T2 tumors (15% v 2%, p=0.01), and to receive chemotherapy (21% v 2%, p<0.001). In the WBR group, the median dose delivered was 42.56 Gy in 16 fractions, with 54% of pts receiving a lumpectomy cavity boost (median dose 10 Gy). In the APBI group, the median dose delivered was 34 Gy in 10 twice daily fractions utilizing an intraoperatively-placed high dose rate brachytherapy applicator. There was no difference in overall quality of life (8.5 v 8.9, p=0.14), pain (2.1 v 2.1, p=0.21) or fatigue (3.0 v 3.0, p=0.21) between the APBI and WBR groups, respectively. The mean overall BCTOS (31.6 v 34.3, p=0.52) was similar between groups, as was the BCTOS overall cosmetic status, and individual cosmetic measures including breast size, nipple appearance, breast shape, and breast heaviness (all p>0.05). Individual BCTOS functional measures, including arm heaviness, breast/arm swelling, arm/shoulder range of motion, and joint stiffness were similar between groups, all p>0.05. A higher proportion of pts receiving WBR reported breast elevation (slight: 33% v 16%, moderate: 25% v 8%, p=0.01). Skin color change relative to baseline was also more common in the WBR group (p=0.01), with a trend towards greater telangiectasia formation (p=0.053). For the APBI and WBR groups, most pts reported excellent (48% v 54%) or good (41 v 40%) cosmesis, with no difference between groups (p=0.37). APBI and WBR are associated with excellent and comparable 1-year PROs. In this sample, APBI resulted in a lesser degree of patient-reported breast elevation and skin color change relative to baseline.

Efficacy and safety of accelerated partial breast irradiation: a meta-analysis of published randomized studies.

Background and purposeAccelerated partial breast irradiation (APBI) technology has theoretical advantages in comparison with traditional adjuvant radiation therapy (whole-breast irradiation; WBI) after breast-conserving surgery. However, published randomized controlled trials have shown inconsistent outcomes. Therefore, a comprehensive assessment of the effectiveness and safety of APBI technology is needed.ResultsA total of 7 studies of 7452 patients were included in this analysis. All 7 studies reported local recurrence as an outcome. Meta-analysis of 5 trials that included 6486 patients showed significantly different 5-year local recurrence rates for APBI and WBI groups (hazard ratio = 4.54, 95% confidence interval: 1.78–11.61, p = 0.002). Further analysis showed that this difference may be related to the choice of treatment methods. Benefit was conferred to the APBI group for the outcome of non-breast cancer deaths. There was no significant difference between the two groups in terms of nodal recurrence, systemic recurrence, overall survival, or mortality rates. Toxicity side effects and cosmetic effects were similar in both groups, but intraoperative radiotherapy seemed to have a greater acute response.Material and methodsSearches for relevant randomized controlled trials of APBI versus WBI were performed using the following sources: PubMed, EMBASE, Cochrane Library, Web of Science. Two independent observers evaluated the identified studies. The meta-analysis was conducted using RevMan 5.2 software.ConclusionsAlthough the analysis showed that patients receiving APBI had a higher local recurrence rate, subgroup analyses suggested that this might be related to treatment options. Patients who receive accurate radiotherapy may have greater benefits. APBI is a promising treatment technology and more phase III clinical trials are expected based on new treatments.

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.

Abstract P3-12-24: Accelerated partial breast irradiation versus whole breast irradiation: short term quality of life results from a phase 3 trial

Abstract Introduction. Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC); potential advantages of APBI include shorter treatment time, improved safety profile, and a cost reduction compared with standard fractionation. We recently published the 5-years results of a phase 3 randomized trial (NCT02104895), showing a very low rate of disease failure. A significant impact on patients compliance in terms of acute and late toxicity was shown. The purpose of the present analysis is to compare the quality of life (QoL) of women with BC treated with either APBI or whole breast irradiation (WBI). Methods. Eligible patients were women aged more than 40 years with early BC suitable for breast conserving surgery. At the end of radiotherapy, patients were asked to compile the EORTC QLQ-C30 as a reliable and valid measure for cancer patients in multicultural clinical research settings, and the BR23 module as a supplementary questionnaire for issues relevant to patients with BC. Overall 205 patients (105 APBI and 100 WBI) fully completed the given questionnaires. Results. The scores of the functional and symptom scales of QLQ-C30 are reported in Table 1 and Table 2, respectively. Significant differences between the two arms emerged by global health status (p=0.0001) and most functional and symptom scales, with better outcomes in the APBI arm. Women treated with APBI reported a significantly better QoL in terms of physical, role, emotional and social functioning. We also found in the APBI arm better outcomes in term of symptoms (fatigue, pain, dyspnoea, insomnia, appetite loss). Concerning the functional and symptom scales of BR23 module, the body image perception and the future perspective were significantly better in the APBI group; no significant difference emerged for sexual functioning. Significant differences emerged also for symptom scales (breast and arm symptoms), with better scores for APBI group. Conclusion. Overall, women treated with APBI reported a significantly better short-term QoL outcome as compared with women treated using WBI. QLQ-C30 functional scale scores in the series: difference between arms and p-value from Mann Whitney U testDomainAPBISDWBISDScore Differencep-valueQL2, mean66.418.849.718.1+16.70.0001PF2, mean86.215.277.717.3+8.50.0001RF2, mean88.519.276.821.6+11.70.0001EF, mean78.617.666.324.3+12.30.0001CF, mean86.818.281.717.8+5.10.014SF, mean88.919.482.319.5+6.60.003QL2, global health status; PF2, physical functioning; RF2, role functioning; EF, emotional functioning; CF, cognitive functioning; SF, social functioning QLQ-C30 symptom scale scores in the series: difference between arms and p-value from Mann Whitney U testDomainAPBISDWBISDScore Differencep-valueFA, mean21.618.735.821.2-14.20.0001NV, mean5.29.68.011.2-2.80.047PA, mean13.219.323.719.6-10.50.0001DY, mean12.421.320.323.6-7.90.006SL, mean19.724.828.725.1-9.00.004AP, mean5.713.420.024.2-14.30.0001CO, mean13.020.420.723.6-7.70.01DI, mean4.814.95.014.5-0.20.88FI, mean14.931.08.014.3+6.90.67FA, fatigue; NV, nausea-vomiting; PA, pain; DY, dyspnoea; SL, insomnia; AP, appetite loss; CO, constipation; DI, diarrhoea; FI, financial difficulties Citation Format: Meattini I, Miccinesi G, Saieva C, Desideri I, Di Brina L, Francolini G, Scotti V, De Luca Cardillo C, Livi L. Accelerated partial breast irradiation versus whole breast irradiation: short term quality of life results from a phase 3 trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-24.

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.

Outcomes of patients with triple-negative breast cancer treated with radiation therapy.

88 Background: This study compares outcomes between different types of loco-regional treatment modalities used in patients with triple negative breast cancers. Methods: 299 patients with triple negative breast cancer diagnosed between April 2004 and August 2011 at a single institution and who were treated with radiation therapy were included in an IRB-approved retrospective review. Electronic charts were reviewed for demographic and pathologic data as well as outcome data including locoregional and distant recurrence. The median follow up period was 3 years. 200 (70%) patients underwent lumpectomy with whole breast irradiation (WBI). 68 (22.7%) patients received mastectomy and radiation while 31(10.4%) patients were treated with lumpectomy with accelerated partial breast irradiation (APBI). Results: Forty-nine patients (16.4%) experienced recurrence (10 local; 6 contralateral; 3 regional; 36 distant). There was a significant (p&lt;0.0001) difference in the proportion of patients that experienced a recurrence in each treatment group: 34% (n=23) in mastectomy with radiation group; 12% (n=23) in lumpectomy with WBI group; 10% (n=3) in lumpectomy with APBI group. On univariate analysis, tumor size, tumor stage, nodal stage, overall stage, total number of positive nodes, total number of nodes removed, and whether or not the patients had an axillary lymph node dissection were significantly associated with recurrence (p&lt;0.05). When these predictor variables, including treatment type, were examined using a stepwise cox proportional hazards regression model for recurrence, the only variables that remained significant were tumor stage (p= 0.0003) and the number of positive nodes (p= 0.0008). Survival curves were significantly different (p = 0.016) between the lumpectomy with WBI group and the mastectomy with radiation group. Over all follow-up times, the probability of survival was smallest for the mastectomy with radiation group. Conclusions: The recurrence pattern for triple negative breast cancers treated with radiation therapy was primarily distant for all treatment modalities. In our patient population, tumor stage and number of positive lymph nodes predicted for recurrence while radiotherapy technique did not.