Accelerated Partial Breast Irradiation Arm 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.

Early Results of the French Multicenter, Randomized SHARE Trial Comparing Whole Breast Irradiation vs. Accelerated Partial Breast Irradiation in Postmenopausal Women with Early-Stage Breast Cancer

The aim is to report toxicity and cosmetic outcomes at 3 and up to 9 years of follow-up of post-menopausal patients randomized to receive either standard whole breast irradiation (WBI), including hypofractionated options, versus accelerated partial breast irradiation (APBI). From December 2010 to July 2015, 1006 patients were enrolled in 34 French centers. Among the whole population, 28 patients who did not meet the final selection criteria or withdrew consent were excluded leading to a modified intention to treat analysis dataset of 978 patients (WBI: n = 488; APBI: n = 490). Median age (65y) and tumor stage pT1 (99%) rates were similar in both arms. Patients had conservative surgery with clip placement in the tumor bed. Clear margins (> 2mm) were observed in 99% of the patients. In both arms, 96-97% of the patients had negative sentinel lymph node biopsy. The median time interval between surgery and radiotherapy was 57d in WBI vs 62d in APBI. WBI schedules consisted of 50 Gy in 25 fr+16 Gy (n = 212) or 40 Gy in 15 fr (n = 156) or 42.5 Gy in 16 fr (n = 120). APBI arm consisted of 38.5 Gy or 40 Gy in 10 fr, 2 fr/day. Overall, 94 patients from the APBI arm finally received standard WBI. For statistical considerations, SHARE trial, sponsored by UNICANCER (NCT01247233) is a non-inferiority randomized controlled trial comparing APBI versus WBI in terms of local control as primary objective. Secondary endpoints were severe toxicity (NCI-CTCAE v4 grade ≥ 2), and cosmetic results. For both outcomes, we estimated the cumulative incidences (CI) using Kalbfleish and Prentice method, considering disease relapse, secondary cancer or death as competing events. Treatment effect (APBI vs WBI) was estimated by cause-specific Hazard Ratios (cs-HR) from Cox models. Median follow-up was 5.8y (range, 0.13-9.5). The number of deaths was 27, and the number of local relapses was 8. Among the 978 patients, 582 and 396 had finally WBI and APBI, respectively. The rates of post-operative hematoma, edema and infection were low: 8-9%, 2%, 3-2%, respectively. When considering any type of severe toxicity, we observed a significant reduction rate in APBI compared to WBI: cs-HR = 0.73 (95% confidence interval: 0.61-0.88); p = 0.001, and 3-year CI of severe toxicity at 45% in WBI vs 36% in APBI arm. The difference was also in favor of APBI when considering breast skin toxicity alone: cs-HR = 0.55 (0.44-0.70), p<0.001 and 3-year CI at 36% in WBI vs 21% in APBI arm. Conversely, for breast other toxicities, WBI was found less toxic than APBI with a 3-year CI of 8% vs 15%, respectively. When considering cosmetic results, we observed no significant difference between the two arms in both evaluations by physicians and patients. Historically SHARE is the first APBI trial that included hypofractionated schedules in the standard arm. We report increased risk of severe toxicity and skin breast toxicity in standard arm as compared with APBI arm without any difference in terms of cosmetic results. Longer follow-up is needed.

Economic evaluation and budget-impact of accelerated partial breast irradiation (APBI) versus standard or hypofractionated whole breast irradiation (WBI) in postmenopausal women with early-stage breast cancer. Results from the French SHARE randomized trial

PurposeThis economic evaluation reports the incremental cost-utility ratio and national budget impact in France of accelerated partial breast irradiation (APBI) vs standard or hypofractionated whole breast irradiation (WBI) in breast cancer patients at low risk of local recurrence. Materials and methodsWe compared 490 women randomized to the APBI (ten fractions delivered twice daily over one week) with 488 women in the WBI arm (one fraction per day delivered five days per week over three or six weeks). We took the perspective of the French national health insurance with a three-year time horizon. The outcome was quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was estimated and uncertainty was explored by probabilistic bootstrapping. Transportation and sick leave costs were added in a sensitivity analysis and a national budget impact analysis based on the incidence of breast cancer estimates in France performed. ResultsAt three years, the average cost per patient was €2,549 (±1,954) in the APBI arm and €4,468 (±1,586) in the WBI arm (p-value < 0.001), radiotherapy was the main driver of the difference between the two arms. No significant difference was found in QALYs. For an average of 60,000 new cases of breast cancer diagnosed annually in France, 28,000 would be eligible for treatment with APBI. A 100% uptake of APBI would result in a yearly30 million€ cost saving. ConclusionAPBI for the treatment of postmenopausal women with early-stage breast cancer is cost saving, with no difference in outcome measured by QALYs.

DCIS: When is accelerated partial breast irradiation an option? A meta-analysis on outcomes and eligibility

BackgroundThe natural history of DCIS may not be progression to invasive breast cancer (IBC). Accelerated partial breast irradiation (APBI) has emerged as an alternative to whole breast radiotherapy (WBRT). The purpose of this study was to assess the impact of APBI on DCIS patients. Materials and methodsEligible studies from 2012 to 2022 were identified in PubMed, Cochrane Library, ClinicalTrials, and ICTRP. A meta-analysis was done comparing recurrence rates, breast-related mortality rates, and adverse events of APBI versus WBRT. A subgroup analysis of 2017 ASTRO Guidelines “Suitable” and “Unsuitable” groups was performed. Forest plots and quantitative analysis were done. ResultsSix studies were eligible (3 on APBI versus WBRT, 3 on APBI suitability). All had a low risk of bias and publication bias. The cumulative incidence was the following for APBI and WBRT respectively: IBTR was 5.7% and 6.3% with odds ratio of 1.09, 95% CI [0.84, 1.42], mortality rate was 4.9% and 5.05%, and adverse events was 48.87% and 69.63%. All had no statistical significance between groups. Adverse events were found to favor the APBI arm. Recurrence rate was significantly less in the Suitable group with an odds ratio 2.69, 95% CI [1.56, 4.67], favoring it over the Unsuitable group. ConclusionAPBI was comparable to WBRT in terms of recurrence rate, breast cancer-related mortality rate, and adverse events. APBI was not inferior to WBRT and showed better safety in terms of skin toxicity. Patients classified as suitable for APBI had significantly lesser recurrence rate.

Abstract PD3-05: Early results of the French multicenter, randomized SHARE trial comparing whole breast irradiation versus accelerated partial breast irradiation in postmenopausal women with early-stage breast cancer

Abstract Purpose: The aim of current analyses is to report toxicity and cosmetic outcomes at 3 and up to 9 years of follow-up of post-menopausal patients randomized to receive either standard external beam whole breast radiotherapy (WBI), including hypofractionated options, versus accelerated partial breast irradiation (APBI). Methods and materials: From December 2010 to July 2015, 1006 patients were enrolled in 34 French centers (503 in each arm). Among the whole population, 28 patients who did not meet the final selection criteria or withdrew consent were excluded leading to a modified intention to treat analysis dataset of 978 patients (WBI: n=488; APBI: n=490). Median age (65y) and tumor stage pT1 (99%) rates were similar in both arms. Patients had conservative surgery with clip placement in the tumor bed. Clear margins (&amp;gt; 2mm) were observed in 99% of the patients. In both arms, 96-97% of the patients had negative sentinel lymph node biopsy (SLNB; median number: 4 in WBI arm and 5 in APBI), luminal BC. Ductal histology was observed 82%. Only 2% and 1% of patients had grade III and pN(i+) disease. The median time interval between surgery and radiotherapy was 57d in WBI vs 62d in APBI. WBI schedules consisted of: 50Gy in 25fr + 16Gy boost (n=212) or 40Gy in 15fr (n=156) or 42.5Gy in 16fr (n=120), while APBI arm consisted of 38.5Gy or 40Gy in 10fr. Overall, 94 patients from the APBI arm finally received standard WBI. For statistical considerations, SHARE trial, sponsored by UNICANCER (NCT01247233) is a non-inferiority randomized controlled trial comparing APBI versus WBI in terms of local control as primary objective. Secondary endpoints were severe toxicity (NCI-CTCAE v4 grade ≥ 2), and cosmetic results, evaluated by doctors and by patients, over the entire follow-up. For both outcomes, we estimated the cumulative incidences (CI) using Kalbfleish and Prentice method, considering disease relapse, secondary cancer or death as competing events. Treatment effect (APBI vs WBI) was estimated by cause-specific Hazard Ratios (cs-HR) from Cox models adjusted on stratification factors. Results: Median follow-up was 5.8y (range, 0.13-9.5). The number of deaths was 27, and the number of local relapses was 8. Among the 978 patients, 582 and 396 had finally WBI and APBI, respectively. The rates of post-operative hematoma, edema and infection were low: 8-9%, 2%, 3-2%, respectively. When considering any type of severe toxicity, we observed a significant reduction rate in APBI compared to WBI: cs-HR=0.73 (95% confidence interval: 0.61-0.88); p=0.001, and 3-year cumulative incidence (CI) of severe toxicity at 45% (41-49) in WBI vs 36% (32-40) in APBI arm. The difference was also in favor of APBI when considering breast skin toxicity alone: cs-HR=0.55 (0.44-0.70), p&amp;lt; 0.001 and 3-year CI at 36% (32-40) in WBI vs 21% (18-25) in APBI arm. Conversely, for breast other toxicities, WBI was found less toxic than APBI: cs-HR= 2.10 (1.51-2.91), p&amp;lt; 0.001, and 3-year CI at 8% (5-10) vs 15% (12-19), respectively. When considering cosmetic results according to the investigator, we observed no significant difference between the two arms: cs-HR=1.04 (0.81-1.33), p=0.26 and 3-year probability of remaining with good to excellent cosmetic results at 77% (73-81) in WBI arm and 78% (74-81) in APBI arm. Findings were similar when considering results according to the patient: cs-HR=1.07 (0.85-1.37), p=0.23, and 3-year probability at 74% (70-78) and 75% (70-79), respectively. Conclusions Historically SHARE is the first APBI trial that included hypofractionated schedules in the standard arm. We reported increased risk of severe toxicity and skin breast toxicity in standard arm as compared with APBI arm without any difference in terms of cosmetic results. Longer follow-up is needed. Citation Format: Yazid Belkacemi, Isabelle Gabelle-Flandin, Marie-Cécile Le Deley, Adeline Petit, Philippe Guilbert, Julien Geffrelot, Christian Carrie, Eleonor Rivin Del Campo, Chantal Hanzen, Claire Charra-Brunaud, Isabelle Lecouillard, Nicolas Magne, Agnès Tallet, Nicolas Leduc, Blaha Belgadi, Philippe Fourneret, Alexandre Coutte, Esther Capelo, Franck Darloy, Muriel Garcia Ramirez, Philippe Dudouet, Pierre Clavere, Jean-Philippe Suchaud, Guillaume Auzac, Thomas Lacornerie, Jérôme Lemonnier, Céline Bourgier, Eric Lartigau. Early results of the French multicenter, randomized SHARE trial comparing whole breast irradiation versus accelerated partial breast irradiation in postmenopausal women with early-stage breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-05.

Outcomes of Breast Brachytherapy in Stage I Breast Cancer – Data from a Large Health System

Accelerated partial breast irradiation (APBI) can be accomplished with a variety of techniques. Randomized trial data exist to support the efficacy of APBI utilizing external beam radiotherapy and interstitial multi-catheter-based brachytherapy, techniques that encompass a large volume of breast tissue. Far less data is available for smaller volume APBI techniques such as intraoperative radiotherapy (IORT) and single-entry brachytherapy devices. NSABP B-39 was the only randomized trial to include single-entry brachytherapy within the APBI arm, but too few patients received this technique to allow for a subset analysis. TARGIT-A is the only trial to evaluate photon IORT with short follow-up. Current study leverages the large patient volume of a university health system to review the experience of smaller volume APBI techniques. We hypothesize that smaller volume APBI would show inferior outcomes in loco-regional tumor control compared to larger volume APBI or whole breast irradiation in stage I breast cancer patients. The shared electronic health record of multiple institutions of a university health system was queried to identify women with either DCIS, T1N0 or T2N0 breast cancer treated with BCS between 2011 and 2014. The data collection included demographic features, known prognostic factors, tumor characteristics, treatment type, and evidence of local or regional recurrence (LRR). For the purposes of this study, the analysis was restricted to those patients treated with IORT or single-entry brachytherapy. The search identified 1386 patients who met criteria. Of these, 112 (8%) were treated with IORT to 20 Gy in a single fraction, and 116 (8%) underwent brachytherapy with a strut-adjusted volume implant (SAVI) device to 34 Gy in 10 fractions delivered twice daily. The demographic and tumor variables are listed below. The five-year rate of LRR among women treated with IORT was 3.4%, and 1.9% for women treated with SAVI brachytherapy using Kaplan-Meier estimate. In the evaluation of treatments for which randomized data are scarce, non-randomized series are vital. Health system consolidation facilitates the compilation of larger multi-hospital experiences. We report on a series of 228 low-risk patients treated with either IORT or SAVI brachytherapy with a single hospital system. The resulting LRR rates are relatively low, reflecting the trend of most modern series. Our next initiative will be to compare these outcomes to those seen for external beam radiotherapy within the same system.Abstract 2089; TableIORT (n = 112)SAVI (n = 116)Median Follow-up (mo.)67 (2.4-102)68 (1-92)Age (median)67 (49-90)59 (43-90)Stage DCIS127 T1mic1- T1a2015 T1b3330 T1c5443 T231Tumor Markers ER+111109 H2N+33 Triple -16 LVI +31 Open table in a new tab

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.

Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial

To report the long-term results of external-beam accelerated partial-breast irradiation (APBI) intensity-modulated radiation therapy (IMRT) Florence phase III trial comparing whole-breast irradiation (WBI) to APBI in early-stage breast cancer. The primary end point was to determine the 5-year difference in ipsilateral breast tumor recurrence (IBTR) between 30 Gy in 5 once-daily fractions (APBI arm) and 50 Gy in 25 fractions with a tumor bed boost (WBI arm) after breast-conserving surgery. Five hundred twenty patients, more than 90% of whom had characteristics associated with low recurrence risk, were randomly assigned (WBI, n = 260; APBI, n = 260) between 2005 and 2013. Median follow-up was 10.7 years. The 10-year cumulative incidence of IBTR was 2.5% (n = 6) in the WBI and 3.7% (n = 9) in the APBI arm (hazard ratio [HR], 1.56; 95% CI, 0.55 to 4.37; P = .40). Overall survival at 10 years was 91.9% in both arms (HR, 0.95; 95% CI, 0.50 to 1.79; P = .86). Breast cancer-specific survival at 10 years was 96.7% in the WBI and 97.8% in the APBI arm (HR, 0.65; 95% CI, 0.21 to 1.99; P = .45). The APBI arm showed significantly less acute toxicity (P = .0001) and late toxicity (P = .0001) and improved cosmetic outcome as evaluated by both physician (P = .0001) and patient (P = .0001). The 10-year cumulative IBTR incidence in early breast cancer treated with external APBI using IMRT technique in 5 once-daily fractions is low and not different from that after WBI. Acute and late treatment-related toxicity and cosmesis outcomes were significantly in favor of APBI.

Abstract GS4-06: Accelerated partial breast or whole breast irradiation after breast conservation surgery for patients with early breast cancer: 10-year follow up results of the APBI IMRT Florence randomized phase 3 trial

Abstract Background. Partial breast irradiation (PBI) is a reasonable alternative for a whole breast irradiation (WBI) in selected early stage breast cancer patients. The 5-year analysis of the APBI IMRT Florence phase 3 trial showed no significant difference in terms of ipsilateral tumor recurrence (IBTR) and survival rates between the two arms. We present the 10-year follow up data. Methods. From March 2005 to June 2013, women aged more than 40 years affected by early BC, with a maximum pathological tumor size of 25 mm, were randomly assigned in a 1:1 ratio to receive either WBI using three-dimensional conformal radiotherapy (3DCRT) or accelerated PBI (APBI) using intensity-modulated radiotherapy (IMRT) technique. Patients in the APBI arm received a total dose of 30 Gy to the tumor bed in five daily fractions. The WBI arm received 50 Gy in 25 fractions, followed by a boost on the tumor bed of 10 Gy in five fractions. The primary end-point, IBTR rate is now assessed at 10 years in the ITT population, as well as secondary endpoints: overall survival (OS), breast cancer specific survival (BCSS), distant metastasis free survival (DMFS), contralateral breast cancer (CBC), and locoregional recurrences (LRR). This trial is registered with ClinicalTrials.gov, number NCT02104895. Results. Of the 520 patients, 260 were enrolled in the APBI-arm and 260 in the WBI-arm; median age was 62.8 years (63.6 in the APBI and 61.6 in the WBI arm, p=0.20). Both treatment-arms achieved a median 10-year follow-up (10.1 in APBI-arm and 10.4 in WBI-arm, p=0.39) and were comparable regarding age, tumor size, grade, tumor type, and adjuvant endocrine treatment. No significant difference in terms of IBTR rates between treatment arms was shown (log rank test p=0.58). In the group who received APBI, the 5-year IBTR was 1.96% (5 events; 95% CI: 0.3;3.7) and the 10-year IBTR was 3.74% (9 events; 95% CI: 1.5;6.3). In the group who received WBI, the 5-year IBTR rate was 1.2% (3 events; 95% CI: 0;2.5) and the 10-year IBTR was 2.5% (6 events; 95% CI: 0.7;4.5). HR for APBI patients compared with WBI patients was 1.33 (p=0.58; 95% CI: 0.49;3.56). There were no significant differences between treatment arms regarding survival outcomes. OS (log rank test p=0.33): APBI 95.4% (95% CI: 93.6;97.2) versus WBI 94.3% (95% CI: 92.3;96.3); HR for APBI patients 0.66 (p=0.33; 95% CI: 0.29;1.53). BCSS (log rank test p=0.55): APBI 98% (95% CI: 96.8;99.2) versus WBI 97.5% (95% CI: 96.2;98.8); HR for APBI patients 0.68 (P=0.55; 95% CI: 0.19;2.42). DMFS (log rank test p=0.45): APBI 97.4% (95% CI: 96.0;98.8) versus WBI 96.1% (95% CI: 94.4;97.8); HR for APBI patients 0.67 (p=0.45; 95% CI: 0.24;1.89). Cumulative incidence estimates of 10-year LRR were 3.9% (95% CI: 2.24;5.56) for APBI versus 3.0% (95% CI: 1.53;4.47) for WBI (log rank test p=0.59). CBC observed after APBI were 5 (1.9%) as compared to 9 (3.5%) after WBI (p=0.42). Conclusion. IBTR rate after 10 years in patients with early breast cancer who were treated with APBI using IMRT technique in 5 fractions is rare and not significantly different from patients treated with WBI. OS, BCSS, DMFS, and LRR control are also comparable. Thus, APBI should be considered a reasonable alternative for a WBI in early breast cancer patients. Citation Format: Icro Meattini, Calogero Saieva, Sara Lucidi, Monica lo Russo, Vieri Scotti, Isacco Desideri, Livia Marrazzo, Gabriele Simontacchi, Monica Mangoni, Carlotta Becherini, Luca Visani, Lisa Paoletti, Erica Moretti, Luca Triggiani, Marco Bernini, Lorenzo Orzalesi, Luis Sanchez, Jacopo Nori, Stefania Pallotta, Simonetta Bianchi, Lorenzo Livi. Accelerated partial breast or whole breast irradiation after breast conservation surgery for patients with early breast cancer: 10-year follow up results of the APBI IMRT Florence randomized phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS4-06.

Abstract GS4-03: RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT)

Abstract Background Whole breast irradiation (WBI) after lumpectomy reduces the risk of local recurrence, thereby avoiding subsequent mastectomy. It is a key component of breast conserving therapy. WBI is usually given in daily fractions over 3-6 weeks. With accelerated partial breast irradiation (APBI), radiation is delivered over a week or less to the surgical cavity with a margin of normal tissue. It was introduced to provide treatment in a shorter more convenient form. 3D-CRT is an attractive approach as it is non-invasive and uses standard techniques for external beam RT that are widely available. The objective of the RAPID trial was to determine if APBI using 3D-CRT was not inferior to WBI following breast conserving surgery (BCS). Methods Women ≥40 years of age with axillary node-negative invasive ductal carcinoma, or ductal carcinoma in situ (DCIS) ≤3cm treated by BCS with clear margins of excision were eligible. Randomization was stratified for age (&amp;lt; or ≥50y), histology (DCIS alone or invasive breast cancer), tumor size (&amp;lt; or ≥1.5cm), ER status (+/-) if invasive disease, and treatment center. Patients were allocated to APBI using 3D-CRT (38.5Gy in 10 fractions delivered twice daily) or WBI (42.5Gy in 16 daily fractions or 50Gy in 25 daily fractions; boost radiation was permitted). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Important secondary outcomes included radiation toxicity and nurse assessed adverse cosmesis (fair or poor on global assessment). The trial was designed to show that the 5-year IBTR rate in the APBI arm was not inferior to the WBI arm by more than 1.5% (hazard ratio [HR] ≤ 2.02) with 85% power and a one-sided alpha of 5%. Results From February 2006 to July 2011, 2135 patients from sites in Canada, Australia, and New Zealand were randomly assigned: 1070 to APBI and 1065 to WBI. The median follow-up was 8.6 years. The mean age of the study population was 61 years; 82% of patients had invasive breast cancer and 18% had DCIS only. For invasive cancers: 60% were &amp;lt; 1.5cm and 90% were ER positive. For DCIS tumors: 68% were &amp;lt; 1.5cm. A total of 65 IBTRs were observed. For the APBI patients, the 5-year and 8-year cumulative rates of IBTR were 2.3% and 3.0%, respectively. The corresponding data for the WBI patients were 1.7% and 2.8%. The HR for APBI versus WBI was 1.27, 90% confidence interval, 0.84 to 1.91. Acute radiation toxicity (occurring within 3 months of treatment start) e.g. radiation dermatitis and breast swelling was less in patients treated with APBI compared with WBI (≥ Grade 2, 28% vs 45%, p&amp;lt;0.001). Late radiation toxicity (beyond 3 months) e.g. breast induration and telangiectasia was greater in patients treated with APBI (≥ Grade 2, 32% vs 13%, p&amp;lt;0.001 and Grade 3, 4.5% vs 1.0%, p&amp;lt;0.001). Adverse cosmesis was higher in patients treated with APBI compared with WBI at 3 years (29% vs 17%, p&amp;lt;0.001) and at 5 years (32% vs 16%, p&amp;lt;0.001). Conclusions The APBI regimen used in our trial was non-inferior to WBI in preventing local recurrence. Although it was associated with less acute toxicity, an increase in late normal tissue toxicity and adverse cosmesis was observed with APBI. Citation Format: Whelan T, Julian J, Levine M, Berrang T, Kim D-H, Gu CS, Germain I, Nichol A, Akra M, Lavertu S, Germain F, Fyles A, Trotter T, Perera F, Balkwill S, Chafe S, McGowan T, Muanza T, Beckham W, Chua B, Olivotto I. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-03.

Abstract P3-12-13: Comparison of accelerated partial breast irradiation (APBI) with whole breast irradiation (WBI) using 3D conformal external beam radiation therapy (3D CRT)

Abstract Purpose: To compare accelerated partial breast irradiation with whole breast irradiation in post breast conservation surgery (BCS) women with breast cancer. Material and methods: Women &amp;gt;35 years of age with invasive or noninvasive breast cancer ≤4 cm treated by BCS were randomized to 3D CRT APBI (34 Gy in 10 fractions given twice daily) or WBI (40 Gy in 16 fractions given once daily ± boost irradiation).The primary outcome was ipsilateral breast tumour recurrence and important secondary outcomes were adverse cosmetic outcome (fair or poor on a HARVARD/NSABP/RTOG breast cosmesis grading scale) and toxicity using the RTOG scores and LENT SOMA scale. Radiation toxicities and cosmesis was assessed directly by radiation oncologist during radiotherapy and in follow up.Patient and tumour characteristics, locoregional recurrence and distant metastases rates were compared using Fisher's exact tests.All statistical tests were two sided p values less than 0.05 were considered statistically significant. Results: Between June 2011 and December 2015, 133 women were randomized to 3D CRT APBI or WBI. Patient characteristics were balanced between two arms. There was an increased rate of acute grade 2 dermatitis in WBI arm(p=0.33). Median follow up was 60 months(range 9-84 months). Grades 1 and 2 late radiation toxicities were higher in the WBI arm compared to the APBI arm; pigmentation, fibrosis and breast shrinkage were significantly more in the WBI arm. Grades 3 and 4 late toxicity was not seen in any of the treatment arms. Adverse cosmesis at last follow up was significantly higher in patients treated with WBI, 32% as compared to 6% with APBI (p=&amp;lt;0.001). Local recurrence with APBI was 3% as compared to 1.5% with WBI and distant metastasis rate was high in WBI arm as compared with APBI, 5.9% vs 3% respectively; both not statisticaly significant. Table 1.Patient and tumor characteristicsCharacteristicsAPBI(n=65)WBI(n=68)p-valueMean age(range)50(36-75)(36-75)50(37-67)(37-67)0.13T- Stage T134(52)37(54) T228(43)28(41)0.96T33(5)3(4) N stage N057(88)59(87) N17(11)28(41)1.00N21(1)1(1) Grade 114(22)12(18) 237(56)40(59)0.5314(22)16(23) Surgical margins Negative60(92)61(90)0.79Positive5(8)7(10) LVI No56(86)55(81)0.49Yes9(14)13(19) ER Positive42(65)45(66) Negative19(29)21(31)1.00Unknown5(6)2(3) PR Positive38(58)39(57) Negative23(35)25(37)1.0Unknown4(7)4(6) Her2-neu Positive7(11)6(9)0.78Chemotherapy Yes35(54)52(76)0.78No30(46)16(24) Hormone therapy Yes49(75)49(72)0.78No16(25)19(28) Trastuzumab Yes3(43)3(50)1.00No4(57)3(50) Conclusion: In women with BCS, APBI was associated with better cosmetic outcome and late radiation toxicities compared to WBI. Local recurrence and distant metastasis was comparable in both the arms. Citation Format: Yadav BS, L S, Sharma SC, Singh R, Dahiya D. Comparison of accelerated partial breast irradiation (APBI) with whole breast irradiation (WBI) using 3D conformal external beam radiation therapy (3D CRT) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-13.

External accelerated partial breast irradiation for ductal carcinoma in situ: long-term follow-up from a phase 3 randomized trial

For a long time, accelerated partial breast irradiation (APBI) effectiveness for ductal carcinoma in situ (DCIS) has been debated, due to conflicting published results. Recent encouraging data from phase 3 trials reopened new perspectives for this radiation approach. The aim of the present study was to analyze the long-term efficacy and safety results of the series of patients with DCIS enrolled in the APBI arm of the APBI-IMRT-Florence phase 3 trial (NCT02104895). Patients were treated in a phase 3 randomized trial comparing whole breast irradiation (50 Gy in 25 fractions to the whole breast, plus 10 Gy in 5 fractions to the tumor bed) to APBI (30 Gy in 5 nonconsecutive fractions) using the intensity-modulated radiotherapy technique. Overall, 22 patients were treated in the APBI arm. Median age was 62 years (mean 59; range 42-75 years). At a median follow-up of 9.2 years (mean 8.8; range 3.8-12.1 years), no contralateral invasive/DCIS occurrence, distant metastasis, or breast cancer-related death were recorded. The 5- and 10-year local recurrence, distant metastasis-free survival, and breast cancer-specific survival were 100%. The 10-year overall survival rate was 90.9%. No late toxicity at 5 and 10 years was recorded. Waiting for pending studies and mature follow-up, we confirmed the efficacy and safety of APBI for low-risk DCIS.

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.

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.

Early Toxicity Results with 3-D Conformal External Beam Therapy (CEBT) from the NSABP B-39/RTOG 0413 Accelerated Partial Breast Irradiation (APBI) Trial

Early Toxicity Results with 3-D Conformal External Beam Therapy (CEBT) from the NSABP B-39/RTOG 0413 Accelerated Partial Breast Irradiation (APBI) Trial

Early toxicity results with 3D conformal external beam therapy (CEBT) from the NSABP B-39/RTOG 0413 accelerated partial breast irradiation (APBI) trial.

1011 Background: APBI is now being used clinically and is being evaluated in 6 clinical trials in which several forms of fractionated external beam for APBI are being used. Recent publications and presentations from small single-institution series have reported significant short-term toxicities related to 3-D CEBT, a type of APBI under evaluation in NSABP B−39/RTOG 0413. Given those results, we believe it necessary to report the current levels of toxicity in the 3−D conformal portion of the APBI arm of our trial. Methods: NSABP B−39/RTOG 0413, a multi-institutional randomized phase III trial, compares whole-breast irradiation with APBI. Included is an electronic CT- data submission process that serves as the basis of a rigorous QA program used in all 3 types of APBI, assuring dosimetric compliance. Closely monitored data on patients randomized to the APBI arm and undergoing 3−D CEBT were reviewed for overall toxicity, specifically for toxicity related to fibrosis-cosmesis and fibrosis-deep connective tissue, based on CTCAEv3.0 and NSABP/RTOG CTCAE criteria. Results: 3,862 patients are enrolled (89.8% of target accrual). Toxicity data are available for 1386 patients randomized to APBI who have received 3−D CEBT, with 974 of the latter group in their 3rd year of follow-up. With a mean time on study of 41.0 months, no significant toxicity-related issues have been raised. The rates of fibrosis-cosmesis and fibrosis-deep connective tissue toxicities are: Grade 2 ≤12%, Grade 3 ≤3% and Grade 4/5 =0% for the 3-D CEBT used in the trial. Conclusions: Contrary to findings in recent published reports the 3-D conformal APBI toxicity rates in our trial are acceptably low. Our trial surpasses others reported in patient number and length of follow-up, emphasizing the importance of large phase III randomized trials with rigorous QA to determine treatment outcomes and avoid the bias that can arise from small single-institution series. The continuation of accrual to this trial is critically important so that APBI efficacy, long-term toxicity, and QOL outcomes can be accurately assessed. Supported by NCI-U10-CA-12027, U10-CA−37377, U10-CA−69974, U10-CA−69651, and U10-CA−21661.

236 Health-related quality of life in patients with early stage breast cancer treated with breast conserving surgery and radiotherapy

Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early–late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results.Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2).No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01).Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited.