External Beam Accelerated Partial Breast Irradiation Research Articles

Effectiveness and Toxicity of Five Fraction Prone Accelerated Partial Breast Irradiation

Accelerated partial breast irradiation (APBI) after breast conserving therapy (BCT) is increasingly used to treat women with early stage breast cancer. Our institution was an early adopter of 5-fraction ABPI and delivers APBI primarily to patients in the prone position. This study reports long term oncologic and cosmetic outcome in a large cohort of women treated with 5-fraction external beam APBI. We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Late toxicities and clinician and patient rated cosmesis were evaluated for patients with > 6 month follow up. Univariate and multivariate logistic regression models were used to identify clinical and dosimetric factors associated with development of acute and late toxicities, clinician and patient rated cosmesis. All statistical tests were two-sided, and the null hypothesis was rejected for p<0.05. Kaplan Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS) and locoregional recurrence-free survival (LR-RFS). Four hundred and forty-two patients received APBI either daily (56%) or every other day (44%). Most of the patients (92%) were treated in the prone position. Average mean heart dose was 23 cGy for left-sided and 11 cGy for right-sided breast cancers. Ipsilateral lung V30% ≤ 30%. At a median follow up of 48 months (range: 5.96 - 155 months), 12 (2.7%) patients developed a local recurrence, 14 (3.2%) patients developed a contralateral breast primary, 10 patients (2.3%) developed a distant metastasis and one patient (0.2%) developed a local recurrence followed by a distant metastasis 1 month later. Out of 258 patients with > 6 month follow up, rates of late grade 1-2 telangiectasia, fibrosis, edema, atrophy and hyperpigmentation were 4%, 18%, 1%, 19% and 7% respectively. There was only one late grade 3 event in a patient who developed significant breast atrophy. The rate of good-excellent physician and patient rated cosmesis was 95% and 89% respectively (N = 256 at median follow up of 80 months). On multivariate logistic regression, patients who did not receive any adjuvant endocrine or chemotherapy were at increased risk of developing a local recurrence. Patients with PR negative disease were at increased risk of distant metastasis. Patient who experienced any grade of acute dermatitis during treatment were at increased risk of any high grade (grade ≥ 2) late adverse event and worse physician rated cosmesis. Daily or every other day treatment did not correlate with worse toxicity or clinical outcomes. Plastic surgery involvement, LVI, EIC, lobular histology, and ER negativity did not correlate with an increased risk of recurrence. Five-year LR-RFS, DFS and OS were 98%, 92.5% and 98.6% respectively. Five- fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity and excellent cosmetic scores at long term follow up.

Accelerated Partial Breast Irradiation (APBI) For HER2+ Early-Stage Breast Cancer

Historically, HER2+ breast cancer exhibited poor outcomes and, hence, has not been well-studied among trials of accelerated partial breast irradiation (APBI). We hypothesized that in contemporary practice with effective HER2-targeted agents, patients with HER2+ breast cancer now have excellent disease control and survival outcomes when treated with adjuvant APBI. Using a prospectively-maintained institutional database, we identified all HER2+ breast cancer patients treated with breast conserving surgery (BCS) and adjuvant APBI from 2000 - 2022. Salient clinicopathologic parameters were collected, as were receipt of systemic and endocrine therapies. All patients received external beam APBI to a total dose of 40Gy in 10 daily fractions over 2 weeks. We analyzed outcomes including local recurrence (LR), regional recurrence, distant recurrence, and death. Cumulative incidence functions were calculated to estimate the incidence of LR with the competing risk of death. All statistical analyses were performed in R version 4.2.2. The study cohort comprised 52 patients with HER2+ breast cancer (median age 64 years; range 44-87). Nearly all had T1 tumors (98%; median size 15 mm; range 1 - 21 mm). Approximately 10% had multifocal disease, with one exhibiting suspicion for lymphovascular invasion. Most patients had ER+ disease (88%). All patients had negative final surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. 42 (81%) received chemotherapy, 40 (77%) endocrine therapy, and 42 (81%) HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range 7 - 226 months for each patient), we observed two LR events, at 14 and 26 months, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any contralateral invasive breast cancer events or breast-specific mortality events. Two deaths were noted in the cohort, both without evidence of disease. Among a cohort of HER2+ early-stage breast cancer patients managed with BCS and APBI, we observed a 2-year LR rate of 3.8% with no regional or distant recurrences, and excellent overall survival. These findings merit longer term follow-up among larger cohorts, although are thus far consistent with the results of contemporary randomized trials of APBI unselected for HER2-status.

PO-1276 Quality of life analysis of adjuvant external beam APBI in prospective randomized trial.

PO-1276 Quality of life analysis of adjuvant external beam APBI in prospective randomized trial.

PO-1277 External beam APBI in early breast cancer - final results of prospective single institution study.

PO-1277 External beam APBI in early breast cancer - final results of prospective single institution study.

Low Toxicity and Excellent Cosmesis with Highly Conformal Accelerated Partial Breast Irradiation Delivered Either Twice Daily or Every Other Day

<h3>Purpose/Objective(s)</h3> Two landmark randomized controlled trials (RCT) of external beam accelerated partial breast irradiation (EB-APBI) using 38.5 Gy/10 fractions (F) BID demonstrated excellent cancer control outcomes in appropriately selected patients but conflicting results regarding cosmesis. A recent RCT reported high rates of acceptable cosmesis using 30 Gy/5F QOD, making the most appropriate schedule for EB-APBI unclear. We utilized the BID regimen largely until the COVID-19 pandemic with strict contouring, dosimetric, and planning guidelines for gross/clinical/planning target volumes (GTV/CTV/PTV) and organs-at-risk (OAR). We report our experience with BID and QOD EB-APBI with a hypothesis that our treatment planning approach would result in acceptable acute toxicity and cosmesis. <h3>Materials/Methods</h3> We identified patients that received EB-APBI from 4/2017 through 12/2021. Clinical, pathologic, acute toxicity, cosmesis and dosimetric data for the lumpectomy (Lump) GTV/CTV/PTV and key OARs (ipsilateral breast [IB V50%, V80% and V100% of the Rx dose] heart (mean dose, V5% Rx dose; V3 Gy], ipsilateral lung [IL V30% Rx dose] and mean total lung dose [TLD]) were collected. Cosmesis was physician-reported using the 4-point NRG Oncology/RTOG Global Cosmetic Score (GCS): Excellent (E)/Good (G)/Fair (F)/Poor (P). We report descriptive statistics to summarize our results. <h3>Results</h3> 245 patients were included with median follow-up 19 months (IQR, 9-30 months): median age, 66 y (IQR, 59-71 y); 51% left-sided; 82% invasive; 100% invasive tumors HR+/HER2-; 95% of DCIS HR+; median invasive tumor size 9.5 mm (IQR, 6-13 mm) and DCIS size 8mm (IQR, 4-12 mm); 96% nodal surgery in invasive disease. Fractionation was BID in 55%, QOD in 45%. 3DCRT was used in 88% with median 6 fields (IQR, 5-7) and 96% were treated prone. Median Lump PTV eval volume was 176 mL and median breast volume 1335 mL resulting in median breast V50%Rx Dose=40.3% (IQR, 34.5-45.8%) and median breast V100=15.6% (IQR, 10.2-18.6%). Lump PTV coverage was high (median V95=100%). The mean heart dose was 35 cGy (IQR, 15-59 cGy), heart V5%=1.1% (IQR, 0-8.1%), and median heart V3Gy=0% (0-0.5%). The IL V30% (median 0%, IQR 0-0.4%) and TLD (median 49 cGy, IQR 26-93.1 cGy) were also low. The majority of patient had no acute toxicity (55% grade 0 dermatitis; 57% grade 0 fatigue; 97% grade 0 pruritis). The rate of E/G cosmesis was 97.1% (N=238) and F/P 2.9% (N=7). In patients with at least 2 years follow-up, rates were 96% E/G (N=95) and 4% F/P (N=4). The IB V100 was marginally associated with increased odds of F/P cosmesis (OR=1.18, 95% CI 0.99-1.42, p=0.07). <h3>Conclusion</h3> With multiple-field 3DCRT in the prone position, EB-APBI can be delivered with low toxicity and great cosmetic results with BID or QOD treatment. Given the low rate of F/P cosmesis, longer follow-up is needed to confirm stability of these results and to help identify optimal dose-volume parameters to minimize the rate of F/P cosmesis.

Accelerated Partial Breast Irradiation Using External Beam or Intraoperative Electron Radiation Therapy: 5-Year Oncological Outcomes of a Prospective Cohort Study

To evaluate the ipsilateral breast tumor recurrence (IBTR) after 2 accelerated partial breast irradiation (APBI) techniques (intraoperative electron radiation therapy [IOERT] and external beam APBI [EB-APBI]) in patients with early-stage breast cancer. Between 2011 and 2016, women ≥60 years of age with breast carcinoma or Ductal Carcinoma In Situ (DCIS) of ≤30 mm and cN0 undergoing breast-conserving therapy were included in a 2-armed prospective multicenter cohort study. IOERT (1×23.3 Gy prescribed at the 100% isodose line) was applied in 1 hospital and EB-APBI (10×3.85 Gy daily) in 2 other hospitals. The primary endpoint was IBTR (all recurrences in the ipsilateral breast irrespective of localization) at 5 years after lumpectomy. A competing risk model was used to estimate the cumulative incidences of IBTR, which were compared using Fine and Gray's test. Secondary endpoints were locoregional recurrence rate, distant recurrence, disease-specific survival and overall survival. Univariate Cox regression models wereestimated to identify risk factors for IBTR. Analyses were performed of the intention to treat (ITT) population (IOERT n=305; EB-APBI n=295), and sensitivity analyses were done of the per-protocol population (IOERT n=270; EB-APBI n=207). The median follow-up was 5.2 years (IOERT) and 5 years (EB-APBI). Cumulative incidence of IBTR in the ITT population at 5 years after lumpectomy was 10.6% (95% confidence interval, 7.0%-14.2%) after IOERT and 3.7% (95% confidence interval, 1.2%-5.9%) after EB-APBI (P=.002). The locoregional recurrence rate was significantly higher after IOERT than EB-APBI (12.1% vs 4.5%, P=.001). There were no differences between groups in other endpoints. Sensitivity analysis showed similar results. For both groups, no significant risk factors for IBTR were identified in the ITT population. In the per-protocol population, surgical margin status of the DCIS was the only significant risk factor for developing IBTR in both treatment groups. Ipsilateral breast tumor recurrences and locoregional recurrence rates were unexpectedly high in patients treated with IOERT, and acceptable in patients treated with EB-APBI.

Abstract P3-19-22: Clinical and cosmetic outcomes of adjuvant stereotactic partial breast irradiation using the GammaPod

Abstract Background: The GammaPod is the first stereotactic body radiation therapy (SBRT) system optimized for treating breast cancer. It is composed of the treatment delivery system, the stereotactic localization and immobilization device, prone patient loading system and a treatment planning system, streamlining radiation therapy for both patient and provider. The GammaPod allows for higher doses in one or several large fractions which differentiates SBRT from conventional techniques. Patients benefit from shorter treatment timelines and more precise targeting. This project investigated the clinical benefit of the GammaPod compared to accelerated partial breast irradiation (APBI) with external beam radiation. Methods: Consecutive patients from 2018-2021 were retrospectively reviewed. All patients were treated with a lumpectomy +/- sentinel lymph node biopsy followed by adjuvant GammaPod stereotactic partial breast irradiation. All patients had at least 1 month of follow up from SBRT completion. The treatment protocol included 30Gy delivered over 5 fractions. Patient, tumor, and dosimetric characteristics were analyzed. Toxicities and cosmesis were recorded prospectively by treating physicians and reviewed retrospectively. Local recurrence was defined as in-breast, or skin/chest wall; regional recurrence was defined as a nodal failure. Results: Forty-nine patients were included. One hundred percent were female and 78% were White. The median age was 63 years, AJCC 8th edition anatomic staging was predominantly stage 0 (29%) and stage 1 (69%), and median tumor size was 8mm. Fifty-five percent of patients were treated for left-sided disease. Seventy-one percent of lesions were invasive carcinomas; 97% were ER+/Her2- and one patient was Her2+. Twenty-nine percent had ductal carcinoma in situ. The most common GammaPod cup sizes were L00 (24%), L01 (16%), M00 (14%), L04 (8%), and L06 (8%). All patients received surgery prior to radiation therapy and the median days elapsed from surgery to radiation therapy was 53 days (34-272). One patient underwent adjuvant chemotherapy prior to radiation therapy for her2+ disease. Median total RT dose was 30Gy (27-43). All patients were treated in 5 fractions with a median beam time of 14.57 minutes and a median variation of 2.56 minutes between fractions. The median days elapsed in treatment was 10 days (4-20). Five patients were undergoing reirradiation. The median follow up time was 8.25 months (.9-27mo) and one patient had regional reoccurrence. Of the 41 patients with recorded cosmesis results, 98% experienced positive (excellent or good) cosmesis outcomes. Eighty-eight percent experienced excellent cosmesis at follow up and no patients experienced poor cosmesis. All recorded toxicities were grade 1 or less. Thirty-three percent of patients experienced blisters, 27% experienced some degree of hyperpigmentation/hypopigmentation, and 14% experienced contact dermatitis from the immobilization device. Other toxicities ≤ 6.1% included erythema, pain, desquamation, cellulitis/mastitis, and petechiae. Conclusion: We present an initial analysis of the novel GammaPod for SBRT adjuvant radiation treatment for early stage breast cancer. The use of the GammaPod yielded positive cosmesis results and was well tolerated with a minimal side effect profile compared to external beam APBI. Therefore, the GammaPod offers a promising alternative to external beam ABPI in terms of post radiation cosmesis and patient satisfaction. Citation Format: Kayla Paulosky, Sarah Ruff, Stewart J Becker, Mariana Guerrero, Sarah McAvoy, Elizabeth M Nichols. Clinical and cosmetic outcomes of adjuvant stereotactic partial breast irradiation using the GammaPod [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-22.

MRI-Guided APBI Using Brachytherapy PTV Margins is Well Tolerated With Low Ipsilateral Breast Tumor Recurrence Risk

External beam accelerated partial breast irradiation (APBI) utilizes Planning Target Volume (PTV) expansions of 2 to 2.5 cm beyond the surgical cavity to assure treatment of target breast tissue. Decreasing the volume of irradiated breast with external beam accelerated partial breast irradiation (APBI) is a potential way to minimize dose to organs at risk and adverse cosmetic outcomes. Magnetic resonance guided radiation therapy (MRgRT) allows detailed pre-fraction imaging and continuous intrafraction monitoring which allows for external beam APBI treatments using a brachytherapy-style 1 cm surgical bed to PTV margin. We have previously shown that MRgRT APBI results in an average 52% reduction in PTV. In this study we report the outcomes of patients treated with reduced-margin APBI via MRgRT.Patients included women with early stage, node negative breast cancers treated with breast conserving surgery and adjuvant MRgRT APBI from March 2014 to July 2019. PTV was defined as the surgical cavity plus a uniform 1-cm margin of breast tissue (excluding chest wall, pectoral muscles, and 5mm from skin). The PTV received 38.5 Gy in ten fractions over five treatment days. Volumetric MR imaging was acquired prior to each fraction to localize the surgical cavity and a sagittal cine MR imaging during each treatment to monitor intrafraction motion; gating to the surgical bed was used as needed.242 patients were treated with MRgRT APBI with reduced margins. Eighty-one (33.5%) patients had pure DCIS and 161 (66.5%) patients had pT1N0 disease. Seventy-three (90.1%) patients with pure DCIS had hormone sensitive disease and 141 (87.6%) patients with invasive disease had hormone sensitive, her2/neu negative disease. Stratifying by ASTRO APBI Consensus guidelines, 36% of patients were categorized as Cautionary and one patient was Unsuitable solely due to age < 40. At a median follow up of 36 months (range, 14 - 82), two patients (0.8%) had biopsy-proven in-breast tumor recurrence (IBTR), both of whom were successfully salvaged. Per the Aaronson-modified Harris scale, providers reported 100% of patients had good/excellent cosmesis prior to APBI and at last follow-up. Nearly two thirds of patients experienced no acute skin toxicity with the remaining having small regions of grade 1 erythema. There were no observed CTCAEv4.0 grade 3+ toxicities following APBI.APBI with reduced margins using MR-IGRT is safe and has excellent cosmetic outcomes with acceptably low initial rates of IBTR.

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.

OPAR: A Multicenter Phase II Randomized Trial of Fractionation Schedules for Once-a-Day Accelerated Partial Breast Irradiation (APBI)

<h3>Purpose/Objective(s)</h3> APBI is the delivery of radiotherapy (RT) to the tumor bed after breast conserving surgery (BCS) often given over a week or less. An attractive approach to deliver APBI is by external beam 3DCRT or IMRT. Previous studies have suggested that external beam APBI delivered twice-a-day can lead to increased late effects and poor breast cosmesis. The objective of our trial was to determine if two doses for APBI given once-a-day over 1-week result in acceptable long-term morbidity. <h3>Materials/Methods</h3> Eligible patients were > 50 years with DCIS or invasive breast cancer < 3 cm treated by BCS with negative margins and negative axillary nodes. Consenting patients were planned to receive APBI with 3-5 non-coplanar fields using a 3DCRT or IMRT and randomized to 27.5Gy or 30Gy each given in 5 fractions once-a-day over 5-8 days. Cosmetic evaluation with the EORTC Cosmetic Rating System was performed at baseline and 2 years by: a study nurse directly assessing the breast, and a group of oncologists unaware of RT regimen assessing photographs. Patient assessment of cosmesis was also performed at 3 years. Patients were followed for toxicity using the NCI CTCAE and recurrence. The primary outcome was adverse cosmesis (fair or poor global score) by photographic assessment at 2 years. The rate of adverse cosmesis with standard whole breast irradiation was 17% in our previous trial. Based on this consideration and one-sided α of 5% for each group, the upper bound of a one-sided 95% (two-sided 90%) confidence interval (CI) had to be < 23% for the treatment to be acceptable; 140 patients were required for each group. The proportion of patients with adverse cosmesis at 2 years and cosmetic deterioration from baseline to 2 years (excellent/good to fair/poor) with corresponding two-sided 90% CIs were estimated using the Wilson score method. The proportion of patients with any late breast toxicity (edema, induration, and telangiectasia) grades 2-3 at 2 years and local recurrence (LR) were also determined. <h3>Results</h3> Of the 281 patients: 139 were randomized to 27.5Gy and 142 to 30.0Gy. Median follow-up was 3 years. The mean age was 65 years; mean tumor size was 1.2cm. With respect to photographic assessment both schedules met our criteria for acceptability (Table 1). Adverse cosmesis assessed by nurse or patient and toxicity appeared to be less for 27.5Gy compared to 30Gy. No LRs were observed for 27.5Gy and one LR was observed for 30Gy. <h3>Conclusion</h3> According to the study design 27.5Gy and 30Gy resulted in acceptable cosmetic outcomes. In light of recent studies, the lower dose may be preferable in terms of late adverse effects but requires further evaluation.

Implementing stereotactic accelerated partial breast irradiation using magnetic resonance guided radiation therapy

IntroductionAccelerated partial breast irradiation (APBI) seeks to reduce irradiated volumes and radiation exposure for patients while maintaining acceptable clinical outcomes. Magnetic resonance image-guided radiotherapy (MRgRT) provides excellent soft-tissue contrast for treatment localization, which can reduce setup uncertainty, thus reducing margins in the external beam setting. Additionally, stereotactic body radiotherapy (SBRT)-style regimens with high gradients can also be executed. This MR-guided stereotactic APBI (MRgS-APBI) approach can be utilized for a lower number of fractions and spare a greater volume of healthy tissues compared to conventional 3D external beam APBI. MethodsOur MRgS-APBI program was developed for two prospective non-randomized phase I/II clinical trials (20Gyx1 and 8.5Gyx3). Both breast SBRT treatment planning and MRgRT delivery techniques were described in this study. Simulation included both CT and MRI with specialized immobilization to accommodate MR-guided setup and cine-MRI treatment gating. Dosimetry data from 48 single-fraction and 19 three-fraction patients were collected and evaluated. This included planning objectives and SBRT-specific indices. During treatment, setup errors were calculated to evaluate setup reproducibility and duty cycle was calculated using cine-MRI data during gated delivery. ResultsIn both the single- and three- fraction trials combined, 88.5% of the possible dosimetric objectives across all patients were met during planning. The majority of the planning objectives were easily achievable indicating the potential for stricter objectives for subsequent S-APBI treatments. The average magnitude of setup uncertainties was 1.0 cm ± 0.6 cm across all treatments. In the three-fraction trial, the average beam-on duty-cycle for the MRI-gated delivery was 83.0 ± 13.0%. There were no technical MRgS-APBI related issues that resulted in discontinuation of treatment across all patients. ConclusionSBRT-style dosimetry and delivery for APBI is feasible using MR-guidance. The program development and dosimetric outcomes reported here can serve as a guide for other institutions considering the clinical implementation of MR-guided stereotactic APBI.

Five-Fraction Prone Accelerated Partial Breast Irradiation: Long-Term Oncologic, Dosimetric, and Cosmetic Outcome

PurposeRandomized data support accelerated partial breast irradiation (APBI) for early-stage breast cancer with variable techniques and cosmesis outcomes. We have treated patients with 5-fraction prone external beam APBI for over a decade and herein report acute and late outcomes. Methods and MaterialsPatients receiving APBI 600 cGy × 5 between 2010 and 2019 were included. APBI was primarily delivered prone, with opposed tangents targeting the tumor bed expanded by 1.5 cm (cropped 6 mm from skin). Ipsilateral breast was constrained to V50% < 60% and V100% < 35%. Survival was estimated with Kaplan-Meier. Late toxicities and clinician- and patient-rated cosmesis were evaluated for patients with >6 months follow-up (FU). ResultsOf 345 patients meeting criteria, 14 were excluded due to APBI given for ipsilateral breast tumor recurrence (IBTR; n = 3), palliation (n = 9), and incomplete radiation therapy course (n = 2). Of the 331 remaining, median age was 70, 7.2% had ductal carcinoma in situ, and 94.3% were treated prone, with 32% treated every other day and 68% on consecutive days. Mean heart dose was 23.8 cGy for left-sided and 12.7 cGy for right-sided cancers. Ipsilateral lung V30% was 0.4%. At 5-year median FU, there were 7 (2.1%) IBTR, 9 (2.7%) contralateral recurrences, and 1 (0.3%) distant metastasis. Five-year local recurrence-free, disease-free, and overall survival was 99.5%, 96.7%, and 98.1%, respectively. When comparing patients with IBTR versus without, a higher proportion did not receive hormone therapy (71.4% vs. 26.2%, P = .018). Rates of acute grade 1 to 2 dermatitis, fatigue, and pain were 35.4%, 21.8%, and 9.4%, respectively, with no grade 3 toxicity. The rate of good-excellent physician- and patient-rated cosmesis (n = 199, median FU 2.8 years) was 92.5% and 89.4%, respectively. Patients experienced low rates of telangiectasia, fibrosis, and retraction/atrophy. ConclusionsWe report excellent dosimetric, oncologic, cosmetic, and late toxicity outcomes for patients treated with 5-fraction APBI. To our knowledge this is the largest series of women treated with prone APBI.

PO-1106 External beam APBI in early breast cancer: randomised prospective single institution study.

PO-1106 External beam APBI in early breast cancer: randomised prospective single institution study.

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.

Accelerated partial breast irradiation with 3-dimensional conformal and image-guided intensity-modulated radiotherapy following breast conserving surgery – 7-Year results of a phase II trial

PurposeTo present the 7-year results of accelerated partial breast irradiation (APBI) using three-dimensional conformal (3D-CRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) following breast-conserving surgery (BCS). Patients and methodsBetween 2006 and 2014, 104 patients were treated with APBI given by means of 3D-CRT using 3–5 non-coplanar, isocentric wedged fields, or IG-IMRT using kV-CBCT. The total dose of APBI was 36.9 Gy (9 × 4.1 Gy) using twice-a-day fractionation. Survival results, side effects and cosmetic results were assessed. ResultsAt a median follow-up of 90 months three (2.9%) local recurrences, one (0.9%) regional recurrence and two (1.9%) distant metastases were observed. The 7-year local (LRFS), recurrence free survival was 98.9%. The 7-year disease-free (DFS), metastases free (MFS) and overall survival (OS) was 94.8%, 97.9% and 94.8%, respectively. Late side effects included G1 skin toxicity in 15 (14.4%), G1, G2, and G3 fibrosis in 26 (25%), 3 (2.9%) and 1 (0.9%) patients respectively. Asymptomatic (G1) fat necrosis occurred in 10 (9.6%) patients. No ≥ G2 or higher late side effects occurred with IMRT. The rate of excellent/good and fair/poor cosmetic results was 93.2% and 6.8%, respectively. Conclusion7-year results of APBI with 3D-CRT and IG-IMRT are encouraging. Toxicity profile and local tumor control are comparable to other series using multicatheter interstitial brachytherapy. Therefore, these external beam APBI techniques are valid alternatives to whole breast irradiation and brachytherapy based APBI.

Breast Cancer: Toxicity, QoL and Economy after External Beam APBI

Accelerated partial breast irradiation (APBI) is increasingly available approach in adjuvant RT of selected group of the early-stage breast cancer. Accumulating data are showing non-inferiority of both interstitial brachytherapy and external beam radiotherapy via stereotactic body radiotherapy (SBRT). The aim of this single institutional prospective randomized study is to compare the SBRT_APBI with accelerated whole breast irradiation (WBI). The main objective is to evaluate feasibility, safety, tolerance and cosmetic effects of SBRT. Patients with early breast carcinoma after partial mastectomy were screened for eligibility: age ˃ 50, NST histology, size ≤ 2 cm, negative margins ≥ 2 mm, no lymphovascular invasion, ER positive, BRCA negative. Randomization to: surgery bed SBRT (5x 6Gy) and accelerated WBI with tumor bed boost (15x 2.67Gy + 5x 2Gy). 4DCT-based planning, deep inspiration breath hold, daily pre-treatment positioning by cone-beam CT and volumetric arc therapy dose delivery were utilized. Quality of life (QoL) was evaluated by official translation of EORTC questionnaires (QLQ-C30 and QLQ-BR23). Cosmetics and toxicity were evaluated subjectively and objectively using questionnaires, CTCAE criteria and chest photodocumentation. Economy burden was evaluated at the end of radiotherapy by a 4-point graded scale. In this pilot report we present results of first 30/84 planned patients. Both groups (15 patients in each) were well balanced according to baseline characteristics. Median age 66 years, 66 % invasive ductal carcinoma, 70 % grade 1, median tumor size 9 mm. In SBRT group median PTV volume 52 ccm, minimum PTV dose median 29 Gy, maximum PTV dose median 32 Gy. 6 patients with no dermatitis, 9 patients with grade 1 dermatitis in SBRT group and 8 patients with grade 1, six with grade 2 and one with grade 3 skin toxicity in WBI group at the end of therapy. Significantly less skin sensitivity, dryness, pigmentation and fatigue in SBRT arm comparing to control arm. No differences between groups with respect to acute skin toxicity after 1 and 3 months. No significant difference in questionnaires evaluation. Cosmetic results as well as economic analysis favor SBRT technique. Description of two most common VMAT techniques with evaluation of dose coverage of the target and surrounding tissues parameters will be part of poster presentation. Feasibility, toxicity, cosmetic and financial influence of two radiotherapeutic regiments - the SBRT surgery bed radiotherapy and accelerated whole breast irradiation with the boost to tumor bed were compared. SBRT technique is less toxic and easier feasible approach for adjuvant treatment of selected early-stage breast cancer patients. We add to increase level of evidence for establishment of SBRT in indicated patients into daily clinical practice of APBI.

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.

Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique

PurposeTo compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI). MethodsBetween 2011 and 2016 women ≥60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 × 23.3 Gy) or photon EB-APBI (10 × 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year. ResultsHRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS). ConclusionsEB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels.

Tattoo free setup for partial breast irradiation: A feasibility study.

PurposePatients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three‐dimensional (3D) body surface imaging and two‐dimensional (2D) x‐ray imaging‐based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo‐based setups to a patient setup without tattoos.Materials/methodsTwenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x‐ray‐based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error.ResultsAmong ten patients in the “no tattoo” group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the “no tattoo” group were 4.6 vs 5.9 mm in the “tattoo” cohort (P = NS). Mean systematic errors in the “no tattoo” group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the “tattoo” group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the “no tattoo” group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the “tattoo” group.ConclusionsUsing both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin‐based tattoos may no longer be warranted for patients receiving external beam APBI.

A phase II trial to determine the cosmetic outcomes and toxicity of 27 Gy in five-fraction accelerated partial breast irradiation: the ACCEL trial

Accelerated partial breast irradiation (APBI) has been investigated in randomized controlled trials with the goals of reducing side effects and treatment burden. There is accumulating evidence that local control for multi-fraction APBI is not inferior to whole breast irradiation (WBI) but an external beam prescription that can be safely delivered in five consecutive days has not been reported. The aim of this study is to investigate an APBI prescription delivered once per day in 1 week. This is a single-arm, phase II, prospective cohort study. Two hundred seventy-four eligible women with newly diagnosed, early-stage, invasive, or in situ ductal carcinoma treated with breast-conserving surgery and sentinel lymph node biopsy or axillary dissection who are candidates for whole breast radiation without a boost will be recruited. Twenty-seven Gray (Gy) in five fractions will be delivered once daily over five consecutive working days to the target volume. The primary outcome is the rate of global cosmetic deterioration from an excellent or good score at baseline (prior to radiation therapy) to a fair or poor score at 2 years after treatment. The study is powered to demonstrate non-inferiority compared to the use of WBI arm in the RAPID trial. The ACCEL trial aims to demonstrate the safe and effective delivery of a five-fraction APBI treatment using IMRT or 3D-conformal radiation. The study is designed to account for an updated α/β ratio for breast tissue and compares cosmesis to the WBI arm of the RAPID trial. The ACCEL trial was registered in February 2016 and began accrual in the subsequent May. This trial will assess the cosmetic and normal tissue outcomes of external beam APBI delivered in 1 week for early-stage breast cancer. Registration number: NCT02681107 ( clinicaltrials.gov ), registered February 2, 2016.