Adverse Cosmesis Research Articles

Dose Deintensified 3-Day Photon, Proton, or Brachytherapy: A Nonrandomized Controlled Partial Breast Irradiation Trial

BackgroundThe optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy. MethodsA multicenter nonrandomized controlled trial with primary outcome of adverse cosmesis at 3 years versus pre-PBI. Eligibility criteria were ≥ age 50 years treated with breast-conserving surgery for node-negative estrogen receptor positive (ER+) invasive breast cancer or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (RBE) and brachytherapy 21 Gy in 3 fractions. Radiotherapy technique and use of adjuvant endocrine therapy was selected at physician and patient discretion. ResultsBetween June 17, 2015 and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. 126 (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). 54.0% of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline, 2.3% at 3 years (difference -12.2%, 95% CI (-100%, -6.4%)). Adverse cosmesis at last-follow-up, with median follow-up 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient reported outcomes, and just two grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. 5-year local recurrence-free and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences amongst 60 patients with invasive breast cancer and Ki67 ≤ 13.25%. ConclusionsDe-intensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the pre-specified criteria for acceptability. This approach is an attractive option for small node-negative ER+ BC and DCIS patients. Trial registrationClinicalTrials.gov identifier NCT02453737

Measurement of adverse cosmesis in breast cancer: A deep learning approach

Background and PurposeAdverse cosmesis or poor aesthetic appearance of the breast after breast conservation surgery (BCS) and/or radiation therapy (RT) is highly correlated with quality-of-life (QOL) in breast cancer patients. Existing methods for objective assessment of cosmesis utilize human-designed features that are calculated using outlines and/or key-points from breasts. These are complicated and time consuming to obtain. Our purpose is to develop and validate a deep neural network (DNN)-based approach for classifying adverse cosmesis from frontal digital images of patients who have undergone BCS and RT using an approximate region-of-interest (ROI) containing the breast. Materials and MethodsWe used 6 datasets (5 from BCS/RT-related clinical trials) to conduct our study. Training subsets (80% of patients) from 3 datasets (RAPID, OPAR, and PORTO) were used to train 3 independent support vector classifiers for classifying adverse cosmesis using the features extracted from preprocessed, approximate breast ROIs passed through a pretrained DNN, called ResNet-18. The trained classifiers/models were evaluated through 5 experiments: holdout validation, treatment-arm specific validation in RAPID, external validation (included datasets from the remaining 3 trials), assessment of the effect of preprocessing, and comparison with BCCT.core software. Area-under-the receiver operating characteristics (AUC) was used as the primary evaluation measure. Treatment-arm specific probability values were compared by the Mann-Whitney U test. ResultsAUC (0.78, 0.88, 0.94) values increased from RAPID to OPAR and PORTO respectively for holdout validation. The median probability of adverse cosmesis was higher in the same treatment arm in accordance with the interim results of the RAPID trial and differed significantly between the treatment arms (p = 0.006). For external validation, best AUC values were obtained by the model trained in RAPID (AUCs > 0.78). Preprocessing improved the performance to a large extent (average AUC: 0.87 vs 0.79 for internal validation, 0.78 vs 0.64 for external validation). AUCs of the individual models using DNN-based features were higher in 7 of 9 validation tests and statistically similar to the human-designed, dimensionless features extracted from BCCT.core software. ConclusionAppropriately preprocessed, approximate breast ROIs can be represented by DNN-based features to identify adverse cosmesis from frontal images of breast cancer patients treated with BCS/RT. Adaptations to this approach may be necessary for its applicability to images with non-frontal views and different quality. This work serves as a foundation for developing robust DNN-based platforms for evaluating cosmesis in clinical trials.

Multi-Institutional Phase II Trial Using Dose Escalated Five Fraction Stereotactic Partial Breast Irradiation (S-PBI) with GammaPodTM for Early-Stage Breast Cancer

We report on our early experience of a multi-institutional phase II study of dose escalated five fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using the GammaPodTM stereotactic radiation system. Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior safety of Phase I dose escalation has been reported. Dose was 40 Gy delivered in 5 fractions to the CTV, and minimum dose 30 Gy in 5 fractions to the PTV. CTV margin was 1 cm and PTV margin 3 mm. For PTV cavities larger than 100cc, dose was reduced to 35Gy in 5 fractions to the CTV and 30 Gy in 5 fractions to the PTV. Primary endpoint of the study is to determine the 3-year patient global cosmesis score (4-point scale excellent, good, fair, or poor) and adverse cosmesis using a dose escalated approach with smaller PTV margins than conventional methods. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Treatment related toxicity was graded using the NCI version 4.0 and RTOG/EORTC late radiation scale. From 3/2019-10/2021, 74 patients were treated respectively. Of these, 38 were treated to 40Gy and 36 were treated to 35 Gy. Median follow up (f/u) was 24 months (mo), range (r) 3-39mo. Median age was 63 years (r 43-77). Histology included 28 DCIS, and 46 invasive carcinomas. 45/46 invasive tumors were ER+. 60/74 (81%) patients received endocrine therapy, and 7/74 patient received chemotherapy. There were 221 acute grade 1 toxicities, and 28 Grade 2 toxicities. No grade 3 or higher acute toxicities were reported (< 90 days). The most common Grade 2 toxicities were radiation dermatitis (10), breast pain (8), blister (4), skin infection (2), nipple discharge (2), and fatigue (2). In the late period, there were 54 Grade 1 late toxicities, 4 Grade 2 late toxicities, and no Grade 3 or higher late toxicities. Grade 2 toxicities included fibrosis (2), and pain (2). Two patients developed grade 1 asymptomatic nonpalpable fat necrosis both diagnosed at 12 months after radiation treatments. The most common grade 1 late toxicities were breast pain (14), hyperpigmentation (8), fibrosis (10), and fatigue (5). Physicians scored cosmesis excellent or good 70/73 (95.8%), 58/60 (96.7%), 36/36 (100%),17/17(100%) respectively at baseline, 12 months, 24 months, and 36months post SBRT, while patients scored the same periods 62/71 (83.7%), 53/59 (89.8%), 33/36 (91.6%), 17/18 (94.4%). There have been no reports of disease recurrences. Results at 24-month median follow-up, of our dose escalated stereotactic partial breast 5 fraction regimen, has low acute and late toxicity, while maintaining high proportion of excellent/good cosmetic outcomes. Continued analysis of all cohorts is in progress. gov identifier is NCT03581136.

Accuracy and Efficiency of Patient Setup Using Surface Imaging versus Skin Tattoos for Accelerated Partial Breast Irradiation

Skin tattoos represent the standard approach for surface alignment and setup of breast cancer radiation therapy, yet permanent skin markings contribute to adverse cosmesis and patient dissatisfaction. With the advent of contemporary surface-imaging technology, we evaluated setup accuracy and timing between "tattoo-less" and traditional tattoo-based setup techniques. Patients receiving accelerated partial breast irradiation (APBI) underwent traditional tattoo-based setup (TTB), alternating daily with a tattoo-less setup via surface imaging using AlignRT (ART). Following initial setup, position was verified via daily kV imaging, with matching on surgical clips representing ground truth. Translational shifts (TS) and rotational shifts (RS) were ascertained, as were setup time and total in-room time. Statistical analyses used the Wilcoxon signed rank test and Pitman-Morgan variance test. A total of 43 patients receiving APBI and 356 treatment fractions were analyzed (174 TTB fractions and 182 using ART). For tattoo-less setup via ART, the median absolute TS were 0.31 cm in the vertical (range, 0.08-0.82), 0.23 cm in the lateral (0.05-0.86), and 0.26 cm in the longitudinal (0.02-0.72) axes. For TTB setup, the corresponding median TS were 0.34 cm (0.05-1.98), 0.31 cm (0.09-1.84), and 0.34 cm (0.08-1.25), respectively. The median magnitude shifts were 0.59 (0.30-1.31) for ART and 0.80 (0.27-2.13) for TTB. ART was not statistically distinguishable from TTB in terms of TS, except in the longitudinal direction (P=.154, .059, and .021, respectively), and was superior to TTB for magnitude shift (P < .001). The variance of each TS variable was significantly narrower for ART compared with TTB (P ≤ .001 vertical, P=.001 lateral, P=.005 longitudinal). The median absolute RS for ART was 0.64° rotation (range, 0.00-1.90), 0.65° roll (0.05-2.90), and 0.30° pitch (0.00-1.50). The corresponding median RS for TTB were 0.80° (0.00-2.50), 0.64° (0.00-3.00), and 0.46° (0.00-2.90), respectively. ART setup was not statistically different from TTB in terms of RS (P=.868, .236, and .079, respectively). ART showed lower variance than TTB in terms of pitch (P=.009). The median total in-room time was shorter for ART than TTB (15.42 vs 17.25 minutes; P=.008), as was the median setup time (11.12 vs 13.00 minutes; P=.001). Moreover, ART had a narrower distribution of setup time with fewer lengthy outliers versus TTB. These findings suggest that a tattoo-less setup approach with AlignRT may be sufficiently accurate and expeditious to supplant surface tattoos for patients receiving APBI. Further analyses with larger cohorts will determine whether tattoo-based approaches can be replaced by noninvasive surface imaging.

Ultra-Accelerated Photons, Protons or Brachytherapy for Favorable Early Breast Cancer: Long-Term Results of a 3-Fraction Partial Breast Irradiation Trial

<h3>Purpose/Objective(s)</h3> To report long-term outcomes of a novel partial breast irradiation (PBI) regimen. We hypothesized that condensing treatment to 3 fractions and reducing total dose could improve the therapeutic ratio based on emerging evidence that breast cancer (BC) is more sensitive than surrounding normal tissues to high dose fractions. <h3>Materials/Methods</h3> We conducted a phase 2 trial of photon, proton, or brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years and s/p lumpectomy with negative sentinel nodes for estrogen receptor positive (ER+) invasive BC without preoperative chemotherapy or any ductal carcinoma in-situ (DCIS) measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically effective dose as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin and prescribed 21.9 Gy (RBE) in 3 fractions. Intracavitary brachytherapy was prescribed 21 Gy in 3 daily fractions. Radiotherapy was administered on 3 consecutive business days. Primary outcome was nurse-assessed adverse (fair/poor) cosmesis by 4-point Harvard scale at 3 years versus pre-PBI. Patients completed quality of life and self-reported cosmesis surveys. Adverse events were assessed using CTCAE, v 4.0. <h3>Results</h3> Between 2015 and 2017, 162 eligible patients were treated: photons in 56, protons in 49, and brachytherapy in 57. Median patient age was 67 years. 79% had invasive BC (all ER+) and 22% had DCIS (83% ER+). Median tumor size was 1.1 cm. Median Ki67 was 10% (IQR 6-17) and grade was 2-3 in 62%. The median of the mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons <0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. 55% received endocrine therapy. The proportion of patients with adverse cosmesis (by RN assessment) was 14.4% pre-PBI, 4.0% at 3 years, and 5.6% at last follow-up (at median 4.9 years) with six patients (3.8%, 3 photon, 3 brachytherapy) experiencing cosmetic worsening. 92.7%, 95.9%, and 94.7%, of patients in the photon, proton, and brachytherapy cohorts had good or excellent cosmesis at last follow-up. The proportion with adverse cosmesis by self-report was 0% pre-PBI and 2.0% at 3 years. Four patients developed local recurrence (1 photons, 2 protons, 1 brachytherapy). 5-year local recurrence-free, progression-free, and overall survival were 97.9%, 95.1%, and 96.9%, respectively. There were 2 treatment related grade ≥2 adverse events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life. <h3>Conclusion</h3> Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues, was associated with favorable cosmetic outcomes, disease control, and excellent tolerability. This is an attractive option for small node-negative ER+ BC and DCIS.

Feasibility and Short-Term Toxicity of a Consecutively Delivered Five Fraction Stereotactic Body Radiation Therapy Regimen in Early-Stage Breast Cancer Patients Receiving Partial Breast Irradiation.

BackgroundFor appropriately selected patients with early-stage breast cancer (ESBC), accelerated partial breast irradiation (APBI) yields equivalent rates of ipsilateral breast tumor recurrence with mixed results in patient-rated cosmesis compared with whole-breast radiotherapy depending on the technique utilized. When utilizing external beam radiotherapy for APBI, techniques to reduce target margins and overall treatment volume are potentially important to decrease rates of long-term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is a promising technique to deliver APBI because of its increased accuracy and sparing of uninvolved breast tissue. We report the initial results of a prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of a daily five-fraction SBRT regimen for APBI.MethodsTwenty-three patients with ESBC after lumpectomy who met APBI suitability were enrolled. During lumpectomy, a bioabsorbable three-dimensional fixed array tissue marker (BioZorb™, Hologic, Marlborough, MA) was placed for enhanced visualization of the cavity boundaries. Clinical target volume (CTV) was defined as the delineable cavity plus a 1-cm isotropic expansion followed by a 3-mm isotropic planning target volume (PTV) expansion. Patients received 30 Gy delivered in five planned consecutive daily fractions in either prone or supine positioning depending on individual anatomy. Two patients completed the five-fraction treatments in 9-day interval and 11-day interval due to external circumstances. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans utilized 10-MV flattening filter–free beams delivered on a Varian Edge linear accelerator. Local control, toxicity, and nurse/patient-scored cosmesis at pre-treatment baseline, 1 month post-treatment, and at subsequent 6-month intervals were recorded.ResultsTwenty-three patients were accrued at the time of submission with median follow-up of 6 months. No patients experienced grade ≥3 acute toxicity. Of the 10 events reported probably related to SBRT, nine were grade 1 (n = 9/10, 90%). There was no evidence of difference, deterioration, or change in patient or nurse-scored cosmesis from baseline to 1 and 6 months post-treatment. One patient developed nodal failure shortly after APBI.ConclusionsAlthough longer follow-up is needed to assess long-term toxicity and local control, this study demonstrated a five-fraction SBRT regimen delivered over consecutive days is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering APBI in suitable women.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03643861, NCT03643861.

Accelerated hypofractionated breast radiotherapy with simultaneous integrated boost: a feasibility study.

PurposeTo assess the feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) in patients with breast cancer.Materials and MethodsA total of 27 patients after breast-conserving surgery were included in this study. Patients were planned on a four-dimensional computerized tomogram, and contouring was done using RTOG guidelines. The dose was 34 Gy/10#/2 week to the breast and 40 Gy/10#/2 week to the tumor bed as SIB with volumetric modulated arc technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs-at-risk were calculated. Toxicities and cosmesis were assessed using RTOG/LENT/SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) were calculated with Kaplan-Meier curves.ResultsThe mean age of the patients was 42 years. Left and right breast cancers were seen in 17 (63%) and 10 (37%) patients, respectively. The mean values of ipsilateral lung V16 and contralateral lung V5 were 16.01% and 3.74%, respectively. The mean heart doses from the left and right breast were 7.25 Gy and 4.37 Gy, respectively. The mean doses to the contralateral breast, oesophagus, and Dmax to brachial plexus were 2.64 Gy, 3.69 Gy, and 26.95 Gy, respectively. The mean value of thyroid V25 was 19.69%. Grade 1 and 2 acute skin toxicities were observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema, and induration were observed in 1 (3.7%), 2 (7.4%), and 4 (14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient. The median follow-up was 51 months (range, 12 to 61 months). At four years, breast induration, edema, and fibrosis were observed in 1 (3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred in 1 (3.7%) and 2 (7.4%) patients, respectively. DFS and OS at four years were 88% and 92%, respectively.ConclusionWith this radiotherapy schedule, acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS, and OS were good.

Abstract PD7-03: Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial

Abstract Background: Partial breast irradiation (PBI) is an established option for selected patients with early stage breast cancer. The optimal technique, target volume and dose/fractionation for PBI has yet to be defined. The most studied regimen in North America (38.5 Gy in 10 fractions twice daily) has been associated with cosmetic deterioration. We hypothesized that condensing treatment and reducing the total administered dose could improve the therapeutic ratio in luminal breast cancer and DCIS based on emerging evidence that breast cancer is more sensitive than surrounding normal tissues to high dose fractions. Herein, we report cosmetic, tolerability, disease control, and patient reported outcomes of a novel ultra-accelerated PBI regimen. Methods: We conducted a single arm, three cohort trial of photon, proton, and brachytherapy PBI. Technique was selected at physician and patient discretion. Eligible women were age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤ 2.5 cm. The regimen was designed to have comparable biologically equivalent effect as 40 Gy in 15 fractions, assuming an α/β ratio of 3.5. Intracavitary brachytherapy target volume was lumpectomy cavity plus 1 cm and prescribed 21 Gy in 3 fractions. Photon and proton target volumes were post-operative tumor bed plus 1 cm and a 3 mm setup uncertainty margin, prescribed 21.9 Gy (RBE) in 3 fractions, and delivered with image guidance. The primary outcome was the percentage difference in patients with adverse cosmesis (defined as fair or poor cosmesis) at 3 years compared to baseline pre-PBI, as assessed by trained nurses using the 4-point Harvard breast cosmesis scale. Patients also completed quality of life surveys and self-reported cosmesis using the 4-point scale. Locoregional and distant recurrence-free survival was determined using the Kaplan-Meier method. Adverse events were assessed using CTCAE, v 4.0. Results: Between 2015 and 2017, 163 patients were treated: photons in 58, protons in 48, and brachytherapy in 57. Median patient age was 66 years. 129 (79%) patients had invasive breast cancer (all ER+) and 34 (21%) had DCIS (83% ER+). Median tumor size was 1.1 cm. Grade was 2-3 in 102 (63%). The median mean heart/ipsilateral lung doses were photons 0.1/1.6 Gy, protons &amp;lt;0.001/0.1 Gy, and brachytherapy 0.5/0.9 Gy. Median follow-up was 4.1 years (IQR 3.9-5.0). The proportion of patients with adverse cosmesis (by RN assessment) was 14.3% at baseline and 3.8% at 3 years, with four patients (1 photon, 1 proton, 2 brachytherapy) experiencing cosmetic deterioration at 3 years from baseline. The proportion with adverse cosmesis by self-report at 3 years was 2.4%, with three patients (1 photon, 1 proton, 1 brachytherapy) reporting cosmetic deterioration. Four patients developed locoregional recurrence (1 photons, 2 protons, 1 brachytherapy); three were local only and one was local and distant. 4-year locoregional recurrence and distant metastasis-free survival were 97.9% and 97.4%, respectively. There were 2 treatment related ≥ grade 2 late events (grade 2 fibrosis and grade 2 seroma, both brachytherapy associated), and no evidence of deterioration in patient-reported pain, fatigue, breast related or overall quality of life, as assessed by the patient reported outcomes version of the CTCAE, 10-point linear analog scales, and the breast cancer treatment outcomes scale. Conclusions: Ultra-accelerated 3-fraction PBI exquisitely spared normal tissues and was associated with favorable cosmetic outcomes, disease control, and excellent long-term tolerability. This ‘precision-radiotherapy’ approach may optimize the therapeutic ratio over more aggressive radiotherapy options as well as radiotherapy omission, particularly in patients with long life expectancies. Citation Format: Robert Mutter, Tina Hieken, Todd DeWees, Arslan Afzal, Stephanie Kenison, Laura Vallow, Christopher Deufel, Nicholas Remmes, Kathryn Ruddy, Judy Boughey, Keith Furutani, Amy Degnim, James Jakub, Tamara Vern-Gross, Dean Shumway, William Wong, Samir Patel, Lisa McGee, Minetta Liu, Carlos Vargas, Daniel Visscher, Bradley Stish, Deanna Pafundi, Mark Waddle, Michael Golafshar, Michele Halyard, Kimberly Corbin, Sean Park. Ultra-accelerated photon, proton, and brachytherapy partial breast irradiation: Primary results of the Mayo 3-fraction trial [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 PD7-03.

Abstract P3-19-18: Feasibility and short term toxicity of a consecutively delivered 5-fraction stereotactic body radiotherapy in early stage breast cancer patients receiving accelerated partial breast irradiation

Abstract Background: For early stage breast cancer, breast conservation is an appealing option for many women. Interest in reducing the duration and volume of RT has continued in the form of accelerated partial breast irradiation (APBI). Recent work demonstrates that for appropriately selected patients, APBI yields equivalent rates of ipsilateral breast tumor recurrence (IBTR) with improvements in patient rated cosmesis compared to whole breast radiotherapy. When using external beam radiotherapy for APBI, appropriate techniques to reduce setup uncertainty and overall treatment volume are critical to reduce long term adverse cosmesis. Stereotactic body radiotherapy (SBRT) is an attractive technique to deliver APBI because of its excellent accuracy and potentially superior sparing of uninvolved breast tissue. We report here the initial results of our IRB-approved prospective clinical trial investigating feasibility, safety, and cosmetic outcomes of daily, 5-fraction SBRT for APBI in women meeting ASTRO consensus suitability criteria for partial breast irradiation. Methods: We enrolled twenty patients with early stage breast cancer after lumpectomy who met APBI suitability. During lumpectomy, a breast surgeon placed a bioabsorbable 3D fixed array tissue marker (BioZorb™, Hologic, Marlborough, MS) for enhanced visualization of the cavity boundaries. We defined the clinical target volume (CTV) as the delineable cavity plus a 1 cm isotropic expansion. We placed a 3mm isotropic planning target volume (PTV) expansion around the CTV. We treated each woman with 3000cGy delivered in 5 consecutive, daily, free-breathed fractions in either prone or supine positioning depending on individual anatomy. Patient treatment position was free-breathing in the prone position for 17 patients and supine in 3 patients using triggered imaging and fiducial tracking. A maximum PTV of 124cc was allowed to minimize incidence of fat necrosis. Plans used 10MV flattening filter free (FFF) beams delivered on a Varian Edge linear accelerator. We documented the following: adverse events (CTCAE 4.0), causality of the event to SBRT, and nurse- and patient- scored cosmesis (i.e., 1=excellent, 2=good, 3=fair, 4=poor) at pre-treatment baseline, 1 month post-treatment, and at each proceeding 6 month interval. We also clinically surveilled for disease recurrence. Results: We completed accrual and treatment of twenty patients. At time of submission, fourteen patients had completed 6-month follow-up, and eight patients had completed 12-month follow-up. No patients experienced grade ≥3 toxicity. Adverse events reported were mostly grade 1. Eighty-five percent of patient-scored cosmesis were excellent or good at baseline, with no evidence of deterioration at 1-month post-treatment (Baseline = 1.9, 1 month = 1.9; p = 0.914). Eighty-five percent of nurse-scored cosmesis reports were excellent or good at baseline, with no evidence of deterioration between baseline and 1-month post-treatment (Baseline = 1.95, 1 month = 1.90; p = 0.564). Eighty-six percent of patients had excellent or good patient- and nurse-scored cosmesis at 6 months, with either mean score of 1.71. Eighty-eight percent of patients had excellent or good patient- and nurse-scored cosmesis at 12 months, with mean cosmesis score of 1.50 and 1.63, respectively. Local control follow-up is immature, but no patients developed IBTR. Conclusions: Our study demonstrated that consecutive daily 5-fraction breast SBRT for APBI is a safe, efficient, well-tolerated, and cosmetically favorable means of delivering partial breast irradiation in suitable women. As follow-up duration matures, we will report long term cosmetic outcome and recurrence. Citation Format: Yilan Liu, Christopher Veale, Diana Hablitz, Helen Krontiras, Michael Christian Dobelbower, Rachael Lancaster, Markus Bredel, Catherine Parker, Kimberly Keene, Evan Thomas, Drexell Hunter Boggs. Feasibility and short term toxicity of a consecutively delivered 5-fraction stereotactic body radiotherapy in early stage breast cancer patients receiving accelerated partial breast irradiation [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 P3-19-18.

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.

Once Daily Versus Twice Daily External Beam Accelerated Partial Breast Irradiation: A Randomized Prospective Study

The aim of the current study was to compare toxicity, cosmesis, and local control between the once daily and the twice daily fractionation schemes for external beam accelerated partial breast irradiation. From December 2012 to June 2018, we enrolled 113 patients with ductal carcinoma in situ or invasive breast cancer, node negative disease, and tumors less than 3 cm in size to receive accelerated partial breast irradiation (APBI) to a total dose of 38.5 Gy over 10 fractions given either once (oAPBI) or twice daily (tAPBI). Sixty patients were included in the tAPBI arm and 53 patients were included in the oAPBI arm. Median follow-up was 74 months (range, 24-105). The median pain score during treatment was 3 out of 10 in the oAPBI and 5 in the tAPBI (P = .001). No differences were observed in GIII early skin toxicity (P = .4) or GI early pulmonary toxicity (P = 1.0) between the 2 treatment arms. GIII late skin toxicity developed in 3.8% and 11.7% of patients in the oAPBI and tAPBI arms, respectively (P = .001). GIII subcutaneous fibrosis developed in 1.9% and 8.3% of patients in the oAPBI and tAPBI, respectively (P = .001). The rate of patients with adverse cosmesis (poor/fair) was 7.5% at 12 months and at 24 months in the oAPBI arm compared with 21.7% and 26.7% in the tAPBI arm (P = .03 and .008, respectively). oAPBI is a safe, well-tolerated schedule with more favorable outcomes than the tAPBI schedule with regards to late toxicity and cosmesis.

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.

Comparison of Toxicity and Cosmetic Outcomes After Accelerated Partial Breast Irradiation or Whole Breast Irradiation Using 3-Dimensional Conformal External Beam Radiation Therapy

PurposeTo compare rates of acute and late skin toxicities and cosmetic outcomes after accelerated partial breast irradiation (APBI) or whole breast irradiation (WBI) using 3-dimensional conformal external beam radiation therapy in women with breast cancer after breast conservation surgery (BCS). Methods and MaterialsWomen >35 years of age with invasive or noninvasive breast cancer ≤4 cm treated by BCS were randomized to 3D-CRT APBI (34 Gy/10 fractions/5 days) or WBI (40 Gy/16 fractions/3 weeks ± boost irradiation). The primary outcome was ipsilateral breast tumor recurrence. Important secondary outcomes were skin toxicities using Radiation Therapy Oncology Group scores, Late Effects Normal Tissue Task Force and Subjective, Objective, Management, Analytic scales, and adverse cosmetic outcome. This interim analysis focuses on the secondary endpoints of radiation toxicities and cosmesis. Patient and tumor characteristics and rates of adverse cosmetic outcomes and skin toxicities were compared using Fisher exact tests. All statistical tests were 2 sided, with P < .05 considered statistically significant. ResultsBetween June 2011 and December 2015, 133 women with breast cancer were randomized to 3D-CRT APBI or WBI. Patient and tumor characteristics were balanced between the 2 arms. Median follow-up was 60 months (range, 12-93 months). Grade 4 late toxicity was not seen in either of the treatment arms, and grade 3 toxicity was very low for each endpoint assessed in both the groups. The rates of grade ≥2 acute dermatitis were 8% and 15%, respectively, for APBI and WBI (P = .18). Rates of grade ≥1 late radiation toxicities were higher in the WBI arm compared with the APBI arm for breast shrinkage (P = .008), pigmentation (P = .028), fibrosis (P = .040), induration (P = .048), and edema (P = .33). Adverse cosmesis at last follow-up was significantly higher in patients treated with WBI: 33% compared with 6% with APBI (P < .001). ConclusionsIn women with breast cancer after BCS, APBI was associated with better cosmetic outcome and fewer late radiation toxicities than WBI.

Patient-Reported Outcomes and Cosmesis in a Feasibility Study of 4-Dimensional Simulated Image Guided Accelerated Partial Breast Irradiation

PurposeThree-dimensional conformal accelerated partial breast irradiation (APBI) is a treatment option for well selected women with breast cancer, despite reports of adverse cosmetic outcome with this technique. Dose-volume relationships may be responsible for this poor cosmesis. We aimed to determine the feasibility of limiting the exposure of nontarget breast tissue to radiation through smaller planning target volumes achieved through daily image guidance and 4-dimensional computed tomography simulation. Methods and MaterialsEligibility criteria included the following: women, age ≥50 years, Karnofsky performance status score ≥70, stage 0 and I breast cancer treated with breast-conserving surgery, margins clear by ≥2 mm, pathologic tumor size ≤2 cm, and 4-dimensional computed tomography with planning target volumes of 0.2 cm rather than the standard 1.0 cm. A dose of 3850 cGy was prescribed in 10 fractions. The study was considered successful if ≥50% of enrollees met dosimetric constraints on the breast (V50 < 45% and V100 < 23.5%). ResultsThe study achieved its primary endpoint of feasibility of reducing the nontarget breast dose with a breast median of V50 = 31% and V100 = 11%. There were no recurrences and no toxicity grade >3. At baseline, fair/poor cosmesis was low (2.2%). By year 3, adverse cosmesis post-APBI had increased by 13.2% (to 15.4%). Patient decisional satisfaction was reached completely in 84.2% of patients. ConclusionsThis study demonstrated that with 4-dimensional simulated APBI that uses stringent dosimetric constraints and image guidance radiation therapy, it is possible to obtain acceptable cosmetic outcomes. We report no locoregional recurrences in 3 years and no toxicity grade >3. The observed decline in cosmesis was acceptable compared with that of prior published studies, and patient satisfaction with APBI was excellent.

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.

Abstract ES4-2: Treatment morbidity and quality of life considerations

Abstract Partial breast irradiation was introduced to reduce treatment times, improve convenience of radiotherapy and reduce radiation exposure to the breast and surrounding normal tissues. A number of techniques have been developed including interstitial brachytherapy, single catheter-based brachytherapy, intraoperative therapy, and 3 dimensional conformal or intensity modulated radiotherapy. The toxicity profile of partial breast irradiation has been dependent on the different techniques used. In general acute toxicity has been less than that observed with whole breast irradiation, particularly for intraoperative approaches where radiotherapy is delivered at the time of breast conserving surgery. Reports of late toxicity have varied. The majority of trials have observed no increase in late toxicity with interstitial brachytherapy and intraoperative treatment when compared to whole breast irradiation. Some studies of 3D conformal radiotherapy have reported an increase in late radiation toxicity such as telangiectasia of the skin and subcutaneous fibrosis of the breast. Limited data are available on cosmetic outcome and quality of life. Again, results to date have varied with some studies reporting similar cosmetic results and others indicating an increase in adverse cosmesis with partial breast irradiation when compared to whole breast irradiation. This presentation will review mature results from completed trials and discuss radiobiological inferences and implications for clinical decision making. Citation Format: Whelan T. Treatment morbidity and quality of life considerations [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 ES4-2.

Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis

To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association ofrisk factors for these outcomes among all patients and those treated with APBI only. Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.

Adverse Cosmesis with Accelerated Partial-Breast Irradiation

Accelerated partial-breast irradiation (APBI) delivers a much shorter course of radiotherapy than whole-breast irradiation (WBI; ≤1 week and 3–6 weeks,

Interim Cosmetic and Toxicity Results From RAPID: A Randomized Trial of Accelerated Partial Breast Irradiation Using Three-Dimensional Conformal External Beam Radiation Therapy

To report interim cosmetic and toxicity results of a multicenter randomized trial comparing accelerated partial-breast irradiation (APBI) using three-dimensional conformal external beam radiation therapy (3D-CRT) with whole-breast irradiation (WBI). Women age > 40 years with invasive or in situ breast cancer ≤ 3 cm were randomly assigned after breast-conserving surgery to 3D-CRT APBI (38.5 Gy in 10 fractions twice daily) or WBI (42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Secondary outcomes were cosmesis and toxicity. Adverse cosmesis was defined as a fair or poor global cosmetic score. After a planned interim cosmetic analysis, the data, safety, and monitoring committee recommended release of results. There have been too few IBTR events to trigger an efficacy analysis. Between 2006 and 2011, 2,135 women were randomly assigned to 3D-CRT APBI or WBI. Median follow-up was 36 months. Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses (29% v 17%; P < .001), by patients (26% v 18%; P = .0022), and by physicians reviewing digital photographs (35% v 17%; P < .001). Grade 3 toxicities were rare in both treatment arms (1.4% v 0%), but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI (P < .001). 3D-CRT APBI increased rates of adverse cosmesis and late radiation toxicity compared with standard WBI. Clinicians and patients are cautioned against the use of 3D-CRT APBI outside the context of a controlled trial.