Accelerated Partial Breast Irradiation (APBI) For Ductal Carcinoma In Situ.

e12516 Background: Landmark studies of accelerated partial breast irradiation (APBI) included patients with DCIS, but with limited guidance regarding subgroups of in situ disease. Suitability criteria defined by national guidelines for APBI are narrowly constrained among those with DCIS, and controversy persists regarding optimal patient selection. Here, we report disease outcomes for a heterogeneous cohort of patients with DCIS who received APBI. Methods: Using a prospectively maintained institutional database, we identified patients with DCIS who underwent lumpectomy and adjuvant APBI from 2000 to 2022. Clinicopathologic characteristics were collected, and patients were classified as suitable, cautionary, or unsuitable for APBI by the latest American Society for Radiation Oncology (ASTRO) criteria. Outcomes of interest included local recurrence (LR), overall survival (OS), and follow up time. Cumulative incidence functions were calculated to estimate the incidence of LR over time. All statistical analyses were performed in R version 4.2.2. Results: The cohort comprised 176 patients, median age 60 years (IQR 52, 66). Median DCIS size was 9 mm (IQR 4, 15 mm), and approximately 20% had multifocal disease. Most patients had negative final surgical margins (160, 91%), with 10 patients having ≤2 mm margins and 6 having ≤1 mm margins for DCIS. 18 (10%) patients had nuclear grade I disease, 111 (63%) had grade II disease, and 33 (19%) had grade III disease, with a small subset classified as grade I-II or II-III. Most patients (161, 91%) had ER+ DCIS, and 72 (41%) received endocrine therapy. By ASTRO criteria, 118 (67%) patients were suitable for APBI, 57 (32%) cautionary, and 1 (0.6%) was unsuitable. At a median 24 months of follow up (range 2 to 127 months) we observed only one LR, yielding a 2-year LR rate of 0.6%. The LR occurred in the cautionary group, yielding a 2-year LR rate of 1.8% for the cautionary subset. The patient with LR was 56 years old, with 24 mm of high grade DCIS, ER+, with lumpectomy to negative margins, and did not receive endocrine therapy. No breast cancer mortality events were observed. Conclusions: Our early-term results exhibit excellent local control for patients with DCIS who received lumpectomy and APBI, even among those classified as “cautionary” by national guidelines. Although our findings are limited by short follow up, these results suggest that broadening the application of APBI for patients with DCIS may warrant further investigation.

The American Society for Radiation Oncology (ASTRO) issued a consensus statement in 2009 regarding patient selection for accelerated partial breast irradiation (APBI) following breast-conserving surgery (BCS) for breast cancer (BC). We reviewed our single-institution experience with APBI in patients considered "cautionary" by ASTRO to determine patterns of recurrence. An institutional review board-approved, retrospective chart review was conducted from January 2004 to November 2009. We identified 106 "cautionary" patients with 109 BC. All patients were treated with BCS followed by APBI via balloon catheter brachytherapy. "Cautionary" criteria include patients aged 50-59 years, tumor size 2.1-3.0 cm, close margins (<2 mm), focal lymphovascular invasion, estrogen receptor (ER)-negative tumors, invasive lobular carcinoma, or ductal carcinoma in situ (DCIS) ≤ 3 cm. Rates of recurrence at any site were evaluated. Median follow-up was 3 years. There were 3 IBTR (2.8%) at a median of 3.2 years. The 3-year actuarial IBTR rate was 1.8%. Patients with ER-negative invasive cancers had a higher IBTR rate compared with ER-positive patients (11.8% vs. 2.2%), although this did not reach statistical significance (P = 0.18). There were no IBTR in 46 patients with DCIS. On univariate analysis, there was no association between "cautionary" criteria and risk of local, regional, or distant recurrence. Patients considered "cautionary" for APBI based on ASTRO guidelines had low rates of IBTR. ER-negative patients trended toward a higher IBTR rate with APBI compared with ER-positive patients. Longer follow-up is needed to establish the safety of APBI in "cautionary" patients.

To the Editor:Breast-conserving therapy (BCT) has becomestandard care as an alternative to mastectomy in thetreatment of most women with early stage 0, I, and IIbreast cancer (1). BCT includes tumor excision bymeans of lumpectomy followed by a course of dailyfractions of external beam radiation therapy to thewhole breast (45–50 Gy), which can be, and often is,followed by a boost to the tumor bed with an addi-tional 6–10 fractions, which achieves a total dose of60–64 Gy. These treatments typically span 5–7 weeks.Studies looking at the patterns of failure and localrecurrence for patients with breast cancer found thatthe majority (about 90%) of early breast local recur-rences occurred at the site of the original primarytumor (2). This observation and the desire to shortenthe treatment times led to the idea of using acceleratedpartial breast irradiation (APBI), which concentratesthe dose of radiation at the site of the lumpectomycavity and simultaneously limits the dose to otherstructures. This type of therapy is typically given over5 days, which not only reduces the toxicity of irradia-tion but also reduces the total treatment time.Results from trials studying the efficacy of APBIhave been encouraging, in that multiple techniqueshave been effective in maintaining excellent local con-trol and cosmetic outcomes with minimal toxicity(3–6). Several phase III randomized studies of APBIare under way; in addition, we are awaiting the resultsof the National Surgical Adjuvant Breast and BowelProject B 39/Radiation Therapy Oncology Group0413 protocol (B-39) large phase III trial that com-pares ABPI to whole breast irradiation (WBI) in earlystage breast cancer, which is finishing accrual in thenear future (7–10).Ductal carcinoma in situ (DCIS) comprises approxi-mately 25% of all cases of breast cancer diagnosedeach year (1). The National Comprehensive CancerNetwork (NCCN) guidelines continue to recommendBCT with standard adjuvant WBI as a category 1 rec-ommendation for DCIS (11). This recommendation isbased on the results of multiple randomized controlledtrials (12,13) demonstrating the efficacy of this com-bined modality approach. Specifically, these studiesreport an approximate 50% relative risk reduction inlocal control with the addition of adjuvant RT. Nosubgroup of patients with DCIS has proved not tobenefit from postoperative radiotherapy (14,15). In2002, DCIS was included as acceptable for APBI inthe American Society for Breast Surgeons (ASBS)guidelines. The APBI Consensus Statement Task Forceof the American Society for Radiation Oncology(ASTRO) classifies the subset of patients with pureDCIS as “cautionary,” with a recommended tumorcutoff size of 3 cm (16). Recent publications haveshown excellent 5-year follow-up results in patientswith DCIS treated with APBI (17–20).At our institutions we have noted low recurrencerates and excellent or good cosmesis outcomes in100% of the patients treated with APBI after breastconservation surgery (BCS) for patients with DCIS.This letter is in response to requests from brachythera-py specialists to publicize institution-specific dataregarding the use of APBI to treat breast cancer. Wehave now treated over 40 patients with stage 0 breastcancer treated with BCS and adjuvant APBI. Allpatients had biopsy-proven DCIS, and three patientsalso had an invasive component along with DCIS.With a median follow-up was 27 months (range,0–72 months, the overall and cause-specific survivalrates were 95% and 100%, respectively. The24-month actuarial ipsilateral breast tumor recurrence(IBTR) rate was 2.5%, with one patient having arecurrence. Another patient developed a contralateral

92 Background: Limited data are available on the treatment of ductal carcinoma in situ (DCIS) with accelerated partial breast irradiation (APBI). The American Society for Radiation Oncology (ASTRO) consensus guidelines on APBI classify patients with DCIS as “cautionary”. We present the largest series of DCIS patients reported to date treated with APBI using strut-based brachytherapy. Methods: The SAVI Collaborative Research Group (SCRG) database was used to identify APBI patients with DCIS at 15 institutions treated with strut-based brachytherapy. All patients had a histologic diagnosis of DCIS and received monotherapy APBI (34 Gy in 10 fractions). Data on patient age and margin status, implant dosimetry, device size, disease status and toxicity in this population were analyzed. Results: From 2007-2011, 321 patients (322 breasts) with DCIS received APBI using strut-based brachytherapy. Patient ages ranged from 40-88 with a median age of 62. 51 patients were under 50 years of age. Detailed dosimetry data were reported on 245 patients. Long-term follow up was available on 221 breasts (median F/U = 25 months). Sixty patients have been followed for &gt;3 years. Skin spacing was a challenge in a significant number of patients including 52 with skin spacing ≤ 5mm and 20 with skin spacing ≤ 3mm. Median maximum skin dose in those patient groups were 87% and 84% of prescription dose (PD), respectively. Overall reported dosimetry (n=245) was excellent: median percent of target volume receiving 90% PD was 96.9%, median maximum skin dose was 83.2%, V150% and V200% (volume at 150% and 200% PD) were 25.2 cc and 12.7 cc respectively. The ipsilateral recurrence rate was 2.2% (1.1% TR/MM). Late toxicity (grade ≥ 2) was low: hyperpigmentation = 0.0%, telangiectasias =1.4%, seroma = 3.2%, and fat necrosis in 1.8%. Conclusions: APBI using strut-based brachytherapy appears to be an effective treatment for patients with DCIS with acceptably low ipsilateral breast recurrence rates and low rates of late toxicity. 52 patients in our series had skin spacing 5 mm or less. APBI using brachytherapy may not have been possible for these women with other single-entry devices.

Impact of the ASTRO 2024 Guideline on Partial Breast Irradiation Eligibility in Breast Cancer Patients (KROG 24-01).

Background: Ductal carcinoma in situ (DCIS) is a proliferation of malignant epithelial cells of the ducts and terminal lobular units of the breast that do not invade the basement membrane. The incidence of DCIS has increased markedly since the early 1980s, chiefly due to screening mammography. Whole breast radiotherapy has largely been used to treat breast DCIS after lumpectomy. More recently, APBI has increasingly been utilized for breast DCIS. Currently updated American Society of Radiation Oncology (ASTRO) APBI guidelines have included "low risk" DCIS (as defined by RTOG 9804 criteria). The following results further explore clinico-pathologic factors, in addition to the DCIS Score, in order to better define an appropriate DCIS population for APBI. Methods: An exploratory analysis aimed to retrospectively measure the association between clinico-pathologic factors and the DCIS Score result, an optimized 12-gene expression algorithm, and risk of any local failure (in situ or IBC recurrence) in a cohort of women treated with local excision and APBI on prospective phase II (NCT01185145) and phase III (NCT01185132) clinical trials. Multifocal tumors were described only by local pathology and not determined or defined centrally. The DCIS Score assay was performed by quantitative RT-PCR on formalin-fixed paraffin-embedded DCIS tumor specimens by Genomic Health (Redwood City, CA). Descriptive statistics of the cohort and assay results overall and by clinical trial were derived. Univariable Cox proportional hazards regression was used to determine whether there was an association between local failure and categorized DCIS Score group (≥39 vs &amp;lt;39) or other clinico-pathologic factors on the pooled cohort of clinical trial patients. Results: This analysis included 104 evaluable patients (N=18 from NCT01185145 and N=86 from NCT01185132). The median age was 60 (range: 41-80), 79% of patients were postmenopausal, and the median span of DCIS was 6 mm (range 2-25 mm). Over two-thirds of the cohort presented with necrosis (71%). The distribution of DCIS Score results ranged from 0 to 82, with 69% of patients having a DCIS Score result &amp;lt;39. The median follow-up time was longer at 8.2 years in NCT01185145 versus 3.0 years in NCT01185132. There was a total of 6 local recurrences. DCIS Score result was significantly associated with local recurrence in univariable modeling (hazard ratio=10.3 for ≥39 vs &amp;lt;39; p=0.0104). None of the other clinico-pathologic characteristics resulted in any significant correlation with locoregional recurrence. All results were highly variable due to the small number of events. Conclusion: The DCIS Score assay demonstrated risk stratification in this cohort of patients treated with local excision and APBI pooled from two clinical trials. These results are consistent with those recently published by Rakovitch et al (J Natl Cancer Inst 2017). The cohort in this study was dominated by those in the phase III trial. Due to the small number of local recurrence events and limited follow-up time in the phase III trial, caution should be taken when interpreting the results. Further investigations are needed to confirm findings. Citation Format: Leonard CE, Fryman SP, Turner MP, Bennett JP, Carter DL, Sing AP. Association of OncotypeDX® DCIS ScoreTM results with local recurrence in patients with DCIS treated on accelerated partial breast radiotherapy (APBI) protocols [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-08.

A sufficient body of knowledge has developed about ductal carcinoma in situ of the breast to warrant a separate report on standards of care for women with this disease. This consensus report by these four organizations discusses evaluation of the patient, selection of treatment, technical aspects of diagnostic biopsy and definitive local excision, pathologic evaluation, radiation therapy considerations, follow-up care recommendations, and questions for future research.

Utility of Breast Magnetic Resonance Imaging in Determining Candidacy for Partial Breast Irradiation

Should Ductal Carcinoma In Situ (DCIS) be Removed From the ASTRO Cautionary Group for Off-protocol Use of Accelerated Partial Breast Irradiation (APBI)? A Pooled Analysis of Outcomes for 300 Patients With DCIS treated With APBI

Long-Term Outcome of Accelerated Partial Breast Irradiation Using Multi-Lumen Applicators in the Setting of Breast Augmentation

Outcomes After Accelerated Partial Breast Irradiation in Patients With ASTRO Consensus Statement Cautionary Features

1123 Background: DCIS remains a cautionary criterion for APBI by the ASTRO APBI consensus statement. We performed a matched analysis to compare the efficacy of WBI and APBI for patients with DCIS. Methods: Women with DCIS treated with APBI or WBI were reviewed. APBI (n=102) patients with ≥2 y follow-up were matched 1:3 to WBI (n=546) patients with ≥5 y follow-up by age, tumor size, nuclear grade, ER status, margin status, and laterality. Ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), contralateral breast cancer (CLBC) and cause-specific survival (CSS) were compared by cumulative incidence (Gray’s) and competing risks regression (Fine and Gray’s), and overall survival (OS) and disease-free survival (DFS) by Kaplan-Meier (log-rank test). Results: Median follow-up was 4.6 y (2.0-14.7) for APBI and 9.0 y (5.4-27.0) for WBI. Median (range) or percentages are shown (Table). Patients did not differ by match criteria. There were 17 LR, 1 DM, 19 CLBC, 2 CSS, 22 OS, and 19 DFS events during follow-up. The patient groups had similar rates of cancer-related events including ipsilateral and contralateral breast recurrences at both five and eight years. Treatment type, age, tumor size, nuclear grade, ER status, and hormone therapy (HT) were not prognostic of LR or CLBC on uni- and multi-variate analyses. Conclusions: APBI provides equivalent and exemplary outcomes compared to WBI following breast-conserving surgery for DCIS. These findings support previous reports on the efficacy of APBI in the treatment of noninvasive breast carcinoma. Prospective randomized comparison of APBI to WBI for DCIS is needed. [Table: see text]

Trends in the use of implantable accelerated partial breast irradiation for ductal carcinoma in situ: Implications of the recent amendments to the American Society for Radiation Oncology consensus guidelines

Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Ductal Carcinoma In Situ

Practical Implications of the Publication of Consensus Guidelines by the American Society for Radiation Oncology: Accelerated Partial Breast Irradiation and the National Cancer Data Base