Background: Conventional WBI after lumpectomy for early-stage breast cancer decreases ipsilateral breast tumor recurrence (IBTR), yielding comparable results to mastectomy. Accelerated PBI appears effective in reducing IBTR by treating only the tumor bed area. As the majority of IBTR occur at or in the vicinity of the tumor bed, we hypothesized that PBI would be as effective as WBI in controlling IBTR. The primary aim of NSABP B-39/RTOG 0413 was to determine if PBI provides equivalent local tumor control post lumpectomy compared to WBI in pts with early-stage breast cancer. The equivalency test was based on a 50% margin of increase in the hazard ratio (HR=1.5). Secondary endpoints included: overall survival (OS), recurrence-free interval (RFI), distant disease-free interval (DDFI), and toxicity. Methods: Eligible pts had lumpectomy with histologically-free margins and 0-3 positive axillary nodes. Pts were stratified by stage, menopausal status, hormone receptor status, and intent to receive chemotherapy and then randomized to PBI or WBI. PBI was 10 fractions of 3.4-3.85 Gy, given twice daily with either brachytherapy or 3D external beam radiation. WBI was 50 Gy in 2 Gy fractions given daily with a sequential boost to the surgical cavity. Follow-up was every 6 mos for 5 yrs and then annually. All analyses were by intent-to-treat. Results: From 3-21-05 to 4-16-13, 4216 pts were randomized: 2107 PBI; 2109 WBI. 61% were postmenopausal; 81% were hormone receptor-positive; 29% intended to receive chemotherapy. Stage distribution was: DCIS, 24%; invasive pN0, 65%; invasive pN1, 10%. As of 7-31-18, median follow-up was 10.2 yrs. There were 161 IBTRs as first events: 90 PBI v 71 WBI (HR 1.22; 90%CI 0.94-1.58). Per protocol-defined margin, to declare PBI and WBI equivalent regarding IBTR risk, the 90% CI for the observed HR had to lie entirely between 0.667 and 1.5. The percent of pts IBTR-free at 10 yrs was 95.2% PBI v 95.9% WBI. A statistically significant difference in the 10-yr RFI rate favored WBI (91.9% PBI v 93.4% WBI; HR 1.32; 95%CI 1.04-1.68; p=0.02). No statistically significant differences existed between PBI and WBI in DDFI (HR 1.31; 95%CI 0.91-1.91; p=0.15), OS (HR 1.10; 95%CI 0.90-1.35; p=0.35), or DFS (HR 1.12; 95%CI 0.98-1.29; p=0.11). Grade 3 toxicity was 9.6% PBI v 7.1% WBI, and grade 4-5 toxicity was 0.5% v 0.3%, respectively. Discussion: PBI did not meet the criteria for equivalence to WBI in controlling IBTR based on the upper limit of the hazard ratio confidence interval. However, the absolute difference in 10-yr rate of IBTR was <1% (4.8% PBI v 4.1% WBI). The risk of an RFI event was statistically significantly higher for PBI compared to WBI, but the absolute difference in 10-yr RFI rate was also small (8.1% PBI v 6.6% WBI). DDFI, OS, and DFS were not statistically different for PBI v WBI. Grade 3-5 toxicities, although low, were more common for PBI than WBI. The trial population was heterogeneous, ranging from Stage 0-2 breast cancer, and outcome by risk categories are being analyzed. Support: U10CA180868, -180822, UG1CA189867. Citation Format: Vicini FA, Cecchini RS, White JR, Julian TB, Arthur DW, Rabinovitch RA, Kuske RR, Parda DS, Ganz PA, Scheier MF, Winter KA, Paik S, Kuerer HM, Vallow LA, Pierce LJ, Mamounas EP, Costantino JP, Bear HD, Germaine I, Gustafson G, Grossheim L, Petersen IA, Hudes RS, Curran, Jr. WJ, Wolmark N. Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer [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 GS4-04.
BACKGROUNDEighty‐seven institutions participated in a Registry Trial that was designed to collect data on the clinical use of the MammoSite™ breast brachytherapy catheter for delivering breast irradiation. Patient demographics, technical reproducibility, cosmesis, and early toxicity were evaluated.METHODSFrom May 4, 2002 through July 30, 2004, 1419 patients with Stage 0, I, or II breast carcinoma who were undergoing breast‐conserving therapy were enrolled on the trial. The device was placed in 1403 of these patients. The 1237 patients (87% of enrolled patients) who received accelerated partial breast irradiation (APBI) (34 grays prescribed to 1.0 cm in 10 fractions; 95% of patients who received APBI) constituted the study population; 86% of those patients (1068) had Stages I–II breast carcinoma (median tumor size, 10 mm), and 14% of those patients (169) had Stage 0 breast carcinoma. Ninety‐one percent of the patients with invasive carcinoma (977 of 1068 patients) had negative lymph node status, and 99% of all patients had negative margins. The median patient age was 65 years. Systemic chemotherapy alone was administered to 79 patients with invasive carcinoma (7%), hormone therapy was administered to 501 patients (45%), and both were administered to 39 patients (4%). The median follow‐up was 5 months.RESULTSFive hundred fifty‐four catheters (45%) were placed with an open cavity at the time of lumpectomy, and 683 catheters (55%) were placed with a closed cavity after lumpectomy. Skin spacing ranged from 2 mm to 75 mm (median, 10 mm). In 89% of patients, there was a minimum balloon‐to‐skin distance of 7 mm (2% of patients had distances < 5 mm). In terms of cosmetic assessment, 95% of patients (1030 of 1084 patients) who had a cosmetic assessment had a good/excellent result (last follow‐up visit). Cosmetic results at 12 months were good/excellent in 92% of 248 evaluable patients. The median skin spacing (≥ 7 mm vs. < 7 mm) was associated significantly with a good/excellent cosmetic result (96.1% vs. 86.8%; P = 0.0001) overall and at 6 months (P = 0.006). Increasing skin spacing was associated with a good/excellent cosmetic result as a continuous variable (P < 0.0001). In total, 92 of 1140 evaluable patients (8.1%) developed an infection in the breast, which was device‐related in 5.3% of patients (60 of 1140 patients). Good/excellent cosmetic results were noted in 86% of these patients (last follow‐up visit). Fifteen of 442 evaluable patients (3.4%) developed a radiation recall reaction. Good/excellent cosmetic results were noted in 93% of these patients at their last follow‐up visit. One local recurrence (0.1%) was reported (new primary carcinoma).CONCLUSIONSClinical evaluation of the ability of the MammoSite™ breast brachytherapy catheter to deliver APBI demonstrated acceptable technical reproducibility between multiple institutions and use in appropriate groups of patients. Cosmetic results at 12 months (92% good/excellent) were comparable to those reported with whole‐breast RT. Early toxicity rates (infections, radiation recall) appeared to be acceptable. Cancer 2005. © 2005 American Cancer Society.
Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery.Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery. Citation Format: Kuerer HM, Rauch GM, Krishnamurthy S, Adrada BE, Caudle AS, DeSnyder SM, Santiago L, Lucci A, Hobbs BP, Gilcrease M, Hwang R, Candelaria RP, Chavez Mac-Gregor M, Arribas E, Moseley T, Teshome M, Miggins MV, Smith BD, Valero V, Hunt KK, Yang WT. Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-30.
Background: In the management of DCIS clinicians and patients (pts) must choose between the various options for breast conservation treatment based on an assessment of local recurrence (LR) risk. Traditional clinicopathologic (CP) factors such as age, size, grade, margin width or comedo necrosis, provide an average LR risk derived from clinical trials and population studies. The Oncotype DX® 12-gene assay for DCIS gives individual 10-yr LR risk estimates and has now been validated in two studies in a total of 893 pts. We report the 2nd study assessing the impact of the DCIS Score result on XRT recommendations. In addition, surveys assessing pt and physician confidence will provide insight into the overall clinical utility of the DCIS Score result. Baseline characteristics including the pre-assay LR risk and XRT recommendation are described here; final results on change in XRT recommendation from pre- to post-assay and distribution of the score across the CP factors will be presented. Methods: 13 U.S. sites enrolled pts with DCIS from 3/2014-5/2015. Pts with LCIS but no DCIS, invasive BC, or planned mastectomy were excluded. Data were prospectively collected on CP factors, physician estimates of LR risk, DCIS score, and pre/post XRT recommendation. Each pt had a surgeon and radiation oncologist complete study surveys. Pt surveys were also administered pre/post assay for decision conflict and the STAIT anxiety survey. The LR risk estimates and XRT recommendations were analyzed for all physicians as well as by specialty. Descriptive statistics summarized study variables. 95% Clopper-Pearson Exact CIs were calculated for percent change in XRT recommendation. McNemar's test was used to determine if the proportion of pts had a significant change in XRT recommendation post assay. Paired t-tests were used to compare physician estimates of recurrence risk pre/post assay. Results: Of the 121 pts enrolled, median age was 61y (34-83) and 80.2% were postmenopausal. Median size was 8mm and 40% were < 5mm; 22.3% were grade 1, 51.2% grade 2, and 26.4% grade 3. Comedo necrosis was noted in 55.4% and 19% had multiple foci. Median margin width was 3mm and 47.1% had margins 1-3mm. ER and PR by IHC were positive in 88.4% and 75.2% of pts. Among the 242 MD risk assessments, mean 10-yr LR risk was 14.8% (range 4-50%) for any LR; 14.2% for surgeons and 15.3% for radiation oncologists. The pre-assay XRT recommendation was 70.2%; 68.6% for surgeons and 71.9% for radiation oncologists. Conclusions: The role of new molecular tools such as the DCIS Score assay that provide individual risk estimates for LR on treatment decisions is evolving. The DCIS pts enrolled in the study reveal inclusion of baseline features like higher nuclear grade (26%), comedo necrosis (55%) and margin width of 1-3mm (47%) that have historically been associated with XRT use. This represents a continued broadening of the assay use from the predominantly lower risk DCIS cohort in the 1st validation study (E5194). The impact on XRT decisions is critical to establishing the clinical utility of the assay. The decision impact analysis, differences in use of the assay among surgeons and radiation oncologists and the impact on overall confidence with the treatment decision will be presented. Citation Format: Manders JB, Kuerer HM, Smith BD, McCluskey C, Farrar WB, Frazier TG, Li L, Leonard CE, Carter DL, Chawla S, Medeiros LE, Guenther JM, Castellini LE, Buchholz DJ, Mamounas EP, Wapnir IL, Horst KC, Chagpar A, Evans SB, Riker AI, Vali FS, Solin LJ, Jablon L, Recht A, Sharma R, Lu R, Sing AP, Hwang ES, White J. The 12-gene DCIS score assay: Impact on radiation treatment (XRT) recommendations and clinical utility. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-03.
Purpose: Emerging data from cooperative group trials suggests that not all patients with a positive SLN require completion axillary lymph node dissection (ALND). The controversy regarding who will benefit from additional nodal clearance continues, suggesting a need for improved tools to predict non-SLN involvement. We hypothesized that the size of a SLN metastasis evaluated as a continuous variable would be an important predictor of non-SLN involvement. The goal of this study was to determine clinicopathologic factors including SLN metastasis size that predicted non-SLN involvement and to use these factors to construct an improved predictive nomogram. Methods: Using a prospective database, we identified 509 patients with invasive breast cancer from 1996 - 2007 with a positive SLN who underwent ALND. Patients receiving neoadjuvant therapy were excluded. Clinicopathologic data including age, primary tumor size, presence of multifocal disease, histology (invasive ductal vs. invasive lobular vs. mixed invasive), tumor grade, estrogen receptor, progesterone receptor, and HER2/neu status, presence of lymphovascular invasion (LVI), the number of SLNs identified, number of positive SLNs, the maximum SLN metastasis size and the presence of extranodal extension were recorded. For SLNs described only as containing isolated tumor cells, size was recorded as 0.1 mm. Univariate and multivariate logistic regression analyses were performed to identify factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients. Results: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (p<.001), number of positive SLN (p<.001), maximum SLN metastasis size (p<.001), extranodal extension (p<.001), primary tumor size (p=.001), LVI (p=.019) and histology (p=.034). On multivariate analysis, all factors remained significant at the 5% level except LVI. A nomogram was created using these variables. When applied to an external cohort, the nomogram was accurate and discriminating with an area under the receiver operating characteristic curve of .73 (95% CI: .68 - .77). Conclusions: SLN metastasis size is predictive for identifying additional disease in the axilla. These data have been incorporated into a nomogram that accurately predicts the likelihood of having additional, non-SLN metastasis suggesting that routine reporting of the SLN metastasis size would assist with clinical decision making regarding the need to perform a completion ALND. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-08.
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