J.B. Wilkinson

Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysis

BACKGROUND AND PURPOSEnTo compare 12-year outcomes of accelerated partial breast irradiation (APBI) versus whole-breast irradiation (WBI) in patients treated with breast conservation.nnnMATERIALS AND METHODSnA matched-pair analysis was performed using 199 patients receiving WBI and 199 patients receiving interstitial APBI. Match criteria included tumor size, age, nodal status, ER status, and the use of adjuvant hormonal therapy. Patterns of failure and efficacy of salvage treatments were examined.nnnRESULTSnNo differences were seen in the 12-year rates of local recurrence (3.8% vs. 5.0%, p=0.40), regional recurrence (0% vs. 1.1%, p=0.15), disease free survival (DFS) (87% vs. 91%, p=0.30), cause-specific survival (CSS) (93% vs. 95%, p=0.28), or overall survival (OS) (78% vs. 71%, p=0.06) between the WBI and APBI groups, respectively. The rate of distant metastases was lower in the APBI group (10.1% vs. 4.5%, p=.05). Following LR, no difference in outcome was seen between the two groups with 5year post-LR rates of DFS (80% vs. 86%, p=0.55), CSS (88% vs. 75%, p=0.77), and OS (88% vs. 75%, p=0.77), respectively.nnnCONCLUSIONSnWith 12-year follow-up, APBI produced outcomes equivalent to WBI. Following LR, patients treated with APBI also had similar failure patterns to those managed with WBI.

Factors Associated With the Development of Breast Cancer–Related Lymphedema After Whole-Breast Irradiation

PURPOSEnTo determine the rates of breast cancer-related lymphedema (BCRL) in patients undergoing whole-breast irradiation as part of breast-conserving therapy (BCT) and to identify clinical, pathologic, and treatment factors associated with its development.nnnMETHODS AND MATERIALSnA total of 1,861 patients with breast cancer were treated at William Beaumont Hospital with whole-breast irradiation as part of their BCT from January 1980 to February 2006, with 1,497 patients available for analysis. Determination of BCRL was based on clinical assessment. Differences in clinical, pathologic, and treatment characteristics between patients with BCRL and those without BCRL were evaluated, and the actuarial rates of BCRL by regional irradiation technique were determined.nnnRESULTSnThe actuarial rate of any BCRL was 7.4% for the entire cohort and 9.9%, 14.7%, and 8.3% for patients receiving a supraclavicular field, posterior axillary boost, and internal mammary irradiation, respectively. BCRL was more likely to develop in patients with advanced nodal status (11.4% vs. 6.3%, p = 0.001), those who had a greater number of lymph nodes removed (14 nodes) (9.5% vs. 6.0%, p = 0.01), those who had extracapsular extension (13.4% vs. 6.9%, p = 0.009), those with Grade II/III disease (10.8% vs. 2.9%, p < 0.001), and those who received adjuvant chemotherapy (10.5% vs. 6.7%, p = 0.02). Regional irradiation showed small increases in the rates of BCRL (p = not significant).nnnCONCLUSIONSnThese results suggest that clinically detectable BCRL will develop after traditional BCT in up to 10% of patients. High-risk subgroups include patients with advanced nodal status, those with more nodes removed, and those who receive chemotherapy, with patients receiving regional irradiation showing a trend toward increased rates.

Long-Term Impact of Young Age at Diagnosis on Treatment Outcome and Patterns of Failure in Patients with Ductal Carcinoma In Situ Treated with Breast-Conserving Therapy

We reviewed our institutions long‐term experience treating patients diagnosed with ductal carcinoma in situ (DCIS) of the breast with breast‐conserving therapy (BCT) to determine the impact of patient age on outcome over time. All DCIS cases receiving BCT between 1980 and 1993 were reviewed. Patient demographics (including age <45) and pathologic factors were analyzed for effect on outcomes including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included limited surgery (excisional biopsy or lumpectomy) followed by radiotherapy to the whole breast (median whole‐breast dose: 50 Gy, median tumor bed dose: 60.4 Gy). One hundred and forty‐five cases were evaluated; the median follow‐up was 19.3 years. Twenty‐five patients developed an IBTR, for 5‐, 10‐, 15‐, and 20‐year actuarial rates of 9.9%, 12.2%, 13.7%, and 17.5%, respectively. The 10‐year ipsilateral rate of recurrence was 23.3% (<45 years) versus 9.1% (≥45 years) (p = 0.05). Younger patients more frequently developed invasive recurrences (20‐year actuarial rates: 20.4% versus 12.8%, p = 0.22) and true recurrences/marginal misses of the index lesion (23.3% versus 9.7%, p = 0.04) with lower rates of contralateral breast cancer (0.0% and 0.0% versus 12.0% and 20.5%, p = < 0.01, at 10 and 20 years, respectively). Young women under the age of 45 diagnosed with DCIS have a greater risk of local recurrence with different patterns of failure following BCT, which is most notable within 10 years of diagnosis.

Shortened radiation therapy schedules for early-stage breast cancer: a review of hypofractionated whole-breast irradiation and accelerated partial breast irradiation.

Breast‐conserving therapy consisting of segmental mastectomy followed by whole‐breast irradiation (WBI) has become widely accepted as an alternative to mastectomy as a treatment for women with early‐stage breast cancer. WBI is typically delivered over the course of 5–6 weeks to the whole breast. Hypofractionated whole‐breast irradiation and accelerated partial breast irradiation have developed as alternative radiation techniques for select patients with favorable early‐stage breast cancer. These radiation regimens allow for greater patient convenience and the potential for decreased health care costs. We review here the scientific rationale behind delivering a shorter course of radiation therapy using these distinct treatment regimens in this setting as well as an overview of the published data and pending trials comparing these alternative treatment regimens to WBI.

Ductal carcinoma in situ of the breast: Evaluating the role of radiation therapy in the management and attempts to identify low-risk patients

Ductal carcinoma in situ of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with ductal carcinoma in situ include mastectomy or breast-conserving therapy. Although several randomized trials have confirmed a >50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared with breast-conserving surgery alone, controversy persists regarding whether or not RT is needed in selected “low-risk” patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery is associated with higher rates of local recurrence even after selecting patients with optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead focusing on approaches such as multigene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multigene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of RT.

Propensity-score matched pair comparison of brachytherapy-based accelerated partial breast irradiation versus whole breast Canadian hypofractionation.

65 Background: Given the initial report of the RAPID trial with greater morbidity for 3-D conformal external beam APBI [3D-APBI] vs. Canadian Hypofractionation [CHfx], a propensity-score matched-pair analysis of brachytherapy-based APBI [B-APBI] vs. CHfx was performed to assess efficacy, toxicities, and cosmesis.nnnMETHODSnEarly-stage breast cancer patients treated with B-APBI or CHfx were reviewed. With ≥ 1y follow-up [FU], B-APBI (n=108) pts were matched 1:1 to CHfx (n=108) by age, T-stage, nodal/ER status, endocrine or chemotherapy and laterality. Ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastasis (DM), contralateral breast cancer (CLBC), cause-specific survival (CSS), overall survival (OS) and disease-free survival (DFS) were compared by Kaplan-Meier (log-rank test). Toxicities were graded per CTCAE v3 and comesis per Harvard criteria.nnnRESULTSnMedian FU was 5.7 y (1.0-17.8) for B-APBI and 2.1 y (1.0-5.7) for CHfx [p < 0.001]. Patients did not differ by match criteria. In comparing B-APBI to CHfx, median age was 69.0 vs. 70.0 [p = 0.72]; for laterality, T-stage, nodal/ER status, endocrine or chemotherapy, no significance [NS] was noted between the 2 groups [p = 0.79, 1.0, 0.60, 0.09, 0.15, and 0.16 respectively]. Comparing B-APBI to CHfx, NS was seen in 5-y actuarial rates of IBTR [1% vs. 0% p = 0.35], RR [0% both], DM [3.4% vs. 0% p = 0.25], CLBC [2.3% vs. 2% p = 0.63], CSS [94.3% vs. 100% p = 0.47], OS [87.7% vs. 88.3% p = 0.71] & DFS [97.5% vs. 100% p = 0.52]. The majority of maximal late toxicities were Gr 1-2. Of toxicities analyzed, including pigmentary changes, edema, pain, induration, volume reduction, telangiectasia, fat necrosis and seroma, only Gr 2-3 hyperpigmentation was significantly higher in the CHfx [8% B-APBI vs. 22% CHfx p = 0.017]. Good/excellent cosmesis was seen in > 93% in both groups.nnnCONCLUSIONSnWith FU of >5 yrs, B-APBI has similar efficacy and cosmesis but less morbidity vs. CHfx; the lesser toxicity of B-APBI vs. CHfx is in contradistinction to the RAPID results comparing 3D-APBI vs. CHfx. Further FU and more patients are needed to substantiate these findings.

Clinical efficacy of 2-day versus 5-day accelerated partial breast irradiation delivered via balloon-based brachytherapy: Results of a matched pair analysis.

148 Background: This analysis compares the efficacy of a 2-day vs. 5-day accelerated partial breast irradiation (APBI) schedule in treatment of early-stage breast cancer.nnnMETHODSnPatients were treated between 6/2000 and 1/2011 with balloon-based brachytherapy using a 2-day (700 cGy x 4 BID) or a 5-day (340 cGy x 10 BID) fractionation. The CTV was a 1cm expansion from the balloon surface with a single-lumen device used in all cases. To compare efficacy between the two treatment groups, a matched-pair analysis was performed using a 1:2 ratio which paired 38 two-day with 76 five-day patients. Match criteria included minimal follow-up (FU) > 1.0 yr, clinical stage, age (+/- 3 yrs), and ER status. Clinical outcomes analyzed include local-regional recurrence [LR, RR] distant metastases (DM), disease-free, cause-specific and overall survival [DFS, CSS, and OS].nnnRESULTSnNo significant differences were noted for age (p=0.838), clinical stage (p=1.000), ER (p=1.000), tumor size (p=0.236), margin status (p=0.556), nodal stage (p=0.381), PR (p=0.749), use of chemotherapy (p=0.927) or endocrine therapy (p=0.129). Per the ASTRO Consensus Guidelines, no differences were noted in the clinical groups between the 2-and 5-day treatments with the majority categorized as suitable or cautionary (2-day: 92% vs. 5-day: 87% p=0.436). With a mean FU of 4.7 yrs (4.9 yrs for 2-day vs. 4.5 yrs for 5-day, p=0.279), no differences were seen in the 5-year actuarial rates of LR (0.0% vs. 2.6%, p=0.359), DFS (94.4% vs. 96.1%, p=0.618), CSS (100% vs. 94.9 %, p=0.207), or OS (97.3% vs. 92.5%, p=0.811) between the 2-and 5-day groups, respectively. There was no RR in either group. DM rates were similar for both (5.6% vs. 1.3 %, p=0.456).nnnCONCLUSIONSnWith near 5-year FU for the 2-day schedule, APBI with the 2-day regimen yielded outcomes equivalent to the 5-day schema. Reduced on-treatment days by such hypofractionation offers flexibility in clinical and patient scheduling. Further FU and more patients will be needed to substantiate equivalence of hypofractionated APBI. An HIC-approved protocol randomizing patients between the 2 vs. 5-day treatments is currently open for accrual at our institution.

Impact of the number of cautionary/unsuitable risk factors on outcomes following accelerated partial breast irradiation.

146 Background: Current guidelines for APBI stratify appropriateness of treatment outside of a clinical trial. Limited data are available, however, regarding the impact of the number of risk factors (RFs) per patient on clinical outcomes.nnnMETHODSn692 patients were treated with APBI at a single institution between 10/1992 and 10/2011. Patients were stratified by the ASTRO guidelines as suitable, cautionary, and unsuitable. Outcomes including ipsilateral/contralateral breast tumor recurrence (IBTR/CBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause specific survival (CSS), and overall survival (OS) were evaluated by risk group and number of RFs.nnnRESULTSnMedian follow-up was 5.2 years (range: 0-18.3).Distribution within CP risk-groups was suitable: 240, cautionary: 343, and unsuitable: 109 patients. Increased IBTR (2.0% v. 0.6%, p=0.03), DM (6.5% v. 1.5%, p=0.02), and decreased DFS (92% v. 98%, p=0.01) were noted for patients with 2+ cautionary RFs (n=115) vs. 1 RF (n=228). Those with 2+ unsuitable RFs had higher RR (7.7% v. 1.7%, p=0.05). Pooled analysis revealed increased IBTR/RR for patients with 3+ combined cautionary/unsuitable RFs vs. 2 or fewer combined RFs (Table). Univariate analysis showed increased DM with increasing tumor size/T-stage (p<0.01), ER negativity (p=0.04), LVSI (p=0.01), + LN (p<0.01), and increasing number of RFs (p<0.01). No single RF was associated with an increased risk of local recurrence on UVA.nnnCONCLUSIONSnThree or more cautionary or unsuitable APBI RFs is associated with higher local, regional, and distant recurrence. Patients with fewer than 3 total RFs have a 98% locoregional control at 5 years and likely remain good candidates for APBI. Future attempts to risk stratify patients may need to account for the number of RF present in order to appropriately classify patients. [Table: see text].

Evaluation of current consensus panel guidelines for APBI: A pooled analysis of William Beaumont Hospital and American Society of Breast Surgeons MammoSite registry trial data.

145 Background: To determine whether the ASTRO Consensus Panel (CP) guidelines for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite Registry Trial.nnnMETHODSn2,127 cases of early-stage breast cancer were treated using APBI (WBH: n=678; ASBrS: n=1,449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3D-CRT, n=206) while all Registry Trial patients received balloon-based brachytherapy. Patients with complete coding necessary for ASTRO CP assignment (n=1,813) were divided into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CP group.nnnRESULTSnMedian age was 65 years (32-94 years) and median tumor size was 10.0mm (0-45mm). The WBH cohort had more node-positive disease (6.9% vs. 2.6%, p<0.01) and cautionary patients (49.5% vs. 41.8%, p=0.06). Five-year rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%, respectively. When analyzed by CP group, the rate of IBTR was not statistically higher for suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (p=0.20). The non-significant increase in IBTR for grouped cautionary/unsuitable categories was due to increased elsewhere failures/new primaries (p=0.04), not true recurrences (1.1-1.2%, all groups, p=0.94). A higher rate of DM was observed within the cautionary and unsuitable groups (3.3-3.6% vs. 0.7% for suitable, p=0.01), although cause-specific survival was the same for all patient categories (98.0-98.6%, all groups, p=0.47).nnnCONCLUSIONSnExcellent outcomes following breast conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CP guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure within the largest patient population of cases treated with APBI to date.