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Purpose: We applied the American Society of Therapeutic Radiology and Oncology (ASTRO) Consensus Panel (CP) guidelines for the use of accelerated partial breast irradiation (APBI) to patients treated with this technique to determine the ability of the guidelines to differentiate patients with significantly different clinical outcomes. Methods and Materials: A total of 199 patients treated with APBI and 199 with whole-breast irradiation (WBI) (matched for tumor size, nodal status, age, margins, receptor status, and tamoxifen use) were stratified into the three ASTRO CP levels of suitability ('suitable,' 'cautionary,' and 'unsuitable') to assess rates of ipsilateral breast tumor recurrence (IBTR), regional nodal failure, distant metastases, disease-free survival, cause-specific survival, and overall survival based on CP category. Median follow-up was 11.1 years. Results: Analysis of the APBI and WBI patient groups, either separately or together (n = 398), did not demonstrate statistically significant differences in 10-year actuarial rates of IBTR when stratified by the three ASTRO groups. Regional nodal failure and distant metastasis were generally progressively worse when comparing the suitable to cautionary to unsuitable CP groups. However, when analyzing multiple clinical, pathologic, or treatment-related variables, only patient age was associated with IBTR using WBI (p = 0.002). Conclusions: The ASTRO CPmore » suitable group predicted for a low risk of IBTR; however, the cautionary and unsuitable groups had an equally low risk of IBTR, supporting the need for continued refinement of patient selection criteria as additional outcome data become available and for the continued accrual of patients to Phase III trials.« less

Background It is generally believed that ipsilateral breast failures (IBFs) after breast-conserving therapy (BCT) develop from incompletely eradicated carcinoma. We previously suggested that monomorphic epithelial proliferations (MEPs) in the breast may be a pool of partially transformed clones from which breast carcinomas can arise and that radiation therapy (RT) may also reduce the risk of IBF by eradicating MEPs. We examined salvage mastectomy specimens in patients experiencing an IBF to define the relationship between MEPs and IBFs and an additional potential mechanism for IBF risk reduction by RT. Methods and Materials The location, number, and distribution of radiation changes and MEPs relative to 51 IBFs were mapped in salvage mastectomy specimens from BCT patients with adequately excised, initial carcinomas (negative lumpectomy margins). Results All 51 salvage mastectomies had diffuse, late radiation changes. None had active fibrocystic lesions. MEPs were predominantly located in the immediate vicinity of the IBFs. A mean of 39% of MEP cases were located within the IBF, 46% were located within 2 cm of the IBF, and 14% were 2–3 cm from the IBF. Conclusions MEPs appear to be a pool of partially transformed precursor lesions that can give rise to ductal carcinoma in situ and invasive carcinomas (CAs). Many IBFs may arise from MEPs that reemerge after RT. Radiation may also reduce IBF risk after BCT (including in patients with negative margins) by primarily eradicating MEPs.

Accelerated partial breast irradiation has become an important component of the management of early-stage breast cancer. While local control following APBI continues to be excellent with acceptable rates of acute and late toxicities, further refinement of patient selection guidelines and completion of the ongoing Phase III trials remain priorities for this growing segment of radiation oncology.

Purpose To evaluate the 10-year outcomes of intermediate- and high-risk prostate cancer patients treated with a prospective dose escalation hypofractionated trial of pelvic external beam radiation therapy (P-EBRT) with a high-dose-rate (HDR) brachytherapy boost. Methods and Materials From 1992 to 2007, 472 patients were treated with a HDR boost at William Beaumont Hospital. They had at least one of the following: a prostate-specific antigen (PSA) level of >10 ng/ml, a Gleason score of ≥7, or clinical stage ≥T2b. Patients received 46-Gy P-EBRT and an HDR boost. The HDR dose fractionation was divided into two dose levels. The prostate biologically equivalent dose (BED) low-dose-level group received 268 Gy . Phoenix biochemical failure (BF) definition was used. Results Median follow-up was 8.2 years (range, 0.4-17 years). The 10-year biochemical failure rate of 43.1% vs. 18.9%, ( p 0.001), the clinical failure rate of 23.4% vs. 7.7%, ( p 0.001), and the distant metastasis of 12.4% vs. 5.7%, ( p = 0.028) were all significantly better for the high-dose level group. On Cox multivariate analysis, higher BED levels ( p = 0.017; hazard ratio [HR] = 0.586), pretreatment PSA assays ( p 0.001, HR=1.022), and Gleason scores ( p = 0.004) were significant variables for reduced biochemical failure. Higher dose levels ( p , 0.002; HR, 0.397) and Gleason scores ( p 0.001) were significant for clinical failure. Grade 3 genitourinary complications were 2% and 3%, respectively, and grade 3 gastrointestinal complication was Conclusions This prospective trial using P-EBRT with HDR boost and hypofractionated dose escalation demonstrates a strong dose-response relationship for intermediate- and high-risk prostate cancer patients. The improvement at 10 years for locoregional control with higher radiation doses (BED, > 268Gy) has significantly decreased biochemical and clinical failures as well as distant metastasis.

Purpose Brachytherapy is a method for delivering partial-breast irradiation after breast-conserving surgery (BCS). It is currently used in the community setting, although its efficacy has yet to be validated in prospective comparative trials. Frequency and factors influencing use have not been previously identified. Methods In a nationwide database of 6,882 Medicare beneficiaries (age ≥ 65 years) with private supplemental insurance (MarketScan Medicare Supplemental), claims codes identified patients treated with brachytherapy versus external-beam radiation after BCS for incident breast cancer (diagnosed from 2001 to 2006). Logistic regression modeled predictors of brachytherapy use. Results Frequency of brachytherapy use as an alternative to external-beam radiation after BCS increased over time (< 1% in 2001, 2% in 2002, 3% in 2003, 5% in 2004, 8% in 2005, 10% in 2006; P < .001). Increased use correlated temporally with US Food and Drug Administration approval and Medicare reimbursement of brachytherapy technology. Brachytherapy use was more likely in women with lymph node–negative disease (odds ratio [OR], 2.19; 95% CI, 1.17 to 4.11) or axillary surgery (OR, 1.74; 95% CI, 1.23 to 2.44). Brachytherapy use was also more likely in women with non–health maintenance organization insurance (OR, 1.81; 95% CI, 1.24 to 2.64) and in areas with higher median income (OR, 1.58; 95% CI, 1.05 to 2.38), lower density of radiation oncologists (OR, 1.78; 95% CI, 1.11 to 2.86), or higher density of surgeons (OR, 1.57; 95% CI, 1.07 to 2.31). Conclusion Despite ongoing questions regarding efficacy, breast brachytherapy was rapidly incorporated into the care of older, insured patients. In our era of frequently emerging novel technologies yet growing demands to optimize costs and outcomes, results provide insight into how clinical, policy, and socioeconomic factors influence new technology diffusion into conventional care.

Over the last 2 decades, we have seen major advances in the application of radiotherapy after breast-conserving surgery. Two important contributions are the use of whole-breast hypofractionation and accelerated partial-breast irradiation. Three large randomized trials comparing whole-breast hypofractionation versus conventional fractionation for early breast cancer have shown similar rates of local recurrence and morbidity. As a result, whole-breast hypofractionation is now an option for selected patients after breast-conserving surgery. The delivery of accelerated partial-breast irradiation (APBI) has been studied using techniques of multicatheter interstitial brachytherapy, balloon-based brachytherapy, external-beam radiotherapy, and intraoperative radiotherapy. Multiple single and multi-institutional data have been published indicating good long-term results with APBI (in highly selected, low-risk patients) in terms of tumor control and toxicity. However, the long-term results of large, phase III trials comparing APBI with whole-breast irradiation are still pending.

Dosimetric findings in patients treated with the Contura multilumen balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional Phase IV registry trial are presented.Computed tomography-based three-dimensional planning with dose optimization was performed. For the trial, new ideal dosimetric goals included (1) ≥95% of the prescribed dose (PD) covering ≥90% of the target volume, (2) a maximum skin dose ≤125% of the PD, (3) maximum rib dose ≤145% of the PD, and (4) the V150 ≤50 cc and V200 ≤10 cc. The ability to concurrently achieve these dosimetric goals using the Contura MLB was analyzed.144 cases were available for review. Using the MLB, all dosimetric criteria were met in 76% of cases. Evaluating dosimetric criteria individually, 92% and 89% of cases met skin and rib dose criteria, respectively. In 93% of cases, ideal target volume coverage goals were met, and in 99%, dose homogeneity criteria (V150 and V200) were satisfied. When skin thickness was ≥5 mm to7 mm, the median skin dose was limited to 120.1% of the PD, and when skin thickness was5 mm, the median skin dose was 124.2%. When rib distance was5 mm, median rib dose was reduced to 136.5% of the PD. When skin thickness was7 mm and distance to rib was5 mm, median skin and rib doses were jointly limited to 120.6% and 142.1% of the PD, respectively.The Contura MLB catheter provided the means of achieving the imposed higher standard of dosimetric goals in the majority of clinical scenarios encountered.

Background: Ongoing phase III trials are comparing accelerated PBI around the lumpectomy site to standard whole breast irradiation in early stage breast cancer. Recent studies have questioned the late toxicity from PBI delivered with 3DCRT. We evaluated late toxicity on patients (pts) treated on RTOG 0319. Methods:52 pts with stage I-II breast cancer, ≥3 cm, negative margins, and < 3 nodes positive were treated with 3DCRT PBI and received 38.5 Gy in 10 BID fractions over 5 days. Median follow-up was 5.3 years (min-max: 1.7-6.4 years). Five pts were deceased at 5 years. NCI CTCAE v3.0 was used to grade adverse events (AEs). At 3 years, 50 pts were available for AE reporting or late toxicity assessment. Results: The treatment-related AEs were primarily grade 1 36.5%, 50% grade 2, and only 3 (5.8%) pts had grade 3 AEs. The grade 3 AEs in these pts were radiation dermatitis, skin fibrosis, telangectasia, and myositis. No baseline self-assessment of breast appearance is available. Patient self-assessment of breast appearance and satisfaction was available in 45 (87%) pts at 1 year and 36 (72%) at 3 years. At 1 year, 82% self reported excellent/good breast appearance and at 3 years, 64%. Pts who reported < excellent/good breast appearance had significantly more grade ≥2 skin AEs (telangectasia, skin atrophy, hyperpigmentation, erythema, skin fibrosis, radiation dermatitis, and breast or nipple/areolar deformity). At 3 years, 31 of 36 pts were satisfied with their treatment, but all 36 would choose 3DCRT PBI again over standard breast RT. Treatment factors were evaluated to establish correlation with patient reported breast appearance. Preliminary observations suggest surgical bed volume, PTV volume, number of beams used, and possible use of bolus are associated with patient reported outcomes (PRO). Surgical factors impacting PRO were not collected. Conclusions: The majority of pts were satisfied with their treatment results at 3 years and would all choose to have 3DCRT PBI again. With a median of 5.3 years, the rate of grade 3 AEs is low. Technical factors from this phase II trial were modified for the phase III NSABP B-39/RTOG 0413 trial, in which bolus is not allowed and both target volumes and required coverage were modified, increasing expectation of improved PRO. Supported by RTOG U10 CA21661, CCOP U10 CA37422 and ATC U24 CA 81647 NCI grants. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-07.

Purpose Previous studies have shown that lumpectomy cavity volumes can change significantly in the weeks following surgery. The effect of this volume change on the surrounding tissue that constitutes the clinical target volume (CTV) for accelerated partial breast irradiation and boost treatment after whole breast irradiation has not been previously studied. In the present study, we used deformable registration to estimate the effect of lumpectomy cavity volume changes on the CTV for accelerated partial breast irradiation and discuss the implications for target construction. Methods and Materials The data from 13 accelerated partial breast irradiation patients were retrospectively analyzed. Deformable registration was used to propagate contours from the initial planning computed tomography scan to a later computed tomography scan acquired at the start of treatment. The changes in cavity volume and CTV, distance between cavity and CTV contours ( i.e., CTV margin), and CTV localization error after cavity registration were determined. Results The mean ± standard deviation change in cavity volume and CTV between the two computed tomography scans was −35% ± 23% and −14% ± 12%, respectively. An increase in the cavity-to-CTV margin of 2 ± 2 mm was required to encompass the CTV, and this increase correlated with the cavity volume change. Because changes in the cavity and CTV were not identical, a localization error of 2–3 mm in the CTV center of mass occurred when the cavity was used as the reference for image guidance. Conclusion Deformable registration suggested that CTV margins do not remain constant as the cavity volume changes. This finding has implications for planning target volume and CTV construction.

BACKGROUND: The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group. METHODS: Patients were classified based on the CS groups of “suitable,” “cautionary,” and “unsuitable.” Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease-free survival, cause-specific survival, and overall survival were assessed. RESULTS: Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the “suitable” criteria, 430 patients (42%) who fit the “cautionary” criteria, and 176 patients (17%) who fit the “unsuitable” criteria. At a median follow-up of 53.5 months, the 5-year actuarial rates of IBTR for the “suitable,” “cautionary,” and “unsuitable” groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio [OR], 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age

This prospective study (Radiation Therapy Oncology Group 0319) examines the use of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Initial data on efficacy and toxicity are presented.Patients with Stage I or II breast cancer with lesionsor =3 cm, negative margins and withor =3 positive nodes were eligible. The 3D-CRT was 38.5 Gy in 3.85 Gy/fraction delivered 2x/day. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Mastectomy-free, disease-free, and overall survival (MFS, DFS, OS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, was used to grade acute and late toxicity.Fifty-eight patients were entered and 52 patients are eligible and evaluable for efficacy. The median age of patients was 61 years with the following characteristics: 46% tumor size1 cm; 87% invasive ductal histology; 94% American Joint Committee on Cancer Stage I; 65% postmenopausal; 83% no chemotherapy; and 71% with no hormone therapy. Median follow-up is 4.5 years (1.7-4.8). Four-year estimates (95% CI) of efficacy are: IBF 6% (0-12%) [4% within field (0-9%)]; INF 2% (0-6%); CBF 0%; DF 8% (0-15%); MFS 90% (78-96%); DFS 84% (71-92%); and OS 96% (85-99%). Only two (4%) Grade 3 toxicities were observed.Initial efficacy and toxicity using 3D-CRT to deliver APBI appears comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate the extent of application, limitations, and value of this particular form of APBI.

Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS.From 2002-2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence.Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%.During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy.

TPS589 Background: This phase III post-NC trial evaluates if CWRNRT post-Mx or whole breast irradiation (WBI) with RNRT after BCS significantly reduces the IBCR-FI rate in pts with PAx nodes that are negative after NC. Secondary aims are OS, LRR-FI, DR-FI, DFS-DCIS, second primary cancer, and comparison of RT effect on cosmesis in reconstructed Mx pts. Correlative science examines RT effect by tumor subtype, molecular outcome predictors for residual disease pts, and predictors for the degree of reduction in locoregional recurrence. Methods: Clinical T1-3, N1 IBC PAx nodes (FNA or core needle biopsy) pts complete ≥12 weeks of NC (anthracycline and/or taxane). HER2+ pts receive anti-HER2 therapy. Following NC BCS or Mx, sentinel node biopsy (≥3 nodes) and/or Ax dissection with histologically negative nodes is performed. ER/PR and HER-2neu status before NC is required. Pts receive required systemic therapy. Radiation credentialing with a facility questionnaire/case benchmark is required. Random assignment for Mx pts is to no CWRNRT or CWRNRT and for BCS pts to WBI or WBI RNRT. Statistics: 1636 pts to be enrolled over 5 yrs (definitive analysis at 7.5 yrs). Study is powered at 80% to test that RT reduces the annual hazard rate of events for IBCR-FI by 35% for an absolute risk reduction of 4.6% (5-yr cumulative rate). Intent-to-treat analysis with 3 interim analyses (43, 86, and 129 events) and a 4th/final analysis at 172 events. Pt-reported outcomes focusing on RT effect will be provided by 736 pts before random assignment and at 3, 6, 12, and 24 mos. Accrual as of 2-2-17 is 534 (32.64%). Contacts: Questions: NRG Oncology Pgh Clin Coord Dpt: 1-800-477-7227 or ccd@nsabp.org . Support: U10 CA-2166; -180868, -180822; 189867; Elekta Clinical trial information: NCT01872975.

e22112Background: We evaluated the use of bioimpedance spectroscopy (BIS) as part of a structured surveillance program for the development of breast cancer-related lymphedema (BCRL) in very high ri...

BACKGROUND: Data on patients who received breast-conserving therapy (BCT) for early stage breast cancer were examined to detect differences in disease presentation, management techniques, long-term treatment outcomes, and toxicities based on race. METHODS: Six hundred ninety-nine women with breast cancer (39 African-American [AA] women and 660 Caucasian [C] women) who received BCT were analyzed on race, clinical and pathologic characteristics at presentation, management techniques, treatment-related toxicities, recurrence, and survival. The median follow-up was 12.2 years. RESULTS: At diagnosis, AA women were younger (aged

Breast-conserving therapy is accepted as a standard of care option for patients with early-stage breast cancer. However, studies examining patterns of failure after treatment suggest that a lengthy course of adjuvant whole breast irradiation delivered as a component of breast-conserving therapy may not always be necessary; indeed, in appropriately selected patients, radiation therapy delivered only to the tumor bed may be acceptable. Several modalities of delivering accelerated partial breast irradiation (APBI) have been developed, the most prevalent being multi-catheter interstitial brachytherapy, the MammoSite breast brachytherapy catheter (Hologic Corporation, Bedford, MA) and three-dimensional conformal external-beam radiation therapy. The purpose of this article is to review the published experiences on the most common modalities of delivering APBI and to outline the current open national phase 3 trial. To date, phase 1/2 studies have demonstrated excellent local control and cosmetic outcomes in early-stage breast cancer patients treated with APBI. As increasing knowledge is accumulated regarding the efficacy and safety of APBI, a consensus will emerge regarding its potential replacement of whole breast irradiation in selected early-stage breast cancer patients.

This prospective study examines the use of three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Four-year data on efficacy, cosmesis, and toxicity are presented.Patients with Stage O, I, or II breast cancer with lesions/=3 cm, negative margins, and negative nodes were eligible. The 3D-CRT delivered was 38.5 Gy in 3.85 Gy/fraction. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Disease-free, overall, and cancer-specific survival (DFS, OS, CSS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) toxicity scale was used to grade acute and late toxicities.Ninety-four patients are evaluable for efficacy. Median patient age was 62 years with the following characteristics: 68% tumor size1 cm, 72% invasive ductal histology, 77% estrogen receptor (ER) (+), 88% postmenopausal; 88% no chemotherapy and 44% with no hormone therapy. Median follow-up was 4.2 years (range, 1.3-8.3). Four-year estimates of efficacy were IBF: 1.1% (one local recurrence); INF: 0%; CBF: 1.1%; DF: 3.9%; DFS: 95%; OS: 97%; and CSS: 99%. Four (4%) Grade 3 toxicities (one transient breast pain and three fibrosis) were observed. Cosmesis was rated good/excellent in 89% of patients at 4 years.Four-year efficacy, cosmesis, and toxicity using 3D-CRT to deliver APBI appear comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate thoroughly the extent of application, limitations, and complete value of this particular form of APBI.

Background: Significant controversy exists regarding the appropriate minimum tumor-free margin width for patients undergoing breast-conserving therapy. The SSO-ASTRO guidelines recommend 'no ink on tumor' based upon a meta-analysis of 33 studies, but this had significant limitations. In order to address these concerns, a meta-analysis of all available data (using 31 of the initial studies) was performed but employing stricter criteria for acceptability and quality of evaluable studies. Methods: Study eligibility criteria were: (1) minimum follow-up of 50 months; (2) explicit pathologic criteria for defining margins; and (3) consistent endpoints associated with local recurrence. The compiled studies were analyzed using generalized linear mixed models for the outcome of local recurrence, with random effects for study and fixed effects for various patient and study characteristics. Results: The analysis incorporated 38 studies, which included 55,302 patients treated from 1968-2010. Two of the previous studies were excluded (one because of short follow-up, and the second because it was updated) with seven new studies added from the previous meta-analysis including an update of a previously included analysis. Median follow-up was 7.2 years. The median age of the cohort was 55 years, 74% of patients had T1 tumors, and 72% were node negative. The crude rate of local recurrence for patients with positive margins was 10.3%, compared to 3.8% for those with negative margins defined as no tumor on ink or wider (p0- Conclusions: The current meta-analysis indicates that having margin widths 2 mm or greater is associated with a lower risk of ipsilateral breast failure than narrower but uninvolved margins. It therefore fails to confirm that 'no-tumor on ink' is optimal. Further analyses are needed to clarify this issue, particularly to identify the critical minimum tumor-free margin for different patient subgroups. Citation Format: Shah C, Verma V, Sayles H, Recht A, Vicini F. Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis [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 GS5-01.

Purpose: Preliminary dosimetric findings in patients managed with the Contura ® Multi-Lumen Balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional phase IV registry trial were reviewed. Material and methods: CT-based 3D planning with dose optimization was performed for all patients. For the study, new ideal dosimetric goals were developed: 1) ≥ 95% of the prescribed dose (PD) covering ≥ 90% of the target volume (TV), 2) a maximum skin dose ≤ 125% of the PD, 3) maximum rib dose ≤ 145% of the PD, and 4) the V150 ≤ 50 cc and V200 ≤ 10 cc. The frequency of concurrently achieving these dosimetric goals using the Contura ® MLB was investigated. Results: 194 cases were evaluable. Employing the MLB, all ideal dosimetric criteria were achieved in 76% of cases. Evaluating dosimetric criteria separately, 90% and 89% of cases met the new ideal skin and rib dose criteria, respectively. In 96%, ideal TV coverage goals were achieved and in 96%, dose homogeneity criteria (V150 and V200) were met. For skin spacing ≥ 5-7 mm, the median skin dose was 121% of the PD and when < 5 mm, the median skin dose was 124.4%. For rib distancees < 5 mm, the median rib dose was reduced to 136.4% of the PD. For skin spacing < 7 mm and distance to rib < 5 mm, the median skin and rib doses were concurrently limited to 121% and 142.8% of the PD, respectively. Conclusions: The Contura ® MLB catheter provides potential improvements in dosimetric capabilities (i.e., reduced skin and rib doses and improved TV coverage) in many clinical scenarios. J Contemp Brachyther 2010; 2, 1: 1-8

The number of positive axillary nodes is a strong prognostic factor in breast cancer, but is affected by variability in nodal staging technique yielding varying numbers of excised nodes. The nodal ratio of positive to excised nodes is an alternative that could address this variability. Our 2006 review found that the nodal ratio consistently outperformed the number of positive nodes, providing strong arguments for the use of nodal ratios in breast cancer staging and management. New evidence has continued to accrue confirming the prognostic significance of nodal ratios in various worldwide population settings. This review provides an updated summary of available data, and discusses the potential application of the nodal ratio to breast cancer staging and prognostication, its role in the context of modern surgical techniques such as sentinel node biopsy, and its potential correlations with new biologic markers such as circulating tumor cells and breast cancer stem cells.

Purpose To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. Methods and Materials A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. Results The Task Force proposed three patient groups: ( 1 ) a "suitable" group, for whom APBI outside of a clinical trial is acceptable, ( 2 ) a "cautionary" group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and ( 3 ) an "unsuitable" group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. Conclusion Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.

The goal of the current study is to help refine guidelines for the need for re-excision and the appropriate amount of breast tissue to re-excise in patients with early breast cancer following excisional breast biopsy when treated with breast-conserving therapy (BCT).The study population consisted of 441 patients derived from a dataset of 607 consecutive cases of stage I and II breast cancer treated with BCT, in which patients underwent primary excisional diagnostic biopsy and subsequent re-excision prior to the initiation of radiation therapy (RT). A single pathologist reviewed all specimens. Re-excision was indicated because tumor was found close to or involving the resection margin. In 333 of the 441 cases, it was possible to measure the extension of carcinoma into the re-excision specimen. Margins were classified as negative (carcinoma4.2 mm from the margin), near (4.2 mm from the margin) or positive. Any carcinoma identified near the final margin was quantified by width of invasive carcinoma and number of ductal carcinoma in situ (DCIS) ducts near the margin and subdivided into three distinct groups: least, intermediate, and greatest amount. These factors were then analyzed to determine the likelihood and extent of residual carcinoma in re-excision specimens. Statistical analysis was performed using Systat version 10 (SPSS Inc., Chicago, IL).The quantity of carcinoma near the initial biopsy margin and the invasive carcinoma-to-specimen dimension ratio demonstrated a significant association with increasing amounts of residual carcinoma at re-excision. Combination of these two variables allowed for a statistically significant (P0.001) calculation of risk index for identifying significant residual invasive carcinoma or DCIS in the adjacent breast parenchyma at re-excision, and yielded stratification into low- (6%), intermediate- (27%), and high-risk (44%) groups. In re-excision specimens, the observed distance of carcinoma extension into adjacent breast tissue was associated with a statistically significant decrease in the ratio of the initial excisional biopsy specimen dimensions and invasive carcinoma dimensions. Combining the initial margin status with the specimen-to-invasive carcinoma maximum dimension ratio yielded an accurate predictor of the maximum distance of tumor extension.Evaluation of the initial excisional biopsy margin status in correlation with the invasive carcinoma-to-specimen maximum dimension ratio may be helpful for (1) identifying patients who require re-excision prior to RT and (2) predicting the quantity of additional breast tissue to excise to ensure adequate surgical margins with BCT.

The American Society of Breast Surgeons enrolled women onto a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System (RTS) breast brachytherapy device. This report examines local recurrence (LR), toxicity, and cosmesis as a function of age in women enrolled onto the trial. A total of 1449 primary early-stage breast cancers were treated in 1440 women. Of these, 130 occurred in women younger than 50 years of age. Fisher’s exact test was performed to correlate age (

Purpose To evaluate cosmetic outcome and radiation recall in the American Society of Breast Surgeons registry trial, as a function of the interval between accelerated partial breast irradiation (APBI) and initiation of chemotherapy (CTX). Methods and Materials A total of 1440 patients at 97 institutions participated in this trial. After lumpectomy for early-stage breast cancer, patients received APBI (34 Gy in 10 fractions) with MammoSite RTS brachytherapy. A total of 148 patients received CTX within 90 days of APBI. Cosmetic outcome was evaluated at each follow-up visit and dichotomized as excellent/good or fair/poor. Results Chemotherapy was initiated at a mean of 3.9 weeks after the final MammoSite procedure and was administered ≤3 weeks after APBI in 54 patients (36%) and >3 weeks after APBI in 94 patients (64%). The early and delayed groups were well balanced with respect to multiple factors that may impact on cosmetic outcome. There was a superior cosmetic outcome in those receiving chemotherapy >3 weeks after APBI (excellent/good in 72.2% at ≤3 weeks vs. excellent/good in 93.8% at >3 weeks; p = 0.01). Radiation recall in those receiving CTX at ≤3 weeks was 9 of 50 (18%), compared with 6 of 81(7.4%) in those receiving chemotherapy at >3 weeks ( p = 0.09). Conclusion The majority of patients receiving CTX after APBI have excellent/good cosmetic outcomes, with a low rate of radiation recall. Chemotherapy initiated >3 weeks after the final MammoSite procedure seems to be associated with a better cosmetic outcome and lower rate of radiation recall. An excellent/good cosmetic outcome in patients receiving CTX after 3 weeks was similar to the cosmetic outcome of the overall patient population who did not receive CTX.

Purpose To examine the clonality relationships among initial invasive breast carcinoma (IBC), ipsilateral breast failure (IBF), and distant metastasis (DM) to determine the effect of local tumor recurrence on the development of DMs. Methods and Materials A total of 18 patients treated with breast-conserving therapy who developed an IBF followed by DMs were studied using a 20 informative-marker, polymerase chain reaction-based allelic imbalance clonality assay. Results Four relationships were identified. First, in 7 cases, the IBF and DMs were clonally related to the initial IBC as one progressively genetic unstable process. Second, in 3 cases, the IBF and DMs were each clonally related to the IBC but clonally distinct from each other. Third, in 3 cases, the IBC and the IBF were clonally related and the DMs were clonally related to the IBFs, with a weak relationship to the initial IBC. Finally, in 5 cases, the IBF was clonally distinct from the initial IBC (new second primary) and the DMs were clonally related to the IBF and clonally distinct from the initial IBC. Conclusion These findings provide molecular evidence demonstrating that some DMs can directly develop from IBFs and support the importance of local tumor control in the overall treatment of breast cancer patients.

Purpose: To present a retrospective multi-institutional experience of patients treated with the MammoSite radiation therapy system (RTS). Methods and Materials: Nine institutions participated in a pooled analysis of data evaluating the clinical experience of the MammoSite RTS for delivering accelerated partial breast irradiation. Between 2000 and 2004, 483 patients were treated with the MammoSite RTS to 34 Gy delivered in 10 fractions. Treatment parameters were analyzed to identify factors affecting outcome. Results: Median follow-up was 24 months (minimum of 1 year). Overall, infection was documented in 9% of patients, but the rate was only 4.8% if the catheter was placed after lumpectomy. Six patients (1.2%) experienced an in-breast failure; four failures occurred remote from the lumpectomy site (elsewhere failure). Cosmetic results were good/excellent in 91% of patients. Treatment parameters identified as significant on univariate analysis were tested in multivariate regression analysis. The closed-cavity placement technique significantly reduced the risk of infection (p = 0.0267). A skin spacing of

Purpose To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Methods and Materials Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: ( 1 ) to bony anatomy, ( 2 ) to the center of mass (COM) of surgical clips, and ( 3 ) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs (ΔCOM Bone , ΔCOM Clips , and ΔCOM Surface ) were determined. Smaller ΔCOMs were interpreted as better localizations. Correlation coefficients were calculated for ΔCOM vs. several variables. Results The ΔCOM Bone (mean, 7 ± 2 [SD] mm) increased with breast volume ( r = 0.4; p = 0.02) and distance from the chest wall ( r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization (ΔCOM Clips Bone ) in 25 of 27 cases. Breast surface matching improved cavity localization (ΔCOM Surface Bone ) in 19 of 27 cases. Mean improvements (ΔCOM Bone − ΔCOM Clips or Surface ) were 4 ± 3 and 2 ± 4 mm, respectively. In terms of percentage of improvement ([ΔCOM Bone − ΔCOM Clips or Surface ]/ΔCOM Bone ), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Conclusions Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.

BACKGROUND. This report presents 3 years of data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite (Cytyc, Bedford, Mass) Breast Brachytherapy Registry Trial. METHODS. A total of 1440 patients (1449 cases) with early stage breast cancer who were undergoing breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1255 (87%) cases had invasive breast cancer (IBC; median size = 10 mm), and 194 (13%) cases had ductal carcinoma in situ (DCIS; median size = 8 mm). Median follow-up was 30.1 months. RESULTS. Twenty-three (1.6%) cases developed an ipsilateral breast tumor recurrence (IBTR) for a 2-year actuarial rate of 1.04% (1.11% for IBC and 0.59% for DCIS). No variables were associated with IBTR. Six (0.4%) patients developed an axillary failure. The percentages of breasts with good to excellent cosmetic results at 12 (n = 980), 24 (n = 752), 36 (n = 403), and 48 months (n = 67 cases) were 95%, 94%, 93%, and 93%, respectively. Breast seromas were reported in 23.9% of cases (30% in open-cavity implants and 19% in closed-cavity implants). Symptomatic seromas occurred in 10.6% of cases, and 1.5% of cases developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 37.5 months, the 3-year actuarial rate of IBTR was 1.79%. CONCLUSIONS. Treatment efficacy, cosmesis, and toxicity 3 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up. Cancer 2008. © 2008 American Cancer Society.

Breast conserving therapy (BCT) has become an accepted option in the management of patients with early-stage breast cancer. However, studies have suggested that a lengthy course of adjuvant whole breast irradiation, as a component of BCT, may not always be necessary and that radiation therapy delivered only to the region of the tumor bed may be acceptable in appropriately selected patients. Several modalities are currently being explored as a means to deliver accelerated partial breast irradiation (APBI), including multicatheter interstitial brachytherapy, the MammoSite breast brachytherapy catheter (Cytyc Corporation, Marlborough, MA), and three-dimensional conformal external-beam radiation therapy. To date, phase 1/2 published data have demonstrated excellent local control rates and cosmesis. As additional data addressing the effectiveness of this treatment approach accumulate, a new standard of care may emerge. This review discusses data accumulated to date exploring the experience with all APBI modalities and presents future studies exploring this concept.

Purpose:Wepresentourongoingclinicalexperienceutilizingthree-dimensional(3D)-conformalradiationtherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer treated with breast-conserving therapy. Methods and Materials: Ninety-one consecutive patients were treated with APBI using our previously reported 3D-CRT technique. The clinical target volume consisted of the lumpectomy cavity plus a 10- to 15 -mm margin. The prescribed dose was 34 or 38.5 Gy in 10 fractions given over 5 consecutive days. The median follow-up was 24 months. Twelve patients have been followed for $4 years, 20 for $3.5 years, 29 for >3.0 years, 33 for $2.5 years, and 46 for $2.0 years. Results: No local recurrences developed. Cosmetic results were rated as good/excellent in 100% of evaluable patients at $ 6 months (n = 47), 93% at 1 year (n = 43), 91% at 2 years (n = 21), and in 90% at $3 years (n = 10). Erythema, hyperpigmentation, breast edema, breast pain, telangiectasias, fibrosis, and fat necrosis were evaluated at 6, 24, and 36 months after treatment. All factors stabilized by 3 years posttreatment with grade I or II rates of 0%, 0%, 0%, 0%, 9%, 18%, and 9%, respectively. Only 2 patients (3%) developed grade III toxicity (breast pain), which resolved with time. Conclusions: Delivery of APBI with 3D-CRT resulted in minimal chronic ($6 months) toxicity to date with good/excellent cosmetic results. Additional follow-up is needed to assess the long-term efficacy of this form of APBI. 2007 Elsevier Inc. Breast cancer, Breast-conserving therapy, Brachytherapy, Partial breast irradiation, Three-dimensional conformal irradiation.

To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation.From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years.The 3-year rates of Gradeor =2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planning target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receivingor =30 Gy (V30) andor =82 Gy (V82), along with prostate volume, were all clinically useful predictors of Gradeor =2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Gradeor =2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Gradeor =2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Gradeor =2 and Grade 3 chronic urinary toxicity.Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to30 cm(3) and the V82 to7 cm(3) when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.

The purpose of our study was to determine the mammographic appearance, detection method, and stage of ipsilateral breast tumor recurrence in women treated with breast-conserving surgery and whole-breast radiation therapy for ductal carcinoma in situ (DCIS).Following institutional review board approval, records of women treated with breast-conserving surgery and radiation therapy for DCIS who developed an ipsilateral breast tumor recurrence from 1981 to 2003 were reviewed retrospectively. Multiinstitutional database records showed 513 women were treated, of whom 42 (8.2%) developed local recurrence. Study criteria were fulfilled and complete records were available for 32 women. Mean age at initial diagnosis was 49 years (range, 26-73 years).Of the 32 patients included in our study, 31 (97%) recurrences were mammographically apparent. Twenty-nine (91%) of 32 were diagnosed exclusively by mammography. Mammographic findings at recurrence were calcifications in 24 (75%) of 32, mass in six (19%) of 32, and distortion in one (3%) of 32. The mean time to recurrence was 4.5 years. Twelve (40%) of 30 had the recurrence in a remote quadrant from the original cancer. Recurrences were DCIS in 17 (53%) of 32, DCIS with microinvasion in six (19%) of 32, invasive ductal cancer in three (9%) of 32, invasive lobular cancer in two (6%) of 32, and mixed DCIS and invasive cancer in four (13%) of 32. Six (67%) of nine patients with invasive cancer (excluding microinvasion) had tumors smaller than 1 cm. Ninety-one percent of recurrences were minimal cancers. All recurrences were stage 0 or 1.Mammography successfully detected ipsilateral breast tumor recurrence, predominantly as calcifications or masses, after breast-conserving surgery with radiation therapy for DCIS in 97% of cases. The recurrences were located at variable distances from the lumpectomy site. Ninety-one percent of recurrences were minimal cancers and all were early stage, connoting excellent prognosis.

Multiple adjuvant radiation therapy options currently exist for women following breast-conserving surgery including standard fractionated whole breast irradiation (WBI), accelerated whole breast irradiation (AWBI), and accelerated partial breast irradiation (APBI). The recent publication of several randomized trials comparing APBI to standard WBI provides Level I evidence supporting APBI. The purpose of this review is to summarize the Level I data supporting APBI in an effort to provide guidance when to offer this treatment approach vs. standard WBI, AWBI, or excision alone and to address questions related to its application. Four contemporary trials with over 2000 patients comparing APBI and WBI have been published and demonstrate no differences in the rates of local/regional recurrence or survival though long-term followup is limited to one study. In addition, reductions in the rates of acute and chronic toxicity and improvements in cosmetic outcome were noted in two of these trials (the University of Florence and the Hungarian Phase III trials, respectively). When contrasting other treatment approaches to APBI, patients treated in studies using AWBI have many comparable clinical and pathologic characteristics, whereas studies investigating endocrine therapy alone (surgery with no adjuvant radiation therapy) have much "lower risk" patients based on clinical, pathologic, and treatment-related criteria. Although significant Level I evidence now exists supporting the use of APBI as an alternative to WBI in selected patients undergoing breast-conserving therapy, additional data are needed to (1) help further refine patient selection criteria, (2) better clarify the optimal partial breast irradiation target and technique for each clinical setting, (3) determine when AWBI, standard WBI, or excision alone may be more appropriate, and (4) investigate if further reductions in fractionation schedules are possible.

Breast cancer‐related lymphedema (BCRL) has become an increasingly important clinical issue as noted by the recent update of the 2015 NCCN breast cancer guidelines which recommends to “educate, monitor, and refer for lymphedema management.” The purpose of this review was to examine the literature regarding early detection and management of BCRL in order to (1) better characterize the benefit of proactive surveillance and intervention, (2) clarify the optimal monitoring techniques, and (3) help better define patient groups most likely to benefit from surveillance programs. A Medline search was conducted for the years 1992–2015 to identify articles addressing early detection and management of BCRL. After an initial search, 127 articles were identified, with 13 of these studies focused on early intervention (three randomized (level of evidence 1), four prospective (level of evidence 2–3), six retrospective trials (level of evidence 4)). Data from two, small (n = 185 cases), randomized trials with limited follow‐up demonstrated a benefit to early intervention (physiotherapy, manual lymphatic drainage) with regard to reducing the rate of chronic BCRL (>50% reduction) with two additional studies underway (n = 1280). These findings were confirmed by larger prospective and retrospective series. Several studies were identified that demonstrate that newer diagnostic modalities (bioimpedance spectroscopy, perometry) have increased sensitivity allowing for the earlier detection of BCRL. Current data support the development of surveillance programs geared toward the early detection and management of BCRL in part due to newer, more sensitive diagnostic modalities.

Breast-conserving therapy (BCT) consisting of lumpectomy and adjuvant radiotherapy represents a standard of care in the management of ductal carcinoma in situ (DCIS). Over the past few decades, several randomized trials have demonstrated a 50 % reduction in the risk of local recurrence with adjuvant radiotherapy and recent prospective studies demonstrate higher rates of local recurrence with the omission of radiotherapy even in “low-risk” patients. As such, adjuvant radiotherapy remains an important component of BCT in women with DCIS.

Minimal data are available regarding selection of an optimal biochemical failure (BF) definition for patients treated with brachytherapy, external beam radiotherapy (EBRT), and combinations of these treatments with or without androgen deprivation (AD). We retrospectively analyzed our institution's experience treating localized prostate cancer in an attempt to determine a BF definition that could be applied for these various treatment modalities.A total of 2376 patients with clinical stage T1-T3 N0 M0 prostate cancer were treated with conventional dose (median, 66.6 Gy) EBRT (n = 1201), high-dose (median, 75.6 Gy) adaptive radiation therapy (n = 465), EBRT + high-dose-rate brachytherapy boost (n = 416), or brachytherapy alone (n = 294) between 1987 and 2003. A total of 496 patients (21%) received neoadjuvant AD with radiation therapy. There were 21924 posttreatment prostate-specific antigen (PSA) measurements. Multiple BF definitions were tested for their sensitivity, specificity, positive predictive value (+PV), and negative PV (-PV) in predicting subsequent clinical failure (CF) (any local failure or distant metastasis), overall survival (OS), and cause-specific survival (CSS). Median follow-up was 4.5 years. The date of BF was the date BF criteria were met (e.g., date of third rise).A total of 290 patients (12%) experienced CF at a median interval of 3.6 years (range, 0.2-15.2 years). The 5- and 10-year CF rates were 12% and 26%, respectively. Three consecutive rises yielded a 46% sensitivity and 84% specificity for predicting CF. The 10-year CF for those 475 patients who experienced three rises (BF) was 37% vs. 17% for those patients who did not meet these criteria (biochemically controlled [BC]). For all patients, the following definitions were superior to three rises for predicting CF for both +PV, and -PV: n + 1 (or =1 ng/mL above nadir), n + 2, n + 3, threshold 2 (any PSAor =2.0 ng/mL at or after nadir), threshold 3, threshold 4, and threshold 5. For the subset of patients treated with EBRT alone, the n + k definitions and threshold k definitions maintained superior predictive capacity. However, the threshold k definitions seemed to maintain a slightly greater separation in 10-year CF rates (43% for BF vs. 13% for BC = 30% difference for threshold 3). Surprisingly, all definitions generally had better predictive capacity for those patients who received brachytherapy or neoadjuvant AD vs. EBRT alone. The endpoints appeared similar for n + 1 vs. threshold 3 and n + 2 vs. threshold 4 in EBRT alone patients, but for brachytherapy or neoadjuvant AD patients, there were similarities for n + 2 vs. threshold 3 and n + 3 vs. threshold 4. This may be a reflection of the lower nadir levels in patients receiving AD (median0.1 ng/mL vs. 0.2 ng/mL for brachytherapy vs. 0.8 ng/mL for EBRT alone, p0.01). When examining CF correlation for the various classes of BF definitions, the threshold k definitions clearly demonstrated the greatest area under the receiver operating characteristic curve, followed by the n + k definitions. For OS, the threshold k definitions again demonstrated the greatest area under the curve, followed by definitions based on specific nadir cutoffs (nadiror =k ng/mL).Biochemical failure definitions applying a PSA threshold at or after the nadir (e.g., threshold 3) demonstrated the highest association with CF, OS, and CSS for all assessed treatment modalities. Definitions incorporating a PSA increase above the nadir value (e.g., nadir + 2 ng/mL) were also superior for all modalities. In general, BF definitions have greater predictive capacity for clinical outcome with brachytherapy or neoadjuvant AD than EBRT alone, possibly because of less "noise" from production of background PSA.

Background This report presents the preliminary results and evaluation of the MammoSite balloon catheter (MammoSite Radiation Therapy System; Cytyc Corporation, Marlboro, MA) as the sole method of delivering partial breast irradiation to the lumpectomy bed with breast-conserving surgery in patients with pure ductal carcinoma in situ (DCIS). Methods Twelve institutions are participating in this phase II clinical study. A total of 133 patients have been enrolled and 100 patients have successfully completed the prescribed radiation therapy. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose rate brachytherapy. Patients who met the following criteria were selected for enrollment into the study: age 45 years or older, unicentric pure DCIS, mammographic lesion of 3 cm or less, negative margins as defined by 1 mm or more, postoperative final gross pathologic size of tumor of 5 cm or less, clinically node negative, and a postlumpectomy mammogram showing the absence of any residual suspicious microcalcifications. The placement of the MammoSite catheter was performed either at the time of the lumpectomy or postlumpectomy. The minimum distance from the balloon surface to the surface of the skin is greater than 5 mm. Data collection points are at time of enrollment, time of implant, 3 months, 6 months, and then yearly at 1- to 5-year follow-up visits. Data collected are local control rates, cosmetic outcome using the Harvard Scale, toxicities, serious adverse events, disease-free survival, cause-specific survival, and contralateral breast failure. The Van Nuys Prognostic Index scores were calculated for each patient. Local recurrence is defined as either invasive or noninvasive recurrence within the target volume. Ipsilateral elsewhere recurrence is defined as either an invasive or noninvasive recurrence occurring outside of the target volume in the previously treated breast. This recurrence is classified as a new primary tumor. Results The mean follow-up period was 9.5 months (range, 1–24 mo). The MammoSite catheter was explanted for the following reasons: inadequate skin distance (5.1%; 6 of 117), poor cavity conformance (5.1%; 6 of 117), positive margins (2.6%; 3 of 117), final histology (.85%; 1 of 117), and physician decision (.85%; 1 of 117). Of the patients in whom the MammoSite was explanted because of skin spacing or cavity conformance, 50% were at sites of new users (institutions that have placed fewer than 10 Mammosite catheters). Cosmetic results were rated as excellent in 63%, good in 35%, and fair in 2% in the 86 patients with a follow-up visit. Two patients were diagnosed with an ipsilateral local recurrence, 1 outside of the target volume and 1 true recurrence/marginal miss. One patient was diagnosed at 8 months and the other was diagnosed at 11 months. Both of these ipsilateral failures were DCIS. The Van Nuys Prognostic Index of these 2 patients was 9 and 8, respectively. Data collected showed the mean age at placement was 60.8 y, mean tumor size was 10.6 mm, mean actual closest surgical margin was 6.8 mm (range, .1–40 mm), a re-excision rate of 35%, postlumpectomy placement was 71%, and the mean skin-to-balloon surface distance was 13 mm with 89% ≥7 mm. No serious adverse events were reported. The infection rate was 4.0%. Conclusions Accelerated partial breast irradiation delivered with the MammoSite balloon was clinically successful in patients entered into a phase II clinical study with pure DCIS, with results comparable with other studies reported in the literature that have evaluated use of the MammoSite balloon brachytherapy for delivery of radiation therapy in early breast cancers. Inadequate skin distance and poor cavity conformance were the main factors limiting the use of the MammoSite device. Cosmetic results were good to excellent in 98%. There have been 2 ipsilateral breast recurrences.

Purpose: We performed a complete pathologic analysis examining extracapsular extension (ECE) and microscopic spread of malignant cells beyond the prostate capsule to determine whether and when clinical target volume (CTV) expansion should be performed. Methods and Materials: A detailed pathologic analysis was performed for 371 prostatectomy specimens. All slides from each case were reviewed by a single pathologist (N.S.G.). The ECE status and ECE distance, defined as the maximal linear radial distance of malignant cells beyond the capsule, were recorded. Results: A total of 121 patients (33%) were found to have ECE (68 unilateral, 53 bilateral). Median ECE distance = 2.4 mm [range: 0.05–7.0 mm]. The 90th-percentile distance = 5.0 mm. Of the 121 cases with ECE, 55% had ECE distance ≥2 mm, 19% ≥4 mm, and 6% ≥6 mm. ECE occurred primarily posterolaterally along the neurovascular bundle in all cases. Pretreatment prostrate-specific antigen (PSA), biopsy Gleason, pathologic Gleason, clinical stage, bilateral involvement, positive margins, percentage of gland involved, and maximal tumor dimension were associated with presence of ECE. Both PSA and Gleason score were associated with ECE distance. In all 371 patients, for those with either pretreatment PSA ≥10 or biopsy Gleason score ≥7, 21% had ECE ≥2 mm and 5% ≥4 mm beyond the capsule. For patients with both of these risk factors, 49% had ECE ≥2 mm and 21% ≥4 mm. Conclusions: For prostate cancer with ECE, the median linear distance of ECE was 2.4 mm and occurred primarily posterolaterally. Although only 5% of patients demonstrate ECE >4 to 5 mm beyond the capsule, this risk may exceed 20% in patients with PSA ≥10 ng/ml and biopsy Gleason score ≥7. As imaging techniques improve for prostate capsule delineation and as radiotherapy delivery techniques increase in accuracy, a posterolateral CTV expansion should be considered for patients at high risk.

The MammoSite device was designed as a breast brachytherapy applicator and is currently used to deliver accelerated partial breast irradiation (APBI). We hypothesized that APBI delivered with the MammoSite device would be well tolerated and be associated with a good cosmetic outcome in patients with ductal carcinoma-in-situ (DCIS).From 2002 to 2004, 191 patients with DCIS were enrolled in a registry trial to assess the MammoSite applicator. Fifteen patients were excluded from analysis because of device- or patient-related factors; 7 patients were excluded after receiving a radiotherapy boost, thus leaving 169 patients available for study. Follow-up information was available for 158 patients. The average length of follow-up was 7.35 months. Forty-three patients had at least 1 year of follow-up.Skin spacing for the MammoSite applicator was as follows:5 mm, 3 patients (1.78%); 5 to 7 mm, 18 patients (10.65%); andor = 7 mm, 148 patients (87.57%). Patients with a device-to-skin distance ofor = 7 mm had the best cosmetic result. Patients with a device-to-skin distance ofor = 7 mm also had a lower incidence of radiation dermatitis. Data on 43 patients who were followed up for at least 1 year confirmed these findings. Additional adverse events were primarily related to skin changes, with breast infections occurring in five patients (3.16%). No patient in the study has experienced a recurrence.APBI delivered via MammoSite is well tolerated in patients with DCIS, and the lowest toxicity was obtained in patients with the greatest device-to-skin distance. Long-term follow-up data regarding patient satisfaction, cosmesis, and efficacy are needed and will be determined from a recently opened large randomized study.

BACKGROUND The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using interstitial brachytherapy. METHODS From April 1993 to December 2001, 199 patients with Stage I–II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at ≤ 6 months, 2 years, and 5 years. RESULTS The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95–99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years. CONCLUSIONS APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95–99% of patients and stabilized at 2 years. Cancer 2006. © 2006 American Cancer Society.

We studied the clonality relationships in invasive breast carcinomas, ipsilateral breast failures (IBFs), and distant metastases (DMs) using a polymerase chain reaction–loss of heterozygosity (LOH) clonality assay to determine whether IBFs can be the source of DMs. Six cases of initial carcinomas, IBFs, and DMs were identified. Carcinoma DNA was extracted from paraffin blocks and analyzed with 20 markers. In 2 cases, the LOH pattern suggested the DM directly resulted from the IBF. In 2 cases, the initial carcinoma, IBF, and DM were one progressive, genetically unstable process. Separate subclones in the initial carcinoma gave rise to the IBF and DM in 1 case, and the DM derived from a second IBF in 1 case. The relationships of initial carcinomas, IBFs, and DMs are complex. DMs seem to be the direct result of IBFs in some cases. Some carcinomas seem to be composed of subclones with different and unrelated IBF and DM potential. Patients with invasive breast carcinoma who sustain an ipsilateral breast failure (IBF) following breast-conserving therapy are at increased risk of distant metastases (DMs) and decreased survival. 1-18 The mechanisms underlying these associations are unclear. It remains controversial whether IBFs can be the source of distant metastases and directly affect overall survival. Comparison of polymerase chain reaction–based loss of heterozygosity (LOH) mutation patterns in carcinomas is a well-characterized and reliable method for evaluating clonality between multiple breast carcinomas. 9-29 Molecular analysis of the IBF and subsequent DMs provides a mechanism to gain insight into some of the issues. We compared the genetic mutation patterns of initial carcinomas, IBFs, and subsequent DMs in 6 cases to study the metastatic dissemination relationships of initial and IBF invasive carcinomas.

We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBF. LOH was ± 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases ( P = .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs ( P = .004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonality. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur. Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.

We reviewed the literature to help clarify the benefits and/or hazards associated with monitoring serum prostate specific antigen (PSA) after treatment with surgery or radiation therapy (RT) for nonmetastatic prostate cancer.A search was performed for 1990 to 2004 using the MEDLINE database, CancerLit database and reference lists of relevant studies to obtain articles addressing the use of serum PSA to follow patients after treatment for prostate cancer. Studies were reviewed to determine 1) if serial PSA monitoring provides an early and accurate surrogate assessment of cancer cure or treatment failure, 2) if any pattern in the PSA profile after treatment provides conclusive evidence of early local vs systemic failure, 3) the magnitude of the lead time to clinical failure that serial PSA monitoring may provide and 4) if the early identification of biochemical failure (BF) with earlier intervention improves outcome.Although a lower PSA nadir after treatment with RT has been associated with cancer cure, 5% to 25% of patients ultimately have failure (beyond 5 years) even with the most optimal biochemical response. The most appropriate BF definitions to use after treatment for prostate cancer with RT remains controversial due to substantial differences in their accuracy, sensitivity, specificity and positive predictive value for clinical outcome. No pattern of PSA kinetics after treatment has conclusively been associated with a specific recurrence site. Biochemical failure definitions in patients treated with RT appear to provide a 6 to 18 month lead time to clinical failure but there are only limited published data to suggest that early intervention of any type (androgen deprivation, RT, surgery, etc) impacts survival.The overall benefit of monitoring serum PSA after treatment for prostate cancer remains controversial. Considering the potential dangers associated with incorrectly assuming the efficacy of new forms of treatment, the toxicity of administering salvage therapies of uncertain efficacy after BF has been identified and the anxiety associated with tracking posttreatment serum PSA, additional studies must be done to determine the appropriate use of this marker in properly treating patients after therapy.

Accelerated partial breast irradiation (APBI) has been investigated for over a decade as a potential alternative adjuvant treatment approach after lumpectomy for women with early-stage breast cancer. The rationale for APBI is based on pathologic data regarding the spread of cancer within the breast and study of the patterns of in-breast recurrence after breast-conserving therapy performed with or without whole-breast irradiation. This report reviews the North American experience using interstitial brachytherapy for APBI. Studies achieving low failure rates have universally been distinguished from those with high failure rates by requiring documented microscopically negative surgical margins, using a target definition consisting of the lumpectomy cavity plus a 1- to 2-cm margin, and having a rigorous quality assurance program to assure target coverage. We conclude that APBI brachytherapy programs that include all of these components have great potential to overcome many of the barriers that have prevented women from pursuing standard breast-conserving therapy.

Historically, the treatment paradigm for early-stage breast cancer has included treatment of the whole breast. Breast conservation therapy (BCT), irradiation of the whole breast following lumpectomy, requires daily treatment for 6 to 6.5 weeks. Although this is a successful and welltolerated treatment, many patients choose to avoid whole breast irradiation as a result of the time and travel difficulties they are unable to overcome. In response, accelerated partial breast irradiation (APBI) has been investigated as a possible alternative to conventional postlumpectomy treatment. By limiting the volume of breast tissue targeted for treatment, the present data suggests that the radiation dose delivery can be safely accelerated and reduced to a treatment time of 5 days. As a result, APBI has the potential to provide more women with an alternative BCT option. This report reviews the background, concepts supporting APBI, treatment techniques used, available data from single institutional studies, and the details of presently active and planned phase III trials. The compilation of the currently available results supports the national phase III trial (National Surgican Adjuvant Breast and Bowel Project [NSABP] B39/Radiation Therapy Oncology Group [RTOG] 0413), which will begin soon, and practitioners are urged to contribute patients. Both inside and outside the trial, a meticulous quality assurance program is required for optimal results using APBI. The importance of future investigation to establish the limitations of this new treatment approach and to define the role of specific treatment techniques is emphasized.

The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT.Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA levelor =0.1 ng/mL and any postoperative PSA levelor =0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT.Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p0.01) and pathologic T stage (median, T3a vs. T2c; p0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p0.01) and positive margins (73% vs. 36%, p0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the 5-year BC rate was 52% for RP+RT vs. 30% for RP (p0.01). The 5-year BC rate for patients with seminal vesicle invasion was 60% for RP+RT vs. 18% for RP (p0.01). For those with positive margins, the 5-year BC rate was 64% for RP+RT vs. 27% for RP (p0.01). The use of adjuvant RT remained statistically significant on multivariate analysis when applying either biochemical failure definition. Adjuvant RT also remained statistically significant when including the postoperative PSA level (30 days after surgery) in the multivariate analyses. In addition, 99 (17%) of the 583 RP patients required salvage prostatic fossa RT (median dose, 59.4 Gy) at a median interval of 1.3 years after surgery (range, 0.1-8.4) for a palpable recurrence (n = 10) or a detectable/rising postoperative PSA level (n = 89). The median PSA level before salvage RT was 0.8 ng/mL (mean, 3.2 ng/mL). The 5-year and 8-year BC rate, using the PSA0.1 ng/mL definition, from the date of salvage RT was 41% and 35%, respectively. The 5-year and 8-year BC rate, using the PSA0.3 ng/mL definition, was 46% and 36%, respectively. The 8-year local recurrence rate after salvage RT was 4%.Adjuvant RT demonstrated improved efficacy against prostate cancer. For patients with poor pathologic features (extracapsular extension, seminal vesicle invasion, positive margins), adjuvant RT improved the biochemical outcome independent of other prognostic factors.