F. Vicini

Six-Year Analysis of Treatment-Related Toxicities in Patients Treated with Accelerated Partial Breast Irradiation on the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial

BackgroundThe American Society of Breast Surgeons (ASBrS) enrolled women in a registry trial to prospectively study patients treated with the MammoSite RTS device. This report presents 6-year data on treatment-related toxicities from the trial.MethodsA total of 1449 primary early-stage breast cancers were treated with accelerated partial breast irradiation (APBI) using the MammoSite device (34xa0Gy in 10 fractions) in 1440 women. Of these, 1255 case (87%) had invasive breast cancer (IBC) (median sizexa0=xa010xa0mm) and 194 cases (13%) had ductal carcinoma in situ (DCIS) (median sizexa0=xa08xa0mm). Median follow-up was 59xa0months. Fisher exact test was performed to correlate categorical covariates with toxicity.ResultsBreast seromas were reported in 28% of cases (35.5% with open cavity and 21.7% with closed cavity placement). Also, 13% of all treated breasts developed symptomatic seromas, and 77% of these seromas developed during the 1st year after treatment. There were 172 cases (11.9%) that required drainage to correct. Use of chemotherapy and balloon fillxa0>50xa0cc were associated with the development of symptomatic seromas. Also, 2.3% of patients developed fat necrosis (FN). The incidence of FN during years 1 and 2 were 0.9% and 0.8%, respectively. Seroma formation, use of hormonal therapy, breast infection, and A/B cup size were associated with fat necrosis. There were 138 infections (9.5%) recorded; 98% occurred during the 1st year after treatment. Chemotherapy and seroma formation were associated with the development of infections.ConclusionsTreatment-related toxicities 6xa0years after treatment with APBI using the MammoSite device are similar to those reported with other forms of APBI with similar follow-up.

Local Control, Toxicity, and Cosmesis in Women Younger Than 50 Enrolled Onto the American Society of Breast Surgeons MammoSite Radiation Therapy System Registry Trial

BackgroundThe 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.MethodsA total of 1449 primary early-stage breast cancers were treated in 1440 women. Of these, 130 occurred in women younger than 50xa0years of age. Fisher’s exact test was performed to correlate age (<50 vs.xa0≥xa050xa0years) with toxicity and with cosmesis. The association of age with LR failure times was investigated by fitting a parametric model.ResultsWomen younger than 50 were more likely to develop fat necrosis: 4.6% (6 of 130) vs. 1.8% (24 of 1319) (Pxa0=xa0.0456). Other toxicities were comparable. At 2xa0years, cosmesis was excellent or good in 87% of assessable women aged <50xa0years (nxa0=xa074) and in 94% of assessable older women (nxa0=xa0751) (Pxa0=xa0.0197). At 3xa0years, this difference disappeared: excellent or good in 90% (56 of 62) of younger women vs. 93% (573 of 614) of older women (Pxa0=xa0.2902). The crude LR rate for the group was 1.7% (25 of 1449). There was no statistically significant difference in LR as a function of age. In women <50, 3.1% (4 of 130) developed a LR; in the older patients, 1.6% (21 of 1319) developed LR (3-year actuarial LR rates, 2.9% vs. 1.7%, respectively; Pxa0=xa0.2284).ConclusionsAccelerated partial breast irradiation with the MammoSite RTS results in low toxicity and produces similar cosmesis and local control at 3xa0years in women younger than 50 when compared with older women.

Intraoperative Radiation Therapy in Breast Cancer: Not Ready for Prime Time

Breast conserving therapy remains one of the most important advances in cancer management in the past century, with multiple trials demonstrating its equivalence to mastectomy with respect to long term cancer outcomes. Unfortunately, studies have documented that adjuvant radiation therapy, a critical component of breast conserving therapy, remains under utilized. Data suggest that treatment duration (5–6.5 weeks) can frequently be attributed to this finding. In light of this and secondary to the increasing costs associated with breast cancer radiation therapy, shortened courses of radiation therapy have been explored including both hypofractionated whole breast irradiation (WBI) and accelerated partial breast irradiation (APBI) that shorten treatment duration to three and one week, respectively. Prospective randomized trials evaluating these techniques have been promising, demonstrating equivalence to traditional WBI with respect to clinical outcomes, toxicities, and breast cosmesis. Intraoperative radiation therapy (IORT) represents an alternative to these techniques that delivers treatment at the time of surgery as a single fraction of radiation (in the majority of cases). Increasingly, IORT is being offered to women with early-stage breast cancer as the definitive radiation therapy modality following breast conserving surgery. What is concerning is that these patients are being offered this, as yet, unproven therapy off-protocol with insufficient data to support its safety and efficacy compared with WBI or alternative techniques (APBI or hypofractionated WBI). This is unfortunate as radiation therapy in breast cancer represents an area of research that has undergone progress in the past five decades through systematic evidence-based treatment paradigm evolution; breast conserving therapy was verified via multiple randomized trials demonstrating comparable outcomes to mastectomy, and postmastectomy radiation therapy similarly demonstrated a survival benefit in several trials before wide-scale incorporation into treatment paradigms. Therefore, the rapid introduction of IORT is concerning as these steps have not been taken prior to wide-scale utilization, leading to a potential for higher rates of local recurrence or increased toxicity. It should be noted that two large randomized trials have been performed to evaluate the role of IORT in early-stage breast cancer compared with WBI, the current standard of care. The targeted intraoperative radiotherapy (TARGIT) trial was a randomized noninferiority trial that included 3,451 women enrolled in 10 countries between 2000 and 2012. Patients were randomized to IORT (delivered at the same time as surgery or as a separate procedure) or WBI; however, 21 % of the prepathology IORT patients received WBI because of predefined factors including lobular carcinoma in situ, extensive intraductal component, lymphovascular space invasion, node positivity, or other factors specific to each institution. IORT was delivered using a 50-kv X-ray source to deliver 20 Gy to the surface of the excision cavity (5 Gy at 1 cm). While initial data with short follow-up (median follow-up 2 years) and limited events (n = 11) was promising, a recent update found that IORT, even with WBI supplementation in one-fifth of the Society of Surgical Oncology 2013

The Increasing Role of Lymphedema Screening, Diagnosis and Management as Part of Evidence-Based Guidelines for Breast Cancer Care.

To the Editor: Cancer survivorship is increasingly being incorporated into standard treatment algorithms, particularly with improved clinical outcomes and increasing numbers of long-term survivors (1). As a result, national organizations including the National Comprehensive Cancer Network (NCCN), the American Cancer Society (ACS), and the American Society of Clinical Oncology have created survivorship guidelines and programs (2–4). Survivorship includes a variety of issues that are part of post-oncologic care including management of complications associated with treatment. For patients with breast cancer, one such issue is the potential to develop breast cancer-related lymphedema (BCRL) and the role of early diagnosis and treatment as part of routine follow-up care. The risk of developing BCRL remains for a lifetime and is one of the most feared side effects of breast cancer survivors (5). Considering there are more than 2.8 million breast cancer survivors in the US and that one in five will develop BCRL, the potential number of women at risk for this dreaded complication is substantial (6). In 2015, for the first time, the NCCN guidelines for breast cancer now include a reference to BCRL stating that to “educate, monitor, and refer for lymphedema management” is part of routine followup care for women treated for breast cancer (7). What is the significance of this statement? Incorporation of BCRL education, screening, diagnosis, and management as part of the evidence-based guideline is imperative, as data support the increasing prevalence of BCRL due to improved recognition of the complication as well as an increase in long-term survivors (6). Further, the potential for an increased incidence of BCRL has emerged with increasing utilization of regional nodal irradiation. As such, incorporating BCRL screening into standard follow-up programs allows for early diagnosis, the potential for early intervention and brings the issue to the forefront for clinicians. For example, the 2012 National Lymphedema Network position paper entitled “Screening and Early Detection of BCRL: The Imperative” addresses the rationale for lymphedema screening as a method to detect and subsequently treat BCRL at an early, subclinical stage in an effort to “reverse the progression to chronic, irreversible lymphedema (8).” Undiagnosed and/or untreated BCRL can lead to chronic sequela including persistent swelling, infections, and functional limitations in the affected limb (5). It is important to note that the change in followup standard comes at a time when the treatment paradigm for BCRL is rapidly changing. Previously, the diagnosis of BCRL was made using techniques that (i) had limited ability to detect early BCRL (in the subclinical phase of the process), (ii) were logistically cumbersome and/or time consuming, and (iii) lacked standardized criteria for diagnosis and management (9). However, techniques such as bioimpedance spectroscopy and perometry allow for the detection of BCRL in its subclinical phase and have been developed in a way that allow for routine incorporation into the clinic (10,11). The importance of these new diagnostic modalities which allow for the early diagnosis of BCRL and subsequently early treatment has been demonstrated with recent publications that support the concept of improved outcomes with treatment of BCRL in the early, low-volume phase of the process (11,12). These principles are additionally seen in current models for BCRL. For example, Brunelle et al. have recently published the Massachusetts General Hospital model for prospective screening of BCRL which incorporates a multidisciplinary team approach and demonstrated the rationale for preoperative assessment, standardized measurement techniques, Address correspondence and reprint requests to: Frank A. Vicini, MD, FACR, Michigan HealthCare Professionals/21st Century Oncology, 28595 Orchard Lake Rd, Farmington Hills, MI 48334, USA, or e-mail: frank.vicini@21co.com

P3-13-04: Functional and Cosmetic Outcomes Following Post-Mastectomy Irradiation with Tissue Expander/Implant Reconstruction.

Purpose : To examine the rate of breast reconstruction failure and cosmetic outcomes following post-mastectomy radiation therapy (PMRT) with temporary tissue expander or implant in place. Methods and Materials : Ninety-four patients with 95 primary breast malignancies underwent mastectomy and immediate tissue expander reconstruction followed by PMRT. Ninety tissue expanders and five implants were irradiated. All patients received a dose of 5,400 cGy given in 180 cGy fractions. Twenty-one patients (22%) received tangents alone and seventy-four patients (78%) were treated with tangents and a supraclavicular field via a mono-isocentric technique. Bolus was used in 91 patients (96%). Eighty-eight patients (93%) received chemotherapy and 78 patients (82%) received endocrine therapy. Results : With a median follow up of 22.4 months, nineteen patients (20%) developed a reconstruction failure. Ten patients lost their tissue expanders with a median time to reconstruction failure of 7 months (range 3–9 months) while ten patients lost their permanent implant with a median time to loss of 19 months (range 9–31 months) following PMRT. The one and two-year actuarial rate of reconstruction failure was 11.2% and 24.9%, respectively. The most common cause of failure was infection (37%), followed by skin break down (21%), extrusion of expander or implant (16%), fibrosis/eschar (11%), trauma (11%) and pain (5%). Out of the 19 failures, eight patients were salvaged with an autologous flap reconstruction. Univariate analysis was performed to examine the association between age, chemotherapy, hormonal therapy, smoking status, hypertension, diabetes, menopause status, weight and the use of a third supraclavicular RT field on reconstruction failure. However no risk factors were found to be associated with reconstruction failure. In patients who did not have reconstruction failure, good/excellent cosmesis was observed in 79% of patients and fair/poor cosmesis was observed in 21% of patients. Conclusions : In our series of women with a high risk of recurrence, PMRT with a tissue expander in place followed by a prosthetic implant provides good cosmesis in the majority of women with an acceptable risk of expander or implant loss. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-04.

Low Risk Ductal Carcinoma In Situ (DCIS) Treated with Breast Conserving Surgery & Accelerated Partial Breast Irradation (APBI): Comparison of the Mammosite Registry Trial with Intergroup Study E5194.

Purpose/Objective(s): Recent data from Intergroup Study E5194 prospectively defined a low risk subset of ductal carcinoma in situ (DCIS) patients where radiation therapy was omitted after local excision alone. At 5 years, they found a 6.8% ipsilateral breast event rate (IBTR) in selected low/intermediate grade (LIG) patients and a 13.7% IBTR in selected high grade (HG) patients. The purpose of our study was to determine the IBTR in DCIS patients treated on the American Society of Breast Surgeons (ASBrS) MammoSite® Breast Brachytherapy registry trial who met the criteria of E5194 treated with local excision and adjuvant APBI.Material/Methods: A total of 194 patients with DCIS were treated between 2002 and 2004 on the Mammosite registry trial; of these, 69 patients met the enrollment criteria for E5194: 1. LIG: low to intermediate grade with a pathological size > 0.3cm but 3mm (n=40) or 2. HG: high grade, pathological size 3mm (n=29). All patients were treated with lumpectomy followed by adjuvant APBI (34 Gy in 3.4 Gy fractions). Median follow-up for surviving patients was 50.7 months (range, 0-73.4). Hormonal therapy was given to 51% of these patients (compared to 30% of patients on E5194). The clinical-pathologic data and long term outcomes for each patient were entered into a database for statistical analysis using SAS (v 8.2).Results: The median age of the entire cohort was 62.5 years. In the LIG cohort, the median size was 0.8cm. In the HG cohort, the median size was 0.6cm. In the LIG cohort, the 5-year IBTR was 0%, compared to 6.8% at 5 years in E5194. In the HG cohort, the 5-year IBTR was 5.3% compared to 13.7% at 5years in E5194. The overall the 5-year IBRT was 2% and there were no cases of elsewhere or regional failures in the entire cohort. The 5-year contralateral breast event rate was 0% and 5.6% in LIG and HG patients, respectively (compared to 3.5% and 4.2%, respectively, in E5194). The 5-year disease free survival and overall survival rate was 92.4% and 96.5%, respectively. In all patients with DCIS (n=194) treated with Mammosite on the registry trial, the 5-year actuarial IBTR, DFS, and OS was 3.1%, 93.8% and 98.2%, respectively.Conclusion: Adjuvant accelerated partial breast irradiation using Mammosite is a relatively convenient form of radiotherapy which shortens treatment time to 1 week. This study found that patients who met the criteria of E5194 treated with APBI had extremely low rates of recurrence (0% vs. 6.8% in the low to intermediate grade and 5.3% vs. 13.7% in the high grade). We conclude that all patients with DCIS who were eligible for E5194 have appreciable benefit from adjuvant APBI. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 951.

Three year analysis of patient demographics, treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite® registry in patients (age <50 or ≥ 50) treated with accelerated partial breast irradiation (APBI).

Abstract #5126 Background: We present 3 year data on patient demographics, treatment efficacy, cosmesis, and early toxicity for patients enrolled on the American Society of Breast Surgeons MammoSite (Hologic Bedford, MA) Registry based upon patient age ( 50 was not significant at 3 YO (9.7% vs 6.4%, p=0.2902). No difference due to age was found for seroma formation, breast infection, telengectasia, retraction, skin spacing, placement method, bra size and balloon volume.u2028 Discussion: Treatment efficacy, cosmesis, early toxicity and IBTR 3 years after treatment with APBI using the MammoSite device were similar for IBC and DCIS patients for age Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5126.