Acute toxicities after proton beam therapy following breast‐conserving surgery for breast cancer: Multi‐institutional prospective PCG registry analysis

We investigated adverse events (AEs) and clinical outcomes for proton beam therapy (PBT) after breast‐conserving surgery (BCS) for breast cancer. From 2012 to 2016, 82 patients received PBT in the prospective multi‐institutional Proton Collaborative Group registry. AEs were recorded prospectively at each institution. Median follow‐up was 8.1 months. Median dose was 50.4 Gy in 28 fractions. Most patients received a lumpectomy bed boost (90%) and regional nodal irradiation (RNI)(83%). Six patients (7.3%) experienced grade 3 AEs (5 with dermatitis, 5 with breast pain). Body mass index (BMI) was associated with grade 3 dermatitis (P = .015). Fifty‐eight patients (70.7%) experienced grade ≥2 dermatitis. PBT including RNI after BCS is well‐tolerated. Elevated BMI is associated with grade 3 dermatitis.     

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

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

The efficacy and safety of hypofractionated radiotherapy with concurrent anti‐HER‐2 therapy following breast‐conserving therapy for breast cancer

The purpose of this study was to report rates and severities of radiation‐related toxicities and analyze disease‐control outcomes in patients who have received hypofractionated whole breast radiation (HF) with concurrent trastuzumab with or without pertuzumab. We conducted a retrospective cohort study including women with stage I‐III HER2‐positive breast cancer who received HF at the University of Pennsylvania between 1/2005 and 5/2018 with concurrent trastuzumab with or without pertuzumab. Fractionation was 266 cGy daily to a total dose of 4256 cGy with or without a sequential tumor bed boost. Eighty patients were included in the cohort with a median follow‐up time of 21.44 months. There was one grade 3 acute toxicity (fatigue) and no grade 3 late toxicities. 91% and 25% of patients experienced grade 1‐2 acute and late skin reactions, respectively. An excellent‐good cosmetic outcome was reported by 74% and 95% of patients and physicians, respectively. No patients experienced tumor recurrences, and the only death was due to a secondary cause. These results suggest that hypofractionated whole breast radiation administered concurrently with anti‐HER‐2 therapies is efficacious and has acceptable toxicity in early‐stage breast cancer patients treated with lumpectomy. Continued follow‐up is warranted to evaluate long‐term outcomes.     

Partial Breast Irradiation or Whole Breast Radiotherapy for Early Breast Cancer: A Meta‐Analysis of Randomized Controlled Trials

Abstract: The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast‐radiation therapy (WBRT). We conducted a systematic review and meta‐analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674–1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506–1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278–7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396–3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p < 0.0001) compared with whole breast‐radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast‐radiation. Nevertheless the issue of loco‐regional recurrence needs to be further addressed.     

Outcomes with intraoperative radiation therapy for early‐stage breast cancer

Adjuvant radiation therapy has been associated with improved local control following breast‐conserving surgery. Traditionally, treatment has been delivered with whole breast irradiation over 3‐6 weeks or partial breast irradiation over 1‐3 weeks. However, intraoperative radiation therapy (IORT) has emerged as a technique that delivers a single dose of radiotherapy at the time of surgery for early‐stage breast cancers. We report initial outcomes and acute toxicities with intraoperative radiation from a single institution. Patients with DCIS or Stage I‐II breast cancer who underwent lumpectomy and sentinel lymph node biopsy (nodal sampling excluded in some cases) were included. All patients in this analysis were treated with IORT as at the time of surgery, 20 Gy in 1 fraction with 50 kV x‐ray. Patients were treated at a single institution between 2011 and 2019. Follow‐up was per standard institutional protocol. Two hundred and one patients were included in the analysis, with a median follow‐up of 23 months (range: 0‐73 months). Median age was 71 years old. Overall, 4 (2.0%) patients had DCIS, 186 (92.5%) patients had Stage 1 disease, and 11 patients had (5.5%) Stage 2 disease. All patients were estrogen receptor‐positive, 175 (87.9%) progesterone receptor‐positive, and 1 (0.5%) HER2 amplified. The crude rate of local recurrence was 2.0% (n = 4) and distant metastasis rate was 0.5% (n = 1). The rate of arm lymphedema was 0.5% (n = 1) and chronic telangiectasia rate was 1.1% (n = 2). Intraoperative radiation therapy, in a cohort of low‐risk patients, demonstrated low rates of recurrence and reproducibility in a multi‐disciplinary setting. Further follow‐up, analysis of patient satisfaction and cosmesis, and comparison to whole breast irradiation and partial breast techniques is necessary in order to further validate these findings.     

Ten daily fractions for partial breast irradiation. Long‐term results of a prospective phase II trial

Partial breast irradiation (PBI) is an effective adjuvant treatment after breast conservative surgery for selected early‐stage breast cancer patients. However, the best fractionation scheme is not well defined. Hereby, we report the 5‐year clinical outcome and toxicity of a phase II prospective study of a novel regimen to deliver PBI, which consists in 40 Gy delivered in 10 daily fractions. Patients with early‐stage (pT1‐pT2, pN0‐pN1a, M0) invasive breast cancer were enrolled after conservative surgery. The minimum age at diagnosis was 60 years old. PBI was delivered with 3D‐conformal radiotherapy technique with a total dose of 40 Gy, fractionated in 10 daily fractions (4 Gy/fraction). Eighty patients were enrolled. The median follow‐up was 67 months. Five‐year local control (LC), disease‐free survival (DFS), and overall survival (OS) were 95%, 91%, and 96%, respectively. Grade I and II subcutaneous fibrosis were documented in 23% and 5% of cases. No grade III late toxicity was observed. PBI delivered in 40 Gy in 10 daily fractions provided good clinical results and was a valid radiotherapy option for early‐stage breast cancer patients.     

The Impact of Intermediate Time between Chemotherapy and Hypofractionated Radiotherapy to the Radiation Induced Skin Toxicity for Breast Adjuvant Treatment

To evaluate the impact of intermediate time between chemotherapy and radiotherapy (ITCR) to skin toxicity for a hypofractionated irradiation schedule. Forty‐four patients with stage I–II invasive breast cancer receiving postoperative radiotherapy (RT) after lumpectomy and axillary dissection were studied. All patients received RT with 6 MV linear accelerator (LINAC) with a total tumor dose of 53 Gy (Equivalent dose‐EQD2‐ 60 Gy), 2.65 Gy per fraction, in 20 fractions. All patients received six cycles of cyclophosphamide methotrexate fluorouracil chemotherapy i.v. every 21 days. Acute and late effects and cosmetic results were assessed using the European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group (EORTC/RTOG) Rating System. The mean follow‐up was 7 years. The spearman rho test showed that there was a significant correlation between short ITCR and acute skin toxicity 3 months post RT, by means of acute radiation induced morbidity. None of the related late‐toxicity parameters was correlated with the ITCR. However, there was significantly higher acute toxicity when the ITCR was less than 20 days (p < 0.05). We may suggest that when a hypofractionated irradiation schedule is used for breast cancer patients, then the ITCR should be more than 20 days from chemotherapy.     

Extreme Oncoplasty: Breast Conservation for Patients Who Need Mastectomy

Extreme oncoplasty is a breast conserving operation, using oncoplastic techniques, in a patient who, in most physicians' opinions, requires a mastectomy. These are generally large, greater than 5 cm multifocal or multicentric tumors. Many will have positive lymph nodes. Most will require radiation therapy, even if treated with mastectomy. Sixty‐six consecutive patients with multifocal, multicentric, or locally advanced tumors that spanned more than 50 mm were studied (extreme cases). All patients underwent excision and oncoplastic reconstruction using a standard or split wise pattern reduction and immediate contralateral surgery for symmetry. All received postexcisional standard whole breast radiation therapy with a boost to the tumor bed. The extreme cases were compared with 245 consecutive patients with unifocal or multifocal tumors that spanned 50 mm or less (standard cases). All extreme patients were advised to have a mastectomy; all sought a breast conserving second opinion. Diagnostic evaluation included digital mammography, ultrasound, MRI, and PET‐CT (if invasive). Standard cases did extremely well. No ink on tumor was achieved 96% of the time among 245 patients. The median tumor size was 21 mm (mean 23 mm). Margins equal or greater than 1 mm were achieved in 88.6% of patients. Seventeen (6.9%) standard patients underwent re‐excision to achieve wider margins and only one patient (0.4%) was converted to mastectomy. With 24 months of median follow‐up, three patients (1.2%) experienced local recurrence. For extreme cases, no ink on tumor was achieved 83.3% of the time, which is comparable to published positive margin rates after standard lumpectomy. The median tumor size was 62 mm (mean 77 mm). Margins equal or greater than 1 mm were achieved in 54.5% of patients. Six (9.1%) extreme patients underwent re‐excision to achieve wider margins and four patients (6.1%) were converted to mastectomy. With a follow‐up of 24 months, one patient (1.5%) experienced a local recurrence. Extreme oncoplasty is a promising new concept. It allows successful breast conservation in selected patients with greater than 5 cm multifocal/multicentric tumors. It may be useful in patients with locally advanced tumors following neo‐adjuvant chemotherapy. From a quality of life point of view, it is a better option than the combination of mastectomy, reconstruction, and radiation therapy. Long‐term data on recurrence and survival are not available, using this approach. Based on historical data, it is expected the local recurrence will be somewhat higher but that there will be little or no impact on survival.     

Initial outcomes with image‐guided partial breast irradiation delivered with intensity‐modulated radiation therapy

Patients were treated at a single institution to a dose of 30 Gy in five fractions delivered every other day using image‐guided intensity modulated radiation therapy (IMRT) partial breast irradiation. A total of 34 patients were treated with a median follow‐up of 4.6 months. The rate of acute Grade 1 dermatitis was 23.5% (n = 8), and Grade 1 fatigue was 17.6% (n = 6), with no Grade 2 or higher acute toxicities. The rate of chronic Grade 1 dermatitis was 25.0% (n = 6), Grade 1 fat necrosis 4.2% (n=1), with no patients demonstrating other chronic toxicities. Image‐guided APBI delivered with IMRT is associated with low rates of acute and chronic toxicity though additional follow‐up is warranted.     

Intraoperative Radiotherapy of Early Breast Cancer Using Low‐Kilovoltage X‐Rays‐Reasons for Omission of Planned Intraoperative Irradiation

The purpose of this study is to investigate reasons for omission of a planned intraoperative radiotherapy (IORT) during breast‐conserving surgery (BCS). Between 2002 and 2009, in 297 women an IORT during BCS was planned. In 55 women this irradiation was finally not performed. We retrospectively analyzed pre‐, peri‐, and postoperative data of these 55 women. Main reasons for omission of an IORT were insufficient tumor–skin distance (n = 20, 35.1%), an oversized wound cavity (n = 14, 24.6%), and a combination of both (n = 8, 14%). Further reasons (n = 12, 21.1%) were temporal shortage, unplanned maintenance work of the Intrabeam^® device, unsuitable anatomicosurgical conditions, and ineligible histologic findings. Apart from suitable anatomic conditions, a precise preoperative ultrasonography as well as a strict interdisciplinary preoperative management is important for successful application of IORT.     

Intraoperative radiation therapy for breast cancer—Immediate and 30‐month oncological outcomes

There is growing evidence that intraoperative radiation therapy (IORT) may be a viable option in selected patients with early breast cancer. This study reports our 4‐year experience with IORT. The perioperative outcome and imaging data of all patients who underwent IORT for early breast cancer at a tertiary medical center in 2014‐2018 were retrospectively retrieved. The cohort included 158 patients aged 52‐84 years (mean 68) with stage I (n = 137) or II (n = 21) breast cancer. Mean applicator size was 4.13 cm; IORT added a mean of 29 minutes to the operative time. Minor wound infections (n = 18, 11.4%) requiring antibiotics and drainage were the only postoperative complication. In 25 patients (15%), postoperative mammography demonstrated a seroma (n = 22) or fat necrosis (n = 3). The risk of wound infection or a new postoperative imaging finding was unrelated to patient age, operative time, tumor size, or comorbid diabetes or obesity. After a mean of 30 months' follow‐up, none of the patients who met the institutional criteria for IORT had local recurrence, regardless of age, histology, tumor grade, KI67 proliferation index, pathologic stage, Recurrence Score, or additional whole‐breast irradiation or adjuvant treatment. Patients for whom a Recurrence Score was determined (n = 55, 35%) had a significantly higher tumor grade, pathologic stage, and whole‐breast irradiation/adjuvant chemotherapy rate than the remaining patients. IORT may be a safe alternative to traditional external beam radiation in well‐selected patients with early breast cancer, with few minor complications and good 30‐month outcome.     

Shortened Radiation Therapy Schedules for Early‐Stage Breast Cancer: A Review of Hypofractionated Whole‐Breast Irradiation and Accelerated Partial Breast Irradiation

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

Adjuvant radiotherapy versus observation following lumpectomy in ductal carcinoma in‐situ: A meta‐analysis of randomized controlled trials

The role of adjuvant radiotherapy (RT) following lumpectomy for ductal carcinoma in‐situ (DCIS) was addressed in four major randomized controlled trials (RCTs) which were conducted two to three decades ago. Initial results of these trials suggested the protective role of RT in reducing the ipsilateral breast recurrences. Long‐term results of all these four trials, based on more than 10‐years follow‐up data, have recently been published. A meta‐analysis of four published RCTs which have addressed the role of adjuvant RT following lumpectomy for DCIS was conducted. Review manager (Cochrane Collaboration's software) version RevMan 5.2 was used for analysis. Evaluated events were ipsilateral breast recurrences (both DCIS and invasive), regional recurrences, contralateral breast events, distant recurrences, and overall mortality. The events were entered as dichotomous variable. The present meta‐analysis included four RCTs and a total of 3680 patients – 1710 received adjuvant RT following lumpectomy while 1970 patients did not receive any adjuvant treatment. Patients who received RT had almost half of risk of ipsilateral breast recurrence (RR = 0.53, 95% CI = 0.45‐0.62) and regional recurrence (RR = 0.54, 95% CI = 0.32‐0.91) compared to those who did not receive adjuvant treatment – there was absolute risk reduction in 15% (95% CI = 12%‐17%) for ipsilateral breast recurrences in adjuvant RT treated patients. There was no significant difference in distant recurrence (RR = 1.06, 95% CI = 0.74‐1.53), contralateral breast events (RR = 1.22, 95% CI = 0.98‐1.52) and overall mortality (RR = 0.93, 95% CI = 0.79‐1.09). Though addition of postoperative RT to lumpectomy does not reduce overall mortality, the present meta‐analysis confirms that it decreases the ipsilateral breast and regional recurrence by almost half.     

Malignant Phyllodes Tumor of the Breast: Treatment and Prognosis

Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50 years (21–76), and the mean size of the tumor was 6 cm. Thirty‐four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1 cm. Remaining 6 (8.6%) patients treated with BCS margins were <1 cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5 years. The extent of surgery was not significantly related to the 5‐year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5‐year NED survival rates in BCS (tumor‐free margin ≥1 cm) and BCS with irradiation (tumor‐free margin <1 cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor‐free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor‐free margins are <1 cm.     

Relation between Hypofractionated Radiotherapy,Toxicity and Outcome in Early Breast Cancer

To compare adjuvant conventional radiotherapy (C‐RT) to hypofractionated schedule (HF‐RT) in early breast cancer. Between May 2012 and September 2015, 120 patients were included in the analysis. All patients underwent conservative surgery and adjuvant RT. RT was delivered in C‐RT (50 Gy; 2 Gy/fr) or HF‐RT (42.5 Gy; 2.66 Gy/fr), followed by a tumor bed boost (10 Gy; 2 Gy/fr). RT‐induced toxicity was recorded and compared between groups. Toxicity results were graded according to the Common Terminology Criteria for Adverse Events guidelines. A multivariate analysis was performed of the factors associated with acute toxicity onset. Mild acute skin toxicity was observed in 71.7% of patients. No grade 4 toxicity was observed. From the multivariate analysis, Breast volume and RT fractionation significantly affected acute radiation‐related toxicity. No increase in late toxic effects has been reported between C‐RT and HF‐RT schedules. Overall, the 2‐year disease free survival was 94.4%. HF‐RT represents a valid adjuvant treatment option in early breast cancer patients, without negative impact on acute and late radiation sequelae, as well as tumor control.     

Accelerated Partial Breast Irradiation Via the Mammosite® Catheter: Preliminary Reports of a Single-Institution Experience

Abstract: Several studies have shown that the majority of in‐breast recurrences following lumpectomy are at or near the original tumor site while ipsilateral breast recurrences further afield occur rarely. This suggests that the radiation dose could be delivered exclusively to the tumor bed, allowing larger fractions to be used without increasing toxicity and shortening the total treatment time. We investigated the use of the MammoSite irradiation system with a view to analyzing complications, cosmesis and patient comfort. Between 2004 and 2007 intracavity brachytherapy was given to 30 patients using the MammoSite device. The reference isodose was prescribed to the lumpectomy cavity with a 1 cm margin. Geometric parameters and anatomic position of the applicator after implantation were checked via CT, x‐ray and ultrasound. Analysis was done for patient quality of life, cosmesis, early and late complications. Forty‐nine patients received a proposal for MammoSite brachytherapy. Nine declined, 40 enrolled while 10 were excluded for various reasons ( Table 5 ). A total of 30 patients were actually treated to 34 Gy (2 × 3.4 Gy) in 5 days. We observed 3 cases (10%) of infection within 3 months of implantation. Symptomatic seroma was seen in five patients (16.6%) at 6 months, in three (10%) at 12 months, and in just one patient (3.3%) at 18 months. Good to excellent cosmetic results were achieved in 75% by patient and physician ratings. Accelerated partial breast irradiation using the MammoSite catheter produces favorable short‐term outcomes, limited toxic effects on skin, and optimal cosmetic results. Patient tolerance for the treatment is very high. Critical issues may regard the importance of good cavity conformance and adequate balloon‐skin distance in avoiding possible dose excesses to the skin. For a selected patient group, this could be a valid alternative to conventional whole breast irradiation.

Table 5. Causes of Exclusion from the Protocol

Breast conservation for male breast cancer: Case report of intraoperative radiation

Male breast cancer (MBC) comprises <1% of all breast cancers in the United States. MBC is typically treated with total mastectomy while the majority of female breast cancer is treated with breast conservation therapy combined with various forms of radiation. One method that has developed over the last two decades is the use of intraoperative radiation therapy (IORT) as a type of accelerated partial breast irradiation to direct the treatment field to the tumor bed. Since overall prognosis and systemic therapy recommendations for MBC are similar to breast cancer in women, we describe the first case of MBC treated with BCS and IORT. Our patient is a 62‐year‐old male who was found to have a right breast 1.6 cm palpable mass at the 10:00 position 1 cm radially from the nipple. Core biopsy demonstrated invasive ductal carcinoma, moderately differentiated, estrogen and progesterone receptor positive, and Her 2 Negative. The patient had a strong desire for breast conservation, and needed to minimize daily radiation treatments due to his work schedule. After discussion among our multidisciplinary tumor board, we felt this patient to be suitable for BCS and IORT given his age, favorable tumor subtype, size, and clinically early stage breast cancer. A right axillary sentinel lymph node biopsy and central lumpectomy was performed. The INTRABEAM device (Carl Zeiss Meditec, Oberkochen, Germany) was utilized for radiation delivery. The patient had negative margins on his final pathology. The postoperative course was uneventful and at the 6 month follow‐up visit there were no issues and he had an excellent cosmetic outcome. BCS and IORT is an option in appropriately selected male patients with favorable subtype early stage breast cancer.     

Utilization of BioZorb implantable device in breast‐conserving surgery

BioZorb fiducial marker is an implantable device made of six clips to mark the surgical site of tissue removal in three dimensions. The marker facilitates focused radiation therapy, while allowing for tissue ingrowth during the healing process with resorption by the body overtime. Current literature investigating the use of the BioZorb is limited and focused on its value for radiation treatment. Our objective was to investigate the feasibility and surgical complications associated with the BioZorb in breast‐conserving surgery. From April 2015 to June 2018, 89 patients who underwent 91 partial mastectomies with planned adjuvant radiation therapy and placement of the BioZorb. Demographics, type of BioZorb used, complication rate, and postoperative examinations were analyzed. A total of 89 patients who were a median age of 59 years (range 34‐84) underwent 91 operations with BioZorb placement—86.8% underwent a partial mastectomy (n = 79), and 13.2% underwent a breast wide re‐excision for margins at the time of BioZorb placement (n = 12). Of the 79 partial mastectomies, 21.5% (n = 17) were palpable tumors. Location of the tumor and subsequent BioZorb placement was most often in the upper outer quadrant (40.7%), followed by upper inner (27.5%), lower outer (20.9%), and lower inner quadrants (10.9%). 92.3% (n = 84) had a single BioZorb placed, 5.5% (n = 5) had two BioZorbs placed in a single lumpectomy cavity, and 2.2% (n = 2) had two BioZorbs placed in separate lumpectomy cavities of the same breast. Of the 10 different tissue marker sizes used, a 2 × 3 cm BioZorb was most commonly used (37/98, 37.8%), followed by 3 × 4 cm (25/98, 25.5%) and 1 × 3 × 2 (9/98, 9.2%). A total of five patients underwent immediate bilateral breast reduction following placement of the BioZorb. Of the 91 operations, 22 patients had a subsequent reoperation for positive margins after initial placement of the BioZorb, of which 86.4% retained the BioZorb . During these reoperations, only 1 patient had the BioZorb removed due to discomfort (4.5%) and two had it removed due to subsequent mastectomy (9.1%). At a median time of 1.1 years, the BioZorb continued to be palpable on clinical breast examination in 63.6% of patients. The longest time that the BioZorb continued to be palpable was 2.8 years. Additional imaging was ordered because a clinician palpated a mass, unaware it was the BioZorb 8.8% of the time (n = 8). Thirty‐day complications include 3.3% of patients with an infection requiring antibiotics (n = 3) and 2.2% with an abscess requiring aspiration and antibiotics without removal of the BioZorb. One patient had migration of the BioZorb from the breast to the axilla which resulted in surgical explant at 9 months post‐op. BioZorb is feasible to use in breast‐conserving surgery with few short‐ and long‐term complications, but will result in a palpable mass that may persist for more than 1 year. Explantation is rare.     

Tissue Compliance Meter is a More Reproducible Method of Measuring Radiation‐Induced Fibrosis than Late Effects of Normal Tissue–Subjective Objective Management Analytical in Patients Treated with Intracavitary Brachytherapy Accelerated Partial Breast Irradiation: Results of a Prospective Trial

Identification of radiation‐induced fibrosis (RIF) remains a challenge with Late Effects of Normal Tissue–Subjective Objective Management Analytical (LENT‐SOMA). Tissue compliance meter (TCM), a non‐invasive applicator, may render a more reproducible tool for measuring RIF. In this study, we prospectively quantify RIF after intracavitary brachytherapy (IB) accelerated partial breast irradiation (APBI) with TCM and compare it with LENT‐SOMA. Thirty‐nine women with American Joint Committee on Cancer Stages 0‐I breast cancer, treated with lumpectomy and intracavitary brachytherapy delivered by accelerated partial breast irradiation (IBAPBI), were evaluated by two raters in a prospective manner pre‐IBAPBI and every 6 months post‐IBAPBI for development of RIF, using TCM and LENT‐SOMA. TCM classification scale grades RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe, corresponding to a change in TCM (ΔTCM) between the IBAPBI and nonirradiated breasts of ≤2.9, 3.0–5.9, 6.0–8.9, ≥9.0 mm, respectively. LENT‐SOMA scale employs clinical palpation to grade RIF as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Correlation coefficients—Intraclass (ICC), Pearson (r), and Cohen's kappa (κ)—were employed to assess reliability of TCM and LENT‐SOMA. Multivariate and univariate linear models explored the relationship between RIF and anatomical parameters [bra cup size], antihormonal therapy, and dosimetric factors [balloon diameter, skin‐to‐balloon distance (SBD), V150, and V200]. Median time to follow‐up from completion of IBAPBI is 3.6 years (range, 0.8–4.9 years). Median age is 69 years (range, 47–82 years). Median breast cup size is 39D (range, 34B–44DDD). Median balloon size is 41.2 cc (range, 37.6–50.0 cc), and median SBD is 1.4 cm (range, 0.2–5.5 cm). At pre‐IBAPBI, TCM measurements demonstrate high interobserver agreement between two raters in all four quadrants of both breasts ICC ≥ 0.997 (95% CI 0.994–1.000). After 36 months, RIF is graded by TCM scale as 0, 1, 2, and 3 in 10/39 (26%), 17/39 (43%), 9/39 (23%), and 3/39 (8%) of patients, respectively. ΔTCM ≥6 mm (moderate‐severe RIF) is statistically different from ΔTCM ≤3 mm (none‐mild RIF) (p < 0.05). At 36 months post‐IBAPBI, TCM measurements for two raters render ICC = 0.992 (95% CI 0.987–0.995) and r = 0.983 (p < 0.0001), whereas LENT‐SOMA demonstrates κ = 0.45 (95% CI 0.18–0.80). SBD and V150 are the only factors closest to 0.05 significance of contributing to RIF. This prospective study indicates that TCM is a more reproducible method than LENT‐SOMA in measuring RIF in patients treated with IBAPBI. This tool renders a promising future application in assessing RIF.     

Once‐weekly hypofractionated radiotherapy for breast cancer: First results of a phase II clinical trial

Hypofractionated radiotherapy (HF) in 15 or 16 daily fractions is well established as an alternative in early breast cancer after breast‐conserving surgery. Evidences for a whole‐breast treatment even shorter, in 5‐10 fractions, are still scarce. Women 50 years or older, with early breast tumor (pT1‐2pN0), after breast‐conserving surgery were eligible to enter in this phase II trial and received whole breast once‐weekly hypofractionated radiotherapy (wHF‐RT) to a total dose of 30 Gy, in 5 fractions of 6 Gy. During treatment and in post‐treatment follow‐up the toxicity was assessed and graduated according to the “Common Terminology Criteria for Adverse Events” (CTCAE), v3.0. Breast pictures for esthetic comparison were taken in 5 timepoints and 2 breast surgeons independently graduated the cosmetics changes. The trial was registered with ClinicalTrials.gov, number NCT01965483. From October 2013 to November 2015, 44 patients were enrolled in the trial and treated according to the protocol of wHF‐RT. The median age was 70.5 years (51‐88 years), and the median follow‐up was 22 months (9‐33 months). Skin erythema was the most common acute adverse event. At the end of radiation, 30 patients (68.2%) had any grade of radiation dermatitis. Concerning cosmetic appearance, there was no significant difference between pretreatment and 1 year assessments. The 2‐year overall survival and disease‐free survival were, respectively 96.8% and 97.7%. There was only one distant recurrence and no local or regional recurrence. Once‐weekly hypofractionated radiotherapy is a feasible and well tolerated alternative for early breast cancer adjuvant management with acceptable acute toxicity and esthetic outcomes.