Phase II Trial of Five-Fraction Accelerated Partial Breast Irradiation Using Noninvasive Image-Guided Breast Brachytherapy.

PURPOSE/OBJECTIVE(S): NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in the fraction number is desirable. Final results of a prospective phase II trial are reported. MATERIALS/METHODS: NIBB APBI was delivered using 28.5Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2mm. The primary endpoint was grade ≥ 2 subcutaneous fibrosis/induration <30%. Secondary endpoints included any late toxicity, cosmetic outcome, and local control. RESULTS: 40 patients were treated with a median follow-up of 59.7 months. The mean age was 67 years (50-89 years) and tumor size was 1.0cm (0.3-2.0cm). 80% had invasive carcinoma. The mean breast separation with compression was 6.7cm (3.5-8.9cm). The 5-year actuarial local control was 96.6% and overall survival was 96.9%. Grade 2 and 3 late toxicities were 15% and 0%, respectively. The rate of grade 2 subcutaneous fibrosis/induration was 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia; 22.5% grade 1 and 15% grade 2. Only breast separation was associated with telangiectasia risk, p=0.002. Overall cosmetic outcome was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. CONCLUSIONS: NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0cm. The local failure rate was appropriately low. Further investigation of this technique is warranted.

Comparison of Tumor Bed Delineation Using a Novel Radiopaque Filament Marker Versus Surgical Clips for Targeting Breast Cancer Radiotherapy.

BACKGROUND: Accuracy of tumor bed (TB) delineation is essential for targeting boost doses or partial breast irradiation. Multiple studies have shown high interobserver variability with standardly used surgical clip markers (CMs). We hypothesize that a radiopaque filament marker (FM) woven along the TB will improve TB delineation consistency. METHODS: An FDA-approved FM was intraoperatively used to outline the TB of patients undergoing lumpectomy. Between January 2020 and January 2022, consecutive patients with FM placed after either (1) lumpectomy or (2) lumpectomy with oncoplastic reconstruction were identified and compared with those with CM. Six "experts" (radiation oncologists specializing in breast cancer) across 2 institutions independently defined all TBs. Three metrics (volume variance, dice coefficient, and center of mass [COM] deviation). Two-tailed paired samples t tests were performed to compare FM and CM cohorts. RESULTS: Twenty-eight total patients were evaluated (14 FM and 14 CM). In aggregate, differences in volume between expert contours were 29.7% (SD ± 58.8%) with FM and 55.4% (SD ± 105.9%) with CM ( P < 0.001). The average dice coefficient in patients with FM was 0.54 (SD ± 0.15), and with CM was 0.44 (SD ± 0.22) ( P < 0.001). The average COM deviation was 0.63 cm (SD ± 0.53 cm) for FM and 1.05 cm (SD ± 0.93 cm) for CM; ( P < 0.001). In the subset of patients who underwent lumpectomy with oncoplastic reconstruction, the difference in average volume was 21.8% (SD ± 20.4%) with FM and 52.2% (SD ± 64.5%) with CM ( P <0.001). The average dice coefficient was 0.53 (SD ± 0.12) for FM versus 0.39 (SD ± 0.24) for CM ( P < 0.001). The average COM difference was 0.53 cm (SD ± 0.29 cm) with FM versus 1.25 cm (SD ± 1.08 cm) with CM ( P < 0.001). CONCLUSION: FM consistently outperformed CM in the setting of both standard lumpectomy and complex oncoplastic reconstruction. These data suggest the superiority of FM in TB delineation.

Predictors of Pneumonitis in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Definitive Chemoradiation Followed by Consolidative Durvalumab.

Purpose: In patients with locally advanced, unresectable non-small cell lung cancer (NSCLC), the standard of care is concurrent chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab. Pneumonitis is a known adverse event of both radiation therapy and immune checkpoint inhibitors such as durvalumab. We sought to characterize pneumonitis rates and dosimetric predictors of pneumonitis in a real-world population of patients with NSCLC treated with definitive CRT followed by consolidative durvalumab. Methods and Materials: Patients with NSCLC from a single institution who were treated with definitive CRT followed by consolidative durvalumab were identified. Outcomes of interest included pneumonitis incidence, type of pneumonitis, progression-free survival, and overall survival. Results: Sixty-two patients were included in our data set treated from 2018 to 2021 with a median follow-up of 17 months. The rate of grade 2+ pneumonitis in our cohort was 32.3%, and the rate of grade 3+ pneumonitis was 9.7%. Lung dosimetry parameters including V20 ≥30% and mean lung dose (MLD) >18 Gy were found to be correlated with increased rates of grade 2+ and grade 3+ pneumonitis. Patients with a lung V20 ≥30% had a grade 2+ pneumonitis rate at 1 year of 49.8% compared with 17.8% in patients with a lung V20 <30% (P = .015). Similarly, patients with an MLD >18 Gy had a grade 2+ pneumonitis rate at 1 year of 52.4% compared with 25.8% in patients with an MLD ≤18 Gy (P = .01). Moreover, heart dosimetry parameters including mean heart dose ≥10 Gy were found to be correlated with increased rates of grade 2+ pneumonitis. The estimated 1-year overall survival and progression-free survival of our cohort were 86.8% and 64.1%, respectively. Conclusions: The modern management of locally advanced, unresectable NSCLC involves definitive chemoradiation followed by consolidative durvalumab. Pneumonitis rates were higher than expected in this cohort, particularly for patients with a lung V20 ≥30%, MLD >18 Gy, and mean heart dose ≥10 Gy, suggesting that more stringent radiation planning dose constraints may be needed.

Quantifying risk using FMEA: An alternate approach to AAPM TG-100 for scoring failures and evaluating clinical workflow.

PURPOSE: Renovation of the brachytherapy program at a leading cancer center utilized methods of the AAPM TG-100 report to objectively evaluate current clinical brachytherapy workflows and develop techniques for minimizing the risk of failures, increasing efficiency, and consequently providing opportunities for improved treatment quality. The TG-100 report guides evaluation of clinical workflows with recommendations for identifying potential failure modes (FM) and scoring them from the perspective of their occurrence frequency O, failure severity S, and inability to detect them D. The current study assessed the impact of differing methods to determine the risk priority number (RPN) beyond simple multiplication. METHODS AND MATERIALS: The clinical workflow for a complex brachytherapy procedure was evaluated by a team of 15 staff members, who identified discrete FM using alternate scoring scales than those presented in the TG-100 report. These scales were expanded over all clinically relevant possibilities with care to emphasize mitigation of natural bias for scoring near the median range as well as to enhance the overall scoring-system sensitivity. Based on staff member perceptions, a more realistic measure of risk was determined using weighted functions of their scores. RESULTS: This new method expanded the range of RPN possibilities by a factor of 86, improving evaluation and recognition of safe and efficient clinical workflows. Mean RPN values for each FM decreased by 44% when changing from the old to the new clinical workflow, as evaluated using the TG-100 method. This decreased by 66% when evaluated with the new method. As a measure of the total risk associated with an entire clinical workflow, the integral of RPN values increased by 15% and decreased by 31% with the TG-100 and new methods, respectively. CONCLUSIONS: This appears to be the first application of an alternate approach to the TG-100 method for evaluating the risk of clinical workflows. It exemplifies the risk analysis techniques necessary to rapidly evaluate simple clinical workflows appropriately.

Multi-institutional registry study evaluating the feasibility and toxicity of accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy.

PURPOSE: The noninvasive image-guided breast brachytherapy (NIBB) technique is a novel noninvasive yet targeted method for accelerated partial breast irradiation. We established a multi-institutional registry to evaluate the toxicity and efficacy of this technique across various practice settings. METHODS AND MATERIALS: Institutions using the NIBB technique were invited to participate. Data for acute/late toxicity, cosmetic outcome, and tumor recurrence were collected. Toxicity and cosmetic outcome were graded based on the Common Terminology Criteria for Adverse Events version 3.0 and NRG/Radiation Therapy Oncology Group scale, respectively. Treatment variables were analyzed for association with outcomes. RESULTS: A total of 252 patients from eight institutions were analyzed. The median age was 69 years. The mean tumor size was 1.1 cm (0.1-4.0 cm). Treatment was delivered 10 fractions (34-36 Gy) in 75% and five fractions (28.5 Gy) in 22%. B.i.d. fractionation was used in 9%. Acute radiation dermatitis was Grade 0-1, 2, and 3 in 77%, 19%, and 4%, respectively. One hundred ninety-one patients with a median followup of 18 months (4-72 months) were evaluable for late outcomes. Late toxicity Grades 2 and 3 were observed in 8.8% and 1%, respectively. Cosmetic outcome was excellent, good, and fair/poor in 62%, 36%, and 2%, respectively. B.i.d. fractionation was associated with higher acute and late toxicity. Second-generation applicators were associated with lower late toxicity and better cosmetic outcome. Actuarial freedom from ipsilateral breast tumor recurrence and true recurrence were 98.3% and 98.3% at 2 years and 90.9% and 95.4% at 5 years, respectively. CONCLUSIONS: Accelerated partial breast irradiation using NIBB was well tolerated with a low rate of acute and late toxicity across various practice settings. Ipsilateral breast tumor recurrence and cosmetic outcomes were favorable. b.i.d. fractionation was associated with higher toxicity. Longer followup is needed to confirm late endpoints.

Update on Partial Breast Irradiation.

For early-stage breast cancer, partial breast irradiation (PBI) allows for reduction in the irradiated volume of normal tissues by confining the radiation target to the area surrounding the lumpectomy cavity after breast-conserving surgery. This approach has been supported by phase 2 data. However, widespread adoption of PBI has awaited the results of randomized controlled trials. This review discusses the results of randomized controlled trials comparing whole breast irradiation to PBI, including the recently published National Surgical Adjuvant Breast and Bowel Project (NSABP) B39/Radiotherapy Oncology Group (RTOG) 0413, and the Canadian RAPID trials. PBI techniques, dose/fractionation schedules, and patient selection are also reviewed.

Mammographically guided noninvasive breast brachytherapy: Preoperative partial breast radiotherapy markedly improves targeting accuracy and decreases irradiated volume.

PURPOSE: Mammographically based noninvasive image-guided breast brachytherapy (NIBB) partial breast irradiation (PBI) is ideally suited for preoperative treatment. We hypothesize that delivering NIBB PBI to the preoperative tumor volume compared with the postoperative lumpectomy bed would simplify target identification and allow for a reduction in irradiated volume along each orthogonal axis. METHODS AND MATERIALS: Patients with invasive breast cancer treated with NIBB PBI at our institution were identified. Preoperative NIBB treatments were modeled along orthogonal craniocaudal and mediolateral axes with an applicator encompassing the gross lesion plus a 1 cm clinical target volume margin. Preoperative treatment volumes were calculated along each axis using the selected applicator surface area multiplied by the preoperative mammogram separation. The actual applicator size and breast separation from the first fraction of postoperative treatment was used to calculate the postoperative treatment volume. Paired -test was used to compare the preoperative and postoperative treatment separation, area, and volume for each patient. RESULTS: Forty-eight patients with Stage I-II breast cancer had imaging and treatment data available for review. Along the axis, the mean preoperative treatment volume was significantly less than the mean postoperative treatment volume (116 cm 3 vs. 204 cm 3, respectively; p < 0.0001). Similarly, along the mediolateral axis, the mean preoperative treatment volume was significantly less than the mean postoperative treatment volume (125 cm 3 vs. 216 cm 3, respectively; p < 0001). CONCLUSIONS: Based on our retrospective comparison, PBI delivered using NIBB to the preoperative tumor may reduce the volume of healthy breast tissue receiving radiation as compared with NIBB to the postoperative tumor bed.

Phase 2 Trial of Accelerated Partial Breast Irradiation (APBI) Using Noninvasive Image Guided Breast Brachytherapy (NIBB).

PURPOSE: Noninvasive image guided breast brachytherapy (NIBB) is a novel approach to delivery of accelerated partial breast irradiation (APBI) that may hold advantages over established techniques. NIBB is not invasive but maintains a high level of precision by using breast immobilization via breast compression and image guidance; it therefore does not require large planning tumor volume margins. We present the primary outcomes of this prospective phase 2 study (BrUOG Br-251). METHODS AND MATERIALS: Eligible patients with early-stage breast cancer underwent NIBB APBI using a dose 34 Gy in 10 fractions delivered daily or twice a day. Treatment was delivered using an Ir-192 high-dose-rate source via specialized applicators. Two orthogonal treatment axes were used for each fraction. The primary endpoints were late toxicity and cosmesis assessed at 2 and 5 years. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Cosmesis was assessed using the NRG/Radiation Therapy Oncology Group scale. Ipsilateral breast tumor recurrence was defined as any recurrence or new primary in the treated breast. RESULTS: Forty patients underwent protocol treatment. Median patient age was 68 years (50-92 years). Mean tumor size was 1.1 cm (0.3-3.0 cm). Among the cohort, 62.5% had invasive carcinoma and 37.5% had ductal carcinoma in situ. Thirty-nine percent elected to receive hormone therapy. No grade ≥3 late toxicities were observed at any time point. Grade 2 toxicity was 5% and 10% at 2 and 5 years, respectively. Telangiectasia grade 1 and 2 occurred in 27.5% and 5%, respectively. Breast separation of >7 cm was associated with telangiectasia (P < .01). The rate of good to excellent cosmetic outcome was 95% at 2 years and 100% at 5 years. With a median follow-up of 68 months, the actuarial 5-year freedom from ipsilateral breast tumor recurrence was 93.3% (±4.8%), and overall survival was 93.7% (±4.4%). CONCLUSIONS: NIBB to deliver APBI is well tolerated with a low incidence of significant late toxicity and has favorable cosmetic outcomes. Continued evaluation of the NIBB APBI technique in a larger cohort is warranted.

Novel and programmatic improvements to the workflow associated with the AccuBoost breast brachytherapy procedure.

PURPOSE: While the noninvasive breast brachytherapy (NIBB) treatment procedure, known as AccuBoost, for breast cancer patients is well established, the treatment quality can be improved by the efficiency of the workflow delivery. A formalized approach evaluated the current workflow through failure modes and effects analysis and generated insight for developing new procedural workflow techniques to improve the clinical treatment process. METHODS AND MATERIALS: AccuBoost treatments were observed for several months while gathering details on the multidisciplinary workflow. A list of possible failure modes for each procedure step was generated and organized by timing within the treatment process. A team of medical professionals highlighted procedural steps that unnecessarily increased treatment time, as well as introduced quality deficiencies involving applicator setup, treatment planning, and quality control checks preceding brachytherapy delivery. Procedural improvements and their impact on the clinical workflow are discussed. RESULTS: The revised clinical workflow included the following key procedural enhancements. Prepatient arrival: Improvement of prearrival preparation requires advance completion of dose calculation documentation with patient-specific setup data. Patient arrival pretreatment: Physicists carry out dwell time calculations and check the plan, while the therapist concurrently performs several checks of the ensuing hardware configuration. TREATMENT: An electronic method to export the associated HDR brachytherapy paperwork to the electronic medical record system with electronic signatures and captured approvals was generated. Posttreatment: The therapist confirms the applicators were appropriately positioned, and treatment was delivered as expected. CONCLUSIONS: The procedural improvements reduced the overall treatment time, improved consistency across users, and eased performance of this special procedure for all participants.

New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab.

PURPOSE: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients. PATIENTS AND METHODS: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities. RESULTS: A total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040). CONCLUSION: New cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.

Multi-institutional validation of brain metastasis velocity, a recently defined predictor of outcomes following stereotactic radiosurgery.

INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting. METHODS: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (<4 BMV), intermediate (4-13 BMV), and high-risk groups (>13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS. RESULTS: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV < 4, BMV 4-13, and BMV > 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p < 0.0001). After multivariate regression modeling, melanoma histology (ß: 10.10, SE: 1.89, p < 0.0001) and number of initial brain metastases (ß: 1.52, SE: 0.34, p < 0.0001) remained predictive of BMV (adjusted R2 = 0.06). CONCLUSIONS: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.

The American Brachytherapy Society consensus statement for electronic brachytherapy.

PURPOSE: Brachytherapy is utilized in the treatment of many different malignancies; although traditionally performed with low-dose-rate or high-dose-rate techniques, more recently, electronic brachytherapy (EB) has emerged as a potential alternative. At this time, there are no evidence-based guidelines to assist clinicians in patient selection for EB and concerns exits regarding differences in dosimetry as compared to traditional brachytherapy techniques. As such, the American Brachytherapy Society appointed a group of physicians and physicists to create a consensus statement regarding the use of EB. METHODS AND MATERIALS: Physicians and physicists with expertise in brachytherapy created a site-directed consensus statement for appropriate patient selection and utilization of EB based on a literature search and clinical experience. RESULTS: EB has been utilized to deliver accelerated partial breast irradiation with, thus far acceptable local control and toxicity rates including a randomized trial that used EB to deliver intraoperative radiotherapy; however, prospective data with large patient numbers and long-term follow up are needed. Increasing numbers of patients have been treated with EB for nonmelanomatous skin cancers; although, preliminary data are promising, there is a lack of data comparing EB to traditional radiotherapy techniques as well as a lack of long-term follow up. For treatment of the vaginal cuff with EB, small retrospective studies have been reported without long-term follow up. CONCLUSIONS: In light of a randomized trial in breast showing higher rates of recurrence and the lack of prospective data with mature follow up with other sites, as well as concerns regarding dosimetry, it is not recommended that EB be utilized for accelerated partial breast irradiation, nonmelanomatous skin cancers, or vaginal cuff brachytherapy outside prospective clinical trials at this time.

Local failure and vertebral body fracture risk using multifraction stereotactic body radiation therapy for spine metastases.

PURPOSE: Single-fraction radiation surgery for spine metastases is highly effective. However, a high rate (20-39%) of vertebral body fracture (VBF) has been associated with large, single-fraction doses. We report our experience using multifraction stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: All patients who were treated with multifraction SBRT for spine metastases at our institution between 2009 and 2017 were retrospectively analyzed. SBRT was delivered in 2 to 5 fractions using the Cyberknife System (Accuray, Sunnyvale, CA). Patients were followed clinically and with magnetic resonance imaging every 3 to 6 months. Local control, complications (including VBF), and overall survival were evaluated. Patient, disease, and treatment variables were analyzed for a statistical association with outcomes. RESULTS: A total of 83 patients were treated to 98 spine lesions with a median follow-up of 7.6 months. Histologies included non-small cell lung cancer (NSCLC; 24%), renal cell carcinoma (RCC; 18%), and breast cancer (12%). Surgery or vertebroplasty were performed before SBRT in 21% of cases. Patients received a median SBRT dose of 24 Gy in a median of 3 fractions. Local control was 93% at 6 months and 84% at 1 year. Higher prescribed dose, higher biologic effective dose, higher minimum dose to 90% of the planning target volume, tumor histology, and smaller tumor volume predicted improved local control. The cumulative dose was 23 Gy versus 26 Gy for patients with and without failure (P = .02), higher biologic effective dose 39 Gy versus 46 Gy, (P = .01), and higher minimum dose to 90% of the planning target volume 23 Gy versus 26 Gy (P = .03). VBF occurred in 4.2% of all cases and 5.3% of those without surgery or vertebroplasty prior to SBRT. Only preexisting VBF predicted risk of post-SBRT VBF (P < .01). CONCLUSIONS: Multifraction SBRT results in a high local control rate for metastatic spinal disease with a low VBF rate, which suggests a favorable therapeutic ratio compared with single-fraction SBRT.

Five fraction accelerated partial breast irradiation using noninvasive image-guided breast brachytherapy: Feasibility and acute toxicity.

PURPOSE: To improve efficiency, convenience, and cost, a prospective phase II trial was initiated to evaluate accelerated partial breast irradiation delivered with noninvasive image-guided breast brachytherapy (NIBB) via five once-daily fractions. METHODS AND MATERIALS: Women ≥50 years old with early-stage breast cancer undergoing breast conserving surgery were enrolled. Eligibility criteria included invasive carcinoma ≤2.0 cm or ductal carcinoma in situ ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and margins negative by 2 mm. Patients received a total dose of 28.5 Gy in five daily fractions. NIBB was delivered using two orthogonal axes for each fraction. Applicators were selected to encompass the lumpectomy cavity with a 1.0 cm clinical target volume margin and 0 to 0.5 cm planning target volume margin. Acute and late toxicity was assessed based on CTCAE v3.0. RESULTS: Forty patients with a mean age of 67 years underwent protocol treatment. Mean tumor size was 1.0 cm (0.3-2.0 cm). Eighty percent had invasive carcinoma and the remainder had ductal carcinoma in situ. Mean tumor bed volume was 21 cc (5-79 cc) and mean breast volume was 1319 cc (499-3044 cc). Mean breast separation with compression was 6.7 cm (3.5-8.9 cm). All patients tolerated well. Median discomfort with compression was 1 (range: 0-7) on a 10-point pain scale. Acute skin reaction was Grade 0-1 in 70%, Grade 2 in 28%, and Grade 3 in 3%. Acute skin toxicity was not associated with breast size but was associated with larger breast separation with compression (p < 0.01) and larger applicator size (p < 0.01). No Grade 3+ late toxicity or local recurrences have been observed at a median followup of 14 months. CONCLUSIONS: Accelerated partial breast irradiation delivered using NIBB over five daily fractions is a convenient treatment option that is feasible and well tolerated.

BRCA1 Mutations Associated With Increased Risk of Brain Metastases in Breast Cancer: A 1: 2 Matched-pair Analysis.

BACKGROUND: Brain metastases (BM) occur in ∼5% of breast cancer patients. BRCA1-associated cancers are often basal-like and basal-like cancers are known to have a predilection for central nervous system metastases. We performed a matched-pair analysis of breast cancer patients with and without BRCA mutations and compared the frequency of BM in both groups. MATERIALS AND METHODS: From a database of 1935 patients treated for localized breast cancer at our institution from 2009 to 2014 we identified 20 patients with BRCA1 or BRCA2 mutations and manually matched 40 patients without BRCA mutations accounting for age, stage, estrogen receptor expression, and human epidermal growth factor receptor 2 (HER2) expression. Comparisons of freedom from brain metastasis, brain metastasis-free survival, and overall survival were made using the log rank test. Testing for a basal-type phenotype using the immunohistochemistry definition (ER/PR/HER2 and either CK 5/6 or EGFR) was performed for BRCA patients who developed BM and their matched controls. RESULTS: We analyzed 60 patients: 20 BRCA and 40 were matched controls. Median follow-up was 37 and 49 months, respectively. Three years freedom from brain metastasis was 84% for BRCA patients and 97% for BRCA controls (P=0.049). Three years brain metastasis-free survival was 84% and 97% for the BRCA+ and controls, respectively (P=0.176). Mean time to brain failure was 11 months from diagnosis for the BRCA patients. All 3 BRCA1 patients who developed BM were of a basal-type triple negative phenotype. CONCLUSIONS: Breast cancer patients with germline BRCA1 mutations appear to have a shorter interval to brain progression while accounting for confounding factors.

American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy.

PURPOSE: To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB). METHODS AND MATERIALS: The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel. RESULTS: Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V150 < 45 cc, and V200 < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected. CONCLUSIONS: IMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB.

Current Treatment of Metastatic Spine Tumors - Surgery and Stereotactic Radiosurgery.

There has been significant progress and innovation in the treatment of patients with metastatic spinal tumors over the last two to three decades that has impacted our ability to provide individualized care that improves a patient's quality of life and degree of neurologic impairment. Advances in surgical techniques and radiation delivery modalities have dramatically improved our ability to decrease local tumor recurrence rates, improve pain control, and provide more durable spinal stability. Modern day spine tumor resection and reconstruction techniques have been shown to improve and prolong patients' ability to ambulate, maintain continence, and reduce the need for pain medications. Spinal radiosurgery, the focused delivery of radiation to a target in the spine, has significantly enhanced the ability to provide a high degree of local tumor control in a non-invasive manner, even for tumors that are deemed radioresistant by conventional radiation therapy standards. In most patients, a combination of treatment modalities, including both surgery and radiation, is the mainstay of any comprehensive treatment plan for metastatic spinal tumors. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].