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Supplementary Figure 3 from Alterations of the HBP1 Transcriptional Repressor Are Associated with Invasive Breast Cancer

Invasive breast cancer has a high risk of recurrence to incurable disease and needs improved prognostic and therapeutic tools. Our work combines clinical and molecular analyses to show that the transcriptional repressor HBP1 may be a new target for invasive breast cancer. Previous work indicated that HBP1 regulated proliferation and senescence and inhibited Wnt signaling. Two of these functions have been associated with invasive breast cancer. In 76 breast tumors, we identified 10 HBP1 mutations/variants that were associated with fully invasive breast cancer. In a separate analysis, we found that a subset of invasive breast cancer specimens also had reduced HBP1 mRNA levels. These clinical correlations suggested that mutation or reduction of HBP1 occurs in invasive breast cancer and that HBP1 might regulate the proliferation and invasiveness of this breast cancer type. Analysis of the HBP1 mutants showed they were functionally defective for suppressing Wnt signaling. To test the consequences of reduced HBP1 levels, we used RNA interference to knock down HBP1 and observed increased Wnt signaling, tumorigenic proliferation, and invasiveness in cell and animal breast cancer models. Lastly, statistical analysis of a breast cancer patient database linked reduced HBP1 expression to breast cancer recurrence. In considering two-gene criteria for relapse potential, reduced expression of HBP1 and SFRP1, which is another Wnt inhibitor that was recently linked to invasive breast cancer, strikingly correlated with recurrence. Together, these data indicate that HBP1 may be a molecularly and clinically relevant regulator of breast cancer transitions that eventually lead to poor prognosis. [Cancer Res 2007;67(13):6136–45]

Supplementary Figure 2 from Alterations of the HBP1 Transcriptional Repressor Are Associated with Invasive Breast Cancer

Supplementary Figure 1 from Alterations of the HBP1 Transcriptional Repressor Are Associated with Invasive Breast Cancer

Supplementary Table 1 from Alterations of the HBP1 Transcriptional Repressor Are Associated with Invasive Breast Cancer

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.

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.

Adjuvant radiation therapy (RT) following breast-conserving surgery (BCS) represents a standard approach for most patients treated with breast-conserving therapy (BCT) for early-stage breast cancer. The first-generation of adjuvant RT schedules delivered daily treatment to the whole breast over 5–7 weeks. Although efficacious, this presented patients with a protracted course of treatment, reducing compliance and quality of life. While hypofractionated whole-breast irradiation (WBI) has become the standard, and part of the second-generation of RT regimens, it still requires 3–4 weeks. Concurrently, partial-breast irradiation (PBI) has also been explored as a technique to complete RT in a much shorter time period (1–3 weeks). There are now seven trials confirming the efficacy of this shorter treatment approach compared with standard WBI. In an effort to further reduce treatment duration, ultra-short WBI and PBI regimens have recently emerged as the third-generation of breast radiation schedules, allowing for the completion of treatment in 5 days or less. With respect to WBI, recent data from the FAST-Forward trial (which evaluated five fractions of WBI delivered in 1 week) demonstrated no difference in clinical outcomes at 5 years, with limited difference in toxicity, compared with hypofractionated 3-week WBI. Regarding PBI, published data on five-fraction regimens delivered in 2 weeks have also demonstrated comparable outcomes at 10 years, with reduced toxicities with long-term follow-up. This report will review additional ongoing studies evaluating even shorter courses of adjuvant RT treatment (one to five fractions), including single-fraction PBI or WBI.

Several randomized trials have been performed comparing partial breast irradiation (PBI) and whole breast irradiation (WBI) though controversy remains, including regarding differences by PBI technique. We performed a meta-analysis to compare results between WBI versus PBI and between PBI techniques. A systematic review was performed to identify modern randomized studies listed in MEDLINE from 2005 to 2020. PBI trials were divided into external beam radiation and brachytherapy techniques, with intraoperative radiation excluded. A Bayesian logistic regression model evaluated the risk of ipsilateral breast tumor recurrence (IBTR) and acute and chronic toxicities. The primary outcome was IBTR at 5 years with WBI compared with PBI. A total of 9758 patients from 7 studies were included (4840-WBI, 4918-PBI). At 5 years, no statistically significant difference in the rate of IBTR was noted between PBI (1.8%, 95% HPD 0.68–3.2%) and WBI (1.7%, 95% HPD 0.92–2.4%). By PBI technique, the 5-year rate of IBTR rate for external beam was 1.7% and 2.2% for brachytherapy. Rates of grade 2 + acute toxicity were 7.1% with PBI versus 47.5% with WBI. For late toxicities, grade 2/3 rates were 0%/0% with PBI compared with 1.0%/0% with WBI. IBTR rates were similar between PBI and WBI with no significant differences noted by PBI technique; PBI had reduced acute toxicities compared to WBI. Because studies did not provide toxicity data in a consistent fashion, definitive conclusions cannot be made with additional data from randomized trials needed to compare toxicity profiles between PBI techniques.

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).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.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 of7 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%).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.

The annual meeting of the American Society of Clinical Oncology is the largest multidisciplinary oncology-focused conference in the world. With more than 4900 total abstracts in 2021 alone, it is difficult for individuals to evaluate all the results. This article presents a review of 32 selected abstracts across all disease sites, focusing on those of greatest relevance to radiation oncologists.

Our purpose was to examine current practice patterns in non-English-speaking patients with breast cancer undergoing deep inspiratory breath hold (DIBH).An anonymous, voluntary REDCap survey was distributed to 60 residency program coordinators of US radiation oncology departments to survey their faculty and recent graduates. Eligibility was limited to board-certified radiation oncologists who had treated breast cancer within the prior 6 months.There were 69 respondents, 53 of whom were eligible. Forty-two percent (n = 22) of eligible respondents were from the main site at an academic center, with 28% (n = 15) representing a satellite site and 30% (n = 16) from private practice. Fifty-three percent reported at least 10% of their patients were non-English speaking. Ninety percent offered DIBH at their institution; of those, 74% used DIBH for at least one-fourth of their patients with breast cancer. Ninety-eight percent of those who use DIBH performed coaching at simulation, with 32% answering they would be "less likely" to use DIBH for non-English speakers. When used, 94% take into consideration potential language barriers for proper execution of DIBH. However, 51% had an interpreter present 76% to 100% of the time at computed tomography simulation, which decreased to 31% at first fraction and 11% at subsequent treatments. For non-English-speaking patients undergoing DIBH coaching without a certified interpreter, 55% of respondents indicated that they provided verbal coaching in English, 32% indicated "not applicable" because they always use a certified interpreter, 11% used visual aids, and 32% indicated "other." Of those who answered "other," the most commonly cited response was using therapists or staff who spoke the patient's native language.Disparities in the application of DIBH exist despite its established utility in reducing cardiac dose. This study provides evidence that language barriers may affect physician treatment practices from initial consideration of DIBH to subsequent delivery. These data suggest that breast cancer treatment considerations and subsequent execution are negatively affected in non-English-speaking patients.

Purpose BioZorb® (Focal Therapeutics, Aliso Viejo, CA) is an implantable 3-dimensional bioabsorbable marker used for tumor bed volume (TBV) identification during postoperative radiation therapy (RT) planning. We aimed to calculate and compare RT TBVs between two cohorts managed with and without the device. Methods and Materials Data from patients with breast cancer who were treated at Rhode Island Hosptial, Providence RI between May 1, 2015 and April 30, 2016 were retrospectively reviewed and grouped based on 3-dimensional bioabsorbable marker placement. Pathology reports were used to calculate tumor excision volume (TEV) after breast conservation. Specifically, the three dimensions provided were multiplied to generate a cubic volume, defined as TEV. TBV was calculated using treatment volumes generated with Philips Pinnacle3 treatment planning software (Andover, MA). Linear regression analyses assessed the relationship between excised TEV and TBV. T tests compared the slopes of the best fit lines for plots of TEV versus TBV. Results In this retrospective case-control study, 116 patients undergoing breast RT were identified; of whom 42 received a 3-dimensional bioabsorbable marker and 74 did not. The mean TEVs were 102.7 cm3 with the device and 103.2 cm3 without the device, and the mean TBVs for the same groups were 27.5 cm3 and 40.1 cm3, respectively. The TBV standard errors for patients who did and did not receive 3-dimensional bioabsorbable markers were 23.739 and 38.685, respectively. The t tests found the slopes of the lines of best fit for these cohorts to be statistically significantly different (P = .001), with smaller TBVs achieved with 3-dimensional bioabsorbable marker placement. Conclusions When comparing TBVs between patients contemporaneously treated with or without a 3-dimensional bioabsorbable marker, device placement was associated with statistically significantly smaller TBVs in the setting of similar TEVs.

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.

Multiple large prospectively randomized trials of postoperative partial breast irradiation (PBI) have established it as a viable alternative to whole-breast irradiation for risk-adapted breast conserving management of early stage disease. An area of controversy remains regarding the relative efficacy, safety, and utility of intraoperative radiation therapy as a PBI technique. This is particularly true regarding the use of a 50 kV x-ray device, whereby the inherent dosimetry of the applicator results in a low dose of radiation to an exceedingly small volume of tissue. A critical analysis of the current clinical data would strongly support the view that intraoperative radiation therapy with a 50 kV x-ray device is associated with inferior outcomes compared with the variety of currently available modalities used for postoperative PBI.

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 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.

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.

OBJECTIVES: Radiation therapy (RT) is often an integral component of postoperative breast cancer management. Three dimensional (3D) bioabsorbable markers have been designed to assist CT-based tumor bed targeting during the RT process. There have been limited reports detailing complications following placement of such devices. This retrospective analysis attempts to identify demographic and treatment characteristics associated with complications after 3D bioabsorbable marker placement in a cohort of breast cancer patients treated at an academic medical center. METHODS: Records of 160 patients receiving a 3D bioabsorbable marker during initial breast surgery for DCIS or breast cancer were reviewed. Ten devices were removed at subsequent re-excision or mastectomy; therefore, 150 patients were ultimately evaluable. Demographic, tumor and operative/treatment characteristics were collected. Variables including body mass index (BMI), diabetes mellitus (DM), smoking, chemotherapy or RT use and excision volume (EV) were analyzed using multivariable logistic regression analysis (MVA). Endpoints included reoperation for wound complications (re-op), receipt of postoperative antibiotics (abx) and clinically palpable 3D bioabsorbable marker. RESULTS: Median follow-up was 8.2 months. Six (6/150, 4%) patients required re-op for wound complications and 5 required 3D bioabsorbable marker removal due to complications. Twenty (20/150, 13.3%) patients received abx for clinically detected postoperative wound infections. At last follow-up, 61 (61/150, 40.6%) patients noted persistent perceived fullness of the device at the lumpectomy site, and the 3D bioabsorbable marker remained palpable by the physician in 95 (95/150, 63.3%) patients. On MVA, DM and larger EV were associated with greater rates of re-op (p=0.020 and 0.012, respectively, Table 1). Mean EV was 279 cc among the re-op cohort and 85.5 cc among the no re-op cohort. DM, receipt of chemotherapy and larger EV were associated with postoperative abx prescription (p=0.005, 0.009 and 0.005, respectively, Table 2). Mean EV was 169.6 cc among those who received abx and 81.5 cc among those who did not. Larger EV was the only statistically significant predictor of a clinically palpable bioabsorbable marker during follow-up (p=0.044). Table 1. Multivariable Analysis: Reoperation for Wound ComplicationsVariablep-valueBMI0.986Diabetes0.020Smoking0.999Excision Volume0.012Chemotherapy0.079Radiation0.113 Table 2. Multivariable Analysis: Prescription of AntibioticsVariablep-valueBMI0.571Diabetes0.005Smoking0.099Excision Volume0.005Chemotherapy0.009Radiation0.958 CONCLUSIONS: Rates of re-op for wound complications (4%) and postoperative infection (13.3%) were higher than expected among this cohort receiving 3D bioabsorbable markers, and were relatively high compared to historical surgical series managed without such devices. The present analysis suggests that those with larger EV, DM or receiving chemotherapy may be at greater risk for post-operative complications when a 3D bioabsorbable marker is placed. These factors should be considered when assessing candidacy for device placement. Citation Format: Foster BC, Graves TA, Taneja C, Wiggins DL, Hepel JT, Wazer DE, Leonard KL. Identifying optimal candidates for three-dimensional bioabsorbable marker placement during breast cancer treatment: Incidence and predictors of postoperative complications [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 P2-12-12.

PURPOSE: To develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer. METHODS AND MATERIALS: Members of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience. RESULTS: Increasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selec- tion for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age ($50 years old), tumor size (#3 cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment. CONCLUSIONS: These guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection. 2013 Published by Elsevier Inc. on behalf of American Brachytherapy Society.

PURPOSE/OBJECTIVE(S) Anxiety during radiation simulation and/or treatments is common in cancer patients and is frequently treated with anxiolytic medications. Specifically, mask anxiety has been documented in patients requiring a thermoplastic mask for immobilization and has the potential to disrupt the safety and efficacy of treatments. We sought to identify factors that predict for anxiolytic requirement (AR) during mask immobilization. MATERIALS/METHODS Patients who received radiation therapy with a thermoplastic mask covering their entire face (including eyes, nose, and mouth) at a single institution from 2019-2020 were identified and charts were retrospectively reviewed. The use of anxiolytic medications during simulation/treatments, possible predictive factors, and absolute number and percentage of missed treatment days were recorded. If patients underwent multiple radiation treatments, only the first was evaluated. Factors analyzed include gender, spoken language, ECOG performance status, smoking history, past psychiatric history (anxiety, depression, panic attacks, dementia, alcohol abuse, claustrophobia, or post-traumatic stress disorder), previous use of anxiety-related medications, treatment site, mask type, treatment modality, and dexamethasone use. Regression analysis using a generalized linear model was used to create predictive models for AR and for missed radiation treatments. RESULTS A total of 250 patients were evaluated, of whom 124 were female and 126 were male. Median age was 63 years and median ECOG performance status was 1. Thirty-nine percent of patients had a history of anxiety, 4% of claustrophobia, 30% of depression, and 41% were previously prescribed at least one outpatient anxiety-related medication. Thirty patients (12%) required an anxiolytic medication during radiation simulation and/or treatments and 67 patients (27%) missed at least one planned treatment fraction. On multivariate analysis, history of anxiety (P = 0.0002, OR = 5.6) and claustrophobia (P = 0.003, OR = 7.7) were independently predictive of AR. Additionally, AR and head and neck treatment site were independently predictive of percentage of missed radiation fractions (P < 0.01) and AR and IMRT were independently predictive of absolute missed radiation fractions (P < 0.01). CONCLUSION History of anxiety and claustrophobia were independently predictive of AR during radiation simulation/treatments with a thermoplastic mask. These factors can be detected in patient charts prior to consultation and therefore have the potential to allow for early identification of individuals who may be at higher risk for anxiety during their radiation experience. Furthermore, patients who required anxiolytics during radiation therapy tended to miss more treatment days, possibly indicating that optimal anxiety management has not yet been achieved.

Purpose/objective(s) Treatment-related lymphopenia may be prognostic for poorer survival in anal squamous cell carcinoma (ASCC). With current randomized trials evaluating the potential role of immunotherapy in localized ASCC, the contribution of host immunity will become increasingly important. We sought to identify clinical, tumor, and dosimetric predictors for severe lymphopenia during chemoradiation (CRT) for ASCC. Materials/methods Patients who underwent CRT for ASCC from 2008-2020 at two Comprehensive Cancer Centers were identified and charts were reviewed. Only those who received 5-fluorouracil and mitomycin C concurrent with IMRT to 50.4-59.4 Gy were included. Lymphopenia was graded per CTCAE v5.0 with absolute lymphocyte count (ALC) nadir Results A total of 119 patients were identified with a median age of 59 years. Forty-seven patients (39%) had T3/4 disease and 57 patients (49%) had node positive disease. Fifty-eight patients (49%) developed grade 4 lymphopenia during CRT or within 1 month of completing treatment. On multivariate analysis pre-treatment ALC (P = 0.006, OR = 0.31), GTVp volume (P = 0.010, OR = 1.23), and iliac crest V40 (P = 0.013, OR = 1.08) were predictive of grade 4 lymphopenia. History of previous malignancy was associated with reduced risk of grade 4 lymphopenia (P = 0.030, OR = 0.04). TPD and PTVtv were not independently predictive of grade 4 lymphopenia, though patients with a higher TPD and smaller PTVtv were significantly more likely to develop grade 4 lymphopenia (P = 0.038) compared to those with both high TPD and PTVtv or both low TPD and PTVtv. Conclusion Severe lymphopenia is common during CRT for ASCC and certain patients are at higher risk for developing this treatment-related toxicity. Pre-treatment lymphocyte count, larger tumor volume, and dose to the iliac crests are each independent predictors of grade 4 lymphopenia. Additionally, closer observation should be employed when treating patients with higher prescription doses and smaller PTV total volumes. With ongoing efforts to incorporate immunotherapy in the treatment of ASCC, using predictors to detect patients at risk for severe lymphopenia will be increasingly important.

Purpose/objective(s) To examine current practice patterns in non-English speaking breast cancer patients undergoing Deep Inspiratory Breath Hold (DIBH). We hypothesize that disparities in DIBH utilization exist between English and non-English speaking patients. Materials/methods An anonymous, voluntary online survey was distributed to residency program coordinators of U.S. radiation oncology departments to survey their faculty and recent graduates. Eligibility was limited to board-certified radiation oncologists who have treated breast cancer within the prior 6 months. Results There were 66 respondents, 50 of whom were eligible. 70% (n = 35) of eligible respondents were from academic sites. Slightly over half (52%) of respondents reported that at least 10% of their patients were non-English speaking. Most offered DIBH at their institution (92%) and of those, 82% of responding radiation oncologists used DIBH for at least a quarter or more of their breast cancer patients. Nearly all of those who use DIBH (98%) used coaching at the time of simulation, with about a third (37%) answering they would be "less likely" to utilize DIBH for non-English speaking patients. If DIBH is used for non-English speaking patients, 86% would take into consideration potential language barriers for proper execution of DIBH. However, slightly over one-half of respondents had an interpreter present 76-100% of the time at CT simulation. At the first DIBH treatment, 31% used an interpreter 76-100% of the time. And at each subsequent treatment, 11% used an interpreter 76-100% of the time. Conclusion Disparities in the application of DIBH exist despite its established utility in reducing cardiac dose. This study provides evidence that language barriers may impact physician treatment practices from initial consideration of DIBH to subsequent delivery. Even within a limited sampling of self-reported responses, this data suggests that breast cancer treatment considerations and subsequent execution are negatively affected in non-English speaking patients.

PURPOSE/OBJECTIVE(S) The accuracy of tumor bed (TB) delineation is essential for targeting boost dose or partial breast irradiation. Surgical clip markers (CM) are standardly used. However, despite using CM, multiple studies have shown high interobserver variability in TB delineation. We hypothesize that a radiopaque filament marker (FM) woven along the TB at the time of lumpectomy will improve accuracy of TB delineation. MATERIALS/METHODS An FDA-approved radiopaque filament was intraoperatively used to outline the tumor bed of patients undergoing lumpectomy. Between January 2020 and September 2020, 10 consecutive patients with the FM and 10 consecutive patients with the standard CM were identified for comparison. Five "experts," defined as board-certified radiation oncologists specializing in breast cancer, independently contoured all 20 tumor beds. Dice coefficients were then calculated for each patient by comparing the intersection and aggregate of each expert's contours with that of the other experts individually. An intersection and aggregate of the contours of all 5 experts was also analyzed for each patient. Dice coefficient of 1 represents perfect contour agreement, and 0 represents no agreement. Two-tailed paired samples t-tests were performed to compare dice coefficients between FM and CM cohorts. Furthermore, the center of mass (COM) coordinates were calculated to analyze the distance of the COM of each expert's contour to that of the aggregate of the other experts' contours for each patient. Two-tailed unpaired samples t-tests were performed to compare COM distances between FM and CM cohorts. RESULTS For FM, mean dice coefficient and standard deviation for each expert was: 0.61 ± 0.09, 0.60 ± 0.10, 0.60 ± 0.10, 0.60 ± 0.09, and 0.55 ± 0.11, respectively. By comparison, for CM, mean dice coefficient and standard deviation for each expert was: 0.48 ± 0.22, 0.42 ± 0.25, 0.47 ± 0.21, 0.47 ± 0.22, and 0.40 ± 0.22, respectively. Thus, TB delineation agreement was significantly improved with FM (P = 0.0013, P = 0.0001, P = 0.0013, P = 0.0006, and P = 0.0008, respectively). Furthermore, the COM distance of each expert's contour to that of the aggregate of all experts' contours was significantly reduced (P < 0.001) from a mean of 0.96 cm ± 0.89 cm for CM to 0.25 cm ± 0.19 cm for FM. CONCLUSION Radiopaque filament resulted in significantly improved interobserver variability in tumor bed delineation compared with standard surgical clips. This difference was clinically meaningful with a reduction in mean COM contour disagreement from almost 1cm to 2.5mm, and suggests marked superiority of the radiopaque filament in targeting boost dose and/or partial breast irradiation.

To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB).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.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 to60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to0.75 (0.85 preferred), VIMB 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.

Stereotactic body radiation therapy (SBRT) boost to primary and nodal disease after chemoradiation has potential to improve outcomes for advanced non-small cell lung cancer (NSCLC). A dose escalation study was initiated to evaluate the maximum tolerated dose (MTD).Eligible patients received chemoradiation to a dose of 50.4 Gy in 28 fractions and had primary and nodal volumes appropriate for SBRT boost (120 cc and60 cc, respectively). SBRT was delivered in 2 fractions after chemoradiation. Dose was escalated from 16 to 28 Gy in 2 Gy/fraction increments, resulting in 4 dose cohorts. MTD was defined when ≥2 of 6 patients per cohort experienced any treatment-related grade 3 to 5 toxicity within 4 weeks of treatment or the maximum dose was reached. Late toxicity, disease control, and survival were also evaluated.Twelve patients (3 per dose level) underwent treatment. All treatment plans met predetermined dose-volume constraints. The mean age was 64 years. Most patients had stage III disease (92%) and were medically inoperable (92%). The maximum dose level was reached with no grade 3 to 5 acute toxicities. At a median follow-up time of 16 months, 1-year local-regional control (LRC) was 78%. LRC was 50% at24 Gy and 100% at ≥24 Gy (P=.02). Overall survival at 1 year was 67%. Late toxicity (grade 3-5) was seen in only 1 patient who experienced fatal bronchopulmonary hemorrhage (grade 5). There were no predetermined dose constraints for the proximal bronchial-vascular tree (PBV) in this study. This patient's 4-cc PBV dose was substantially higher than that received by other patients in all 4 cohorts and was associated with the toxicity observed: 20.3 Gy (P.05) and 73.5 Gy (P=.07) for SBRT boost and total treatment, respectively.SBRT boost to both primary and nodal disease after chemoradiation is feasible and well tolerated. Local control rates are encouraging, especially at doses ≥24 Gy in 2 fractions. Toxicity at the PBV is a concern but potentially can be avoided with strict dose-volume constraints.

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.

Purpose To report updated feasibility and reproducibility results for high-dose-rate noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT) in the setting of expanded patient and treatment facility number. Methods and Materials Fifteen independent community-based and academic centers reported 518 early-stage breast cancer patients from July 2007 to February 2015 on a privacy-encrypted online data registry. All patients' treatment included lumpectomy followed by combination of WBRT and NIBB. NIBB was completed with commercially available (AccuBoost, Billerica, MA) mammography-based system using high-dose-rate 192 Ir emissions along orthogonal axes. Harvard scale was used to grade cosmesis. Results Total patient cohort had median followup of 12 months (1–75 months) with subset of 268 having available cosmesis. Greater than 2- and 3-year followup was 29% and 14%, respectively. Entire cohort had 97.4% excellent/good (E/G) breast cosmesis and freedom from recurrence of 97.6% at the final followup. WBRT timing with respect to NIBB delivery demonstrated no statistically significant difference in E/G cosmesis. Achieved E/G cosmesis rate was also not statistically significant ( χ 2 p -value = 0.86) between academic and community institutions with 97.8% vs. 96.6%. Conclusions NIBB represents an alternative method for delivery of breast tumor cavity boost that has shown feasibility in a diverse group of both academic and community-based practices with reproducible early cosmesis and tumor control results. Recommendations are updated noting ideal timing of boost delivery likely to be before or early during WBRT given equal cosmesis and less documented treatment discomfort.

Objective: Our objective was to report safety and efficacy of stereotactic radiosurgery (SRS) to the surgical bed following resection of brain metastases. Methods: Eighty-seven consecutive patients who underwent cavity-directed SRS to the operative bed for the treatment of brain metastases between 2002 and 2010 were evaluated. SRS required a gadolinium-enhanced, high-resolution, T1-weighted magnetic resonance imaging for tumor targeting and delivered a median dose of 18 Gy (14-22 Gy) prescribed to encompass the entire resection cavity. Whole brain irradiation was reserved for salvage. Patients were followed every 3 months with clinical examination and magnetic resonance imaging. Overall survival, local and regional recurrence, and factors affecting these outcomes were evaluated using Kaplan-Meier and log-rank analyses. Results: The median imaging follow-up was 7.1 months, with >40% of patients having imaging for ≥1 year. Local control at 1 and 2 years was 82% and 75%, respectively. Cavity recurrence was more common with a tumor diameter >3 cm (P < .020) or resection cavity volume >14 mL (P 3 cm were 100%, 86%, and 72%, respectively. Neither subtotal resection nor target margins >2 mm to 3 mm affected local control. The median overall survival was 14.3 months with actuarial 5-year survival of 20%. Actuarial regional central nervous system recurrence was 44% at 1 year. On univariate analysis, only the presence of extracranial disease was associated with survival (P < .001) and central nervous system failure (P < .030). Conclusions: Excellent local control is achievable with cavity-directed SRS in well-selected patients, particularly for lesions with diameter

Radiation therapy in combination with surgery, chemotherapy, and endocrine therapy as indicated, has led to excellent local and distant control of early stage breast cancers. With the majority of these patients surviving long term, mitigating the probability and severity of late toxicities is vital. Radiation to the breast, with or without additional fields for nodal coverage, has the potential to negatively impact long term cosmetic outcome of the treated breast as well as cause rare, but severe, complications due to incidental dosage to the heart, lungs and contralateral breast. The long-term clinical side-effects of breast radiation have been studied extensively. This review aims to discuss the risk of developing late complications following breast radiation and how modern techniques can be used to diminish these risks.

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.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.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 (p0.01) and larger applicator size (p0.01). No Grade 3+ late toxicity or local recurrences have been observed at a median followup of 14 months.Accelerated partial breast irradiation delivered using NIBB over five daily fractions is a convenient treatment option that is feasible and well tolerated.

PURPOSE: Noninvasive image-guided breast brachytherapy (NIBB) is an attractive novel approach to deliver accelerated partial breast irradiation (APBI). Calculations of equivalent uniform dose (EUD) were performed to identify the appropriate APBI dose for this technique. METHODS AND MATERIALS: APBI plans were developed for 15 patients: five with three- dimensional conformal APBI (3D-CRT), five with multi-lumen intracavitary balloons (m-IBB), and five simulating NIBB treatment. Prescription doses of 34.0 and 38.5 Gy were delivered in 10 fractions for m-IBB and 3D-CRT, respectively. Prescription doses ranging from 34.0 to 38.5 Gy were considered for NIBB. Dose-volume histogram data from all 3D-CRT, m-IBB, and NIBB plans were used to calculate the biologically effective EUD and corresponding EUD to the PTV_eval using the following equation: EUD 5 EUBED/(n (1 þ EUD/a/b)). An a/b value of 4.6 Gy was assumed for breast tumor. EUD for varying NIBB prescription doses were compared with EUD values for the other APBI techniques. RESULTS: Mean PTV_eval volume was largest for 3D-CRT (372.9 cm 3 ) and was similar for NIBB and m-IBB (88.7 and 87.2 cm 3 , respectively). The EUD value obtained by prescribing 38.5 Gy with 3D-CRT APBI was 38.6 Gy. The EUD value of 34.0 Gy prescribed with m-IBB was 34.4 Gy. EUD values for NIBB ranged from 33.9 to 38.2 Gy for prescription doses ranging from 34.0 to 38.5 Gy. CONCLUSIONS: Using EUD calculations to compare APBI techniques and treatment doses, a prescription dose of 36.0 Gy in 10 fractions using NIBB has a comparable biologic equivalent dose to other established brachytherapy techniques. 2015 American Brachytherapy Society. Published

Stereotactic radiosurgery (SRS) represents a treatment option for patients with brain metastases from small cell lung cancer (SCLC) following prior cranial radiation. Inferior local control has been described. We reviewed our failure patterns following SRS treatment to evaluate this concern.Individuals with SCLC who received SRS for brain metastases from 2004 to 2011 were identified. Central nervous system (CNS) disease was detected and followed by gadolinium-enhanced, high-resolution magnetic resonance (MR) imaging. SRS dose was prescribed to the tumor periphery. Local recurrence was defined by increasing lesion size or enhancement, MR-spectroscopy, and perfusion changes consistent with recurrent disease or pathologic confirmation. Any new enhancing lesion not identified on the SRS planning scan was considered a regional failure. Overall survival (OS) and CNS control were evaluated using the Kaplan-Meier method. Factors predicted to influence outcome were tested by univariate log-rank analysis and Cox regression.Fifteen males and 25 females (median age of 61 years [range, 36-79]) of which 39 received prior brain irradiation were identified. In all, 132 lesions (3.3 per patient) between 0.4 and 4.7 cm received a median dose of 16 Gy (12-22 Gy). Thirteen metastases (10%) ultimately recurred locally with 6- and 12-month control rates of 81% and 69%, respectively. Only 1 of 110 metastases2 cm recurred. Local failure was more likely for size2 cm (P.001) and dose16 Gy (P.001). The median OS was 6.5 months, and the time to regional CNS recurrence was 5.2 months. For patients with single brain metastases, both OS (P = .037) and regional CNS recurrence (P = .003) were improved. CNS control (P = .001), and survival (P = .057), were also longer for patients with controlled systemic disease.Local control following SRS for SCLC metastases is achievable for lesions2 cm. For metastases2 cm, local failure is more common than expected. Patients with controlled systemic disease and limited CNS involvement would benefit most from aggressive treatment.

Introduction Tumor bed boost improves local control and is an important part of breast-conserving therapy. Data on the use of a hypofractioned tumor bed boost are needed. We performed a retrospective analysis of patients treated with hypofractionated whole breast irradiation (WBI) and hypofractionated boost to examine acute and delayed outcomes. Materials and Methods We examined the records of patients treated with hypofractionated WBI and tumor bed boost after lumpectomy for Stage 0 to II breast cancer. Local control, toxicity, and cosmetic outcome were evaluated. Patient, tumor, and treatment characteristics were evaluated including excision volume, surgical technique, surgical complications, chemotherapy, endocrine therapy administration, radiation dose, fractionation, and technique. Results A total of 143 patients received hypofractionated WBI with hypofractionated boost between 2010 and 2015. The median follow-up was 16.8 months. The median patient age was 65 years. Patient stage was 0, I, and II in 25%, 68%, and 7%, respectively. All patients received hypofractionated WBI with 42.5 Gy in 16 fractions. Sixty-one percent of women received a boost regimen of 2.66 Gy/fraction for 3 fractions. Boost techniques included noninvasive breast brachytherapy, electrons, 3-dimensional conformal radiation therapy, or a combination of techniques. Acute skin reaction was grade 1 in 65% and grade 2 in 32%. Good or excellent cosmetic outcome was achieved in 94% of patients. Subcutaneous fibrosis was the most common delayed toxicity in 19%, of which 86% was grade 1. There were no local recurrences. Conclusions Hypofractionated tumor bed boost is well-tolerated with a low rate of toxicity and high rate of good-to-excellent cosmetic outcome.

PURPOSE: Utilization of stereotactic radiosurgery (SRS) for brainstem metastases (BSM) is increasing. Multi-fraction SRS (MF-SRS) is a potential means of obtaining therapeutic gain while limiting toxicity. However, most available data assesses only single-fraction SRS (SF-SRS). This study aims to evaluate the efficacy and safety of SF-SRS and MF-SRS for BSM. METHODS: Data was retrospectively collected for patients with BSM treated with SRS between 2003–2018 at a single institution. Kaplan-Meier method was used to evaluate overall survival (OS) and local control (LC). Independent t-test was used for correlations between groups. RESULTS: 29 patients (31 lesions) were identified; 13 patients (15 lesions) underwent SF-SRS and 16 patients (16 lesions) underwent MF-SRS. Median follow-up was 6.8 months (1–80.8 months). Post-SRS MRI was available for 78% of patients. Median dose was 16Gy (12–18 Gy) for SF-SRS and 24 Gy (18–30 Gy) for MF-SRS. MF-SRS was delivered in a median of 3 fractions (3–5). There was a trend toward larger mean tumor volume with MF-SRS (1.297 vs 0.302mL, p=0.055). OS was 64.8% at 6 months and 49.3% at 12 months. LC was 90.9% at 6 months and 69.9% at 12 months. LC was similar between SF-SRS and MF-SRS at 6 months (100% vs 79.5%, p=0.143) and 12 months (50.0% vs 79.5%, p=0.812). Among the 4 patients who experienced local recurrence, 3 received salvage whole brain radiation and median OS was 8.1 months after LF. Distant CNS failures occurred in 40.3% of patients at 6 months and 72.4% at 12 months. Tumor volume >0.5 mL was associated with worse LC at 6 months (64.3% vs 100%, p=0.022). One patient developed symptomatic radiation necrosis (1/29 lesions, 3.4%) after MF-SRS. CONCLUSION: SRS is a safe and effective treatment for small BSM. Outcomes were not different between SF-SRS and MF-SRS but analysis is limited by small sample size.

Background To compare clinical outcomes and toxicity in patients treated with NIBB boost with those in patients treated with external beam (EB) boost. Patients and Methods Women with early stage breast cancer treated with WBI and NIBB boost were identified. Control subjects treated with EB boost identified as the best possible match with respect to age, stage, chemotherapy use, and fractionation were chosen for a 2:1 comparison. Acute toxicity, late toxicity, and oncologic outcomes were reviewed. The McNemar nonparametric test was used to evaluate marginal homogeneity between matched pairs. Results One hundred forty-one patients were included in the analysis: 47 patients treated with NIBB boost and 94 matched control subjects treated with EB boost (electron, n = 93) or 3-D conformal radiation (n = 1). Grade 2+ desquamation developed in 18 patients (39%) treated with NIBB boost and in 49 patients (52%) treated with EB boost ( P = .07). Breast size, electron energy, and fractionation predicted for acute desquamation ( P P P = .006). Median follow-up was 13.6 months. One patient (2%) who received NIBB had Grade 2+ skin/subcutaneous fibrosis 15 months after completion of treatment. Among those treated with EB, 9 patients (9.5%) developed Grade 2+ subcutaneous fibrosis, and 1 patient had recurrent cellulitis. There was statistically significantly less combined skin/subcutaneous toxicity in those treated with NIBB than in those treated with EB ( P = .046). Conclusion NIBB boost is associated with favorable short-term clinical outcomes compared with EB.

Daniel G. Petereit, Rapid City Regional Cancer Center, Rapid City, SD Steven J. Frank, University of Texas MD Anderson Cancer Center, Houston, TX Akila N. Viswanathan, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Beth Erickson, Medical College of Wisconsin, Milwaukee, WI Patricia Eifel, University of Texas MD Anderson Cancer Center, Houston, TX Paul L. Nguyen, Brigham and Women’s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA David E. Wazer, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, and Rhode Island Hospital, The Alpert Medical School of Brown University, Providence, RI

BACKGROUND According to the 2013 National Comprehensive Cancer Network guidelines, pelvic radiation therapy (RT) is one of the preferred regimens for patients with metastatic rectal cancer (mRC). The objective of this study was to analyze patterns of care and outcomes data for the receipt of RT among patients with mRC using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS Patients with stage IV rectal or rectosigmoid cancer were identified in the SEER database (2004-2009). Patients were stratified according to their primary disease site (rectum vs rectosigmoid), tumor (T) classification, and lymph node (N) classification. Treatment regimens (with or without surgical resection, with or without RT) were recorded. The Fisher exact test was used to compare RT rates based on stratified factors. Two and five-year survival rates were compared among treatment groups. RESULTS In total, 6873 patients with stage IV rectal cancer and 3417 patients with rectosigmoid cancer were identified. Overall, 20.5% of patients with rectal cancer underwent surgery alone, whereas 38.7% received RT with or without surgery. Within the rectosigmoid group, 51.4% of patients underwent surgery alone, and 15.1% received RT with or without surgery. The use of RT differed significantly between patients with in situ (Tis) through T2 tumors versus T3/T4 tumors (P

Object The goal of this study was to evaluate outcomes in patients with ≥ 10 CNS metastases treated with Gamma Knife stereotactic radiosurgery (GK-SRS). Methods Patients with ≥ 10 brain metastases treated using GK-SRS during the period between 2004 and 2010 were identified. Overall survival and local and regional control as well as necrosis rates were determined. The influence of age, sex, histological type, extracranial metastases, whole-brain radiation therapy, and number of brain metastases was analyzed using the Kaplan-Meier method. Univariate (log-rank) analyses were performed, with a p value of < 0.05 considered significant. Results Fifty-three patients with ≥ 10 brain metastases were treated between 2004 and 2010. All had a Karnofsky Performance Status score of ≥ 70. Seventy-two percent had either non–small cell lung cancer (38%) or breast cancer (34%); melanoma, small cell lung cancer, renal cell carcinoma, and testicular, colon, and ovarian cancer contributed the remaining 28%. On average, 10.9 lesions were treated in a single session. Sixty-four percent of patients received prior whole-brain radiation therapy. The median survival was 6.5 months. One-year overall survival was 42% versus 14% when comparing breast cancer and other histological types, respectively (p = 0.074). Age, extracranial metastases, number of brain metastases, and previous CNS radiation therapy were not significant prognostic factors. Although the median time to local failure was not reached, the median time to regional failure was 3 months. Female sex was associated with longer time to regional failure (p = 0.004), as was breast cancer histological type (p = 0.089). No patient experienced symptomatic necrosis. Conclusions Patients with ≥ 10 brain metastases who received prior CNS radiation can safely undergo repeat treatment with GK-SRS. With median survival exceeding 6 months, aggressive local treatment remains an option; however, rapid CNS failure is to be expected. Although numbers are limited, patients with breast cancer represent one group of individuals who would benefit most, with prolonged survival and extended time to CNS recurrence.

PurposeTo develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer.Methods and MaterialsMembers of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience.ResultsIncreasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selection for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age (≥50 years old), tumor size (≤3cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment.ConclusionsThese guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection.

OBJECTIVES Proton therapy (PT) is a potentially promising, but costly, radiation modality. Assessment of such new health technologies is becoming increasingly important in the era of constrained budgets. This study attempts to establish how PT utilization might fit into the existing radiation oncology armamentarium. MATERIALS AND METHODS All patients treated in 2007 with radiation therapy at an academic institution were individually evaluated as potential PT candidates. Seven potential adoption scenarios were developed, ranging from PT being superior (A), to being clinically reasonable with some published evidence (B1-B3), to being clinically appealing but without published evidence (C). Two sensitivity analyses (D and E) were also performed. RESULTS One thousand forty-two patients were treated using 19,749 treatment fractions. PT could be used in 6% of treatment courses and 3% of treatment fractions in scenario A, in 12% and 7% in scenario B1, in 17% and 17% in scenario B2, in 8% and 17% in scenario B3, in 24% and 30% in scenario C, in 37% and 30% in scenario D, and 67% and 79% in scenario E. Introduction of PT would increase treatment delivery cost over baseline by 2%, 2%, 18%, 27%, 45%, 29%, and 141%, respectively. CONCLUSIONS The degree of PT utilization would depend on the strictness of selection criteria, and would likely range from 6% to 25%, with concomitant cost increase from minimal to 40%. Ultimate adoption of PT in the United States may depend on individual facilities and payors performing similar analyses and setting individual adoption criteria.

PURPOSE : The purpose of the study was to identify patient characteristics that predict for increased cardiac exposure through dosimetric analysis of the anatomy of a cohort of women treated with left-sided tangential breast radiation. Statistical analyses estimations for the appropriate sample sizes required for detection of significant differences in cardiac mortality at 15 years were conducted, assuming a threshold V25 for radiation-induced coronary artery disease (CAD) beyond which women are at risk for radiation-induced coronary artery disease. METHODS AND MATERIALS : Detailed heart dosimetry was recorded. Clinical factors (age, history of CAD, diabetes, receipt of cardiotoxic agents, weight/body mass index) and anatomic factors (heart volume, breast volume, cardiac contact distance) were recorded for each patient. RESULTS : The average heart V25 was 3.57%. The median percentage of the heart included in the tangential beam was 4.02%. There were no clinical or anatomic factors that predict suboptimal heart anatomy (ie, V25 of ≥6%) on multivariate analysis. The sample size calculations using thresholds for induction of CAD of V25 ≥1%, 6%, and 10% yielded sample sizes of 1314, 9504, and 61,342, respectively; considering node-positive breast cancer mortality and 15% loss to follow-up, these change to 2237, 16,166, and 104,334, respectively. CONCLUSIONS : Current studies with modern radiotherapy techniques would be underpowered to detect a difference in cardiac mortality where only some women are at risk. The heart, chest wall, and breast have a complex relationship to tangential breast radiation, and their interplay prevented this anatomic metric's success.