Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or ß-Sheet Conformations on Time of SIVmac251 Acquisition.

The monoclonal antibodies (MAbs) NCI05 and NCI09, isolated from a vaccinated macaque that was protected from multiple simian immunodeficiency virus (SIV) challenges, both target an overlapping, conformationally dynamic epitope in SIV envelope variable region 2 (V2). Here, we show that NCI05 recognizes a CH59-like coil/helical epitope, whereas NCI09 recognizes a ß-hairpin linear epitope. In vitro, NCI05 and, to a lesser extent, NCI09 mediate the killing of SIV-infected cells in a CD4-dependent manner. Compared to NCI05, NCI09 mediates higher titers of antibody-dependent cellular cytotoxicity (ADCC) to gp120-coated cells, as well as higher levels of trogocytosis, a monocyte function that contributes to immune evasion. We also found that passive administration of NCI05 or NCI09 to macaques did not affect the risk of SIVmac251 acquisition compared to controls, demonstrating that these anti-V2 antibodies alone are not protective. However, NCI05 but not NCI09 mucosal levels strongly correlated with delayed SIVmac251 acquisition, and functional and structural data suggest that NCI05 targets a transient state of the viral spike apex that is partially opened, compared to its prefusion-closed conformation. IMPORTANCE Studies suggest that the protection against SIV/simian-human immunodeficiency virus (SHIV) acquisition afforded by the SIV/HIV V1 deletion-containing envelope immunogens, delivered by the DNA/ALVAC vaccine platform, requires multiple innate and adaptive host responses. Anti-inflammatory macrophages and tolerogenic dendritic cells (DC-10), together with CD14+ efferocytes, are consistently found to correlate with a vaccine-induced decrease in the risk of SIV/SHIV acquisition. Similarly, V2-specific antibody responses mediating ADCC, Th1 and Th2 cells expressing no or low levels of CCR5, and envelope-specific NKp44+ cells producing interleukin 17 (IL-17) also are reproducible correlates of decreased risk of virus acquisition. We focused on the function and the antiviral potential of two monoclonal antibodies (NCI05 and NCI09) isolated from vaccinated animals that differ in antiviral function in vitro and recognize V2 in a linear (NCI09) or coil/helical (NCI05) conformation. We demonstrate that NCI05, but not NCI09, delays SIVmac251 acquisition, highlighting the complexity of antibody responses to V2.

Ultra-Short Fraction Schedules as Part of De-intensification Strategies for Early-Stage Breast Cancer.

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.

Outcomes with Partial Breast Irradiation vs. Whole Breast Irradiation: a Meta-Analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adjuvant Radiotherapy in Early-Stage Breast Cancer: Evidence-Based Options.

BACKGROUND: Patients with a diagnosis of early-stage breast cancer are offered the option of either mastectomy or breast-conserving therapy (BCT) secondary to multiple randomized trials demonstrating equivalent long-term outcomes. Traditionally, BCT has used standard whole-breast irradiation (SWBI) after breast-conserving surgery, although several alternatives have emerged during the past few decades. METHODS: This report reviews key studies supporting each radiation technique and its respective eligibility criteria to assist clinicians in deciding which adjuvant radiotherapy options are appropriate for their patients. RESULTS: In the past, completion of SWBI required 5-7 weeks of daily treatments. During the past two decades, alternatives to SWBI have emerged including hypofractionated whole-breast irradiation (3-4 weeks), accelerated partial-breast irradiation (1-3 weeks), and endocrine therapy alone. Multiple randomized trials have established the equivalence of these alternative strategies to SWBI for appropriately selected patients. Additionally, the current guidelines for patient selection demonstrate a large amount of overlap in the selection criteria for each technique. CONCLUSION: Clinicians must evaluate patient and pathologic criteria and engage in informed discussions with patients when determining which adjuvant radiation techniques are appropriate. Future strategies being explored include using tumor genetics to identify low-risk patients and switching from paradigms that omit radiotherapy to those that omit endocrine therapy.

Patterns of care of radiation therapy in patients with stage IV rectal cancer: a Surveillance, Epidemiology, and End Results analysis of patients from 2004 to 2009.

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 < .001) and between those with N0 disease versus N1/N2 disease (P < .001). The 2-year and 5-year survival rates differed between treatment groups, with the highest survival rates observed among those who received combined surgery and RT. CONCLUSIONS: The primary treatments for patients with mRC include RT with or without surgery. RT is used more commonly in patients with primary rectal (vs rectosigmoid) tumors, N0 disease, or Tis-T2 tumors. Treatment with combination surgery and RT is associated with prolonged survival.

Intraoperative radiation therapy: a critical analysis of the ELIOT and TARGIT trials. Part 2--TARGIT.

BACKGROUND: Two randomized intraoperative radiation therapy trials for early-stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. METHODS: The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. RESULTS: With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus EBRT patients were 4.4 and 0.4 %, respectively, p = 0.0001. A low-risk ELIOT group was identified with a 5-year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 and 1.3 %, respectively, p = 0.042. CONCLUSIONS: With 5.8 years of median follow-up, IOERT appears to have a subset of low risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols.

Intraoperative radiation therapy: a critical analysis of the ELIOT and TARGIT trials. Part 1--ELIOT.

INTRODUCTION: Two randomized intraoperative radiation therapy trials for early-stage breast cancer were recently published. The ELIOT Trial used electrons (IOERT), and the TARGIT-A Trial Update used 50-kV X-rays (IORT). These studies were compared for similarities and differences. The results were analyzed and used to determine which patients might be suitable for single-dose treatment. METHOD: The primary sources of data were the ELIOT Trial and TARGIT-A Trial, as well as a comprehensive analysis of the peer-reviewed literature of accelerated partial breast irradiation (APBI) using 50-kV X-rays or electrons. Studies published or presented prior to March 2014 were analyzed for efficacy, patient restrictions, complications, and outcome. RESULTS: With a median follow-up of 5.8 years, the 5-year recurrence rates for ELIOT versus external beam radiation therapy (EBRT) patients were 4.4 % and 0.4 %, respectively, p = .0001. A low-risk ELIOT group was identified with a 5-year recurrence rate of 1.5 %. With a median follow-up of 29 months, the 5-year recurrence rates for the TARGIT-A versus EBRT patients were 3.3 % and 1.3 %, respectively, p = .042. CONCLUSION: With 5.8 years of median follow-up, IOERT appears to have a subset of low-risk women for whom IOERT is acceptable. With 29 months of median follow-up the results of IORT with 50-kV devices are promising, but longer follow-up data are required. At the current time, single-fraction IOERT or IORT patients should be treated under strict institutional protocols.

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.

Breast brachytherapy: Building a bright future on the foundation of a rich history of advancement in technology, technique, and patient-centered care.

For over 20 years, the concept of accelerated partial breast irradiation (APBI) has received considerable attention. Initially concentrating on the appropriateness of APBI as an alternative treatment to whole breast radiotherapy, investigation and innovation evolved towards dose delivery and technique appropriateness. The purpose of this article is to review the pertinent literature that supports the role brachytherapy serves in delivering APBI and the recognized brachytherapy techniques for dose delivery. Publications establishing techniques utilizing multicatheter brachytherapy, single-entry brachytherapy applicators, permanent breast seed implantation brachytherapy, noninvasive breast brachytherapy and electronic brachytherapy are described. The use of brachytherapy for repeat breast conservation therapy is additionally reviewed. A historical perspective and potential direction of future investigation and innovation are presented.

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.

HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.

Elicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability.

Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases.

Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these trimers from their native membrane-bound context. To assess whether glycosylation could limit these base responses, we introduced sequons encoding potential N-linked glycosylation sites (PNGSs) into base-proximal regions. Expression and antigenic analyses indicated trimers bearing six-introduced PNGSs to have reduced base recognition. Cryo-EM analysis revealed trimers with introduced PNGSs to be prone to disassembly and introduced PNGS to be disordered. Protein-base and glycan-base trimers induced reciprocally symmetric ELISA responses, in which only a small fraction of the antibody response to glycan-base trimers recognized protein-base trimers and vice versa. EM polyclonal epitope mapping revealed glycan-base trimers -even those that were stable biochemically- to elicit antibodies that recognized disassembled trimers. Introduced glycans can thus mask the protein base but their introduction may yield neo-epitopes that dominate the immune response.

Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy.

BACKGROUND: To assess the potential mechanisms that may underlie increased local failure in triple negative (TN) breast cancers, an analysis was performed of the risk of residual carcinoma after lumpectomy with correlation to pathologic factors, including molecular phenotype. METHODS: A review of pathologic specimens was performed for women with invasive breast cancer treated with lumpectomy followed by reexcision. Data were collected on age; tumor size, grade, and nodal stage; estrogen receptor, progesterone receptor, and human endothelial growth factor receptor 2 (Her2); extensive intraductal component; lymphovascular invasion; margins; and reexcision findings. Univariate and multivariate logistic regression analyses were performed to evaluate for associations between pathologic features of the lumpectomy specimen and reexcision findings. Molecular phenotypes were defined by conventionally used immunohistochemical pattern. RESULTS: Data were collected on 369 patients with breast cancer. The median age was 57 years, median tumor size was 1.5 cm, 36% had positive margins, 32% had positive lymph nodes, 73.5% had the luminal A subtype, 9.5% had the luminal B subtype, 4.5% were Her2-enriched, and 12.5% were TN. Overall, 32% of patients had invasive cancer in their reexcision specimens, and 51% of those with the TN subtype had residual invasive disease on reexcision compared with 30% to 31% for other subtypes. On univariate analysis, age, tumor size, margin status, lymphovascular invasion, nodal status, and TN subtype were associated with elevated risk of residual invasive cancer. On multivariate analysis using a forward stepwise model, TN subtype maintained significance, with an odds ratio of 3.28 (P = .002). CONCLUSION: TN subtype has a statistically significant association with an increased risk of residual tumor. This suggests the putative increase in the risk of local failure in TN patients may be related to increased residual tumor burden.

Adjuvant therapy of pancreatic cancer.

Adjuvant therapy for pancreatic cancer remains controversial. However, both sides of the Atlantic Ocean agree that at least gemcitabine should be the pivotal agent offered to all patients. The role of radiation therapy remains somewhat inconclusive but chemoradiation, whether in the neoadjuvant or adjuvant setting is a standard option often utilized in the USA. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago, IL, USA. We present the summary of the findings from Abstracts #4020, #4021, #4040 and #4049 and discuss the impact on this group of patients. 

New tools and novel approaches in treating locally advanced pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is one of the most aggressive malignant tumors and represents the fourth leading cause of cancer-related death. The median survival of locally advanced pancreatic carcinoma is ten to thirteen months. In this year's American Society of Clinical Oncology (ASCO) Annual Meeting, several studies were presented with novel approaches towards treating locally advanced pancreatic cancer. Wild et al. (Abstract #4055) explored a novel tool of selective delivery of TNF-alpha intratumoral injection. This approach limited the systemic toxicity, and suggested survival benefit in only the subgroup of patients with locally advanced pancreatic adenocarcinoma with stage T1-T3. Two studies were presented which were designed to assess the use of two novel agents, targeting signaling pathways, in addition to gemcitabine. Van Laethem et al. (Abstract #4050) are testing the MEK inhibitor, BAY 86-9766 in combination with gemcitabine. However, treatment related toxicity is still of concern. In the other study, Evans et al. (Abstract #TPS4134) are testing the combination of dasatinib and gemcitabine. This is a placebo-controlled, randomized, double blind phase II study. However, results are not available. Stereotactic body radiotherapy (SBRT) is an emerging technology with the comparative efficacy of single fraction radiotherapy (as is used in radiosurgery) vs. fractionated SBRT still unknown. Herman et al. (Abstract #4045) examined the role of fractionated SBRT in locally advanced pancreatic cancer. The phase II results showed a median overall survival of 15.9 months, suggesting that SBRT may be an emerging tool in the multi-modality treatment of locally advanced pancreatic cancer.

Is kV Intraoperative Radiation Therapy an Acceptable Method for Partial Breast Irradiation?

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.

American Society of Clinical Oncology 2021 Annual Meeting Highlights for Radiation Oncologists.

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.

Disparities in Radiation Therapy: Practice Patterns Analysis of Deep Inspiratory Breath Hold Use in Non-English Speakers.

PURPOSE: Our purpose was to examine current practice patterns in non-English-speaking patients with breast cancer undergoing deep inspiratory breath hold (DIBH). METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Delivery of Adjuvant Radiation in 5 Days or Less After Lumpectomy for Breast Cancer: A Systematic Review.

PURPOSE: Recent data have been published supporting the application of ultrashort radiation therapy (RT) regimens for women with early stage breast cancer after breast conserving surgery. What has remained controversial is whether and how to apply accelerated whole breast irradiation (AWBI) or accelerated partial breast irradiation (APBI) approaches in these patients, as well as the consideration of intraoperative RT (IORT). METHODS AND MATERIALS: We performed a systematic review of the literature searching for randomized and prospective data published evaluating ultrashort RT delivered in 5 days or less with APBI, AWBI, or IORT. RESULTS: We identified 2 randomized studies evaluating AWBI (n = 5,011 patients) with 5 to 10 year follow-up, which supported the use of ultrashort course AWBI compared with hypofractionated whole breast irradiation (WBI). We identified 7 randomized trials evaluating APBI (compared with WBI) in 5 days or less (n = 8528) with numerous (n = 55) prospective studies as well, with the data supporting short course APBI. Finally, we identified 2 randomized trials evaluating IORT; however, both trials demonstrated elevated rates of recurrence with IORT compared with WBI. CONCLUSIONS: The current body of data available for ultrashort adjuvant RT regimens delivered in 5 days or less after breast conserving surgery overwhelmingly support their utilization. Although data for both exist, APBI regimens have, by far, greater numbers of patients and longer follow-up compared with AWBI. Also, given increased rates of recurrence seen with IORT with long-term follow-up, this should not be considered a standard approach at this time.