Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.

An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID] ∼100) on a 208-strain panel.

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 -linked glycosylation sites (PNGSs) into base-proximal regions. Expression and antigenic analyses indicated trimers bearing six-introduced PNGSs to have reduced base recognition.

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.

Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV 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 β-hairpin linear epitope. , NCI05 and, to a lesser extent, NCI09 mediate the killing of SIV-infected cells in a CD4-dependent manner.

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.

Partial breast irradiation: An updated consensus statement from the American brachytherapy society.

Purpose: In recent years, results with mature follow-up have been reported for several Phase III trials randomizing women to receive whole breast irradiation (WBI) versus varying modalities of partial breast irradiation (PBI). It is important to recognize that these methods vary in terms of volume of breast tissue treated, dose per fraction, and duration of therapy. As such, clinical and technical guidelines may vary among the various PBI techniques.

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.

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.

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.

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

Purpose: Renovation of the brachytherapy program at a leading cancer center utilized methods of the AAPM TG-100 report to objectively evaluate current clinical brachytherapy workflows and develop techniques for minimizing the risk of failures, increasing efficiency, and consequently providing opportunities for improved treatment quality. The TG-100 report guides evaluation of clinical workflows with recommendations for identifying potential failure modes (FM) and scoring them from the perspective of their occurrence frequency O, failure severity S, and inability to detect them D. The current study assessed the impact of differing methods to determine the risk priority number (RPN) beyond simple multiplication.

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

Purpose: The noninvasive image-guided breast brachytherapy (NIBB) technique is a novel noninvasive yet targeted method for accelerated partial breast irradiation. We established a multi-institutional registry to evaluate the toxicity and efficacy of this technique across various practice settings.

Methods And Materials: Institutions using the NIBB technique were invited to participate.

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.

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.

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

Purpose: Mammographically based noninvasive image-guided breast brachytherapy (NIBB) partial breast irradiation (PBI) is ideally suited for preoperative treatment. We hypothesize that delivering NIBB PBI to the preoperative tumor volume compared with the postoperative lumpectomy bed would simplify target identification and allow for a reduction in irradiated volume along each orthogonal axis.

Methods And Materials: Patients with invasive breast cancer treated with NIBB PBI at our institution were identified.

Update on Partial Breast Irradiation.

For early-stage breast cancer, partial breast irradiation (PBI) allows for reduction in the irradiated volume of normal tissues by confining the radiation target to the area surrounding the lumpectomy cavity after breast-conserving surgery. This approach has been supported by phase 2 data. However, widespread adoption of PBI has awaited the results of randomized controlled trials.

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

Purpose: While the noninvasive breast brachytherapy (NIBB) treatment procedure, known as AccuBoost, for breast cancer patients is well established, the treatment quality can be improved by the efficiency of the workflow delivery. A formalized approach evaluated the current workflow through failure modes and effects analysis and generated insight for developing new procedural workflow techniques to improve the clinical treatment process.

Methods And Materials: AccuBoost treatments were observed for several months while gathering details on the multidisciplinary workflow.

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

Purpose: To evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients.

Patients And Methods: All patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets).

Three-Dimensional Bioabsorbable Tissue Marker Placement is Associated with Decreased Tumor Bed Volume Among Patients Receiving Radiation Therapy for Breast Cancer.

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.