Imaging research laboratories are rapidly creating machine learning systems that achieve expert human performance using open-source methods and tools. These artificial intelligence systems are being ...developed to improve medical image reconstruction, noise reduction, quality assurance, triage, segmentation, computer-aided detection, computer-aided classification, and radiogenomics. In August 2018, a meeting was held in Bethesda, Maryland, at the National Institutes of Health to discuss the current state of the art and knowledge gaps and to develop a roadmap for future research initiatives. Key research priorities include: 1, new image reconstruction methods that efficiently produce images suitable for human interpretation from source data; 2, automated image labeling and annotation methods, including information extraction from the imaging report, electronic phenotyping, and prospective structured image reporting; 3, new machine learning methods for clinical imaging data, such as tailored, pretrained model architectures, and federated machine learning methods; 4, machine learning methods that can explain the advice they provide to human users (so-called explainable artificial intelligence); and 5, validated methods for image de-identification and data sharing to facilitate wide availability of clinical imaging data sets. This research roadmap is intended to identify and prioritize these needs for academic research laboratories, funding agencies, professional societies, and industry.
Apoptosis ligand 2/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL)-a member of the tumor necrosis factor cytokine family-induces apoptosis by activating the extrinsic pathway ...through the proapoptotic death receptors DR4 and DR5. Recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) has broad potential as a cancer therapy. To the best of our knowledge, this is the first in-human clinical trial to assess the safety, tolerability, pharmacokinetics, and antitumor activity of multiple intravenous doses of rhApo2L/TRAIL in patients with advanced cancer.
This phase I, open-label, dose-escalation study treated patients with advanced cancer with rhApo2L/TRAIL doses ranging from 0.5 to 30 mg/kg/d, with parallel dose escalation for patients without liver metastases and with normal liver function (cohort 1) and for patients with liver metastases and normal or mildly abnormal liver function (cohort 2). Doses were given daily for 5 days, with cycles repeating every 3 weeks. Assessments included adverse events (AEs), laboratory tests, pharmacokinetics, and imaging to evaluate antitumor activity.
Seventy-one patients received a mean of 18.3 doses; seven patients completed all eight treatment cycles. The AE profile of rhApo2L/TRAIL was similar in cohorts 1 and 2. The most common AEs were fatigue (38%), nausea (28%), vomiting (23%), fever (23%), anemia (18%), and constipation (18%). Liver enzyme elevations were concurrent with progressive metastatic liver disease. Two patients with sarcoma (synovial and undifferentiated) experienced serious AEs associated with rapid tumor necrosis. Two patients with chondrosarcoma experienced durable partial responses to rhApo2L/TRAIL.
At the tested schedule and dose range, rhApo2L/TRAIL was safe and well tolerated. Dose escalation achieved peak rhApo2L/TRAIL serum concentrations equivalent to those associated with preclinical antitumor efficacy.
To endorse the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline on adjuvant and salvage radiotherapy after prostatectomy. The American Society of ...Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations.
The guideline on adjuvant and salvage radiotherapy after prostatectomy was reviewed for developmental rigor by methodologists. An ASCO endorsement panel then reviewed the content and recommendations.
The panel determined that the guideline recommendations on adjuvant and salvage radiotherapy after prostatectomy, published in August 2013, are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the guideline on adjuvant and salvage radiotherapy after prostatectomy, adding one qualifying statement that not all candidates for adjuvant or salvage radiotherapy have the same risk of recurrence or disease progression, and thus, risk-benefit ratios are not the same for all men. Those at the highest risk for recurrence after radical prostatectomy include men with seminal vesicle invasion, Gleason score 8 to 10, extensive positive margins, and detectable postoperative prostate-specific antigen (PSA).
Physicians should discuss adjuvant radiotherapy with patients with adverse pathologic findings at prostatectomy (ie, seminal vesicle invasion, positive surgical margins, extraprostatic extension) and salvage radiotherapy with patients with PSA or local recurrence after prostatectomy. The discussion of radiotherapy should include possible short- and long-term adverse effects and potential benefits. The decision to administer radiotherapy should be made by the patient and multidisciplinary treatment team, keeping in mind that not all men are at equal risk of recurrence or clinically meaningful disease progression. Thus, the risk-benefit ratio will differ for each patient.
Pertuzumab, a recombinant humanized monoclonal antibody (2C4), binds to extracellular domain II of the HER-2 receptor and blocks its ability to dimerize with other HER receptors. Pertuzumab ...represents a new class of targeted therapeutics known as HER dimerization inhibitors. A clinical study was conducted to investigate safety and pharmacokinetics of pertuzumab and to perform a preliminary assessment of HER dimerization inhibition as a treatment strategy.
Patients with incurable, locally advanced, recurrent or metastatic solid tumors that had progressed during or after standard therapy were recruited to a dose-escalation study of pertuzumab (0.5 to 15 mg/kg) given intravenously every 3 weeks.
Twenty-one patients received pertuzumab and 19 completed at least two cycles. Pertuzumab was well tolerated. Overall, 365 adverse events were reported and 122 considered to be possibly drug related. Of these, 116 were of grade 1 to 2 intensity. The pharmacokinetics of pertuzumab were similar to other humanized immunoglobulin G antibodies, supporting a 3-week dosing regimen. Trough plasma concentrations were in excess of target concentrations at doses greater than 5 mg/kg. Two patients, one with ovarian cancer (5.0 mg/kg) and one with pancreatic islet cell carcinoma (15.0 mg/kg), achieved a partial response. Responses were documented by Response Evaluation Criteria in Solid Tumors after 1.5 and 6 months of pertuzumab therapy, and lasted for 11 and 10 months, respectively. Stable disease lasting for more than 2.5 months (range, 2.6 to 5.5 months) was observed in six patients.
These results demonstrate that pertuzumab is well tolerated, has a pharmacokinetic profile which supports 3-week dosing, and is clinically active, suggesting that inhibition of dimerization may be an effective anticancer strategy.
The aims were to assess the safety, pharmacokinetics, maximum tolerated dose, and antitumor activity of AMG 102, a fully human hepatocyte growth factor/scatter factor (HGF/SF)-neutralizing monoclonal ...antibody, in patients with solid tumors.
Patients (N = 40) with refractory advanced solid tumors were enrolled into six sequential dose-escalation cohorts (0.5, 1, 3, 5, 10, or 20 mg/kg AMG 102 i.v. every 2 weeks) and a dose-expansion cohort (20 mg/kg AMG 102 every 2 weeks). Safety, anti-AMG 102 antibody formation, pharmacokinetics, tumor response, and exploratory biomarkers were assessed.
AMG 102 was well tolerated up to the planned maximum dose of 20 mg/kg, and the maximum tolerated dose was not reached. Treatment-related adverse events were generally mild and included fatigue (13%), constipation (8%), nausea (8%), vomiting (5%), anorexia (5%), myalgia (5%), and hypertension (5%). Two patients experienced dose-limiting toxicities: one patient (0.5 mg/kg cohort) experienced grade 3 hypoxia and grade 3 dyspnea and one patient (1 mg/kg cohort) experienced grade 3 upper gastrointestinal hemorrhage. No anti-AMG 102 antibodies were detected, and AMG 102 had linear pharmacokinetics within the dose range investigated. Sixteen of 23 (70%) evaluable patients had a best response of stable disease with progression-free survival ranging from 7.9 to 40 weeks. Circulating levels of the biomarker HGF/SF (bound and unbound) increased in a dose-dependent manner, whereas soluble c-Met concentrations were generally similar across doses.
AMG 102 is safe and well tolerated, has a favorable pharmacokinetic profile, and will be further investigated as a monotherapy and in combination with other agents.
Artificial intelligence (AI) has been implemented in multiple fields of medicine to assist in the diagnosis and treatment of patients. AI implementation in radiology, more specifically for breast ...imaging, has advanced considerably. Breast cancer is one of the most important causes of cancer mortality among women, and there has been increased attention towards creating more efficacious methods for breast cancer detection utilizing AI to improve radiologist accuracy and efficiency to meet the increasing demand of our patients. AI can be applied to imaging studies to improve image quality, increase interpretation accuracy, and improve time efficiency and cost efficiency. AI applied to mammography, ultrasound, and MRI allows for improved cancer detection and diagnosis while decreasing intra- and interobserver variability. The synergistic effect between a radiologist and AI has the potential to improve patient care in underserved populations with the intention of providing quality and equitable care for all. Additionally, AI has allowed for improved risk stratification. Further, AI application can have treatment implications as well by identifying upstage risk of ductal carcinoma in situ (DCIS) to invasive carcinoma and by better predicting individualized patient response to neoadjuvant chemotherapy. AI has potential for advancement in pre-operative 3-dimensional models of the breast as well as improved viability of reconstructive grafts.
Interoperability is a major focus of the quickly evolving world of Health IT. Easy, yet secure and confidential exchange of imaging exams and the associated reports must be a part of the solutions ...that are implemented. The availability of historical exams is essential in providing a quality interpretation and reducing inappropriate utilization of imaging services. Today, the exchange of imaging exams is most often achieved via a compact disc. We describe the virtues of this solution as well as challenges that have surfaced. Internet- and cloud-based technologies employed for many consumer services can provide a better solution. Vendors are making these solutions available. Standards for Internet-based exchange are emerging. Just as radiology converged on DICOM as a standard to store and view images, we need a common exchange standard. We will review the existing standards and how they are organized into useful workflows through Integrating the Healthcare Enterprise profiles. Integrating the Healthcare Enterprise and standards development processes are discussed. Health care and the domain of radiology must stay current with quickly evolving Internet standards. The successful use of the "cloud" will depend on both the technologies and the policies put into place around them, both of which we discuss. The radiology community must lead the way and provide a solution that works for radiologists and clinicians with use of the electronic medical record. We describe features we believe radiologists should consider when adding Internet-based exchange solutions to their practice.
To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and ...timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease.
An expert panel and writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature was performed, which included a search of online databases, bibliographic review, and consultation with content experts. A priori criteria were used to select studies for analysis and study authors were contacted when necessary.
There were 10 randomized controlled trials, six systematic reviews, and one Markov model available to inform the guidelines.
A full discussion between practitioner and patient should occur to determine which therapy is best for the patient. Bilateral orchiectomy or luteinizing hormone releasing hormone agonists are the recommended initial treatments. Nonsteroidal antiandrogen therapy may be discussed as an alternative, but steroidal antiandrogens should not be offered as monotherapy. Patients willing to accept the increased toxicity of combined androgen blockage for a small benefit in survival should be offered nonsteroidal antiandrogen in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.
Emerging SARS-CoV-2 variants may threaten global vaccination efforts and the awaited reduction in outbreak burden. In this study, we report a novel variant carrying the L452R mutation that emerged ...from a local B.1.362 lineage, B.1.362+L452R. The L452R mutation is associated with the Delta and Epsilon variants and was shown to cause increased infection and reduction in neutralization in pseudoviruses. Indeed, the B.1.362+L452R variant demonstrated a X4-fold reduction in neutralization capacity of sera from BNT162b2-vaccinated individuals compared to a wild-type strain. The variant infected 270 individuals in Israel between December 2020 and March 2021, until diminishing due to the gain in dominance of the Alpha variant in February 2021. This study demonstrates an independent, local emergence of a variant carrying a critical mutation, L452R, which may have the potential of becoming a variant of concern and emphasizes the importance of routine surveillance and detection of novel variants among efforts undertaken to prevent further disease spread.
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