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At least 109 records · Page 6

Single- and Multifraction Stereotactic Radiosurgery Dose/Volume Tolerances of the Brain

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy investigating normal tissue complication probability (NTCP) after hypofractionated radiation therapy, data from published reports (PubMed indexed 1995-2018) were pooled to identify dosimetric and clinical predictors of radiation-induced brain toxicity after single-fraction stereotactic radiosurgery (SRS) or fractionated stereotactic radiosurgery (fSRS).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response

Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Research-Driven Radiation Oncology: A Narrative on the Ongoing Legacy of Henry S. Kaplan

In this rapidly evolving time of precision medicine and scientifically based cancer care, how radiation oncology became a strong research-based scientific discipline in the United States after its separation from diagnostic radiology might be lost. The importance of generational mentorship, “family trees,” and interpersonal relationships can be difficult or impossible to trace absent personal narrative recollections of those involved. Henry S. Kaplan is a central figure and the focal point for 3 generations of research-based academic department chairs. This report establishes a first draft of a living record of the radiation oncology history of the Kaplan legacy to serve as an example of how knowledge networks grow and flourish and as an impetus for others to trace the legacy of other radiation oncology academic “trees.”.

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Tumor Control Probability of Radiosurgery and Fractionated Stereotactic Radiosurgery for Brain Metastases

As part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, tumor control probability (TCP) after stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) for brain metastases was modeled based on pooled dosimetric and clinical data from published English-language literature.

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Clinical Natural Language Processing for Radiation Oncology: A Review and Practical Primer

Natural language processing (NLP), which aims to convert human language into expressions that can be analyzed by computers, is one of the most rapidly developing and widely used technologies in the field of artificial intelligence. Natural language processing algorithms convert unstructured free text data into structured data that can be extracted and analyzed at scale. In medicine, this unlocking of the rich, expressive data within clinical free text in electronic medical records will help untap the full potential of big data for research and clinical purposes. Recent major NLP algorithmic advances have significantly improved the performance of these algorithms, leading to a surge in academic and industry interest in developing tools to automate information extraction and phenotyping from clinical texts. Thus, these technologies are poised to transform medical research and alter clinical practices in the future. Radiation oncology stands to benefit from NLP algorithms if they are appropriately developed and deployed, as they may enable advances such as automated inclusion of radiation therapy details into cancer registries, discovery of novel insights about cancer care, and improved patient data curation and presentation at the point of care. However, challenges remain before the full value of NLP is realized, such as the plethora of jargon specific to radiation oncology, nonstandard nomenclature, a lack of publicly available labeled data for model development, and interoperability limitations between radiation oncology data silos. Successful development and implementation of high quality and high value NLP models for radiation oncology will require close collaboration between computer scientists and the radiation oncology community. Here, we present a primer on artificial intelligence algorithms in general and NLP algorithms in particular; provide guidance on how to assess the performance of such algorithms; review prior research on NLP algorithms for oncology; and describe future avenues for NLP in radiation oncology research and clinics.

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Radiation Oncology in the Land of the Pyramids: How Sudan Continues to Push the Frontiers of Cancer Care in Eastern Africa

When faced with illness, Sudanese patients have traditionally relied primarily on folklore healers. In the recent past, Sudan increased its health care spending and placed ever-greater importance on medical education. Although traditional remedies still play an important role, Sudanese patients increasingly consult conventional medicine. Not only infectious diseases but also a rising burden of noncommunicable conditions, including cancer, represent major health care challenges. Therefore, Sudan will need to make the best out of the limited resources available and further increase investment in health care to confront these trends successfully. Sudan was one of the first African countries to recognize the importance of radiation oncology in multidisciplinary cancer care and began investing in it in the 1960s. Today, there are 4 comprehensive cancer centers in the country, which offer radiation therapy and employ 10 radiation therapy machines for a population of about 45 million people. This proportion is an indication that Sudan still has an underfunded health care system with a lack of infrastructure and human resources. The present manuscript intends to provide a well-rounded overview of radiation oncology in Sudan today.

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Poly(lactic- co -glycolic acid) Nanoparticles as Delivery Systems for the Improved Administration of Radiotherapeutic Anticancer Agents

This letter reports the development of poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) as delivery systems that could potentially encapsulate and improve the administration of radiotherapeutic anticancer agents. Different metal ions (Ba, Gd, and Ce) were used as surrogates of α-emitting radionuclides ( 223 Ra, 225 Ac, and 227 Th), and their encapsulation within the PLGA NPs ( D h < 300 nm) was evaluated. The initial concentration of metal ions, the metal salt (nitrate vs chloride), and the presence of chelators influenced the concentration of surrogate ions within the PLGA NPs. This letter shows the potential of PLGA NPs to encapsulate radionuclides, particularly α-emitters, for their application in nuclear medicine.

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The effect of protein mutations on drug binding suggests ensuing personalised drug selection

The advent of personalised medicine promises a deeper understanding of mechanisms and therefore therapies. However, the connection between genomic sequences and clinical treatments is often unclear. We studied 50 breast cancer patients belonging to a population-cohort in the state of Qatar. From Sanger sequencing, we identified several new deleterious mutations in the estrogen receptor 1 gene (ESR1). The effect of these mutations on drug treatment in the protein target encoded by ESR1, namely the estrogen receptor, was achieved via rapid and accurate protein–ligand binding affinity interaction studies which were performed for the selected drugs and the natural ligand estrogen. Four nonsynonymous mutations in the ligand-binding domain were subjected to molecular dynamics simulation using absolute and relative binding free energy methods, leading to the ranking of the efficacy of six selected drugs for patients with the mutations. Our study shows that a personalised clinical decision system can be created by integrating an individual patient’s genomic data at the molecular level within a computational pipeline which ranks the efficacy of binding of particular drugs to variant proteins.

59 BASIC BIOLOGICAL SCIENCES↗

Line curvature algorithm in laser ektacytometry of red blood cells

The iso-intensity line curvature algorithm in laser ektacytometry of red blood cells is investigated by numerical simulation. The algorithm is designed to measure the average deformability, as well as the width and asymmetry of the red blood cell deformability distribution in a blood sample under study. The accuracy and scope of the algorithm are determined. Using a bimodal ensemble as an example, the possibility of determining the fraction of weakly deformable red blood cells in a blood sample by laser ektacytometry is demonstrated. (laser medicine)

60 APPLIED LIFE SCIENCES↗

The Auger Radioisotope Microscope: an instrument for characterization of Auger electron multiplicities and energy distributions

We describe a new instrument, the Argonne Auger Radioisotope Microscope (ARM), capable of characterizing the Auger electron (AE) emission of radionuclides, including candidates relevant in nuclear medicine. Our approach relies on event-by-event ion–electron coincidence, time-of-flight, and spatial readout measurement to determine correlated electron multiplicity and energy distributions of Auger decays. We present a proof-of-principle measurement with the ARM using x-ray photoionization of stable krypton beyond the K-edge and identify a bifurcation in the electron multiplicity distribution depending on the emission of K-LX electrons. Extension of the ARM to the characterization of radioactive sources of AE emissions is enabled by the combination of two recent developments: (1) cryogenic buffer gas beam technology to introduce Auger emitters into the detection region with well-defined initial conditions, and (2) large-area micro-channel plate detectors with multi-hit detection capabilities to simultaneously detect multiple electrons emitted in a single decay.

Auger emitters↗

State-of-the-art γ-ray assay of 86 Y for medical imaging

An emerging direction in nuclear medicine is the coupling of a therapeutic isotope with an imaging isotope to form a so-called theranostic pair, which allows one to quantitatively track and image the delivery of the therapeutic isotope. 90 Y is used in several therapy applications and a convenient candidate imaging partner is the positron emitter 86 Y. A 27.6 MBq source of 86 Y was produced at the University of Wisconsin and assayed with the Gammasphere array at Argonne National Laboratory. Over 200 γ-ray transitions were identified, more than double that which was previously known. In conclusion, the positron emission probability inferred from the present level scheme leads to 27.9(12)%, an important (≈14%) reduction with respect to the previously recommended value.

59 ≤ A ≤ 89↗

Global harmonization of immediate‐release solid oral drug product bioequivalence recommendations and the impact on generic drug development

Immediate-release (IR) solid oral drug products constitute a significant portion of approved drug products and products under development. Bioequivalence (BE) assessment for these oral products is important for establishing therapeutic equivalence for generic products to their respective comparator products. In December 2022, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the first new draft guideline on BE for IR solid oral dosage forms (M13A). To support the development of ICH M13A, we comprehensively reviewed the landscape of oral IR products approved by the U.S. Food and Drug Administration (FDA) and compared BE recommendations for these products in the current U.S. FDA and European Medicines Agency (EMA) BE guidances. We utilized databases including Drugs@FDA, Orange Book, and product-specific guidances (PSGs) published on the U.S. FDA and EMA websites to collect information. Oral IR products account for 46% of all FDA-approved new drug applications currently listed in Orange Book with 82.5% solids, 0.9% semi-solids, and 16.6% liquids. For all published U.S. FDA PSGs for solid oral IR products, in vivo BE studies with pharmacokinetic (PK) endpoints account for 88% of BE approaches recommended. Of these PK BE studies, 86.5% recommended fasting and fed BE studies, while only 15.9% EMA PSGs recommended both fasting and fed BE studies. This review helps clarify the scope of U.S. solid oral IR products impacted by the new ICH M13A draft guideline and demonstrates how recommendations in draft ICH M13A could significantly harmonize BE recommendations for IR oral products to facilitate global drug development.

60 APPLIED LIFE SCIENCES↗

Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy

Immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in a variety of tumors, but resistance during treatment is a major issue. In this review, we describe the utility of PD-L1 expression levels, mutation burden, immune cell infiltration, and immune cell function for predicting the efficacy of PD-1/PD-L1 blockade therapy. Furthermore, we explore the mechanisms underlying immunotherapy resistance caused by PD-L1 expression on tumor cells, T cell dysfunction, and T cell exhaustion. Based on these mechanisms, we propose combination therapeutic strategies. We emphasize the importance of patient-specific treatment plans to reduce the economic burden and prolong the life of patients. The predictive indicators, resistance mechanisms, and combination therapies described in this review provide a basis for improved precision medicine.

60 APPLIED LIFE SCIENCES↗

Predictive Radiation Oncology – A New NCI–DOE Scientific Space and Community

With a widely attended virtual kickoff event on January 29, 2021, the National Cancer Institute (NCI) and the Department of Energy (DOE) launched a series of 4 interactive, interdisciplinary workshops—and a final concluding “World Café” on March 29, 2021—focused on advancing computational approaches for predictive oncology in the clinical and research domains of radiation oncology. These events reflect 3,870 human hours of virtual engagement with representation from 8 DOE national laboratories and the Frederick National Laboratory for Cancer Research (FNL), 4 research institutes, 5 cancer centers, 17 medical schools and teaching hospitals, 5 companies, 5 federal agencies, 3 research centers, and 27 universities. Here we summarize the workshops by first describing the background for the workshops. Participants identified twelve key questions—and collaborative parallel ideas—as the focus of work going forward to advance the field. These were then used to define short-term and longer-term “Blue Sky” goals. In addition, the group determined key success factors for predictive oncology in the context of radiation oncology, if not the future of all of medicine. These are: cross-discipline collaboration, targeted talent development, development of mechanistic mathematical and computational models and tools, and access to high-quality multiscale data that bridges mechanisms to phenotype. The workshop participants reported feeling energized and highly motivated to pursue next steps together to address the unmet needs in radiation oncology specifically and in cancer research generally and that NCI and DOE project goals align at the convergence of radiation therapy and advanced computing.

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Moly 99 Reactor Case Study

Molybdenum-99 (Moly 99) is a critical raw material for Technetium (Tc) 99m, a radioactive isotope most widely used in nuclear medicine procedures. Moly 99 has a short half-life of about six hours, which means it cannot be stockpiled. When Moly 99 decays, it turns into Tc 99m, which has a half-life of 214,000 years. The photon energy emitted from the decay of Moly 99 is used in a variety of nuclear imaging technologies such as gamma cameras. Furthermore, radiopharmaceutical manufacturers use the photon energy emitted from the decay of Moly 99 to produce generators for hospitals, clinics, and radiopharmacies. Once Moly 99 decays to Tc 99m, it is used to make individual patient doses for a variety of diagnostic imaging procedures. The Moly 99 Reactor Design is a conceptual blueprint for Moly 99 production that does not use weapon-grade uranium; instead, the reactor has a target core of low-enriched uranium. The reactor design is small, reaching a foot-and-a-half in height and diameter and consumes less than two megawatts of power. The reactor's only purpose is for medical isotope production and with every fission, Moly 99 is produced.

07 ISOTOPE AND RADIATION SOURCES↗

American Chemical Society's summer school in nuclear and radiochemistry. Final report

The ACS Summer Schools in Nuclear and Radiochemistry (herein called “Summer Schools”) were held each year at San Jose State University (SJSU) and Brookhaven National Laboratory (BNL). The Summer Schools are an intensive, six-week program that includes both a lecture component covering fundamental principles of nuclear chemistry and radiochemistry and a laboratory component providing hands-on experience for the students to observe and test many of the basic principles that they learn about in lecture and in the special seminars. Each site hosts 12 undergraduate students annually. Participants are selected from a nation-wide pool of applicants who are currently enrolled as undergraduates seeking bachelors’ degrees, preferably in disciplines of physical sciences or engineering. To broaden the students’ perspectives on nuclear science, prominent research scientists active in nuclear and/or radiochemical research participate in a Guest Lecture Series. Symposia emphasizing nuclear security, nuclear medicine, and career opportunities are conducted as a part of the program.

07 ISOTOPE AND RADIATION SOURCES↗

Irradiation of 20L LEU Uranyl Sulfate Solution for Production of Mo-99

Argonne National Laboratory, with support from the National Nuclear Security Administration’s Office of Material Management and Minimization, is assisting SHINE Medical Technologies in the development of accelerator-driven production of 99 Mo using low-enriched uranium (LEU). Technetium-99m ( 99m Tc), a daughter of 99 Mo, is a workhorse of nuclear medicine, used in approximately 40,000 medical testing procedures each day just in the U.S.

07 ISOTOPE AND RADIATION SOURCES↗

Production of Astatine-211 for Translational Science in Radiotherapy (Research Performance Progress Report)

In this proposal we outline the methods to improve the isotope production of astatine-211 at the University of Pennsylvania Cyclotron Facility. Astatine-211 is an isotope that emits alpha- radiation and has high potential for treating otherwise untreatable cancers. The goal of this proposal is two fold, 1) Optimize current production of astatine-211 and maintain routine production and 2) develop new isotope production target systems and chemical isolation systems. By completing this proposal we will ensure that the University of Pennsylvania Cyclotron Facility continues to build it’s isotope program in an effort that unites under DOE isotope network supply initiatives with the overall goal of increasing the national supply of isotopes. The University of Pennsylvania is uniquely located in the northeast corridor of the United States of America and has access to dozens of institutions that could use astatine-211 in their research. With the support of the DOE we have the opportunity to provide additional momentum to this growing field of research and will be able to provide the foundation for economical development of astatine-211 research and application in medicine.

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