PURPOSE To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. METHODS ASCO convened an Expert Panel and conducted a systematic review of the literature. RESULTS Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. RECOMMENDATIONS Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.Additional information is available at www.asco.org/neurooncology-guidelines.
BACKGROUND Recognizing the rapidly increasing interest and evidence in using metastasis-directed radiotherapy (MDRT) for oligometastatic disease (OMD), ESTRO and ASTRO convened a committee to establish consensus regarding definitions of OMD and define gaps in current evidence. METHODS A systematic literature review focused on curative intent MDRT was performed in Medline, Embase and Cochrane. Subsequent consensus opinion, using a Delphi process, highlighted the current state of evidence and the limitations in the available literature. RESULTS Available evidence regarding the use of MDRT for OMD mostly derives from retrospective, single-centre series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. Consensus was reached that OMD is largely independent of primary tumour, metastatic location and the presence or length of a disease-free interval, supporting both synchronous and metachronous OMD. In the absence of clinical data supporting a maximum number of metastases and organs to define OMD, and of validated molecular biomarkers, consensus supported the ability to deliver safe and clinically meaningful radiotherapy with curative intent to all metastatic sites as a minimum requirement for defining OMD in the context of radiotherapy. Systemic therapy induced OMD was identified as a distinct state of OMD. High-resolution imaging to assess and confirm OMD is crucial, including brain imaging when indicated. Minimum common endpoints such as progression-free and overall survival, local control, toxicity and quality-of-life should be reported; uncommon endpoints as deferral of systemic therapy and cost were endorsed. CONCLUSION While significant heterogeneity exists in the current OMD definitions in the literature, consensus was reached on multiple key questions. Based on available data, OMD can to date be defined as 1-5 metastatic lesions, a controlled primary tumor being optional, but where all metastatic sites must be safely treatable. Consistent definitions and reporting are warranted and encouraged in ongoing trials and reports generating further evidence to optimize patient benefits.
PURPOSE This guideline provides updated evidence-based recommendations addressing recent developments in the management of patients with brain metastases, including advanced radiation therapy techniques such as stereotactic radiosurgery (SRS) and hippocampal avoidance whole brain radiation therapy and the emergence of systemic therapies with central nervous system activity. METHODS The American Society for Radiation Oncology convened a task force to address 4 key questions focused on the radiotherapeutic management of intact and resected brain metastases from nonhematologic solid tumors. The guideline is based on a systematic review provided by the Agency for Healthcare Research and Quality. Recommendations were created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS Strong recommendations are made for SRS for patients with limited brain metastases and Eastern Cooperative Oncology Group performance status 0 to 2. Multidisciplinary discussion with neurosurgery is conditionally recommended to consider surgical resection for all tumors causing mass effect and/or that are greater than 4 cm. For patients with symptomatic brain metastases, upfront local therapy is strongly recommended. For patients with asymptomatic brain metastases eligible for central nervous system-active systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended. For patients with resected brain metastases, SRS is strongly recommended to improve local control. For patients with favorable prognosis and brain metastases receiving whole brain radiation therapy, hippocampal avoidance and memantine are strongly recommended. For patients with poor prognosis, early introduction of palliative care for symptom management and caregiver support are strongly recommended. CONCLUSIONS The task force has proposed recommendations to inform best clinical practices on the use of radiation therapy for brain metastases with strong emphasis on multidisciplinary care.
Background The COVID-19 pandemic has caused radiotherapy resource pressures and led to increased risks for lung cancer patients and healthcare staff. An international group of experts in lung cancer radiotherapy established this practice recommendation pertaining to whether and how to adapt radiotherapy for lung cancer in the COVID-19 pandemic. Methods For this ESTRO & ASTRO endorsed project, 32 experts in lung cancer radiotherapy contributed to a modified Delphi consensus process. We assessed potential adaptations of radiotherapy in two pandemic scenarios. The first, an early pandemic scenario of risk mitigation, is characterized by an altered risk–benefit ratio of radiotherapy for lung cancer patients due to their increased susceptibility for severe COVID-19 infection, and minimization of patient travelling and exposure of radiotherapy staff. The second, a later pandemic scenario, is characterized by reduced radiotherapy resources requiring patient triage. Six common lung cancer cases were assessed for both scenarios: peripherally located stage I NSCLC, locally advanced NSCLC, postoperative radiotherapy after resection of pN2 NSCLC, thoracic radiotherapy and prophylactic cranial irradiation for limited stage SCLC and palliative thoracic radiotherapy for stage IV NSCLC. Results In a risk-mitigation pandemic scenario, efforts should be made not to compromise the prognosis of lung cancer patients by departing from guideline-recommended radiotherapy practice. In that same scenario, postponement or interruption of radiotherapy treatment of COVID-19 positive patients is generally recommended to avoid exposure of cancer patients and staff to an increased risk of COVID-19 infection. In a severe pandemic scenario characterized by reduced resources, if patients must be triaged, important factors for triage include potential for cure, relative benefit of radiation, life expectancy, and performance status. Case-specific consensus recommendations regarding multimodality treatment strategies and fractionation of radiotherapy are provided. Conclusion This joint ESTRO-ASTRO practice recommendation established pragmatic and balanced consensus recommendations in common clinical scenarios of radiotherapy for lung cancer in order to address the challenges of the COVID-19 pandemic.
pH-responsive nanogels prepared via RAFT-mediated PISA show tunable swelling, high colloidal stability, and reversible behaviour, highlighting their potential for smart delivery, biosensing, and adaptive biomaterials.
Purpose Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. Methods and Materials A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. Results In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. Conclusions This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.
PURPOSE The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. RESULTS The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1 and detailed herein. MATERIALS AND METHODS The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. CONCLUSIONS This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.
Abstract Neutrino–nuclear responses associated with astro-neutrinos, single beta decays and double beta decays are crucial in studies of neutrino properties of interest for astro-particle physics. The present report reviews briefly recent studies of the neutrino–nuclear responses from both experimental and theoretical points of view in order to obtain a consistent understanding of the many facets of the neutrino–nuclear responses. Subjects discussed in this review include (i) experimental studies of neutrino–nuclear responses by means of single beta decays, charge-exchange nuclear reactions, muon- photon- and neutrino–nuclear reactions, and nucleon-transfer reactions, (ii) implications of and discussions on neutrino–nuclear responses for single beta decays, for astro-neutrinos, and for astro-neutrino nucleosynthesis, (iii) theoretical aspects of neutrino–nuclear responses for beta and double beta decays, for nuclear muon capture and for neutrino–nucleus scattering, and (iv) critical discussions on nucleonic and non-nucleonic spin–isospin correlations and renormalization (quenching or enhancement) effects on the axial weak coupling. Remarks are given on perspectives of experimental and theoretical studies of the neutrino–nuclear responses and on future experiments of double beta decays.
Afzaal Tufail, Saeed Akkad, Natasha E. Hatton
et al.
Bioconjugation at N-terminal α-oxo aldehydes is challenging when proline is adjacent due to competing cyclisation. In this study we show aldol bioconjugations can outcompete this cyclisation at acidic pH in modifications of peptides and proteins.
PURPOSE American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS “Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline”2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations. RESULTS The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses “Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline.”2 RECOMMENDATIONS Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V12Gy to brain tissue to ≤ 10 cm3 is conditionally recommended. Additional information is available at www.asco.org/neurooncology-guidelines.
I take a reflection of the mathematical method of integration applied in physics and astrophysics in the research. I examine the theoretical premise of integration entailed in its applications in the fields, and with qualitative comparative analysis, regard the inconsistency of the mathematical method in physical and astrophysical theories. I seek to uncover the formal science’s affinity to the natural sciences in the research, and assert that number theory and set theory are better substitutes in modern physics and astrophysics. With a relativistic (astro-)physics perspective, I discuss and compare the representations of causality, capacities for deviations, and error tolerance with the methodological approach. I discuss the implications with the example of the Cosmic Microwave Background, and conclude with the teleology of the (astro-)physical sciences.
M. Harkenrider, N. Abu-Rustum, Kevin Albuquerque
et al.
PURPOSE With the results of several recently published clinical trials, this guideline informs on the use of adjuvant radiation therapy (RT) and systemic therapy in the treatment of endometrial cancer. Updated evidence-based recommendations provide indications for adjuvant RT and the associated techniques, the utilization and sequencing of adjuvant systemic therapies, as well as the impact of surgical staging techniques and molecular tumor profiling. METHODS The American Society for Radiation Oncology (ASTRO) convened a multidisciplinary task force to address 6 key questions that focused on the adjuvant management of patients with endometrial cancer. The key questions emphasized the 1) indications for adjuvant RT, 2) RT techniques, target volumes, dose-fractionation, and treatment planning aims, 3) indications for systemic therapy, 4) sequencing of systemic therapy with RT, 5) impact of lymph node assessment on utilization of adjuvant therapy, and 6) impact of molecular tumor profiling on utilization of adjuvant therapy. Recommendations were based on a systematic literature review and created using consensus-building and ASTRO's Guideline Methodology for quality of evidence grading and strength of recommendation. RESULTS The task force recommends RT (either vaginal brachytherapy or external beam radiation therapy [EBRT]) be given based on the patient's clinical-pathologic risk factors to reduce risk of vaginal and/or pelvic recurrence. When EBRT is delivered, intensity modulated radiation therapy with daily image guided radiation therapy is recommended to reduce acute and late toxicity. Chemotherapy is recommended for patients with FIGO stage I-II with high-risk histologies and those with FIGO stage III-IVA with any histology. When sequencing chemotherapy and RT, there is limited data and no prospective data to support an optimal sequence. Sentinel lymph node mapping is recommended over pelvic lymphadenectomy for surgical nodal staging, and use of adjuvant therapy should be based on the pathologic ultrastaging status with isolated tumor cells treated as node negative and micrometastasis treated as node positive. The available data on molecular characterization of endometrial cancer is compelling and should be increasingly considered when making recommendations for adjuvant therapy. CONCLUSIONS These recommendations guide evidence-based best clinical practices on the use of adjuvant therapy for endometrial cancer.
PURPOSE This guideline provides evidence-based recommendations for adults with isocitrate dehydrogenase (IDH)-mutant grade 2 and grade 3 diffuse glioma, as classified in the 2021 World Health Organization (WHO) Classification of Tumours. It includes indications for radiation therapy (RT), advanced RT techniques, and clinical management of adverse effects. METHODS The American Society for Radiation Oncology convened a multidisciplinary task force to address 4 key questions focused on the RT management of patients with IDH-mutant grade 2 and grade 3 diffuse glioma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS A strong recommendation for close surveillance alone was made for patients with oligodendroglioma, IDH-mutant, 1p/19q codeleted, WHO grade 2 after gross total resection without high-risk features. For oligodendroglioma, WHO grade 2 with any high-risk features, adjuvant RT was conditionally recommended. However, adjuvant RT was strongly recommended for oligodendroglioma, WHO grade 3. A conditional recommendation for close surveillance alone was made for astrocytoma, IDH-mutant, WHO grade 2 after gross total resection without high-risk features. Adjuvant RT was conditionally recommended for astrocytoma, WHO grade 2, with any high-risk features and strongly recommended for astrocytoma, WHO grade 3. Dose recommendations varied based on histology and grade. Given known adverse long-term effects of RT, consideration for advanced techniques such as intensity modulated radiation therapy/volumetric modulated arc therapy or proton therapy were given as strong and conditional recommendations, respectively. Finally, based on expert opinion, the guideline recommends assessment, surveillance, and management for toxicity management. CONCLUSIONS Based on published data, the American Society for Radiation Oncology task force has proposed recommendations to inform the management of adults with IDH-mutant grade 2 and grade 3 diffuse glioma as defined by WHO 2021 classification, based on the highest quality published data, and best translated by our task force of subject matter experts.
Observations of transient phenomena like Gamma-Ray Bursts (GRBs), Fast Radio Bursts (FRBs), stellar flares and explosions (novae and supernovae), combined with the detection of novel cosmic messengers like high-energy neutrinos and gravitational waves has revolutionized astrophysics over the last years. The discovery potential of both ulti-messenger and multi-wavelength follow-up observations as well as serendipitous observations could be maximized with a novel tool which allows for quickly acquiring an overview over relevant information associated with each new detection. Here we present Astro-COLIBRI, a novel and comprehensive platform for this challenge. Astro-COLIBRI's architecture comprises a public RESTful API, real-time databases, a cloud-based alert system and a website as well as apps for iOS and Android as clients for users. Astro-COLIBRI evaluates incoming messages of astronomical observations from all available alert streams in real time, filters them by user specified criteria and puts them into their MWL and MM context. The clients provide a graphical representation with an easy to grasp summary of the relevant data to allow for the fast identification of interesting phenomena, provides an assessment of observing conditions at a large selection of observatories around the world, and much more. Here the key features of Astro-COLIBRI are presented. We outline the architecture, summarize the used data resources, and provide examples for applications and use cases. Focussing on the high-energy domain, we'll discuss the use of the platform in searches for high-energy gamma-ray counterparts to high-energy neutrinos, gamma-ray bursts and gravitational waves.
PURPOSE This updated report on stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) is part of a series of consensus-based white papers previously published addressing patient safety. Since the first white papers were published, SRS and SBRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The complexity and sub-millimeter accuracy, and delivery of a higher dose per fraction requires an emphasis on best practices for technical, dosimetric, and quality assurance (QA). Therefore, quality and patient safety considerations for these techniques remain an important area of focus. METHODS The American Society for Radiation Oncology (ASTRO) convened a task force to assess the original SRS/SBRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who select "strongly agree" or "agree" indicated consensus. SUMMARY This white paper builds on the previous version and uses other guidance documents to broadly address SRS and SBRT delivery, primarily focusing on processes related to quality and safety. SRS and SBRT require a team-based approach, staffed by appropriately trained and credentialed specialists as well as significant personnel resources, specialized technology, and implementation time. A thorough feasibility analysis of resources is required to achieve the clinical and technical goals and thoroughly discussed with all personnel prior to undertaking new disease sites. A comprehensive QA program must be developed, using established treatment guidelines, to ensure SRS and SBRT are performed in a safe and effective manner. Patient safety in SRS/SBRT is everyone's responsibility and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to ensure the highest levels of safety.
PURPOSE The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy (RT) for small-cell lung cancer (SCLC). Because of the relevance of this topic to ASCO membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations. METHODS The ASTRO guideline on RT for SCLC was reviewed for developmental rigor by methodologists. Then, an ASCO Expert Panel reviewed the content and the recommendations. RESULTS The ASCO Expert Panel determined that the recommendations from ASTRO guideline on RT for SCLC, published in June 2020, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed ASTRO guideline on RT for SCLC with a few discussion points. RECOMMENDATIONS Recommendations addressed thoracic radiotherapy for limited-stage SCLC, role of stereotactic body radiotherapy in stage I or II node-negative SCLC, prophylactic cranial radiotherapy, and thoracic consolidation for extensive-stage SCLC.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
In 2017, the ASTRO Board of Directors prioritized radiopharmaceutical therapy (RPT) as a leading area for new therapeutic development, and the ASTRO RPT Workgroup was created. Herein the Workgroup has developed a framework for RPT curriculum development upon which education leaders can build to integrate this modality into radiation oncology resident education. Through this effort, the Workgroup aims to provide a guide to ensure robust training in an emerging therapeutic area within the context of existing radiation oncology training in radiation biology, medical physics, and clinical radiation oncology. The framework first determines the core RPT knowledge required to select patients, prescribe, safely administer, and manage related adverse events. Then, it defines the most important topics for preparing residents for clinical RPT planning and delivery. This framework is designed as a tool to supplement the current training that exists for radiation oncology residents. The final document was approved by the ASTRO Board of Directors in the Fall of 2021.