Impact of Salvage Surgery and Re-irradiation for Radiation Failed Recurrent Skull Base Meningiomas

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Intracranial meningiomas: an update of the 2021 World Health Organization classifications and review of management with a focus on radiation therapy

Meningiomas account for approximately one third of all primary intracranial tumors. Arising from the cells of the arachnoid mater, these neoplasms are found along meningeal surfaces within the calvarium and spinal canal. Many are discovered incidentally, and most are idiopathic, although risk factors associated with meningioma development include age, sex, prior radiation exposure, and familial genetic diseases. The World Health Organization grading system is based on histologic criteria, and are as follows: grade 1 meningiomas, a benign subtype; grade 2 meningiomas, which are of intermediately aggressive behavior and usually manifest histologic atypia; and grade 3, which demonstrate aggressive malignant behavior. Management is heavily dependent on tumor location, grade, and symptomatology. While many imaging-defined low grade appearing meningiomas are suitable for observation with serial imaging, others require aggressive management with surgery and adjuvant radiotherapy. For patients needing intervention, surgery is the optimal definitive approach with adjuvant radiation therapy guided by extent of resection, tumor grade, and location in addition to patient specific factors such as life expectancy. For grade 1 lesions, radiation can also be used as a monotherapy in the form of stereotactic radiosurgery or standard fractionated radiation therapy depending on tumor size, anatomic location, and proximity to dose-limiting organs at risk. Optimal management is paramount because of the generally long life-expectancy of patients with meningioma and the morbidity that can arise from tumor growth and recurrence as well as therapy itself

Pseudoprogression After Proton Therapy of Pediatric Spinal Pilocytic Astrocytoma and Myxopapillary Ependymoma

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ACR-ARS Practice Parameter for the Performance of Proton Beam Therapy

PURPOSE: This practice parameter for the performance of proton beam radiation therapy was revised collaboratively by the American College of Radiology (ACR) and the American Radium Society (ARS). This practice parameter was developed to serve as a tool in the appropriate application of proton therapy in the care of cancer patients or other patients with conditions in which radiation therapy is indicated. It addresses clinical implementation of proton radiation therapy, including personnel qualifications, quality assurance (QA) standards, indications, and suggested documentation. MATERIALS AND METHODS: This practice parameter for the performance of proton beam radiation therapy was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters - Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS. RESULTS: The qualifications and responsibilities of personnel, such as the proton center Chief Medical Officer or Medical Director, Radiation Oncologist, Radiation Physicist, Dosimetrist and Therapist, are outlined, including the necessity for continuing medical education. Proton therapy standard clinical indications and methodologies of treatment management are outlined by disease site and treatment group (e.g. pediatrics) including documentation and the process of proton therapy workflow and equipment specifications. Additionally, this proton therapy practice parameter updates policies and procedures related to a quality assurance and performance improvement program (QAPI), patient education, infection control, and safety. CONCLUSION: As proton therapy becomes more accessible to cancer patients, policies and procedures as outlined in this practice parameter will help ensure quality and safety programs are effectively implemented to optimize clinical care

ACTION:a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma

BACKGROUND: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.METHODS: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.</p

ACTION:a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma

BACKGROUND: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.METHODS: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.</p

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

PurposeWe compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity.Methods and MaterialsWe reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity.ResultsAt 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742; nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction.ConclusionsSurvival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function

Framework for sustained climate assessment in the United States

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society, 100(5), (2019): 897-908, doi:10.1175/BAMS-D-19-0130.1.As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal “climate assessment consortium” to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit–cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.This report would not have been possible without the support and participation of numerous organizations and individuals. We thank New York State Governor Andrew M. Cuomo for announcing in his 2018 State of the State agenda that the IAC would be reconvened. The New York State Energy Research and Development Authority (Contract ID 123416), Columbia University’s Earth Institute, and the American Meteorological Society provided essential financial support and much more, including sage advice and moral support from John O’Leary, Shara Mohtadi, Steve Cohen, Alex Halliday, Peter deMenocal, Keith Seitter, Paul Higgins, and Bill Hooke. We thank the attendees of a workshop, generously funded by the Kresge Foundation in November of 2017, that laid a foundation for the idea to establish a civil-society-based assessment consortium. During the course of preparing the report, IAC members consulted with individuals too numerous to list here—state, local, and tribal officials; researchers; experts in nongovernmental and community-based organizations; and professionals in engineering, architecture, public health, adaptation, and other areas. We are so grateful for their time and expertise. We thank the members and staff of the National Academy of Sciences, Engineering, and Medicine’s Committee to Advise the U.S. Global Change Research Program for providing individual comments on preliminary recommendations during several discussions in open sessions of their meetings. The following individuals provided detailed comments on an earlier version of this report, which greatly sharpened our thinking and recommendations: John Balbus, Tom Dietz, Phil Duffy, Baruch Fischhoff, Brenda Hoppe, Melissa Kenney, Linda Mearns, Claudia Nierenberg, Kathleen Segerson, Soroosh Sorooshian, Chris Weaver, and Brian Zuckerman. Mary Black provided insightful copy editing of several versions of the report. We also thank four anonymous reviewers for their effort and care in critiquing and improving the report. It is the dedication, thoughtful feedback, expertise, care, and commitment of all these people and more that not only made this report possible, but allow us all to continue to support smart and insightful actions in a changing climate. We are grateful as authors and as global citizens. Author contributions: RM, SA, KB, MB, AC, JD, PF, KJ, AJ, KK, JK, ML, JM, RP, TR, LS, JS, JW, and DZ were members of the IAC and shared in researching, discussing, drafting, and approving the report. BA, JF, AG, LJ, SJ, PK, RK, AM, RM, JN, WS, JS, PT, GY, and RZ contributed to specific sections of the report

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Outcomes and Pattern of Care for Spinal Myxopapillary Ependymoma in the Modern Era-A Population-Based Observational Study

(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p \u3c 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE