Intracranial Control With Combination BRAF and MEK Inhibitor Therapy in Patients With Metastatic Melanoma.

Purpose/Objectives Combination BRAF (vemurafenib, dabrafenib, or encorafenib) plus MEK (trametinib, cobimetinib, or binimetinib) inhibitor therapy is now widely used in the treatment of metastatic melanoma. However, data for intracranial response to these drugs are limited. We aimed to evaluate the intracranial efficacy of BRAF plus MEK inhibitors in patients with BRAF-mutant melanoma with brain metastases (BM) and to determine patterns of failure of these new agents to inform optimal integration of local intracranial therapy. Materials and methods We retrospectively reviewed charts of patients with BRAF-mutant melanoma with metastasis to the brain with at least one untreated brain metastasis at the time of initiation of BRAF plus MEK inhibitors at our institution from 2006 to 2020. We collected per-patient and per-lesion data on demographics, treatment modality, and outcomes. The cumulative incidence of local (LF), distant intracranial (DF), and extracranial failure (EF) were calculated with competing risk analysis with death as a competing risk and censored at the last brain MRI follow-up. LF was calculated on a per-lesion basis while DF and EF were calculated on a per-patient basis. DF was defined as any new intracranial lesions. Overall survival (OS) was analyzed using Kaplan-Meier. Logistic regression was used to identify predictors for LF. Results We identified 10 patients with 63 untreated brain metastases. The median age was 50.5 years. The median sum of the diameters of the five largest untreated brain metastases per patient was 20 mm (interquartile range 15-39 mm) and the median diameter for all measurable lesions was 4 mm. Median follow-up time was 9.0 months (range 1.4 months-46.2 months). Median OS was 13.6 months. The one-year cumulative incidence of LF, DF, and EF was 17.1%, 88.6, and 71.4%, respectively. The median time to LF, DF, and EF from the start of BRAF plus MEK inhibitors was 9.0 months, 4.7 months, and 7.0 months, respectively. The larger size of the BM was associated with LF on univariate analysis (odds ratio 1.13 per 1 mm increase in diameter, 95% confidence interval 1.019 to 1.308, p<0.02). Two (20%) patients eventually received stereotactic radiosurgery, and 2 (20%) received whole-brain radiotherapy for intracranial progression. Conclusion Although patients with BRAF-mutant melanoma with BM had fair local control on BRAF plus MEK inhibitors, the competing risk of death and distant intracranial and extracranial progression was high. Patients with larger brain metastases may benefit from local therapy

The Assistant Clinical Research Coordinator Program: A Pathway for Recruitment in Radiation Oncology

PURPOSE: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology. METHODS AND MATERIALS: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution\u27s clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale. RESULTS: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path. CONCLUSIONS: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions

Freakatistics - Discussion Assignments for the Statistics Classroom

This paper proposes and discusses how to use an assignment based on Freakonomics as a way to foster critical thinking and statistical literacy skills within the classroom. © 2014 Copyright Taylor and Francis Group, LLC

CyberKnife NeuroRadiosurgery. A practical Guide

This book is a practical guide on image-guided robotic (CyberKnife\uae) radiosurgery of the brain and the spine. The volume introduces the radiosurgical community to the potential of image-guidance in the treatment of neurosurgical diseases including neuro-oncological, vascular and functional disorders. Principles of image-guided radiosurgery, including physics and radiobiology are considered. Each chapter provides a critical review of the literature and analyses of several aspects to offer an assessment of single and hypofractionated treatments. Based on the authors\u2019 experience, tables or summaries presenting the treatment approaches and associated risks are included as well. Providing a practical guide to define the selection of dose, fractionation schemes, isodose line, margins, imaging, constraints to the structures at risk will support safe practice of neuroradiosurgery. This book aims to shed new light on the treatment of neoplastic and non-neoplastic diseases of the central nervous system using the CyberKnife\uae image-guided robotic radiosurgery system. It will be adopted by neurosurgery residents and neurosurgery consultants as well as residents in radiation oncology and radiation oncologists; medical physicists involved in radiosurgery procedures may also benefit from this book

Current status and recent advances in resection cavity irradiation of brain metastases

Despite complete surgical resection brain metastases are at significant risk of local recurrence without additional radiation therapy. Traditionally, the addition of postoperative whole brain radiotherapy (WBRT) has been considered the standard of care on the basis of randomized studies demonstrating its efficacy in reducing the risk of recurrence in the surgical bed as well as the incidence of new distant metastases. More recently, postoperative stereotactic radiosurgery (SRS) to the surgical bed has emerged as an effective and safe treatment option for resected brain metastases. Published randomized trials have demonstrated that postoperative SRS to the resection cavity provides superior local control compared to surgery alone, and significantly decreases the risk of neurocognitive decline compared to WBRT, without detrimental effects on survival. While studies support the use of postoperative SRS to the resection cavity as the standard of care after surgery, there are several issues that need to be investigated further with the aim of improving local control and reducing the risk of leptomeningeal disease and radiation necrosis, including the optimal dose prescription/fractionation, the timing of postoperative SRS treatment, and surgical cavity target delineation. We provide a clinical overview on current status and recent advances in resection cavity irradiation of brain metastases, focusing on relevant strategies that can improve local control and minimize the risk of radiation-induced toxicity

Correlation between small-volume spinal cord doses for spine stereotactic body radiotherapy (SBRT).

PurposeDoses to small spinal cord isodose volume (such as those ranging from Dmax 0.0 cc to 0.5 cc) as well as to large volumes (such as those ranging from 0.5 cc to 3.0 cc) are critical parameters to guide safe practice of spine SBRT. We here report a mathematical formula that links the most probable dose volume limits together for common spine SBRT cases.Methods and materials: A dose ripple formula parameterized with equivalent dose radius (EDR) was derived to model spinal cord small-volume doses for a spine SBRT treatment. A cohort of spine SBRT cases (n=68), treated with either a robotic x-band linac or a conventional S-band linac, was selected to verify the model predictions. The mean prescription dose was 22± 4 Gy (range, 12-40 Gy) delivered in 2±1 fractions. The mean and median target volume was 39.4±42.5 cc and 30.3 cc (range, 0.24-264.2 cc), respectively. Direct correlations between the spinal cord Dmax and variable spinal cord doses of increasing isodose volumes (ranging from 0.0 cc to 3.0 cc) of different planning organ-at-risk volumes (PRVs) were investigated. The PRV structures for the study included the true cord, thecal sac and the true cord plus variable margins ranging from 1.0 mm to 3.0 mm.ResultsNo direct linear correlation was observed amongst the small volume doses to the spinal cord PRVs. However, strong linear correlations (R2 > 0.96) for all the studied PRVs were observed when correlating EDRs amongst isodose volumes ranging from 0.0 cc to 3.0 cc. In particular, EDR dependence was found to differ significantly for the thecal sac versus the spinal cord with or without 1-3 millimeter margins. With strong EDR correlation, the most probable relationship among the small-volume dose limits was derived for the spinal cord PRVs.ConclusionAn analytical formula linked the most probable pin-point/small isodose volume doses with relatively large isodose volume doses of the spinal cord for spine SBRT. As a result, a small number of dose limits such as Dmax or D(0.35cc) are likely sufficient to surrogate the spinal cord dose tolerance for consistent treatment planning optimization and outcome analysis

by “peak

Sample classification from protein mass spectrometry