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      Case Report of AdAPT-001-Mediated Sensitization to a Previously Failed Checkpoint Inhibitor in a Metastatic Chordoma Patient

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          Abstract

          Chordoma is a rare, but aggressive bone tumor with a high recurrence rate that primarily arises at the cranial and caudal ends of the axial skeleton. Systemic chemotherapies are not effective against the tumor, and outside of surgical resection and radiation, no approved options are available. Prognosis depends on the extent of surgical resection, with the more the better, and adjuvant radiotherapy. Herein is presented the first-ever case of a recurrent chordoma patient that responded to the combination of one dose of an experimental TGF-beta trap carrying oncolytic adenovirus, known as AdAPT-001, followed by immune checkpoint inhibitor therapy, despite prior progression on an anti-PD-1. This case report highlights the potential of AdAPT-001 as a treatment modality in combination with checkpoint inhibition for recurrent chordoma.

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          Most cited references14

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          CARE 2013 Explanations and Elaborations: Reporting Guidelines for Case Reports.

          Well-written and transparent case reports (1) reveal early signals of potential benefits, harms, and information on the use of resources; (2) provide information for clinical research and clinical practice guidelines (CPGs), and (3) inform medical education. High-quality case reports are more likely when authors follow reporting guidelines. During 2011-2012 a group of clinicians, researchers, and journal editors developed recommendations for the accurate reporting of information in case reports that resulted in the CARE (CAse REport) Statement and Checklist. They were presented at the 2013 International Congress on Peer Review and Biomedical Publication, have been endorsed by multiple medical journals, and translated into nine languages. This explanation and elaboration document has the objective to increase the use and dissemination of the CARE Checklist in writing and publishing case reports. Each item from the CARE Checklist is explained and accompanied by published examples. The explanations and examples in this document are designed to support the writing of high-quality case reports by authors and their critical appraisal by editors, peer reviewers, and readers. This article and the 2013 CARE Statement and Checklist, available from the CARE website [www.care-statement.org] and the EQUATOR Network, [www.equator-network.org] are resources for improving the completeness and transparency of case reports.
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            Chordoma: incidence and survival patterns in the United States, 1973-1995.

            Chordoma, a rare tumor arising from notochordal remnants, has been described to date only by single-institution case series or small population-based surveys. We used data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, 1973-1995, to calculate age-adjusted incidence and survival rates for 400 cases of microscopically confirmed chordoma and to derive information regarding case distribution and risk of second cancer. The age-adjusted chordoma incidence rate (IR) of 0.08 per 100,000 was age-dependent, more common in males (IR 0.10) than females (IR 0.06) and rare among patients aged <40 years and blacks. Within the axial skeleton 32% of cases were cranial, 32.8% spinal and 29.2% sacral. Young age (<26 years; p = 0.0001) and female sex (p = 0.037) were associated with greater likelihood of cranial presentation. There was no overall increased risk for second primary cancers after chordoma. Median survival was 6.29 years; 5- and 10-year relative survival rates were 67.6% and 39.9%, respectively. Comparison with other bone sarcomas revealed racial disparities in incidence for the two developmental tumors, chordoma and Ewing's sarcoma. This study provides new data regarding incidence and survival patterns of chordoma in the US. Additional epidemiologic studies are required to elucidate the genetic and environmental determinants underlying this rare, distinctive neoplasm.
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              Chordoma: current concepts, management, and future directions.

              Chordoma is a rare bone cancer that is aggressive, locally invasive, and has a poor prognosis. Chordomas are thought to arise from transformed remnants of notochord and have a predilection for the axial skeleton, with the most common sites being the sacrum, skull base, and spine. The gold standard treatment for chordomas of the mobile spine and sacrum is en-bloc excision with wide margins and postoperative external-beam radiation therapy. Treatment of clival chordomas is unique from other locations with an enhanced emphasis on preservation of neurological function, typified by a general paradigm of maximally safe cytoreductive surgery and advanced radiation delivery techniques. In this Review, we highlight current standards in diagnosis, clinical management, and molecular characterisation of chordomas, and discuss current research. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Case Rep Oncol
                Case Rep Oncol
                CRO
                CRO
                Case Reports in Oncology
                S. Karger AG (Basel, Switzerland )
                1662-6575
                28 March 2023
                Jan-Dec 2023
                28 March 2023
                : 16
                : 1
                : 172-176
                Affiliations
                [a ]Pacific Neuroscience Institute and Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA, USA
                [b ]EpicentRx Inc., La Jolla, CA, USA
                Author notes
                Correspondence to: Bryan Oronsky, boronsky@ 123456epicentrx.com
                Article
                529503
                10.1159/000529503
                10051040
                37008834
                0d6a44bb-50b8-4d1e-ba36-2a9e958b4640
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ( http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.

                History
                : 17 August 2022
                : 27 January 2023
                : 2023
                Page count
                Figures: 2, References: 15, Pages: 5
                Funding
                EpicentRx Inc. is the sponsor of the BETA PRIME clinical trial (NCT04673942).
                Categories
                Case Report

                Oncology & Radiotherapy
                chordoma,oncolytic virus,adenovirus,tgf-bata,immunotherapy,case report
                Oncology & Radiotherapy
                chordoma, oncolytic virus, adenovirus, tgf-bata, immunotherapy, case report

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