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The report presents a metastatic high-grade pleomorphic sarcoma case with a BRIP1 mutation showing durable complete remission on olaparib, alongside a literature review of BRIP1 biology and PARP-inhibitor activity. A 67-year-old patient achieved radiologic complete response within two months and maintained remission for 36 months.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/complete-remission-with-olaparib-in-brip1-mutated-metastatic-high-grade-pleomorphic-sarcoma-a-genomic-profiling-based-tumor-treatment-example-case-study-and-literature-review/373739/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/complete-remission-with-olaparib-in-brip1-mutated-metastatic-high-grade-pleomorphic-sarcoma-a-genomic-profiling-based-tumor-treatment-example-case-study-and-literature-review/373739.png","ImageObject",300,407,{"name":92,"@type":93},"Aldword","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What clinical challenge does the article address in high-grade metastatic sarcoma patients?","Question",{"text":112,"@type":113},"It addresses the poor prognosis and limited treatment options, which are often chemotherapy-based with palliative intent.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was the treatment target identified in the case described?",{"text":117,"@type":113},"Genomic profiling using next-generation sequencing detected a BRIP1 mutation, which supported using olaparib.",{"name":119,"@type":110,"acceptedAnswer":120},"What was the patient’s response and duration of remission on olaparib?",{"text":121,"@type":113},"Pulmonary metastases regressed within two months, with ongoing complete remission for 36 months at the time of reporting.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},373739,1790319887,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},2336478940917,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","REVIEW ARTICLE  \nComplete remission with olaparib in BRIP1-mutated metastatic high-grade pleomorphic sarcoma: case study and literature review – an example of a genomic profiling-based tumor treatment, in a cancer type with high unmet clinical need  \nAlexander D. J. Thoofta,b* , Sofie Jorisc* , Celine Jacobsa,b , David Creytensd , Sylvie Rotteya,b , Brigitte Maese,f , Philippe Aftimosg  and Lore Lapeirea,+b   \na Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium; bDepartment of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium; c Department of Medical Oncology, University Hospital Brussels, Brussels, Belgium; dDepartment of Pathology, Ghent University Hospital, Ghent University, Ghent, Belgium; e Laboratory for Molecular Diagnostics, Jessa Hospital, Hasselt, Belgium; fFaculty of Medicine and Life Sciences, LCRC, University of Hasselt, Hasselt, Belgium; gClinical Trials Conduct Unit, Institut Jules Bordet – Hôpital Universitaire de Bruxelles, Brussels, Belgium  \nABSTRACT  \nBackground and purpose: Patients with high-grade metastatic sarcoma have a poor prognosis and limited treatment options, mostly involving chemotherapy with palliative intent. In the past years, next generation sequencing has proven its benefit in cancer diagnostics and prediction of treatment response to targeted therapy.  \nPatient/material and methods: We present a case of response and long-term complete remission under treatment with the poly(ADP-ribose) polymerase inhibitor (PARP-inhibitor) olaparib in a patient with metastatic high-grade pleomorphic sarcoma, with an next generation sequencing detected BRIP1-mutation. Additionally, a literature search regarding the pathophysiology of BRIP1-mutations and the role of PARPinhibitors in BRIP1-mutated cancer was conducted.  \nResults: A 67-year-old female patient was diagnosed with a high-grade intra-abdominal pleomorphic sarcoma, which was surgically resected. One year later, metastatic lesions in the right lung were observed. Genomic profiling identified a BRIP1-mutation. Based on this finding, the patient was included in the PRECISION-2 olaparib study, which evaluates the efficacy of olaparib in advanced cancers of any type harboring mutations in a homologous recombination gene. Within 2 months of olaparib treatment, regression of the pulmonary metastases was observed with ongoing complete remission for currently 36 months. A review of the available literature highlights the importance of BRIP1 in the homologous recombination repair pathway and its role as a cancer susceptibility gene. Studies in BRIP1-mutated breast cancer, ovarian cancer, and prostate cancer suggest a clinical benefit of PARP-inhibitor use.  \nInterpretation: We here describe the first case of a metastatic BRIP1-mutated sarcoma, undergoing a complete radiologic response to olaparib treatment. We highlight an underexplored role of homologous recombination deficiency in non-traditional cancer types and postulate a tumor-agnostic approach to the use of PARP-inhibitors in BRIP1-mutated tumors.  \nARTICLE HISTORY  \nReceived 15 March 2025 Accepted 3 September 2025  \nPublished 23 September 2025  \nKEYWORDS  \npoly(ADP-ribose) polymerase inhibitors; BRIP1 protein; human; sarcoma; recombinational DNA repair; remission induction; highthroughput nucleotide sequencing; precision medicine  \nIntroduction  \nSoft-tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors with locally destructive growth and high risk of both local and distant recurrences.  \nThe standard of care treatment for high-grade STS in adult patients is a wide surgical excision with R0-margins often followed by adjuvant radiotherapy (RT) and in selected cases adjuvant chemotherapy [1] . Neoadjuvant treatment in the form of chemotherapy or RT can be considered in case of technically unresectable/borderline resectable tumors[2]. Inoligometastatic setting, local treatment such as a pulmonary wedge r","cbCaihK6Fa0AvCBQ","https://ap.wps.com/l/cbCaihK6Fa0AvCBQ","pdf",2366452,12,"English","# Abstract\n# Introduction\n## Standard of care and treatment options in high-grade soft-tissue sarcoma\n## Chemotherapy outcomes and limitations\n# Article history\n# Keywords","[{\"question\":\"What clinical challenge does the article address in high-grade metastatic sarcoma patients?\",\"answer\":\"It addresses the poor prognosis and limited treatment options, which are often chemotherapy-based with palliative intent.\"},{\"question\":\"How was the treatment target identified in the case described?\",\"answer\":\"Genomic profiling using next-generation sequencing detected a BRIP1 mutation, which supported using olaparib.\"},{\"question\":\"What was the patient’s response and duration of remission on olaparib?\",\"answer\":\"Pulmonary metastases regressed within two months, with ongoing complete remission for 36 months at the time of reporting.\"}]","Complete remission with olaparib in BRIP1-mutated metastatic high-grade pleomorphic sarcoma - an example of genomic profiling-based tumor treatment, case study and literature review | PDF",1790200331]