Please use this identifier to cite or link to this item: http://hdl.handle.net/11434/1260
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dc.contributor.authorRome, Robert-
dc.contributor.otherGarsed, Dale-
dc.contributor.otherAlsop, Kathryn-
dc.contributor.otherFereday, Sian-
dc.contributor.otherEmmanuel, Catherine-
dc.contributor.otherKennedy, Catherine-
dc.contributor.otherEtemadmoghadam, Dariush-
dc.contributor.otherGao, Bo-
dc.contributor.otherGebski, Val-
dc.contributor.otherGarès, Valérie-
dc.contributor.otherChristie, Elizabeth-
dc.contributor.otherWouters, Maartje-
dc.contributor.otherMilne, Katy-
dc.contributor.otherGeorge, Joshy-
dc.contributor.otherPatch, Ann-Marie-
dc.contributor.otherLi, Jason-
dc.contributor.otherArnau, Gisela Mir-
dc.contributor.otherSemple, Timothy-
dc.contributor.otherGadipally, Sreeja-
dc.contributor.otherChiew, Yoke-Eng-
dc.contributor.otherHendley, Joy-
dc.contributor.otherMikeska, Thomas-
dc.contributor.otherZapparoli, Giada-
dc.contributor.otherAmarasinghe, Kaushalya-
dc.contributor.otherGrimmond, Sean-
dc.contributor.otherPearson, John-
dc.contributor.otherWaddell, Nicola-
dc.contributor.otherHung, Jillian-
dc.contributor.otherStewart, Colin-
dc.contributor.otherSharma, Raghwa-
dc.contributor.otherAllan, Prue-
dc.contributor.otherRambau, Peter-
dc.contributor.otherTraficante, Nadia-
dc.contributor.otherMcNally, Orla-
dc.contributor.otherMileshkin, Linda-
dc.contributor.otherHamilton, Anne-
dc.contributor.otherAnanda, Sumitra-
dc.contributor.otherGrossi, Marisa-
dc.contributor.otherCohen, Paul-
dc.contributor.otherLeung, Yee-
dc.contributor.otherBeale, Philip-
dc.contributor.otherBlomfield, Penny-
dc.contributor.otherFriedlander, Michael-
dc.contributor.otherBrand, Alison-
dc.contributor.otherDobrovic, Alexander-
dc.contributor.otherKöbel, Martin-
dc.contributor.otherHarnett, Paul-
dc.contributor.otherNelson, Brad-
dc.contributor.otherBowtell, David-
dc.contributor.otherdeFazio, Anna-
dc.date.accessioned2017-11-15T01:26:09Z-
dc.date.available2017-11-15T01:26:09Z-
dc.date.issued2017-10-
dc.identifier.citationClin Cancer Res. 2017 Oct 23. pii: clincanres.1621.2017en_US
dc.identifier.issn1078-0432en_US
dc.identifier.issn1557-3265en_US
dc.identifier.urihttp://hdl.handle.net/11434/1260-
dc.description.abstractPURPOSE: Women with epithelial ovarian cancer generally have a poor prognosis, however a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths. EXPERIMENTAL DESIGN: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical, and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing. RESULTS: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8+ tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR-deficiency and RB1 loss were correlated and co-occurrence was significantly associated with prolonged survival. CONCLUSIONS: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR-deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients.en_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.subjectEpithelial Ovarian Canceren_US
dc.subjectHigh-Grade Serous Canceren_US
dc.subjectHGSCen_US
dc.subjectOvarian Canceren_US
dc.subjectImmunohistochemicallyen_US
dc.subjectGenome Sequencingen_US
dc.subjectLong Progression-Free Survivalen_US
dc.subjectChemotherapyen_US
dc.subjectPathogenic Germlineen_US
dc.subjectSomatic Mutationsen_US
dc.subjectKi-67 Stainingen_US
dc.subjectCD8+ Tumor-Infiltrating Lymphocytesen_US
dc.subjectLong-Term Survivorsen_US
dc.subjectClinical Determinantsen_US
dc.subjectPathological Determinantsen_US
dc.subjectMolecular Determinantsen_US
dc.subjectTreatment Responseen_US
dc.subjectLong-PFSen_US
dc.subjectMultiple Responderen_US
dc.subjectLong-Term Survivorsen_US
dc.subjectHomologous Recombinationen_US
dc.subjectHRen_US
dc.subjectPrognosisen_US
dc.subjectHR-Deficiencyen_US
dc.subjectRB1 Lossen_US
dc.subjectCancer Services Clinical Institute, Epworth HealthCare, Victoria, Australiaen_US
dc.titleHomologous recombination DNA repair pathway disruption and retinoblastoma protein loss are associated with exceptional survival in high-grade serous ovarian cancer.en_US
dc.typeJournal Articleen_US
dc.identifier.doi10.1158/1078-0432.CCR-17-1621en_US
dc.identifier.journaltitleClinical Cancer Researchen_US
dc.description.pubmedurihttps://www.ncbi.nlm.nih.gov/pubmed/29061645en_US
dc.description.affiliatesCancer Research, Peter MacCallum Cancer Centre.en_US
dc.description.affiliatesResearch, Peter MacCallum Cancer Centre.en_US
dc.description.affiliatesCancer Genetics and Genomics Laboratory and Australian Ovarian Cancer Study, Peter MacCallum Cancer Centre.en_US
dc.description.affiliatesDepartment of Gynaecological Oncology, Centre for Cancer Research, The Westmead Institute for Medical Research, University of Sydney.en_US
dc.description.affiliatesGynaecological Oncology and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute.en_US
dc.description.affiliatesNHMRC Clinical Trials Centre, University of Sydney.en_US
dc.description.affiliatesNHMRC Clinical Trials Centre.en_US
dc.description.affiliatesCancer Genomics and Genetics Program, Peter MacCallum Cancer Centre.en_US
dc.description.affiliatesDeeley Research Centre, BC Cancer Agency.en_US
dc.description.affiliatesDeeley Research Centre, British Columbia Cancer Agency.en_US
dc.description.affiliatesComputational Sciences and Statistical Analysis, Jackson Laboratory for Genomic Medicine.en_US
dc.description.affiliatesDepartment of Medical Genomics, QIMR Berghofer Medical Research Instituteen_US
dc.description.affiliatesPeter MacCallum Cancer Centre.en_US
dc.description.affiliatesWestmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute.en_US
dc.description.affiliatesTranslational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute.en_US
dc.description.affiliatesUniversity of Melbourne Centre for Cancer Research,, University of Melbourne.en_US
dc.description.affiliatesResearch, QIMR Berghofer Medical Research Institute.en_US
dc.description.affiliatesGynaecological Oncology, Westmead Hospital.en_US
dc.description.affiliatesDept of Histopathology, King Edward Memorial Hospital.en_US
dc.description.affiliatesDepartment of Tissue Pathology, ICPMR, Sydney West Area Health Service.en_US
dc.description.affiliatesPathology, Peter MacCallum Cancer Centre.en_US
dc.description.affiliatesUniversity of Calgary.en_US
dc.description.affiliatesDepartment of Obstetrics and Gynaecology, Royal Women's Hospital.en_US
dc.description.affiliatesDivision of Haematology and Medical Oncology, Peter MacCallum Cancer Centre.en_US
dc.description.affiliatesMedical Oncology, Peter MacCallum Cancer Centreen_US
dc.description.affiliatesGynecologic Oncology, St John of God Hospital Bendat Family Cancer Centre Subiaco.en_US
dc.description.affiliatesDivision of Obstetrics and Gynaecology, University of Western Australia.en_US
dc.description.affiliatesSydney Cancer Centre, Concord Repatriation General Hospital.en_US
dc.description.affiliatesThe Royal Hobart Hospital.en_US
dc.description.affiliatesMEDICAL ONCOLOGY, University of New South Wales.en_US
dc.description.affiliatesDepartment of Gynaecological Oncology, Crown Princess Mary Cancer Centre.en_US
dc.description.affiliatesPathology, University of Calgary.en_US
dc.description.affiliatesCrown Princess Mary Cancer Centre, Westmead Hospital.en_US
dc.description.affiliatesCentre for Cancer Research, University of Sydney, Westmead Institute for Medical Research.en_US
dc.type.studyortrialCase Series and Case Reportsen_US
dc.type.contenttypeTexten_US
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