期刊
CLINICAL CANCER RESEARCH
卷 24, 期 3, 页码 569-580出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-17-1621
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资金
- Department of Health and Human Services through Victorian Cancer Agency [ECSG15011]
- National Health and Medical Research Council of Australia (NHMRC) [APP631701]
- Cancer Australia [APP632595, APP1004673]
- National Breast Cancer Foundation [CG12-07, 509303]
- Canadian Institutes of Health Research [MOP142436]
- U.S. Army Medical Research and Materiel Command [W81XWH-08-1-0684, W81XWH-08-1-0685, DAMD17-01-1-0729]
- Cancer Australia
- Cancer Council Victoria
- Queensland Cancer Fund
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Foundation of Western Australia
- Cancer Council Tasmania
- NHMRC [400413, 400281, 310670, 628903]
- Agar family
- Ovarian Cancer Australia
- Peter MacCallum Cancer Centre Foundation
- Cancer Institute New South Wales [12/RIG/1-17, 15/RIG/1-16]
- University of Sydney Cancer Research Fund
- Cancer Institute NSW through Sydney West Translational Cancer Research Centre
Purpose: 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 thorn 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. (C) 2017 AACR.
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