| 000 | 04906nam a22008537a 4500 | ||
|---|---|---|---|
| 003 | OSt | ||
| 005 | 20240305193716.0 | ||
| 008 | 221010b |||||||| |||| 00| 0 eng d | ||
| 022 | _a Online ISSN 1557-3265 | ||
| 022 | _aPrint ISSN 1078-0432 | ||
| 028 | _b Phone: +255 28 298 3384 | ||
| 028 | _b Fax: +255 28 298 3386 | ||
| 028 | _b Email: vc@bugando.ac.tz | ||
| 035 | _a Website: www.bugando.ac.tz | ||
| 040 | _cDLC | ||
| 041 | _aEnglish | ||
| 245 | _aHomologous Recombination DNA Repair Pathway Disruption and Retinoblastoma Protein Loss Are Associated with Exceptional Survival in High-Grade Serous Ovarian Cancer | ||
| 260 |
_aMwanza, Tanzania: _b American Association for Cancer Research & _b Catholic University of Health and Allied Sciences [CUHAS – Bugando] _c2018/2/1 |
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| 300 | _aPages 569-580 | ||
| 490 | _vClinical Cancer Research Volume 24 Issue 3 | ||
| 520 | _aAbstract 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+ 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. Clin Cancer Res; 24(3); 569–80. ©2017 AACR. | ||
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_a Nadia Traficante _944533 |
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_aAnna deFazio _944469 |
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_a David DL Bowtell _944534 |
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_a Brad H Nelson _944535 |
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_aPaul Harnett _944536 |
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_a Martin Köbel _944499 |
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_a Alexander Dobrovic _944537 |
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_aAlison Brand _944538 |
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_a Michael Friedlander _944539 |
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_a Penny Blomfield _944540 |
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_a Philip Beale _944541 |
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| 700 |
_aRobert M Rome _944542 |
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_a Yee C Leung _944543 |
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| 700 |
_aPaul A Cohen _944544 |
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_a Marisa Grossi _944545 |
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_a Sumitra Ananda _944546 |
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_aAnne Hamilton _944547 |
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_a Linda Mileshkin _944548 |
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_a Orla McNally _944549 |
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_aPeter F Rambau _922887 |
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_a Prue E Allan _944550 |
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| 700 |
_aRaghwa Sharma _944414 |
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_aColin JR Stewart _944551 |
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_aJillian Hung _944430 |
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_a Nicola Waddell _944552 |
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| 700 |
_aJohn V Pearson _944553 |
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_a Sean M Grimmond _944554 |
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| 700 |
_aKaushalya Amarasinghe _944555 |
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_aGiada V Zapparoli _944556 |
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_aThomas Mikeska _944557 |
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_a Joy Hendley _944558 |
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| 700 |
_a Yoke-Eng Chiew _944559 |
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_a Sreeja R Gadipally _944560 |
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_a Timothy Semple _944561 |
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_a Gisela Mir Arnau _944562 |
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_aJason Li _944563 |
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_aAnn-Marie Patch _944564 |
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_a Joshy George _944565 |
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_a Katy Milne _944566 |
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| 700 |
_aMaartje CA Wouters _944567 |
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| 700 |
_aElizabeth L Christie _944568 |
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_a Valérie Garès _944569 |
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_a Val Gebski _944570 |
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| 700 |
_aBo Gao _914627 |
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| 700 |
_a Dariush Etemadmoghadam _944571 |
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| 700 |
_aCatherine J Kennedy _944445 |
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| 700 |
_aCatherine Emmanuel _944572 |
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_a Sian Fereday _944573 |
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| 700 |
_aKathryn Alsop _944574 |
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_aDale W Garsed _944575 |
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_aAustralian Ovarian Cancer Study Group _944576 |
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_2ddc _cVM |
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_c19128 _d19128 |
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