Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer
We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer. Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients
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| Veröffentlicht in: | Gynecologic oncology 2025-01, Vol.192, p.120-127 |
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| creator | Graves, Stephen Sullivan, Mackenzie W. Adkoli, Anusha Zhou, Qin Iasonos, Alexia Selenica, Pier Aghajanian, Carol Liu, Ying L. Tew, William Sonoda, Yukio Ellenson, Lora H. Chi, Dennis O'Cearbhaill, Roisin E. Weigelt, Britta Grisham, Rachel N. |
| description | We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer.
Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients |
| doi_str_mv | 10.1016/j.ygyno.2024.11.011 |
| format | Article |
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Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables.
Increasing GIS as a continuous variable was associated with improved PFS and OS in our cohort. Overall, median PFS was significantly longer in patients with HRD ovarian cancer (35.4 months, 25.4–NE) than in those with HRP disease (14.9 months, 13.1–16.2; p < 0.001). Median OS was 36.2 months (32.4–NE) for HRP and not reached for HRD (p = 0.002). Notably, in patients with HRP ovarian cancer, we observed a shorter median PFS in those who received a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) than in those who did not (12.7 months for HRP with PARPi vs 15.2 months for HRP without PARPi).
Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation.
•Progression-free survival was significantly longer among patients with BRCA1/2 wild-type HRD ovarian cancer.•Genomic instability score as a continuous variable was significantly associated with progression-free and overall survival.•In patients with HRP status, those treated with PARP inhibitor maintenance had lower median progression-free survival.</description><identifier>ISSN: 0090-8258</identifier><identifier>ISSN: 1095-6859</identifier><identifier>EISSN: 1095-6859</identifier><identifier>DOI: 10.1016/j.ygyno.2024.11.011</identifier><identifier>PMID: 39647188</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>BRCA-negative homologous recombination deficiency outcomes ; Homologous recombination deficiency testing ; Maintenance therapy ; Ovarian cancer ; Overall survival ; PARP inhibitor</subject><ispartof>Gynecologic oncology, 2025-01, Vol.192, p.120-127</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1901-78e015c5ae466e7f5b22e1e90581e1c7bb3d7b6d39c6515531f1cc6c5ec5d4343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ygyno.2024.11.011$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39647188$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Graves, Stephen</creatorcontrib><creatorcontrib>Sullivan, Mackenzie W.</creatorcontrib><creatorcontrib>Adkoli, Anusha</creatorcontrib><creatorcontrib>Zhou, Qin</creatorcontrib><creatorcontrib>Iasonos, Alexia</creatorcontrib><creatorcontrib>Selenica, Pier</creatorcontrib><creatorcontrib>Aghajanian, Carol</creatorcontrib><creatorcontrib>Liu, Ying L.</creatorcontrib><creatorcontrib>Tew, William</creatorcontrib><creatorcontrib>Sonoda, Yukio</creatorcontrib><creatorcontrib>Ellenson, Lora H.</creatorcontrib><creatorcontrib>Chi, Dennis</creatorcontrib><creatorcontrib>O'Cearbhaill, Roisin E.</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Grisham, Rachel N.</creatorcontrib><title>Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer</title><title>Gynecologic oncology</title><addtitle>Gynecol Oncol</addtitle><description>We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer.
Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables.
Increasing GIS as a continuous variable was associated with improved PFS and OS in our cohort. Overall, median PFS was significantly longer in patients with HRD ovarian cancer (35.4 months, 25.4–NE) than in those with HRP disease (14.9 months, 13.1–16.2; p < 0.001). Median OS was 36.2 months (32.4–NE) for HRP and not reached for HRD (p = 0.002). Notably, in patients with HRP ovarian cancer, we observed a shorter median PFS in those who received a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) than in those who did not (12.7 months for HRP with PARPi vs 15.2 months for HRP without PARPi).
Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation.
•Progression-free survival was significantly longer among patients with BRCA1/2 wild-type HRD ovarian cancer.•Genomic instability score as a continuous variable was significantly associated with progression-free and overall survival.•In patients with HRP status, those treated with PARP inhibitor maintenance had lower median progression-free survival.</description><subject>BRCA-negative homologous recombination deficiency outcomes</subject><subject>Homologous recombination deficiency testing</subject><subject>Maintenance therapy</subject><subject>Ovarian cancer</subject><subject>Overall survival</subject><subject>PARP inhibitor</subject><issn>0090-8258</issn><issn>1095-6859</issn><issn>1095-6859</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><recordid>eNp9kUGP0zAUhC0EYrsLvwAJ-cglqV8cO8mBQ6mARVoJCcHZcuyX4iq1i52myq_Yv4xLF46c3mW-Gc0bQt4AK4GBXO_LZbf4UFasqkuAkgE8IytgnShkK7rnZMVYx4q2Eu0NuU1pzxjjDKqX5IZ3sm6gbVfkcZNSME5PLnja43RG9HSHPhycoc6nSfdudNNCkwkRqfaWHmPYRUwpE8UQEddhxqjHkaZTnN2sx8zRY3ZEPyV6dtNP6vE8LtQ6vfMhoaU-ox--bTewrmiYdXTaU6O9wfiKvBj0mPD1070jPz59_L69Lx6-fv6y3TwUBjoGRdMiA2GExlpKbAbRVxUCdky0gGCavue26aXlnZEChOAwgDHSCDTC1rzmd-Td1Te3-XXCNKmDSwbHUXsMp6Q41FI0XSMvUn6VmhhSijioY3QHHRcFTF2WUHv1Zwl1WUIBqLxEpt4-BZz6A9p_zN_XZ8H7qwBzzdlhVMnklxm0LqKZlA3uvwG_AdRHngM</recordid><startdate>20250101</startdate><enddate>20250101</enddate><creator>Graves, Stephen</creator><creator>Sullivan, Mackenzie W.</creator><creator>Adkoli, Anusha</creator><creator>Zhou, Qin</creator><creator>Iasonos, Alexia</creator><creator>Selenica, Pier</creator><creator>Aghajanian, Carol</creator><creator>Liu, Ying L.</creator><creator>Tew, William</creator><creator>Sonoda, Yukio</creator><creator>Ellenson, Lora H.</creator><creator>Chi, Dennis</creator><creator>O'Cearbhaill, Roisin E.</creator><creator>Weigelt, Britta</creator><creator>Grisham, Rachel N.</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20250101</creationdate><title>Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer</title><author>Graves, Stephen ; Sullivan, Mackenzie W. ; Adkoli, Anusha ; Zhou, Qin ; Iasonos, Alexia ; Selenica, Pier ; Aghajanian, Carol ; Liu, Ying L. ; Tew, William ; Sonoda, Yukio ; Ellenson, Lora H. ; Chi, Dennis ; O'Cearbhaill, Roisin E. ; Weigelt, Britta ; Grisham, Rachel N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1901-78e015c5ae466e7f5b22e1e90581e1c7bb3d7b6d39c6515531f1cc6c5ec5d4343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>BRCA-negative homologous recombination deficiency outcomes</topic><topic>Homologous recombination deficiency testing</topic><topic>Maintenance therapy</topic><topic>Ovarian cancer</topic><topic>Overall survival</topic><topic>PARP inhibitor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Graves, Stephen</creatorcontrib><creatorcontrib>Sullivan, Mackenzie W.</creatorcontrib><creatorcontrib>Adkoli, Anusha</creatorcontrib><creatorcontrib>Zhou, Qin</creatorcontrib><creatorcontrib>Iasonos, Alexia</creatorcontrib><creatorcontrib>Selenica, Pier</creatorcontrib><creatorcontrib>Aghajanian, Carol</creatorcontrib><creatorcontrib>Liu, Ying L.</creatorcontrib><creatorcontrib>Tew, William</creatorcontrib><creatorcontrib>Sonoda, Yukio</creatorcontrib><creatorcontrib>Ellenson, Lora H.</creatorcontrib><creatorcontrib>Chi, Dennis</creatorcontrib><creatorcontrib>O'Cearbhaill, Roisin E.</creatorcontrib><creatorcontrib>Weigelt, Britta</creatorcontrib><creatorcontrib>Grisham, Rachel N.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gynecologic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Graves, Stephen</au><au>Sullivan, Mackenzie W.</au><au>Adkoli, Anusha</au><au>Zhou, Qin</au><au>Iasonos, Alexia</au><au>Selenica, Pier</au><au>Aghajanian, Carol</au><au>Liu, Ying L.</au><au>Tew, William</au><au>Sonoda, Yukio</au><au>Ellenson, Lora H.</au><au>Chi, Dennis</au><au>O'Cearbhaill, Roisin E.</au><au>Weigelt, Britta</au><au>Grisham, Rachel N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer</atitle><jtitle>Gynecologic oncology</jtitle><addtitle>Gynecol Oncol</addtitle><date>2025-01-01</date><risdate>2025</risdate><volume>192</volume><spage>120</spage><epage>127</epage><pages>120-127</pages><issn>0090-8258</issn><issn>1095-6859</issn><eissn>1095-6859</eissn><abstract>We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer.
Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables.
Increasing GIS as a continuous variable was associated with improved PFS and OS in our cohort. Overall, median PFS was significantly longer in patients with HRD ovarian cancer (35.4 months, 25.4–NE) than in those with HRP disease (14.9 months, 13.1–16.2; p < 0.001). Median OS was 36.2 months (32.4–NE) for HRP and not reached for HRD (p = 0.002). Notably, in patients with HRP ovarian cancer, we observed a shorter median PFS in those who received a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) than in those who did not (12.7 months for HRP with PARPi vs 15.2 months for HRP without PARPi).
Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation.
•Progression-free survival was significantly longer among patients with BRCA1/2 wild-type HRD ovarian cancer.•Genomic instability score as a continuous variable was significantly associated with progression-free and overall survival.•In patients with HRP status, those treated with PARP inhibitor maintenance had lower median progression-free survival.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39647188</pmid><doi>10.1016/j.ygyno.2024.11.011</doi><tpages>8</tpages></addata></record> |
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| source | Elsevier ScienceDirect Journals Complete |
| subjects | BRCA-negative homologous recombination deficiency outcomes Homologous recombination deficiency testing Maintenance therapy Ovarian cancer Overall survival PARP inhibitor |
| title | Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer |
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