Clinical implications of tumor-based next-generation sequencing in high-grade epithelial ovarian cancer
© 2023 American Cancer Society..
BACKGROUND: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer.
METHODS: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival.
RESULTS: Of 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002-14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high-grade serous carcinoma.
CONCLUSIONS: tbNGS often yields clinically relevant information. Detailed analysis of population-level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools.
PLAIN LANGUAGE SUMMARY: Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:129 |
|---|---|
| Enthalten in: |
Cancer - 129(2023), 11 vom: 01. Juni, Seite 1672-1680 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Foster, Katherine I [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 11.05.2023 Date Revised 27.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/cncr.34724 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM354362186 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM354362186 | ||
| 003 | DE-627 | ||
| 005 | 20240427231933.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/cncr.34724 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1390.xml |
| 035 | |a (DE-627)NLM354362186 | ||
| 035 | |a (NLM)36930815 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Foster, Katherine I |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical implications of tumor-based next-generation sequencing in high-grade epithelial ovarian cancer |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.05.2023 | ||
| 500 | |a Date Revised 27.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 American Cancer Society. | ||
| 520 | |a BACKGROUND: Tumor-based next-generation sequencing is used inconsistently as a tool to tailor treatment of ovarian cancer, yet beyond detection of somatic BRCA1 and BRCA2 mutations, the clinical benefit is not well established. This study aimed to assess the clinical relevance of tumor-based next-generation sequencing (tbNGS) in patients with ovarian cancer | ||
| 520 | |a METHODS: This retrospective study included patients with high-grade epithelial ovarian carcinoma. tbNGS results were identified in the electronic medical record using optical character recognition and natural language processing. Genetic, clinical, and demographic information was collected. Progression-free survival (PFS) and overall survival were calculated and compared using log-rank tests. Multivariate Cox regression and clustering analyses were used to identify patterns of genetic alterations associated with survival | ||
| 520 | |a RESULTS: Of 1092 patients in the described population, 409 (37.5%) had tbNGS results. Nearly all (96.1% [393/409]) had one or more genetic alterations. In 25.9% (106/409) of patients, an alteration that aligned with a targeted treatment was identified, and in an additional 48.7% (199/409), tbNGS results suggested eligibility for an investigational agent or clinical trial. The most frequent alterations were TP53, PIK3CA, and NF1 mutations, and CCNE1 amplification. Together, BRCA1 and BRCA2 mutations were associated with longer PFS (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.92; p = .02), whereas AKT2 amplification was associated with shorter PFS (HR, 3.86; 95% CI, 1.002-14.88; p < .05). Multivariate Cox regression and clustering analyses identified several combinations of genetic alterations that corresponded to outcomes in patients with high-grade serous carcinoma | ||
| 520 | |a CONCLUSIONS: tbNGS often yields clinically relevant information. Detailed analysis of population-level tumor genomics may help to identify therapeutic targets and guide development of clinical decision support tools | ||
| 520 | |a PLAIN LANGUAGE SUMMARY: Although more and more patients with ovarian cancer are undergoing tumor-based next-generation sequencing to identify genetic mutations in their tumors, the benefits of such testing are not well established. In a group of over 400 patients with ovarian cancer who underwent tumor-based next-generation sequencing in the course of their treatment, nearly all patients had one or more genetic alterations detected, and one out of four patients had a mutation that qualified them for a personalized treatment option | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a genetic testing | |
| 650 | 4 | |a high-throughput nucleotide sequencing | |
| 650 | 4 | |a mutation | |
| 650 | 4 | |a natural language processing | |
| 650 | 4 | |a ovarian epithelial carcinoma | |
| 650 | 4 | |a ovarian neoplasms | |
| 650 | 4 | |a retrospective studies | |
| 700 | 1 | |a Shaw, Kenna R M |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Jeff |e verfasserin |4 aut | |
| 700 | 1 | |a Westin, Shannon N |e verfasserin |4 aut | |
| 700 | 1 | |a Yap, Timothy A |e verfasserin |4 aut | |
| 700 | 1 | |a Glassman, Deanna M |e verfasserin |4 aut | |
| 700 | 1 | |a Jazaeri, Amir A |e verfasserin |4 aut | |
| 700 | 1 | |a Rauh-Hain, Jose A |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Sanghoon |e verfasserin |4 aut | |
| 700 | 1 | |a Fellman, Bryan M |e verfasserin |4 aut | |
| 700 | 1 | |a Ju, Zhenlin |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yuexin |e verfasserin |4 aut | |
| 700 | 1 | |a Fleming, Nicole D |e verfasserin |4 aut | |
| 700 | 1 | |a Sood, Anil K |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer |d 1948 |g 129(2023), 11 vom: 01. Juni, Seite 1672-1680 |w (DE-627)NLM000028649 |x 1097-0142 |7 nnns |
| 773 | 1 | 8 | |g volume:129 |g year:2023 |g number:11 |g day:01 |g month:06 |g pages:1672-1680 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/cncr.34724 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 129 |j 2023 |e 11 |b 01 |c 06 |h 1672-1680 | ||