Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

Jamie E Medina; Akshaya V Annapragada; Pien Lof; Sarah Short; Adrianna L Bartolomucci; Dimitrios Mathios; Shashikant Koul; Noushin Niknafs; Michael Noe; Zachariah H Foda; Daniel C Bruhm; Carolyn Hruban; Nicholas A Vulpescu; Euihye Jung; Renu Dua; Jenna V Canzoniero; Stephen Cristiano; Vilmos Adleff; Heather Symecko; Daan van den Broek; Lori J Sokoll; Stephen B Baylin; Michael F Press; Dennis J Slamon; Gottfried E Konecny; Christina Therkildsen; Beatriz Carvalho; Gerrit A Meijer; Claus Lindbjerg Andersen; Susan M Domchek; Ronny Drapkin; Robert B Scharpf; Jillian Phallen; Christine A R Lok; Victor E Velculescu

doi:10.1158/2159-8290.CD-24-0393

Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

Jamie E Medina, Akshaya V Annapragada, Pien Lof, Sarah Short, Adrianna L Bartolomucci, Dimitrios Mathios, Shashikant Koul, Noushin Niknafs, Michael Noe, Zachariah H Foda, Daniel C Bruhm, Carolyn Hruban, Nicholas A Vulpescu, Euihye Jung, Renu Dua, Jenna V Canzoniero, Stephen Cristiano, Vilmos Adleff, Heather Symecko, Daan van den BroekLori J Sokoll, Stephen B Baylin, Michael F Press, Dennis J Slamon, Gottfried E Konecny, Christina Therkildsen, Beatriz Carvalho, Gerrit A Meijer, Claus Lindbjerg Andersen, Susan M Domchek, Ronny Drapkin, Robert B Scharpf, Jillian Phallen, Christine A R Lok, Victor E Velculescu

Gastrokirurgisk Afd.

Abstract

Ovarian cancer is a leading cause of death for women worldwide in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I-IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I-IV. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC=0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.

Originalsprog	Engelsk
Tidsskrift	Cancer Discovery
ISSN	2159-8274
DOI	https://doi.org/10.1158/2159-8290.CD-24-0393
Status	E-pub ahead of print - 30 sep. 2024

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10.1158/2159-8290.CD-24-0393

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Medina, J. E., Annapragada, A. V., Lof, P., Short, S., Bartolomucci, A. L., Mathios, D., Koul, S., Niknafs, N., Noe, M., Foda, Z. H., Bruhm, D. C., Hruban, C., Vulpescu, N. A., Jung, E., Dua, R., Canzoniero, J. V., Cristiano, S., Adleff, V., Symecko, H., ... Velculescu, V. E. (2024). Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers. Cancer Discovery. Advance online publication. https://doi.org/10.1158/2159-8290.CD-24-0393

Medina, JE, Annapragada, AV, Lof, P, Short, S, Bartolomucci, AL, Mathios, D, Koul, S, Niknafs, N, Noe, M, Foda, ZH, Bruhm, DC, Hruban, C, Vulpescu, NA, Jung, E, Dua, R, Canzoniero, JV, Cristiano, S, Adleff, V, Symecko, H, van den Broek, D, Sokoll, LJ, Baylin, SB, Press, MF, Slamon, DJ, Konecny, GE, Therkildsen, C, Carvalho, B, Meijer, GA, Andersen, CL, Domchek, SM, Drapkin, R, Scharpf, RB, Phallen, J, Lok, CAR & Velculescu, VE 2024, 'Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers', Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-24-0393

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title = "Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers",

abstract = "Ovarian cancer is a leading cause of death for women worldwide in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I-IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I-IV. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC=0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.",

author = "Medina, {Jamie E} and Annapragada, {Akshaya V} and Pien Lof and Sarah Short and Bartolomucci, {Adrianna L} and Dimitrios Mathios and Shashikant Koul and Noushin Niknafs and Michael Noe and Foda, {Zachariah H} and Bruhm, {Daniel C} and Carolyn Hruban and Vulpescu, {Nicholas A} and Euihye Jung and Renu Dua and Canzoniero, {Jenna V} and Stephen Cristiano and Vilmos Adleff and Heather Symecko and {van den Broek}, Daan and Sokoll, {Lori J} and Baylin, {Stephen B} and Press, {Michael F} and Slamon, {Dennis J} and Konecny, {Gottfried E} and Christina Therkildsen and Beatriz Carvalho and Meijer, {Gerrit A} and Andersen, {Claus Lindbjerg} and Domchek, {Susan M} and Ronny Drapkin and Scharpf, {Robert B} and Jillian Phallen and Lok, {Christine A R} and Velculescu, {Victor E}",

year = "2024",

month = sep,

day = "30",

doi = "10.1158/2159-8290.CD-24-0393",

language = "English",

journal = "Cancer Discovery",

issn = "2159-8274",

publisher = "American Association for Cancer Research",

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TY - JOUR

T1 - Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

AU - Medina, Jamie E

AU - Annapragada, Akshaya V

AU - Lof, Pien

AU - Short, Sarah

AU - Bartolomucci, Adrianna L

AU - Mathios, Dimitrios

AU - Koul, Shashikant

AU - Niknafs, Noushin

AU - Noe, Michael

AU - Foda, Zachariah H

AU - Bruhm, Daniel C

AU - Hruban, Carolyn

AU - Vulpescu, Nicholas A

AU - Jung, Euihye

AU - Dua, Renu

AU - Canzoniero, Jenna V

AU - Cristiano, Stephen

AU - Adleff, Vilmos

AU - Symecko, Heather

AU - van den Broek, Daan

AU - Sokoll, Lori J

AU - Baylin, Stephen B

AU - Press, Michael F

AU - Slamon, Dennis J

AU - Konecny, Gottfried E

AU - Therkildsen, Christina

AU - Carvalho, Beatriz

AU - Meijer, Gerrit A

AU - Andersen, Claus Lindbjerg

AU - Domchek, Susan M

AU - Drapkin, Ronny

AU - Scharpf, Robert B

AU - Phallen, Jillian

AU - Lok, Christine A R

AU - Velculescu, Victor E

PY - 2024/9/30

Y1 - 2024/9/30

N2 - Ovarian cancer is a leading cause of death for women worldwide in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I-IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I-IV. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC=0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.

AB - Ovarian cancer is a leading cause of death for women worldwide in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker (CA-125 and HE4) analyses to evaluate 591 women with ovarian cancer, benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity >99% and sensitivity of 72%, 69%, 87%, and 100% for stages I-IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100% of ovarian cancers for stages I-IV. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC=0.88, 95% CI=0.83-0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation.

U2 - 10.1158/2159-8290.CD-24-0393

DO - 10.1158/2159-8290.CD-24-0393

M3 - Journal article

C2 - 39345137

SN - 2159-8274

JO - Cancer Discovery

JF - Cancer Discovery

ER -

Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers

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