A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

Kathryn L Terry; Helena Schock; Renée T Fortner; Anika Hüsing; Raina N Fichorova; Hidemi S Yamamoto; Allison F Vitonis; Theron Johnson; Kim Overvad; Anne Tjønneland; Marie-Christine Boutron-Ruault; Sylvie Mesrine; Gianluca Severi; Laure Dossus; Sabina Rinaldi; Heiner Boeing; Vassiliki Benetou; Pagona Lagiou; Antonia Trichopoulou; Vittorio Krogh; Elisabetta Kuhn; Salvatore Panico; H Bas Bueno-de-Mesquita; N Charlotte Onland-Moret; Petra H Peeters; Inger Torhild Gram; Elisabete Weiderpass; Eric J Duell; Maria-Jose Sanchez; Eva Ardanaz; Nerea Etxezarreta; Carmen Navarro; Annika Idahl; Eva Lundin; Karin Jirström; Jonas Manjer; Nicholas J Wareham; Kay-Tee Khaw; Karl Smith Byrne; Ruth C Travis; Marc J Gunter; Melissa A Merritt; Elio Riboli; Daniel Cramer; Rudolf Kaaks

doi:10.1158/1078-0432.CCR-16-0316

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

Kathryn L Terry, Helena Schock, Renée T Fortner, Anika Hüsing, Raina N Fichorova, Hidemi S Yamamoto, Allison F Vitonis, Theron Johnson, Kim Overvad, Anne Tjønneland, Marie-Christine Boutron-Ruault, Sylvie Mesrine, Gianluca Severi, Laure Dossus, Sabina Rinaldi, Heiner Boeing, Vassiliki Benetou, Pagona Lagiou, Antonia Trichopoulou, Vittorio KroghElisabetta Kuhn, Salvatore Panico, H Bas Bueno-de-Mesquita, N Charlotte Onland-Moret, Petra H Peeters, Inger Torhild Gram, Elisabete Weiderpass, Eric J Duell, Maria-Jose Sanchez, Eva Ardanaz, Nerea Etxezarreta, Carmen Navarro, Annika Idahl, Eva Lundin, Karin Jirström, Jonas Manjer, Nicholas J Wareham, Kay-Tee Khaw, Karl Smith Byrne, Ruth C Travis, Marc J Gunter, Melissa A Merritt, Elio Riboli, Daniel Cramer, Rudolf Kaaks

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.

RESULTS: We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.

CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases.

Original language	English
Pages (from-to)	4664-4575
Journal	Clinical Cancer Research
Volume	22
Issue number	18
Early online date	2016 Apr 8
DOIs	https://doi.org/10.1158/1078-0432.CCR-16-0316
Publication status	Published - 2016 Sept 15

Subject classification (UKÄ)

Cancer and Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1078-0432.CCR-16-0316

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Terry, K. L., Schock, H., Fortner, R. T., Hüsing, A., Fichorova, R. N., Yamamoto, H. S., Vitonis, A. F., Johnson, T., Overvad, K., Tjønneland, A., Boutron-Ruault, M.-C., Mesrine, S., Severi, G., Dossus, L., Rinaldi, S., Boeing, H., Benetou, V., Lagiou, P., Trichopoulou, A., ... Kaaks, R. (2016). A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort. Clinical Cancer Research, 22(18), 4664-4575. https://doi.org/10.1158/1078-0432.CCR-16-0316

@article{e91031e6db614003a92449c959297fc3,

title = "A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort",

abstract = "PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.RESULTS: We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases.",

author = "Terry, {Kathryn L} and Helena Schock and Fortner, {Ren{\'e}e T} and Anika H{\"u}sing and Fichorova, {Raina N} and Yamamoto, {Hidemi S} and Vitonis, {Allison F} and Theron Johnson and Kim Overvad and Anne Tj{\o}nneland and Marie-Christine Boutron-Ruault and Sylvie Mesrine and Gianluca Severi and Laure Dossus and Sabina Rinaldi and Heiner Boeing and Vassiliki Benetou and Pagona Lagiou and Antonia Trichopoulou and Vittorio Krogh and Elisabetta Kuhn and Salvatore Panico and Bueno-de-Mesquita, {H Bas} and Onland-Moret, {N Charlotte} and Peeters, {Petra H} and Gram, {Inger Torhild} and Elisabete Weiderpass and Duell, {Eric J} and Maria-Jose Sanchez and Eva Ardanaz and Nerea Etxezarreta and Carmen Navarro and Annika Idahl and Eva Lundin and Karin Jirstr{\"o}m and Jonas Manjer and Wareham, {Nicholas J} and Kay-Tee Khaw and {Smith Byrne}, Karl and Travis, {Ruth C} and Gunter, {Marc J} and Merritt, {Melissa A} and Elio Riboli and Daniel Cramer and Rudolf Kaaks",

note = "Copyright {\textcopyright}2016, American Association for Cancer Research.",

year = "2016",

month = sep,

day = "15",

doi = "10.1158/1078-0432.CCR-16-0316",

language = "English",

volume = "22",

pages = "4664--4575",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research",

number = "18",

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Terry, KL, Schock, H, Fortner, RT, Hüsing, A, Fichorova, RN, Yamamoto, HS, Vitonis, AF, Johnson, T, Overvad, K, Tjønneland, A, Boutron-Ruault, M-C, Mesrine, S, Severi, G, Dossus, L, Rinaldi, S, Boeing, H, Benetou, V, Lagiou, P, Trichopoulou, A, Krogh, V, Kuhn, E, Panico, S, Bueno-de-Mesquita, HB, Onland-Moret, NC, Peeters, PH, Gram, IT, Weiderpass, E, Duell, EJ, Sanchez, M-J, Ardanaz, E, Etxezarreta, N, Navarro, C, Idahl, A, Lundin, E, Jirström, K , Manjer, J, Wareham, NJ, Khaw, K-T, Smith Byrne, K, Travis, RC, Gunter, MJ, Merritt, MA, Riboli, E, Cramer, D & Kaaks, R 2016, 'A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort', Clinical Cancer Research, vol. 22, no. 18, pp. 4664-4575. https://doi.org/10.1158/1078-0432.CCR-16-0316

TY - JOUR

T1 - A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

AU - Terry, Kathryn L

AU - Schock, Helena

AU - Fortner, Renée T

AU - Hüsing, Anika

AU - Fichorova, Raina N

AU - Yamamoto, Hidemi S

AU - Vitonis, Allison F

AU - Johnson, Theron

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Boutron-Ruault, Marie-Christine

AU - Mesrine, Sylvie

AU - Severi, Gianluca

AU - Dossus, Laure

AU - Rinaldi, Sabina

AU - Boeing, Heiner

AU - Benetou, Vassiliki

AU - Lagiou, Pagona

AU - Trichopoulou, Antonia

AU - Krogh, Vittorio

AU - Kuhn, Elisabetta

AU - Panico, Salvatore

AU - Bueno-de-Mesquita, H Bas

AU - Onland-Moret, N Charlotte

AU - Peeters, Petra H

AU - Gram, Inger Torhild

AU - Weiderpass, Elisabete

AU - Duell, Eric J

AU - Sanchez, Maria-Jose

AU - Ardanaz, Eva

AU - Etxezarreta, Nerea

AU - Navarro, Carmen

AU - Idahl, Annika

AU - Lundin, Eva

AU - Jirström, Karin

AU - Manjer, Jonas

AU - Wareham, Nicholas J

AU - Khaw, Kay-Tee

AU - Smith Byrne, Karl

AU - Travis, Ruth C

AU - Gunter, Marc J

AU - Merritt, Melissa A

AU - Riboli, Elio

AU - Cramer, Daniel

AU - Kaaks, Rudolf

PY - 2016/9/15

Y1 - 2016/9/15

N2 - PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.RESULTS: We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases.

AB - PURPOSE: About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.EXPERIMENTAL DESIGN: We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis.RESULTS: We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker.CONCLUSIONS: CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases.

U2 - 10.1158/1078-0432.CCR-16-0316

DO - 10.1158/1078-0432.CCR-16-0316

M3 - Article

C2 - 27060155

SN - 1078-0432

VL - 22

SP - 4664

EP - 4575

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 18

ER -

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

Abstract

Subject classification (UKÄ)

UN SDGs

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