Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer

Jaana Oikkonen, Kaiyang Zhang, Liina Salminen, Ingrid Schulman, Kari Lavikka, Noora Andersson, Erika Ojanperä, Sakari Hietanen, Seija Grénman, Rainer Lehtonen, Kaisa Huhtinen, Olli Carpén, Johanna Hynninen, Anniina Färkkilä, Sampsa Hautaniemi

Research output: Contribution to journalArticleScientificpeer-review

Abstract

PURPOSECirculating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early detection of cancers or for monitoring treatment efficacy, the value of ctDNA in guiding treatment decisions in solid cancers is controversial. Here, we monitored ctDNA to detect clinically actionable alterations during treatment of high-grade serous ovarian cancer, the most common and aggressive form of epithelial ovarian cancer with a 5-year survival rate of 43%.PATIENTS AND METHODSWe implemented a clinical ctDNA workflow to detect clinically actionable alterations in more than 500 cancer-related genes. We applied the workflow to a prospective cohort consisting of 78 ctDNA samples from 12 patients with high-grade serous ovarian cancer before, during, and after treatment. These longitudinal data sets were analyzed using our open-access ctDNA-tailored bioinformatics analysis pipeline and in-house Translational Oncology Knowledgebase to detect clinically actionable genomic alterations. The alterations were ranked according to the European Society for Medical Oncology scale for clinical actionability of molecular targets.RESULTSOur results show good concordance of mutations and copy number alterations in ctDNA and tumor samples, and alterations associated with clinically available drugs were detected in seven patients (58%). Treatment of one chemoresistant patient was changed on the basis of detection of ERBB2 amplification, and this ctDNA-guided decision was followed by significant tumor shrinkage and complete normalization of the cancer antigen 125 tumor marker.CONCLUSIONOur results demonstrate a proof of concept for using ctDNA to guide clinical decisions. Furthermore, our results show that longitudinal ctDNA samples can be used to identify poor-responding patients after first cycles of chemotherapy. We provide what we believe to be the first comprehensive, open-source ctDNA workflow for detecting clinically actionable alterations in solid cancers.
Original languageEnglish
JournalJCO Precision Oncology
Issue number3
Pages (from-to)1-12
Number of pages12
ISSN2473-4284
DOIs
Publication statusPublished - 3 May 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 3122 Cancers

Cite this

Oikkonen, Jaana ; Zhang, Kaiyang ; Salminen, Liina ; Schulman, Ingrid ; Lavikka, Kari ; Andersson, Noora ; Ojanperä, Erika ; Hietanen, Sakari ; Grénman, Seija ; Lehtonen, Rainer ; Huhtinen, Kaisa ; Carpén, Olli ; Hynninen, Johanna ; Färkkilä, Anniina ; Hautaniemi, Sampsa. / Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer. In: JCO Precision Oncology. 2019 ; No. 3. pp. 1-12.
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title = "Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer",
abstract = "PURPOSECirculating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early detection of cancers or for monitoring treatment efficacy, the value of ctDNA in guiding treatment decisions in solid cancers is controversial. Here, we monitored ctDNA to detect clinically actionable alterations during treatment of high-grade serous ovarian cancer, the most common and aggressive form of epithelial ovarian cancer with a 5-year survival rate of 43{\%}.PATIENTS AND METHODSWe implemented a clinical ctDNA workflow to detect clinically actionable alterations in more than 500 cancer-related genes. We applied the workflow to a prospective cohort consisting of 78 ctDNA samples from 12 patients with high-grade serous ovarian cancer before, during, and after treatment. These longitudinal data sets were analyzed using our open-access ctDNA-tailored bioinformatics analysis pipeline and in-house Translational Oncology Knowledgebase to detect clinically actionable genomic alterations. The alterations were ranked according to the European Society for Medical Oncology scale for clinical actionability of molecular targets.RESULTSOur results show good concordance of mutations and copy number alterations in ctDNA and tumor samples, and alterations associated with clinically available drugs were detected in seven patients (58{\%}). Treatment of one chemoresistant patient was changed on the basis of detection of ERBB2 amplification, and this ctDNA-guided decision was followed by significant tumor shrinkage and complete normalization of the cancer antigen 125 tumor marker.CONCLUSIONOur results demonstrate a proof of concept for using ctDNA to guide clinical decisions. Furthermore, our results show that longitudinal ctDNA samples can be used to identify poor-responding patients after first cycles of chemotherapy. We provide what we believe to be the first comprehensive, open-source ctDNA workflow for detecting clinically actionable alterations in solid cancers.",
keywords = "3122 Cancers",
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day = "3",
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Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer. / Oikkonen, Jaana; Zhang, Kaiyang; Salminen, Liina; Schulman, Ingrid; Lavikka, Kari; Andersson, Noora; Ojanperä, Erika; Hietanen, Sakari; Grénman, Seija; Lehtonen, Rainer; Huhtinen, Kaisa; Carpén, Olli; Hynninen, Johanna; Färkkilä, Anniina; Hautaniemi, Sampsa.

In: JCO Precision Oncology, No. 3, 03.05.2019, p. 1-12.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Prospective Longitudinal ctDNA Workflow Reveals Clinically Actionable Alterations in Ovarian Cancer

AU - Oikkonen, Jaana

AU - Zhang, Kaiyang

AU - Salminen, Liina

AU - Schulman, Ingrid

AU - Lavikka, Kari

AU - Andersson, Noora

AU - Ojanperä, Erika

AU - Hietanen, Sakari

AU - Grénman, Seija

AU - Lehtonen, Rainer

AU - Huhtinen, Kaisa

AU - Carpén, Olli

AU - Hynninen, Johanna

AU - Färkkilä, Anniina

AU - Hautaniemi, Sampsa

N1 - doi: 10.1200/PO.18.00343

PY - 2019/5/3

Y1 - 2019/5/3

N2 - PURPOSECirculating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early detection of cancers or for monitoring treatment efficacy, the value of ctDNA in guiding treatment decisions in solid cancers is controversial. Here, we monitored ctDNA to detect clinically actionable alterations during treatment of high-grade serous ovarian cancer, the most common and aggressive form of epithelial ovarian cancer with a 5-year survival rate of 43%.PATIENTS AND METHODSWe implemented a clinical ctDNA workflow to detect clinically actionable alterations in more than 500 cancer-related genes. We applied the workflow to a prospective cohort consisting of 78 ctDNA samples from 12 patients with high-grade serous ovarian cancer before, during, and after treatment. These longitudinal data sets were analyzed using our open-access ctDNA-tailored bioinformatics analysis pipeline and in-house Translational Oncology Knowledgebase to detect clinically actionable genomic alterations. The alterations were ranked according to the European Society for Medical Oncology scale for clinical actionability of molecular targets.RESULTSOur results show good concordance of mutations and copy number alterations in ctDNA and tumor samples, and alterations associated with clinically available drugs were detected in seven patients (58%). Treatment of one chemoresistant patient was changed on the basis of detection of ERBB2 amplification, and this ctDNA-guided decision was followed by significant tumor shrinkage and complete normalization of the cancer antigen 125 tumor marker.CONCLUSIONOur results demonstrate a proof of concept for using ctDNA to guide clinical decisions. Furthermore, our results show that longitudinal ctDNA samples can be used to identify poor-responding patients after first cycles of chemotherapy. We provide what we believe to be the first comprehensive, open-source ctDNA workflow for detecting clinically actionable alterations in solid cancers.

AB - PURPOSECirculating tumor DNA (ctDNA) detection is a minimally invasive technique that offers dynamic molecular snapshots of genomic alterations in cancer. Although ctDNA markers can be used for early detection of cancers or for monitoring treatment efficacy, the value of ctDNA in guiding treatment decisions in solid cancers is controversial. Here, we monitored ctDNA to detect clinically actionable alterations during treatment of high-grade serous ovarian cancer, the most common and aggressive form of epithelial ovarian cancer with a 5-year survival rate of 43%.PATIENTS AND METHODSWe implemented a clinical ctDNA workflow to detect clinically actionable alterations in more than 500 cancer-related genes. We applied the workflow to a prospective cohort consisting of 78 ctDNA samples from 12 patients with high-grade serous ovarian cancer before, during, and after treatment. These longitudinal data sets were analyzed using our open-access ctDNA-tailored bioinformatics analysis pipeline and in-house Translational Oncology Knowledgebase to detect clinically actionable genomic alterations. The alterations were ranked according to the European Society for Medical Oncology scale for clinical actionability of molecular targets.RESULTSOur results show good concordance of mutations and copy number alterations in ctDNA and tumor samples, and alterations associated with clinically available drugs were detected in seven patients (58%). Treatment of one chemoresistant patient was changed on the basis of detection of ERBB2 amplification, and this ctDNA-guided decision was followed by significant tumor shrinkage and complete normalization of the cancer antigen 125 tumor marker.CONCLUSIONOur results demonstrate a proof of concept for using ctDNA to guide clinical decisions. Furthermore, our results show that longitudinal ctDNA samples can be used to identify poor-responding patients after first cycles of chemotherapy. We provide what we believe to be the first comprehensive, open-source ctDNA workflow for detecting clinically actionable alterations in solid cancers.

KW - 3122 Cancers

U2 - 10.1200/PO.18.00343

DO - 10.1200/PO.18.00343

M3 - Article

SP - 1

EP - 12

JO - JCO Precision Oncology

JF - JCO Precision Oncology

SN - 2473-4284

IS - 3

ER -