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| ID | Type | Description | Link |
|---|---|---|---|
| 965193 | Other Grant/Funding Number | EU HORIZON 2020 |
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| Name | Class |
|---|---|
| University of Helsinki | OTHER |
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Chemotherapy resistance is the greatest contributor to mortality in advanced cancers and severe challenges remain in finding effective treatment modalities to cancer patients with metastasized and relapsed disease. High-grade serous ovarian cancer (HGSOC) is typically diagnosed at a stage where the disease is already widely spread to the abdomen and current standard of practice treatment consists of surgery followed by platinum-taxane based chemotherapy and maintenance therapy. While 90% of HGSOC patients show no clinically detectable signs of cancer after surgery and chemotherapy, only 43% of the patients are alive five years after diagnosis because of chemoresistant cancer.
This prospective, observational trial focuses on revealing major mechanisms causing chemoresistance in HGSOG patients and derive personalized treatment regimens for chemotherapy resistant HGSOC patients. The investigators recruit newly diagnosed advanced stage HGSOC patients who are then thoroughly followed during their cancer treatment. Longitudinal sampling includes digitalized H&E stained histology slides mainly collected during routine diagnostics, fresh tumor & ascites samples for next-generation sequencing/proteomics (WGS, RNA-seq, DNA-methylation, ATAC-seq, ChIP-seq, mass cytometry, etc.) and ex vivo experiments, plasma samples for circulating tumor DNA (ctDNA) analyses. Broad range of clinical parameters such as laboratory and radiologic parameters (e.g., FDG PET/CT), given cancer treatments and their outcomes are collected. Radiomic analyses are performed to PET/CT and CT scans. Long-term patient derived organoid lines are established from fresh tumor tissues. Actionable genomic alterations are searched.
The general objective is to establish a clinically useful precision oncology approach based on multi-level data collected in longitudinal setting, and translate the most potent and validated discoveries into clinical use. DECIDER project will produce AI-powered diagnostic tools, cutting-edge software platforms for clinical decision-making, novel data analysis & integration methods, and high-throughput ex vivo drug screening approaches.
Specific aims include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HGSOC patients treated with Neoadjuvant chemotherapy (NACT) | Other | Diagnostic laparoscopy followed with 3-4 cycles of platinum-taxane NACT and interval debulking surgery (IDS). Treatment response is monitored with FDG PET/CT. IDS is followed by standard adjuvant therapy (ESGO/ESMO + local guidelines). Digital H&E slides and WGS, RNAseq are obtained from performed surgeries including relapse operations/ascites drainages. Patients are followed with longitudinal ctDNA sampling. |
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| HGSOC patients treated with primary debulking surgery (PDS) | Other | PDS is followed by standard adjuvant therapy (ESGO/ESMO + local guidelines). Digital H&E slides and WGS, RNAseq obtained from PDS and possible relapse operations/ascites drainages when performed. Patients are followed with longitudinal ctDNA sampling. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| WGS and RNA sequencing | Genetic |
|
| Measure | Description | Time Frame |
|---|---|---|
| Successful clinical translation | The magnitude of successful clinical translation is measured by the number of times project-derived personalized medicine has impacted patients care by application of novel and existing biomarkers and therapies. | 5 years |
| Successful prediction of patient outcome with AI methods | Proportion of patients whose disease outcome (PFS, OS) is predicted correctly with digital histopathology images, genomic data and routine laboratory values | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Successful validation of potentially druggable genetic alterations | Number of potentially druggable genetic alterations found and validated with in-vitro methods | 5 years |
| Successful prediction of genomic features from tumor histology |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Johanna Hynninen | Contact | +358 50 5383554 | johanna.hynninen@utu.fi | |
| Sampsa Hautaniemi | Contact | +358503364765 | sampsa.hautaniemi@helsinki.fi |
| Name | Affiliation | Role |
|---|---|---|
| Sampsa Hautaniemi, DTech, Prof | University of Helsinki | Study Director |
| Johanna Hynninen, MD, PhD | Turku University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Turku University Hospital | Recruiting | Turku | 20520 | Finland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40885189 | Derived | Afenteva D, Yu R, Rajavuori A, Salvadores M, Launonen IM, Lavikka K, Zhang K, Pirttikoski A, Marchi G, Jamalzadeh S, Isoviita VM, Li Y, Micoli G, Erkan EP, Falco MM, Ungureanu D, Lahtinen A, Oikkonen J, Hietanen S, Vaharautio A, Sur I, Virtanen A, Farkkila A, Hynninen J, Muranen TA, Taipale J, Hautaniemi S. Multi-omics analysis reveals the attenuation of the interferon pathway as a driver of chemo-refractory ovarian cancer. Cell Rep Med. 2025 Sep 16;6(9):102316. doi: 10.1016/j.xcrm.2025.102316. Epub 2025 Aug 29. | |
| 37207655 |
| Label | URL |
|---|---|
| Project web site | View source |
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| circulating tumor DNA (ctDNA) | Genetic |
|
| FDG PET/CT imaging | Diagnostic Test |
|
Number of genomic features that can be successfully recognized from tumor histology
| 5 years |
| Prediction of primary treatment response from tumor histology using H&E stained whole slide images and AI-based methods | Number of patients whose outcome (primary therapy outcome, PFS) is predicted correctly | 5 years |
| Establishment of an updated version of Chemoresponse score (CRS) for measuring histological effect in tumor tissue after chemotherapy | Predictive power of the updated CRS at interval surgery is compared with traditional CRS | 5 years |
| Derived |
| Lahtinen A, Lavikka K, Virtanen A, Li Y, Jamalzadeh S, Skorda A, Lauridsen AR, Zhang K, Marchi G, Isoviita VM, Ariotta V, Lehtonen O, Muranen TA, Huhtinen K, Carpen O, Hietanen S, Senkowski W, Kallunki T, Hakkinen A, Hynninen J, Oikkonen J, Hautaniemi S. Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma. Cancer Cell. 2023 Jun 12;41(6):1103-1117.e12. doi: 10.1016/j.ccell.2023.04.017. Epub 2023 May 18. |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D000073336 | Whole Genome Sequencing |
| D017423 | Sequence Analysis, RNA |
| D000074141 | Circulating Tumor DNA |
| ID | Term |
|---|---|
| D017422 | Sequence Analysis, DNA |
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
| D000073888 | Cell-Free Nucleic Acids |
| D009696 | Nucleic Acids |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D004273 | DNA, Neoplasm |
| D004247 | DNA |
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