Chemoresistance of Trophoblastic Tumors

Study Overview
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Brief Summary
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Gestational trophoblastic tumors are characterized by their development from placental tissue and their high invasive and metastatic potential. These are rare tumors (1/50 000 pregnancies) affecting young women for whom conservative fertility treatments are preferred. The therapeutic strategy is based on a chemotherapy whose choice of protocol is based on a clinico-biological score, FIGO score, which includes tumor size, gonadotropic chorionic hormone level used as quantitative tumor marker, number and localization. metastases. A FIGO score ≤6 allows the use of monochemotherapy (methotrexate) with a 5-year survival of approximately 99.7%. Scores of 7 to 12 and ≥13 require multidrug therapy (EMA-CO) and are associated with 5-year survival of 95.1% and 61.6%, respectively. The chemotherapies currently used for the treatment of trophoblastic tumors have been described between the 1950s (methotrexate) and the 1980s (EMA-CO) and have a well documented toxicity regarding the risk of secondary tumors, early menopause or even death by toxicity. . To date, apart from the FIGO score, there is no predictor of resistance to chemotherapy in gestational trophoblastic tumors. However, among patients with a FIGO score ≤6 and receiving methotrexate in the first line, 9 to 46% will have a resistance and require a second line of treatment. Similarly, if the score is ≥7, 10 to 30% of patients receiving EMA-CO will require at least a second line of multidrug therapy. The hypothesis of PrediCTTro study is that tissue samples of gestational choriocarcinoma present a transcriptomic profile associated with the risk of further resistance to single or multiagent chemotherapy. The objective of PrediCTTro is to identify a transcriptomic signature able to predict resistance to single or multiagent chemotherapy.

Official Title
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Prediction of Chemoresistance in Patients Treated for Gestational Trophoblastic Tumors

Conditions
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Trophoblastic Tumor

Intervention / Treatment
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* Other: chemoresistance signature


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: confirmed gestational trophoblastic tumor histology hCG follow-up of at least 12 months after hCG normalization registration in the French Reference Center for Trophoblastic Diseases Exclusion Criteria: tissue specimen (block/biopsy) not available degraded quality of tissue sample not compatible with transcriptome analysis (>20% of necrosis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| methotrexate sensitive<br>patients with gestational choriocarcinoma cured with methotrexate alone | Other: chemoresistance signature<br>* to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy<br>|
| methotrexate resistant<br>patients with gestational choriocarcinoma not cured with methotrexate alone | Other: chemoresistance signature<br>* to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy<br>|
| polychemotherapy sensitive<br>patients with gestational choriocarcinoma cured with polychemotherapy | Other: chemoresistance signature<br>* to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy<br>|
| polychemotherapy resistant<br>patients with gestational choriocarcinoma not cured with polychemotherapy | Other: chemoresistance signature<br>* to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy<br>|
| hydatidiform moles without malignant transformation<br>patients treated for hydatidiform moles but who did not turn into trophoblastic tumors (=controls) | Other: chemoresistance signature<br>* to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy<br>|
| placental site trophoblastic tumors<br>patients with placental site trophoblastic tumors not cured with polychemotherapy | Other: chemoresistance signature<br>* to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcription profile associated with the resistance to chemotherapy | The expression level of 800 genes involved in oncogenesis canonical pathways and immune tolerance will be assessed and correlated with the resistance to single or multiagent chemotherapy. | 10 months |