Genomic and Epigenomic Alterations After Cancer Treatment in Pregnancy

Summary

Participation Requirements

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Rationale: Cancer is the second leading cause of death during the reproductive years and affects between 1:1000 and 2000 pregnant women. Previous studies from our group have shown that chemotherapeutic cancer treatment in pregnancy has reassuring outcomes in terms of cognitive and cardiac neonatal o...

Rationale: Cancer is the second leading cause of death during the reproductive years and affects between 1:1000 and 2000 pregnant women. Previous studies from our group have shown that chemotherapeutic cancer treatment in pregnancy has reassuring outcomes in terms of cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However fetal growth restriction (FGR), which places an infant at significant risk of perinatal morbidity and mortality, is more common in women who were systemically treated during pregnancy compared to the non-cancer population. The possibility that chemotherapy during pregnancy causes placental (epi)genetic damage, and consequently induces FGR, or affects offspring DNA leading to potential deleterious effects later in life, such as cancer or other diseases, has not been investigated so far. As the cytotoxic effects of chemotherapy at DNA level have been well established, it could be speculated that chemotherapy-induced DNA damage may interfere with fetal and childhood health in the long term. The results of this study will lead to an increased understanding of potential toxic effects of chemotherapy for the unborn child and may therefore contribute to the development of safe and solid treatment regimens for pregnant cancer patients and their children. Objectives: To obtain a fundamental understanding if and which chemotherapeutic agents used for treating cancer during pregnancy are associated with placental and/or offspring (epi)genetic changes, potentially causing FGR and childhood/adult diseases later in life. Study design: This international multicentre prospective observational trial functions as an extension of the CIP-study (Cancer in Pregnancy, S25470) and aims to collect placental tissue, cord blood and meconium and neonatal buccal cells at birth. Parental peripheral blood and buccal cells will be collected and used as reference. Minimal requirement to participate in this study is participation in Part I.IA of the original CIP-study. Through this CIP-study the investigators are able to gather pregnancy-, malignancy- and placenta-related data. Placental tissue is only collected from women who are also willing to participate or are already participating in Part I.IB (placental histopathology) of the CIP-study. Study population: All patients with histological proven cancer during pregnancy and an ongoing pregnancy (?24 weeks of gestation) treated with chemotherapy (alkylating agents, anthracyclines, taxanes and/or platinum derivates) or other treatment options (surgery, radiotherapy and/or systemic treatment other than chemotherapy, or none). Main study parameters/endpoints: determination of potential (sub)chromosomal alterations and/or changes in DNA methylation in placental tissue, and in cord blood and buccal cells of the newborn, and the association with chemotherapy concentrations measured in respectively placental or newborn tissue. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There are no risks associated nor benefits expected with participation in this study.

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