Report
Teaser, summary, work performed and final results
Periodic Reporting for period 1 - CRADLE (Cancer treatment during pregnancy: from fetal safety to maternal efficacy)
Teaser
The evolution in drug regulation of the last 50 years has left pregnant women and their fetuses orphaned. This is particularly problematic for cancer during pregnancy, which raises a difficult and conflicting medical ethical decision process and which has recently become...
Summary
The evolution in drug regulation of the last 50 years has left pregnant women and their fetuses orphaned. This is particularly problematic for cancer during pregnancy, which raises a difficult and conflicting medical ethical decision process and which has recently become increasingly frequent. In 2012 we published the first prospective study indicating that antenatal exposure to cancer treatment can overall be considered safe. Building on this proof of concept, the current proposal wants to take a groundbreaking step towards developing a standard of care for cancer during pregnancy by addressing –in an integrated fashion- the challenges at the level of the fetus, the mother and the fetomaternal barrier. At the core of this proposal lies an international registry of pregnant women with cancer, along with a registry of their children, and biobanks of maternal, placental, cord blood and tumoral tissues. Research track ‘child’ aims to deliver robust evidence of fetal safety. Research track ‘mother’ aims to address the emerging concerns in the oncological management of the mother, and specifically, the possible distinct biology of pregnancy-associated breast cancer, the most frequent cancer type in pregnancy. The research approach includes large-scale clinical follow-up studies along with laboratory studies on patient biomaterials, including pharmacological investigations and RNA-sequencing studies. Complementary to these studies is research track ‘placenta’ in which cutting-edge models of human placental research are used to address the poorly understood physiological basis of the placental barrier function in this specific situation. This ambitious program will rely on a multidisciplinary team of experts.
This project aims to establish groundbreaking progress towards a standard of care for cancer in pregnancy by addressing –in an integrated fashion- the remaining concerns of antenatal exposure to chemotherapy for the fetus, the emerging concerns for the efficacy of the oncological management for the mother, and the poorly understood physiological basis of the placental barrier in this specific context. We defined 5 major objectives, corresponding to 5 distinct research programs.
1. We will use the growing registry of children within INCIP to deliver robust prospective evidence on the risk profile of antenatal exposure to chemotherapy for fetal cardiac and neuropsychological development.
2. Using the INCIP patient registry we will define the epidemiology of chemotherapy-associated IUGR. We will study the pathophysiology through a prospective study on biomaterials of chemotherapy-treated pregnant patients from INCIP, supported by investigations in an experimental setting.
3. Using prospective clinical studies in pregnant cancer patients from INCIP we will study the currently existing concerns with regards to staging, chemotherapy and psycho-emotional guidance during pregnancy.
4. Using cutting-edge models of human placental research we will characterize the dynamics of transplacental passage of the 4 most commonly used chemotherapeutics in pregnancy, as well as the underlying mechanisms of efflux transport and drug metabolism.
5. Using a two-phase retrospective/prospective study involving large-scale RNA-sequencing studies of tumor tissue from INCIP breast cancer patients, we will determine whether PP-BC exhibits a specific molecular signature with prognostic relevance.
Work performed
\"1. We are using the growing registry of children within INCIP to deliver robust prospective evidence on the risk profile of antenatal exposure to chemotherapy for fetal cardiac and neuropsychological development.
This is a multicenter prospective follow-up of children identified through the INCIP registry. The study is ongoing.
Also, see publication Vandenbroucke T. et al. NEJM 2015. Pediatric outcome after Maternal Cancer Diagnosed during Pregnancy.
2. Using the INCIP patient registry we will define the epidemiology of chemotherapy-associated IUGR. We will study the pathophysiology through a prospective study on biomaterials of chemotherapy-treated pregnant patients from INCIP, supported by investigations in an experimental setting.
Results: an interim analysis is being performed
3. Using prospective clinical studies in pregnant cancer patients from INCIP we will study the currently existing concerns with regards to staging, chemotherapy and psycho-emotional guidance during pregnancy.
See publication Vandenbroucke T et al. Psycho-oncology 2016. Psychological distress and cognitive coping in pregnant women diagnosed with cancer and their partners.
4. Using cutting-edge models of human placental research we will characterize the dynamics of transplacental passage of the 4 most commonly used chemotherapeutics in pregnancy, as well as the underlying mechanisms of efflux transport and drug metabolism.
At the end of 2017 Sigrid Conings will defend her PhD, copromoted by F. Amant, on \"\"Transplacental transport of paracetamol and its metabolites\"\".
5. Using a two-phase retrospective/prospective study involving large-scale RNA-sequencing studies of tumor tissue from INCIP breast cancer patients, we will determine whether PP-BC exhibits a specific molecular signature with prognostic relevance.
Sequencing and analysis of samples are ongoing.
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Final results
Not only may the scientific deliverables of this proposal constitute a major step forward to the well-being of both mother and fetus in a pregnancy complicated by cancer, the methodological approach may also provide critical impetus to further research in this field.
Website & more info
More info: http://www.cancerinpregnancy.org.