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Project

PROGNOSTIC FACTORS FOR OBSTETRIC AND ONCOLOGICAL OUTCOME IN PREGNANT WOMEN WITH CANCER Chemotherapy in pregnancy: from fetal safety to maternal efficacy

BACKGROUND

The rarity of cancer and pregnancy hampering research, resulted in the arise of an International Network on cancer, Infertility and Pregnancy (INCIP). When cancer coincidences with pregnancy, the oncological and obstetric management is challenged by concerns on general health and prognosis of both the mother and the unborn child. Whenever possible, an oncological treatment plan according to the general standards of care for non-pregnant women should be offered in order to preserve maternal prognosis. Over the years, re-assuring reports on obstetric and neonatal outcomes following cytotoxic treatment during pregnancy are published. As a result, the management of pregnant cancer patients has shifted, offering cancer-specific oncological treatment depending on the gestational age whenever possible, instead of pregnancy termination or treatment delay until after delivery. Pregnant cancer patients are at risk of adverse obstetric outcomes, both directly through cancer treatment and indirectly by maternal physical and psychological stress. Population-based studies have shown an increased risk of pregnancy termination, stillbirth, preterm birth (both spontaneous and elective), small for gestational age (SGA) neonates and neonatal death in pregnancies complicated by cancer, however, they often lack information or power on the exact impact of antenatal treatment. The use of chemotherapy during pregnancy does raise two main issues. First of all, chemotherapy crosses the placenta and can impact fetal development and growth. Previous research focused on the occurrence of small for gestational age (SGA) neonates, however lacked information on fetal growth restriction (FGR), defined as fetuses who do not reach their growth potential. FGR is diagnosed prenatally and is a more reliable outcome regarding to the neonatal risks on short- and long-term, compared to SGA. An important second concern are gestational physiological changes resulting in chemodilution and a plausible reduced drug efficacy of chemotherapy. In this Phd we AIMED to further investigate and build evidence regarding the fetal safety and maternal outcome following cancer treatment during pregnancy.

METHODOLOGY

We expanded the INCIP registry in order to enlarge the numbers enabling sub-analyses with regard to obstetric and neonatal outcome per cancer or treatment type. We performed a final analysis of women with a primary or recurrent invasive cancer during pregnancy or women who conceived while receiving invasive cancer treatment between 1996 and 2021 (n=2172). Logistic regression models were used to assess evolution of management and outcomes over time, specific factors for adverse obstetric and neonatal outcomes and the association between prognostic factors and small for gestational age (SGA). Where applicable, multiple imputation was used for missing values. For the analyses of fetal growth, prenatal serial scan information was collected. For survival analysis of Hodgkin lymphoma we selected non-pregnant control patients from the University Hospitals of Leuven, Rotterdam and Groningen, matched on stage, age, period at diagnosis with INCIP cases. For breast cancer, we collaborated with the German Breast Group(GBG) and we performed multivariable Cox Hazard Regression analysis.

RESULTS

Overall, women with cancer are at risk of preterm onset of labor, preterm delivery and fetal growth restriction (chapter 1 and 6). The administration of antenatal chemotherapy even more increases the risk. A term delivery is encouraged in this population, to assure an optimal outcome for the child, as prematurity is a major risk factor for impaired neurocognitive outcome. As a counterpart, while awaiting term delivery in this high risk population, there is an increased risk of preterm onset of labor. Other risk factors identified in this thesis for preterm onset of labor are metastatic and hematological disease (chapter 1). Observational data on obstetric and neonatal outcomes of registered pregnant women with Hodgkin lymphoma, non-Hodgkin lymphoma, urological cancers and gastric cancer were published to guide physicians in clinical management (chapter 2). This thesis builds further on the evidence that chemotherapy during pregnancy does not induce congenital malformations, as long as it is administered after 12 weeks of gestation (chapter 3). We observed the outcomes of women with oncological surgery and G-CSF during pregnancy (chapter 4 and 5).

Fetal growth restriction is common in pregnant cancer patients (chapter 6). Cancer stage (metastatic disease), cancer type (hematological cancer), maternal weight gain during pregnancy, maternal hypertension and smoking play a role. An early gestational age at cancer diagnosis is strongly related to lower birthweight percentiles. In this thesis, we showed that there appears to be a direct dose-response effect of chemotherapy on neonatal birthweight (chapter 1). We confirm that overall maternal prognosis in breast cancer and Hodgkin lymphoma appears unaffected by pregnancy, also when chemotherapy is given during pregnancy (chapter 7 and 8).

CONCLUSION

Results of this thesis support the current clinical practice of treating pregnant women with cancer by the standards of care recommended for non-pregnant women as much as possible. Chemotherapy in pregnancy for breast cancer and Hodgkin lymphoma does not seem to impact maternal survival. The undoubtedly progress we made in preserving the pregnancy when at the same time cancer is diagnosed, is associated with an increased risk of adverse obstetric outcomes (spontaneous preterm delivery and fetal growth restriction). Knowledge of risk factors including the use of chemotherapy, cancer stage and maternal general health and nutritional status is crucial to tailor and organize the obstetric follow up by an experienced multidisciplinary team. Indeed, care for pregnant cancer patients continuously requires balancing of maternal and fetal benefits and risks.

Date:20 Sep 2017 →  16 Jun 2023
Keywords:cancer, pregnancy
Disciplines:Endocrinology and metabolic diseases, Gynaecology and obstetrics, Nursing
Project type:PhD project