herapeutic radiation often results in signiicant fetal exposure depending on the dose, tumor location, field size, and gestational age. Potential adverse efects include fetal malformation, intellectual disability, growth restriction, sterility, and carcinogenesis (Brent, 1999; Stovall, 1995). In the 2 weeks following fertilization, exposure typically leads to chromosomal damage and embryonic death. he next most susceptible period is during organogenesis in weeks 2 through 8, and exposure can cause malformation. These might develop above a threshold dose of 0.1 to 0.2 Gy. During weeks 8 through 25, the fetal central nervous system is especially vulnerable. The threshold dose for intellectual disability at 8 to 15 weeks' gestation approximates 0.06 Gy, and at 16 to 25 weeks it is about 0.25 Gy (Kal, 2005; Otake, 1996). After 25 weeks' gestation, susceptibility is less, although no gestational age is considered safe for therapeutic radiation exposure. hus, radiotherapy to the maternal abdomen is contraindicated. With some head and neck cancers, however, radiotherapy to supradiaphragmatic areas can be used relatively safely with abdominal shielding of the fetus (Amant, 2015a).
Various antineoplastic drugs may be given for primary treatment or for adjunctive therapy. Although chemotherapy often improves long-term maternal outcomes, many are reluctant to employ it during pregnancy. Concerns for the fetus include malformations, growth restriction, intellectual disability, and the risk of future childhood malignancies. Risks are dependent primarily on fetal age at exposure, and most agents are potentially detrimental in the irst trimester during organogenesis. Indeed, in one review, 14 percent of major malformations were attributable to irst-trimester exposure to cytotoxic drugs (National Toxicology Program, 2013).
Ater the first trimester, most antineoplastic drugs are without immediate obvious adverse fetal sequelae (Abdel-Hady, 2012; Vercruysse, 2016). Similarly, late mutagenic efects appear limited (Amant, 2015b; Cardonick, 2015). Although not always practicable, some recommend that chemotherapy be withheld in the 3 weeks before expected delivery because neutropenia or pancytopenia might cause undue risk for maternal infection or hemorrhage. Another concern is that neonatal hepatic and renal clearance of chemotherapy metabolites is limited (Ko, 2011). For these reasons, most cytotoxic chemotherapy agents are contraindicated with breastfeeding (Pistilli, 2013).
Drugs designed to stimulate hemopoiesis are commonly used with cancer treatments. Some of these include the granulocyte colony-stimulating factors filgrastim (Neupogen) and pegilgrastim (Neulasta). If required in pregnancy, limited data support the safety of these agents (Boxer, 2015). Red blood cells can be stimulated by erythropoietin alfa (Procrit), which from case reports also appears safe in pregnancy (Sienas, 2013). However, maternal hypertension is a known potential risk.
he two main types of targeted therapy are monoclonal antibodies and small molecule inhibitors. Both block the actions of specific enzymes, proteins, or other molecules involved in cancer cell growth. hese drugs are designed to treat an everexpanding list of cancers, and some are described in later discussions of specific tumors. Most of these compounds are labeled by the Food and Drug Administration (FDA) as class
D, and data are limited regarding their pregnancy or breastfeeding efects.