Chemo and Radiotherapy Safe for Fetus During Later Pregnancy

Roxanne Nelson

September 28, 2014

MADRID — In utero exposure to chemotherapy appears to be safe, for the most part, when administered after the first trimester, according to data presented here at the European Society for Medical Oncology Congress 2014.

Dr. Frederic Amant

"Fear about the risks of chemotherapy administration should not be a reason to terminate a pregnancy, delay cancer treatment for the mother (which can jeopardize outcomes), or deliver a baby prematurely," said lead researcher Frederic Amant, MD, from University Hospitals Leuven in Belgium.

A case–control study on the developmental outcome of children exposed to chemotherapy in utero showed that chemotherapy does not adversely affect mental development or cardiac functioning.

The mental development of children almost 2 years of age did not differ significantly between those exposed to chemotherapy and control subjects. Cardiac dimensions and functions were also within the normal range for both groups.

However, chemotherapy is contraindicated during the first trimester of pregnancy, cautioned Hatem A. Azim Jr., MD, from the Jules Bordet Institute in Brussels, during a discussion of the study. "We can usually wait until the second trimester," he said.

Dr. Azim noted that "abortion should not be considered except in cases of aggressive disease diagnosed very early in the pregnancy," and that "premature delivery should be avoided unless complications require early induction of labor."

A conference attendee asked about the safety of anthracyclines, which are a widely used and effective treatment for a large spectrum of childhood cancers. Their use is limited by associated progressive and clinically significant cardiotoxic effects, which can be acute, early, or late. Dr. Azim noted that anthracyclines appear to be safe during pregnancy, "but at the end of the day, we must treat the mother and her desire to keep the pregnancy."

There are not a lot of data, but the adverse events appear to be minimal in children who are several years old now, compared with those not exposed to these drugs. "I don't think there are enough data for me to stop offering anthracyclines in pregnancy at this time," he said.

Dr. Amant added that the key to therapy is individualization. "By definition, all types of chemotherapy are not safe," he said.

Previous Evidence

In Europe, approximately 2500 to 5000 pregnant women are diagnosed with cancer every year; however, it remains unclear how systemic chemotherapy affects the development of the fetus. Thus, oncologists have been hesitant to administer chemotherapy to pregnant cancer patients.

A small study, which Dr. Amant presented at the 2011 European Multidisciplinary Cancer Congress, showed that children exposed to chemotherapy in utero did not appear to suffer any detrimental effects in terms of general health or neurologic or cardiac functioning.

Two review articles published in 2012 supported these findings, and led to the conclusion that pregnancy should be preserved whenever possible with breast and gynecologic cancers. These are the 2 most common malignancies diagnosed during pregnancy, and pregnancy does not have a deleterious effect on the prognosis of either. It is possible to provide standard therapy to the mother while safeguarding the fetus, the review authors noted.

Normal Development Observed

In their study, Dr. Amant and colleagues evaluated 38 children who were exposed to chemotherapy in utero and 38 who were not.

The exposed children, from Belgium, the Netherlands, and Italy, were recruited from the International Network for Cancer, Infertility and Pregnancy registry. They were matched with control subjects for gestational age and, when possible, sex.

Median age of the exposed children was 20.5 months and of the control children was 22.0 months (range, 18 - 42 months). The most common maternal malignancies were breast cancer (61%) and hematologic cancers (22%), and 61% of the women received anthracyclines.

Assessments were conducted with the Bayley Scales of Infant Development, the Mental Developmental Index (MDI), electrocardiography, and echocardiography.

Mean MDI score was within the normal range for both groups, and the difference between the exposed and control groups was not significant (99.13 vs 101.47). There was no correlation between the number of chemotherapy cycles during pregnancy and MDI, Dr. Amant reported.

There was a positive correlation between gestational age and MDI for all children in the study, and the MDI tended to increase 2.65 points for each week of gestational age.

For those who underwent cardiac testing, cardiac dimensions and functions were within the normal range, with a mean fractional shortening of 36% (range, 32% - 42%).

Safety of Radiotherapy

In a related study, Dr. Amant and colleagues explored the impact of radiotherapy during pregnancy.

They evaluated 16 children (median age, 6 years) exposed to radiotherapy in utero and 10 women (median age, 33 years) exposed to antenatal radiotherapy. Overall, the long-term cardiac, neuropsychologic, behavioral, and general health outcomes were within normal ranges.

At 1.5, 3.0, 6.0, or 9.0 years of age, the children were assessed with echocardiography, a clinical neurologic examination, cognitive tests, and questionnaires about health and behavior. Adults were examined with similar measurement tools.

Echocardiographic data from the exposed group were compared with data from an age- and sex-matched control group, and neurocognitive data were compared with data from test-specific age-appropriate norms.

The median maternal irradiation was 48 Gy (range, 12 - 70), and estimated fetal irradiation was 91 mGy (range, 0 - 1690). There was no linear relation between fetal dose of radiation and cognitive outcome.

One child had a severe cognitive delay, but the researchers note that this patient was exposed to a relatively low dose of radiotherapy (34 mGy) and there were confounding complications in the pregnancy.

This is the first long-term follow-up study of children exposed to medical radiation in utero, and larger series are needed to strengthen the findings, Dr. Amant and colleagues note.

It is an important clinical topic, said Fedro Alessandro Peccatori, MD, director of the fertility and procreation unit in the division of gynecologic oncology at the European Institute of Oncology in Milan.

"The main message is that neuropsychologic, behavioral, and general health outcomes were within the normal range in all but 3 of the 16 children studied," he said in a statement. "Pregnancy, particularly advanced pregnancy, has been traditionally considered a contraindication to radiotherapy."

Even though new radiation techniques and more sophisticated simulations of the received fetal dose could change this scenario, "caution remains mandatory when giving radiotherapy to a pregnant woman, particularly in the third trimester," Dr. Peccatori added.

The authors have disclosed no relevant financial relationships.

European Society for Medical Oncology (ESMO) Congress 2014: Abstracts 267PD_PR and 49LBA_PR. Presented September 27, 2014.

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