Radiobiological Effects on a Fetus

Due to Radiation Therapy

MaryKate Janita
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Kharod S, Greenwalt J, Dessaigne C, Yeung A. Pregnancy testing in patients undergoing

radiation therapy. Ecancermedicalscience. 2017;11(752-769):1-5.
While it has been proven that radiation can cause death, malformations, and growth

disturbances in fetuses, pregnancy screening guidelines have not been implemented in radiation

oncology. This research article studies the amount of radiation patients who properly receive

pregnancy screening, in order to identify if guidelines should be implemented. Researchers

retrospectively reviewed the medical records of all female patients between about a years’ time

that had received some type of radiation treatment for cancer. To fit “appropriate standards”

patients were premenopausal and had to of received either a urine or blood pregnancy test fewer

than fifteen days before treatment.1 The results of this study found that of the 131 female

patients, with a median age of 48 years old, 27% were considered “no risk” due to previous

hysterectomy, while 72% (95 patients) were considered “at risk.”1(p753) The results showed that

47% received a pregnancy test any time prior to radiation. However, of the 47%, only 17%

received “appropriate” testing prior to radiation. Therefore, 17% of patient received proper

pregnancy testing while 83% did not.

Overall, while this study doesn’t specifically look at the effects of radiation of pregnancy

patients, it looks at preventative measures taking to avoid fetal radiation which is just as

important. This study specifically draws on data from the past, making it a retrospective, or

longitudinal, cohort study. These studies are the third highest level of evidence based practice

and are often used to address awareness of a certain topic.2 These studies compare groups of

individuals that share a common exposure but also differ, such as in this study, women receiving

radiation and whether they had a pregnancy test or not. This study set appropriate standards prior

to analyzing data which increases the accuracy of results. However, researchers in these types of

studies rely on accurate record keeping,2 therefore if errors were made in the patient’s medical
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records, this could poorly affect the accuracy of the results. This study also has poor validity due

to selection bias. Patients must be women and premenopausal, however researchers only focused

on patients from their institution. This also creates a conflict of interest. To improve this study

and the validity, researchers should draw data from multiple institutions. With an increase in

patient population, they could even take the study further by seeing if patients who did not

receive proper pregnancy testing ended up being pregnant. This would further stress why

determining pregnancy status prior to radiation therapy is essential.

This study is important in clinical practice because while there are not set guidelines for

pregnancy testing in radiation therapy, institutions can set their own protocols regarding testing

for the safety of the patients. Pregnancy tests prior to radiation therapy will prevent fetal

exposures which can be deadly or lead to effects such as growth retardation, malformations, and

increased chances of childhood cancers. Awareness on this topic may eventually lead to set

guidelines implemented for all institutions of radiation oncology.

Öğretici, A, Uğur A, Canan K, Hatice B. Investigation of Conformal and Intensity-

Modulated Radiation Therapy Techniques to Determine the Absorbed Fetal Dose in

Pregnant Patients with Breast Cancer. Medical Dosimetry. 2016; 41.2: 95-99.
This research study investigates the absorbed fetal dose in pregnant patients receiving

treatment for breast cancer. Radiation has both stochastic and deterministic biological

effects. Some of these effects are genetic mutations, increased chance of childhood cancer,

mental retardation, malformations, and fetal death.3 These effects depend on gestational age at

time of exposure. The two treatment techniques that were compared in this study were IMRT vs.

3D conformal, both effective ways to treat breast cancer. While the uterus and fetus are not in the

treatment field, tissues and structures in the body are still able to receive dose due to scatter

radiation. Due to ethical standards, dose could not be measured in vivo, therefore, a
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thermoluminescence dosimeter (TLD) and an anthropomorphic phantom were used. The PTV,

OARs, and uterus were virtually created by a radiologist according to their positioning in the

body on CT images. The fetus was assumed to be 35 cm from the breast, however volume

changes were considered due to fetal development using a 9-point geometry setup.3(p96) This

setup included all the possible locations of a fetus during the first trimester. For this study, the

first trimester was the area of focus due to the radiosensitivity and size of the fetus during this

time of development. The population to fit this study was for patients having breast conserving

surgery, left breast treatment, treated with 6MV photons to 50Gy for 25 fractions. The 3D

conformal field used two opposing tangential fields and the IMRT technique used five gantry

angles with dynamic MLCs. Each treatment was repeated five times and there were up to nine

TLDs measuring dose in the phantom.

For the first trimester, 5cGy was used as a threshold due to the lack of studies showing

congenital risks at lower doses.3(p98) The Wilcoxon method was used to compare the two

treatment techniques and how they relate to the threshold. The overall results found that IMRT

technique caused up to five times the amount of fetal dose radiation than 3D- CRT. The fetal

dose for 3D-CRT was 1.39cGy or .03% of the tumor dose, while IMRT fetal dose was 8.48cGy

or .17% of the tumor dose.3(98) The technique which used 3D-CRT proved to be under the

threshold, while the IMRT was over the threshold, which can have significant risks for the fetus.

In this control study, researchers attempt to answer whether radiation treatment delivered

in the standard 3D-CRT technique or IMRT technique would expose the fetus to less

radiation. Due to not being able to conduct this experiment with real patients, a phantom is used.

This causes issues with the reliability of the phantom and how it compares to the human body. It

also effects the internal validity of the research because of having no patient population to test
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therefore no randomization. The quantitative results of this research were measured using the

Wilcoxon method. This method is used to compare similar samples and repeated measurements

on single samples, such as how each treatment was repeated multiple times for better accuracy

with TLD measurements. To analyze data, a p value of <0.05 was considered statistically

significant. When looking at fetal dose for each treatment on the two different phantoms, the p

values were .008 and .005.3(98) This means that there is a significant relationship between dose to

the fetus and the type of technique used to treat them. This shows strength in the results, further

improving the overall validity of the study.

This research is important in clinical practice because more and more women are being

diagnosed with breast cancer prior to menopause, which increases the probability of pregnancy

during treatment. Information on the best treatment modalities is vital for physicians who may be

caring for pregnant patients. It also points out factors to take into consideration such as patient

height, fetal developmental stage, and location of the fetus. It is proven that factors such as dose,

dose rate, and stage of gestation all contribute to the effect on embryos. By using a safer

treatment technique along with adjusting dose and dose rate, the safety of treating pregnant

patients could improve. While treating a pregnant patient is not desired, it may begin to be more

common as age of diagnosis in patients continues to decrease as time goes on, therefore further

research on this subject should be conducted for patient safety.

Wo J, Akila V. Impact of Radiotherapy on Fertility, Pregnancy, and Neonatal Outcomes in

Female Cancer Patients. International Journal of Radiation Oncology, Biology, Physics.
2009; 73.5:1304-1312
This article is a systematic review on research and literature regarding the impact of

radiation therapy on fertility, pregnancy, and neonatal outcomes among female patients. This

article focuses on effects on women trying to conceive following radiation treatment. When the
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fetus is directly exposed to radiation, it can cause congenital effects, however, when the ovum or

sperm is irradiated, it can lead to genetic effects, or mutations in the fetus or embryo. Radiation

causes direct DNA damage to ovarian follicles, which can lead to atrophy, damaged ovarian

cells, and decreased hormonal production.4(p1305) Additionally, pelvic irradiation puts females at

risk for spontaneous miscarriages, preterm labor/delivery, low birth-weight infants, and placental

abnormalities. Chiarelli et al.4, compared pregnancy risks in 340 pelvic irradiation patients to

patients treated with non-sterilizing agents and surgery, and found that irradiated patients were

more likely to have low-birth-weight infants and perinatal infant mortality. Similarly, Green et

al.4, conducted a questionnaire for roughly 2,000 cancer survivors, and found a trend in increased

risk of miscarriages in women whose ovaries were in or near the radiation field. More

importantly, it was also found that shielding the ovaries during irradiation did not increase the

chance of miscarriage.4(p1308) Additionally, fetal malposition, early or threatened labor, low birth

weight, and prematurity were all related to higher radiation doses.

Overall, this article provides a high level of evidence due to the numerous studies it

analyzes. Each of these studies investigate similar questions, for instance the impact of radiation

on fertility and neonatal outcomes. While this article is more objective due to the multiple studies

that are analyzed, it fails to report the databases in which it pulled these studies from, which

increases chances of selection bias. It also fails to mention the criteria of how these sources were

selected, such as through keyword search, which creates inclusion bias. However, many of the

studies found similar results among the different populations, which increase external validity as

well as accuracy of the results. To improve upon this review, the databases as well as the criteria

used to find articles should be included.

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All in all, this review is important to clinical practice because it analyzes effects of

pregnancy, fetus development, and neonatal outcomes after irradiation. While it is evident that

treating patients while pregnant can have substantial effects on the fetus, it is also essential to

remember that radiation can cause DNA mutations that can one-day effect embryos and fetuses

in the future. When irradiating females who may one day become pregnant, it is important to

take every precaution possible to decreasing the chances of these effects. This is especially

important when treating pediatric patients or young adult women. For example, taking the time

to setup patients properly prior to imaging to reduce the amount of additional radiation needed

due to setup errors. Also, remembering ALARA, or in other words, when treating areas of the

body use effective yet reasonable doses. These tools can be used in clinic to help decrease the

negative effects radiation can have on fertility, pregnancy, and neonatal outcomes.
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Works Cited
1. Kharod S, Greenwalt J, Dessaigne C, Yeung A. Pregnancy testing in patients undergoing
radiation therapy. Ecancermedicalscience. 2017;11:752-769
2. LaMorte, W. Prospective Versus Retrospective Cohort Studies. Boston University of
School of Public Health. Published September 21. 2016. Accessed December 3,
2017.
http://sphweb.bumc.bu.edu/otlt/MPHModules/EP/EP713_CohortStudies/EP713_
CohortStudies2.html
3. Öğretici, A, Uğur A, Canan K, Hatice B. Investigation of Conformal and
Intensity-Modulated Radiation Therapy Techniques to Determine the Absorbed
Fetal Dose in Pregnant Patients with Breast Cancer. Medical Dosimetry. 2016;
41.2: 95-99.
4. Wo J, Akila V. Impact of Radiotherapy on Fertility, Pregnancy, and Neonatal
Outcomes in Female Cancer Patients. International Journal of Radiation
Oncology, Biology, Physics. 2009; 73.5:1304-1312