Journal of Medical Imaging and Radiation Oncology 53 (2009) 559–568

R EVIEW ARTIC L E ara_2124 559..568

Pregnancy and radiotherapy: Management options for

minimising risk, case series and comprehensive
literature review
SA Luis,1 DRH Christie,2 A Kaminski,3 L Kenny3 and MH Peres2
1
Auckland City Hospital, Auckland, New Zealand; and 2Premion and 3The Royal Brisbane and Women’s Hospital, Queensland, Australia

SA Luis MBBS; DRH Christie FRANZCR; Summary

A Kaminski FRANZCR; L Kenny FRANZCR;
MH Peres FRANZCR.
Correspondence
Dr Sushil Allen Luis, Auckland City Hospital,
Park Road, Grafton, Auckland, New Zealand.
Email: sushill@adhb.govt.nz
Conflicts of interest: None
Submitted 5 July 2009; accepted 22 July 2009.
doi:10.1111/j.1754-9485.2009.02124.x
This article reviews the efficacy and safety of radiotherapy in patients with
cancer who are pregnant. Our review provided extended follow-up results in
nine cases, presents a technical discussion on measures taken to minimise
foetal radiation exposure and provides a comprehensive summary of the
literature. Nine patients who received radiotherapy while pregnant are
described. The clinical presentation and outcomes of these and 100 additional
cases identified on a systematic literature review are presented. Comparisons
of scattered radiation doses from three linear accelerators are presented. The
average maternal follow-up in our series was 8.9 years with one patient
having a recurrence of their astrocytoma. In terms of foetal outcome, there
were one death in utero, one elective termination of pregnancy and one on
which no data were available. Six children, on whom long-term follow-up
(average 10.3 years) was obtainable, were in good health. Overall, there had
been 109 cases of radiotherapy in pregnancy that met our search criteria with
13 adverse outcomes and a median follow-up of 37 months. Comparisons of
three linear accelerators demonstrated significant differences in the amount
of scattered radiation to the abdominal surface. In summary radiotherapy
during pregnancy can be associated with a significant number of adverse
outcomes. While it may be difficult for a patient not to attribute these effects
to radiotherapy, it is also difficult to define the mechanisms by which radio-
therapy would have caused them, if that were the case.

Key words: foetus; neoplasm; pregnancy; radiation; radiotherapy.

foetal outcomes vary significantly and can range from no

Introduction
Malignancy during pregnancy occurs in approximately 1
in 1000 pregnancies.1,2 The most common cancers
affecting pregnant women are cancers of the uterine
cervix, breast and lymph nodes. In the non-pregnant
patient, irradiation currently has a role in the treatment
of all of these. Malignancy during pregnancy poses
special challenges because of the conflict between the
need to optimally treat the mother, while minimising
risk to both mother and foetus. The risks to the foetus
are highly dependent on gestational age as shown in
Table 1, and are described in detail by the American
Association of Physicists in Medicine (AAPM).1 Potential
or minimal detectable abnormalities to major adverse
outcomes, including mental retardation, malignancy and
foetal death.
Estimation of foetal size and position, as well as pro-
jected growth over the duration of treatment, are
essential in radiotherapy planning in order to minimise
the foetal radiation exposure. Useful techniques for the
minimisation of foetal radiation exposure include the
use of lead shielding and modification of radiotherapy
techniques, including the use of multileaf collimators
(MLC), reducing the field size and modifying the beam
energy. These techniques are well described by the
AAPM1 and provide a useful guide for practitioners

© 2009 The Authors

Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists 559
SA Luis et al.
Table 1. Risks of radiotherapy to foetus during fetal development
(reproduced with permission from AAPM)1
Gestational age (weeks) Risk
Less than 10 Lethal (especially prior to implantation: <8 days
post-conception)†, malformations†, small head
size†, growth retardation†, sterility, cataracts,
malignant disease
10–27 Small head size†, severe mental retardation†,
growth retardation†, sterility†, malformations,
cataracts, malignant disease
More than 27 Small head size, growth retardation, sterility,
cataracts, malignant disease
†High incidence.
considering the use of radiotherapy in the pregnant
patient.
This report provides detailed information and long-
term follow-up for nine cases in which radiotherapy was
administered during pregnancy in our two institutions
and a review of the literature. A detailed review of the
most recently treated case is provided. We highlight the
significant impact of the choice of treatment machine in
determining the level of radiation scattered to the foetus,
an issue not previously noted in the literature. We
provide information about long-term follow-up of the
patients and the offspring, which generally has not been
included in other reports. We present in detail the most
recent case, noteworthy, because the offspring suffered
a significant adverse outcome. We highlight the difficul-
ties in attributing causation to the radiotherapy in that
setting.
Methods
A recent referral of a pregnant patient for radiotherapy
prompted a retrospective review of cases treated previ-
ously while pregnant. Premion started providing radio-
therapy in 1988 and currently operates five radiotherapy
treatment centres in Queensland. Since then, there have
been four patients treated while pregnant at their
centres. The records held at the Royal Brisbane Hospital
were also reviewed, and six patients who were treated
while pregnant were identified. All of the patients were
treated using megavoltage beams from linear accelera-
tors. All, but one of the patients, were treated with
external abdominal shielding to protect the foetus. The
one exception was a patient who commenced treatment
prior to becoming aware of her early pregnancy. The
shielding was constructed in accordance with the guide-
lines of the AAPM. Sheets of lead were supported by
scaffolding to produce shielding from the beam edge to
a point where the uterus was covered from any scattered
radiation from the machine head (Figure 1).
Prior to the treatment of the index case, measure-
ments with an ionisation chamber (0.6 cc farmer) and
560
Fig. 1. Photograph of Case 1 with abdominal shielding in the treatment
position.
PTW unidose electrometer were conducted in conjunc-
tion with a water phantom in order to determine the
effectiveness and optimal position of the shielding for the
planned patient treatment. Measurements were taken on
the surface of the phantom at the ‘assumed’ fundus
position and also at a typical foetal depth so that a
correction value could be calculated and applied to the
real patient surface measurements in order to gain a
representative foetal dose value during treatment. All
measurements were normalised in order to convert
recorded values into Gray. A further set of measure-
ments taken with the ionisation chamber at the same
positions with and without the shielding in place allowed
a ratio of shielded to unshielded values to be deter-
mined, which provides an indication of internal scatter as
compared with total scatter.
During the treatment of the index case, an ultrasound
examination was performed weekly and the location of
the upper limit of the uterine fundus marked on the
patient’s skin. Monitoring of the doses under the shield-
ing was performed. Six measurements were taken with
the same ionisation chamber, electrometer combination
placed at the fundus according to ultrasound measure-
ments during treatment in order to monitor foetal doses.
Estimates of the foetal dose were made by relating these
measurements to an internal foetal dose, based on pre-
treatment dosimetric investigation using a phantom,
composed of different-sized water containers, to simu-
late the patient.
De-identified copies of the treated patients’ medical
records were obtained for review and the patients were
contacted by telephone by their treating medical team to
ascertain the outcomes of the pregnancies. The most
recently treated case is described in detail and with
reference to the rationale for choice of linac and shielding
set-up.
Additionally, a literature review was performed and
the results are presented in Tables 6 and 7. Medline
(1950 to March, Week 1, 2008), PubMed (up to April
© 2009 The Authors
Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists
 Pregnancy and radiotherapy

Table 2. Patient details

Patient Malignancy Treatment (excluding Time since

Radiotherapy) treatment (years)

1 High-grade astrocytoma Surgery 4

2 Melanoma Nil 9
3 Malignant fibrous histiocytoma Surgery 14
4 Basal cell carcinoma Surgery 9
5 Hodgkin’s Disease Chemotherapy 9
6 Hodgkin’s Disease Chemotherapy 12
7 Parotid mucoepidermoid carcinoma Surgery 10
8 Left renal haemangiopericytoma Surgery 11
9 Hodgkin’s Disease Nil 10

2007) and Cochrane database (Issue 1, 2008) searches
were performed with search terms ‘radiotherapy’ and
‘pregnancy’ and were limited to English. All papers that
reported cases in which external beam radiotherapy was
used during pregnancy with reported foetal outcome
were included, with the exception of those that reported
pelvic tumours. Radiotherapy for pelvic tumours in preg-
nancy was excluded because of the high foetal doses
administered and the high incidence of spontaneous or
therapeutic terminations of pregnancy. Papers that
reported elective terminations were excluded, as foetal
outcome resulting from exposure to radiotherapy could
not be determined. Papers that reported the use of
concurrent chemoradiotherapy in pregnancy were also
excluded so that foetal outcome from radiation exposure
could be more clearly demonstrated without the con-
founding factor of chemotherapy exposure. All papers
that reported the use of radioiodine, implantable radio-
active sources, and brachytherapy were excluded. A
manual search of the reference lists of all the retrieved
papers was conducted to identify any further relevant
papers.
Results
A detailed summary of nine cases treated at our institu-
tions is presented in Tables 2–4. Further details of case
1 are provided later including information on linac choice
and shielding design. All patients were treated with
external beam radiotherapy, and any other additional
treatment modalities used have been indicated on
Table 2. More detailed information can be obtained by
contacting the corresponding author, where such infor-
mation is required for future reviews.
The patients in this case series had a mean age of
30.5 years, with an age range of 19–41 years. All cases,
with the exception of case 1, had no evidence of disease
recurrence at the time of follow-up. There were no sig-
nificant long-term maternal side effects from the treat-
ment, except in case 2, where the patient suffered from
ongoing dry eyes, xerostomia, dental caries and unilat-
eral blindness. Seven of the nine pregnancies were
carried to term, one foetus died in utero and one was
terminated following the diagnosis of concurrent malig-
nancy. Six of the seven live births had no evidence of
congenital abnormalities. Long-term follow-up was avail-
able for the seven children.
Detailed review of the most recent case
(case 1)
This patient presented following a seizure and was
described by her family as showing bizarre behaviour. A
CT scan revealed a large lesion in the left frontal region.

Table 3. Radiotherapy details

Patient Area treated Beam energy Dose (Gray) Number of Fractions Overall time (days) Mulitleaf collimators

1 Left frontal region of the brain 6 MeV photons 54.00 30 – Yes

2 Left infraorbital nerve 6 MV photons and 6 MeV 55.00 30 – No
electrons
3 Left scapula 9 MeV electrons 60.00 48 (twice daily) 38 No
4 Left forehead 9 MeV electrons 50.00 – – No
5 Neck 6 MV photons 36.75 20 29 Yes
6 Neck 6 MV photons 35.00 20 28 Yes
7 Face and neck 6 MV photons 57.80 35 40 Yes
8 Left renal bed 6 MV photons 45.00 25 36 Yes
9 Neck 6 MV photons 36.00 25 – Yes

© 2009 The Authors

Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists 561
SA Luis et al.

Table 4. Foetal/child factors and outcome

Patient Gestation at start of Foetal dose Pregnancy Child’s gender Birth Current age
radiotherapy (weeks) estimate (mGy) complications weight (g) of child (years)

1 20 2.7 ⫾ 1 Died in utero Male 3865 ND

2 22 ND Gestational diabetes Male ND 9
3 21 290 Nil Female 4430 14
4 26 ND Nil Male 9
5 25 46 Nil Female 2150 9
6 24 50 Nil Female 1910 11
7 20 ND ND Female ND 10
8 10 (retrospective, 700 Pregnancy terminated ND ND ND
pt initially unaware)
9 22 ND Nil Male ND ND

ND, no data.

This was biopsied and sub-totally removed, revealing an

anaplastic astrocytoma. She elected to undergo post-
operative radiotherapy while pregnant, which was com-
pleted uneventfully.
After radiotherapy, death in utero was diagnosed at
38 weeks, 2 days gestation at a routine antenatal clinic
visit on ultrasound examination after failure to auscul-
tate foetal heart sounds. There was no history of reduced
foetal movements, vaginal loss or signs of infection.
On foetal autopsy, a large thrombus in the foetal
inferior vena cava with bilateral extension into renal
veins was seen. The kidneys showed changes secondary
to a degree of venous infarction. A microscopy of the
kidney showed a thin cortex with approximately five
layers of glomeruli, suggesting an insult to nephrogen-
esis occurring at approximately 28 weeks gestation. The
placenta showed changes of foetal thrombotic vas-
culopathy with thrombosis of foetal stem vessels and
recanalisation of some vessels. The placenta showed
areas of infarction of varying duration. However, body
weight, foot length, crown/rump, crown/heel length and
head circumference were consistent with a gestational
age of approximately 41 weeks, suggesting death in
utero was close to the time of delivery.
The patient has recently re-presented with a recur-
rence of her tumour, 45 months after the completion of
radiotherapy and is currently receiving a second course
of post-operative radiotherapy.
Choice of linac
Three linear accelerators were available for treatment at
the Premion centre in Tugun. Measurements of dose rate
were made on phantoms with measurements taken on
each linac at an isocentre height of 60 cm from the
central axis, consistent with the brain to fundus distance.
Measurements for a 10 ¥ 10 cm2 beam with the collima-
tor at 0 and 90 degrees were compared. These measure-
ments showed that the NR-2091 Varian Clinac 2100C
with collimator set to 90 degrees and MLC in parked
mode produced the least scatter radiation to the abdomi-
nal surface. A comparison with the other models tested
is provided in Table 5.
Shielding setup
A shield was constructed using layers of lead with a
length of 120 cm from a roll with a width of 38 cm. Each
sheet was bent at a right angle so that there was con-
tinuous shielding anteriorly and laterally. While there is
no theoretical upper limit to the desirable shield thick-
ness, since any increase in thickness will further reduce
the foetal dose, practical limitations exist because of the
size and weight of the shield. The combined thickness of
the sheets resulted in a lead block of at least 75 mm in
thickness. By cutting the rolls into 22 sheets (264 cm),
the total weight was 200.64 kg (= 26.4m ¥ 0.38 m ¥

Table 5. Comparison of scattered doses from three machines available for the treatment of case 1

Model Multileaf Measured dose rate Measured dose rate

collimators at 6 MV (%)† at 10 MV (%)†

BW Varian 600C No 0.018 ND

HL Varian Clinac 2100C No 0.029 0.031
NR-2091 Varian Clinac 2100C with collimator at 0 degrees Yes 0.015 0.014
NR-2091 Varian Clinac 2100C with collimator at 90 degrees Yes 0.011 0.009

†Scattered doses given as percentage of prescribed dose. ND, no data.

© 2009 The Authors

562 Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists

20 kg/m2). These sheets were individually cut, shaped
and placed upon a supporting pallet. As this would
exceed the support capacity of the treatment couch, a
mobile free-standing standard aluminium construction
scaffolding was used to support it. The shield was
wheeled and positioned over the patient for each treat-
ment. Bracing was attached between the support legs in
both the lateral and longitudinal dimensions to prevent
them from spreading and collapsing. The final frame
design was larger in all dimensions than was strictly
necessary to support the shield in order to provide
the necessary stability. The limitation on the load capac-
ity of the frame required a compromise to be achieved
between the thickness and area covered by the lead. The
height of the pallet was pre-set to ensure that it would
bring the shield as close to the patient’s abdomen as
possible while still ensuring comfort. This was based
upon a set of measurements of patient and field dimen-
sions taken during simulation. The average fundal
radiation measurement was 2.7 mGy, and shielding
reduced the scatter from the treatment arrangement by
approximately 50%, suggesting that the only contribut-
ing factor to the foetal dose was as a result of internal
scatter.
Results of literature review
Full details of all cases included after the literature
search can be found in Tables 6 and 7. A total of 100
patients who were treated with radiotherapy during
pregnancy who met the inclusion criteria were identified.
Of these, 59 papers identified patient age, 83 identified
treatment dose, 64 identified foetal radiation dose, 46
identified gestation at the start of radiotherapy and 50
identified long-term follow-up. The median patient age
was 26 (range 17–45) years old. The mean treatment
dose was 39 (standard deviation (SD) = 17) Gy. The
median foetal radiation dose was 0.16 (interquartile
range (IQR) = 0.055–13) Gy. In those studies, reporting
long-term infant follow-up, the median follow-up dura-
tion was 24 (IQR 9.75–118.5) months. The literature
review demonstrated that in the 100 cases reviewed, 11
were adverse long-term foetal outcomes, including two
spontaneous abortions and five perinatal deaths.
Discussion
Our case review demonstrates that radiotherapy can be
administered to pregnant patients, but adverse out-
comes may occur. Most previous reports include a
technical discussion of the measures taken to minimise
foetal doses, but few describe the outcome of extended
follow-up, which is relevant given the potential for
radiotherapy to increase the risk of childhood compli-
cations. Six of the nine offspring in our series had long-
term follow-up available. With regard to the offspring,
there was one death in utero, one elective termination
© 2009 The Authors
Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists
Pregnancy and radiotherapy
of pregnancy, one on which no data is available and in
the remaining six cases, no major foetal abnormalities
were noted. All six children, on whom long-term
follow-up was obtained, were in good health with an
average age of 10.3 years. Unfortunately, foetal dose
estimates were available in just five of the nine cases
in our case review, which is a weakness of our retro-
spective case review.
In the case where pregnancy was terminated, the
pregnancy was not anticipated by the patient, and the
abdomen was estimated to have received a dose that
carried a high risk of complications. This highlights the
need to exclude the possibility of pregnancy in women of
child-bearing age that require irradiation.
One infant suffered from hypospadias, which was
surgically corrected. Hypospadias affects one in 250
male newborns and is usually an isolated anomaly.39
Suspected causes of hypospadias include in utero expo-
sure to chemicals capable of estrogenic or androgenic
endocrine disruption, such as polychlorbiphenyls and
phytoestrogens, androgen receptor abnormalities, or
anomalies in the hypothalamic-pituitary-gonadal axis
maturation.39,40 As the child’s mother had received
cranial irradiation, effects on the maternal pituitary
gland, and hence, maternal hormonal levels, cannot be
excluded as a possible mechanism for this anomaly.
Case 1 demonstrates that when adverse foetal out-
comes occur in pregnant patients undergoing radio-
therapy, it is tempting for the patient to attribute the
abnormality to an adverse effect of the radiotherapy. We
could find no evidence that radiotherapy was responsible
for the stillbirth, although the pathologist postulated that
endothelial damage associated with the radiotherapy
could have resulted in the release of thrombotic factors
that crossed the placenta. No support for this postulate
could be found in the literature, nor was any radiation
biologist or oncologist consulted before it was included in
the patient’s medical record.
Our literature review indicated that there are few
reports that have commented on long-term follow-up of
the offspring. Overall, with the inclusion of the nine
cases in this case report, there have been 109 cases of
radiotherapy used in pregnancy published in the litera-
ture that met our search criteria. Of those papers
describing long-term follow-up, the median follow-up
duration was 37 months, with a maximal follow up of
372 months. Of the cases published, there were 13
adverse outcomes, two spontaneous abortions, five
perinatal deaths, one still birth, one sensorineural
hearing loss, one case of learning difficulties and scolio-
sis, one case of undescended testis and ventricular
septal defect, one case of hypospadias and one case of
developmental delay, failure to thrive, expressive prob-
lems and attention deficit disorder. Just four of these
cases reporting adverse outcomes reported an esti-
mated foetal dose, with all four cases reporting an
exposure of <0.1 Gy: a dose at which rates of foetal
563
564
SA Luis et al.

Table 6. Summary of literature (includes this case series)

Malignancy [reference] Number of Maternal age Treatment Shielding used Estimated foetal Gestation at Number Offspring follow Number of
reported in years dose in Gy (yes/unknown/no) radiation dose commencement followed up up duration range reported cases
cases (median) (median) in Gy (median) of radiotherapy in only at birth (median) where with adverse
weeks (median) long term follow outcomes in
up available offspring
(months)

Basal cell carcinoma 1 28 (28) 50.0 (50.0) 1/0/0 – (–) 26 (26) 0 108 (108) 0
Brain3–7 7 22–41 (29) 40.0–54.0 (42.0) 2/1/4 0.00270–0.08000 (0.03000) 18–28 (21) 3‡ 9–38 (22) 1
Breast8–12 23 28–45 (41) 30.0–78.0 (41.0) 2/19/2 0.03900–0.16000 (0.15000) 2–24 (17.5) 23† – (–) 2
Hodgkin’s lymphoma13–29 58 17–35 (25) 6.0–44.0 (36.0) 31/10/17 0.00100–10.00000 (0.08500) 1–33 (20) 24‡ 12–372 (–)¶ 3
Low-grade fibrosarcoma of 1 24 (24) 76.0 (76.0) 1/0/0 0.18000 (0.18000) 10 (10) 0 14 (14) 0
knee30
Malignant schwannoma cervical 1 24 (24) 60.0 (60.0) 1/0/0 0.03600 (0.03600) 17 (17) 1 – (–) 0
plexus31
Malignant Histiocytoma 1 24 (24) 60.0 (60.0) 1/0/0 0.29000 (0.29000) 21 (21) 0 168 (168) 0
Maxillary sinus 1 33 (33) 90.0 (90.0) 1/0/0 0.00003 (0.00003) – (–) 1 – (–) 0
adenocarcinoma32
Melanoma33 2 34–36 (35) 32.0–55.0 (43.5) 2/0/0 0.05000 (0.05000) 22–24 (23) 1 108 (108) 2
Metastatic Breast carcinoma to 1 30 (30) 30 (30) 0/1/0 – (–) 10 (10) 1 – (–) 1
lumbar spine19
Nasopharyngeal34,35 5 29 (29) 60.0–70.0 (65.0) 1/4/0 0.05700 (0.05700) 8–32 (24) 4§ 120–240 (–) 3
Non-Hodgkin’s lymphoma36–38 3 28–35 (29) 2.0–52.0 (26.0) 1/1/1 0.01800–0.10000 (0.06000) 4–30 (23) 0 6–72 (9) 1
Parotid mucoepidermoid 1 25 (25) 57.8.0 (57.8.0) 1/0/0 – (–) 20 (20) 0 120 (120) 0
carcinoma
Pulmonary carcinoid 1 41 (41) 50.0 (50.0) 1/0/0 – (–) – (–) – – (–) 0
Tongue29,36 3 29–32 (29) 39.0–64.0 (41.0) 1/2/0 0.09000 (0.09000) 22–28 (26) 0 2–48 (48) 0

†Includes two perinatal deaths. ‡Includes one perinatal death. §Includes three perinatal deaths. ¶Individual patient follow-up not specified. Follow-up duration for the group of patients with
nasopharyngeal carcinoma was between 120 and 240 months. Median follow up for breast cancer patients could not be determined as data include a case series of 16 patients without individual
follow-up data: these patients had been followed up for between 12 and 372 months.

© 2009 The Authors

Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists
 Table 7. Summary of cases with adverse outcomes

Author (case number) Malignancy Age of Beam energy Treatment Shielding Region treated Foetal Gestation at Follow up duration Health of child
[reference] patient dose (Gy) used radiation start of for child
(years) dose (Gy) Radiotherapy (months after
(weeks) birth)

© 2009 The Authors

Luis et al. (1) High grade 38 6 MeV photons 54 Yes Brain 0.0027 20 – Died in utero
astrocytoma
King et al.12 Breast cancer Chest wall, axilla Perinatal death
King et al.12 Breast cancer Chest wall, axilla Perinatal death
Mulvihill et al. (9)19 Hodgkin’s disease 25 Mantle 3 ~192 Sensory loss because of inner ear
defect
Mulvihill et al. (11)19 Hodgkin’s disease 24 Mediastinum, 28 ~132 Slow learner, scoliosis
supraclaviclular
fossae
Jacobs et al. (N)20 Hodgkin’s disease 23 6 MeV 44 No Breast 0.09 At conception Spontaneous abortion
Luis et al. (2) Melanoma 36 6 MV photons and 55 Yes Left infraorbital 22 108 Hypospadias successfully corrected
6 MeV electrons nerve
Daly et al.33 Metastatic 34 32 Yes Axilla 0.05 24 At birth Undescended left testicle at the
melanoma external inguinal ring.
Uncomplicated, restricted,
perimembranous ventricular
septal defect.
Mulvihill et al. (10)19 Metastatic breast 30 30 Lumbar spine 10 Spontaneous abortion

Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists
carcinoma to
lumbar spine
Jie-Hua et al.35 Nasopharyngeal 60–70 Nasopharynx, neck, Perinatal death
carcinoma supraclavicular
fossae
Jie-Hua et al.35 Nasopharyngeal 60–70 Nasopharynx, neck, Perinatal death
carcinoma supraclavicular
fossae
Jie-Hua et al.35 Nasopharyngeal 60–70 Nasopharynx, neck, Perinatal death
carcinoma supraclavicular
fossae
Spitzer et al.37 Non-Hodgkin’s 35 18 MeV electrons 26 Yes Chest wall, <0.1 30 ~72 Foetal distress during delivery. At
lymhoma & 10MV photons mediastinum 6 years, remains below 5th
percentile for height and weight.
Has expressive problems,
attention deficit disorder, delayed
co-ordination and motor
development.†

†Following radiotherapy, growth of the fundal height slowed significantly. At 38 weeks gestation, the patient ruptured membranes spontaneously and developed chorioamnionitis. Labour was induced
with pitocin but the fetal heart rate tracing showed moderate variable decelerations and a fetal scalp pH was 7.21. A primary transverse lower segment Caesarean section was performed through a
Phannenstiel incision. The baby was a viable female weighing 2015 g, with Apgar scores of 8 at 1 min and 9 at 5 min. At 6 years, she remains below the 5th percentile for height and weight, has
expressive problems, attention deficit disorder, and delayed co-ordination and motor development.

565
Pregnancy and radiotherapy
SA Luis et al.
abnormalities are said to appear indistinguishable
from the background rate of spontaneous congenital
abnormalities.1 Only eight cases reporting adverse out-
comes reported gestation at the start of radiotherapy.
Of these, two cases were less than 10 weeks gestation,
four cases were between 10 and 27 weeks inclusive and
two cases were greater than 27 weeks gestation. In the
cases where radiotherapy was commenced at less than
10 weeks gestation, spontaneous abortion and sensory
loss because of inner ear defect occurred, which are
consistent with the expected risks published by the
AAPM given the gestational age.1 There were two
malformations occurring in the 10- to 27-week group,
which was again consistent with the expected risk.33
There was a case of spontaneous abortion occurring
with radiotherapy at 10 weeks gestation,19 and a child
with learning difficulties and scoliosis at 28 weeks
gestation:19 these risks are more in keeping with the
less than 10 weeks and 10- to 27-week groups, respec-
tively and hence consistent with the risks documented
by the AAPM.1 As reported in our case review, there
was a death in utero occurring with radiotherapy given
at 20 weeks gestation. While it is suggested that
this is not an expected risk1 as we have mentioned
earlier, it is difficult to ascertain if this foetal death was
attributable to radiotherapy or not. While the risk of
malformation and mental retardation are small above
25–28 weeks gestation, Spitzer et al.37 reported a
case in which a child, whose mother was treated at
30 weeks gestation, has expressive problems, atten-
tion deficit disorder, delayed co-ordination and motor
development.
A particularly striking finding was the major difference
in the scattered doses generated by different treatment
machines. Prior to the treatment of case 1, the scattered
doses from the three machines available in the depart-
ment were compared. The results are shown in Table 5.
The machine with MLC produced a dramatically lower
reading and was thus selected for the treatment of the
patient. It is recommended to other departments that in
the future, if treating a pregnant patient, compare the
scattered doses prior to treatment and use a machine
with MLC. If no machine with MLC is available, then
consideration should be given to transferring the patient
to another department where it is available.
As the need to treat a pregnant patient arises infre-
quently, there is an onus for the treating staff to consider
abdominal shielding requirements, constraints and pos-
sible solutions, followed by its design, construction, vali-
dation and implementation. The need to address each
of these from first principles is potentially very time-
consuming and inconsistent with the clinical imperative
to commence treatment quickly. An ideal solution would
be a purpose-built, dedicated shielding device that is
always available for use in these circumstances. This
would reduce the delay to commencement of treatment
and allow the design to be optimised for weight-bearing
566 Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists
capacity, ease of use and safety. While the high fabri-
cation cost of AUS$3500, including labour, materials and
lead for the shield, was deemed to be disproportionate to
the benefits of having such a device available for long-
term use, it may be both beneficial and financially fea-
sible at larger treatment centres. It should also be noted
that while a temporary solution was chosen on the basis
of cost, the scaffolding was required to be reconstructed
and an engineer’s certification is sought because of con-
cerns from treating radiotherapists regarding safety. The
total cost of the shielding device, including scaffold hire,
assembly and disassembly (twice), engineer’s certifica-
tion, and sheet lead, was AUS$4035.
While many individual cases are reported, very few
case series on the use of radiotherapy in pregnancy are
available in the literature. Fewer still provide long-term
details of maternal and offspring outcome. While this is
the third largest case series published in the literature, it
is still limited by the small total number of cases avail-
able. The results of our literature review are likely to be
affected by publishing bias. Additionally, no constraints
were placed on the date of publication of the cases
included in our review, and so some radiotherapy tech-
niques previously employed may no longer be in use.
Unfortunately, in light of this, firm conclusions as to the
safety of radiotherapy in pregnancy cannot be drawn.
The absolute incidence of adverse events described in
our case series and literature review is rare, and hence,
it is not possible to ascertain if these outcomes are of
statistical significance. Our case series and literature
review serve to further highlight the fact that there is a
paucity of available information on the foetal outcomes
of radiotherapy in pregnancy.
Conclusion and recommendations
We have reported the third largest series of pregnant
patients receiving radiotherapy, with the longest
follow-up of the offspring, noting that a high incidence of
complications or birth defects was not detected. The
following specific recommendations are offered on the
basis of our review:
1 If radiotherapy is to be given, the different treatment
machines available within the department should be
compared as the potential for scattered doses to the
foetus may vary considerably.
2 Where possible, an extended follow-up of patients
and their offspring should be undertaken as there is
relatively little information about this available in
the literature. Ideally, if possible, a national or inter-
national registry of such cases should be set up and an
extended follow-up should be recorded.
3 The manufacturers of radiotherapy treatment
machines should consider having advice available
about the design and use of shielding for pregnant
patients but this is not currently available.
© 2009 The Authors

Acknowledgements
The authors would like to thank Brendan Hill for his input
into the physics aspects of this paper as well as his help
in revising the paper.
References
1. Stovall M, Blackwell CR, Cundiff J et al. Foetal dose
from radiotherapy with photon beams: report of
AAPM Radiation Therapy Committee Task Group No.
36. [erratum appears in Med Phys 1995 Aug; 22 (8):
1353–4]. Med Phys 1995; 22: 63–82.
2. Podgorsak MB, Meiler RJ, Kowala H, Kishel SP, Orner
JB. Technical management of a pregnant patient
undergoing radiation therapy to the head and neck.
Med Dosim 1999; 24: 121–8.
3. Scrimger J, Urtasum RC. Foetal dose during
irradiation of head tumor. J Can Assoc Radiol 1973;
24 (3): 280–2.
4. Sneed PK, Albright NW, Wara WM, Prados MD, Wilson
CB. Foetal dose estimates for radiotherapy of brain
tumors during pregnancy. Int J Radiat Oncol Biol
Phys 1995; 32 (3): 823–30.
5. Imai A, Kawabata I, Tamaya T. Primary brain
malignant lymphoma newly diagnosed during
pregnancy. J Med 1995; 26 (5–6): 333–6.
6. Isla A, Alvarez F, Gonzalez A, Garcia-Grande A,
Perez-Alvarez M, Garcia-Blazquez M. Brain tumor and
pregnancy. Obstet Gynecol 1997; 89 (1): 19–23.
7. Magne N, Marcie S, Pignol JP, Casagrande F,
Lagrange JL. Radiotherapy for a solitary brain
metastasis during pregnancy: a method for reducing
foetal dose. Br J Radiol 2001; 74 (883): 638–41.
8. Cohen Y, Tatcher M, Robinson E. Radiotherapy in
pregnancy. A case report with estimation of the dose
to the fetus. Radiol Clin Biol 1973; 42 (1): 34–9.
9. Ngu SL, Duval P, Collins C. Foetal radiation dose in
radiotherapy for breast cancer. Australas Radiol
1992; 36 (4): 321–2.
10. Van der Giessen PH. Measurement of the peripheral
dose for the tangential breast treatment technique
with Co-60 gamma radiation and high energy X-rays.
Radiother Oncol 1997; 42 (3): 257–64.
11. Kouvaris JR, Antypas CE, Sandilos PH, Plataniotis GA,
Tympanides CN, Vlahos LJ. Postoperative tailored
radiotherapy for locally advanced breast carcinoma
during pregnancy: a therapeutic dilemma. Am J
Obstet Gynecol 2000; 183 (2): 498–9.
12. King RM, Welch JS, Martin JK, Coulam CB. Carcinoma
of the breast associated with pregnancy. Surg
Gynecol Obstet 1985; 160: 228–32.
13. Woo SY, Fuller LM, Cundiff JH et al. Radiotherapy
during pregnancy for clinical stages IA–IIA Hodgkin’s
disease. Int J Radiat Oncol Biol Phys 1992; 23 (2):
407–12.
14. Stewart HL Jr, Monto RW. Hodgkin’s disease and
pregnancy. Am J Obstet Gynecol 1952; 63 (3):
570–8.
© 2009 The Authors
Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists
Pregnancy and radiotherapy
15. Kushner JI. Pregnancy complicating Hodgkin’s disease
(lymphogranuloma malignum). Am J Obstet Gynecol
1941; 42: 536–8.
16. Becker MH, Hyman GA. Management of Hodgkin’s
disease coexistent with pregnancy. Radiology 1965;
85 (4): 725–8.
17. McSwain B, Haber A Jr. Hodgkin’s disease
complicated by pregnancy. South Med J 1951; 44
(2): 105–9.
18. Thomas PR, Biochem D, Peckham MJ. The
investigation and management of Hodgkin’s disease
in the pregnant patient. Cancer 1976; 38 (3):
1443–51.
19. Mulvihill JJ, McKeen EA, Rosner F, Zarrabi MH.
Pregnancy outcome in cancer patients. Experience in
a large cooperative group. Cancer 1987; 60 (5):
1143–50.
20. Jacobs C, Donaldson SS, Rosenberg SA, Kaplan HS.
Management of the pregnant patient with Hodgkin’s
disease. Ann Intern Med 1981; 95 (6): 669–75.
21. Nisce LZ, Tome MA, He S, Lee BJ 3rd, Kutcher GJ.
Management of coexisting Hodgkin’s disease and
pregnancy. Am J Clin Oncol 1986; 9 (2):
146–51.
22. Covington EE, Baker AS. Dosimetry of scattered
radiation to the fetus. JAMA 1969; 209 (3):
414–5.
23. Conley JG, Jacobson A. Modified radiation therapy
regimen for Hodgkin’s disease in the third trimester
of pregnancy. AJR Am J Roentgenol 1977; 128 (4):
666–7.
24. Smith HN, Spaulding L. Hodgkin’s disease in
pregnancy. South Med J 1978; 71 (4): 374–6.
25. Tawil E, Mercier JP, Dandavino A. Hodgkin’s disease
complicating pregnancy. J Can Assoc Radiol 1985; 36
(2): 133–7.
26. Friedman E, Jones GW. Foetal outcome after
maternal radiation treatment of supradiaphragmatic
Hodgkins disease. Can Med Assoc J 1993; 149 (9):
1281–3.
27. Leung JT, Kuan R, Patel V. Radiotherapy for
Hodgkin’s disease in pregnancy. Australas Radiol
1996; 40 (2): 146–8.
28. Cygler J, Ding GX, Kendal W, Cross P. Foetal dose for
a patient undergoing mantle field irradiation for
Hodgkin’s disease. Med Dosim 1997; 22 (2):
135–7.
29. Nuyttens JJ, Prado KL, Jenrette JM, Williams TE.
Foetal dose during radiotherapy: clinical
implementation and review of the literature. Cancer
Radiother 2002; 6 (6): 352–7.
30. Nair RP, Nair TK, El-Akkad S. Evaluation of foetal
dose from megavoltage irradiation of the knee
and neonate followup. Med Phys 1983; 10 (6):
862–5.
31. Moeckli R, Ozsahin M, Pache G, Valley JF, Mirimanoff
RO, Azria D. Foetal dose reduction in head and neck
radiotherapy of a pregnant woman. Z Med Phys
2004; 14 (3): 168–72.
567
SA Luis et al.
32. Fetoni AR, Galli J, Frank P, Marmiroli L, Motta S,
Almadori G. Management of advanced
adenocarcinoma of maxillary sinus in a young woman
during pregnancy: a case report. Otolaryngol Head
Neck Surg 2002; 126 (4): 432–4.
33. Daly TA, Burmeister BH, Smithers BM, Doody J, Kane
A. Radiotherapy for metastatic melanoma presenting
in pregnancy. Australas Radiol 2006; 50 (6):
598–603.
34. Wong F, Sai-Ki O, Cheung F, Shiu W. Pregnancy
outcome following radiotherapy for naso-pharyngeal
carcinoma. Eur J Obstet Gynecol Reprod Biol 1986;
22 (3): 157–60.
35. Jie-Hua Y, Caisen L, Yuhua H. Pregnancy and
nasopharyngeal carcinoma: a prognostic evaluation of
27 patients. Int J Radiat Oncol Biol Phys 1984; 10:
851–855.
568
36. Shibuya H, Saiot M, Horiuchi JI, Suzuki S. Treatment
of malignant head and neck tumors during pregnancy
– a report of 3 cases. Acta Oncol 1987; 26 (3):
237–8.
37. Spitzer M, Citron M, Ilardi CF, Saxe B. Non-Hodgkin’s
lymphoma during pregnancy. Gynecol Oncol 1991;
43 (3): 309–12.
38. Castelo-Branco C, Torne A, Cararach V, Iglesias X.
Mycosis fungoides and pregnancy. Oncol Rep 2001; 8
(1): 197–9.
39. Behrman RE, Kliegman RM, Jenson HB (eds). Nelson
textbook of pediatrics, 17th edn. Saunders,
Philadelphia, PA, 2004.
40. Greenspan FS, Gardner DG (eds). Basic and clinical
endocrinology, 7th edn. McGraw-Hill, New York,
2004.
© 2009 The Authors
Journal compilation © 2009 The Royal Australian and New Zealand College of Radiologists