F1000Research 2013, 2:246 Last updated: 16 MAY 2019

CASE REPORT
Case Report: Pregnancy in a patient with recurrent glioblastoma 
[version 1; peer review: 2 approved]
Birgit Flechl1, Marco Ronald Hassler1, Gerhard Kopetzky2, Peter Balcke2, 
Christine Kurz3, Christine Marosi1,4
1Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, 1090 Vienna, Austria
2Department of Internal Medicine I, General Hospital of St. Pölten, 3100 St. Pölten, Austria
3Department of Obstetrics and Gynaecology, Clinical Division of Endocrinology, Medical University of Vienna, 1090 Vienna, Austria
4Comprehensive Cancer Center-Central Nervous System Tumours Unit (CCC-CNS), Medical University of Vienna, 1090 Vienna, Austria

First published: 15 Nov 2013, 2:246 ( Open Peer Review

v1 https://doi.org/10.12688/f1000research.2-246.v1)
Latest published: 15 Nov 2013, 2:246 (
https://doi.org/10.12688/f1000research.2-246.v1)
Reviewer Status    

Abstract   Invited Reviewers
We report the case of a woman with relapsed glioblastoma multiforme 1   2
(GBM) who recently gave birth. She announced her pregnancy shortly after
the sixth cycle of a dense regimen of temozolomide, prescribed for treating version 1
the first recurrence of glioblastoma. Three years ago, in April 2008, she had  
published report report
undergone gross total resection of a glioblastoma multiforme in the 15 Nov 2013
postcentral region of the right hemisphere and had subsequently received
treatment according to the actual standard therapy consisting of
radiotherapy up to 60 Gy with concomitant and adjuvant temozolomide. 1 Deborah Blumenthal, Tel-Aviv Sourasky
The complete amount of temozolomide given before this pregnancy was Medical Center, Tel-Aviv, Israel
20.9 mg/m2. Nevertheless, she delivered a 1890 g child by caesarean
2 Mari-Paule Thiet, University of California, San
section in the 32/6 week of pregnancy. The child showed no anomalies and
Francisco, CA, USA
is developing normally under close surveillance by paediatricians.
Any reports and responses or comments on the
Keywords
glioblastoma, pregnancy under chemotherapy article can be found at the end of the article.

Corresponding author: Christine Marosi ([email protected])
Competing interests: The author(s) declare that they have no competing interests.
Grant information: The Medical University of Vienna supported this work.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright: © 2013 Flechl B et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article
are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).
How to cite this article: Flechl B, Hassler MR, Kopetzky G et al. Case Report: Pregnancy in a patient with recurrent glioblastoma [version
1; peer review: 2 approved] F1000Research 2013, 2:246 (https://doi.org/10.12688/f1000research.2-246.v1)
First published: 15 Nov 2013, 2:246 (https://doi.org/10.12688/f1000research.2-246.v1) 

 
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Introduction section, distal progression in the brain was diagnosed on MRI and
Cases of pregnancy and giving birth are rare in patients with malig- she was referred for radiotherapy of the distant recurrence.
nant gliomas. Besides the grim prognosis of malignant gliomas, the
actual standard therapy of glioblastoma adversely affects fertility1. Discussion
In fact, radiotherapy aimed at the hypothalamus and the pituitary Temozolomide has been classified to pregnancy category D by the
gland exceeding 45 Gy could impair the synthesis of gonadotropins, US Food and Drug Administration, which means that animal stud-
while chemotherapy with alkylating agents such as temozolomide ies have revealed evidence of embryo lethality induced by the drug.
is associated with impaired ovarian function leading to premature Moreover, malformations have been observed in animals, therefore
menopause1–3. However, there are some reports of pregnancies in women are advised to avoid becoming pregnant during temozolo-
women with malignant gliomas1,4–11, describing women whose mide intake. However, we report here the pregnancy of a woman
brain tumors were diagnosed during pregnancy, as well as women with GBM, treated with radio/chemotherapy using a protocol de-
who already had undergone treatment for malignant gliomas and scribed by Stupp et al.12 and further dose dense temozolomide in
who became pregnant afterwards. Our recent patient is an exam- relapse 5 days of seven, as described by Strik et al.15.
ple of a patient whose fertility was not suppressed by glioblastoma
multiforme (GBM) and its treatment. There are some previous reports on pregnancies in women with ma-
lignant glioma. Nadine Johnson retrospectively reported the obstet-
Case ric outcomes of women with intracranial neoplasms, from Ontario,
The patient is a 37 year old woman, born in Austria. She had two Canada, covering the experience of 6000 deliveries. In this data-
children (13 and 15 years) before her GBM diagnosis. She was diag- base, Johnson et al. identified 25 pregnancies in women who had
nosed with GBM in the right frontal lobe in April 2008, and treated been diagnosed with intracranial neoplasms, including 12 patients
according to a current treatment standard consisting of a gross to- with gliomas8. This review discusses neurological deterioration due
tal resection of the tumor, fractionated confocal radiotherapy up to to the hormonal changes causing fluid retention during pregnancy
60 Gy (2 Gy/fraction) and concomitant and adjuvant chemotherapy and the complications and the management of increased cranial
with temozolomide12. Diagnosis and treatment were performed at pressure at the time of delivery. There are some small series and
the Medical University of Vienna (MUV). Following the concomi- case reports on the same issues4,7–10,14,16,17.
tant therapy, she experienced amenorrhea for 6 months, followed
by irregular menstrual cycles with oligomenorrhea. Two years later, Deborah Blumenthal (2008) reported a series of 6 women with
a local recurrence of GBM was diagnosed. She underwent a sec- malignant glioma with unplanned pregnancies during glioma
ond resection and followed 6 cycles of dose dense temozolomide, treatment. Several women even had drug exposure during the first
100 mg/m2 orally for five days per week, with a drug holiday over trimester of pregnancy, three with PCV (procarbazine, cyclophos-
every weekend. She became pregnant less than three weeks after phamide, vincristine), and three with temozolomide17. All gave
the last intake of the sixth cycle of temozolomide, after a total dose birth to healthy, full term infants with no evidence of congeni-
of temozolomide of 20.9 g/m2 (Table 1). tal malformations. Sadly, five of the six mothers died within the
following 2.5 years due to recurrence of disease17.
Both parents wanted to carry the child to term. They were offered
intensified pregnancy monitoring and genetic counselling, but no An adverse effect on disease outcome during pregnancy has been
genetic tests were performed. During pregnancy the child devel- observed in six of eight pregnancies in women with low grade glio-
oped normally as followed by close meshed ultrasound controls and mas followed by the French low grade glioma (LGG) group, possi-
the mother was doing well until week 27, when she developed signs bly due to the decreased immune surveillance during pregnancy or
of increased intracranial pressure as well as weakness of the left to the presence of potential hormonal receptors on glioma cells4,16.
leg. She was admitted to the local general hospital for observance In a later series on 12 pregnancies of women with LGG followed
and anti edematous treatment. As the mother’s condition worsened, by the same research group published 2010, the growth rate of the
she received corticosteroids to induce lung maturation of the fetus, gliomas increased during pregnancy as measured by successive
and the child was delivered after 32 weeks and 6 days of preg- MRI scans16.
nancy by caesarean section using the Misgav Ladach method13,14.
The child showed Apgar scores of 8/9/9, one, five and ten minutes However, the prolonged survival of our patient 18+ months after
after birth, respectively, weighed 1876 g, cried spontaneously and the diagnosis of a relapsed glioblastoma appears noteworthy. This
was neurologically inconspicuous. The infant did not need further case also should bring to mind the necessity of repeated counsel-
respiratory assistance after the third day of life, and was discharged ling about contraception – even in patients where the probability
from the neonatal intensive care unit after an uncomplicated stay of persistent fertility is minimal, as in the patient described in this
without any signs of neurological or any other organ deficit, weigh- report. In fact, regardless of all the apprehensions of medical pro-
ing 2.5 kg. The child has shown normal growth and development fessionals about this pregnancy, the patient and her husband were
ever since. simply happy about it. They wanted to keep this child, even if it
would have meant severe adverse complications for the mother.
The mother underwent her third neurosurgical procedure two weeks after They perceived this pregnancy as a gift of life and enjoyed every
delivery, followed by chemotherapy with fotemustine 100 mg/m2 every moment, even when it was steadily overshadowed by the glioblas-
three weeks for six cycles combined with bevacizumab 10 mg/kg toma. They remembered perfectly well that they had been told that
every two weeks 6 weeks later. Eight months after the caesarean pregnancy should be avoided during and after the glioma treatment,

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Table 1. Total temozolomide dose before the pregnancy.

Temozolomide scheme Temozolomide dose

Concomitant phase 42 days at 75 mg/m 2
3150 mg/m2
5× 150 mg/m2+ 5× 5×200
Adjuvant treatment 5750 mg/m2
mg/m2
Dose 1st line treatment - 8900 mg/m2
Dose temozolomide 6× 100 mg/m × 5 days × 4
2
12000 mg/m2
relapse weeks/month
Total dose 20.900 mg/m2

and that they even had signed this as a part of the regular consent for
treatment; but on the other hand they told us that this pregnancy had Author contributions
been the only happy event for them in all those years. BF was a major contributor in writing and interpreting the manu-
script. RMH has made substantial contributions to the conception
They also tried to organize further care for the child, as the pos- and design of the manuscript. GK and PB delivered essential patient
sibility of the baby losing its mother during childhood is very high. data. CK was involved in revising the report critically for important
As the patient and her husband are aware of the grim prognosis intellectual content. CM made substantial contributions to the con-
of recurrent GBM, they planned to raise the child with multiple ception and design of the report, coordinated the tasks and timelines
psychological parents, including its grown up siblings and the two and was involved in writing and interpreting the manuscript. All
sisters of the mother. authors read and approved the final version of the manuscript.

Conclusion
Competing interests
This report shows that pregnancy and the birth of a healthy infant
The author(s) declare that they have no competing interests.
can occur even in women that have been heavily pretreated with
alkylating agents and that conception can occur as early as three
weeks after the last intake of chemotherapy. Grant information
The Medical University of Vienna supported this work.
Consent
Written informed consent was obtained from the patient for the The funders had no role in study design, data collection and analysis,
publication of this case report. decision to publish, or preparation of the manuscript.

References

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Open Peer Review

Current Peer Review Status:

Version 1

Reviewer Report 21 March 2014

https://doi.org/10.5256/f1000research.2872.r4214

© 2014 Thiet M. This is an open access peer review report distributed under the terms of the Creative Commons

Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly cited.

Mari-Paule Thiet 
Departments of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San
Francisco, CA, USA

This article describes a single case of pregnancy following a diagnosis and treatment of recurrent
glioblastoma. It illustrates that spontaneous pregnancy can be achieved after high doses of
chemotherapy. There is a review of the current literature regarding outcomes of pregnancy in patients with
brain tumors.

Competing Interests: No competing interests were disclosed.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that
it is of an acceptable scientific standard.

Reviewer Report 14 January 2014

https://doi.org/10.5256/f1000research.2872.r3122

© 2014 Blumenthal D. This is an open access peer review report distributed under the terms of the Creative Commons

Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly cited.

Deborah Blumenthal 
Oncology Division, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel

The report, "Pregnancy in a patient with recurrent glioblastoma" illustrates a notable case of a 37 year-old

woman with recurrent glioblastoma (GB)  who became pregnant within 3 weeks of a (6–cycle) dose-dense
temozolomide regimen. The case is notable for preservation of fertility, essentially during alkylating
treatment; positive outcome of the child at planned 32 week delivery by C-section and normal growth and
development at 18 months; and for survival of the mother with recurrent GB 18+ months from recurrence.
 
The authors mention prior related works in the literature regarding the effects of pregnancy on patients
 
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The authors mention prior related works in the literature regarding the effects of pregnancy on patients
with malignant glioma; a series of patients who conceived (with positive fetal outcome) during active
alkylator treatment and documentation of accelerated growth rates of gliomas during pregnancy.
 
This report is encouraging for those patients concerned about fertility issues, but should not be interpreted
as a guarantee for either male or female patients that fertility will be preserved after alkylating
chemotherapy. Additionally, a disclaimer should be made for the potential (confirmed by animal studies
on embryo-lethality with exposure to these drugs) danger to the exposed fetus, despite the reported good
outcomes of these children.

Competing Interests: No competing interests were disclosed.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that
it is of an acceptable scientific standard.

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