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Title of the article:
Advanced Case of Glioblastoma Multiforme (GBM) and Pregnancy an Ethical Dilemma:
Case Report and Review of the Literature
Abstract:
Glioblastoma multiforme (GBM) is the most common and most malignant form of the
glial tumors. Advanced and treated GBM is rarely associated with pregnancy for many
reasons. GBM presenting during pregnancy carries unique challenges to the patient,
baby, family and health care providers. We describe an unusual case of advanced
Glioblastoma Multiforme (GBM) and pregnancy at 18th weeks gestation associated
with Ethical Dilemma. We manage to deliver the baby through caesarian section at
weeks 28th safely. This case occur at Intensive care unit of tertiary care hospital,
university-affiliated. Although, recurrent GBM carry dismal prognosis, pregnancy can
still be carried and multidisciplinary team work is the key for successful outcome.
KEY WORDS:
Glioblastoma Multiforme; pregnancy; chemotherapy; complications; diagnosis; treatment
Text
Introduction
Glioblastoma multiforme (GBM) is the most common and most malignant form of the glial
tumors. The etiology of GBM is unknown in most cases. However, suggested causes include
genetic factors, cell phone use, head injury, N-nitroso compounds, occupational hazards,
electromagnetic field exposure and possibly race [1, 2, 3 ]. Advanced and treated GBM is
rarely associated with pregnancy for many reasons. Exposure to the standard therapy of
glioblastoma usually adversely affects fertility [4]. Radiotherapy at a dose exceeding 45 Gy
usually impairs the synthesis of gonadotropins, whereas the newer chemotherapy with
alkylating agents such as temozolomide is associated with impaired ovarian function leading
to premature menopause [4, 5, 6]. GBM presenting during pregnancy carries unique
challenges to the patient, baby, family and health care providers. Additionally, evidence
relating to timing of surgery and the use of radiotherapy and chemotherapy in pregnancy is
still limited. In a situation like this, the potential benefits to the mother must be balanced
against the risks to the fetus [7, 8].
Case Report
A 36 year old lady gravida 10, para 7, (G10P7+2) who is known to have advanced and nonoperable right parital Glioblastoma Multiforme (GBM) that was diagnosed with Brain MRI
(Fig. 1) and brain biopsy on late 2012 (Fig. 2a & b), she received concurrent chemo-radiation
with (60 Gyr /30 fraction) treatment with oral temozolomide (TMZ) (75 mg/m2) a total dose of
6 grams and the treatment ended on 25/12/2012. This was followed by adjuvant TMZ for
another 5 cycles (the total dose 8.750 grams) and the course completed on 5/2013.
Three months after completing her adjuvant chemotherapy she started to experience a
deterioration on her vision that began on the left side then the right side followed, a follow up
brain MRI showed minimal interval changes in the surrounding edema with no significant
tumor progression (Fig. 3). The patient was seen by the ophthalmology and neurosurgery
services and they recommended a Ventriculo-Perotineum (VP) shunt, which was done on
2/9/2013 and she was discharged after that.
Few months later, she presented to the emergency department with fever and a decreased
level of consciousness. On examination, her BP was 114/86 mmHg, pulse of 135 beats per
minute, and T 38.6C. Her oxygen saturation on room air was 98% with normal Glasgow
Coma Scale (GCS), but neurologically she had left sided hemiplegia. Chest and
Cardiovascular examinations were unremarkable. Abdominal exam showed fullness in the
lower abdomen. Ultra sound pelvis revealed a viable fetus at 18 weeks of gestation with no
obvious congenital anomaly.
Accordingly she was hospitalized and treated with the appropriate antibiotics. The patient,
husband and her family were informed with her pregnancy as well as the risk and anticipated
complications that might happen during this pregnancy. It was clearly stated by the patient
and her husband that they would like to carry on with the current pregnancy. Initially the
family was in favor of terminating the pregnancy, but after family counseling there decision
was to support the couples’ choice. The case was referred to the high risk pregnancy
services and the religious committee, the situation was discussed in details and the final
decision was to carry on the pregnancy with closely monitoring the mother.
Shortly after admission, she developed a decrease in her level of consciousness for which
she was intubated, mechanically ventilated and admitted in the ICU for further management.
The repeated brain MRI showed significant Brain edema with intra tumor bleed (Fig.4).
Neurosurgery recommendation was for no surgical intervention and advice for close
observation and conservative management. A follow up US showed normal female fetus with
no congenital anomaly. The husband and the family were updated again of the patient
condition and they insisted to carry on with the pregnancy. In the ICU, she continued on
mechanical ventilation and required tracheostomy, however, she remained in coma with
GCS of 3 to 4 but hemodynamically stable.
A Multidisciplinary team meeting was held which included an ICU consultant, a medical
oncologist, a high risk obstetrician and a neonatologist to discuss the situation of the patient
and the expected outcome. Based on the limited evidence in the literature and the family
wish the final plan was to:
1. Give full support to the mother and chemotherapy as directed by the medical oncology
team.
2. Have an elective Cesarean Section (C/S) at the 28th week.
3. Have an emergency C/S at the 24th week if mother got arrested.
4. No intervention before the 24th week.
At 28 week she had elective C/S and the female baby was normal for gestational age with
birth weight of 890 gram, Apgar scores were 8/1, 9/10, her post delivery period complicated
with acute respiratory distress syndrome, sepsis, and jaundiced, but ultimately she recovered
and was discharged home on stable condition.
The mother was transferred back to the ICU; two weeks later she was assessed for
chemotherapy after a base line brain MRI(Fig.5). She was started on palliative TMZ 5/28 day
cycle, 2 days later she developed cardiac arrest, for which she was resuscitated but not
revived, and pronounced dead.
Discussion
GBM is the most aggressive primary brain tumor and usually carries a poor prognosis.
Recurrent disease also has a worse outcome and pregnancy makes the situation more
challenging. There is no clear guideline for how to manage a pregnant woman with GBM and
the management depends only on case reports and small series in the literature. The
administration of chemotherapy during pregnancy especially during the first trimester is risky
and can induce harmful effects on both the mother and the fetus and in fact the current
recommendations are based on animal and epidemiological studies. For the fetus the
expected problems include congenital anomaly, organ toxicity, growth retardation and
developmental delay beside potential carcinogenesis. The mother risk would include still
birth, spontaneous abortion, and maternal sterility.
The common chemotherapy drugs used include Temozolamide (TMZ), Procarbazine,
Lomustine, and Vincristine (PCV). Alkylating agents are recognized to cross the placenta and
therefore fetal toxicity can happen. The magnitude of the damage usually depends on the
gestational age and duration of exposure to these medications. Bevacizomab which is an
angiogenesis inhibitor is used as first line therapy for recurrent GBM. It is considered
category C. Although radiotherapy is an important part of GBM treatment, it was not possible
as she had her radiation in less than a year as directed by the radiation oncology team.
Surgery is always an option for recurrent GBM and craniotomy can be safely done during
pregnancy particularly early trimester.
We used the best available evidence in the literature to manage this patient. The
multidisciplinary management approach as well as frequent family meetings were the key
factor in managing this patient and her baby.
Conclusion
Advanced and recurrent GBM carry dismal prognosis, pregnancy can still be carried.
Continuous family counseling and multidisciplinary team work approach is the fundamental
factor for successful outcome.
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