Pregnancy and gliomas

Women with a glioma diagnosis, and especially with a lower grade glioma diagnosis which often occurs during the child-bearing years, may find themselves with a difficult decision to make: to have or not have children.

This page reviews some of the published research on pregnancy in women with a glioma diagnosis, and especially how the biology of pregnancy may interact with tumour biology. This sort of knowledge is essential before making the crucial decision whether or not to bear children.

Grade II and III gliomas: 8 cases

A French study (1) reviewed the records of all eight pregnancies from a total cohort of 443 lower grade glioma patients between 1992 and 2007. In five cases, the glioma was diagnosed before pregnancy and in three cases the diagnosis was given during pregnancy. In six of eight cases, a possible negative interaction between pregnancy and glioma behaviour was observed, such as clinical worsening or increased tumour growth rates.

  • Case 1: a 26-year-old women underwent subtotal resection of a grade 2 oligodendroglioma in June 2002. Seizure activity was controlled with one anti-epileptic drug (gabapentin). The tumour velocity of diametric expansion was measured to be 2.7 mm per year between December 2002 and February 2004. Soon afterward in early 2004, the woman became pregnant. Starting from September (month 5 of pregnancy), the woman had recurrent seizures in spite of three antiepileptic drugs (gabapentin, lamotrigine, clonazepam). The tumour velocity of diametric expansion (VDE) increased to 11.1 mm per year during this time. Childbirth occurred in December. Following childbirth, the seizures were again controlled with a single drug and the tumour VDE slowed to 4.8 mm per year. Temozolomide therapy was introduced at that time and the woman was alive at 34 months of follow-up at the time of the study.
  • Case 2: a 27-year-old woman underwent subtotal resection of a grade 2 oligodendroglioma in April 1998. The residual tumour was stable for 2 years. The woman then became pregnant and in February 2000 at month 6 of pregnancy the woman suffered from sudden intracranial hypertension caused by a huge contrast-enhanced cystic tumour recurrence. A cyst puncture was performed and the woman gave Caesarean birth in the seventh month. In March the tumour was removed revealing malignant progression to a grade 3 oligodendroglioma. Radiotherapy was then given and the woman was living a normal life at 6 years of follow-up.
  • Case 3: a 32-year-old woman underwent subtotal resection of a grade 2 astrocytoma in December 1990. Radiotherapy followed surgery. In April 1995 at month 6 of pregnancy, partial seizures occurred, and the woman gave birth in July. Two months later, in September, MRI showed a recurrent tumour with large ring-like contrast-enhancement, followed by a subtotal resection in October. Examination showed malignant progression to secondary glioblastoma. Chemotherapy failed to save the woman’s life, which sadly ended a year later.
  • Case 4: at month 6 of pregnancy, a 24-year-old woman presented with headaches and left hemiparesthesia. After giving birth, an MRI showed a contrast-enhancing tumour which proved to be a grade 3 oligodendroglioma upon examination following total resection. Radiation therapy followed, and the woman was living a normal life after 6 years of follow-up.
  • Case 5: during the 9th month of pregnancy, a 33-year-old woman presented with partial seizures, which led to the finding of an enhancing grade 3 astrocytoma. Right hemiparesis led to a Caesarean birth and total tumour removal 9 days later. Radiation and two cycles of carmustine chemotherapy followed surgery. At 10 years of follow-up the woman had permanent right hemiparesis without tumour recurrence.
  • Case 6: at month 5 of pregnancy, a 26-year-old woman presented with headaches and seizure, leading to the discovery of a large non-enhancing tumour in the fronto-temporal lobes. Anti-epileptic therapy with carbamazepine was started at that time. One month following delivery, she was hospitalized with intractable epilepsy and MRI revealed tumour progression with nodular contrast-enhancement. Sadly the woman died two days later from status epilepticus.
  • Case 7: a 28-year-old woman underwent subtotal resection for a grade 2 oligodendroglioma in January 2002. She received radiotherapy for tumour progression in October 2004. The woman then became pregnant in 2006 and gave birth without tumour-related incident after one year of follow-up.
  • Case 8: a 16-year-old woman presented with a non-enhancing brain tumour in 1993, which a biopsy in 1995 revealed to be a grade 2 oligodendroglioma. Radiotherapy followed biopsy. She became pregnant in 1998 and gave birth, and was living a normal life after 9 years of follow-up.

The authors of this study speculate on a possible link between sex hormones produced during pregnancy, and their interaction with hormonal receptors on glial cells of the central nervous system. Such an interaction could lead to increased tumour growth rates and/or malignant progression. “If a pregnancy is decided, we advise performing a very close neurological follow-up with repeated control MRIs in addition to rigorous obstetrical monitoring.”

Change in tumour growth rates during pregnancy

In 2010, the same group published another study specifically designed to show the influence of pregnancy on tumour growth rate, or the velocity of diametric expansion (VDE). 11 cases of women diagnosed with grade 2 gliomas prior to pregnancy were studied.

In six women (7 pregnancies) treated for their tumour with surgery alone, the mean VDE before pregnancy was 2.3 mm per year. In five patients treated with radiotherapy and/or chemotherapy, the mean VDE before pregnancy was -2.5 mm per year, signifying tumour regression.

An increase in seizure activity was observed during five pregnancies, and patchy areas of contrast-enhancement became evident during two pregnancies. The tumour growth rate increased in all 12 pregnancies. During 9 pregnancies, the VDE increased to twice the velocity observed pre-pregnancy. In the surgery-only group, the mean VDE increased from 2.3 mm per year to 6.4 mm per year during pregnancy. In the radiotherapy/chemotherapy group the mean VDE increased to 6.1 mm per year. In three out of five patients in this subgroup, the tumour was shrinking before pregnancy, but began to increase in diameter during pregnancy.

Seizure activity and symptoms decreased after delivery in all five women whose seizures had worsened during pregnancy. In the surgery-only group, the mean tumour VDE decreased to 4.7 mm per year post delivery. In the radiotherapy/chemotherapy group, in one case the VDE turned negative (tumour regression) reverting to pre-pregnancy behaviour. In another case the VDE slowed down after delivery, but remained higher than before pregnancy. The tumour VDE before, during, and after pregnancy for 12 individual pregnancies are tabulated on page 4 of the study.

Mirroring their previous study, this study found significantly (>2 times) increased growth rates in tumours in 9 out of 12 pregnancies (75%), with increases in seizure frequency in 40%.

Revised Figure

Figures A and B, increased growth rates of gliomas during pregnancy, surgery-only group. Figure D, bottom, shows one case in which tumour regression prior to pregnancy switched to tumour progression during and after pregnancy.

References
  1. Influence of pregnancy in the behavior of diffuse gliomas: clinical cases of a French glioma study group. Pallud et al. 2009.
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  2. Pregnancy increases the growth rates of World Health Organization grade II gliomas. Pallud et al. 2010.
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