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Abstract Page 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. References 1. Farrell CJ, Plotkin SR. Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes. Neurol Clin. Nov 2007;25(4):925-46, viii. 2. Hardell L, Carlberg M, Söderqvist F, Mild KH, Morgan LL. Long-term use of cellular phones and brain tumours: increased risk associated with use for > or =10 years. Occup Environ Med. Sep 2007;64(9):626-32. 3. Lahkola A, Auvinen A, Raitanen J, Schoemaker MJ, Christensen HC, Feychting M, et al. Mobile phone use and risk of glioma in 5 North European countries. Int J Cancer. Apr 15 2007;120(8):1769-75. 4. McGrane J, Bedford T, Kelly S: Successful pregnancy and delivery after concomitant temozolomide and radiotherapy treatment of glioblastoma multiforme. Clin Oncol (R Coll Radiol). 2012; 24(4): 311. 5. Peres .R.M et all : assessment of fetal risk associated with exposure to cancer chemotherapy during pregnancy: a multicenter study. Brazilian journal of medical and biological research (2001) 34:1551-1559 6. Preusser M, Seywald S, Elandt K, et al.: Pilot study on sex hormone levels and fertility in women with malignant gliomas. J Neurooncol. 2012; 107(2): 387–94 7. Jayasekera BA, Bacon AD, Whitfield PC. Management of glioblastoma multiforme in pregnancy. J Neurosurg. 2012 Jun;116(6):1187-94. 8. Charles B et all: the clinical management of intracranial neoplasm in pregnancy. Clinical obs and gyn (2005)48:1,24-34 9. David V et all :successful pregnancy following continuous treatment with combination chemotherapy before conception and throughout pregnancy .cancer (1984) 54:800-803 10. Deborah T et all .management of malignant gliomas during pregnancy . cancer (2008)113: 334954 11. Alberto I et all , brain tumor and pregnancy . obstet gyneno (1997)89:1-23 12. Srupp R et all ,changing paradigms-An Up date on the multidisciplinary management of malignant glioma.the oncologist (2006) 11:165-180