Risk factors, surgical outcome, and quality of life in patients with cranial or spinal meningioma

Sammanfattning: Meningiomas comprise approximately 30-38% of all cranial tumours and represent the largest group of primary intracranial and intraspinal tumours. Gliomas, of any grade, account for approximately 28% and glioblastomas 15% of the cranial tumours, as comparison. Roughly 2% of all meningiomas are spinal, constituting 25-45% of all spinal intradural tumours. Despite extensive research in this field, there is still no consensus on the best strategies for surgical resection, follow-up, and supplementary treatments. Risk factors for meningioma development and factors affecting health-related quality of life (HRQoL) and return to work for this heterogenous patient group are poorly understood. This thesis aimed to study population-based cohorts with cranial and spinal meningiomas to bring greater clarity to some of these questions. In study I, a 25-year follow-up of patients with parasagittal meningiomas was conducted, revealing that radical resection was of great importance to reduce recurrence, morbidity, and tumour mortality. Furthermore, more than 15 years of radiological follow-up was necessary to detect late recurrences. Study II evaluated the surgical results for meningiomas that engaged major venous sinuses, demonstrating that microscopic radicality was difficult to achieve and that supplementary stereotactic gamma knife radiosurgery was beneficial and should be considered as an adjuvant treatment directly after surgery. In study III, a large epidemiologic survey of a female Swedish population was conducted to understand a possible connection between sex hormones and risk of developing a meningioma during and after pregnancy. Contradictory to our hypothesis, there was no increased risk for diagnosing a meningioma during pregnancy or 1-year postpartum, thus indicating that pregnancy should not be seen as a risk factor for meningioma. Study IV on spinal meningiomas revealed that surgery was associated with a significant improvement in neurological function independently predicted by a shorter time from diagnosis to surgery and the degree of spinal cord compression. Elderly patients benefitted to same degree as non-elderly patients from surgical intervention without increased complications. Study V analysed the HRQoL and frequency of return to work among patients operated on for a spinal meningioma. Ninety-six percent of patients were satisfied with the surgical results. Despite a high median age at surgery, and unlike cranial meningiomas or lumbar spinal stenosis, the HRQoL at long-term follow-up was equivalent to a matched sample of the general population. All patients working before their operation returned to work postoperatively, most of them within three months. Study VI evaluated long-term follow-up and HRQoL for patients treated for cranial WHO grades 2 and 3 meningiomas. Despite dismal prognoses with 93% of the mortality attributed to meningiomas, a large subgroup comprising both grades 2 and 3 was alive at 10 years follow- up after one operation or operations supplemented with gamma knife radiosurgery, showing a longer overall survival compared to previous reports. In contrast, fractionated radiotherapy and chemotherapy had little benefit when introduced for recurrent or progressive disease. The surviving meningioma patients showed HRQoL measurements comparable to those of the general population, except for significantly more anxiety and depression. Despite suffering from a chronic disease and in contrast to previous reports, all patients who were working before surgery returned to work after surgery. In conclusion, based on the findings of this thesis, we recommend long-term radiological follow-up and supplementary gamma knife radiosurgery for tumour control of cranial meningiomas. The effects of sex hormones are multi-faceted and require further in-depth studies. Spinal meningiomas should be treated rapidly after diagnosis for all ages to promote excellent neurological outcomes and HRQoL measures. Despite the chronic nature of the disease, subgroups of WHO grades 2 and 3 meningiomas can yield long-term outcomes and HRQoL measures.