Brain Tumours: Insights into the Misery and a Horizon of Hope
Our brain is the essence of self. Brains craft our minds, define and limit our volition, forge our aspirations and etch our achievements. Dysfunction of the brain, therefore, evokes inordinate emotional perturbations. The spectrum of disorders afflicting our brains includes trauma, strokes, tumours, degenerations and infections.
There is considerable clarity on the aetiopathogenesis of traumatic brain injury, strokes, infections and degenerations. But, the genesis of brain tumours remains enigmatic.
Both genes and the environment play a role in brain tumour causation. This is the crux of the two-hit hypothesis. Genetic vulnerability is, in essence, an imbalance between tumour inhibiting and promoting genes. Genomics and proteomics (the study of protein messengers of the genome) with an environmental trigger result in a tumour. Genetic syndromes which render victims exquisitely susceptible to brain tumours include neurofibromatosis and other phacomatoses. These inherited disorders have an autosomal dominant pattern of inheritance.
Environmental factors accused of and incriminated in brain tumour causation include radiation, chemical agents and viruses.
The relationship between mobile phone use and brain tumour genesis is an issue of concern. In animal experiments, DNA strand breaks produced by electromagnetic radiations were shown to be mutagenic and possibly carcinogenic. Population-based human studies could not establish an aetiological relationship between mobile phone use and cancers. It is prudent to limit cell phone use by children. Viruses like cytomegalovirus may initiate glioblastomas. Radiation exposure may also initiate a brain tumour.
Types of brain tumours
Brain tumours include gliomas, meningiomas, neuromas, pituitary tumours, pineal gland tumours, embryological tumours and metastases. Gliomas are intra-axial tumours. These arise from glial (supporting) cells which include astrocytes (structural struts and milieu maintenance units), oligodendroglia (insulating cells) and microglia (immune function). Astrocytomas arise from astrocytes), Oligodendrogliomas from oligodendrocytes and ependymomas from ependymal cells which line the ventricles of the brain. Gliomas may be benign or malignant.
Glioblastoma Multiforme (GBM), the commonest (36%) of the Gliomas, is ferociously malignant. Outcomes are abysmal. Even with multimodality therapy including surgery, radiation and chemotherapy, the average life expectancy after detection is only 15 months. Patients with benign brain tumours may have a near-normal life expectancy.
Cerebral metastases are secondary tumours. Primary tumours which metastasise to the brain may be in the lung, the skin, the GI tract or virtually any other organ in the human body.
The reason why some tumours have a predilection for cerebral metastases involve intrinsic factors in both the ‘seed’ (malignant cells in the circulation) and the ‘soil’ (brain parenchyma). Surgery is offered to patients with cerebral metastases if they are in good health, under 65 years of age and if the primary disease is under control. Radiation is a better option for disseminated secondaries.
Therapeutic options
Benign brain tumours can be cured by surgery. Malignant tumours merit surgical resection followed by radio and chemotherapy. Deep-seated tumours may be managed by a biopsy followed by stereotactic radiosurgery. Not all brain tumours merit treatment. Small benign tumours discovered incidentally on imaging are called incidentalomas. Prolactin producing pituitary tumours respond to drugs like bromcryptine or cabergoline and do not need surgery. The diagnosis of prolactinoma is confirmed by serum prolactin levels. Germinomas and Lymphomas are tumours which respond well to radiation.
Removing tumour through surgery
Most brain tumours are removed through a craniotomy. The skull is opened with a high-speed drill. An operating microscope is used to facilitate maximum tumour removal without incurring a major neurological deficit. Surgical aggression balances the risks of surgery against the risks of tumour growth and recurrence. Small tumours can be removed through a ‘mini’ craniotomy. Neuro-navigation technology uses real-time tracking of surgical instruments against a pre-recorded MR or CT image. Intraoperative MR imaging is available within some operating theatre suites to check for completeness of resection. Intravenous administration of certain fluorescent dyes helps delineate tumour margins from surrounding normal brain.
Surgery for brain tumours has become increasingly safe over the past few decades. Intraoperative MRI is used to ascertain the totality of tumour resections. Robotics has a limited role in brain tumour surgery. One of the first surgical robots designed, the Puma, and newer versions have been used for stereotactic biopsies and accurate placement of electrodes in functional neurosurgery.
Radiation and chemotherapy
Malignant tumours usually merit post-operative Radiotherapy to prevent a recurrence. Radiation is by a linear accelerator with a high dose aimed at the tumour resection cavity. A dose of around 30 Gy is given over 4 weeks. Small deeply located tumours may be managed after a biopsy with stereotactic radiosurgery. The relative impermeability of the blood-brain barrier and neurotoxicity concern restricts the use of chemotherapy. Immunotherapy based regimes have not realised their potential in the treatment of brain tumours.
Outcomes of patients with brain tumours have improved significantly over the past few decades. Improvements in micro-neurosurgical and skull base techniques, the availability of modern imaging and surgical adjuncts like neuro-navigation and intraoperative MRI have contributed to better outcomes. Amid these technological marvels, it is important to remember that compassion and a common-sense approach of the treating surgical team contribute more to optimal outcomes than any marvel of technology.
The author is Senior Consultant Neurosurgery, KIMS, Thiruvananthapuram. (Views expressed are his own.)