Overview Of Ongoing Research And Developments In The Field Of Treating Brain Tumours - Dr G Sudheer Kumar

The incidence of central nervous system tumours in India ranges from 5 to 8 per 100,000 population. Tumours of the central nervous system constitute approximately 2% of all malignancies. Yearly incidence of brain tumours in India is 40,000-50,000 and 20 percent of them are children. The type of tumour and its clinical behaviour depends on the population demographic.

The current treatment strategies for the treatment of brain tumours include surgical resection, radiation treatment and to a lesser extent chemotherapy. All the above modalities have their limitations. A combination of the above modalities yields better outcomes.

Inspite of the best efforts at treating them, brain tumours do menacingly recur, sometimes leaving us with no further treatment options. There is an urgent need to develop newer and better treatment options to improve the longevity and quality of life of patients with brain tumours.

The inclusion of newer modalities (which are being researched and experimented) into the present treatment protocols will help us in achieving this goal.

A. Intraoperative Modalities

Every neurosurgeon would be excited about the prospect of improving their ability of the extent to which a brain tumour is resected. Any new technology that facilitates this would be a welcome change.

1. Intraoperative ultrasound (ioUS): Usage of ioUS has dramatically evolved as it is easily affordable, portable and can be fit into existing theatre infrastructure without any changes.

Improvement in image quality of ioUS and the ease of learning it has made it an essential tool in a neurosurgeons armamentarium in resection of brain tumours.

Advanced techniques such as doppler US (doUS) using the doppler effect to image blood flow and contrast-enhanced ultrasound (ceUS) using intravenously injected gas filled microbubbles have further accentuated its role in resection of brain tumours.

2. Intraoperative MRI (iMRI): It is a modality where an MRI is incorporated into the OR infrastructure and is utilised at various stages of tumour surgery.

It remains the gold standard against which all the other intraoperative modalities are compared as it helps plan the surgery, localise the tumour and also provides real time guidance during tumour resection, thus enabling safe and maximal resection of the tumour.

Usage of iMRI has clearly shown to have improved the extent of resection of brain tumours, thus improving outcomes. The major drawbacks of this modality are its cost, the space required in the OR to accommodate it, the cumbersome process and the lengthy surgical times.

Nevertheless, with fast evolving technology and changing times, it has the potential of becoming an indispensable neurosurgical tool.

3. Intraoperative fluorescence: It is a modality in which various dyes are used to differentiate the tumour from the healthy brain tissue intraoperatively by giving the tumour a certain colour.

This colour can then be visualised either by the naked eye or under a microscope. 5-aminolevulinic acid, indocyanine green and to a lesser extent Fluorescein sodium are the commonly used drugs. The usage of such dyes improves the precision with which a tumour is resected by delineating its borders in real time.

4. Intraoperative AI and robotics: Like in any field of science and some other surgical branches, the use of AI has been under evaluation in microneurosugery. This modality is still embryonic, but with evolving technology the opportunities seem limitless.

Advantages include overcoming surgical fatigue, reduction in tremors, and increased precision. NeuroArm is an experimental robotic system which showed some promising results in this field and is still in its nascent stage.

Limitations that need to be overcome include poor haptic feedback as fine movements required for microsurgical resection of brain tumours can be confused by AI for tremors, limited instrument selection and most importantly the cost.

5. Nanosurgical resection: It is also a promising modality in its nascent stage. This modality makes use of a hand held scanner which is used to detect scattering nanoparticles within the tumour, thereby enabling maximal safe resection of the tumour.

Its effectiveness was studied on a genetically engineered mouse model with glioblastoma multiforme in which the whole tumour excision could be done.

B. Minimally Invasive Modalities

These modalities are used in conjunction with surgery or as stand-alone therapies depending on the need.

6. Laser interstitial thermal therapy (LiTT): It is a minimally invasive procedure that uses heat as a modality to destroy areas of abnormal cells, such as tumours. This modality can be used as a stand-alone treatment modality under MRI guidance or in combination with surgical resection.

Tumours close to eloquent cortex and tumours which a deep and inaccessible can be targeted with this modality. The smaller the tumour, the better the response to this therapy. The main drawback of this therapy is its cost and availability in very few centres across the globe.

7. Focused ultrasound therapy: It is a treatment modality on which clinical trials are still ongoing. It involves focusing beams of ultrasonic energy precisely and accurately on targets deep within the brain which in turn cause opening of the blood-brain barrier temporarily to improve levels of therapeutic agents, heat ablation or activation of sono-sensitive agents at the target.

For more pronounced effects, it can be combined with radiation therapy or prior to surgery to help mark the boundaries of the tumour.

8. Tumour treating fields: Tumour treating fields are a modality where a device is used to deliver painless electrical pulses to interrupt brain tumour cell division, which in turn slows their growth and spread. The device is worn as a cap on the head.

C. Other Modalities

9. Immunotherapy: It is a treatment modality which utilises a person's own immune system to fight cancer. CNS immunotherapies including cancer vaccines (like rindopepimut in GBM), immune checkpoint inhibitors (anti-PD-1 like nivolumab and pembrolizumab), oncolytic virus therapy (adenovirus and herpes simplex based), and chimeric antigen receptor (CAR) T cell therapy.

It is a branch which is still in its infancy with regard to treating CNS tumours and many trials are underway to study their effectiveness either alone or in combination.

10. Targeted therapy: This modality involves targeting specific molecular pathways preventing tumour growth and progression. Example - Targeted inhibitors of EGFR such as erlotinib and gefitinib, bevacizumab which targets VEGF, lonafarnib which targets RAS are all under evaluation.

Treatment of brain tumours has always been a multidisciplinary effort, and there are ongoing efforts in each sub speciality to better the existing treatment protocols.

With the advent of these different treatment modalities, a new era of treating brain tumours has begun, which might offer hope and much needed respite to both the surgeon and the patient alike.