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.
