Targeting brain tumours

Dr Nirasha Chiranjan informs us about the new developments in radiotherapy in the treatment of brain tumours.

Radiotherapy can prolong survival in most malignant brain tumours and may be curative in others. In the setting of benign and malignant brain tumours, radiotherapy may be used solely; may be used before or after surgery; and may be used concurrently with chemotherapy. 

Radiation works at a cellular level to damage the DNA of cancer cells thereby preventing cell division and inducing death of these cells¹. The duration may vary from a single treatment to daily treatment for six weeks.

Radiotherapy has evolved into an advanced modality that allows for good tumour control and quality of life whilst minimising adverse side effects. The improvement in precision and accurate radiation beam delivery is largely due to advanced imaging technology and the ability to track a tumour.

There are different radiation techniques employed in treating brain tumours: external beam radiotherapy, internal radiotherapy and stereotactic radiotherapy. Each technique is utilised according to the type of brain tumour, size, presence of distant disease, and proximity to critical structures. 

3D conformal external beam radiotherapy (3DCRT) 

External beam radiotherapy is the delivery of precise high-energy radiation beams from the radiation machine to the tumour. It can be planned three dimensionally which allows for better conformation of the radiation to the tumour shape and sparing of normal tissue from high-dose radiation. This in turn results in fewer radiotherapy side effects. 

Intensity modulated radiotherapy (IMRT)

IMRT is an advanced form of 3D conformal radiotherapy that uses smaller radiation beams of varying intensities to target a tumour. It conforms to the tumour shape more accurately and can deliver higher doses of radiation more effectively^2-4.

Stereotactic radiotherapy techniques

Stereotactic radiotherapy is a non-invasive technique that delivers radiation in a single fraction (dose) or very limited number of fractions. It’s a very advanced, effective form of external beam radiation. 

Stereotactic radiotherapy techniques target small, well-defined benign and malignant tumours as well as functional abnormalities in the brain.

Stereotactic radiosurgery (SRS) is non-surgical and refers to a single fraction treatment of intracranial (within the brain) and spinal targets. It’s delivered by a neurosurgeon and radiation oncologist. 

Stereotactic body radiotherapy (SBRT) refers to multi-fractional (two to five fractions) treatments of cranial (brain), spinal and extracranial (body) sites. These techniques use multiple narrow radiation beams and deliver large radiation doses in a shorter time span. 

Immobilisation and specialised scanning techniques are imperative to achieve reproducibility and precision as well as to prevent adverse side effects. This focused technique allows radiation to be delivered to areas of the brain and spine that would be deemed inoperable^5-8.

Proton therapy

This refers to a form of external beam radiation that uses protons instead of photons to produce radiation beams. Photons are highly penetrating and have an exit dose thus irradiating more healthy tissue. 

Protons, however, deliver their maximal dose at a prescribed depth known as the Bragg Peak. Proton beams can be directed so that the Bragg Peak occurs within the tumour thereby sparing normal healthy tissue. It’s a favourable treatment option for children as it may limit radiation exposure to healthy growing brain tissue. Thus, preventing secondary malignancies, developmental delays, hormonal deficiencies and effects on healthy muscle and bones. Protons can also be used for unusually shaped tumours in eloquent areas (controls function) of the brain^9-11. 

References:

1. Revell SH. Relationship between chromosome damage and cell death, Liss A (Ed), New York City 1983. p.113.
2. Guerrero Urbano MT, Nutting CM. Clinical use of intensity-modulated radiotherapy: part I. Br J Radiol 2004; 77:88.
3. Chan JL, Lee SW, Fraass BA, et al. Survival and failure patterns of high-grade gliomas after three-dimensional conformal radiotherapy. Journal of Clinical Oncology.2002;20(6):1635-42.
4. Tanaka M, Ino Y, Nakagawa K, Tago M, Todo T. High-dose Conformation Radiotherapy for Supratentorial Malignant Glioma: A Historical Comparison. Lancet Oncology. 2005; 6: 953-960.
5. Andrews DW, Scott CB, Sperduto PW, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004;363:1665-1672.
6. Laws ER, Sheehan JP, Sheehan JM, et al. Stereotactic radiosurgery for pituitary adenomas: a review of the literature. Neuro oncology. 2004;69(1-3):257-72
7. Brennan C, Yang TJ, Hilden P, et al. A phase 2 trial of stereotactic radiosurgery boost after surgical resection for brain metastases. Int J Radiat Oncol Biol Phys 2014; 88:130.
8. Brown PD, Ballman KV, Cerhan JH, et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC·3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18:1049.
9. Weber DC, Lomax AJ, Rutz HP, et al. Spot-scanning proton radiation therapy for recurrent, residual and untreated intracranial meningiomas. Radiotherapy Oncology.2004;71(3):247-9.
10. Brown AP, Barney CL, Grosshans DR, et al. Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma. Int J Radiat Oncol Biol Phys 2013; 86:277.
11. Eaton BR, Esiashvili N, Kim S, et al. Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival. Int J Radiat Oncol Biol Phys 2016; 94:133.
12. Gabayan A, Sanan A, Bastin K, et al. Gliasite Radiotherapy System for Treatment of Recurrent Malignant Glioma: A Multi-Institutional Analysis. Proceedings from the 46th Annual Meeting of the American Society of Therapeutic Radiology and Oncology, held in Atlanta GA , October 2004. Abstract #1002.

MEET OUR EXPERT  – DR NIRASHA CHIRANJAN

Dr Nirasha Chiranjan is a radiation oncologist. Her special interests are the breast, gynaecological, head and neck, and central nervous system cancers. She is based at the Life Flora Hospital, Sandton Oncology (Morningside) and Ahmed Kathrada Cancer Institute. (cancersa.co.za/nirasha)