Radiation therapy in the management of brain tumors

Dr. Karan Chanchlani

Consultant: Radiation oncology Manipal Hospital, Baner, Pune

Pune, 20th May 2024: Brain tumors are relatively less common tumors (2.3% of all cancers) that occur in the central nervous system (brain and less commonly spinal cord). Primary Brain Tumors can be benign or more commonly malignant (cancerous) tumors. Despite the malignant nature, they rarely spread outside the CNS to the other parts of the body. However these are associated with high morbidity and mortality and have devastating effects on the life of the patients, given the organ involved. Glioblastoma and high grade gliomas followed by low grade gliomas are the common adult brain tumors. High grade tumors have a very high propensity of relapse or “progression” of disease despite the initial treatment. Embryonal tumors like medulloblastma and low grade gliomas are the common childhood or pediatric brain tumors. Optic Pathway gliomas are particularly challenging tumors occuring mainly in children and young adults. Although usually low grade, preserving the vision while treating such tumors can be challenging as well as gratifying and requires highly skilled team of Neuro-surgeons and Neuro-oncologists along with cutting edge technology. Benign tumors like meningiomas, pituitary adenomas, central neurocytomas etc have excellent long-term outcomes with surgery although they often require additional/adjuvant treatment. Metastases or spread from cancers of other parts of the body to the brain also form a significant chunk of brain tumors with breast and lung cancers being the most common primary sites in Indian scenario.

Neurosurgical resection is the first step in the management as it helps to debulk the tumor, relieve the compression and pressure inside the brain and provides valuable tissue diagnosis for exact typing and grading of the tumor to guide for further treatment. Sometimes, it is difficult or even risky to operate upon certain deep seated tumors, especially that are close to critical structures like the brainstem, optic apparatus, etc. In such cases, we have to rely upon the radiological diagnosis itself. Advanced techniques such as neuronavigation, intraoperative MRI, and awake craniotomy have improved precision and safety of neurosurgical procedures. Stereotactic Radiosurgery (SRS) is a minimally invasive option for certain tumors.

Radiotherapy remains the cornerstone of treatment in brain tumors. Typically, it is delivered in a protracted fashion of small dose fractions, 5 days a week, over 5-6 weeks depending upon the tumor type and grade. Radiation is indicated in all high grade tumors as postoperative adjuvant therapy to improve the local control and prevent relapse or progression of disease. Chemotherapy (oral or less commonly intravenous) is often used in combination to potentiate the effects of radiation. Re-irradiation is also one of the treatment options in cases of recurrent tumors progressing after the first line of treatment. In low grade brain tumors, radiation therapy is required in certain situations like neurological deficits (paralysis etc.), large tumors, tumors where it may not be possible to completely remove surgically, or in recurrent cases. There is some concern about long term effects of radiation therapy in low grade tumors given that these patients have longer survival. However, modern techniques of conformal radiation delivery with robust and highly sophisticated planning ensure that radiation therapy in low grade tumors is safe and efficacious, thereby increasing the quantum of therapeutic benefit. MRI with special 3D sequences allow accurate delineation of target volumes and techniques like Intensity Modulated Radiotherapy (IMRT), Arc Therapy (Rapidarc/VMAT), and proton therapy target these tumors with prescribed dose of radiation more conformally, minimizing damage to surrounding brain tissue. It is crucial to combine these with Image Guidance (IGRT) during treatment in order to reduce the “safety margins” (PTV margins) thereby enabling precision targeting of the tumor and reducing exposure to normal brain tissues further and minimizing long term effects. 

Pediatric brain tumors like medulloblastomas have a very good chance of cure if treated appropriately by a multi-disciplinary Neuro-Oncology team. Hence it is crucial to consider the long term effects of the treatment (radio and chemotherapy) while designing the treatment regimens. These tumors are peculiar in that they have very high chances of spreading through the CSF along the entire neural axis i.e. the brain and spinal cord. Cranio-Spinal Irradiation (CSI) is a highly effective but challenging technique requiring meticulous planning of radiation doses to the entire length of neural axis while minimizing the exposure to surrounding organs that extend from the head-neck to the torso. Helical delivery of radiation can be helpful, although planning and imaging with multiple isocentres using feathering and Rapidarc/VMAT technique, is equally precise. 

Particle therapy has the highest physical advantage in terms of controlling doses to the surrounding normal organs. Molecular testing often helps to identify subset of children who can safely receive de-escalated therapy (reduced dose CSI), minimizing the long-term effects of treatment. Conversely, treatment can be intensified (eg adding chemo) in potentially unfavorable subsets where meticulous radiation planning and techniques can help better tolerance of concurrent chemo-radiation therapy.

Benign brain tumors pose a different set of challenges in that they do not grow rapidly, have lesser fraction of cells in the proliferative phase of cell cycle and have good long term control and prognosis. Yet they can be damaging locally, for example vision loss, hormonal imbalances in pituitary adenoma; facial nerve palsy, hearing loss in case vestibular schwannomas; seizures and focal neurological deficits/paralysis in case of meningiomas. Often it is difficult to remove such tumors completely with surgery, especially the ones that occur as part of syndromes with multiple tumors. Precise targeting of these tumors with Stereotactic Radiation therapy is an excellent treatment option. By virtue of their benign nature and low proliferative index, these tumors are excellent cases for Hypofractionated Radiation therapy wherein the tumor is precisely targeted with short courses of radiation with higher doses per session than conventional RT and the entire dose is delivered in 1-5 sessions/fractions. This is called as Stereotactic Radiotherapy (SRT) when delivered in <5 fractions and Stereotactic Radiosurgery (SRS) in a Single Fraction. There is a radiobiological advantage to this approach compared with conventional more fractionated RT. 

SRS/SRT has also been explored in the arena of Brain Metastases where the conventional approach of treating the whole brain with RT (WBRT) had significant neurocognitive side-effects. With advances in Chemo and Targeted therapies for primary cancers, survival of patients with brain mets has improved significantly. Consequently, long term effects of WBRT causing neurocognitive decline has a significant impact on the Quality of Life (QoL) of these patients. Advanced radiation techniques like Hippocampal Sparing and Stereotactic Radiation have a significant impact in the overall life of these patients. There is upcoming data on the successful combination of SRT/SRS with Immunotherapy with supra-additive benefits.

To conclude, technical advances in the planning and delivery of radiation therapy for brain tumors has significantly impacted the survival and QoL of these patients. Judicious use of technology combined with multiple-disciplinary approach is vital for successful treatment of these tumors.