Cancer treatments are experiencing one of their most dynamic and exciting periods. There is hope yet!

The overall survival for patients with brain metastasis is generally relatively low, so we need to address old pessimistic treatment philosophies. One of the most critical factors in the success of treatments is improving the quality of life for patients.

Brain metastases are the most common adult brain tumour. They occur in approximately 20–40% of patients with advanced cancers, with lung, breast, melanoma, and renal cell carcinomas the most common. The blood-brain barrier can significantly reduce the concentrations of many chemotherapy agents, making the central nervous system a pharmacologic sanctuary for metastatic progression.

Note we now use the terms: “solitary” brain metastasis = only metastatic lesion in the entire body; “single” brain metastasis = only metastatic lesion in the brain.

I’d like to focus on treatments for metastatic brain lesions and explain why we now have more than one solution.

TREATING THE WEEDS OR THE WHOLE LAWN

There are two approaches to treating brain metastases. First, treating the whole brain, which can be considered the whole lawn, or treating each metastatic cancerous lesion as they pop up, i.e. the weeds. 

Treating brain metastases has historically involved radiating the entire brain. There is no doubt that Whole Brain RadioTherapy (WBRT) can treat and stop the intracranial progression of metastases that are not obvious but are present. However, we also know that you cannot completely get rid of weeds even when trying to clean the whole garden. Thus today, there is a move toward a more radical approach – where we treat each weed as they pop up. This was an approach that was born out of the need to spare the cognitive decline that occurs. Ultimately what matters most is quality of life while surviving as long as we can. 

One of the main drivers in a more radical approach has been the evolution of Prognostic Models. Older trials incorporated the RTOG recursive partitioning analysis (RPA) developed by Gaspar in 1997, which used performance status, age <65, controlled primary disease, and no extracranial metastases. e.g. all of the above used to give a median overall survival of approx. Seven months while it could be as low as four months for those who were advanced. We now know that the original RPA underestimates survival in the modern era. Newer models like the Diagnosis Specific -Graded prognostic assessment (GPA) (Sperduto 2012)) adds the number of mets; histological types, and for lung cancer adds EGFR and ALK mutational status. Recent studies have shown that the median survival has increased (12 months to nearly two years in patients with high lungmolGPA scores). There are apps developed that help guides us. 

However, if there is ever a lesson to be learnt: no patient is a statistic!

The field of cancer treatment is experiencing one of its most exciting and dynamic periods; stereotactic radiosurgery (SRS) is one such advancement. With SRS, it is possible to treat many smaller metastatic lesions ‘weeds’ by targeting only the tumour volume. This allows for less morbidity (less brain destruction) and, therefore, less cognitive decline. The goal is that the patient should be able to resume normal activities. This can include working, driving, or taking care of children. 

General Management Paradigms:

For patients with symptomatic brain metastases: steroids and anticonvulsants are generally not indicated in the absence of symptoms. An urgent neurosurgical consult is indicated for patients with large and/or symptomatic brain metastases associated with increased pressure.

Asymptomatic Brain Metastases:

• Single brain lesions: tumour ablation is the goal
• SRS alone
• Neurosurgical resection +/− postoperative SRS to the resection cavity. Resection is often preferred for large, symptomatic, or threatening lesions.

Limited brain metastases:

• SRS alone preferred

More extensive brain metastases:

• WBRT or
• SRS to multiple lesions with close MRI surveillance

For single brain metastases, tumour ablation (surgery or SRS) has been associated with improved survival. Compared to supportive care, surgery alone, and SRS alone, the addition of WBRT improves disease control but does not improve survival. WBRT is associated with measurable declines in cognitive function and QOL. Postoperative SRS to the surgical cavity improves local control but not survival. 

However, there is a place for WBRT, especially for multiple large lesions, in those who are not well, whose prognosis is poor, and where any radical treatment won’t significantly alter the patients’ survival and quality of life. Thus a complete replacement of WBRT will not and should not be considered. We must also recognise that doing less can be doing more. We have evidence from the important QUARTZ trial showing no significant difference in survival and quality of life when adding WBRT to good old supportive care for those in very poor condition. We should not forget that best supportive care is mandatory.

What is stereotactic radiotherapy? SRS focuses beams of high-dose radiation at tumour sites with sub-millimetre accuracy – to achieve local control in just a few short treatments. It targets precisely to destroy cancer cells with minimal damage to surrounding healthy tissues. Treatment can be delivered in just one to five fractions, i.e. treatments, through hypofractionation, i.e. higher than conventional radiation doses. It does not mean an increase in side effects. We can decrease the devastating cognitive decline that occurs with WBRT. In addition, it allows for repeat ‘salvage’ treatments which WBRT does not always permit. 

There is a large body of evidence that this treatment given at the right time to the right patient can make a difference to outcomes. SRS is becoming the recommended therapy for many metastatic cancers and even for certain primary cancers, often replacing surgery. 

Treating brain metastasis needs a multidisciplinary team with a neurosurgeon and oncologist to ensure the safe implementation to the right patient, mainly because of its complexity.  Important factors are the patient’s fitness, performance status and age, location, number and size of the lesions, disease state beyond the brain, and ultimately, patient preference. SRS candidacy is evolving. Historically, SRS was offered for 1–3 or 4 lesions; however, there is a growing literature supporting SRS for 4–10+ lesions, suggesting that SRS candidacy should be individualised. Recently we are learning about the heterogeneity of tumours meaning multiple biopsies might be needed in some cases before treatments. Brain biopsy is often unnecessary when the probability of metastases being the same as the primary tumour, e.g. prior brain metastases, multiple brain lesions, metastases to other organs, rising tumour markers, etc. However, it can also be from a new tumour as it’s not uncommon to get other tumours; it can also be a tumour that is resistant to some treatments. This can help the oncologist give new appropriate therapies.  As emerging systemic agents demonstrate improved CNS penetration and activity – brain metastases paradigms will likely evolve to incorporate multi-treatment approaches involving local and systemic treatment. Treatment is now more personalised by using an effective combination of surgery, chemotherapy, radiation therapy, targeted and immunotherapy. 

Essentially this technique has revolutionised the treatment of metastatic cancer, providing an additional option for patients instead of chemotherapy being the only palliative option. Now, stereotactic body radiotherapy (SBRT) is used for lesions in the rest of the body with the same result.

In the era of healthcare today, it is about providing a patient with new treatment options. New treatment strategies continue to emerge in cancer medicine, and new technologies are being discovered every day. Some of these can provide new hope to patients who have already given up on conventional treatments. 

Although more expensive than WBRT, the cost of SRS can be offset by other costs that patients incur, e.g. transport; patients can even continue to work. However, because it’s currently expensive should not mean it cannot be accessed. There is a need to ensure that medical aids accept there is convincing good evidence of the benefits of improving local control, survival and quality of life. What more can we ask for?

Cancer patients can be helped to live with, and not for, their disease. 

Dr.Prinitha Pillay is a specialist Radiation Oncology in Gauteng. She is practising in Johannesburg ,offering radiation cancer treatments ,Comprehensive palliative care and psycho-social support .She offers a variety of treatments including Breast Cancer Treatment, Gynaecological, Gastrointestinal, Lung Cancer Treatment, Paediatric, Head and Neck, Prostate Cancer Treatment, Brain Cancer Treatment, Dermatological and Musculoskeletal Cancer Treatment. 

LEARN MORE at www.treatingcancer.co.za where we use this state of the art technique.