The Future of Brain Tumor Treatment for Millions of Patients Each Year – Stereotactic Radiosurgery (SRS)

Brain tumors are a widespread condition. The number of patients diagnosed with cancer globally will grow from 17 million (2018) to 27.5 million (2040).¹ Of those, it is estimated that at in least 9%,² or 1.5 million of those patients, their cancers will spread – metastasize – to the brain (others estimate even higher, 20-50%, or 3.4-8.5 million patients per year).³ The cancers that spread to the brain most commonly include lung, breast, melanoma, renal cell, colorectal, and others.³ To defend against these brain tumors, historically, surgery has been the first line of defense.

We have come a long way from the first successful brain surgery performed for cancer in 1887 at Jefferson Medical College by Dr. William W. Keen on Theodore Daveler in Philadelphia, PA. When Daveler was 3 years old, he fell out of a window onto his head. By age 26, he was suffering from near complete blindness, daily seizures, paralysis, headaches and other symptoms of a brain tumor. Daveler pleaded with Keen to attempt the surgical removal of his tumor. On December 15, 1887, at the site of the scar caused by the fall, Dr. Keen made an incision, and with his bare finger discovered a 3 ounce tumor, recused it manually, and tied up blood vessels with catgut.  Daveler lived another 30 years thereafter and was cured of the majority of his symptoms.⁴

Along with chemotherapy and targeted therapies, one of the most important advances in medicine to treat brain tumors has been the use of radiation to slow and halt cancer growth without blood, cuts or drugs, which began regularly in the 1950s across leading hospitals in North America and Europe.⁵  At the time, given the size and design of the radiation systems, targeting techniques were basic, and for brain tumors, a technique now called “Whole Brian Radiotherapy” (WBRT) was utilized – to the benefit of patients at the time, especially those with multiple tumors in the brain.

At the same time, in 1949, Dr. Lars Leksell – a young Swedish physician – sought out ways to target tumors deep-set in the brain with precision radiation. After traveling to Philadelphia to observe a conventional brain surgery system developed by Drs. Spiegel and Wycis, Leksell patented a system to achieve millimeter accuracy for brain radiation treatments delivered, which coincided with the advancement of imaging technologies for targeting such as computed tomography (CT) and magnetic resonance imaging (MRI). His invention – the Gamma Knife – is now used in hundreds of hospitals around the world, delivering accurate, precision “radiosurgery” to patients. “Radiosurgery” or Stereotactic Radiosurgery (SRS) reflects the precision of the radiation delivered versus other techniques.⁶

Radiation has been proven over the years to be an effective treatment for brain metastases, with evidence beginning to emerge in the 1950s.⁷ While there has been an ongoing debate around the mechanics, timing and dose of radiation delivery (should it be delivered in 1 or multiple sittings? At what dose for each?), in 1980 the results of a study by physicians at the Thomas Jefferson University showed that for patients with brain metastases, outcomes after WBRT alone were poor, with all patient median overall survival of only 3-4 months.⁸ In 1990, Dr. Patchell at the University of Kentucky and his team demonstrated that for patients with a single brain metastasis, WBRT combined with surgery increased overall survival significantly vs. WBRT alone, from 15 weeks with WBRT alone, to 40 weeks for WBRT combined with surgery.⁹ Finally, a number of studies emerged in recent years to show the effectiveness of SRS, which is radiation delivered to brain tumors with millimeter accuracy.¹⁰

SRS has been used as a pre-surgery treatment, post-surgery treatment, or as a standalone treatment, and has been studied extensively. In these studies, SRS has been determined to be equivalent to WBRT in terms of overall survival, while avoiding the diminished cognitive function, diminished quality of life and diminished verbal function associated with WBRT.¹⁰ In summary, whether a physician chooses to irradiate a brain metastasis prior to, after, or in lieu of surgery, SRS delivers a clinical outcome equivalent to WBRT, without the diminished brain function and neurologic side effects associated with WBRT.

Additionally, SRS can even replace brain surgery in many instances for the treatment of cancer metastasis.¹¹ Even for most primary benign brain cancers with tumors close to sensitive structures, such as meningiomas of the skull base, SRS can be a favored standalone treatment.¹¹

SRS can be delivered to the brain by a number of medical devices – the Gamma Knife (Elekta), CyberKnife (Accuray), Novalis Tx (Varian / BrainLab), and, more recently, the Zap-X (Zap Surgical Systems). Given the radiation sources involved, to protect a hospital or free-standing facility, each device is typically enclosed in a purpose-built concrete vault with very thick concrete walls. Some devices, for example the Gamma Knife, are powered by a radioactive core which must be replaced periodically. Used properly, no matter to which device one has access, each of these devices can deliver a largely clinically equivalent SRS treatment.

However, it has been decades since a brand new device has been developed to deliver brain SRS.  Only the Zap-X, which began treating patients in 2019, is new on the scene. Why would any provider buy a new device if the clinical effect is similar to an existing one?

Comparing the Zap-X to other solutions, the advantages include, first – cost. The Zap-X is self-shielded, and usually does not require the cost and complexity of a concrete bunker. Additionally, because it is driven by a linear accelerator instead of a radioactive core there is no need to periodically replace the radioactive core.  Second – accessibility for practitioners and for patients. For practitioners – the Zap-X can be installed in a location with no concrete vault, and its modern software incorporates machine-driven treatment planning enabling rapid training.  For patients – the Zap-X lacks the metal frame that is screwed in place used for targeting with some other devices.  From a clinical, cost, and accessibility perspective, practitioners and patients alike have reasons to choose the Zap-X when seeking first-in-class clinical delivery of precision SRS for brain metastasis.

The benefits of Stereotactic Radiosurgery (SRS) as compared to Whole Brain Radiotherapy (WBRT) are clear. Whether clinicians and patients choose access to SRS on a Zap-X or another device, the proliferation of SRS globally is a step forward for both practitioners and patients.

References:

1. Global Cancer Facts & Figures. International Agency for Research on Cancer. American Cancer Society: https://www.cancer.org/research/cancer-facts-statistics/global.html. Accessed Feb 11 2020.
2. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases.  Curr Oncol Rep 2012 Feb;(14):48-54 PMID 22012633
3. Treatment of Brain Metastases – Won Kim, MD | UCLAMDChat Webinars.  UCLA Health: https://www.youtube.com/watch?v=3SkStmGbvUg. Accessed Feb 11 2020.
4. Keen, WW. Three successful cases of cerebral surgery.  In: Mears, JE, ed. Transactions of the American Surgical Association. Philadelphia: P. Blakiston, Son & Co;1888:293-317.
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7. Chao JH, Phillips R, Nickson JJ. Roentgen-ray therapy of cerebral metastases. Cancer. 1954;7:682–9.
8. Borgelt B, Gelber R, Kramer S, Brady LW, Chang CH, Davis LW, Perez CA, Hendrickson FR. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 1980 Jan;6(1):1-9.
9. Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990;322(8):494-500.
10. Choosing Wisely: Ten Things Physicians and Patients Should Question. American Society for Radiation Oncology (ASTRO): http://www.choosingwisely.org/wp-content/uploads/2015/02/ASTRO-Choosing-Wisely-List.pdf. Released September 15, 2014; updated June 21, 2016 and June 9, 2017; Last reviewed 2019. Accessed Feb 11 2020.
11. Chen JCT, Girvigian MR.  Stereotactic Radiosurgery: Indications and Results — Part 2. Perm J. 2006 Spring;10(1):9-15.