Nitesh V. Patel, B.A., Shabbar F. Danish, M.D.

Division of Neurosurgery, Robert Wood Johnson Medical School (RWJMS), New Brunswick, NJ

Gamma Knife surgery (GKS) represents a type of knife-less non-invasive surgery that serves as an alternative to traditional surgery. It is categorized as stereotactic radiosurgery since it involves both 3-dimensional (3D) images and single-session radiation therapy. GKS has fewer risks when compared to conventional surgical options, such as open-skull brain surgery. There is no risk of infection, bleeding, stroke, or seizures because there are no incisions or manipulation of the brain. Additionally, there is no anesthesia-induced risk since, typically, only mild sedation is needed. All cases are done as outpatient procedures with patients going home the same day, and in many instances going to work the following day. GKS is the only radiosurgery developed exclusively for treatment in the brain, and should not be confused with CyberKnife, Novalis, or XKnife- machines that specialize in treating regions outside the brain. The Gamma Knife differs from these other modalities in terms of accuracy, radiation delivery and distribution. The Gamma Knife uses a stereotactic frame to stabilize the patient’s head, therefore providing sub-millimeter accuracy (1.0 mm or less). Meanwhile the other modalities are frameless and rely on linear accelerometry, leading to relatively less accuracy. In terms of radiation delivery, GKS has less radiation scatter and thus less spread of the radiation to unwanted areas of the body. Today, nearly 500,000 patients worldwide have been treated with the Gamma Knife and nearly 20+ years of scientific literature support its efficacy.

The newest update of GKS, the Gamma Knife PerfeXion system, involves a sphere-like helmet with 192 sources through which the radiation is delivered. MRI-derived skull/brain reconstruction can be used to generate a 3D model. Through stereotactic mapping, the 3D model can be used to localize a specified lesion with x,y,z coordinates in 3D space. The Gamma Knife system utilizes gamma rays derived from the nuclear decay of a Cobolt-60 radioisotope. Each of the 192 sources can deliver a beam of gamma rays that then penetrate the tissue in the beam’s trajectory. By choosing the optimal combination of angles, the gamma ray beam can be precisely focused onto the lesion using 3D modeling from images. The PerfeXion should not be confused with older versions of the GammaKnife. The PerfeXion is fully automated, which results in reduced treatment times, and as a result less radiation scatter to normal body parts. It employs a much wider inlet, which is less claustrophobia-inducing.

Am I a candidate?

Those patients that have an abnormality or tumor in a difficult to reach location are considered as candidates. Other candidates include patients that are not healthy enough for standard open-skull surgery and those for whom less invasive treatment is preferred – such as those with other major co-morbidities. The typical conditions that are treated with the GKS include: brain tumors, trigeminal neuralgia, pituitary tumors, and arteriovenous malformations (AVMs).

Are there any risks?

The risks of Gamma Knife surgery are minimal when compared to standard open surgery. However, as with any medical procedure there are risks. Early complications are usually temporary and include: edema formation near the treatment site leading to headaches, scalp irritation or sensitivity, and fatigue for several days to weeks post-operatively.

What Can I expect?

Although the procedure is usually in an outpatient setting, the time frame usually involves a large portion of the day. It is recommended that you bring a family member or friend with you who can take you home. Prior to the procedure, you’ll have an intravenous (IV) tube placed to deliver medications and fluids to keep you hydrated. Before the procedure begins, a lightweight stereotactic frame will be attached to your head with four pins. The frame is designed to stabilize your head such that all points within your head remain constant relative to the frame. This is critical for accurate and precise lesion localization. A localized anesthetic will be given before the pins are placed – at 4 points total, 2 at the front and 2 at the back of your head. Usually, none of your hair will be shaved. After this, you’ll have additional MRIs taken of your brain and then you’ll lie with your head in the Gamma Knife helmet with the stereotactic frame in place. During the procedure, you won’t feel the radiation and will be able to communicate with the doctors through a microphone.

What Types of Tumors Can be Treated?

Benign or “not so benign” tumors, such as meningiomas, can be successfully treated with GKS. Since meningiomas are commonly treated with stereotactic radiosurgery, there is a need to elaborate on the scientific and clinical components of this tumor type. They originate from the arachnoid cap cells of the arachnoid meningeal layer. On the cellular and genetic level, the origin of typical meningiomas is closely linked to malfunctions in the neurofibromatosis type 2 (NF2) and 4.1B (DAL-1) genes. Other involved genes include BAM22, break point cluster region (BCR), and TIMP-1, the last being implicated in higher-grade meningiomas. Atypical meningiomas are also related to genetic malfunctions including mutations in chromosomes 1, 6, 10, 14, and 18. Through the World Health Organization (WHO), meningiomas are classified based on their pathological and histological morphology (Table 1).

Grade II and III meningiomas are more likely to develop invasive disease and have a higher rate of recurrence with a lower overall survival rate. Studies have shown that Grade I cases have a recurrence-free survival in nearly 90% of cases, while that with Grades II/III have recurrence in 30-50% of cases at 3-5 years, even after complete resection.

Typically, active observation is primary in asymptomatic and incidentally diagnosed cases. For symptomatic cases, surgical resection is the treatment of choice. Postoperative complications can occur in 5-30% of cases, depending on the location of the tumor. Radiosurgery is the treatment of choice when standard open surgery is contraindicated, there is incomplete resection, or there is a Grade II / III meningioma – the last due to the risk of recurrence. After radiosurgery, the risk of recurrence remains but careful monitoring can help to catch potential recurrences early and allow for a decision on additional radiotherapy. Studies of patients with varying types of meningiomas have shown that survival may approach 85% at the 5-7 year time point after GKS.

A recent study revealed that GammaKnife was just as effective as fractionated radiation in the control of skull base meningiomas, and provided much better quality of life to patients versus those who underwent open surgery. GammaKnife has control rates of 95% for cavernous sinus meningiomas, making open surgery for these lesions unnecessary and an obsolete treatment strategy in most cases. In a large study examining long term results after GammaKnife, patients experienced >95% control, with >70% of tumors shrinking over a 10 year observation period.

Adjuvant therapies such as radiation and medical therapy has been investigated in the medical community, however they remain controversial. The main question that remains to be answered is whether adjuvant therapy is better than simply watchful waiting. Medical therapies that have been investigated include hormonal therapies such as anti-progesterone therapy or immunotherapy with alpha-interferon. These approaches have shown modest results and may be useful when the tumor cells express receptors for these substances. More substantial results have been demonstrated with hydroxyurea, however, there are studies still investigating this. Recently, pre-clinical studies have pointed towards drugs such as trabectedin and histone deacetylase inhibitors as potential therapies. Nonetheless, several clinical trials are under way to test candidate drugs such as platelet-derived growth factor receptor and anti-angiogenic therapies.

What is the outcome like?

The outcome depends on the type of tumor, location, and patient’s medical history. For benign tumors, there is usually a failure of tumor cells to reproduce over the course of 1-2 years. The outcomes after meningioma treatment are typically positive; however, even a benign meningioma can be “malignant” if it’s in an “anatomically-bad” place. For malignant tumors, usually, the tissue shrinks faster (few months) since vascular supply is compromised as a result of GKS. However, other, non-tumor conditions, such as AVMs and trigeminal neuralgia, can take several months to years to fully go away.

What happens after the surgery?

Usually, the patient goes home the same day and then will follow-up as an outpatient with his or her neurosurgeon and radiation oncologist. Depending on the patient’s course, additional imaging such as CAT-Scan (CT) or Magnetic Resonance Imaging (MRI) may be ordered. At each visit, the physician will perform a neurological exam to evaluate the patient’s function.

Helpful References

1. A typical treatment day. International RadioSurgery Association. http://www.irsa.org/treatment.html. Accessed Aug. 3, 2010.
2. Gamma Knife® surgery. International RadioSurgery Association. http://www.irsa.org/gamma_knife.html. Accessed Aug. 3, 2010.
3. Stereotactic radiosurgery. American Association of Neurological Surgeons.http://www.aans.org/Patient%20Information/Conditions%20and%20Treatments/Stereotactic%20Radiosurgery.aspx. Accessed Aug. 3, 2010.
4. Vestibular schwannoma (acoustic neuroma) and neurofibromatosis. National Institute on Deafness and Other Communication Disorders.http://www.nidcd.nih.gov/health/hearing/acoustic_neuroma.html. Accessed Aug. 4, 2010.
5. Trigeminal neuralgia fact sheet. National Institute of Neurological Disorders and Stroke.http://www.ninds.nih.gov/disorders/trigeminal_neuralgia/detail_trigeminal_neuralgia.htm. Accessed Aug. 3, 2010.
6. Stereotactic radiosurgery overview. International RadioSurgery Association. http://www.irsa.org/radiosurgery.html. Accessed Aug. 3, 2010.
7. Kavanagh G, et al. Complications of cranial stereotactic radiosurgery. http://www.uptodate.com/home/index.html. Accessed Aug. 4, 2010.
8. Marta, Gustavo Nader, Sebastião Francisco Miranda Correa, and Manoel Jacobsen Teixeira. “Meningioma: review of the literature with emphasis on the approach to radiotherapy.” Expert Review of Anticancer Therapy 11.11 (2011): 1749-1758.
9. Marosi, Christine, et al. “Meningioma.” Critical reviews in oncology/hematology67.2 (2008): 153-171.
10. Alexiou, George A., et al. “Management of meningiomas.” Clin Neurol Neurosurg 112.3 (2010): 177-182.
11. Sioka, Chrissa, and Athanassios P. Kyritsis. “Chemotherapy, hormonal therapy, and immunotherapy for recurrent meningiomas.” Journal of neuro-oncology 92.1 (2009): 1-6.
12. Wen, Patrick Y., et al. “Medical therapies for meningiomas.” Journal of neuro-oncology 99.3 (2010): 365-378.
13. Pollock, Bruce E. “Stereotactic radiosurgery of benign intracranial tumors.”Journal of neuro-oncology 92.3 (2009): 337-343.
14. Vranic, Andrej, Matthieu Peyre, and Michel Kalamarides. “New insights into meningioma: from genetics to trials.” Current Opinion in Oncology(2012).