Radiation oncologists at the University of Alabama at Birmingham Heersink School of Medicine and Vanderbilt University Medical Center share their pioneering experiences using Varian platforms for stereotactic radiosurgery (SRS).
Varian TrueBeam and Edge radiosurgery systems were recently cleared by the US Food and Drug Administration (FDA) for the treatment of medically refractory essential tremor in adults. This is good news for the patients who suffer with debilitating tremors and for whom other treatments are either not effective, not acceptable, or inappropriate. The newly cleared SRS solution from Varian is good news for radiation therapy departments with already-established frameless, linac (linear accelerator)-based stereotactic radiosurgery programs.
“Essential tremor represents a non-malignant condition; however, it can manifest as a significantly incapacitating disorder with marked social repercussions. The therapeutic arsenal for essential tremor is limited, and patients frequently develop resistance to available pharmacological interventions as the disease progresses. Consequently, there arises a clinical necessity for additional interventions. Deep brain stimulation is an invasive yet very effective surgical procedure. Notably, not all patients meet the criteria for deep brain stimulation due to underlying medical comorbidities, or they may be disinclined to pursue it due to its invasive nature. As an alternative, incisionless radiosurgical ablation, specifically SRS thalamotomy, is a feasible therapeutic option for such patients. We are excited to have demonstrated that the TrueBeam and Edge systems represent an innovative platform for SRS thalamotomy that allows patients to be treated fast and non-invasively with highly robust and reliable targeting and treatment delivery,” says Markus Bredel, MD PhD, Professor of Radiation Oncology, Sharon A. Spencer Distinguished Endowed Chair for Translational Radiation Oncology, and Director for Functional Brain Radiosurgery at the University of Alabama at Birmingham Heersink School of Medicine.
“Radiation oncology centers need to know that they already have the expertise to treat essential tremors. With their current equipment, training, and physics assistance, this treatment is feasible and practical for any radiosurgery program,” adds Anthony Cmelak, MD, Professor and Senior Medical Director of Radiation Oncology, who has been treating these patients under clinical trials using Varian linacs for more than 10 years at Vanderbilt University Medical Center in Nashville, Tennessee.1,2
Improved treatment for a common functional problem
Essential tremor is one of the most common neurological movement disorders, afflicting about 5.8 percent of people aged 65 or older.3 While not life-threatening, it can significantly degrade quality of life, making simple tasks of daily living extremely difficult; forcing early retirement; and contributing to social isolation.4,5
Varian’s TrueBeam and Edge systems can now fill a significant gap in options for patients, who typically range in age from 40 to 80 years or older and many of whom have complicating comorbidities. The first line of treatment for essential tremor is medical therapy with drugs, most commonly propranolol or primidone. However, 40 percent of patients stop taking prescribed medications for a variety of reasons, including intolerable side effects or disappointing results.6
Dr. Bredel relates their experience. “About 50 percent of the tremor patients we evaluate for radiosurgery are individuals who don't want DBS, while 50 percent of the patients are not suitable for DBS for medical reasons.” Frame-based radiosurgical thalamotomy, a less invasive alternative to DBS, has proven effective, but the procedure can take hours and require sedation. Clinicians at UAB Medical Center in Birmingham, Alabama, have been offering essential tremor patients a frameless radiosurgery option on their Varian Edge radiosurgery system under the auspices of a single-arm clinical trial.7 This trial, created by radiation oncologists Bredel and his then colleague, Evan Thomas, MD, PhD (now at Ohio State University), was designed to demonstrate the safety and feasibility of a frameless linac-based technique for treating essential tremor.
Interim results of that trial, involving 60 patients, contributed to FDA clearance of the Varian SRS solution for Edge and TrueBeam. “We have been treating essential tremor on the Edge system for approximately seven years, so we have a good grasp on what to expect,” said Professor Bredel. Preliminary results have been presented at international and national conferences and outcomes will be published soon. In the meantime, a paper published in February AJNR 2023, identified the optimal area in the brain that was targeted in the trial.8
While surgical thalamotomy and deep brain stimulation (DBS) can be effective options for medically refractory patients, not all are fit for the required anesthesia. And not all want these options, reported Vanderbilt’s Dr. Cmelak “The majority of our essential tremor patients range from 60 to 80 or older. We find that a significant number of them don’t want a craniotomy or an implant in their brain because of the risks for infection, bleeding, or stroke.” “Certainly, radiosurgical data from tremor patients who were treated with Gamma Knife show good results and safety.9 We know from treating brain tumors, brain metastases, trigeminal neuralgia, and various intercranial processes with linear-accelerator-based radiation that we can be as accurate and as effective as would be possible with Gamma Knife,” said Cmelak. “So, we were interested in determining whether a noninvasive, frameless approach to radiosurgical thalamotomy provides improvement in the measures of refractory essential tremor comparable to frame-based radiosurgery.” Based on their study, from 2013 through 2019, the answer is affirmative. “Overall treatment response rate, assessed by the Fahn-Tolosa-Marín (FTM) tremor rating scale, was 83% at 6 months. Results of the Vanderbilt study were published in 2022.2
Multidisciplinary collaboration is key
With FDA’s 510(k) clearance of these SRS solutions from Varian, radiation oncology centers with Varian TrueBeam and Edge systems have the green light to treat essential tremor. However, both UAB’S Dr. Bredel and Vanderbilt’s Dr. Cmelak agree that the selection of patients for this treatment approach requires close collaboration with referring neurologists who specialize in movement disorders, as well as with neurosurgeons. “In general, we tend to use the neurosurgeon’s expertise to determine the VIM (ventral intermediate nucleus) thalamic target to ensure collaboration and to continue the referral process. Referrals have been trending up progressively,” Dr. Cmelak reported. Similarly, at UAB, neurosurgeons are involved in every single case involving brain radiosurgery. “Frameless linac-based radiosurgery is an accurate procedure which takes only a small fraction of the time that it takes to treat using the Gamma Knife, and it comes with high levels of patient satisfaction—that’s a compelling message for neurosurgeons,” explains Dr. Bredel.
Dr. Cmelak pointed to one more persuasive benefit of Varian’s SRS solution on frameless linac-based systems—clinical efficiency. “Being able to treat your cancer patients in the morning and then treat your functional neurologic patients in the afternoon or vice versa on the same system is a huge advantage.” Dr. Bredel concurred, “A major advantage of frameless radiosurgery is that it's completely noninvasive,” observed Bredel. “Further, the patient undergoes this procedure on an Edge or TrueBeam system using a high intensity, high throughput mode (2400 monitor units per minute) with continuous surface-guided treatment monitoring. The procedure takes 30 minutes on average and the patient goes home with no recovery time required.”
The information captured herein represents the genuine experience of the attributed individuals and may not necessarily represent the views of Varian or the above-referenced institutions. Individuals were not compensated for their participation.
1 Stereotactic Radiosurgery for Essential Tremor and Parkinsonian Tremor. ClinicalTrials.gov ID NCT01734122. Accessed October 26, 2023.
2 Khattab MH, Cmelak AJ, Sherry AD, et al. Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery. Int J Radiat Oncol Biol Phys. 2022 Jan 1;112(1):121-130. doi: 10.1016/j.ijrobp.2021.08.021. Epub 2021 Aug 25. PMID: 34454047.
3 Louis, E.D and McCreary, M. How Common is Essential Tremor? Update on the Worldwide Prevalence of Essential Tremor. Tremor Other Hyperkinetic Movements (New York, NY). 2021 Jul 9; 11:28.
4 Agarwal S, Biagioni MC. Essential Tremor. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.
5 Gerbasi ME, Nambiar S, Reed S, et al. Essential tremor patients experience significant burden beyond tremor: A systematic literature review. Front Neurol. 2022 Jul 22;13:891446. doi: 10.3389/fneur.2022.891446.
6 Vetterick, C, Lyons KE, et al. The Hidden Burden of Disease and Treatment Experiences of Patients with Essential Tremor: A Retrospective Claims Data Analysis. Advances in Therapy. 2022; 39(12): 5546–5567.
7 RAD 1601: EDGE Radiosurgery for Intractable Essential Tremor and Tremor-Dominant Parkinson's Disease. ClinicalTrials.gov Identifier: NCT03305588 accessed October 26, 2023.
8 Middlebrooks EH, Popple RA, Greco E. et al. Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy. American Journal of Neuroradiology Feb 2023, 44 (2) 157-164. DOI: 10.3174/ajnr.A7778
9 Witjas, T, et al. A prospective single-blind study of Gamma Knife thalamotomy for tremor. Neurology 2015; 85:1562-1568.