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Table of Contents
Year : 2022  |  Volume : 5  |  Issue : 3  |  Page : 99-106

Brain metastases treated with CyberKnife and TomoTherapy: A report of three cases

Department of Radiation Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China

Date of Submission30-Aug-2022
Date of Decision20-Sep-2022
Date of Acceptance22-Sep-2022
Date of Web Publication13-Oct-2022

Correspondence Address:
Prof. Xia Li
No. 44 Xiaohe Yan Road, Dadong District, Shenyang City, Liaoning Province
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/glioma.glioma_23_22

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This study aimed to compare the safety and efficacy of CyberKnife (CK) versus TomoTherapy for the treatment of brain metastases (BMs). Three cases of BM treated at our hospital – two with CK and one with TomoTherapy – were compared and analyzed. Both treatments showed good therapeutic effects, but CK was more effective. No radiation-related adverse reactions were observed in the three patients. It is concluded that both CK and TomoTherapy can effectively control target lesions by allowing a higher dose in a single treatment while minimizing damage to surrounding normal brain tissue. This can reduce the total number of treatments needed, improve the prognosis of patients, and save medical resources.

Keywords: Brain metastasis, case report, cognitive function, CyberKnife, stereotactic radiotherapy, TomoTherapy

How to cite this article:
Zhu L, Li Y, Kong X, Mu A, Zhang Y, Chen L, Li X. Brain metastases treated with CyberKnife and TomoTherapy: A report of three cases. Glioma 2022;5:99-106

How to cite this URL:
Zhu L, Li Y, Kong X, Mu A, Zhang Y, Chen L, Li X. Brain metastases treated with CyberKnife and TomoTherapy: A report of three cases. Glioma [serial online] 2022 [cited 2023 Jan 28];5:99-106. Available from: http://www.jglioma.com/text.asp?2022/5/3/99/358552

  Introduction Top

Brain metastases (BMs) are the most common type of central nervous system malignancy and a frequent complication of advanced malignancies: 10%–40% of patients with malignant tumors will develop BMs during their clinical course. With the increase in systemic therapy options for tumor patients, improvements in treatment efficacy, prolongation of patient survival, and progress in magnetic resonance imaging (MRI) technology, the number of patients with BMs is increasing yearly. Available treatments for BMs include systemic and local therapies, but most drugs cannot penetrate the blood–brain barrier, with third-generation tyrosine kinase inhibitors being an exception. Local treatment still plays an important role in the treatment of BMs.[1] The survival rate of patients with multiple BMs is low, and the role of surgery in local treatment – which includes neurosurgical resection, whole-brain radiotherapy (WBRT), and stereotactic radiosurgery (SRS) – is gradually diminishing. Radiotherapy is typically recommended as the initial local treatment for patients with BMs.[2],[3] BMs are most frequently associated with lung cancer, breast cancer, and melanoma (67%–80% of BM cases).[2] The clinical manifestations and prognosis of BMs vary with tumor size and the number and location of the lesions. Distant cerebral recurrence occurs in 40%–60% of patients who receive focal therapy, and local recurrence occurs within 1 year after stereotactic radiotherapy in 10%–25% of patients.[4] Thus, more effective local therapies are needed. Technologic advances have led to the innovation of novel tools for treatment including Gamma Knife, CyberKnife (CK), and TomoTherapy and highly accurate radiotherapy techniques such as proton radiotherapy and volumetric modulated arc therapy.[5] The clinical applicability of these technologies is constantly improving.[6] At the same time, there is increasing awareness of the risk of treatment-related neurocognitive impairment caused by hippocampal neural progenitor cell damage that reduces patients' quality of life, which is as important as disease prognosis.[7]

To date, there have been no large-sample comparisons of high-end radiotherapy technologies and equipment, and various guidelines have not established the optimal instruments and segmentation times for BM radiotherapy. Nonetheless, there is an urgent need in clinical practice to determine an effective radiotherapy method that can achieve accurate sculpting and dose for the target volume while minimizing damage to the surrounding normal tissue. Of the three cases reported in this paper, two were treated with CK radiotherapy and one with TomoTherapy. It is hoped that comparing the tumor characteristics, treatment methods, dose, side effects, and follow-up results of the cases can clarify the clinical indications of and help to define a standardized protocol for the new radiotherapy technologies.

  Case Reports Top

Case 1

Case 1 was a 51-year-old male who was admitted to the hospital with a chief complaint of lung cancer with BM for 1 year and worsening of left limb inactivity for 1 week. The patient had no family history of tumor and no history of occupational contact; however, he had a history of hypertension for 5 years and was on self-administered antihypertensive medication. He had no history of allergy. The patient received chemotherapy combined with immunotherapy and stereotactic radiotherapy (45 Gy/10 F) for two BMs (left temporal and right occipital lobes) at 1 month after he was diagnosed with lung cancer and BM. After 10 months, he was admitted to the hospital because of increasing inactivity of the left limb. The admission examination revealed 26 new intracranial metastatic lesions suggesting intracranial progression. Secondary radiotherapy (TomoTherapy) was administered including gross tumor volume 49 Gy/14 F for metastatic lesions and planning target volume 35 Gy/14 F for the whole brain. Lesions in head-enhanced MRI image and TOMO treatment plan for Case 1 are shown in [Figure 1] and [Figure 2], respectively.
Figure 1: Head-enhanced MRI image of case 1. (A) Before treatment. (B) 1 month after radiotherapy. (C) 6 months after radiotherapy. Arrows indicate lesions. MRI: Magnetic resonance imaging

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Figure 2: TOMO treatment plan for Case 1. (A) Intracranial isodose field dose distribution. (B) Dose-volume histogram. Arrows indicate the intracranial metastatic lesion

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Case 2

A 70-year-old male patient was admitted to the hospital with a chief complaint of ureteral malignant tumor for more than 3 years and BM for 1 week. The patient had no family history of tumor, no history of occupational exposure, disease, or allergy. The patient underwent left ureteral and partial cystectomy for ureteral malignancy. Postoperative pathology showed high-grade urothelial carcinoma with deep muscularis invasion. Postoperative gemcitabine intravesical chemotherapy was administered. The 23-month follow-up postsurgery showed right lung metastasis, mediastinal lymph node metastasis, and pancreatic tail metastasis, and the right lung biopsy pathology confirmed metastasis of urinary origin. Adjuvant chemotherapy (albumin paclitaxel + platinum) was administered for four cycles, and the curative effect was a partial response. At 27 months postsurgery, pembrolizumab monotherapy was administered. At 31 months postsurgery, new metastatic lesions were observed in the lung, and the efficacy (partial response) of the RC18 and pembrolizumab combination for two cycles followed by sacituzumab govitecan plus pembrolizumab for two cycles was evaluated. At 36 months postsurgery, the patient developed dizziness, blurred vision, and unstable gait. An examination revealed three intracranial metastatic lesions. CK radiotherapy was administered to the lesion in the right occipital lobe (37.5 Gy/5 F) and those in the right temporal lobe and left cerebellum (28.5 Gy/3 F), and the process was smooth. Lesions in head-enhanced MRI image and CK treatment plan for three-dimensional (3D) image beam distribution of Case 2 are shown in [Figure 3] and [Figure 4], respectively.
Figure 3: Head-enhanced MRI image of case 2. (A) Before treatment. (B) 1 month after radiation therapy. Arrows indicate lesions. MRI: Magnetic resonance imaging

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Figure 4: CK treatment plan for 3D image beam distribution of Case 2. Axial dose distribution of intracranial metastatic lesions irradiated by CyberKnife (top left in A–D). CK irradiation field distribution (top right in A and D). Dose-volume histogram (top right in B and C). Sagittal dose distribution of intracranial metastatic lesions irradiated by CK (bottom left in A, C, and D). CK irradiation field distribution (bottom left in B). Coronal dose distribution of intracranial metastatic lesions irradiated by CK (bottom right A and D). CK treatment plans the dose received by normal tissues (bottom right B and C). Arrows indicate the intracranial metastatic lesions. 3D: Three-dimensional, CK: CyberKnife

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Case 3

Case 3 was a 75-year-old male. The patient was admitted with the chief complaint of colon cancer and BM for 1 month. The patient had a family history of cancer (both his father and sister had esophageal cancer) but no history of occupational exposure, disease, or allergy. The patient underwent radical resection of right-sided colon cancer at the Fourth Hospital of Shenyang. Postoperative pathology showed moderately differentiated adenocarcinoma with invasion into the outer membrane layer but no lymph node metastasis. At 45 months postsurgery, the patient experienced dizziness and unsteady gait. Brain MRI showed multiple intracranial metastatic carcinoma lesions. At 46 months postsurgery, CK at 30 Gy/3 F was administered at our hospital. Lesions in head-enhanced MRI image and CK treatment plan for 3D image beam distribution of Case 3 are shown in [Figure 5] and [Figure 6], respectively.
Figure 5: Head-enhanced MRI image of case 3. (A) Before radiation therapy. (B) 1 month after radiation therapy. (C) 3 months after radiation therapy. Arrows indicate lesions. MRI: Magnetic resonance imaging

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Figure 6: CK treatment plan for 3D image beam distribution of Case 3. Axial dose distribution of intracranial metastatic lesions irradiated by CyberKnife (top left in A and B). Dose-volume histogram (top right in A and B). CK irradiation field distribution (bottom left in A and B). CyberKnife treatment plans the dose received by normal tissues (bottom right in A). Sagittal dose distribution of intracranial metastatic lesions irradiated by CyberKnife (bottom right in B). Arrows indicate the intracranial metastatic lesions. 3D: Three-dimensional, CK: CyberKnife

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The clinical characteristics of patients with BMs and the treatment data of each case presented in this report are described in [Table 1] and [Table 2].
Table 1: Clinical characteristics of patients with brain metastases

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Table 2: CyberKnife and TomoTherapy parameters for patients with brain metastases

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The ethical approval and written consent were waived by our institutional review board owing to the retrospective nature of this case report.

  Discussion Top

WBRT and SRS are the current radiotherapy options for BMs. WBRT has been used for decades as a palliative treatment for symptomatic patients with BMs with long expected survival and who are receiving no other treatments. It has also been widely used as a prophylactic treatment for systemic cancers with a high risk of intracranial spread. The American Society for Radiation Oncology recommends the use of WBRT combined with SRS for the treatment of patients with <4 BMs as it has been shown to significantly improve survival in patients with a single BM. However, the toxicity of WBRT should be considered, and long-term sequelae after treatment can significantly affect the quality of life of patients.[5] SRS options for BM include Gamma Knife, CK, TomoTherapy, and intensity-modulated radiation therapy (IMRT). The treatment plan for multiple BMs is relatively complex because the lesions are usually surrounded by many critical and radiation-sensitive structures including the brainstem and eye. Radiation-induced necrosis of brain tissue is a very serious side effect of these methods.[8]

Gamma Knife is the best-known SRS system and is used to treat >50% of patients with BMs. The principle of the Gamma Knife system for targeting specific brain areas with radiation is relatively simple: it uses 201 concentrically placed cobalt-60 energy sources to focus beams from different angles onto precisely defined points inside the skull. The patient's position is fixed by a rigid metal head frame that allows accurate beam delivery from multiple directions and fixed radiation doses.[5],[8]

The radiation devices used in our cases were CK and TomoTherapy. CK uses 6-mV photon beams generated by a compact linear accelerator mounted on a robotic arm with six translational and rotational degrees of freedom. In contrast to Gamma Knife, CK relies on image-guided radiotherapy to track the target in space and time and is a frameless treatment option for patients with BMs that can provide accurate beam delivery in the submillimeter range.[5] TomoTherapy is a form of IMRT that uses a helical 360° radiation delivery system. Treatment planning involves comparing daily preprocessed computed tomography (CT) scans to those performed during simulation for image-guided radiotherapy. The rapid opening and closing of the leaf in a collimator that rotates around the patient allows TomoTherapy to deliver radiation doses to the complex-shaped tumor area while limiting the exposure of normal tissue. Thus, compared with traditional IMRT, TomoTherapy can provide a more precise dose gradient around the target, thereby more effectively preserving surrounding normal structures and potentially reducing radiation-related side effects.[9]

CK and TomoTherapy are among the most advanced radiologic devices as both involve “sculpting” the radiation dose to minimize exposure of normal tissue surrounding the tumor. However, clinical data on the efficacy and safety of these two technologies are lacking,[10] and few studies have directly compared CK and TomoTherapy to each other or to other SRS systems. Additionally, the choice of treatment technology for patients with BMs should be based on patient characteristics such as whether it is secondary radiotherapy and the location and number of lesions. There are still no standard recommended treatments using CK and TomoTherapy.

Information on radiotherapy equipment and evaluation plan for patients with brain metastases

All CK patients were treated with the CK M6 system, which provides the maximum range of motion in the 3D treatment space without the limitations inherent to the C-arm design and allows accurate delivery of a large band of heteroplanar beams. Patients are able to lie comfortably without head restraints, gating devices, breath-holding, chest compression, or need for re-registration. The CK M6 series minimizes the amount of marginal, healthy tissue that is irradiated, reducing the risk of side effects. The precision and flexibility of the CK system robotic arm along with the synchronous respiratory tracking system provide the industry's only proven technology to track tumor movement and make automatic adjustments in real time.

Patients receiving TomoTherapy were treated with TOMO-HD (Accuray). Treatment and imaging were homologous; 6 mV was delivered at the time of treatment, which was reduced to 3.5 mV at the time of imaging; the image was clear and the mechanical error associated with traditional image-guided radiotherapy dual-source double beams has been eliminated from the instrument design. Daily image-guided correction of setup errors, reduction of planning target volume projection range through improved accuracy, and provision of tools for adaptive treatment (monitoring anatomic structure and dose changes during treatment, and replanning using megavoltage CT) can protect normal tissue from damage to a greater extent and improve the therapeutic gain ratio.

The safety and efficacy of the two treatment instruments were evaluated based on their ability to preserve intracranial nerve function and reduce tumor volume as determined by MRI scans performed at the end of the follow-up period for each patient.

Evaluation of neurological function and physical status during treatment and clinical outcomes of patients are shown in [Table 3] and [Table 4].
Table 3: Evaluation of neurological function and physical status during treatment

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Table 4: Clinical outcomes of patients

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Summary of the current situation and prospects for clinical application of the new radiotherapy devices

In this study, CK and TomoTherapy were used for radiotherapy in patients with BMs. Each one of these instruments has its own advantages. CK technology has high therapeutic accuracy (e.g., high mechanical accuracy through focused irradiation, real-time tracking and calibration of target position, and spherical noncoplanar focused irradiation from the six-dimensional robotic hand), and the combined application of noncoplanar multicenter irradiation, target tracking, respiratory management radiotherapy, and other technologies is feasible to implement. Patients' compliance and comfort during treatment are good. Tumor tracking methods used with CK include 6D-skull, X-sight, metal marker house tracking (Fiducial), synchronous respiratory tracking (Sychrony), vertebral positioning combined with synchronous respiratory tracking (X-sightlung). Specific and appropriate tracking methods can be selected according to the tumor site. For intracranial lesions, the skull is the main target.[8] The optimal radiation dose can be achieved by isocentric or multicentric irradiation. CK also allows the possibility of reverse, 3D, and 4D planning.[11],[12]

TomoTherapy is among the most widely used radiotherapy techniques; at present, it is the only radiotherapy instrument that uses spiral CT scanning to treat cancer. Its innovative design perfectly combines a linear accelerator and spiral CT, overcoming limitations of traditional accelerators and illuminating tumors with 360° focused tomography under CT guidance, thus providing effective and accurate treatment of malignant tumors. TomoTherapy has the following advantages. (1) The use of CT makes this system highly accurate. The image quality of the unique fan-beam megavolt CT is significantly higher than that obtained using the cone-beam kilovolt CT of conventional accelerators, and the impact dose of scattering lines from a single scan is as low as 1–2 cGy. (2) Clinical data from many hospitals in China and elsewhere have confirmed that TomoTherapy has significantly increased the survival rate of patients with BMs and reduced radiation-induced complications compared with traditional radiotherapy methods. (3) Simplified TomoTherapy is ideal for complex and difficult tumor cases. The system frame is rotated 6 times/min, and multiple tumor lesions can be irradiated simultaneously through the helical irradiation mode of multiple subfields, thereby reducing the risk of repeated irradiation to normal tissue. (4) Because of its unique design and functionality, TomoTherapy can be used to treat tumors located in any part of the body. (5) High-cost performance of TomoTherapy protects normal tissues to the greatest extent possible while maximizing the radiation dose that can be delivered to tumors, thereby improving survival rate and reducing the incidence of complications. These attributes confer TomoTherapy with significant advantages over conventional radiotherapy in terms of overall treatment cost.[13],[14]

The comparison of three patients with BMs treated with CK and TomoTherapy showed that both methods can meet the needs of precision radiotherapy for intracranial lesions while minimizing damage to surrounding normal brain tissue. The major findings from this study were as follows. (1) Therapeutic effect: both methods had good clinical efficacy as reflected by tumor retraction, with TomoTherapy showing superiority over CK. (2) Collateral injury: there was no obvious neurologic impairment or cognitive decline in the two groups over a maximum follow-up time of 8 months. (3) Number of treatments: CK achieved the same treatment effect as traditional radiotherapy methods but within a shorter time, which can spare medical resources while being more convenient to patients. (4) Cost: as an emerging radiotherapy instrument, the cost of treatment with CK is still relatively high and the equipment is only available at a few Class III Grade A hospitals in China; however, the cost will soon be covered by medical insurance. On the other hand, TomoTherapy is more affordable and the treatment is already covered by insurance.

  Conclusion Top

There were certain limitations to this study. Although the patients were treated at the same medical institution by technicians with the same skill level, because of the small number of patients who were compared and considerable differences in their tumor characteristics, the finding may not be representative of the results that can be achieved with the two techniques. In terms of the observed improvement of intracranial edema, the results were biased because two patients received intracranial pressure- and edema-reducing drugs (bevacizumab and mannitol) during the treatment. Additionally, the maximum follow-up time of the three patients was just 8 months, which may be too soon for sequelae of nerve damage to manifest; long-term follow-up is needed in order to compare the risk of neurologic injury with CK versus TomoTherapy.

At present, CK and TomoTherapy are relatively sophisticated radiotherapy instruments in China for the treatment of BMs. Our comparison of three cases of BM treated with these methods shows that both can effectively irradiate the whole tumor volume. CK had better target coverage and peripheral dose decline rate in the individual patient treatment plan. However, it may not be possible to take into account the homogeneity of the optimal target dose and steep dose drop around the target in every situation. Achieving a balance between and optimizing these two factors requires further research.

In the treatment of our patients with BMs, CK and TomoTherapy significantly shortened the treatment course compared with traditional IMRT instruments. Conventional SRS therapy required 10–15 additional fractionations, but the two patients who were treated with CK reached the radical dose requirement with just 3–5 treatments. This not only shortened the length of hospital stay but was also more convenient to patients and their families and saved medical resources.

Because the three cases reported herein are still under clinical observation and the longest follow-up time was just 8 months at the time of this report, the ability of these technologies to alleviate neurologic injury and cognitive impairment over the long term remains to be determined.



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Institutional review board statement

The ethical approval and written consent were waived by our institutional review board owing to the retrospective nature of this case report.

Declaration of patient consent

The authors certify that they have obtained the patient consent forms. In the forms, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity.

Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1], [Table 2], [Table 3], [Table 4]


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