Archive | 2021
Outcome of intracerebral cavernoma treated by Gamma Knife radiosurgery based on a double-blind assessment of treatment indication
Abstract
Background: The benefit and the risk profile of Gamma Knife radiosurgery (GKRS) for intracerebral cavernoma remains incompletely defined in part due to the natural history of low incidence of bleeding and spontaneous regres‐ sion of this vascular malformation. In this study, we retrieved cases from a prospectively collected database to assess the outcome of intracerebral cavernoma treated with GKRS using a double blinded review process for treatment. Methods: From 2003 to 2018, there were 94 cases of cavernoma treated by GKRS in the doubly blinded assessments by two experienced neurological and approved for GKRS treatment. All the patients received GKRS with margin dose of 11–12 (Gray) Gy and afterwards were assessed for neurological outcome, radiologic response, and quality of life. Results: The median age of the patients was 48 (15–85) years with median follow up of 77 (26–180) months post SRS. The mean target volume was 1.93 ± 3.45 cc. In those who has pre‐SRS epilepsy, 7 of 16 (43.7%) achieved seizure freedom (Engel I/II) and 9 of 16 (56.3%) achieved decreased seizures (Engel III) after SRS. Rebleeding occurred in 2 cases (2.1%) at 13 and 52 months post SRS. The radiologic assessment demonstrated 20 (21.3%) cases of decreased cavernoma volume, 69 (73.4%) were stable, and 5 (7.3%) increased size. Eighty‐seven of 94 (92.5%) cases at the last follow up achieve improvement in their quality of life, but 7 cases (7.4%) showed a deterioration. In statistical analysis, the effective seizure control class (Engel I/II) was highly correlated with patient harboring a single lesion (p < 0.05) and deep seated location of the cavernoma (p < 0.01). New neurological deficits were highly correlated with decreased mental (p < 0.001) and physical (p < 0.05) components of quality of life testing, KPS (p < 0.001), deep seated location (p < 0.01), and increased nidus volume (p < 0.05). Quality of life deterioration either in physical component (p < 0.01), mental component (p < 0.01), and KPS (p < 0.05) was highly correlated with increased cavernoma volume. Conclusion: Low margin dose GKRS for intracerebral cavernoma offers reasonable seizure control and improved quality of life while conferring a low risk of treatment complications including adverse radiation effect. © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Background Intracerebral cavernoma (CM) are uncommon in the general population, with a prevalence ranging from 0.3 to 0.6% based on large autopsy series and prospective cohort studies. The increasing incidence of cavernoma is largely due to diagnostic advances with widespread Open Access *Correspondence: [email protected] The authors Chiung‐Chyi Shen and Meei‐Ling Sheu contributed equally to this work 7 Department of Medical Research and Neurosurgery, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sec.4, Taichung 40705, Taiwan Full list of author information is available at the end of the article Page 2 of 10 Shen et al. Radiat Oncol (2021) 16:164 use of magnetic resonance imaging (MRI) in clinical practice (prevalence 0.4–0.9%) [1–4]. Individuals with CMs can present with seizures (23–50% of cases), headaches (6–52%), focal neurological deficits (20– 45%), or hemorrhages (9–56%) [1, 5–10]. The extent of permanent neurological deficits highly correlates with the number of recurrent hemorrhages, and re-bleeding episodes tend to occur at progressively shorter time intervals [11]. In patients with a symptomatic cavernoma, microsurgery is the best treatment for CM, especially given advances in microsurgical techniques and neuronavigation-guided approaches [12]. For patients with deeper seated or eloquently situated cavernomas, Gamma Knife radiosurgery (GKRS) is considered as an alternative [13–15]. The use of radiosurgery for cavernoma remains controversial especially for the primary goal of reducing the bleeding rate. Some authors have favored radiosurgery for intracranial cavernoma, due to a reduced risk of hemorrhages after a latency period of 2–3 years [16–18]. But others are less convinced about the benefits of SRS for cavernomas for a variety of reasons. First, the hemorrhage rate, particularly for retrospective series, is not simple to calculate due to the appearance of cavernoma in de novo and referral and treatment biases [19]. Second, the high-risk CM patients are usually selected to undergo surgery after SRS and thus deflate the postSRS hemorrhage rates with time [20]. Ironically, in some reports, SRS itself can also induce de novo CM development [21–23]. Furthermore, the risk of a CM rebleeding is typically high for 2–3 years after the initial hemorrhage and, thereafter, cavernoma re-hemorrhage after SRS appears to be reduced after this period of time [24]. The temporal clustering of hemorrhagic events might give a false impression of how aggressive a lesion will be in the long term. The decline in hemorrhagic events observed after treating CMs with SRS could, therefore, be a reflection of the natural history of the lesions rather than the result of radiosurgery [20, 25, 26]. Finally, cavernous malformations are dynamic lesions that may exhibit enlargement, regression, or even de novo formation [10, 27, 28]. Hence, the beneficial effect of SRS in altering the natural history of cavernoma continues to be questioned. The risk of seizures was estimated to be 1.34% per person-year for solitary CMs and 2.48% per person-year for multiple lesions [29]. The assessment of gamma knife on the seizure control rate based on the different study design achieved the seizure free rate from 31 to 53% and decreased seizure frequency from 45 to 66%, but without any treatment-related death [14, 18, 30–32]. Thus, it seems that GKRS seems to be a rational approach for improving seizure frequency associated with a cavernoma. The outcome of radiosurgery on the intracerebral cavernoma remains controversial. One way to verify the actual effect of GKRS is by clinical observation during a longer follow-up period. In addition, one could study the effects of GKRS on quality of life and seizures in cavernoma treatment patients. In this study, we prospectively evaluated the outcomes of GKRS in cavernoma patients who were double-blind assessment by two independent neurosurgeons. Methods Patient population From 2003 to 2018, there were 121 cases of intracranial cavernoma blindly approved by the two independent neurosurgeons excluding the in-charge neurosurgeon for the GKRS based on the patients’ medical records and imaging findings at the Central Bureau of Health Insurance, Taichung, Taiwan, to determine whether GKRS was the appropriate treatment. The approval criteria was based on the consensus of Taiwan Neurosurgical Society on for GKRS including one or more of the following: recurrence of cavernoma after craniotomy, target volume less than 20 cc or maximum diameter less than 3.5 cm, vulnerable location for the nidus removal, severe illness inappropriate for general anesthesia, or KPS > 70. Finally, there were 105 of 121 (86.7%) cases approved for Gamma Knife treatment. There were 11 cases lost to follow up, and, as such, 94 (89.5%) cases were included in this study. The treatment protocol was presented as a schematic flowchart shown in Additional file 1: Figure S1. The study was approved by the ethical committee of Taichung Veterans General Hospital on record No. CE21185B. Radiosurgical technique After the patient had received a local anesthetic agent, the Leksell G head frame was affixed to the head, and the patient was monitored for blood pressure, oxygenation, and electrocardiography. All patients were treated with a Leksell Gamma Knife model D (Elekta AB) by a team consisting of a neurosurgeon, neuroradiologist, radiation oncology, and medical physicist. All patients underwent GKRS with low margin dosage of 11–12 Gy prescribed to the target at the isodose line of 50–60% with radiation dose constrains with optic apparatus < 8 Gy, brain stem < 12 Gy, and lens < 2 Gy. Radiosurgery dose plans, with single or multiple isocenters, were created, and the targeted margin of the cavernoma was considered to be the region characterized by mixed signal change within the T2-weighted signal-defined hemosiderin ring [33]. Imaging technique The target lesions were typically imaged using a 1.5-T MR imaging unit (GE Medical Systems). Target localization Page 3 of 10 Shen et al. Radiat Oncol (2021) 16:164 was performed using T1-weighted, fast-spin-echo T2-weighted, spoiled-gradient recalled, and time-off light imaging. Additional T1-weighted, spoiled-gradient recalled, and time-of-flight sequences were also obtained after administration of gadolinium (Gd). The axial volume acquisition of 256 × 256 matrices was divided into 1-mm thickness without a gap. All patients gave informed consent to receive a Gd injection in accordance with Taiwan guidelines concerning Gd administration during MR imaging examinatio