Microsoft Word - SeferisCH_Imaging_formatat Charalampos Seferis Imaging of vestibular schwannomas following γ-Knife treatment Imaging of vestibular schwannomas following γ-Knife treatment – a series of 79 cases Charalampos Seferis Hygeia Hospital, Athens, Greece, PhD Student in Neurosurgery, University of Medicine and Pharmacy “Gr.T. Popa” Iasi Abstract Gamma-Knife became an established therapeutic alternative for selected cases of vestibular schwannomas (benign tumors rooting from Scwann cells of vestibular nerve). However, the long term results and effects on the tumor and surrounding brain are still a matter of research. We analyze the imagistic findings in the patients with vestibular scwannomas treated with gamma-knife radiosurgery in the Gamma- Knife Department, Hygeia Hospital, Athens. We performed radiosurgery on 79 cases of vestibular scwannomas. 23 of them were first operated with incomplete resection and had gamma-knife performed on residual tumor. Of all cases, one patient died 4 years after the treatment, while 4 cases didn’t comply with the follow-up protocol and were excluded from the study. The other cases underwent a follow-up protocol with MRI sudies at 6, 12, 18, and 24 months following the gamma-knife session. We looked at the tumoral volume, and the evolution of the tumor in relationship with the iradiation dise and isodose curve. Our results confirm the landmark results of Karolinska an Pittsburg studies. We show that small gamma-knife doses are suitable for a satisfactory control of tumoral volume. Stereotactic MRI imaging and multiple doses programs are the main factors contributing to these results. Keywords: vestibular schwannoma, radiosurgery, gamma-knife, MRI Introduction Histologically, vestibular schwannomas are benign tumors that grow from the Schwann cells of the 8th cranian nerve. Due to improved neuroimaging the incidence of vestibular schwannomas within the general population increased. However, despite the advances in introperatory techniques, surgery still carries a risk for morbidity and moratality. Depending on tumors characteristics vestibular schwannomas can be treated by different methods, other than neurosurgery. Radiosurgery is one of these non-invasive techniques that can be used to treat vestibular schwannomas. It uses gamma radiation (photons) and is known as “Gamma-Knife” or “γ-Knife”. We analyze the imagistic findings in the patients with vestibular scwannomas treated with gamma-knife radiosurgery in the Gamma-Knife Department, Hygeia Hospital, Athens. Our results point to the fact that using small doses of radiation (similar to those used in the reference series from Karolinska and Pittsburg) can control the volume of the lesion as shown by the follow-up controls results. Stereotactic MRI and a Romanian Neurosurgery (2011) XVIII 2 multiple dosage program seem to be the main factors in achieving this result. According to published results the method can fail if the doctor decides not to partially exclude the lesions localized ar superior limit of the treated region. Materials and method In the last six years (February 2004 – September 2010) 79 cases of vestibular schwannomas have been treated with gamma-knife radiosurgery in our unit. 23 patients have undergone surgery prior to gamm-knife, and had radiosuergery as an adjuvant therapy on remnant tumor. One patient died 4 years after the gamma-knife treatment because of pre-existing cardiac co-moribidities. 4 patients failed to comply woth the follow-up rpotocol and were excluded from our study. 2 patients declaired that their quality of life deteriorated as a result of radiosurgery. To study the effects of radiation therapy the patients had to comply with a follow-up protocol that included MRI studies at 6, 12, 18, and 24 months after the treatment. The goal of follow-up was to monitor the volume of the schwannoma and to analyze the imagistic aspects as a result of gamma- knife therapy. The radiation dose (Gy) and radiation isodose curve have been measured in relationshipwith their effect in controling the progress of the tumors. The average age of the patients included in our study was 55 years (22-74). Out of 79 cases 9 presented intracanlicular tumors, 19 developed intracanalicular and cisternal tumors, while 51 presented with tumors occupying the cerebello-pontine cistern (table 1.). the main tumor volume (Vm) was 4.72 cm3 (0.2-19.3 cm3). The female to male ration was 51:28. TABLE 2 Characteristics of the 79 vestibular schwannoma patients that underwent gamma-knife surgery Parameters Values Median age (interval) 55 (27 - 74) Female to male ratio 51:28 Tumor localization intracanalicular cerebello-pontine cistern both cisternal and intracanalicular 9 51 19 Previously treated 23 Medium colume in cm3 (interval) 4,72 (0,20- 19,3) Gamma-knife therapy particularities Gamma-knife radiosurgery is base on four principles: 1. “Target” localization, using neuro- imagistic techniques, a stereotactic frame, and computer software to record and alter imaging data. 2. Computing lesion volume 3. Determining the distribution of radiation dose 4. Radiotherapy During a radiosurgery session the median of isodose curve was 48.25%, with an interval of 40-54%. Target localization is extremely important and excluding important cranial structures from being exposed to the gamma radiation (such as cranial nerves, cerebellum, and of course brain stem). During treatment average marginal dose was 12.09 Gy (11 – 14 Gy), and maximal average dose was 19.83 Gy (20.5 – 29.9 Gy). Average tumor volume of treated Charalampos Seferis Imaging of vestibular schwannomas following γ-Knife treatment schwannomas was 4.72 cm3 (0.2 – 19.3 cm3). To protect the undefined segments of the facial and trigeminal nerves that are prone to be included in the designated lesion volume, we administered in these areas doses below 13 and 15 Gy respectively. In two cases where the tumor had an occupying effect involving the brainstem the same dose didn’t reach more than 10 Gy. All patients responded well to the treatment and were released the next morning after treatment completion. None reported neurological problems during hispitalization (such as epileptic seizures). Headache was present in 12 cases, most likely due to the steretactic frame. To address these headaches patients were given oral pain killers for a short period of time (2-3 days) in the period following their release. Follow-up All patients, with one exception, underwent MRI imaging 6 months after the treatment. Six of them didn’t present for the next follow-up session, at 12 months. MRI evaluation criteria included: •Changes in the volume of the vestibular schwannoma •Neuro-imagistic findings like: loss of central enhance (necrosis), local swelling through the cerebral ventricular system. Results The average follow-up period was of 24 months (1 – 51). 84.2% of the patients performed at least one MRI exploration at 6 months. MRI evaluation The solid part of the tumor reacted satisfactory to gamma-knife iradiation. As documented by the MRI images in the first six months this response takes the shape of a central region of necrosis (seen in T1). Acording to published data this phenomena is noticed from the first month (or later than 23 months) and can extend within the tumor in the next 10 months (or even later than 60 months) after the treatment. A small percentage of the patients (11,8%) showed a swelling of the lesion. MRI findings at first follow-upmatch those reported in the literature in 34 cases. Only 2 cases showed a significant change in lesion volume in the 24 months period following gamma-knife therapy (from 0.71 cm3 to 1.1 cm3, and from 19.3 cm3 to 23.1 cm3), while the maximum reduction in tumor volume recorded in our series was from 12.4 to 2.7 cm3. Discussion Optimal radiation dosage for tumor control Optimal radiation dosage for vestibular schwannoma control is still a matter of debate. A review of the literature showed a tendency to decreasing prescription dosage from 25-100 Gy used in the initial studies to 13 Gy in the current protocols. Nóren, et al. have prescribed dosages of 25-35 Gy to the tumor periphery to ensure stopping tumor growth. However, high dose radiation has led to high morbidity due to facial and trigeminal nerve damage. In addition, possible preservation of hearing may be compromised when using a high dosage. First of all, a reduced radiation dose lowers the probability of cranial nerve neuropathy. Second of all, small doses have a better chance, at least in theory, to preserve hearing close to preoperative levels. Third of all, a lower dose should theoretically reduce or minimize the degree of swelling of the tumor that may occur after treatment. Romanian Neurosurgery (2011) XVIII 2 Figure 1 Left: Male, 62 yrs. Old, before therapy. Dose 12Gy (45%), volume 3,4 cm³. Right: control at 6 months (central necrosis) Figure 2 Upper left: Male, 73 yrs., before therapy. Dose 11 Gy, tumor volume 5.6 cm³. At 24 months after gamma-knife tumor volume 3,1 cm³ (lower right). Dimensions before therapy: 3 cm x 2 cm, and after therapy: 2 cm x 1,4 cm. Charalampos Seferis Imaging of vestibular schwannomas following γ-Knife treatment Figure 3 Female, 44 yrs., before therapy. Dose 11 Gy (50%). After 6, 12, and 24 months respectively. Tumor volume before therapy 12,4 cm³, 24 months after therapy 3cm³. Larson et al. proposed the use of a single dose of 13.5 Gy, given the biological effect of delayed tissue response. Flickinger and ass. have questioned whether or not the tumor control rate could be reduced by a dose smaller than 13 Gy. In this study, we had satisfactory results in patients treated with a median marginal dose of 12.09 Gy (11-14 Gy). Thus, in our experience it is possible to obtain satisfactory long-term control of the tumor at a marginal dose less than 11 Gy. Tumor control rate was in no way worse than those reported in earlier series, where significantly higher doses were used. Optimal dosage for preservation of cranial nerves It has been suggested that the facial nerve tolerates marginal doses up to 15 Gy, but doses above 14 Gy have been shown to lead to a significant increase in neuropathy incidence, particularly in the patients with large tumors. In the early days of radiosurgery, subjective numbness or hypoesthesia has been reported as major complication of trigeminal nerve radiation damage. The incidence was as high as 19% in both Karolinska and Pittsburgh series. The large tumoral volume and high radiation doses used corroborate to this undesirable consequence of radiation therapy. The incidence of trigeminal neuropathy was reduced to 4% transient neuropathy and 1.6% persistent neuropathy in Charlottesville exerience, where the average marginal dose used was 13.2 Gy. In the present series, no patient developed any kind of sensory deficit. Preservation of hearing has become the main concern in advanced radiosurgery. In this study, 43 of 60 patients with good preoperative hearing, maintain a functional hearing during a Romanian Neurosurgery (2011) XVIII 2 follow-up period of 21 months. Numerous studies have reported a total rate of 33-55% of hearing preservation in a 2-4 years period after treatment. A definite inverse correlation exists between the dimensions of the tumor and the probability of hearing preservation. Prasad and colleagues have reported a marginal inverse correlation between the dose used and the likelihood of hearing preservation, especially manifest at a dose higher than 13 Gy. In our series, neither the volume of the tumor nor the marginal dose appear to play a critical role in postoperative hearing preservation. In contrast, pure tone audiometry before Gamma Knife surgery seems to be a good possible measure for evaluating the results. Loss of central contrast enhance Loss of central enhancing on MRI imaging was observed in 54% of patients of Prasad et al., 70% of Nóren, et al. and 63% of Flickinger, et al series. In this study, this phenomenon was observed in 63.3% of cases. This is a common observation after radiosurgery. More research is required to clarify the pathogenesis. Backlund reported that tumor necrosis was found in a histological study, which corresponds to the central region of enhanced MRI image. Seo, et al. showed using scanning with 99Tc (human serum albumin - dietulenetriamin pentaacetic acid-photon) positron emission computed tomography reduced vascularization of vestibular schwannoma 1 to 2 years after radiosurgery,. Spiegelman and colleagues have suggested that ischemia was produced by tumor associated acute edema. Fukoka and colleagues suggested that apoptosis may be a possible mechanism. Based on these observations, it is aceeptable to consider that the loss of radiological central enhancing is a reliable indicator of long- term good control. This hypothesis, however, requires additional data from more patients and longer-term follow-up. Failed treatment In no case was there any evidence of active tumor growth. It has to be considered that labyrinth schwanomas can swell without regrowing after radiosurgery. It is suggested that the modest doses currently in use may reduce this tendency. Conclusions Using small doses of radiation (similar to those used in the reference series from Karolinska and Pittsburg, smaller than the usual doses used in other gamma-knife units) can control the volume of the lesion as shown by the follow-up controls results. Stereotactic MRI and a multiple dosage program seem to be the main factors in achieving this result. 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