A total of 96 male Wistar rats weighing between 200 and 240 g were housed in cages (two rats per cage) and maintained in environmentally controlled rooms (22–24°C) with a 12-h light/dark cycle. Experiments involving animals were approved by the Animal Care and Ethics Committee of Tianjin Medical University (Tianjin, China). A maximum dose of 60 Gy was administered into the right parietal cortex via the Leksell gamma knife model C (Elekta Instrument AB, Stockholm, Sweden) by using a 4-mm collimator (Elekta Instrument AB, Stockholm, Sweden) as described previously (13 (link)). The selection of the radiation dose was based on previous studies (14 (link),15 (link)). A rat anesthetized with 10% chloraldurat (3 ml/kg) was fixed in a stereotactic brain frame. Following obtaining high-resolution magnetic resonance (MR) images, the center of the irradiation area was calculated with reference to a standard rat stereotactic atlas (16 ) and the cerebral structures visible on the MR images. Leksell Gamma Plan software (Elekta Instrument AB) was used to attain target localization for the radiosurgery. The control animals were treated identically but did not receive any radiation.
Leksell gamma knife model c
Manufactured by Elekta
The Leksell Gamma Knife model C is a stereotactic radiosurgery system designed for the treatment of intracranial lesions. It utilizes multiple beams of gamma radiation to precisely target and ablate specific areas of the brain while minimizing exposure to surrounding healthy tissue.
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6 protocols using leksell gamma knife model c
1
Gamma Knife Irradiation in Wistar Rats
2
SRS and TKIs for Brain Metastases
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All metastatic tumors in the brain were treated with SRS using Leksell Gamma Knife model C (Elekta, Stockholm, Sweden). We obtained T1-weighted, high-dose gadolinium enhanced images, with an injected gadolinium volume of 0.4 mmol/kg. We used multiple isocenters to insure a highly conformal dose distribution and defined a prescription dose as a dose covering at least 93% of the target volume. To irradiate the tumor margins, the median peripheral dose of 23 Gy (range, 15-25 Gy) was prescribed at the median 50% isodose line (range, 34-65%). After SRS, the patients were observed to detect any acute adverse effects.
Patients treated with SRS and TKIs for brain metastases received the TKIs within 2 weeks of commencing SRS. These patients received oral gefitinib (Iressa; AstraZeneca, London, UK) 250 mg or erlotinib (Tarceva; Roche, Basel, Switzerland) 150 mg once daily. The other patients were treated with systemic chemotherapy. The guideline recommendations about application of EGFR-TKI treatment for lung cancer patients harboring activating EGFR mutation were changed from the second line treatment to the first line treatment in Korea in 2010. Among various systemic therapy, regimen was chosen for each patient regarding patients' preference, side effect and previous treatment history.
Patients treated with SRS and TKIs for brain metastases received the TKIs within 2 weeks of commencing SRS. These patients received oral gefitinib (Iressa; AstraZeneca, London, UK) 250 mg or erlotinib (Tarceva; Roche, Basel, Switzerland) 150 mg once daily. The other patients were treated with systemic chemotherapy. The guideline recommendations about application of EGFR-TKI treatment for lung cancer patients harboring activating EGFR mutation were changed from the second line treatment to the first line treatment in Korea in 2010. Among various systemic therapy, regimen was chosen for each patient regarding patients' preference, side effect and previous treatment history.
3
Stereotactic Radiosurgery for Brain Metastases
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SRS was performed on the Leksell Gamma Knife Model C (Elekta, Stockholm, Sweden) prior to May 2009, and Perfexion after May 2009. Same day headframe fixation was used for immobilization. Patients underwent a contrast-enhanced stereotactic magnetic resonance imaging scan of the brain with headframe in place. The GammaPlan Treatment Planning System (AB Elekta, Stockholm, Sweden) was used to develop the treatment plan. Median marginal dose prescribed was 18–22 Gy and was generally prescribed to the 50% isodose line. The dose selected was based on guidelines previously described by Shaw et al.19 (link). The targeting of the resection cavity of the metastasis was previously described by Jensen et al.20 (link).
4
Stereotactic Radiosurgery for Brain Metastases
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Patients selected for SRS alone at our institution had one to four brain metastases, Karnofsky performance status (KPS) ≥70, and life expectancy ≥3 months. Occasionally, patients were found to have additional occult metastases at the time of SRS and >4 lesions were treated with SRS alone. SRS was performed using a Leksell Gamma Knife Model C (Elekta, Inc., Stockholm, Sweden). Target lesions were identified using high-resolution magnetic resonance imaging (MRI) with intravenous gadolinium contrast. The target volume included the contrast-enhancing lesion with a 1–2 mm margin. Dose was prescribed based on tumor size according to Radiation Oncology Therapy Group (RTOG) study 90–05 (16 (link)). The median dose to the tumor margin was 20 Gy (range 14–22) generally prescribed to the 50% isodose line. Lesser margins and/or lower doses were used when tumors were near the brainstem or other sensitive structures.
5
Stereotactic Radiosurgery for Chordoma
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In all 53 cases, a Leksell stereotactic frame was fixed to the patient’s skull under local anesthesia. High-resolution contrast-enhanced magnetic resonance imaging (MRI) was performed, utilizing a slice thickness of 2 mm for treatment planning. Radiosurgery was performed using the Leksell Gamma Knife model B (Elekta AB) before 2007, the Leksell Gamma Knife model C (Elekta AB) between January 2007 and October 2011, and the Leksell Gamma Knife Perfexion (Elekta AB) thereafter. Multiple dose planning sessions were carried out using the GammaPlan system (Elekta Instruments).
In the cohort evaluated in the present study, the mean prescribed radiation dose was 13.5 Gy (range, 10–16 Gy), for which the equivalent dose in 2-Gy fractions (EQD2; calculated assuming an α/β = 3 for chordomas) ranged from 26 to 60.8 Gy (mean, 44.8 Gy). The mean isodose line was 45.8% (range, 40–50%); the mean maximum dose was 29.4 Gy (range 22–33.3 Gy); and the mean tumor volume was 17.1 cm3 (range, 1.1–62.2 cm3). Some patients had complicated radiotherapy histories, so the average total EQD2 for these patients was 60.3 Gy (range, 26–200 Gy) (Table 1
In the cohort evaluated in the present study, the mean prescribed radiation dose was 13.5 Gy (range, 10–16 Gy), for which the equivalent dose in 2-Gy fractions (EQD2; calculated assuming an α/β = 3 for chordomas) ranged from 26 to 60.8 Gy (mean, 44.8 Gy). The mean isodose line was 45.8% (range, 40–50%); the mean maximum dose was 29.4 Gy (range 22–33.3 Gy); and the mean tumor volume was 17.1 cm3 (range, 1.1–62.2 cm3). Some patients had complicated radiotherapy histories, so the average total EQD2 for these patients was 60.3 Gy (range, 26–200 Gy) (
6
EGFR-TKI and WBRT with SRS for Brain Metastases
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A total of 181 patients all received EGFR-TKI oral treatment (icotinib 125 mg/day, tid; gefitinib 250 mg qd; erlotinib 150 mg qd). The total dose of WBRT was 30 Gy administered in 10 fractions (3 Gy fractions once a day, 5 days a week). All metastatic tumors in the brain were treated with SRS using Leksell Gamma Knife model C (Elekta, Stockholm, Sweden). To irradiate the tumor margins, the median peripheral dose of 18.2 Gy (range: 15.5–20.5 Gy) was prescribed at the median 45.9% isodose line (range: 40–70%). All patients underwent imaging examinations after two courses of chemotherapy or every 4 ±1 week for the first 2 months of EGFR-TKI treatment. Patients underwent chest, abdomen, and pelvic CT and brain MRI every 3 months until disease progression. The tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, including complete remission (CR), partial remission (PR), stable disease (SD), and progression of disease (PD).
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