Hypofractionated stereotactic radiosurgery for large-sized skull base meningiomas.

PURPOSE: Although stereotactic radiosurgery (SRS) has been proven to be effective and safe for treating intracranial meningiomas, concerns have been raised about the use of SRS for large-sized tumors involving the skull base that frequently encroach onto adjacent critical neural structures. The purpose of this study was to investigate the role of hypofractionated SRS as a therapeutic option for large-sized skull base meningiomas. METHODS: Thirty-one consecutive patients (median age: 55 years, 9 men and 22 women) who had been treated with hypofractionated SRS using CyberKnife for large-sized skull base meningiomas (> 10 cm3 in volume, median of 18.9 cm3, range 11.6-58.2 cm3) were enrolled. All patients harbored middle or posterior skull base tumors, most frequently of cavernous sinus (n = 7, 22.6%), petroclival (n = 6, 19.4%), or tentorial edge (n = 6, 19.4%) locations. SRS was delivered in five daily fractions (range 3-5 fractions) with a median cumulative dose of 27.8 Gy (range 22.6-27.8 Gy). RESULTS: With a median follow-up of 57 months (range 9-98 months), tumor control was achieved for 28 (90.3%) of 31 patients. Treatment response on MRI included partial response (volume decrease > 20%) in 17 (54.8%) patients, stable in 11 (35.5%), and progression (volume increase > 20%) in 3 (9.7%). Of 21 patients with cranial neuropathy, 20 (95.2%) showed improved neurological status. CONCLUSIONS: Our current results suggest a promising role of hypofractionated SRS for large-sized skull base megningiomas in terms of tumor control and neurological outcomes. It is a reasonable therapeutic option for select patients.

Single-fraction versus hypofractionated stereotactic radiosurgery for medium-sized brain metastases of 2.5 to 3 cm.

PURPOSE: Given recently suggested utility of hypofractionated stereotactic radiosurgery (SRS) in treating large brain metastases (BMs) > 3 cm, we sought to prospectively control tumor size variable to investigate the efficacy and safety of hypofractionated SRS for medium-sized BMs (2.5 to 3 cm) compared with single-fraction SRS. METHODS: Between 2011 and 2015, a total of 100 patients with newly diagnosed BMs (n = 105) of 2.5 to 3 cm had been treated with either single-fraction (n = 67; median dose 20 Gy) or hypofractionated SRS (n = 38; median cumulative dose 35 Gy in 5 daily fractions). No patients received any prior or upfront whole brain radiotherapy. In each patient, treatment outcome was measured by local tumor control (LTC), overall and progression-free survival (OS and PFS), and the occurrence of radiation necrosis (RN). RESULTS: With a median follow-up of 14 months, significant differences were observed between the single-fraction versus hypofractionated SRS groups in the incidence of RN (29.9% vs. 5.3%, P < 0.001) and LTC (1-year LTC rates 66.6% vs. 92.4%, P = 0.028). There were no differences in PFS (median 6 months vs. 6 months, P = 0.381) and OS (median 13 months vs. 18 months, P = 0.239). Treatment-related adverse events ( ≥ grade 2 toxicity by CTCAE ver. 4.0) occurred more frequently in single-fraction group, although the difference did not reach statistical significance (56.3% vs. 36.1%, P = 0.084). CONCLUSIONS: Our results suggest a better safety and efficacy profile of hypofractionated SRS for medium-sized BMs compared with single-fraction SRS. Further prospective studies are needed to confirm these results.

Comparing phase- and amplitude-gated volumetric modulated arc therapy for stereotactic body radiation therapy using 3D printed lung phantom.

PURPOSE: To compare the dosimetric impact and treatment delivery efficacy of phase-gated volumetric modulated arc therapy (VMAT) vs amplitude-gated VMAT for stereotactic body radiation therapy (SBRT) for lung cancer by using realistic three-dimensional-printed phantoms. METHODS: Four patient-specific moving lung phantoms that closely simulate the heterogeneity of lung tissue and breathing patterns were fabricated with four planning computed tomography (CT) images for lung SBRT cases. The phantoms were designed to be bisected for the measurement of two-dimensional dose distributions by using EBT3 dosimetry film. The dosimetric accuracy of treatment under respiratory motion was analyzed with the gamma index (2%/1 mm) between the plan dose and film dose measured under phase- and amplitude-gated VMAT. For the validation of the direct usage of the real-time position management (RPM) data for respiratory motion, the relationship between the RPM signal and the diaphragm position was measured by four-dimensional CT. By using data recorded during the beam delivery of both phase- and amplitude-gated VMAT, the total time intervals were compared for each treatment mode. RESULTS: Film dosimetry showed a 5.2 ± 4.2% difference of gamma passing rate (2%/1 mm) on average between the phase- vs amplitude-gated VMAT [77.7% (72.7%-85.9%) for the phase mode and 82.9% (81.4%-86.2%) for the amplitude mode]. For delivery efficiency, frequent interruptions were observed during the phase-gated VMAT, which stopped the beam delivery and required a certain amount of time before resuming the beam. This abnormality in phase-gated VMAT caused a prolonged treatment delivery time of 366 s compared with 183 s for amplitude-gated VMAT. CONCLUSIONS: Considering the dosimetric accuracy and delivery efficacy between the gating methods, amplitude mode is superior to phase mode for gated VMAT treatment.

Hypofractionated stereotactic radiosurgery for pituitary metastases.

Pituitary metastases (PMs) are uncommon, representing only 1% of pituitary lesions. The diagnosis of PMs can be challenging and an optimal management remains to be determined. Here, we present a pilot clinical study on the efficacy and safety of hypofractionated stereotactic radiosurgery (SRS) with an optimized dosimetric plan in treating PMs. Between June 2013 and December 2014, seven consecutive patients (4 men and 3 women; median age 62 years) had been diagnosed with PMs based on their characteristic clinical and radiological features and subsequently treated using hypofractionated SRS. Primary cancers originated from the lung (n = 5) or the breast (n = 2). All patients presented with diabetes insipidus (DI). Anterior pituitary and visual dysfunction were combined in 4 and 3 patients, respectively. On magnetic resonance imaging (MRI), PMs involved the pituitary stalk and/or the posterior lobe in all patients. SRS of a cumulative marginal dose 31 Gy with dose-volume constraints for the optic apparatus was delivered in 5 daily fractions. As results, tumor was locally controlled in all patients with substantial responses on MRI (including complete remission in 4 patients). The median survival time was 14 months (range, 6-24 months) after SRS. DI and visual dysfunction improved in all patients, although anterior pituitary dysfunction did not recover. No patients experienced any deterioration in visual, pituitary, or other cranial nerve functions. These results suggest a promising role of hypofractionated SRS in treating PMs in terms of both tumor control and functional outcomes.

Radiosurgical decompression for benign perioptic tumors causing compressive cranial neuropathies: a feasible alternative to microsurgery?

Several studies have reported the efficacy and safety of hypofractionated stereotactic radiosurgery (hSRS) in the treatment of benign perioptic tumors. This study went further and evaluated the feasibility of hSRS in the treatment of those causing compressive cranial neuropathies (CCNs) among perioptic tumors with special consideration of functional improvement. Twenty-six patients with CCNs (CN II = 19; CN III/IV/VI = 9; CN V = 3) caused by perioptic tumors underwent hSRS between 2011 and 2015. hSRS was delivered in five fractions with a median marginal dose of 27.8 Gy (≈14 Gy in a single fraction, assuming an α/ß of three) to a tumor volume of 8.2 ± 8.3 cm3. All tumors except one shrank after treatment, with a mean volume decrease of 35 % (range 4-84 %) during the mean follow-up period of 20 months. In 19 patients (38 eyes) with compressive optic neuropathy, vision improved in 55.3 % of eyes (n = 21), was unchanged in 36.8 % (n = 14), and worsened in 7.9 % (n = 3) (2.6 % after excluding two eyes deteriorated due to transient tumor swelling). A higher conformity index (p = 0.034) and volume of the optic apparatus receiving >23.0 Gy (p = 0.019) were associated with greater tumor shrinkage. A greater decrease in tumor volume (p = 0.035) was associated with a better improvement in vision. Ophthalmoplegia and facial hypesthesia improved in six of nine (66.7 %) and three of three (100 %) patients, respectively. There was no newly developed neurological deficit. Decompressive SRS for benign perioptic tumors causing CCN is feasible using hypofractionation, representing a useful alternative to microsurgical resection.

Experiences on two different stereotactic radiosurgery modalities of Gamma Knife and Cyberknife in treating brain metastases.

BACKGROUND: In this study, we compared the dosimetric properties between Gamma Knife (GK) and Cyberknife (CK), and investigated the clinical implications in treating brain metastases (BMs). METHODS: Between 2011 and 2013, 77 patients treated with either single-fraction GK for small BMs (n = 40) or fractionated CK for large BMs >3 cm (n = 37) were analyzed. Among a total of 160 lesions, 81 were treated with GK (median, 22 Gy) and 38 (large lesions) with three- or five-fraction CK (median, 35 Gy). The median tumor volume was 1.0 cc (IQR, 0.12-4.4 cc) for GK and 17.6 cc (IQR, 12.8-23.7 cc) for fractionated CK. A lesion-to-lesion dosimetric comparison was performed using the identical contour set in both systems. RESULTS: The mean dose to tumor was significantly higher in GK by 1.25-fold (P < 0.001), whereas normal tissue volume receiving 90-10 % of prescription dose was significantly larger in CK by 1.26-fold (P < 0.001). Nevertheless, no differences were observed in local tumor control (rates at 1 year, 89.7 % vs 87.0 %; P = 0.594) and overall survival (median, 14 vs 16 months; P = 0.493) between GK and fractionated CK groups. The incidences of radiation necrosis were also not different (12.3 % vs 15.8 %; P = 0.443). CONCLUSIONS: Despite slightly inferior dosimetric properties of CK, fractionated CK for large BMs appears to be as effective and safe as single-fraction GK for small BMs, representing fractionation as an effective strategy for enhancing efficacy and moderating toxicity in stereotactic radiosurgery for BMs.

Automated Field-In-Field (FIF) Plan Framework Combining Scripting Application Programming Interface and User-Executed Program for Breast Forward IMRT.

PURPOSE: To develop an one-click option on treatment planning system that enables for the automated breast FIF planning by combining the Eclipse Scripting application programming interfaces and user-executed programming in Windows. METHODS: Scripting application programming interfaces were designed to promote automation in clinical workflow associated with radiation oncology. However, scripting cannot provide all functions that users want to perform. Thus, a new framework proposes to integrate the benefits of the scripting application and user-executed programming for the automated field-in-field technique. We adopted the Eclipse Scripting applications, which provide an interface between treatment planning system server and client and enable for running the executed program to create dose clouds and adjust the planning parameters such as multi-leaf collimator placements and monitor unit values. Importantly, all tasks are designed to perform with one-click option on treatment planning system, including the automated pushback of the proposed plan to the treatment planning system. RESULTS: The plans produced from the proposed framework were validated against the manual field-in-field plans with 40 retrospective breast patient cases in planning efficiency and plan quality. The elapsed time for running the framework was less than 1 minute, which significantly reduced the manual multi-leaf collimator/monitor unit adjustment time. It decreased the total planning time by more than 50%, relative to the manual field-in-field planning. In dosimetric aspects, the mean and maximum dose of the heart, lung, and whole breast did not exceed 1% deviation from the manual plans in most patient cases, while maintaining the target dose coverage and homogeneity index inside the target volume. From numerical analysis, the automated plans were demonstrated to be sufficiently close to the manual plans. CONCLUSION: The combination of scripting applications and user-executed programming for automated breast field-in-field planning accomplished a significant enhancement in planning efficiency without degrading the plan quality, relative to the manual field-in-field procedure.

Dosimetric evaluation of respiratory gated volumetric modulated arc therapy for lung stereotactic body radiation therapy using 3D printing technology.

PURPOSE: This study aimed to evaluate the dosimetric accuracy of respiratory gated volumetric modulated arc therapy (VMAT) for lung stereotactic body radiation therapy (SBRT) under simulation conditions similar to the actual clinical situation using patient-specific lung phantoms and realistic target movements. METHODS: Six heterogeneous lung phantoms were fabricated using a 3D-printer (3DISON, ROKIT, Seoul, Korea) to be dosimetrically equivalent to actual target regions of lung SBRT cases treated via gated VMAT. They were designed to move realistically via a motion device (QUASAR, Modus Medical Devices, Canada). Using the lung phantoms and a homogeneous phantom (model 500-3315, Modus Medical Devices), film dosimetry was performed with and without respiratory gating for VMAT delivery (TrueBeam STx; Varian Medical Systems, Palo Alto, CA, USA). The measured results were analyzed with the gamma passing rates (GPRs) of 2%/1 mm criteria, by comparing with the calculated dose via the AXB and AAA algorithms of the Eclipse Treatment Planning System (version 10.0.28; Varian Medical Systems). RESULTS: GPRs were greater than the acceptance criteria 80% for all film measurements with the stationary and homogeneous phantoms in conventional QAs. Regardless of the heterogeneity of phantoms, there were no significant differences (p > 0.05) in GPRs obtained with and without target motions; the statistical significance (p = 0.031) was presented between both algorithms under the utilization of heterogeneous phantoms. CONCLUSIONS: Dosimetric verification with heterogeneous patient-specific lung phantoms could be successfully implemented as the evaluation method for gated VMAT delivery. In addition, it could be dosimetrically confirmed that the AXB algorithm improved the dose calculation accuracy under patient-specific simulations using 3D printed lung phantoms.

Gated Volumetric-Modulated Arc Therapy vs. Tumor-Tracking CyberKnife Radiotherapy as Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Dosimetric Comparison Study Focused on the Impact of Respiratory Motion Managements.

PURPOSE: To assess the potential dosimetric benefits associated with the CyberKnife (CK) tumor tracking capability, wherein an extra margin for respiratory tumor motion is not required, when compared to respiratory-gated volumetric-modulated arc therapy (VMAT) for hepatocellular carcinoma (HCC). METHODS: Twenty-nine HCC patients previously treated with double-arc VMAT were enrolled. In each VMAT plan, the individual internal target volume (ITV) margin around the tumor was determined by measuring its motion over 30-70% of respiratory phases using four-dimensional computed tomography, followed by a 5-mm isotropic margin for the planning target volume (PTV). For each VMAT plan, two CK plans were generated using the original (CKoriginal, ITV included) and modified PTVs (CKmodified, ITV excluded) for comparison. In each case, the CKoriginal and CKmodified plans were compared to the original VMAT plan in terms of the dosimetric parameters including the conformity index (CI), PTV coverage (CO), organs at risk (OAR) doses, and normal liver tissue sparing. RESULTS: The original PTVs with median 24 cc (range, 9-65 cc) were significantly reduced to median 12 cc (range, 5-41 cc) in the CKmodified plans. Statistically significant differences in plan qualities were observed between the VMAT and the CK plans: mean CI, 1.05 in VMAT vs. 1.17 in both CK plans (p < 0.001); and mean CO, 93.0% in VMAT vs. 96.6% in CKoriginal and 96.9% in CKmodified (p < 0.001). The average volume of normal liver tissue receiving > 15 Gy was significantly decreased in the CKmodified plan, as compared to that in the VMAT and CKoriginal plans, by 1.75- and 1.61-fold, respectively. CONCLUSIONS: The tumor tracking capability of the CK system can significantly decrease the volume of normal liver tissue receiving > 15 Gy, while maintaining high precision in target localization, conformity, tumor coverage, and dose sparing of the OAR. Therefore, it can be a valuable SBRT option, particularly for HCC patients with poor liver function.

Verification of Accuracy of CyberKnife Tumor-tracking Radiation Therapy Using Patient-specific Lung Phantoms.

PURPOSE: To investigate the accuracy of the CyberKnife Xsight Lung Tracking System (XLTS) compared with that of a fiducial-based target tracking system (FTTS) using patient-specific lung phantoms. METHODS AND MATERIALS: Three-dimensional printing technology was used to make individualized lung phantoms that closely mimicked the lung anatomy of actual patients. Based on planning computed tomographic data from 6 lung cancer patients who underwent stereotactic ablative radiation therapy using the CyberKnife, the volume above a certain Hounsfield unit (HU) was assigned as the structure to be filled uniformly with polylactic acid material by a 3-dimensional printer (3D Edison, Lokit, Korea). We evaluated the discrepancies between the measured and modeled target positions, representing the total tracking error, using 3 log files that were generated during each treatment for both the FTTS and the XLTS. We also analyzed the γ index between the film dose measured under the FTTS and XLTS. RESULTS: The overall mean values and standard deviations of total tracking errors for the FTTS were 0.36 ± 0.39 mm, 0.15 ± 0.64 mm, and 0.15 ± 0.62 mm for the craniocaudal (CC), left-right (LR), and anteroposterior (AP) components, respectively. Those for the XLTS were 0.38 ± 0.54 mm, 0.13 ± 0.18 mm, and 0.14 ± 0.37 mm for the CC, LR, and AP components, respectively. The average of γ passing rates was 100% for the criteria of 3%, 3 mm; 99.6% for the criteria of 2%, 2 mm; and 86.8% for the criteria of 1%, 1 mm. CONCLUSIONS: The XLTS has segmentation accuracy comparable with that of the FTTS and small total tracking errors.