LINAC based stereotactic radiosurgery for multiple brain metastases: guidance for clinical implementation.

Introduction: Stereotactic radiosurgery (SRS) is a promising treatment option for patients with multiple brain metastases (BM). Recent technical advances have made LINAC based SRS a patient friendly technique, allowing for accurate patient positioning and a short treatment time. Since SRS is increasingly being used for patients with multiple BM, it remains essential that SRS be performed with the highest achievable quality in order to prevent unnecessary complications such as radionecrosis. The purpose of this article is to provide guidance for high-quality LINAC based SRS for patients with BM, with a focus on single isocenter non-coplanar volumetric modulated arc therapy (VMAT). Methods: The article is based on a consensus statement by the study coordinators and medical physicists of four trials which investigated whether patients with multiple BM are better palliated with SRS instead of whole brain radiotherapy (WBRT): A European trial (NCT02353000), two American trials and a Canadian CCTG lead intergroup trial (CE.7). This manuscript summarizes the quality assurance measures concerning imaging, planning and delivery. Results: To optimize the treatment, the interval between the planning-MRI (gadolinium contrast-enhanced, maximum slice thickness of 1.5 mm) and treatment should be kept as short as possible (< two weeks). The BM are contoured based on the planning-MRI, fused with the planning-CT. GTV-PTV margins are minimized or even avoided when possible. To maximize efficiency, the preferable technique is single isocenter (non-)coplanar VMAT, which delivers high doses to the target with maximal sparing of the organs at risk. The use of flattening filter free photon beams ensures a lower peripheral dose and shortens the treatment time. To bench mark SRS treatment plan quality, it is advisable to compare treatment plans between hospitals. Conclusion: This paper provides guidance for quality assurance and optimization of treatment delivery for LINAC-based radiosurgery for patients with multiple BM.

Impact of the calculation resolution of AAA for small fields and RapidArc treatment plans.

PURPOSE: To investigate the impact of the calculation resolution of the anisotropic analytical algorithms (AAA) for a variety of small fields in homogeneous and heterogeneous media and for RapidArc plans. METHODS: Dose distributions calculated using AAA version 8.6.15 (AAA8) and 10.0.25 (AAA10) were compared to measurements performed with GafChromic EBT film, using phantoms made of polystyrene or a combination of polystyrene and cork. The accuracy of the algorithms calculated using grid resolutions of 2.5 and 1.0 mm was investigated for different field sizes, and for a limited selection of RapidArc plans (head and neck, small meningioma, and lung). Additional plans were optimized to create excessive multileaf collimator modulation and measured on a homogenous phantom. Gamma evaluation criterion of 3% dose difference and 2- or 1-mm distance to agreement (DTA) were applied to evaluate the accuracy of the algorithms. RESULTS: For fields < or = 3 x 3 cm2, both versions of AAA predicted lower peak doses and broader penumbra widths than the measurements. However, AAA10 and a finer calculation grid improved the agreement. For RapidArc plans with many small multileaf collimator (MLC) segments and relatively high number of monitor units (MU), AAA8 failed to identify small dose peaks within the target. Both versions performed better in polystyrene than in cork. In homogeneous cork layers, AAA8 underestimated the average target dose for a clinical lung plan. This was improved with AAA10 calculated using a 1 mm grid. CONCLUSIONS: AAA10 improves the accuracy of dose calculations, and calculation grid of 1.0 mm is superior to using 2.5 mm, although calculation times increased by factor of 5. A suitable upper MU constraint should be assigned during optimization to avoid plans with high modulation. For plans with a relative high number of monitor units, calculations using 1 mm grid resolution are recommended. For planning target volume (PTV) which contains relatively large area of low density tissue, users should be aware of possible dose underestimation in the low density region and recalculation with AAA10 grid 1.0 mm is recommended.

Intra-fraction and Inter-fraction analysis of a dedicated immobilization device for intracranial radiation treatment.

BACKGROUND: Immobilization devices are crucial to minimize patient positioning uncertainties in radiotherapy (RT) treatments. Accurate inter and intra-fraction motions is particularly important for intracranial and stereotactic radiation treatment which require high precision in dose delivery. Recently, a new immobilization device has been developed specifically for the radiation treatment of intracranial malignancies. To date, no data are available on the use of this device in daily clinical practice. The aim of this study is to investigate the intra and inter-fraction variations, patient comfort and radiographer confidence of the immobilization system from two distinct institutions: HagaZiekenhuis, Den Haag, Netherlands and IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy. MATERIAL AND METHOD: Sixteen patients (10 diagnosed with brain metastases and 6 with primary central nervous systemic tumor) from IRCCS Ospedale Sacro Cuore Don Calabria and 17 patients (all diagnosed with brain metastases tumor) from HagaZiekenhuis were included in this study. The median target volume was 436 cc (range 3.2-1628 cc) and 4.58 cc (range 0.4-27.19 cc) for IRCCS and Haga, respectively. For patients treated in IRCCS Sacro Cuore Don Calabria, the median dose prescription was 30 Gy (range 27-60 Gy) and median number of fractions 10 (range 3-30). In Haga the median dose prescription was 21 Gy (range 8-21 Gy) and the median number of fraction was 1 (range 1-3). The immobilization device was assembled during CT simulation. A short interview to the patient regarding the device's comfort level was conducted at the end of the simulation procedure. Additionally, simulation setup time and radiographer (RTT) procedures (i.e. mask preparation) were evaluated. Prior to radiation treatment delivery, an automatic rigid match on the cranial bones between cone beam computed tomography (CBCT) and planning-CT was performed. A couch shift was performed subsequently. An extra post-treatment CBCT was acquire after the treatment delivery. This post-treatment CBCT was matched with pre-treatment CBCT to identify any possible intra-fraction motion. All online matches were validated by experienced radiation oncologist or RTT. A total of 126 CBCT's were analyzed offline by radiation oncologist/medical physicist. The data of the pre-treatment CBCT match was used to quantify inter-fraction motion. The post-treatment CBCT was matched with pre-treatment CBCT to identify any possible intra-fraction motion. RESULTS: During the molding of the mask, all patients responded positive to the comfort. Median time required by the RTTs to assemble the immobilization system was 9 min (range 6-12 min). In terms of comfort, all patients reported a good-to high level of satisfaction. The RTTs also respond positively towards the use of the locking mechanism and clips. Results of positioning uncertainties were comparable between the two institutes. The mean inter-fraction motion for all translational and rotational directions were < 2 mm (SD < 4 mm) and < 0.5°(SD < 1.5°), respectively, while the mean intra-fraction motions were < 0.4 mm (SD < 0.6 mm) and 0.3° (SD < 0.5°). CONCLUSIONS: This study demonstrates the efficacy and feasibility of the immobilization device in the intracranial radiation treatment. Both patient comfort and preparation time by RTTs are considered adequate. In combination with online daily imaging procedure, this device can achieve submillimeter accuracy required for intracranial and stereotactic treatments.

Dosimetric impact of the interplay effect during stereotactic lung radiation therapy delivery using flattening filter-free beams and volumetric modulated arc therapy.

PURPOSE: We investigated the dosimetric impact of the interplay effect during RapidArc stereotactic body radiation therapy for lung tumors using flattening filter-free (FFF) beams with different dose rates. METHODS AND MATERIALS: Seven tumors with motion ≤20 mm, treated with 10-MV FFF RapidArc, were analyzed. A programmable phantom with sinusoidal longitudinal motion (30-mm diameter "tumor" insert; period = 5 s; individualized amplitude from planning 4-dimensional computed tomography) was used for dynamic dose measurements. Measurements were made with GafChromic EBT III films. Plans delivered the prescribed dose to 95% of the planning target volume, created by a 5-mm expansion of the internal target volume. They comprised 2 arcs and maximum dose rates of 400 and 2400 MU/min. For 2400 MU/min plans, measurements were repeated at 3 different initial breathing phases to model interplay over 2 to 3 fractions. For 3 cases, 2 extra plans were created using 1 full rotational arc (with contralateral lung avoidance sector) and 1 partial arc of 224° to 244°. Dynamic and convolved static measurements were compared by use of gamma analysis of 3% dose difference and 1 mm distance-to-agreement. RESULTS: For 2-arc 2400 MU/min plans, maximum dose deviation of 9.4% was found in a single arc; 7.4% for 2 arcs (single fraction) and <5% and 3% when measurements made at 2 and 3 different initial breathing phases were combined, simulating 2 or 3 fractions. For all 7 cases, >99% of the area within the region of interest passed the gamma criteria when all 3 measurements with different initial phases were combined. Single-fraction single-arc plans showed higher dose deviations, which diminished when dose distributions were summed over 2 fractions. All 400 MU/min plans showed good agreement in a single fraction measurement. CONCLUSION: Under phantom conditions, single-arc and single-fraction 2400 MU/min FFF RapidArc lung stereotactic body radiation therapy is susceptible to interplay. Two arcs and ≥2 fractions reduced the effect to a level that appeared unlikely to be clinically significant.

Dosimetric impact of intrafraction motion during RapidArc stereotactic vertebral radiation therapy using flattened and flattening filter-free beams.

PURPOSE: To study the dosimetric impact of relatively short-duration intrafraction shifts during a single fraction of RapidArc delivery for vertebral stereotactic body radiation therapy (SBRT) using flattened (FF) and flattening filter-free (FFF) beams. METHODS AND MATERIALS: The RapidArc plans, each with 2 to 3 arcs, were generated for 9 patients using 6-MV FF and 10-MV FFF beams with maximum dose rates of 1000 and 2400 MU/min, respectively. A total of 1272 plans were created to estimate the dosimetric consequences in target and spinal cord volumes caused by intrafraction shifts during one of the arcs. Shifts of 1, 2, and 3 mm for periods of 5, 10, and 30 seconds, and 5 mm for 5 and 10 seconds, were modelled during a part of the arc associated with high doses and steep dose gradients. RESULTS: For FFF plans, shifts of 2 mm over 10 seconds and 30 seconds could increase spinal cord Dmax by up to 6.5% and 13%, respectively. Dosimetric deviations in FFF plans were approximately 2-fold greater than in FF plans. Reduction in target coverage was <1% for 83% and 96% of the FFF and FF plans, respectively. CONCLUSION: Even short-duration intrafraction shifts can cause significant dosimetric deviations during vertebral SBRT delivery, especially when using very high dose rate FFF beams and when the shift occurs in that part of the arc delivering high doses and steep gradients. The impact is greatest on the spinal cord and its planning-at-risk volume. Accurate and stable patient positioning is therefore required for vertebral SBRT.

Fast arc delivery for stereotactic body radiotherapy of vertebral and lung tumors.

PURPOSE: Flattening filter-free (FFF) beams with higher dose rates and faster delivery are now clinically available. The purpose of this planning study was to compare optimized non-FFF and FFF RapidArc plans for stereotactic body radiotherapy (SBRT) and to validate the accuracy of fast arc delivery. METHODS AND MATERIAL: Ten patients with peripheral lung tumors and 10 with vertebral metastases were planned using RapidArc with a flattened 6-MV photon beam and a 10-MV FFF beam for fraction doses of 7.5-18 Gy. Dosimetry of the target and organs at risk (OAR), number of monitor units (MU), and beam delivery times were assessed. GafChromic EBT2 film measurements of FFF plans were performed to compare calculated and delivered dose distributions. RESULTS: No major dosimetric differences were seen between the two delivery techniques. For lung SBRT plans, conformity indices and OAR doses were similar, although the average MU required were higher with FFF plans. For vertebral SBRT, FFF plans provided comparable PTV coverage, with no significant differences in OAR doses. Average beam delivery times were reduced by a factor of up to 2.5, with all FFF fractions deliverable within 4 min. Measured FFF plans showed high agreement with calculated plans, with more than 99% of the area within the region of interest fulfilling the acceptance criterion. CONCLUSION: The higher dose rate of FFF RapidArc reduces delivery times significantly, without compromising plan quality or accuracy of dose delivery.

Stereotactic radiotherapy for peripheral lung tumors: a comparison of volumetric modulated arc therapy with 3 other delivery techniques.

PURPOSE: Volumetric modulated arc therapy (RapidArc) allows for fast delivery of stereotactic body radiotherapy (SBRT) delivery in stage I lung tumors. We compared dose distributions and delivery times between RapidArc and common delivery techniques in small tumors. METHODS: In 18 patients who completed RapidArc SBRT for tumors measuring <70 cm(3), new treatment plans were generated using non-coplanar 3D conformal fields (conf-SBRT) and dynamic conformal arc radiotherapy (DCA). For 9 patients with tumors adjacent to the chest wall, co-planar intensity-modulated radiotherapy (IMRT) plans were also generated. PTV dose coverage, organs at risk (OAR) doses and treatment delivery times were assessed. RESULTS: RapidArc plans achieved a superior conformity index (CI) and lower V(45 Gy) to chest wall (p<0.05) compared to all other techniques. RapidArc led to a small increase in V(5 Gy) to contralateral lung compared to conf-SBRT (4.4±4% versus 1.2±1.8%, p=0.011). For other OAR, RapidArc and conf-SBRT plans were comparable, and both were superior to DCA plans. Delivery of a 7.5 Gy-fraction required 3.9 min (RapidArc), 11.6 min (conf-SBRT), and 12 min (IMRT). CONCLUSIONS: In stage I lung tumors measuring <70 cm(3), RapidArc plans achieved both the highest dose conformity and shortest delivery times.

Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): planning considerations and early toxicity.

PURPOSE: To study the dosimetric predictors of early clinical toxicity following SBRT in patients with lung tumors and planning target volumes (PTV) exceeding 80 cm(3). METHODS: Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc™) were assessed. All were either unfit or refused to undergo surgery or chemoradiotherapy. PTV planning objectives were as used in the ROSEL study protocol. Clinical toxicity was scored using Common Toxicity Criteria AE4.0. Lung volumes receiving 5, 10, 15, and 20 Gy (V(5), V(10), V(15) and V(20)) and mean lung dose were assessed and correlated to symptomatic radiation pneumonitis (RP). RESULTS: Median age, age-adjusted Charlson-comorbidity score and PTV size were 74, 7.5 and 137 cm(3), respectively. At a median follow-up of 12.8 months, 8 deaths were recorded: 5 arising from comorbidity, 2 were potentially treatment-related and 1 had local recurrence. RP was reported in 5 patients (grade 2 in 3 and grade 3 in 2). All RP occurred in plans without a high priority optimization objective on contralateral lung. Acute RP was best predicted by contralateral lung V(5) (p<0.0001). CONCLUSION: After SBRT using RapidArc in lung tumors >80 cm(3), the contralateral lung V(5) best predicts RP. Limiting contralateral lung V(5) to <26% may reduce acute toxicity.