Radiosurgery For Multiple Brain Metastases Research Articles

Stereotactic Radiosurgery of Multiple Brain Metastases: A Review of Treatment Techniques.

The advancement of systemic targeted treatments has led to improvements in the management of metastatic disease, particularly in terms of survival outcomes. However, brain metastases remain less responsive to systemic therapies, underscoring the significance of local interventions for comprehensive disease control. Over the past years, the threshold for treating brain metastases through stereotactic radiosurgery has risen. Yet, as the number of treated metastases increases, treatment complexity and duration also escalate. This trend has made multi-isocenter radiosurgery treatments, such as those with the Gamma Knife, challenging to plan and lengthy for patients. In contrast, single-isocenter approaches employing linear accelerators offer an efficient and expeditious treatment option. This review delves into the literature, comparing different linear-accelerator-based techniques with each other and in relation to dedicated systems, focusing on dosimetric considerations and feasibility.

Multiple Brain Metastases Radiosurgery with CyberKnife Device: Dosimetric Comparison between Fixed/Iris and Multileaf Collimator Plans.

In our institution, stereotactic radiosurgery of multiple brain metastases is performed with the CyberKnife® (CK) device, using fixed/Iris collimators. In this study, nineteen fixed/Iris plans were recalculated with the multileaf collimator (MLC), to assess if it is possible to produce plans with comparable dosimetric overall quality. For consistent comparisons, MLC plans were re-optimized and re-normalized in order to achieve the same minimum dose for the total planning target volume (PTVtot). Conformation number (CN), homogeneity index (HI) and dose gradient index (DGI) metrics were evaluated. The dose to the brain was evaluated as the volume receiving 12 Gy (V12) and as the integral dose (ID). The normal tissue complication probability (NTCP) for brain radionecrosis was calculated as a function of V12. The reoptimized plans were reviewed by the radiation oncologist and were found clinically acceptable according to the The American Association of Physicists in Medicine (AAPM) Task Group-101 protocol. However, fixed/Iris plans provided significantly higher CN (+8.6%), HI (+2.2%), and DGI (+44.0%) values, and significantly lower ID values (-35.9%). For PTVtot less than the median value of 2.58cc, fixed/Iris plans provided significantly lower NTCP values. On the other side, MLC plans provided significantly lower treatment times (-18.4%), number of monitor units (-33.3%), beams (-46.0%) and nodes (-21.3%). CK-MLC plans for the stereotactic treatment of brain multi metastases could provide an important advantage in terms of treatment duration. However, to contain the increased risk for brain radionecrosis, it could be useful to calculate MLC plans only for patients with large PTVtot.

Dosimetric Impact of Lesion Number, Size, and Volume on Mean Brain Dose with Stereotactic Radiosurgery for Multiple Brain Metastases.

We evaluated the effect of lesion number and volume for brain metastasis treated with SRS using GammaKnife® ICON™ (GK) and CyberKnife® M6™ (CK). Four sets of lesion sizes (<5 mm, 5-10 mm, >10-15 mm, and >15 mm) were contoured and prescribed a dose of 20 Gy/1 fraction. The number of lesions was increased until a threshold mean brain dose of 8 Gy was reached; then individually optimized to achieve maximum conformity. Across GK plans, mean brain dose was linearly proportional to the number of lesions and total GTV for all sizes. The numbers of lesions needed to reach this threshold for GK were 177, 57, 29, and 10 for each size group, respectively; corresponding total GTVs were 3.62 cc, 20.37 cc, 30.25 cc, and 57.96 cc, respectively. For CK, the threshold numbers of lesions were 135, 35, 18, and 8, with corresponding total GTVs of 2.32 cc, 12.09 cc, 18.24 cc, and 41.52 cc respectively. Mean brain dose increased linearly with number of lesions and total GTV while V8 Gy, V10 Gy, and V12 Gy showed quadratic correlations to the number of lesions and total GTV. Modern dedicated intracranial SRS systems allow for treatment of numerous brain metastases especially for ≤10 mm; clinical evidence to support this practice is critical to expansion in the clinic.

Multicenter analysis of stereotactic radiosurgery for multiple brain metastases from EGFR and ALK driven non-small cell lung cancer

IntroductionPatients with brain metastases (BrMs) arising from EGFR and ALK driven non-small cell lung cancer (NSCLC) have favorable prognoses and evolving treatment options. We evaluated multicenter outcomes for stereotactic radiosurgery (SRS) to multiple (≥4) BrMs, where randomized data remain limited. MethodsData were collected retrospectively from 5 academic centers on EGFR and ALK NSCLC who received SRS to ≥4 BrMs with their first SRS treatment between 2008 and 2018. Analyzed endpoints included overall survival (OS), freedom from CNS progression (FFCNSP), and freedom from whole-brain radiotherapy (FFWBRT). ResultsEighty-nine patients (50 EGFR, 39 ALK) received a total of 159 SRS treatments to 1,080 BrMs, with a median follow up of 51.3 months. The median number of BrMs treated with SRS treatment-1 was 6 (range 4–26) and median for all treatments was 9 (range 4–47). Sixteen patients (18 %) had received WBRT prior to SRS treatment-1. The median OS was 24.2, 21.2, and 33.2 months for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, only receipt of a next-generation tyrosine kinase inhibitor was associated with OS (HR 0.40, p = 0.005). No differences in OS were observed based on number of BrMs treated. The median FFCNSP was 9.4, 11.6, and 7.5 months, for all patients, EGFR, and ALK subsets, respectively. After multivariable adjustment, the number of BrMs (continuous) treated during treatment-1 was the only negative prognostic factor associated with FFCNSP (HR 1.071, p = 0.045). The 5-year FFWBRT was 73.6 %. ConclusionsThis multicenter analysis over a >10-year period demonstrated favorable OS, FFCNSP, and FFWBRT, in patients with EGFR and ALK driven NSCLC receiving SRS to ≥4 BrMs. These data support SRS as an option in the upfront and salvage setting for higher burden CNS disease in this population.

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series.

BackgroundPatients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions.Materials and methodsThis study is a retrospective analysis of SRS for brain metastasis using VMAT. The primary endpoints were local disease-free survival (LDFS) and overall survival (OS). The secondary outcomes were intracranial disease-free survival (IDFS) and meningeal disease-free survival (MDFS).ResultsThe average number of treated lesions was 5.79 (range: 2–20) per treatment in a total of 113 patients. The mean prescribed dose was 18 Gy (range: 12–24 Gy). The median LDFS was 46 months. The LDFS in 6, 12, and 24 months was for 86%, 79%, and 63%, respectively. Moreover, brain progression occurred in 50 patients. The median overall survival was 47 months. The OS in 75%, 69%, and 61% patients was 6, 12, and 24 months, respectively. IDFS was 6 and 24 months in 35% and 14% patients, respectively. The mean MDFS was 62 months; it was 6 and 24 months for 87% and 83% of patients. Acute severe toxicity was relatively rare. During follow-up, the rates of radionecrosis and neurocognitive impairment were low (10%).ConclusionThe use of VMAT–SRS for multiple BM was feasible, effective, and associated with low treatment-related toxicity rates. Thus, treatment with VMAT is a safe technique to plan to achieve local control without toxicity.

Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems

PurposeAutomated treatment planning systems are available for linear accelerator (linac)-based single-isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) of brain metastases. In this study, we compared plan quality between Brainlab Elements Multiple Brain Metastases (Elements MBM) software which utilizes dynamic conformal arc therapy (DCAT) and Varian HyperArc (HA) software using a volumetric modulated arc therapy (VMAT) technique.Patients and methodsBetween July 2018 and April 2021, 36 consecutive patients ≥ 18 years old with 367 metastases who received SIMT SRS at UPMC Hillman Cancer San Pietro Hospital, Rome, were retrospectively evaluated. SRS plans were created using the commercial software Elements MBM SRS (Version 1.5 and 2.0). Median cumulative gross tumor volume (GTV) and planning tumor volume (PTV) were 1.33 cm3 and 3.42 cm3, respectively. All patients were replanned using HA automated software. Extracted dosimetric parameters included mean dose (Dmean) to the healthy brain, volumes of the healthy brain receiving more than 5, 8,10, and 12 Gy (V5Gy, V8Gy, V10Gy and V12Gy), and doses to hippocampi.ResultsBoth techniques resulted in high-quality treatment plans, although Element MBM DCAT plans performed significantly better than HA VMAT plans, especially in cases of more than 10 lesions). Median V12Gy was 13.6 (range, 1.87–45.9) cm3 for DCAT plans and 18.5 (2.2–62,3) cm3 for VMAT plans (p < 0.0001), respectively. Similarly, V10Gy, V8Gy, V5Gy (p < 0.0001) and median dose to the normal brain (p = 0.0001) were favorable for DCAT plans.ConclusionsBoth Elements MBM and HA systems were able to generate high-quality plans in patients with up to 25 brain metastases. DCAT plans performed better in terms of normal brain sparing, especially in patients with more than ten lesions and limited total tumor volume.

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series

Background: Patients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions . Materials and methods: This study is a retrospective analysis of SRS for brain metastasis using VMAT. The primary endpoints were local disease-free survival (LDFS) and overall survival (OS). The secondary outcomes were intracranial disease-free survival (IDFS) and meningeal disease-free survival (MDFS). Results: The average number of treated lesions was 5.79 (range: 2–20) per treatment in a total of 113 patients. The mean prescribed dose was 18 Gy (range: 12–24 Gy). The median LDFS was 46 months. The LDFS in 6, 12, and 24 months was for 86%, 79%, and 63%, respectively. Moreover, brain progression occurred in 50 patients. The median overall survival was 47 months. The OS in 75%, 69%, and 61% patients was 6, 12, and 24 months, respectively. IDFS was 6 and 24 months in 35% and 14% patients, respectively. The mean MDFS was 62 months; it was 6 and 24 months for 87% and 83% of patients. Acute severe toxicity was relatively rare. During follow-up, the rates of radionecrosis and neurocognitive impairment were low (10%). Conclusion: The use of VMAT–SRS for multiple BM was feasible, effective, and associated with low treatment-related toxicity rates. Thus, treatment with VMAT is a safe technique to plan to achieve local control without toxicity.

Single-isocenter stereotactic radiosurgery for multiple brain metastases: Impact of patient misalignments on target coverage in non-coplanar treatments

Frameless single-isocenter non-coplanar stereotactic radiosurgery (SRS) for patients with multiple brain metastases is a treatment at high geometrical complexity. The goal of this study is to analyze the dosimetric impact of non-coplanar image guidance with stereoscopic X-ray imaging. Such an analysis is meant to provide insights on the adequacy of safety margins, and to evaluate the benefit of imaging at non-coplanar configurations.The ExacTrac® (ET) system (Brainlab AG, Munich, Germany) was used for stereoscopic X-ray imaging in frameless single-isocenter non-coplanar SRS for multiple brain metastases. Sub-millimeter precision was found for the ET-based pre-treatment setup, whereas a degradation was noted for non-coplanar treatment angles. Misalignments without intra-fractional positioning corrections were reconstructed in 6 degrees of freedom (DoF) to resemble the situation without non-coplanar image guidance.Dose recalculation in 20 SRS patients with applied positioning corrections did not reveal any significant differences in D98% for 75 planning target volumes (PTVs) and gross tumor volumes (GTVs). For recalculation without applied positioning corrections, significant differences (p<0.05) were reported in D98% for both PTVs and GTVs, with stronger effects for small PTV volumes. A worst-case analysis at increasing translational and rotational misalignment revealed that dosimetric changes are a complex function of the combination thereof.This study highlighted the important role of positioning correction with ET at non-coplanar configurations in frameless single-isocenter non-coplanar SRS for patients with multiple brain metastases. Uncorrected patient misalignments at non-coplanar couch angles were linked to a significant loss of PTV coverage, with effects varying according to the combination of single DoF and PTV geometrical properties.

P122 - Stereotactic radiosurgery for multiple brain metastases: dosimetric performance of two planning techniques and two setup approaches

P122 - Stereotactic radiosurgery for multiple brain metastases: dosimetric performance of two planning techniques and two setup approaches

P72 - Stereotactic radiosurgery for multiple brain metastases: does MR/CT co-registration improve target localization accuracy compared to the MR-only approach?

P72 - Stereotactic radiosurgery for multiple brain metastases: does MR/CT co-registration improve target localization accuracy compared to the MR-only approach?

Simultaneous radiosurgery for multiple brain metastases: technical overview of the UCLA experience

Purpose/objective(s)To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins.Materials/methodsEight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0 mm, 1 mm and 2 mm margins were created, including plans with variable margins, where targets more than 6 cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements.ResultsThe V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from 0 to 1 mm and tripled when change from 0 to 2 mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6 cm away from the isocenter. With 0.5 mm re-positioning threshold, 57.4% of the time the patients are repositioned. Reducing the threshold to 0.25 mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. The 90th percentile of translational movements in all directions is 0.7 mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2 mm and 0.2 degrees, respectively.ConclusionsBased on the data presented, we have switched our modus operandi from 2 to 1 mm PTV margins, with an eventual goal of using 0.5 and 1.0 mm variable margins when an automated margin assignment method becomes available. The 0.5 mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.

Practical Considerations for Single Isocenter LINAC Radiosurgery of Multiple Brain Metastases

The purpose of this paper is to summarize treatment guidelines for the performance of single isocenter LINAC radiosurgery of multiple brain metastases developed and used by 3 experienced centers. This article is not meant to provide consensus guidelines. Rather, this is a practical, “how we do it” reference without substantial discussion. To serve as a treatment reference, the great majority of the information is presented in topic-specific tables.

Predicting the effect of indirect cell kill in the treatment of multiple brain metastases via single-isocenter/multitarget volumetric modulated arc therapy stereotactic radiosurgery.

PurposeDue to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m‐bm) when using single‐isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT‐VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions.Material and MethodsNine complex patients with 61 total tumors (2‐16 tumors/patient) were planned using SIMT‐VMAT with geometry similar to HyperArc with a 10MV‐FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02–11.5) and 1.9 cc (0.11–18.8) with an average distance to isocenter of 5.4 cm (2.2–8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m‐bm via SIMT‐VMAT.ResultsPatient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed.ConclusionsRadiosurgery of m‐bm using SIMT‐VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation‐induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m‐bm using a SIMT‐VMAT plan.

Dynamic conformal arcs-based single-isocenter VMAT planning technique for radiosurgery of multiple brain metastases

Multiple small beamlets in the delivery of highly modulated single-isocenter HyperArc VMAT plan can lead to dose delivery errors associated with small-field dosimetry, which can be a major concern for stereotactic radiosurgery for multiple brain lesions. Herein, we describe and compare a clinically valuable dynamic conformal arc (DCA)-based VMAT (DCA-VMAT) approach for stereotactic radiosurgery of multiple brain lesions using flattening filter free beams to minimize this effect. Original single-isocenter HyperArc style VMAT and DCA-VMAT plans were created on 7 patients with 2 to 8 brain lesions (total 35 lesions) for 10 MV- flattening filter free beam. 20 Gy was prescribed to each lesion. For identical planning criteria, DCA-VMAT utilizes user-controlled field aperture shaper before VMAT optimization. Plans were evaluated for conformity and target coverage, low- and intermediate dose spillages to brain volume that received more than 30% (V30%) and 50% (V50%) of prescription dose. Additionally, mean brain dose, V8, V12 and maximal dose to adjacent organs-at-risk (OAR) including hippocampi were reported. Total monitor units, beam modulation factor, treatment delivery efficiency, and accuracy were recorded. Comparing with original VMAT, DCA-VMAT plans provided similar tumor dose, target coverage and conformity, yet tighter radio-surgical dose distribution with lower dose to normal brain V30% (p = 0.009), V50% (p = 0.05) and other OAR including lower dose to hippocampi. Lower total number of monitor units and smaller beam modulation factor reduced beam on time by 2.82 min (p < 0.001), on average (maximum up to 3.8 min). Beam delivery accuracy was improved by 8%, on average (p < 0.001) and maximum up to 13% in some cases for DCA-VMAT plans. This novel DCA-VMAT approach provided excellent plan quality, reduced dose to normal brain, and other OAR while significantly reducing beam-on time for radiosurgery of multiple brain lesions–improving patient compliance and clinic workflow. It also provided less MLC modulation through the targets–potentially minimizing small field dosimetry errors as demonstrated by quality assurance results. Incorporating DCA-based VMAT optimization in HyperArc module for radiosurgery of multiple brain lesions merits future investigation.

Single-Isocenter Volumetric Modulated Arc Therapy (VMAT) Radiosurgery for Multiple Brain Metastases: Potential Loss of Target(s) Coverage Due to Isocenter Misalignment

PurposeA single-isocenter volumetric modulated arc therapy (VMAT) treatment to multiple brain metastatic patients is an efficient stereotactic radiosurgery (SRS) option. However, the current clinical practice of single-isocenter SRS does not account for patient setup uncertainty, which degrades treatment delivery accuracy. This study quantifies the loss of target coverage and potential collateral dose to normal tissue due to clinically observable isocenter misalignment.Methods and materialsNine patients with 61 total tumors (2-16 tumors/patient) who underwent Gamma Knife® SRS were replanned in Eclipse™ using 10 megavoltages (MV) flattening-filter-free (FFF) bream (2400 MU/min), using a single-isocenter VMAT plan, similar to HyperArc™ VMAT plan. Isocenter was placed in the geometric center of the tumors. The prescription was 20 Gy to each tumor. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02-11.5 cc) and 1.9 cc (0.11-18.8 cc), respectively, derived from MRI images. The average isocenter to tumor distance was 5.5 cm (1.6-10.1 cm). Six-degrees of freedom (6DoF) random and systematic residual set up errors within [±2 mm, ±2o] were generated using an in-house script in Eclipse based on our pre-treatment daily cone-beam CT imaging shifts and recomputed for the simulated VMAT plan. Relative loss of target coverage as a function of tumor size and distance to isocenter were evaluated as well as collateral dose to organs-at risk (OAR).ResultsThe average beam-on time was less than six minutes. However, loss of target coverage for clinically observable setup errors were, on average, 7.9% (up to 73.1%) for the GTV (p < 0.001) and 21.5% for the PTV (up to 93.7%; p < 0.001). The correlation was found for both random and systematic residual setup errors with tumor sizes; there was a greater loss of target coverage for small tumors. Due to isocenter misalignment, OAR doses fluctuated and potentially receive higher doses than the original plan.ConclusionA single-isocenter VMAT SRS treatment (similar to HyperArc™ VMAT) to multiple brain metastases was fast with < 6 min of beam-on time. However, due to small residual set up errors, single-isocenter VMAT, in its current use, is not an accurate SRS treatment modality for multiple brain metastases. Loss of target coverage was statistically significant, especially for smaller lesions, and may not be clinically acceptable if left uncorrected. Further investigation of correction strategies is underway.

Effect of setup error in the single-isocenter technique on stereotactic radiosurgery for multiple brain metastases.

In conventional stereotactic radiosurgery (SRS), treatment of multiple brain metastases using multiple isocenters is time‐consuming resulting in long dose delivery times for patients. A single‐isocenter technique has been developed which enables the simultaneous irradiation of multiple targets at one isocenter. This technique requires accurate positioning of the patient to ensure optimal dose coverage. We evaluated the effect of six degrees of freedom (6DoF) setup errors in patient setups on SRS dose distributions for multiple brain metastases using a single‐isocenter technique. We used simulated spherical gross tumor volumes (GTVs) with diameters ranging from 1.0 to 3.0 cm. The distance from the isocenter to the target's center was varied from 0 to 15 cm. We created dose distributions so that each target was entirely covered by 100% of the prescribed dose. The target's position vectors were rotated from 0°–2.0° and translated from 0–1.0 mm with respect to the three axes in space. The reduction in dose coverage for the targets for each setup error was calculated and compared with zero setup error. The calculated margins for the GTV necessary to satisfy the tolerance values for loss of GTV coverage of 3% to 10% were defined as coverage‐based margins. In addition, the maximum isocenter to target distance for different 6DoF setup errors was calculated to satisfy the tolerance values. The dose coverage reduction and coverage‐based margins increased as the target diameter decreased, and the distance and 6DoF setup error increased. An increase in setup error when a single‐isocenter technique is used may increase the risk of missing the tumor; this risk increases with increasing distance from the isocenter and decreasing tumor size.

Radiosurgery for Multiple Brain Metastases using Volumetric Modulated Arc Therapy: Clinical Outcomes and Toxicity from a Single-Institutional Series

To analyze clinical outcomes and toxicities in patients with multiple brain metastases undergoing SRS using VMAT technique. Retrospective analyzes of SRS for brain metastasis using VMAT in a single institution from 2012 to 2019. GTV was defined on enhanced lesion at Magnetic Resonance Image overlapped to planning CT, expanded for PTV from 1 to 2mm. All the patients used thermoplastic mask for frameless image-guided radiosurgery, using cone beam CT with 6D positioning and surface-guided set-up were applied in some cases. The collected data were demographic and histopathologic features, local control, brain and systemic control from patient charts. Local control (LC) was analyzed from SRS treatment to local progression (any failure inside the brain). Other treatments, and toxicities (acute and late) were also evaluated. There were 75 patients with totalizing 418 lesions. The average number of treated lesions was 5.6 (range 2 – 19). Patients with 2 lesions were the most prevalent (18.6%). The primary sites were lung (45%), breast (29.3%), melanoma (8%), colon (8%), and others (8.7%). Most patients already had received systemic therapy before SRS (chemotherapy in 52, targeted therapy or immunotherapy in 36). Only 3 patients underwent hypofractionated treatments (2 in 3 fractions and 1 in 5 fractions). The median single-shot dose was 18 (12 – 24) Gy. The median follow-up was 7.3 months (1 – 40). The 1-, and 2-year local recurrence free survival were respectively 65% and 47.3%. The mean time to local recurrence was 7.1 months. The 1-year brain recurrence free survival and overall survival were respectively 28% and 36%. There were 11 local recurrences and 30 non-local tumors, having 7 of them leptomeningeal spread. Grade 1 or 2 acute toxicities were present in 7.1% (headache, seizures, perilesional edema), whereas late toxicities including radionecrosis and neurocognitive impairment were seen respectively in 3.38%, and in 3.44%. The use of VMAT – SRS for multiple brain metastases was feasible, effective, and with low treatment-related toxicity rates. We might infer that the simultaneous treatment provided by VMAT is an advantageous way to yield local control without compromise toxicity.

Executive summary from American Radium Society's appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases.

The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines. The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness. The panel agreed that SRS alone is usually appropriate for those with good performance status and 2-10 asymptomatic BM, and usually not appropriate for >20 BM. For 11-15 and 16-20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2-4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options. For patients with 2-10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.

Single-Isocenter Volumetric Modulated Arc Therapy vs. CyberKnife M6 for the Stereotactic Radiosurgery of Multiple Brain Metastases.

Introduction: Stereotactic radiosurgery (SRS) is becoming more frequently used for patients with multiple brain metastases (BMs). Single-isocenter volumetric modulated arc therapy (SI-VMAT) is an emerging alternative to dedicated systems such as CyberKnife (CK). We present a dosimetric comparison between CyberKnife M6 and SI-VMAT, planned at RayStation V8B, for the simultaneous SRS of five or more BM.Patients and Methods: Twenty treatment plans of CK-based single-session SRS to ≥5 brain metastases were replanned using SI-VMAT for delivery at an Elekta VersaHD linear accelerator. Prescription dose was 20 or 18 Gy, conformally enclosing at least 98% of the total planning target volume (PTV), with PTV margin-width adapted to the respective SRS technique. Comparatively analyzed quality metrics included dose distribution to the healthy brain (HB), including different isodose volumes, conformity, and gradient indices. Estimated treatment time was also compared.Results: Median HB isodose volumes for 3, 5, 8, 10, and 12 Gy were consistently smaller for CK-SRS compared to SI-VMAT (p < 0.001). Dose falloff outside the target volume, as expressed by the gradient indices GI_high and GI_low, was consistently steeper for CK-SRS compared to SI-VMAT (p < 0.001). CK-SRS achieved a median GI_high of 3.1 [interquartile range (IQR), 2.9–1.3] vs. 5.0 (IQR 4.3–5.5) for SI-VMAT (p < 0.001). For GI_low, the results were 3.0 (IQR, 2.9–3.1) for CK-SRS vs. 5.6 (IQR, 4.3–5.5) for SI-VMAT (p < 0.001). The median conformity index (CI) was 1.2 (IQR, 1.1–1.2) for CK-SRS vs. 1.5 (IQR, 1.4–1.7) for SI-VMAT (p < 0.001). Estimated treatment time was shorter for SI-VMAT, yielding a median of 13.7 min (IQR, 13.5–14.0) compared to 130 min (IQR, 114.5–154.5) for CK-SRS (p < 0.001).Conclusion: SI-VMAT offers enhanced treatment efficiency in cases with multiple BM, as compared to CyberKnife, but requires compromise regarding conformity and integral dose to the healthy brain. Additionally, delivery at a conventional linear accelerator (linac) may require a larger PTV margin to account for delivery and setup errors. Further evaluations are warranted to determine whether the detected dosimetric differences are clinically relevant. SI-VMAT could be a reasonable alternative to a dedicated radiosurgery system for selected patients with multiple BM.

Interinstitutional Plan Quality Assessment of 2 Linac-Based, Single-Isocenter, Multiple Metastasis Radiosurgery Techniques

PurposeInterest and application of stereotactic radiosurgery for multiple brain metastases continue to increase. Various planning systems are available for linear accelerator (linac)–based single-isocenter multiple metastasis radiosurgery. Two of the most advanced systems are BrainLAB Multiple Metastases Elements (MME), a dynamic conformal arc (DCA) approach, and Varian RapidArc (RA), a volumetric modulated arc therapy (VMAT) approach. In this work, we systematically compared plan quality between the 2 techniques. Methods and MaterialsThirty patients with 4 to 10 metastases (217 total; median 7.5; Vmin = 0.014 cm3; Vmax = 17.73 cm3) were planned with both Varian RA and MME at 2 different institutions with extensive experience in each respective technique. All plans had a single isocenter and used Varian linac equipped with high-definition multileaf collimator. RA plans used 2 to 4 noncoplanar VMAT arcs with 10 MV flattening filter-free beam. MME plans used 4 to 9 noncoplanar DCAs and 6 MV flattening filter-free beam, (minimum planning target volume [PTVmin] = 0.49 cm3; PTVmax = 27.32 cm3; PTVmedian = 7.05 cm3). Prescriptions were 14 to 24 Gy in a single fraction. Target coverage goal was 99% of volume receiving prescription dose (D99% ≥ 100%). Plans were evaluated by Radiation Therapy Oncology Group/Paddick conformity index (CI) score, 12 Gy volume (V12Gy), V8Gy, V5Gy, mean brain dose (Dmean), and beam-on time. ResultsConformity was favorable among RA plans (median: MME CIRTOG = 1.38; RA CIRTOG = 1.21; P < .0001). V12Gy and V8Gy were lower for RA plans (median: MME V12 = 23.7 cm3; RA V12 = 19.2 cm3; P = .0001; median: MME V8Gy = 53.6 cm3; RA V8Gy = 44.1 cm3; P = .024). V5Gy was lower for MME plans (median: MME V5Gy = 141.4 cm3; RA V5Gy = 142.8 cm3; P = .009). Mean brain was lower for MME plans (median: MME Dmean = 2.57 Gy; RA Dmean = 2.76 Gy; P < .0001). ConclusionsFor linac-based multiple metastasis stereotactic radiosurgery, RapidArc VMAT facilitates favorable conformity and V12Gy/V8Gy volume compared with the MME DCA plan. MME planning facilitates reduced dose spill at levels ≤V5Gy.