Single-isocenter Volumetric Modulated Arc Therapy Research Articles

Predicting voxel-level dose distributions of single-isocenter volumetric modulated arc therapy treatment plan for multiple brain metastases.

Brain metastasis is a common, life-threatening neurological problem for patients with cancer. Single-isocenter volumetric modulated arc therapy (VMAT) has been popularly used due to its highly conformal dose and short treatment time. Accurate prediction of its dose distribution can provide a general standard for evaluating the quality of treatment plan. In this study, a deep learning model is applied to the dose prediction of a single-isocenter VMAT treatment plan for radiotherapy of multiple brain metastases. A U-net with residual networks (U-ResNet) is employed for the task of dose prediction. The deep learning model is first trained from a database consisting of hundreds of historical treatment plans. The 3D dose distribution is then predicted with the input of the CT image and contours of regions of interest (ROIs). A total of 150 single-isocenter VMAT plans for multiple brain metastases are used for training and testing. The model performance is evaluated based on mean absolute error (MAE) and mean absolute differences of multiple dosimetric indexes (DIs), including (D max and D mean) for OARs, (D 98, D 95, D 50, and D 2) for PTVs, homogeneity index, and conformity index. The similarity between the predicted and clinically approved plan dose distribution is also evaluated. For 20 tested patients, the largest and smallest MAEs are 3.3% ± 3.6% and 1.3% ± 1.5%, respectively. The mean MAE for the 20 tested patients is 2.2% ± 0.7%. The mean absolute differences of D 98, D 95, D 50, and D2 for PTV60, PTV52, PTV50, and PTV40 are less than 2.5%, 3.0%, 2.0%, and 3.0%, respectively. The prediction accuracy of OARs for D max and D mean is within 3.2% and 1.2%, respectively. The average DSC ranges from 0.86 to 1 for all tested patients. U-ResNet is viable to produce accurate dose distribution that is comparable to those of the clinically approved treatment plans. The predicted results can be used to improve current treatment planning design, plan quality, efficiency, etc.

Understanding the Effect of Prescription Isodose in Single-Fraction Stereotactic Radiosurgery on Plan Quality and Clinical Outcomes for Solid Brain Metastases.

There is wide variation in treatment planning strategy for central nervous system (CNS) stereotactic radiosurgery. We sought to understand what relationships exist between intratumor maximum dose and local control (LC) or CNS toxicity, and dosimetric effects of constraining hotspots on plan quality of multiple metastases volumetric modulated arc therapy radiosurgery plans. We captured brain metastases from 2015 to 2017 treated with single-isocenter volumetric modulated arc therapy radiosurgery. Included tumors received single-fraction stereotactic radiosurgery, had no previous surgery or radiation, and available follow-up imaging. Our criterion for local failure was 25% increase in tumor diameter on follow-up MRI or pathologic confirmation of tumor recurrence. We defined significant CNS toxicity as Radiation Therapy Oncology Group irreversible Grade 3 or higher. We performed univariate and multivariate analyses evaluating factors affecting LC. We examined 10 stereotactic radiosurgery plans with prescriptions of 18 Gy to all targets originally planned without constraints on the maximum dose within the tumor. We replanned each with a constraint of Dmax 120%. We compared V50%, mean brain dose, and Dmax between plans. Five hundred and thirty tumors in 116 patients were available for analysis. Median prescription dose was 18 Gy, and median prescription isodose line (IDL) was 73%. Kaplan-Meier estimate of 12-month LC only tumor volume (HR 1.43 [1.22-1.68] P < .001) was predictive of local failure on univariate analysis; prescription IDL and histology were not. In multivariate analysis, tumor volume impacted local failure (HR 1.43 [1.22-1.69] P < .001) but prescription IDL did not (HR 0.95 [0.86-1.05] P = .288). Only a single grade 3 and 2 grade 4 toxicities were observed; tumor volume was predictive of CNS toxicity (HR 1.58 [1.25-2.00]; P < .001), whereas prescription IDL was not (HR 1.01 [0.87-1.17] P = .940). The prescription isodose line had no impact on local tumor control or CNS toxicity. Penalizing radiosurgery hotspots resulted in worse radiosurgery plans with poorer gradient. Limiting maximum dose in gross tumor causes increased collateral exposure to surrounding tissue and should be avoided.

Overcoming Problems Caused by Offset Distance of Multiple Targets in Single-isocenter Volumetric Modulated Arc Therapy Planning for Stereotactic Radiosurgery.

The purpose of the study is to investigate the impact of large target offset distances on the dose distribution and gamma passing rate (GPR) in single-isocenter multiple-target stereotactic radiosurgery (SIMT SRS) using volumetric modulated arc therapy (VMAT) with a flattening filter-free (FFF) beam from a linear accelerator. Two targets with a diameter of 1 cm were offset by "±2, ±4, and ±6 cm from the isocenter in a verification phantom for head SRS (20 Gy/fr). The VMAT plans were created using collimator angles that ensured the two targets did not share a leaf pair from the multi-leaf collimator. To evaluate the low-dose spread intermediate dose spill (R50%), GPRs were measured with a criterion of 3%/2 mm using an electronic portal imaging device and evaluated using monitor unit (MU), modulation complexity score for VMAT (MCSv), and leaf travel (LT) parameters. For offsets of 2, 4, and 6 cm, the respective parameters were: R50%, 4.75 ± 0.36, 5.13 ± 0.36, and 5.11 ± 0.33; GPR, 95.01%, 93.82%, and 90.67%; MU, 5893 ± 186, 5825 ± 286, and 5810 ± 396; MCSv, 0.24, 0.16, and 0.13; and LT, 189.21 ± 36.04, 327.69 ± 67.01, and 430.39 ± 114.34 mm. There was a spread in the low-dose region from offsets of ≥4 cm and the GPR negatively correlated with LT (r = -0.762). There was minimal correlation between GPR and MU or MCSv. In SIMT SRS VMAT plans with an FFF beam from a linear accelerator, target offsets of <4 cm from the isocenter can minimize the volume of the low-dose region receiving 10 Gy or more. During treatment planning, it is important to choose gantry, couch, and collimator angles that minimize LT and thereby improve the GPR.

Using a fixed-jaw technique to achieve superior delivery accuracy and plan quality in single-isocenter multiple-target stereotactic radiosurgery for brain metastases

To quantify the influence of the minimum dynamic leaf gap (DLG) on delivery accuracy and plan quality and determine whether the fixed-jaw technique can be used to reduce the adverse effects of DLG in single-isocenter volumetric modulated arc therapy (VMAT) stereotactic radiosurgery (SRS) for multiple brain metastases (BMs). Twelve patients, each with two BMs, were enrolled in this study. For each patient, five simulated cases were generated by adjusting the intertarget distance (ITD; range, 1–5 cm). For each case, two single-isocenter VMAT SRS plans with and without the fixed-jaw technique were designed. For the plan without the fixed-jaw technique, the jaw positions were automatically set to cover two targets (AJ-VMAT). For the other plan, the jaw was fixed to cover one lesion when another lesion was irradiated (FJ-VMAT). Dosimetric parameters and delivery parameters of two plans were compared. FJ-VMAT plans achieved similar target conformity, lower dose spillages (V10%, V25%), and lower normal brain tissue (NBT) mean dose, and better gradient index than AJ-VMAT plans regardless of ITD but with more monitor units and longer beam-on time (P < 0.05). For ITD ≥2 cm, FJ-VMAT plans also yielded lower V50% and 12-Gy isodose volume for NBT compared to AJ-VMAT, and the reduction became more distinct as the ITD increased. In addition, FJ-VMAT generated a significantly higher gamma passing rate for each criterion (P < 0.05), especially for larger ITDs (≥2 cm) and tighter criteria (2%/1 mm) with a 4% improvement. Compared to conventional AJ-VMAT, FJ-VMAT could reduce the adverse effects from minimum DLG with superior delivery accuracy and plan quality in single-isocenter VMAT SRS for multiple BMs.

Evaluation of correlation between intrafractional residual setup errors and accumulation of delivered dose distributions in single isocenter volumetric modulated arc therapy for multiple brain metastases

PurposeTo evaluate the displacement of gross tumor volume (GTV) positions caused by intrafractional residual setup errors (RSEs) and to accumulate delivered dose distributions considering intrafraction RSEs in fractionated-stereotactic radiotherapy (f-SRT) with single isocenter volumetric modulated arc therapy (SI-VMAT) for multiple brain metastases. MethodsOverall, 72 consecutive patients who underwent f-SRT with SI-VMAT for multiple brain metastases were included. For all patients, 6D correction was performed using the ExacTrac X-ray (ETX) system. GTV displacement (ΔD) was calculated considering the intrafractional RSEs measured by the ETX system during irradiation. The correlation between ΔD and the distance from the isocenter to each GTV (d) was analyzed. Computed tomography (CT) images considering the intrafractional RSEs were generated for five patients with ΔD > 1 mm. The delivered dose distributions for all fractions were reconstructed on the corresponding CT, followed by their accumulation. ResultsThe 95th percentile of ΔD from 7,270 resultant center positions of 417 GTVs was 0.92 mm. No correlation was observed between ΔD and d. For 53 GTVs from five patients with ΔD > 1 mm, the difference of GTV D99.5% and D0.5% between the planned and accumulated values was −0.4 ± 2.5% and −1.0 ± 0.8%, respectively. There was no correlation between d and the difference of GTV D99.5% and D0.5%. ConclusionsWe found no significant difference in GTV D99.5% and D0.5%, despite the location of GTVs far from the isocenter. However, it should be noted that this result was because the intrafractional RSEs were reduced to a clinically acceptable level.

Feasibility of using ring-mounted Halcyon Linac for single-isocenter/two-lesion lung stereotactic body radiation therapy.

PurposeTo demonstrate the plan quality and delivery efficiency of volumetric‐modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single‐isocenter/two‐lesion lung stereotactic body radiation therapy (SBRT).Materials/methodsSixteen previously treated non‐coplanar VMAT single‐isocenter/two‐lesion lung SBRT plans delivered with SBRT‐dedicated C‐arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single‐isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage and evaluated. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D 2cm were compared. The normal lung V5Gy, V10Gy, V20Gy, mean lung dose (MLD), and dose to organs at risk (OAR) were evaluated. Treatment delivery parameters, including beam‐on time, were recorded.ResultsHalcyon plans were statistically similar to clinically delivered TrueBeam plans. No statistical differences in target conformity, dose heterogeneity, or intermediate‐dose spillage were observed (all, p > 0.05). Halcyon plans, on average, demonstrated statistically insignificant reduced maximum dose to most adjacent OAR and normal lung. However, Halcyon yielded statistically significant lower maximal dose to the ribs (p = 0.041) and heart (p = 0.026), dose to 1 cc of ribs (p = 0.035) and dose to 5 cc of esophagus (p = 0.043). Plan complexity slightly increased as seen in the average increase of total monitor units, modulation factor, and beam‐on time by 480, 0.48, and 2.78 min, respectively. However, the estimated overall treatment time was reduced by 2.22 min, on average. Mean dose delivery accuracy of clinical TrueBeam plans and the corresponding Halcyon plans was 98.9 ± 0.85% (range: 98.1%–100%) and 98.45 ± 0.99% (range: 97.9%–100%), respectively, demonstrating similar treatment delivery accuracy.ConclusionSBRT treatment of synchronous lung lesions via single‐isocenter VMAT on Halcyon RDS is feasible and dosimetrically equivalent to clinically delivered TrueBeam plans. Halcyon provides excellent plan quality and shorter overall treatment time that may improve patient compliance, reduce intrafraction movement, improve clinic efficiency, and potentially offering lung SBRT treatments for underserved patients on a Halcyon only clinic.

Longitudinal Grouping of Target Volumes for Volumetric-Modulated Arc Therapy of Multiple Brain Metastases.

PurposeTreatment of multiple brain metastases with single-isocenter volumetric modulated arc therapy causes unnecessary exposure to normal brain tissue. In this study, a longitudinal grouping method was developed to reduce such unnecessary exposure.Materials and MethodsThis method has two main aspects: grouping brain lesions longitudinally according to their longitudinal projection positions in beam’s eye view, and rotating the collimator to 90° to make the multiple leaf collimator leaves conform to the targets longitudinally group by group. For 11 patients with multiple (5–30) brain metastases, two single-isocenter volumetric modulated arc therapy plans were generated using a longitudinal grouping strategy (LGS) and the conventional strategy (CVS). The prescription dose was 52 Gy for 13 fractions. Dose normalization to 100% of the prescription dose in 95% of the planning target volume was adopted. For plan quality comparison, Paddick conformity and the gradient index of the planning target volume, and the mean dose, the V100%, V50%, V25%, and V10% volumes of normal brain tissue were calculated.ResultsThere were no significant differences between the LGS and CVS plans in Paddick conformity (p = 0.374) and the gradient index (p = 0.182) of the combined planning target volumes or for V100% (p = 0.266) and V50% (p = 0.155) of the normal brain. However, the V25% and V10% of the normal brain which represented the low-dose region were significantly reduced in the LGS plans (p = 0.004 and p = 0.003, respectively). Consistently, the mean dose of the entire normal brain was 12.04 and 11.17 Gy in the CVS and LGS plans, respectively, a significant reduction in the LGS plans (p = 0.003).ConclusionsThe longitudinal grouping method can decrease unnecessary exposure and reduces the low-dose range in normal brain tissue.

Effective method to reduce the normal brain dose in single-isocenter hypofractionated stereotactic radiotherapy for multiple brain metastases.

Island blocking and dose leakage problems will lead to unnecessary irradiation to normal brain tissue (NBT) in hypofractionated stereotactic radiotherapy (HSRT) for multiple brain metastases (BM) with single-isocenter volumetric modulated arc therapy (VMAT). The present study aimed at investigating whether reducing the number of metastases irradiated by each arc beam could minimize these two problems. A total of 32non-small-cell lung cancer (NSCLC) patients with multiple BM received HSRT (24-36 Gy/3 fractions) with single-isocenter VMAT, where each arc beam only irradiated partial metastases (pm-VMAT), were enrolled in this retrospective study. Conventional single-isocenter VMAT plans, where each arc beam irradiated whole metastases (wm-VMAT), was regenerated and compared with pm-VMAT plans. Furthermore, the clinical efficacy and toxicities were evaluated. Pm-VMAT achieved similar target coverage as that with wm-VMAT, with better dose fall-off (P < 0.001) and NBT sparing (P < 0.001). However, pm-VMAT resulted in more monitor units (MU) and longer beam-on time (P < 0.001). The intracranial objective response rate and disease control rate for all patients were 75% and 100%, respectively. The local control rates at 1year and 2year were 96.2% and 60.2%, respectively. The median progression-free survival and overall survival were 10.3months (95% confidence interval [CI] 6.8-13.2) and 18.5months (95% CI 15.9-20.1), respectively. All treatment-related adverse events were grade1 or2, and 3lesions (2.31%) from 2patients (6.25%) demonstrated radiation necrosis after HSRT. HSRT with pm-VMAT is effective and has limited toxicities for NSCLC patients with multiple BM. Pm-VMAT could provide better NBT sparing while maintaining target dose coverage.

Transition From Manual to Automated Planning and Delivery of Volumetric Modulated Arc Therapy Stereotactic Radiosurgery: Clinical, Dosimetric, and Quality Assurance Results

PurposeProperly planned single isocenter volumetric modulated arc therapy (VMAT) radiosurgery plans exhibit high quality and efficiency. We report here the largest clinical experience to date, to our knowledge, comparing manual planning with a new automated platform designed to standardize and simplify radiosurgery planning and delivery processes. MethodsWe treated 693 patients with single isocenter VMAT radiosurgical plans generated by either our conventional manual (mVMAT) or a recently implemented automated (HyperArcTM) technique. All plans targeted the gross tumor volume without margin. Radiochromic film was used for patient-specific quality assurance (PSQA). We evaluated local control and toxicity data for a subgroup of 107 patients having 377 metastatic tumors that were treated with HyperArc. ResultsThe median Radiation Therapy Oncology Group (RTOG) conformity index was 1.14 and was not different between the 2 techniques. The median Paddick gradient index was 5.42 for HyperArc versus 7.09 for mVMAT (P < .001). The median mean brain doses were 4.6% and 5.1% for HyperArc and mVMAT, respectively (P = .04). The PSQA for both techniques met clinical criteria, but 97% of the HyperArc plans satisfied the gamma tolerance limit recommended by the American Association of Physicists in Medicine Task Group No. 218, compared with 94% of the mVMAT plans (P = .02). The median treatment-planning times were not significantly different. The median treatment times were 10.5 and 11.4 minutes for HyperArc and mVMAT, respectively (P < .001). The Kaplan-Meier estimate of local control was 90.1% at 1 year. ConclusionsHyperArc produces high-quality radiosurgical plans that are at least as good as mVMAT plans created by an expert manual planner with easier planning and more efficient delivery workflow. A less experienced planner can produce very high-quality radiosurgical plans even for patients with more than 10 targets. The use of a single-isocenter technique for multiple targets with no PTV margin did not compromise clinical outcomes, and 1-year local control for treated targets remained congruent with historical series.

A novel restricted single-isocenter stereotactic body radiotherapy (RESIST) method for synchronous multiple lung lesions to minimize setup uncertainties.

Treating multiple lung lesions synchronously using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can improve treatment efficiency and patient compliance. However, due to set up uncertainty, aligning multiple lung tumors on a single daily cone beam CT (CBCT) image has shown clinically unacceptable loss of target(s) coverage. Herein, we propose a Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST), an alternative treatment that mitigates patient setup uncertainties. Twenty-one patients with two lung lesions were treated with single-isocenter VMAT-SBRT using a 6MV-FFF beam to 54 Gy in 3 fractions (n = 7) or 50 Gy in 5 fractions (n = 14) prescribed to 70-80% isodose line. To minimize setup uncertainties, each plan was re-planned using the RESIST method, utilizing a single-isocenter placed at the patient's mediastinum. It allows for an individual plan to be created for each tumor, using the first plan as the base-dose for the second plan, while still allowing both tumors to be treated in the same session. The technique uses novel features in Eclipse, including dynamic conformal arc (DCA)-based dose and aperture shape controller before each VMAT optimization. RESIST plans provided better target dose conformity (p < 0.001) and gradient indices (p < 0.001) and lower dose to adjacent critical organs. Using RESIST to treat synchronous lung lesions with VMAT-SBRT significantly reduces plan complexity as demonstrated by smaller beam modulation factors (p < 0.001), without unreasonably increasing treatment time. RESIST reduces the chance of a geometric miss due by allowing CBCT matching of one tumor at a time. Placement of isocenter at the mediastinum avoids potential patient/gantry collisions, provides greater flexibility of noncoplanar arcs and eliminates the need for multiple couch movements during CBCT imaging. Efficacy of RESIST has been demonstrated for two lesions and can potentially be used for more lesions. Clinical implementation of this technique is ongoing.

Management of multiple brain metastases via dual-isocenter VMAT stereotactic radiosurgery.

Single-isocenter volumetric modulated arc therapy (VMAT) stereotactic radiosurgery (SRS) techniques to treat multiple brain metastases simultaneously can significantly improve treatment delivery efficiency, patient compliance, and clinic workflow. However, due to large number of brain metastases sharing the same MLC pair causing island blocking, there is higher low- and intermediate-dose spillage to the normal brain and higher dose to organs-at-risk (OAR). To minimize this problem and improve plan quality, this study proposes a dual-isocenter planning strategy that groups lesions based on hemisphere location (left vs right sided) in the brain parenchyma, providing less island blocking reducing the MLC travel distance. This technique offers simplified planning while also increasing patient comfort and compliance by allowing for large number of brain metastases to be treated in 2 groups. Seven complex patients with 5 to 16 metastases (64 total) were planned with a single-isocenter VMAT-SRS technique using a 10MV-FFF beam with a prescription of 20 Gy to each lesion. The isocenter was placed at the approximate geometric center of the targets. Each patient was replanned using the dual-isocenter approach, generating 2 plans and placing each isocenter at the approximate geometric center of the combined targets of each side with corresponding non-coplanar partial arcs. Compared to single-isocenter VMAT, dual-isocenter VMAT plans provided similar target coverage and dose conformity with less spread of intermediate dose to normal brain with reduction of dose to OAR. Reduction in total monitor units and beam on time was observed, but due to the second isocenter setup and verification, overall treatment time was increased. Dual-isocenter VMAT-SRS planning for multiple brain metastases is a simplified approach that provides superior treatment options for patient compliance who may not tolerate longer traditional treatment times as with individual isocenters to each target. This planning technique significantly reduces the amount of low- and intermediate-dose spillage, further sparing OAR and normal brain, potentially improving target accuracy though localization of left vs right-sided tumors for each isocenter set up.

Risk of target coverage loss for stereotactic body radiotherapy treatment of synchronous lung lesions via single-isocenter volumetric modulated arc therapy.

Treating multiple lung lesions synchronously via single‐isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance. However, aligning multiple lung tumors accurately on single pretreatment cone beam CTs (CBCTs) can be problematic. Tumors misaligned could lead to target coverage loss. To quantify this potential target coverage loss due to small, clinically realistic setup errors, a novel simulation method was developed. This method was used on 26 previously treated patients with two metastatic lung lesions. Patients were treated with 4D CT‐based, highly conformal noncoplanar VMAT plans (clinical VMAT) with 6MV‐flattening filter free (FFF) beam using AcurosXB dose calculation algorithm with heterogeneity corrections. A single isocenter was placed approximately between the lesions to improve patient convenience and clinic workflow. Average isocenter to tumor distance was 5.9 cm. Prescription dose was 54 Gy/50 Gy in 3/5 fractions. For comparison, a plan summation (simulated VMAT) was executed utilizing randomly simulated, clinically relevant setup errors, obtained from pretreatment setup, per treatment fraction, in Eclipse treatment planning system for each of the six degrees of freedom within ± 5.0 mm and ± 2°. Simulations yielded average deviations of 27.4% (up to 72% loss) (P < 0.001) from planned target coverage when treating multiple lung lesions using a single‐isocenter plan. The largest deviations from planned coverage and desired biological effective dose (BED10, with α/β = 10 Gy) were seen for the smallest targets (<10 cc), some of which received < 100 Gy BED10. Patient misalignment resulted in substantial decrease in conformity and increase in the gradient index, violating major characteristics of SBRT. Statistically insignificant differences were seen for normal tissue dose. Although, clinical follow‐up of these patients is ongoing, the authors recommend an alternative treatment planning strategy to minimize the probability of a geometric miss when treating small lung lesions synchronously with single‐isocenter VMAT SBRT plans.

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.

Initial Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) Treatment of Multiple Synchronous Lung Lesions

Stereotactic body radiotherapy (SBRT) treatment of early-stage inoperable non-small-cell lung cancer (NSCLC) patients has shown greater than 90% local control rates at 3 years. However, patients with significant co-morbidities who present with multiple synchronous lung masses may benefit from treatment of multiple lesions synchronously by either single isocenter volumetric modulated arc therapy (VMAT) flattening filter free (FFF) or a 3DCRT and IMRT system plans. The goal is to reduce treatment time and improve patient compliance. We report our initial clinical outcomes of cancer patients with multiple (<5) lung lesions synchronously treated with lung SBRT. Thirty patients with multiple peripherally located lung masses (two n = 27, three n = 2, five n = 1, total 65 lesions) were treated synchronously with either single isocenter non-coplanar VMAT-SBRT (23 patients) or Tomotherapy (7 patients). Respiratory control of target movement was accomplished with abdominal compression. Dose and fractionation varied but the most common prescriptions were 54 Gy/3 fractions and 50 Gy/5 fractions prescribed to 80% isodose line covering the planning target volume. Patients were treated every other day with a daily cone beam-CT/MVCT guided imaging. Average treatment time was less than 10 min /fraction for VMAT and 20 min/fraction for Tomotherapy. Outcomes evaluated include local control rates, radiation pneumonitis and rib toxicity. Median follow-up interval was 8 months (range, 2 to 21 months). The median age of patients treated was 75 years. 20 patients had primary lung disease and 10 patients had metastatic disease to the lung. All plans met RTOG compliance criteria for target coverage and dose to organs at risk and all patients tolerated SBRT treatment. Mean V20Gy was 7.8 ± 4% (range, 3.2-15.7%). Maximal and 1 cc of rib doses were 40 Gy and 31.5 Gy, respectively. Four patients died before follow up and two were lost to follow up. Three patients have initial post-treatment imaging pending. Of twenty-one patients, all achieved complete response to treatment with only one lesion of one patient progressing. However, 10 patients developed distant metastases. During the follow-up period, no patients had adverse pulmonary side effects, developed grade 2+ pneumonitis, chest wall pain or rib fracture. However, 50% of the patients developed radiographic changes that were asymptomatic in nature. Synchronous lung SBRT treatment using a single-isocenter VMAT plan or Tomotherapy to multiple lung lesions was fast, safe and highly effective, with promising initial clinical results in terms of local control rates and no adverse treatment related side effects to lung or ribs. Although ten patients developed either further distant metastases, the local control achieved of treated lesions could preserve the patient’s quality of life or delay systemic therapy. Longer clinical follow up of these patients is needed.

Validation of the clinical applicability of knowledge‐based planning models in single‐isocenter volumetric‐modulated arc therapy for multiple brain metastases

PurposeTo validate the clinical applicability of knowledge‐based (KB) planning in single‐isocenter volumetric‐modulated arc therapy (VMAT) for multiple brain metastases using the k‐fold cross‐validation (CV) method.MethodsThis study comprised 60 consecutive patients with multiple brain metastases treated with single‐isocenter VMAT (28 Gy in five fractions). The patients were divided randomly into five groups (Groups 1–5). The data of Groups 1–4 were used as the training and validation dataset and those of Group 5 were used as the testing dataset. Four KB models were created from three of the training and validation datasets and then applied to the remaining Groups as the fourfold CV phase. As the testing phase, the final KB model was applied to Group 5 and the dose distributions were calculated with a single optimization process. The dose‐volume indices (DVIs), modified Ian Paddick Conformity Index (mIPCI), modulation complexity scores for VMAT plans (MCSv), and the total number of monitor units (MUs) of the final KB plan were compared to those of the clinical plan (CL) using a paired Wilcoxon signed‐rank test.ResultsIn the fourfold CV phase, no significant differences were observed in the DVIs among the four KB plans (KBPs). In the testing phase, the final KB plan was statistically equivalent to the CL, except for planning target volumes (PTVs) D2% and D50%. The differences between the CL and KBP in terms of the PTV D99.5%, normal brain, and Dmax to all organs at risk (OARs) were not significant. The KBP achieved a lower total number of MUs and higher MCSv than the CL with no significant difference.ConclusionsWe demonstrated that a KB model in a single‐isocenter VMAT for multiple brain metastases was equivalent in dose distribution, MCSv, and total number of MUs to a CL with a single optimization.

On the use of single‐isocenter VMAT plans for SBRT treatment of synchronous multiple lung lesions: Plan quality, treatment efficiency, and early clinical outcomes

Cone‐beam computed tomography (CT)‐guided volumetric‐modulated arc therapy (VMAT) plans for stereotactic body radiotherapy (SBRT) treatment of synchronous multiple lung lesions with a flattening filter‐free (FFF) beam is a safe and highly effective treatment option for oligometastases lung cancer patients. Fourteen patients with metastatic non–small‐cell lung cancer (NSCLC) lesions (two to five) received a single‐isocenter VMAT SBRT treatment in our clinic. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB‐based dose calculation algorithm using heterogeneity corrections with a single isocenter placed between/among the lesions. Compared to 10X‐FFF and traditional flattened 6X (6X‐FF) beams, 6X‐FFF beam produced highly conformal radiosurgical dose distribution to each target volume, reduced dose to adjacent organs at risk (OAR), and significantly reduced the lung SBRT fraction duration to < 3.5 min/fraction for 54/50 Gy treatments in 3/5 fractions — significantly improving patient convenience and clinic workflow. Early follow‐up CT imaging (mean, 9 months) results show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow up in a larger patient cohort is ongoing to further validate the outcomes of this treatment approach.

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.

Retrospective quality metrics review of stereotactic radiosurgery plans treating multiple targets using single-isocenter volumetric modulated arc therapy.

PurposeTo characterize key plan quality metrics in multi‐target stereotactic radiosurgery (SRS) plans treated using single‐isocenter volumetric modulated arc therapy (VMAT) in comparison to dynamic conformal arc (DCA) plans treating single target. To investigate the feasibility of quality improvement in VMAT planning based on previous planning knowledge.Materials and methods97 VMAT plans of multi‐target and 156 DCA plans of single‐target treated in 2017 at a single institution were reviewed. A total of 605 targets were treated with these SRS plans. The prescription dose was normalized to 20 Gy in all plans for this analysis. Two plan quality metrics, target conformity index (CI) and normal tissue volume receiving more than 12 Gy (V12Gy), were calculated for each target. The distribution of V12Gy per target was plotted as a function of the target volume. For multi‐target VMAT plans, the number of targets being treated in the same plan and the distance between targets were calculated to evaluate their impact on V12Gy. VMAT plans that had a large deviation of V12Gy from the average level were re‐optimized to determine the possibility of reducing the variation of V12Gy in VMAT planning.ResultsConformity index of multi‐target VMAT plans were lower than that of DCA plans while the mean values of 12 Gy were comparable. The V12Gy for a target in VMAT plan did not show apparent dependence on the total number of targets or the distance between targets. The distribution of V12Gy exhibited a larger variation in VMAT plans compared to DCA plans. Re‐optimization of outlier plans reduced V12 Gy by 33.9% and resulted in the V12Gy distribution in VMAT plans more closely resembling that of DCA plans.ConclusionThe benchmark data on key plan quality metrics were established for single‐isocenter multi‐target SRS planning. It is feasible to use this knowledge to guide VMAT planning and reduce high V12Gy outliers.

Single-Isocenter/Multi-Lesion Synchronous Lung Stereotactic Body Radiation Therapy (SBRT): Plan Quality, Treatment Efficiency and Clinical Outcomes

Patients with multiple primary or metastatic lung lesions may not well tolerate relatively longer SBRT treatments due to distress or shortness of breath, with traditional treatment planning and delivery with individual isocenter per lesion. Treating lesions synchronously with a single-isocenter volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam will decrease treatment time and improve patient comfort. We report dosimetry, treatment efficiency and early clinical outcomes of oligometastases (< 5 lesions) lung cancer patients who underwent synchronous single-isocenter/multiple-lesions VMAT lung SBRT. Fourteen patients with multiple peripherally located non-small-cell-lung cancer (NSCLC) lesions (two n = 12, three n = 1, five n = 1, total 32 lesions) were treated synchronously with highly conformal single-isocenter non-coplanar VMAT-SBRT plan (bilateral lesions n = 6, right lesions n = 5, left lesions n = 3). Single-isocenter was placed between or in the middle of all lesions. Doses were 54 Gy/50 Gy in 3/5 fractions prescribed to 70-80% isodose line. Plans were generated with Acuros-based algorithm and 6MV-FFF beam following RTOG criteria. Plan quality and delivery efficiency were reported. Outcomes evaluated include local control rates, radiation pneumonitis and rib toxicity. Kaplan-Meier (KM) estimates of time-to-local failure were investigated. Median follow-up time was 5 ± 5 months (range 1 to 15 months). Mean isocenter to tumor distance was 5.6 ± 1.9 cm. Mean combined planning target volume (PTV) was 38.7 ± 22.7 cc. All plans were accepted by treating physicians and met RTOG criteria for target coverage and organs at risk (OAR) dose. Average values of conformity index, gradient index, maximum dose at 2 cm away from the PTV and normal lung V20 were 1.05 ± 0.1, 5.1 ± 0.8, 50.1 ± 5.2% and 6.4 ± 3.1%, respectively. All OAR doses were well below RTOG criteria. Additionally, normal lung V10, V5 and mean lung dose were 18.2%, 31.0 % and 5.4 Gy, on average, respectively. Average beam on time was 3.4 ± 1.4 min. One patient died before follow up and one was lost to follow up. Of twelve patients, eleven achieved complete response to treatment with one lesion of one patient progressing. KM estimated 1-year actuarial tumor local control rate was 100%; however, 50% of the patients developed distant metastases. During the follow-up period, no patient had adverse pulmonary effects, developed grade+2 pneumonitis or had chest wall pain/rib fracture. However, four patients developed radiographic changes that were asymptomatic. Synchronous SBRT treatment to oligometastases lung lesions was fast, effective and safe, with promising early clinical outcomes in terms of local control rates and no adverse side effects to lung or ribs. Although six patients had distant failure, the local control of treated lesions could preserve the patient’s quality of life or delay chemotherapy treatment. Longer follow up of these patients is warranted.

Interfractional Target Volume Changes in Brain Metastases during 13-Fraction Stereotactic Radiotherapy

Advances in systemic therapy have greatly improved the prognosis of patients with brain metastases (BMs); long-term local control and reduced radiation toxicity are important. Fractionated stereotactic radiotherapy (SRT) seems to be associated with a reduced risk of radiation necrosis while providing equivalent local control compared to single-fraction or hypofractionated radiosurgery and is used in our institution for patients with a good prognosis or large BMs. As 13-fraction SRT lasts at least 17 days, we conduct adaptive replanning as necessary, based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) performed during 13-fraction SRT. We retrospectively analyzed interfractional volume changes and clinical outcomes of BMs treated with 13-fraction SRT. In total, this study included 23 patients with 27 BMs who received 13-fraction SRT with dynamic conformal arc therapy between July 2015 and November 2018. We excluded patients who received postoperative radiotherapy for the surgical cavity, no contrast-enhanced mid-treatment MRI, or single isocenter volumetric-modulated arc therapy for multiple BMs. The median patient age was 70 years and the median Karnofsky Performance Status was 90. There were 15 lung-cancer patients. The planning target volume (PTV) was established by adding a 1-mm margin to the gross tumor volume (GTV), defined as the volume of the contrast-enhancing lesion. The peripheral dose prescribed to the PTV was 39–44.2 Gy in 13 fractions. The GTV of the initial SRT plan (initial GTV) and the modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were compared. The median initial GTV was 3.8 (range 0.2–26.7) cm3 and the median period from the start of SRT to the mid-treatment MRI scan was 6 (range 3–11) days. In 10 lesions, the mid-treatment GTV had changed by more than 20% (5 had increased and 5 decreased) relative to the initial GTV. Adaptive replanning was conducted for 14 lesions. Of the 10 lesions that had increased or decreased in size by more than 20%, 8 received adaptive replanning. There was no significant relationship between an interfractional GTV volume change of more than 20%, primary disease (lung cancer vs. other cancers), and the presence of necrotic or cystic components. Regarding clinical outcomes, both overall survival rates and local control rates at 6 months were 95.0%, with a median follow-up period of 7.2 months. Two patients experienced grade 3 cerebral edema, two experienced grade 3 seizures, and four experienced grade 1 brain necrosis (CTCAE v5). The mid-treatment GTV changed by more than 20% relative to the initial GTV in almost one-third of lesions receiving 13-fraction SRT. More cases and long-term follow up are required to verify the impact of interfractional volume changes and adaptive replanning on clinical outcomes.