Hypofractionated radiation therapy (RT) offers benefits in the treatment of soft tissue sarcomas (STS), including exploitation of the lower α/β, patient convenience, and cost. This study evaluates ...the acute toxicity of a hypofractionated accelerated RT dose-painting (HARD) approach for postoperative treatment of STS.
This is a retrospective review of 53 consecutive patients with STS who underwent resection followed by postoperative RT. Standard postoperative RT dosing for R0/R1/gross disease with sequential boost (50 Gy + 14/16/20 Gy in 32-35 fractions) were replaced with dose-painting, which adapts dose based on risk of disease burden, to 50.4 and 63, 64.4, 70 Gy in 28 fractions, respectively. The first 10 patients were replanned with a sequential boost RT approach and dosimetric indices were compared. Time-to-event outcomes, including local control, regional control, distant control, and overall survival, were estimated with Kaplan-Meier analysis.
Median follow-up was 25.2 months. Most patients had high-grade (59%) STS of the extremity (63%) who underwent resection with either R1 (40%) or close (36%) margins. Four patients experienced grade 3 acute dermatitis which resolved by the 3-month follow-up visit. The 2-year local control, regional control, distant control, and overall survival were 100%, 92%, 68%, and 86%, respectively. Compared with the sequential boost plan, HARD had a significantly lower field size (total V50 Gy; P = .002), bone V50 (P = .031), and maximum skin dose (P = .008). Overall treatment time was decreased by 4 to 7 fractions, which translated to a decrease in estimated average treatment cost of $3056 (range, $2651-$4335; P < .001).
In addition to benefits in cost, convenience, and improved biologic effect in STS, HARD regimen offers a safe treatment approach with dosimetric advantages compared with conventional sequential boost, which may translate to improved long-term toxicity.
3DVH software (Sun Nuclear Corp., Melbourne, FL) is capable of generating a volumetric patient VMAT dose by applying a volumetric perturbation algorithm based on comparing measurement‐guided dose ...reconstruction and TPS‐calculated dose to a cylindrical phantom. The primary purpose of this paper is to validate this dose reconstruction on an anthropomorphic heterogeneous thoracic phantom by direct comparison to independent measurements. The dosimetric insert to the phantom is novel, and thus the secondary goal is to demonstrate how it can be used for the hidden target end‐to‐end testing of VMAT treatments in lung. A dosimetric insert contains a 4 cm diameter unit‐density spherical target located inside the right lung (0.21g/cm3 density). It has 26 slots arranged in two orthogonal directions, milled to hold optically stimulated luminescent dosimeters (OSLDs). Dose profiles in three cardinal orthogonal directions were obtained for five VMAT plans with varying degrees of modulation. After appropriate OSLD corrections were applied, 3DVH measurement‐guided VMAT dose reconstruction agreed 100% with the measurements in the unit density target sphere at 3%/3 mm level (composite analysis) for all profile points for the four less‐modulated VMAT plans, and for 96% of the points in the highly modulated C‐shape plan (from TG‐119). For this latter plan, while 3DVH shows acceptable agreement with independent measurements in the unit density target, in the lung disagreement with experiment is relatively high for both the TPS calculation and 3DVH reconstruction. For the four plans excluding the C‐shape, 3%/3mm overall composite analysis passing rates for 3DVH against independent measurement ranged from 93% to 100%. The C‐shape plan was deliberately chosen as a stress test of the algorithm. The dosimetric spatial alignment hidden target test demonstrated the average distance to agreement between the measured and TPS profiles in the steep dose gradient area at the edge of the 2 cm target to be 1.0±0.7,0.3±0.3, and 0.3±0.3mm for the IEC X, Y, and Z directions, respectively.
PACS number: 87.55Qr
Frequently, three-dimensional (3D) conformal beams are used in lung cancer stereotactic body radiotherapy (SBRT). Recently, volumetric modulated arc therapy (VMAT) was introduced as a new treatment ...modality. VMAT techniques shorten delivery time, reducing the possibility of intrafraction target motion. However dose distributions can be quite different from standard 3D therapy. This study quantifies those differences, with focus on VMAT plans using unflattened photon beams.
A total of 15 lung cancer patients previously treated with 3D or VMAT SBRT were randomly selected. For each patient, non-coplanar 3D, coplanar and non-coplanar VMAT and flattening filter free VMAT (FFF-VMAT) plans were generated to meet the same objectives with 50 Gy covering 95% of the PTV. Two dynamic arcs were used in each VMAT plan. The couch was set at ± 5° to the 0° straight position for the two non-coplanar arcs. Pinnacle version 9.0 (Philips Radiation Oncology, Fitchburg WI) treatment planning system with VMAT capabilities was used. We analyzed the conformity index (CI), which is the ratio of the total volume receiving at least the prescription dose to the target volume receiving at least the prescription dose; the conformity number (CN) which is the ratio of the target coverage to CI; and the gradient index (GI) which is the ratio of the volume of 50% of the prescription isodose to the volume of the prescription isodose; as well as the V20, V5, and mean lung dose (MLD). Paired non-parametric analysis of variance tests with post-tests were performed to examine the statistical significance of the differences of the dosimetric indices.
Dosimetric indices CI, CN and MLD all show statistically significant improvement for all studied VMAT techniques compared with 3D plans (p < 0.05). V5 and V20 show statistically significant improvement for the FFF-VMAT plans compared with 3D (p < 0.001). GI is improved for the FFF-VMAT and the non-coplanar VMAT plans (p < 0.01 and p < 0.05 respectively) while the coplanar VMAT plans do not show significant difference compared to 3D plans. Dose to the target is typically more homogeneous in FFF-VMAT plans. FFF-VMAT plans require more monitor units than 3D or non-coplanar VMAT ones.
Besides the advantage of faster delivery times, VMAT plans demonstrated better conformity to target, sharper dose fall-off in normal tissues and lower dose to normal lung than the 3D plans for lung SBRT. More monitor units are often required for FFF-VMAT plans.
Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic ...MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions.
We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data.
Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities.
SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone.
In this paper, we describe and characterize a novel biplanar diode array, and demonstrate its applicability to dosimetric QA of step‐and‐shoot IMRT. It is the first commercially available device of ...its kind specifically designed for performing measurements at varying gantry angles. The detector consists of a cylindrical PMMA phantom with two orthogonal detector boards. There are a total of 1069 p‐type 1 mm wide diode detectors covering the measurement area of 20×20cm2 in each of the measurement planes. The orthogonal detector arrays ensure that the dose modulation information is not lost regardless of the beam incidence angle. For absolute calibration, the dose to the reference detector is calculated at the appropriate SSD and radiological depth by the treatment planning system and is scaled by the measured accelerator output. The directly measured rotational response on the central axis shows the maximum variation of approximately ± 3% in the narrow ±1º angular intervals centered on the detector boards. This variation is reduced to less than ± 2% outside of the four similarly centered ± 5% angular intervals. For all detectors, the difference between the measured and the calculated dose for a plan with 12 equally spaced beams is −0.2±0.9%. Of eleven IMRT plans, ten passed the γ (3%,3 mm) criterion at or above 95%, while one passed at 92%. The biplanar diode array is a useful tool for IMRT QA, allowing for essentially instantaneous online analysis of absolute dose errors in 3D.
PACS number: 87.55Qr
Soft tissue sarcomas (STS) are historically radioresistant, with surgery being an integral component of their treatment. With their low α/β, STS may be more responsive to hypofractionated radiation ...therapy (RT), which is often limited by long-term toxicity risk to surrounding normal tissue. An isotoxic approach using a hypofractionated accelerated radiation dose-painting (HARD) regimen allows for dosing based on clinical risk while sparing adjacent organs at risk.
We retrospectively identified patients from 2019 to 2022 with unresected STS who received HARD with dose-painting to high, intermediate, and low-risk regions of 3.0 Gy, 2.5 Gy, and 2.0 to 2.3 Gy, respectively, in 20 to 22 fractions. Clinical endpoints included local control, locoregional control, progression free survival, overall survival, and toxicity outcomes.
Twenty-seven consecutive patients were identified and had a median age of 68 years and tumor size of 7.0 cm (range, 1.2-21.0 cm). Tumors were most often high-grade (70%), stage IV (70%), located in the extremities (59%), and locally recurrent (52%). With a median follow-up of 33.4 months, there was a 3-year locoregional control rate of 100%. The 3-year overall and progression-free survival were 44.9% and 23.3%, respectively. There were 5 (19%) acute and 2 (7%) late grade 3 toxicities, and there were no grade 4 or 5 toxicities at any point.
The HARD regimen is a safe method of dose-escalating STS, with durable 3-year locoregional control. This approach is a promising alternative for unresected STS, though further follow-up is required to determine long-term control and toxicity.
A superposition/convolution GPU‐accelerated dose computation algorithm (the Calculator) has been recently incorporated into commercial software. The algorithm requires validation prior to clinical ...use. Three photon energies were examined: conventional 6 MV and 15 MV, and 10 MV flattening filter free (10 MVFFF). For a set of IMRT and VMAT plans based on four of the five AAPM Practice Guideline 5a downloadable datasets, ion chamber (IC) measurements were performed on the water‐equivalent phantoms. The average difference between the Calculator and IC was −0.3 ± 0.8% (1SD). The same plans were projected on a phantom containing a biplanar diode array. We used the forthcoming criteria for routine gamma analysis, 3% dose–error (global (G) normalization, 2 mm distance to agreement, and 10% low dose cutoff). The γ (3%G/2 mm) average passing rate was 98.9 ± 2.1%. Measurement‐guided three‐dimensional dose reconstruction on the patient CT dataset (excluding the Lung) resulted in a similar average agreement rate with the Calculator: 98.2 ± 2.0%. The mean γ (3%G/2 mm) passing rate comparing the Calculator to the TPS (again excluding the Lung) was 99.0 ± 1.0%. Because of the significant inhomogeneity, the Lung case was investigated separately. The calculator has an alternate heterogeneity correction mode that can change the results in the thorax for higher‐energy beams (15 MV). As this correction is nonphysical and was optimized for simple slab geometries, its application leads to mixed results when compared to the TPS and independent Monte Carlo calculations, depending on the CT dataset and the plan. The Calculator vs. TPS 15 MV Guideline 5a IMRT and VMAT plans demonstrate 96.3% and 93.4% γ (3%G/2 mm) passing rates respectively. For the lower energies, which should be predominantly used in the thoracic region, the passing rates for the same plans and criteria range from 98.6 to 100%. Overall, the Calculator accuracy is sufficient for the intended use.
•Radiation is not typical in the standard of care for cardiac metastases.•MR-guided radiation uses real-time imaging and offers better soft tissue contrast.•Real-time MR-guidance allows for safe high ...dose radiation to cardiac metastases.•MR-guided stereotactic radiation can improve symptoms without acute toxicity.
To assess the safety and efficacy of MR-guided stereotactic body radiation therapy (MRgSBRT) for cardiac metastases.
This single institution retrospective analysis evaluated our experience with MRgSBRT for cardiac metastases. Response rate was compared between pre-RT and post-RT imaging. Symptomatic changes were also tracked and documented.
Between 4/2019 and 3/2020, five patients with cardiac metastases (4 intracardiac and 1 pericardial) were treated with MRgSBRT. Median age at treatment was 73 years (range 64–80) and two patients had pre-existing cardiac disease. Histologies included melanoma and breast adenocarcinoma. Median lesion diameter was 2 cm (range 1.96–5.8 cm). Three patients were symptomatic, one of whom had pulmonary hypertension and RV enlargement. Another patient had an asymptomatic arrythmia. Median PTV prescribed dose was 40 Gy (range 40–50 Gy) and delivered in five fractions on nonconsecutive days. Median PTV volume was 53.4 cc (range 8.7–116.6 cc) and median coverage was 95% (range 84.1–100%). A uniform 3 mm margin was used for real-time gating, allowing a median 7% (range 5–10%) pixel excursion tolerance. Median follow-up was 4.7 months (range 0.9–12.3). Two patients exhibited stable disease, two had a partial response and one exhibited a complete response. All symptomatic patients experienced some relief. There were no acute adverse events, however, one patient without prior cardiac disease developed atrial fibrillation 6 months after treatment. Two patients died of causes unrelated to cardiac MRgSBRT.
In this largest known series of cardiac metastasis MRgSBRT, real-time image guidance enables safe treatment resulting in good response with improving presenting symptoms without acute adverse events.
The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic ...resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions.
Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney U test and Fisher’s exact test.
A total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4–29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0–19.0 mm). The median biologically equivalent dose (α/β = 10) was 105 Gy (range: 75–151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1–25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen.
Previous studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.
Quantum noise is common in CT images and is a persistent problem in accurate ventilation imaging using 4D-CT and deformable image registration (DIR). This study focuses on the effects of noise in ...4D-CT on DIR and thereby derived ventilation data. A total of six sets of 4D-CT data with landmarks delineated in different phases, called point-validated pixel-based breathing thorax models (POPI), were used in this study. The DIR algorithms, including diffeomorphic morphons (DM), diffeomorphic demons (DD), optical flow and B-spline, were used to register the inspiration phase to the expiration phase. The DIR deformation matrices (DIRDM) were used to map the landmarks. Target registration errors (TRE) were calculated as the distance errors between the delineated and the mapped landmarks. Noise of Gaussian distribution with different standard deviations (SD), from 0 to 200 Hounsfield Units (HU) in amplitude, was added to the POPI models to simulate different levels of quantum noise. Ventilation data were calculated using the ΔV algorithm which calculates the volume change geometrically based on the DIRDM. The ventilation images with different added noise levels were compared using Dice similarity coefficient (DSC). The root mean square (RMS) values of the landmark TRE over the six POPI models for the four DIR algorithms were stable when the noise level was low (SD <150 HU) and increased with added noise when the level is higher. The most accurate DIR was DD with a mean RMS of 1.5 ± 0.5 mm with no added noise and 1.8 ± 0.5 mm with noise (SD = 200 HU). The DSC values between the ventilation images with and without added noise decreased with the noise level, even when the noise level was relatively low. The DIR algorithm most robust with respect to noise was DM, with mean DSC = 0.89 ± 0.01 and 0.66 ± 0.02 for the top 50% ventilation volumes, as compared between 0 added noise and SD = 30 and 200 HU, respectively. Although the landmark TRE were stable with low noise, the differences between ventilation images increased with noise level, even when the noise was low, indicating ventilation imaging from 4D-CT was sensitive to image noise. Therefore, high quality 4D-CT is essential for accurate ventilation images.
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