Evaluation of repeatability and reproducibility of radiomic features produced by the fan-beam kV-CT on a novel ring gantry-based PET/CT linear accelerator.

BACKGROUND: The RefleXion X1 is a novel radiotherapy delivery system on a ring gantry equipped with fan-beam kV-CT and PET imaging subsystems. The day-to-day scanning variability of radiomics features must be evaluated before any attempt to utilize radiomics features. PURPOSE: This study aims to characterize the repeatability and reproducibility of radiomic features produced by the RefleXion X1 kV-CT. MATERIALS AND METHODS: The Credence Cartridge Radiomics (CCR) phantom includes six cartridges of varied materials. It was scanned 10 times on the RefleXion X1 kVCT imaging subsystem over a 3-month period using the two most frequently used scanning protocols (BMS and BMF). Fifty-five radiomic features were extracted for each ROI on each CT scan and analyzed using LifeX software. The coefficient of variation (COV) was computed to evaluate the repeatability. Intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) were used to evaluate the repeatability and reproducibility of the scanned images using 0.9 as the threshold. This process is repeated on a GE PET-CT scanner using several built-in protocols as a comparison. RESULTS: On average, 87% of the features on both scan protocols on the RefleXion X1 kVCT imaging subsystem can be considered repeatable as they met COV < 10% criteria. On GE PET-CT, this number is similar at 86%. When we tighten the criteria to COV <5%, the RefleXion X1 kVCT imaging subsystem showed much better repeatability with 81% of features on average whereas GE PET-CT showed only 73.5% on average. About 91% and 89% of the features with ICC > 0.9 respectively for BMS and BMF protocols on RefleXion X1. On the other hand, the percentage of features with ICC > 0.9 on GE PET-CT ranges from 67% to 82%. The RefleXion X1 kVCT imaging subsystem showed excellent intra-scanner reproducibility between the scanning protocols much better than the GE PET CT scanner. For the inter-scanner reproducibility, the percentage of features with CCC > 0.9 ranged from 49% to 80%. between X1 and GE PET-CT scanning protocols. CONCLUSIONS: Clinically useful CT radiomic features produced by the RefleXion X1 kVCT imaging subsystem are reproducible and stable over time, demonstrating its utility as a quantitative imaging platform.

Disease Burden on PET Predicts Outcomes for Advanced NSCLC Patients Treated with First-Line Immunotherapy.

BACKGROUND: First-line immunotherapy (IMT), with or without cytotoxic chemotherapy, is now recommended for most patients with advanced non-small cell lung cancer (NSCLC) with no targetable mutations. We reviewed outcomes for NSCLC patients treated with first-line IMT at our institution to test the hypothesis that measures of disease burden on staging FDG-PET/CT have prognostic value. MATERIALS AND METHODS: Patient, disease, and treatment details were collected. A gradient-based segmentation tool was used to delineate each PET-avid extracranial lesion. Numbers of extrathoracic lesions and metabolic tumor volumes were tabulated. Oligometastatic disease (OMD) was defined as having ≤3 extrathoracic lesions, with any number of thoracic lesions. Progression-free survival (PFS) and overall survival (OS) rates following initiation of IMT were evaluated using the Kaplan-Meier method, and predictors of PFS and OS were assessed using Cox proportional hazards models and logrank tests. RESULTS: One hundred twenty-four patients met inclusion criteria, and 1143 lesions were contoured. The presence of OMD was associated with favorable PFS (median 13.1 vs. 6.9 months; P = .016) and favorable OS (median 36.5 vs. 15.4 months; P = .002). In multivariable models, OMD was associated with favorable PFS (HR = 0.64; P = .034) and favorable OS (HR = 0.61; P = .063), and metabolic tumor volumes exceeding the cohort median (88 cc) was associated with inferior OS (HR = 1.85; P = .028). CONCLUSION: For advanced NSCLC patients receiving first-line IMT, the presence of extrathoracic OMD and low volumetric disease burden on PET are favorable prognostic factors that could be useful stratification factors in clinical trials and may influence clinical decisions about local and systemic therapy.

IAEA-AAPM TRS-483-based reference dosimetry of the new RefleXion biology-guided radiotherapy (BgRT) machine.

PURPOSE: The purpose of this study is to provide data for the calibration of the recent RefleXion TM biology-guided radiotherapy (BgRT) machine (Hayward, CA, USA) following the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) TRS-483 code of practice (COP) (Palmans et al. International Atomic Energy Agency, Vienna, 2017) and (Mirzakhanian et al. Med Phys, 2020). METHODS: In RefleXion BgRT machine, reference dosimetry was performed using two methodologies described in TRS-483 and (Mirzakhanian et al. Med Phys, 2020) In the first approach (Approach 1), the generic beam quality correction factor k Q A , Q 0 f A , f ref was calculated using an accurate Monte Carlo (MC) model of the beam and of six ionization chamber types. The k Q A , Q 0 f A , f ref is a beam quality factor that corrects N D , w , Q 0 f ref (absorbed dose to water calibration coefficient in a calibration beam quality Q 0 ) for the differences between the response of the chamber in the conventional reference calibration field f ref with beam quality Q 0 at the standards laboratory and the response of the chamber in the user's A field f A with beam quality Q A . Field A represents the reference calibration field that does not fulfill msr conditions. In the second approach (Approach 2), a square equivalent field size was determined for field A of 10 × 2 cm 2 and 10 × 3 cm 2 . Knowing the equivalent field size, the beam quality specifier for the hypothetical 10 × 10 cm 2 field size was derived. This was used to calculate the beam quality correction factor analytically for the six chamber types using the TRS-398. (Andreo et al. Int Atom Energy Agency 420, 2001) Here, TRS-398 was used instead of TRS-483 since the beam quality correction values for the chambers used in this study are not tabulated in TRS-483. The accuracy of Approach 2 is studied in comparison to Approach 1. RESULTS: Among the chambers, the PTW 31010 had the largest k Q A , Q 0 f A , f ref correction due to the volume averaging effect. The smallest-volume chamber (IBA CC01) had the smallest correction followed by the other microchambers Exradin-A14 and -A14SL. The equivalent square fields sizes were found to be 3.6 cm and 4.8 cm for the 10 × 2 cm 2 and 10 × 3 cm 2 field sizes, respectively. The beam quality correction factors calculated using the two approaches were within 0.27% for all chambers except IBA CC01. The latter chamber has an electrode made of steel and the differences between the correction calculated using the two approaches was the largest, that is, 0.5%. CONCLUSIONS: In this study, we provided the k Q A , Q 0 f A , f ref values as a function of the beam quality specifier at the RefleXion BgRT setup ( TPR 20 , 10 ( S ) and % d d ( 10 , S ) x ) for six chamber types. We suggest using the first approach for calibration of the RefleXion BgRT machine. However, if the MC correction is not available for a user's detector, the user can use the second approach for estimating the beam quality correction factor to sufficient accuracy (0.3%) provided the chamber electrode is not made of high Z material.

Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer.

The emerging biological understanding of metastatic cancer and proof-of-concept clinical trials suggest that debulking all gross disease holds great promise for improving patient outcomes. However, ablation of multiple targets with conventional external beam radiotherapy systems is burdensome, which limits investigation and utilization of complete metastatic ablation in the majority of patients with advanced disease. To overcome this logistical hurdle, technical innovation is necessary. Biology-guided radiotherapy (BgRT) is a new external beam radiotherapy delivery modality combining positron emission tomography-computed tomography (PET-CT) with a 6 MV linear accelerator. The key innovation is continuous response of the linear accelerator to outgoing tumor PET emissions with beamlets of radiotherapy at subsecond latency. This allows the deposited dose to track tumors in real time. Multiple new hardware and algorithmic advances further facilitate this low-latency feedback process. By transforming tumors into their own fiducials after intravenous injection of a radiotracer, BgRT has the potential to enable complete metastatic ablation in a manner efficient for a single patient and scalable to entire populations with metastatic disease. Future trends may further enhance the utility of BgRT in the clinic as this technology dovetails with other innovations in radiotherapy, including novel dose painting and fractionation schemes, radiomics, and new radiotracers.

Extending the IAEA-AAPM TRS-483 methodology for radiation therapy machines with field sizes down to 10 × 2 cm2.

PURPOSE: The purpose of this study is to provide a calibration methodology for radiation therapy machines where the closest field to the conventional reference field may not meet the lateral charged particle equilibrium (LCPE) condition of the machine-specific reference (msr) field. We provided two methodologies by extending the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) TRS-483 code of practice (COP) (Palmans et al. TRS-483: Dosimetry of small static fields used in external beam radiotherapy: an international code of practice for reference and relative dose determination; 2017) methodology for the calibration of radiation therapy machines with 6 MV flattening filter free (FFF) beam and with field sizes down to 10 ×  2 cm2 . METHODS: Two methods of calibration were provided following the TRS-483. In calibration Method I, the generic correction factors k Q A , Q 0 f A , f ref were calculated using Monte Carlo (MC) for seven detectors and rectangular physical field sizes ranging from 10 × 2 cm2 to 10 × 10 cm2 . In calibration Method II, we extended the methodology in TRS-483 for deriving the equivalent square msr field sizes for rectangular field sizes down to 10 × 2 cm2 . The beam quality specifier for a hypothetical 10 × 10 cm2 field was derived by extending the methodology provided in the TRS-483. Since the beam quality correction values for the conventional reference field ( k Q , Q 0 f ref ) tabulated in TRS-483 are provided only for large reference chambers, we calculated the k Q , Q 0 f ref values analytically for our beam quality specifier and chambers used, using interaction data in TRS-398 (Andreo, et al. TRS-398: Absorbed dose determination in external beam radiotherapy: an international code of practice for dosimetry based on standards of absorbed dose to water; 2001). RESULTS: The k Q A , Q 0 f A , f ref correction values calculated using the first method for chambers with an electrode made of C552 almost did not vary across the different field sizes studied (within 0.1%) while it varied by 1.6% for IBA CC01 with electrode made of steel. Extending the equivalent field and beam quality specifier determination methodology of TRS-483 resulted in a maximum error of 1.3% on the beam quality specifier for the 2 × 2 cm2 field size. However, this had a negligible impact on the k Q A , Q 0 f A , f ref values (less than 0.1%). For chambers with C552 and Al electrode material, the correction factors determined using the two methods of calibration were in agreement to within 0.5%. However, for the chambers with electrode made of higher atomic number (Z), the difference between the two methodologies could be as large as 1.5%. It was shown that this difference can be reduced to less than 0.5% if central electrode perturbation effects and k Q A FFF , Q FFF f A , f ref values introduced in TRS-483 were taken into account. CONCLUSIONS: In this study, applying the k Q A , Q 0 f A , f ref correction values calculated using the calibration Method I to the chamber reading improved the consistency on an absorbed dose determination from 0.5% to 0.1% standard deviation (except for the Exradin A16). For this reason we recommend using calibration Method I. If the k Q A , Q 0 f A , f ref values are not available for the user's detector, calibration Method II can be used to predict the correction factors. However, the second methodology should not be used for chambers with electrode made of high-Z material unless the electrode perturbation effects and k Q A FFF , Q FFF f A , f ref values are taken into account.

Clinical commissioning and use of the Novalis Tx linear accelerator for SRS and SBRT.

The purpose of this study was to perform comprehensive measurements and testing of a Novalis Tx linear accelerator, and to develop technical guidelines for com-missioning from the time of acceptance testing to the first clinical treatment. The Novalis Tx (NTX) linear accelerator is equipped with, among other features, a high-definition MLC (HD120 MLC) with 2.5 mm central leaves, a 6D robotic couch, an optical guidance positioning system, as well as X-ray-based image guidance tools to provide high accuracy radiation delivery for stereotactic radiosurgery and stereotactic body radiation therapy procedures. We have performed extensive tests for each of the components, and analyzed the clinical data collected in our clinic. We present technical guidelines in this report focusing on methods for: (1) efficient and accurate beam data collection for commissioning treatment planning systems, including small field output measurements conducted using a wide range of detectors; (2) commissioning tests for the HD120 MLC; (3) data collection for the baseline characteristics of the on-board imager (OBI) and ExacTrac X-ray (ETX) image guidance systems in conjunction with the 6D robotic couch; and (4) end-to-end testing of the entire clinical process. Established from our clinical experience thus far, recommendations are provided for accurate and efficient use of the OBI and ETX localization systems for intra- and extracranial treatment sites. Four results are presented. (1) Basic beam data measurements: Our measurements confirmed the necessity of using small detectors for small fields. Total scatter factors varied significantly (30% to approximately 62%) for small field measurements among detectors. Unshielded stereotactic field diode (SFD) overestimated dose by ~ 2% for large field sizes. Ion chambers with active diameters of 6 mm suffered from significant volume averaging. The sharpest profile penumbra was observed for the SFD because of its small active diameter (0.6 mm). (2) MLC commissioning: Winston Lutz test, light/radiation field congruence, and Picket Fence tests were performed and were within criteria established by the relevant task group reports. The measured mean MLC transmission and dynamic leaf gap of 6 MV SRS beam were 1.17% and 0.36 mm, respectively. (3) Baseline characteristics of OBI and ETX: The isocenter localization errors in the left/right, posterior/anterior, and superior/inferior directions were, respectively, -0.2 ± 0.2 mm, -0.8 ± 0.2 mm, and -0.8 ± 0.4 mm for ETX, and 0.5 ± 0.7 mm, 0.6 ± 0.5 mm, and 0.0 ± 0.5 mm for OBI cone-beam computed tomography. The registration angular discrepancy was 0.1 ± 0.2°, and the maximum robotic couch error was 0.2°. (4) End-to-end tests: The measured isocenter dose differences from the planned values were 0.8% and 0.4%, measured respectively by an ion chamber and film. The gamma pass rate, measured by EBT2 film, was 95% (3% DD and 1 mm DTA). Through a systematic series of quantitative commissioning experiments and end-to-end tests and our initial clinical experience, described in this report, we demonstrate that the NTX is a robust system, with the image guidance and MLC requirements to treat a wide variety of sites - in particular for highly accurate delivery of SRS and SBRT-based treatments.

Impact of collimator leaf width and treatment technique on stereotactic radiosurgery and radiotherapy plans for intra- and extracranial lesions.

BACKGROUND: This study evaluated the dosimetric impact of various treatment techniques as well as collimator leaf width (2.5 vs 5 mm) for three groups of tumors -- spine tumors, brain tumors abutting the brainstem, and liver tumors. These lesions often present challenges in maximizing dose to target volumes without exceeding critical organ tolerance. Specifically, this study evaluated the dosimetric benefits of various techniques and collimator leaf sizes as a function of lesion size and shape. METHODS: Fifteen cases (5 for each site) were studied retrospectively. All lesions either abutted or were an integral part of critical structures (brainstem, liver or spinal cord). For brain and liver lesions, treatment plans using a 3D-conformal static technique (3D), dynamic conformal arcs (DARC) or intensity modulation (IMRT) were designed with a conventional linear accelerator with standard 5 mm leaf width multi-leaf collimator, and a linear accelerator dedicated for radiosurgery and hypofractionated therapy with a 2.5 mm leaf width collimator. For the concave spine lesions, intensity modulation was required to provide adequate conformality; hence, only IMRT plans were evaluated using either the standard or small leaf-width collimators.A total of 70 treatment plans were generated and each plan was individually optimized according to the technique employed. The Generalized Estimating Equation (GEE) was used to separate the impact of treatment technique from the MLC system on plan outcome, and t-tests were performed to evaluate statistical differences in target coverage and organ sparing between plans. RESULTS: The lesions ranged in size from 2.6 to 12.5 cc, 17.5 to 153 cc, and 20.9 to 87.7 cc for the brain, liver, and spine groups, respectively. As a group, brain lesions were smaller than spine and liver lesions. While brain and liver lesions were primarily ellipsoidal, spine lesions were more complex in shape, as they were all concave. Therefore, the brain and the liver groups were compared for volume effect, and the liver and spine groups were compared for shape. For the brain and liver groups, both the radiosurgery MLC and the IMRT technique contributed to the dose sparing of organs-at-risk(OARs), as dose in the high-dose regions of these OARs was reduced up to 15%, compared to the non-IMRT techniques employing a 5 mm leaf-width collimator. Also, the dose reduction contributed by the fine leaf-width MLC decreased, as dose savings at all levels diminished from 4 - 11% for the brain group to 1 - 5% for the liver group, as the target structures decreased in volume. The fine leaf-width collimator significantly improved spinal cord sparing, with dose reductions of 14 - 19% in high to middle dose regions, compared to the 5 mm leaf width collimator. CONCLUSION: The fine leaf-width MLC in combination with the IMRT technique can yield dosimetric benefits in radiosurgery and hypofractionated radiotherapy. Treatment of small lesions in cases involving complex target/OAR geometry will especially benefit from use of a fine leaf-width MLC and the use of IMRT.

Trilogy image-guided stereotactic radiosurgery.

Full integration of advanced imaging, noninvasive immobilization, positioning, and motion-management methods into radiosurgery have resulted in fundamental changes in therapeutic strategies and approaches that are leading us to the treatment room of the future. With the introduction of image-guided radiosurgery (IGRS) systems, such as Trilogy, physicians have for the first time a practical means of routinely identifying and treating very small lesions throughout the body. Using new imaging processes such as positron emission tomography/computed tomography (PET/CT) scans, clinics may be able to detect these lesions and then eradicate them with image-guided stereotactic radiosurgery treatments. Thus, there is promise that cancer could be turned into a chronic disease, managed through a series of checkups, and Trilogy treatments when metastatic lesions reappear.

Dynamic targeting image-guided radiotherapy.

Volumetric imaging and planning for 3-dimensional (3D) conformal radiotherapy and intensity-modulated radiotherapy (IMRT) have highlighted the need to the oncology community to better understand the geometric uncertainties inherent in the radiotherapy delivery process, including setup error (interfraction) as well as organ motion during treatment (intrafraction). This has ushered in the development of emerging technologies and clinical processes, collectively referred to as image-guided radiotherapy (IGRT). The goal of IGRT is to provide the tools needed to manage both inter- and intrafraction motion to improve the accuracy of treatment delivery. Like IMRT, IGRT is a process involving all steps in the radiotherapy treatment process, including patient immobilization, computed tomography (CT) simulation, treatment planning, plan verification, patient setup verification and correction, delivery, and quality assurance. The technology and capability of the Dynamic Targeting IGRT system developed by Varian Medical Systems is presented. The core of this system is a Clinac or Trilogy accelerator equipped with a gantry-mounted imaging system known as the On-Board Imager (OBI). This includes a kilovoltage (kV) x-ray source, an amorphous silicon kV digital image detector, and 2 robotic arms that independently position the kV source and imager orthogonal to the treatment beam. A similar robotic arm positions the PortalVision megavoltage (MV) portal digital image detector, allowing both to be used in concert. The system is designed to support a variety of imaging modalities. The following applications and how they fit in the overall clinical process are described: kV and MV planar radiographic imaging for patient repositioning, kV volumetric cone beam CT imaging for patient repositioning, and kV planar fluoroscopic imaging for gating verification. Achieving image-guided motion management throughout the radiation oncology process requires not just a single product, but a suite of integrated products to manipulate all patient data, including images, efficiently and effectively.

Performance evaluation of an automated image registration algorithm using an integrated kilovoltage imaging and guidance system.

Image-guided radiation therapy delivery may be used to assess the position of the tumor and anatomical structures within the body as opposed to relying on external marks. The purpose of this manuscript is to evaluate the performance of the image registration software for automatically detecting and repositioning a 3D offset of a phantom using a kilovoltage onboard imaging system. Verification tests were performed on both a geometric rigid phantom and an anthropomorphic head phantom containing a humanoid skeleton to assess the precision and accuracy of the automated positioning system. From the translation only studies, the average deviation between the detected and known offset was less than 0.75 mm for each of the three principal directions, and the shifts did not show any directional sensitivity. The results are given as the measurement with standard deviation in parentheses. The combined translations and rotations had the greatest average deviation in the lateral, longitudinal, and vertical directions. For all dimensions, the magnitude of the deviation does not appear to be correlated with the magnitude of the actual translation introduced. The On-Board Imager (OBI) system has been successfully integrated into a feasible online radiotherapy treatment guidance procedure. Evaluation of each patient's resulting automatch should be performed by therapists before each treatment session for adequate clinical oversight.

Exploring the limits of spatial resolution in radiation dose delivery.

Flexibility and complexity in patient treatment due to advances in radiotherapy techniques necessitates a simple method for evaluating spatial resolution capabilities of the dose delivery device. Our purpose in this investigation is to evaluate a model that describes the ability of a radiation therapy device to deliver a desired dose distribution. The model is based on linear systems theory and is analogous to methods used to describe resolution degradation in imaging systems. A qualitative analysis of spatial resolution degradation using the model is presented in the spatial and spatial frequency domains. The ability of the model to predict the effects of geometric dose conformity to treatment volumes is evaluated by varying multileaf collimator leaf width and magnitude of dose spreading. Dose distributions for three clinical treatment shapes, circular shapes of varying diameter and one intensity modulated shape are used in the evaluation. We show that the model accurately predicts the dependence of dose conformity on these parameters. The spatial resolution capabilities of different radiation therapy devices can be quantified using the model, providing a simple method for comparing different treatment machine characteristics. Also, as different treatment sites have different resolution requirements this model may be used to tailor machine characteristics to the specific site.