A comparison of two methodologies for radiotherapy treatment plan optimization and QA for clinical trials.

BACKGROUND AND PURPOSE: The efficacy of clinical trials and the outcome of patient treatment are dependent on the quality assurance (QA) of radiation therapy (RT) plans. There are two widely utilized approaches that include plan optimization guidance created based on patient-specific anatomy. This study examined these two techniques for dose-volume histogram predictions, RT plan optimizations, and prospective QA processes, namely the knowledge-based planning (KBP) technique and another first principle (FP) technique. METHODS: This analysis included 60, 44, and 10 RT plans from three Radiation Therapy Oncology Group (RTOG) multi-institutional trials: RTOG 0631 (Spine SRS), RTOG 1308 (NSCLC), and RTOG 0522 (H&N), respectively. Both approaches were compared in terms of dose prediction and plan optimization. The dose predictions were also compared to the original plan submitted to the trials for the QA procedure. RESULTS: For the RTOG 0631 (Spine SRS) and RTOG 0522 (H&N) plans, the dose predictions from both techniques have correlation coefficients of >0.9. The RT plans that were re-optimized based on the predictions from both techniques showed similar quality, with no statistically significant differences in target coverage or organ-at-risk sparing. The predictions of mean lung and heart doses from both methods for RTOG1308 patients, on the other hand, have a discrepancy of up to 14 Gy. CONCLUSIONS: Both methods are valuable tools for optimization guidance of RT plans for Spine SRS and Head and Neck cases, as well as for QA purposes. On the other hand, the findings suggest that KBP may be more feasible in the case of inoperable lung cancer patients who are treated with IMRT plans that have spatially unevenly distributed beam angles.

A unified multi-activation (UMA) model of cell survival curves over the entire dose range for calculating equivalent doses in stereotactic body radiation therapy (SBRT), high dose rate brachytherapy (HDRB), and stereotactic radiosurgery (SRS).

PURPOSE: Application of linear-quadratic (LQ) model to large fractional dose treatments is inconsistent with observed cell survival curves having a straight portion at high doses. We have proposed a unified multi-activation (UMA) model to fit cell survival curves over the entire dose range that allows us to calculate EQD2 for hypofractionated SBRT, SRT, SRS, and HDRB. METHODS: A unified formula of cell survival S = n / e D D o + n - 1 using only the extrapolation number of n and the dose slope of Do was derived. Coefficient of determination, R2 , relative residuals, r, and relative experimental errors, e, normalized to survival fraction at each dose point, were calculated to quantify the goodness in modeling of a survival curve. Analytical solutions for α and ß, the coefficients respectively describe the linear and quadratic parts of the survival curve, as well as the α/ß ratio for the LQ model and EQD2 at any fractional doses were derived for tumor cells undertaking any fractionated radiation therapy. RESULTS: Our proposed model fits survival curves of in-vivo and in-vitro tumor cells with R2  > 0.97 and r < e. The predicted α, ß, and α/ß ratio are significantly different from their values in the LQ model. Average EQD2 of 20-Gy SRS of glioblastomas and melanomas metastatic to the brain, 10-Gy × 5 SBRT of the lung cancer, and 7-Gy × 5 HDRB of endometrial and cervical carcinomas are 36.7 (24.3-48.5), 114.1 (86.6-173.1),, and 45.5 (35-52.6) Gy, different from the LQ model estimates of 50.0, 90.0, and 49.6 Gy, respectively. CONCLUSION: Our UMA model validated through many tumor cell lines can fit cell survival curves over the entire dose range within their experimental errors. The unified formula theoretically indicates a common mechanism of cell inactivation and can estimate EQD2 at all dose levels.

Offline Quality Assurance for Intensity Modulated Radiation Therapy Treatment Plans for NRG-HN001 Head and Neck Clinical Trial Using Knowledge-Based Planning.

PURPOSE: This study aimed to investigate whether a disease site-specific, multi-institutional knowledge based-planning (KBP) model can improve the quality of intensity modulated radiation therapy treatment planning for patients enrolled in the head and neck NRG-HN001clinical trial and to establish a threshold of improvements of treatment plans submitted to the clinical trial. METHODS AND MATERIALS: Fifty treatment plans for patients enrolled in the NRG-HN001 clinical trial were used to build a KBP model; the model was then used to reoptimize 50 other plans. We compared the dosimetric parameters of the submitted and KBP reoptimized plans. We compared differences between KBP and submitted plans for single- and multi-institutional treatment plans. RESULTS: Mean values for the dose received by 95% of the planning target volume (PTV_6996) and for the maximum dose (D0.03cc) of PTV_6996 were 0.5 Gy and 2.1 Gy higher in KBP plans than in the submitted plans, respectively. Mean values for D0.03cc to the brain stem, spinal cord, optic nerve_R, optic nerve_L, and chiasm were 2.5 Gy, 1.9 Gy, 6.4 Gy, 6.6 Gy, and 5.7 Gy lower in the KBP plans than in the submitted plans. Mean values for Dmean to parotid_R and parotid_L glands were 2.2 Gy and 3.8 Gy lower in KBP plans, respectively. In 33 out of 50 KBP plans, we observed improvements in sparing of at least 7 organs at risk (OARs) (brain stem, spinal cord, optic nerves (R & L), chiasm, and parotid glands [R & L]). A threshold of improvement of OARs sparing of 5% of the prescription dose was established for providing the quality assurance results back to the treating institution. CONCLUSIONS: A disease site-specific, multi-institutional, clinical trial-based KBP model improved sparing of OARs in a large number of reoptimized plans submitted to the NRG-HN001 clinical trial, and the model is being used as an offline quality assurance tool.

Motion management strategies and technical issues associated with stereotactic body radiotherapy of thoracic and upper abdominal tumors: A review from NRG oncology.

The efficacy of stereotactic body radiotherapy (SBRT) has been well demonstrated. However, it presents unique challenges for accurate planning and delivery especially in the lungs and upper abdomen where respiratory motion can be significantly confounding accurate targeting and avoidance of normal tissues. In this paper, we review the current literature on SBRT for lung and upper abdominal tumors with particular emphasis on addressing respiratory motion and its affects. We provide recommendations on strategies to manage motion for different, patient-specific situations. Some of the recommendations will potentially be adopted to guide clinical trial protocols.

Establishing the feasibility of the dosimetric compliance criteria of RTOG 1308: phase III randomized trial comparing overall survival after photon versus proton radiochemotherapy for inoperable stage II-IIIB NSCLC.

BACKGROUND: To establish the feasibility of the dosimetric compliance criteria of the RTOG 1308 trial through testing against Intensity Modulation Radiation Therapy (IMRT) and Passive Scattering Proton Therapy (PSPT) plans. METHODS: Twenty-six lung IMRT and 26 proton PSPT plans were included in the study. Dose Volume Histograms (DVHs) for targets and normal structures were analyzed. The quality of IMRT plans was assessed using a knowledge-based engineering tool. RESULTS: Most of the RTOG 1308 dosimetric criteria were achieved. The deviation unacceptable rates were less than 10 % for most criteria; however, a deviation unacceptable rate of more than 20 % was computed for the planning target volume minimum dose compliance criterion. Dose parameters for the target volume were very close for the IMRT and PSPT plans. However, the PSPT plans led to lower dose values for normal structures. The dose parameters in which PSPT plans resulted in lower values than IMRT plans were: lung V5Gy (%) (34.4 in PSPT and 47.2 in IMRT); maximum spinal cord dose (31.7 Gy in PSPT and 43.5 Gy in IMRT); heart V5Gy (%) (19 in PSPT and 47 in IMRT); heart V30Gy (%) (11 in PSPT and 19 in IMRT); heart V45Gy (%) (7.8 in PSPT and 12.1 in IMRT); heart V50% (Gy) (7.1 in PSPT and 9.8 in IMRT) and mean heart dose (7.7 Gy in PSPT and 14.9 Gy in IMRT). CONCLUSIONS: The revised RTOG 1308 dosimetric compliance criteria are feasible and achievable.

Structures' validation profiles in Transmission of Imaging and Data (TRIAD) for automated National Clinical Trials Network (NCTN) clinical trial digital data quality assurance.

Transmission of Imaging and Data (TRIAD) is a standard-based system built by the American College of Radiology to provide the seamless exchange of images and data for accreditation of clinical trials and registries. Scripts of structures' names validation profiles created in TRIAD are used in the automated submission process. It is essential for users to understand the logistics of these scripts for successful submission of radiation therapy cases with less iteration.

Investigation into image quality and dose for different patient geometries with multiple cone-beam CT systems.

PURPOSE: To provide quantitative and qualitative image quality metrics and imaging dose for modern Varian On-board Imager (OBI) (ver. 1.5) and Elekta X-ray Volume Imager (XVI) (ver. 4.5R) cone-beam computed tomography (CBCT) systems in a clinical adaptive radiation therapy environment by accounting for varying patient thickness. METHODS: Image quality measurements were acquired with Catphan 504 phantom (nominal diameter and with additional 10 cm thickness) for OBI and XVI systems and compared to planning CT (pCT) (GE LightSpeed). Various clinical protocols were analyzed for the OBI and XVI systems and analyzed using image quality metrics, including spatial resolution, low contrast detectability, uniformity, and HU sensitivity. Imaging dose measurements were acquired in Wellhofer Scanditronix i'mRT phantom at nominal phantom diameter and with additional 4 cm phantom diameter using GafChromic XRQA2 film. Calibration curves were generated using previously published in-air Air Kerma calibration method. RESULTS: The OBI system full trajectory scans exhibited very little dependence on phantom thickness for accurate HU calculation, while half-trajectory scans with full-fan filter exhibited dependence of HU calculation on phantom thickness. The contrast-to-noise ratio (CNR) for the OBI scans decreased with additional phantom thickness. The uniformity of Head protocol scan was most significantly affected with additional phantom thickness. The spatial resolution and CNR compared favorably with pCT, while the uniformity of the OBI system was slightly inferior to pCT. The OBI scan protocol dose levels for nominal phantom thickness at the central portion of the phantom were 2.61, 0.72, and 1.88 cGy, and for additional phantom thickness were 1.95, 0.48, and 1.52 cGy, for the Pelvis, Thorax, and Spotlight protocols, respectively. The XVI system scans exhibited dependence on phantom thickness for accurate HU calculation regardless of trajectory. The CNR for the XVI scans decreased with additional phantom thickness. The uniformity of the XVI scans was significantly dependent on the selection of the proper FOV setting for all phantom geometries. The spatial resolution, CNR, and uniformity for XVI were lower than values measured for pCT. The XVI scan protocol dose levels at the central portion of the phantom for nominal phantom thickness were 2.14, 2.15, and 0.33 cGy, and for additional phantom thickness were 1.56, 1.68, and 0.21 cGy, for the Pelvis M20, Chest M20, and Prostate Seed S10 scan protocols, respectively. CONCLUSIONS: The OBI system offered comparable spatial resolution and CNR results to the results for pCT. Full trajectory scans with the OBI system need little-to-no correction for HU calculation based on HU stability with changing phantom thickness. The XVI system offered lower spatial resolution and CNR results than pCT. In addition, the HU calculation for all scan protocols was dependent on the phantom thickness. The uniformity for each CBCT system was inferior to that of pCT for each phantom geometry. The dose for each system and scan protocol in the interior of the phantom tended to decrease by approximately 25% with 4 cm additional phantom thickness.

Comparative dose evaluations between XVI and OBI cone beam CT systems using Gafchromic XRQA2 film and nanoDot optical stimulated luminescence dosimeters.

PURPOSE: To investigate the effect of energy (kVp) and filters (no filter, half Bowtie, and full Bowtie) on the dose response curves of the Gafchromic XRQA2 film and nanoDot optical stimulated luminescence dosimeters (OSLDs) in CBCT dose fields. To measure surface and internal doses received during x-ray volume imager (XVI) (Version R4.5) and on board imager (OBI) (Version 1.5) CBCT imaging protocols using these two types of dosimeters. METHODS: Gafchromic XRQA2 film and nanoDot OSLD dose response curves were generated at different kV imaging settings used by XVI (software version R4.5) and OBI (software version 1.5) CBCT systems. The settings for the XVI system were: 100 kVp∕F0 (no filter), 120 kVp∕F0, and 120 kVp∕F1 (Bowtie filter), and for the OBI system were: 100 kVp∕full fan, 125 kVp∕full fan, and 125 kVp∕half fan. XRQA2 film was calibrated in air to air kerma levels between 0 and 11 cGy and scanned using reflection scanning mode with the Epson Expression 10000 XL flat-bed document scanner. NanoDot OSLDs were calibrated on phantom to surface dose levels between 0 and 14 cGy and read using the inLight(TM) MicroStar reader. Both dosimeters were used to measure in field surface and internal doses in a male Alderson Rando Phantom. RESULTS: Dose response curves of XRQA2 film and nanoDot OSLDs at different XVI and OBI CBCT settings were reported. For XVI system, the surface dose ranged between 0.02 cGy in head region during fast head and neck scan and 4.99 cGy in the chest region during symmetry scan. On the other hand, the internal dose ranged between 0.02 cGy in the head region during fast head and neck scan and 3.17 cGy in the chest region during chest M20 scan. The average (internal and external) dose ranged between 0.05 cGy in the head region during fast head and neck scan and 2.41 cGy in the chest region during chest M20 scan. For OBI system, the surface dose ranged between 0.19 cGy in head region during head scan and 4.55 cGy in the pelvis region during spot light scan. However, the internal dose ranged between 0.47 cGy in the head region during head scan and 5.55 cGy in the pelvis region during spot light scan. The average (internal and external) dose ranged between 0.45 cGy in the head region during head scan and 3.59 cGy in the pelvis region during spot light scan. Both Gafchromic XRQA2 film and nanoDot OSLDs gave close estimation of dose (within uncertainties) in many cases. Though, discrepancies of up to 20%-30% were observed in some cases. CONCLUSIONS: Dose response curves of Gafchromic XRQA2 film and nanoDot OSLDs indicated that the dose responses of these two dosimeters were different even at the same photon energy when different filters were used. Uncertainty levels of both dosimetry systems were below 6% at doses above 1 cGy. Both dosimetry systems gave almost similar estimation of doses (within uncertainties) in many cases, with exceptions of some cases when the discrepancy was around 20%-30%. New versions of the CBCT systems (investigated in this study) resulted in lower imaging doses compared with doses reported on earlier versions in previous studies.

Characteristics of Gafchromic XRQA2 films for kV image dose measurement.

PURPOSE: In this study, the relevant characteristics of the new Gafchromic XRQA2 film for its application in measuring kV cone beam computed tomography (CBCT) image doses were thoroughly investigated. METHODS: The film was calibrated free in air to air kerma levels between 0 and 9 cGy using 120 kVp photon beams produced by the x-ray volume imager. Films were scanned using transmission and reflection scanning modes with the Epson Expression 10000 XL flat-bed document scanner. The impact of film size, region of interest for the analysis, scan uniformity, scan resolution, scan orientation and alternate scanning sides on the analysis process were investigated. Energy dependence, postirradiation growth of reflectance with time and irradiation angular dependence of the film were tested at different air kerma levels. RESULTS: The net reflectance changed by ∼3% when the size of the film piece changed from 1 cm × 2 cm to 10 cm × 11 cm and changed by ∼1% when ROI changed from 0. 7 cm × 0. 7 cm to 8 cm × 8 cm, suggesting a good uniformity of the film. The film was successfully analyzed using the transmission scanning mode, calibration curves from both transmission and reflection scanning modes showed similar behavior. The calibration uncertainty was somewhat lower when the film was scanned using reflection mode (6% and 8% for reflection and transmission modes, respectively.) Higher scanning resolution came with increasing calibration uncertainty. The calibration uncertainty for reflection and transmission modes increased from ∼3.5% to 7% and from ∼3.5% to 9%, respectively when scanning resolution was changed from 50 to 400 dpi. Scanning the film on alternate sides using transmission mode led to variation of 16%-19% in the net optical density at doses commonly used for CBCT procedures. The film response changed by almost 10% when it was exposed to beams of two different energies (100 and 120 kVp.) Other features of the film such as film orientation, postexposure growth, and irradiation angular dependence were also investigated. CONCLUSIONS: The size of film piece and analysis ROI used for calibration slightly affected the film response. Both transmission and reflection scanning modes can be used to analyze the Gafchromic XRQA2, with the reflection mode having a somewhat lower calibration uncertainty. Scanning films on alternate sides using transmission mode significantly affects the optical density. The film response was shown to be energy dependent. The films reached stability in about 6 h after exposure. The film response was proven to be independent of irradiation angle except when the beam is parallel to the film surface.