Evaluation of tumour motion and internal/external correlation in lung SABR.

OBJECTIVE: This study aims to analyse lung tumour motion and to investigate the correlation between the internal tumour motion acquired from four-dimensional computed tomography (4DCT) and the motion of an external surrogate. METHODS: A data set of 363 4DCT images was analysed. Tumours were classified based on their anatomical lobes. The recorded gross tumour volume (GTV) information included the centroid GTV motion in the superior-inferior, anteroposterior and left-right directions, and in three-dimensions (3D). For the internal/external correlation, the RPM surrogate breathing signals of 260 patients were analysed via an in-house script. The external motion was correlated with the 3D centroid motion, and the maximum tumour motion via Spearman's correlation. The effect of tumour volume on the amount of motion was evaluated. RESULTS: The greatest 3D tumour amplitude was found for tumours located in the lower part of the lung, with a maximum of 26.7 mm. The Spearman's correlation of the internal 3D motion was weak in the upper (r = 0.21) and moderate in the middle (r = 0.51) and the lower (r = 0.52) lobes. There was no obvious difference in the correlation coefficients between the maximum tumour displacement and the centroid motion. No correlation was found between the tumour volume and the magnitude of motion. CONCLUSION: Our results suggest that tumour location can be a good predictor of its motion. However, tumour size is a poor predictor of the motion. ADVANCES IN KNOWLEDGE: This knowledge of the distribution of tumour motion throughout the thoracic regions will be valuable to research groups investigating the refinement of motion management strategies.

A Randomized Feasibility Trial of Stereotactic Prostate Radiation Therapy With or Without Elective Nodal Irradiation in High-Risk Localized Prostate Cancer (SPORT Trial).

PURPOSE: The aim of this study was to establish the feasibility of a randomized clinical trial comparing SABR with prostate-only (P-SABR) or with prostate plus pelvic lymph nodes (PPN-SABR) in patients with unfavorable intermediate- or high-risk localized prostate cancer and to explore potential toxicity biomarkers. METHODS AND MATERIALS: Thirty adult men with at least 1 of the following features were randomized 1:1 to P-SABR or PPN-SABR: clinical magnetic resonance imaging stage T3a N0 M0, Gleason score ≥7 (4+3), and prostate-specific antigen >20 ng/mL. P-SABR patients received 36.25 Gy/5 fractions/29 days, and PPN-SABR patients received 25 Gy/5 fractions to pelvic nodes, with the final cohort receiving a boost to the dominant intraprostatic lesion of 45 to 50 Gy. Phosphorylated gamma-H2AX (γH2AX) foci numbers, citrulline levels, and circulating lymphocyte counts were quantified. Acute toxicity information (Common Terminology Criteria for Adverse Events, version 4.03) was collected weekly at each treatment and at 6 weeks and 3 months. Physician-reported late Radiation Therapy Oncology Group (RTOG) toxicity was recorded from 90 days to 36 months postcompletion of SABR. Patient-reported quality of life (Expanded Prostate Cancer Index Composite and International Prostate Symptom Score) scores were recorded with each toxicity time point. RESULTS: The target recruitment was achieved, and treatment was successfully delivered in all patients. A total of 0% and 6.7% (P-SABR) and 6.7% and 20.0% (PPN-SABR) experienced acute grade ≥2 gastrointestinal (GI) and genitourinary (GU) toxicity, respectively. At 3 years, 6.7% and 6.7% (P-SABR) and 13.3% and 33.3% (PPN-SABR) had experienced late grade ≥2 GI and GU toxicity, respectively. One patient (PPN-SABR) had late grade 3 GU toxicity (cystitis and hematuria). No other grade ≥3 toxicity was observed. In addition, 33.3% and 60% (P-SABR) and 64.3% and 92.9% (PPN-SABR) experienced a minimally clinically important change in late Expanded Prostate Cancer Index Composite bowel and urinary summary scores, respectively. γH2AX foci numbers at 1 hour after the first fraction were significantly higher in the PPN-SABR arm compared with the P-SABR arm (P = .04). Patients with late grade ≥1 GI toxicity had significantly greater falls in circulating lymphocytes (12 weeks post-radiation therapy, P = .01) and a trend toward higher γH2AX foci numbers (P = .09) than patients with no late toxicity. Patients with late grade ≥1 bowel toxicity and late diarrhea experienced greater falls in citrulline levels (P = .05). CONCLUSIONS: A randomized trial comparing P-SABR with PPN-SABR is feasible with acceptable toxicity. Correlations of γH2AX foci, lymphocyte counts, and citrulline levels with irradiated volume and toxicity suggest potential as predictive biomarkers. This study has informed a multicenter, randomized, phase 3 clinical trial in the United Kingdom.

Patient specific evaluation of breathing motion induced interplay effects.

PURPOSE: In lung SABR, interplay between target motion and dynamically changing beam parameters can affect the target coverage. To identify the potential need for motion-management techniques, a comprehensive methodology for pre-treatment estimation of interplay effects has been implemented. METHODS: In conjunction with an alpha-version of VeriSoft and OCTAVIUS 4D (PTW-Freiburg, Germany), a method is presented to calculate a virtual, motion-simulated 3D dose distribution based on measurement data acquired in a stationary phantom and a subsequent correction with time-dependent target-motion patterns. In-house software has been developed to create user-defined motion patterns based on either simplistic or real patient-breathing patterns including the definition of the exact beam starting phase. The approach was validated by programmed couch and phantom motion during beam delivery. Five different breathing traces with extremely altered beam-on phases (0 % and 50 % respiratory phase) and a superior-inferior motion altitude of 25 mm were used to probe the influence of interplay effects for 14 lung SABR plans. Gamma analysis (2 %/2mm) was used for quantification. RESULTS: Validation measurements resulted in >98 % pass rates. Regarding the interplay effect evaluation, gamma pass rates of <92 % were observed for sinusoidal breathing patterns with <25 number of breaths per delivery time (NBs) and realistic patterns with <18 NBs. CONCLUSION: The potential influence of interplay effects on the target coverage is highly dependent on the patient's breathing behaviour. The presented moving-platform-free approach can be used for verification of ITV-based treatment plans to identify whether the clinical goals are achievable without explicit use of a respiratory management technique.

Simultaneous integrated boost (SIB) to dominant intra-prostatic lesions during extreme hypofractionation for prostate cancer: the impact of rectal spacers.

PURPOSE: Boosting dominant intra-prostatic lesions (DILs) has the potential to increase the therapeutic ratio in prostate cancer radiotherapy. In this study, employing 5-fraction stereotactic ablative radiotherapy (SABR) volumetric modulated arc therapy (VMAT) to deliver 40 Gy to the prostate clinical target volume (CTV) while boosting the DIL up to 50 Gy was evaluated for patients before and after rectal spacer insertion. MATERIALS AND METHODS: 24 Computed Tomography (CT) scans of 12 prostate cancer patients with unfavourable intermediate or high risk prostate cancer were employed in this study. At least two treatment plans were generated for each patient to compare pre- and post-spacer insertion plans. Plans were evaluated for target coverage, organs-at-risk doses, and the achievable boost dose level. RESULTS: The CTV coverage was significantly better in plans with a spacer, V40Gy 98.4% versus 97.0% (p = 0.012). Using spacers significantly reduced rectal dose in all 12 patients in this study. It was possible to boost DIL to 50 Gy to without violating dose constraints in 6 of 12 patients and to 47.5 Gy in 3 patients post-spacer insertion. For 3 patients (25%) it was not possible to boost DIL above 45 Gy even with a spacer in situ. Without a spacer, for 6 patient (50%) clinically acceptable plan were only achieved when the DIL dose was lowered to 45 Gy. In five of these 6 patients the dose limiting structure was the urethra (urethra planning risk volume V45Gy [cc] ≤ 0.1 cc constraint). CONCLUSIONS: Clinically acceptable plans for 5 fraction SABR, 40 Gy to the prostate CTV, with a SIB to DIL (45-50 Gy) were achieved. The boost dose achieved was DIL location dependent and primarily affected by DIL's proximity to the urethra. Compared to plans before spacer insertion, higher DIL dose were achieved with spacer in situ for 25% of the patients. Moreover, significant reduction in rectal dose and better target coverage were also achieved for all patients with spacers in situ.

Adaptive radiotherapy for head and neck cancer reduces the requirement for rescans during treatment due to spinal cord dose.

BACKGROUND: Patients treated with radiotherapy for head and neck (H&N) cancer often experience anatomical changes. The potential compromises to Planning Target Volume (PTV) coverage or Organ at Risk (OAR) sparing has prompted the use of adaptive radiotherapy (ART) for these patients. However, implementation of ART is time and resource intensive. This study seeks to define a clinical trigger for H&N re-plans based on spinal cord safety using kV Cone-Beam Computed Tomography (CBCT) verification imaging, in order to best balance clinical benefit with additional workload. METHODS: Thirty-one H&N patients treated with Volumetric Modulated Arc Therapy (VMAT) who had a rescan CT (rCT) during treatment were included in this study. Contour volume changes between the planning CT (pCT) and rCT were determined. The original treatment plan was calculated on the pCT, CBCT prior to the rCT, pCT deformed to the anatomy of the CBCT (dCT), and rCT (considered the gold standard). The dose to 0.1 cc (D0.1cc) spinal cord was evaluated from the Dose Volume Histograms (DVHs). RESULTS: The median dose increase to D0.1cc between the pCT and rCT was 0.7 Gy (inter-quartile range 0.2-1.9 Gy, p < 0.05). No correlation was found between contour volume changes and the spinal cord dose increase. Three patients exhibited an increase of 7.0-7.2 Gy to D0.1cc, resulting in a re-plan; these patients were correctly identified using calculations on the CBCT/dCT. CONCLUSIONS: An adaptive re-plan can be triggered using spinal cord doses calculated on the CBCT/dCT. Implementing this trigger can reduce patient appointments and radiation dose by eliminating up to 90% of additional un-necessary CT scans, reducing the workload for radiographers, physicists, dosimetrists, and clinicians.

An evaluation of techniques for dose calculation on cone beam computed tomography.

OBJECTIVE:: To assess the accuracy and efficiency of four different techniques, thus determining the optimum method for recalculating dose on cone beam CT (CBCT) images acquired during radiotherapy treatments. METHODS:: Four established techniques were investigated and their accuracy assessed via dose calculations: (1) applying a standard planning CT (pCT) calibration curve, (2) applying a CBCT site-specific calibration curve, (3) performing a density override and (4) using deformable registration. Each technique was applied to 15 patients receiving volumetric modulated arc therapy to one of three treatment sites, head and neck, lung and prostate. Differences between pCT and CBCT recalculations were determined with dose volume histogram metrics and 2.0%/0.1 mm gamma analysis using the pCT dose distribution as a reference. RESULTS:: Dose volume histogram analysis indicated that all techniques yielded differences from expected results between 0.0 and 2.3% for both target volumes and organs at risk. With volumetric gamma analysis, the dose recalculation on deformed images yielded the highest pass-rates. The median pass-rate ranges at 50% threshold were 99.6-99.9%, 94.6-96.0%, and 94.8.0-96.0% for prostate, head and neck and lung patients, respectively. CONCLUSION:: Deformable registration, HU override and site-specific calibration curves were all identified as dosimetrically accurate and efficient methods for dose calculation on CBCT images. ADVANCES IN KNOWLEDGE:: With the increasing adoption of CBCT, this study provides clinical radiotherapy departments with invaluable information regarding the comparison of dose reconstruction methods, enabling a more accurate representation of a patient's treatment. It can also integrate studies in which CBCT is used in image-guided radiation therapy and for adaptive radiotherapy planning processes.

Improvement of off-axis SABR plan verification results by using adapted dose reconstruction algorithms for the Octavius 4D system.

PURPOSE: Stereotactic ablative body radiotherapy (SABR) for lung patients can be performed with volumetric-modulated arc therapy (VMAT) plans using off-axis target geometry to allow treatment in their CBCT verified position. For patient-specific quality assurance measurements using the PTW Octavius 4D phantom (PTW, Freiburg, Germany) (OCT4D) in conjunction with an Octavius 1000SRS array (OCT1000) (PTW, Freiburg, Germany), repositioning the phantom off-axis is required to ensure the measurement area coincides with the tumor. The aim of this work is to quantify delivery errors using an array repositioned off-axis and evaluate new software which incorporates corrections for off-axis phantom measurements. METHODS: Dynamic conformal arcs and 25 lung SABR plans were created with the isocenter at the patient midline and the target volume off-axis. Measurements were acquired with an OCT4D phantom in conjunction with a 729 array (PTW, Freiburg, Germany) (OCT729) placed at isocenter. These plans were recalculated and delivered to both the OCT729 and OCT1000 arrays repositioned so that the high-dose region was at the center of the phantom. Comparisons were made using VeriSoft v7.0 (PTW, Freiburg, Germany) and the newly implemented version 7.1 with 2%/2 mm gamma criterion (10% threshold) and results correlated with off-axis distance to the tumor. RESULTS: Average pass rates for VeriSoft v7.0 significantly reduced from 92.7 ± 2.4% to 84.9 ± 4.1% when the phantom was repositioned compared to the isocenter setup for the OCT729. The gamma pass rates significantly decreased the further the phantom was moved off-axis. Significantly higher pass rates were observed for the OCT1000 of 95.7 ± 3.6% and a significant decrease in gamma pass rate with off-axis phantom distance was again observed. In contrast, even with phantom repositioning, the pass rates for analysis with VeriSoft v7.1 were 93.7 ± 2.1% and 99.4 ± 1.1% for OCT729 and OCT1000, respectively. No significant difference in gamma pass rate was observed with off-axis phantom position irrespective of array type with the new software. CONCLUSION: The errors in QA phantom measurements due to dose reconstruction at off-axis target geometry have been demonstrated for conformal arcs and clinical VMAT SABR plans. A novel software solution implemented by the vendor to allow accurate pass rates has been tested. This solution enables high-resolution arrays with small active detection areas to be used for quality assurance of SABR treatment plans in the off-axis treatment position.

Efficacy of a rectal spacer with prostate SABR-first UK experience.

OBJECTIVE: This study assessed the use of implanted hydrogel rectal spacers for stereotactic ablative radiotherapy-volumetric modulated arc therapy (SABR-VMAT) patients, investigating practicality, dosimetric impact, normal tissue complication probability (NTCP) and early toxicity. METHODS: Data from the first 6 patients treated within a prostate SABR and rectal spacer trial were examined to determine spacer insertion tolerability, resultant changes in treatment planning and dosimetry and early toxicity effects. CT scans acquired prior to spacer insertion were used to generate SABR plans which were compared to post-insertion plans. Plans were evaluated for target coverage, conformity, and organs at risk doses with NTCPs also determined from resultant dose fluences. Early toxicity data were also collected. RESULTS: All patients had successful spacer insertion under local anaesthetic with maximal Grade 1 toxicity. All plans were highly conformal, with no significant differences in clinical target volume dose coverage between pre- and post-spacer plans. Substantial improvements in rectal dose metrics were observed in post-spacer plans, e.g. rectal volume receiving 36 Gy reduced by ≥42% for all patients. Median NTCP for Grade 2 + rectal bleeding significantly decreased from 4.9 to 0.8% with the use of a rectal spacer (p = 0.031). To date, two episodes of acute Grade 1 proctitis have been reported following treatment. CONCLUSION: The spacer resulted in clinically and statistically significant reduction in rectal doses for all patients. Advances in knowledge: This is one of the first studies to investigate the efficacy of a hydrogel spacer in prostate SABR treatments. Observed dose sparing of the rectum is predicted to result in meaningful clinical benefit.

Class solutions for SABR-VMAT for high-risk prostate cancer with and without elective nodal irradiation.

BACKGROUND: The purpose of this study is to find the optimal planning settings for prostate SABR-VMAT for high-risk prostate cancer patients irradiated to prostate only (PO) or prostate and pelvic lymph nodes (PPLN). METHODS: For 10 patients, plans using 6MV flattened, flattening-filter-free (FFF) 6MV (6 F) and FFF 10MV (10 F) photon beams with full and partial arc arrangements were generated and compared. The prescribed dose was 40Gy to the prostate with 25Gy to the PLN in 5 fractions. Plans were then evaluated for PTV coverage, dose fall-off, and OAR doses. The number of monitor units and the treatment delivery times were also compared. Statistical differences were evaluated using a paired sample Wilcoxon signed rank test with a significance level of 0.05%. RESULTS: A total of 150 plans were generated for this study. Acceptable PO plans were obtained using single arcs, while two arcs were necessary for PPLN. All plans were highly conformal (CI ≥1.3 and CN ≥0.90) with no significant differences in the PTV dose coverage. 6MV plans required significantly longer treatment time and had higher dose spillage compared to FFF plans. Superior plans were obtained using 10 F 300° partial arcs for PO with the lowest rectal dose, dose spillage and the shortest treatment times. For PPLN, 6 F and 10 F plans were equivalent. CONCLUSIONS: SABR-VMAT with FFF photon beams offers a clear benefit with respect to shorter treatment delivery times and reduced dose spillage. Class solutions using a single 10 F 300° arc for PO and two 10 F or 6 F partial 300° arcs for PPLN are proposed.

Correlation of phantom-based and log file patient-specific QA with complexity scores for VMAT.

The motivation for this study was to reduce physics workload relating to patient- specific quality assurance (QA). VMAT plan delivery accuracy was determined from analysis of pre- and on-treatment trajectory log files and phantom-based ionization chamber array measurements. The correlation in this combination of measurements for patient-specific QA was investigated. The relationship between delivery errors and plan complexity was investigated as a potential method to further reduce patient-specific QA workload. Thirty VMAT plans from three treatment sites - prostate only, prostate and pelvic node (PPN), and head and neck (H&N) - were retrospectively analyzed in this work. The 2D fluence delivery reconstructed from pretreatment and on-treatment trajectory log files was compared with the planned fluence using gamma analysis. Pretreatment dose delivery verification was also car- ried out using gamma analysis of ionization chamber array measurements compared with calculated doses. Pearson correlations were used to explore any relationship between trajectory log file (pretreatment and on-treatment) and ionization chamber array gamma results (pretreatment). Plan complexity was assessed using the MU/ arc and the modulation complexity score (MCS), with Pearson correlations used to examine any relationships between complexity metrics and plan delivery accu- racy. Trajectory log files were also used to further explore the accuracy of MLC and gantry positions. Pretreatment 1%/1 mm gamma passing rates for trajectory log file analysis were 99.1% (98.7%-99.2%), 99.3% (99.1%-99.5%), and 98.4% (97.3%-98.8%) (median (IQR)) for prostate, PPN, and H&N, respectively, and were significantly correlated to on-treatment trajectory log file gamma results (R = 0.989, p < 0.001). Pretreatment ionization chamber array (2%/2 mm) gamma results were also significantly correlated with on-treatment trajectory log file gamma results (R = 0.623, p < 0.001). Furthermore, all gamma results displayed a significant correlation with MCS (R > 0.57, p < 0.001), but not with MU/arc. Average MLC position and gantry angle errors were 0.001 ± 0.002 mm and 0.025° ± 0.008° over all treatment sites and were not found to affect delivery accuracy. However, vari- ability in MLC speed was found to be directly related to MLC position accuracy. The accuracy of VMAT plan delivery assessed using pretreatment trajectory log file fluence delivery and ionization chamber array measurements were strongly correlated with on-treatment trajectory log file fluence delivery. The strong corre- lation between trajectory log file and phantom-based gamma results demonstrates potential to reduce our current patient-specific QA. Additionally, insight into MLC and gantry position accuracy through trajectory log file analysis and the strong cor- relation between gamma analysis results and the MCS could also provide further methodologies to both optimize the VMAT planning and QA process. 

Octavius 4D characterization for flattened and flattening filter free rotational deliveries.

PURPOSE: In this study the Octavius detector 729 ionization chamber (IC) array with the Octavius 4D phantom was characterized for flattening filter (FF) and flattening filter free (FFF) static and rotational beams. The device was assessed for verification with FF and FFF RapidArc treatment plans. METHODS: The response of the detectors to field size, dose linearity, and dose rate were assessed for 6 MV FF beams and also 6 and 10 MV FFF beams. Dosimetric and mechanical accuracy of the detector array within the Octavius 4D rotational phantom was evaluated against measurements made using semiflex and pinpoint ionization chambers, and radiochromic film. Verification FF and FFF RapidArc plans were assessed using a gamma function with 3%∕3 mm tolerances and 2%∕2 mm tolerances and further analysis of these plans was undertaken using film and a second detector array with higher spatial resolution. RESULTS: A warm-up dose of >6 Gy was required for detector stability. Dose-rate measurements were stable across a range from 0.26 to 15 Gy∕min and dose response was linear, although the device overestimated small doses compared with pinpoint ionization chamber measurements. Output factors agreed with ionization chamber measurements to within 0.6% for square fields of side between 3 and 25 cm and within 1.2% for 2 × 2 cm(2) fields. The Octavius 4D phantom was found to be consistent with measurements made with radiochromic film, where the gantry angle was found to be within 0.4° of that expected during rotational deliveries. RapidArc FF and FFF beams were found to have an accuracy of >97.9% and >90% of pixels passing 3%∕3 mm and 2%∕2 mm, respectively. Detector spatial resolution was observed to be a factor in determining the accurate delivery of each plan, particularly at steep dose gradients. This was confirmed using data from a second detector array with higher spatial resolution and with radiochromic film. CONCLUSIONS: The Octavius 4D phantom with associated Octavius detector 729 ionization chamber array is a dosimetrically and mechanically stable device for pretreatment verification of FF and FFF RapidArc treatments. Further improvements may be possible through use of a detector array with higher spatial resolution (detector size and∕or detector spacing).