A dosimetric analysis of respiration-gated radiotherapy in patients with stage III lung cancer

BACKGROUND: Respiration-gated radiotherapy can permit the irradiation of smaller target volumes. 4DCT scans performed for routine treatment were retrospectively analyzed to establish the benefits of gating in stage III non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Gross tumor volumes (GTVs) were contoured in all 10 respiratory phases of a 4DCT scan in 15 patients with stage III NSCLC. Treatment planning was performed using different planning target volumes (PTVs), namely: (i) PTV(routine), derived from a single GTV plus 'conventional' margins; (ii) PTV(all phases )incorporating all 3D mobility captured by the 4DCT; (iii) PTV(gating), incorporating residual 3D mobility in 3–4 phases at end-expiration. Mixed effect models were constructed in order to estimate the reductions in risk of lung toxicity for the different PTVs. RESULTS: Individual GTVs ranged from 41.5 – 235.0 cm(3). With patient-specific mobility data (PTV(all phases)), smaller PTVs were derived than when 'standard' conventional margins were used (p < 0.001). The average residual 3D tumor mobility within the gating window was 4.0 ± 3.5 mm, which was 5.5 mm less than non-gated tumor mobility (p < 0.001). The reductions in mean lung dose were 9.7% and 4.9%, respectively, for PTV(all phases )versus PTV(routine), and PTV(gating )versus PTV(all phases). The corresponding reductions in V(20 )were 9.8% and 7.0%, respectively. Dosimetric gains were smaller for primary tumors of the upper lobe versus other locations (p = 0.02). Respiratory gating also reduced the risks of radiation-induced esophagitis. CONCLUSION: Respiration-gated radiotherapy can reduce the risk of pulmonary toxicity but the benefits are particularly evident for tumors of the middle and lower lobes

Comparison of MR‐guided radiotherapy accumulated doses for central lung tumors with non‐adaptive and online adaptive proton therapy

Background Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking. Purpose We conducted a comparison of accumulated doses for MRgRT, robustly optimized non-adaptive IMPT, and online adaptive IMPT for central lung tumors. A special focus was set on analyzing the accumulated doses to the bronchial tree, a parameter linked to high-grade toxicities. Methods Data of 18 early-stage central lung tumor patients, treated at a 0.35 T MR-linac in eight or five fractions, were analyzed. Three gated treatment scenarios were compared: (S1) online adaptive MRgRT, (S2) non-adaptive IMPT, and (S3) online adaptive IMPT. The treatment plans were recalculated or reoptimized on the daily imaging data acquired during MRgRT, and accumulated over all treatment fractions. Accumulated dose-volume histogram (DVH) parameters of the gross tumor volume (GTV), lung, heart, and organs-at-risk (OARs) within 2 cm of the planning target volume (PTV) were extracted for each scenario and compared in Wilcoxon signed-rank tests between S1 & S2, and S1 & S3. Results The accumulated GTV D98% was above the prescribed dose for all patients and scenarios. Significant reductions (p < 0.05) of the mean ipsilateral lung dose (S2: –8%; S3: –23%) and mean heart dose (S2: –79%; S3: –83%) were observed for both proton scenarios compared to S1. The bronchial tree D0.1cc was significantly lower for S3 (S1: 48.1 Gy; S3: 39.2 Gy; p = 0.005), but not significantly different for S2 (S2: 45.0 Gy; p = 0.094), compared to S1. The D0.1cc for S2 and S3 compared to S1 was significantly (p < 0.05) smaller for OARs within 1–2 cm of the PTV (S1: 30.2 Gy; S2: 24.6 Gy; S3: 23.1 Gy), but not significantly different for OARs within 1 cm of the PTV. Conclusions A significant dose sparing potential of non-adaptive and online adaptive proton therapy compared to MRgRT for OARs in close, but not direct proximity of central lung tumors was identified. The near-maximum dose to the bronchial tree was not significantly different for MRgRT and non-adaptive IMPT. Online adaptive IMPT achieved significantly lower doses to the bronchial tree compared to MRgRT

Verifying 4D gated radiotherapy using time-integrated electronic portal imaging: a phantom and clinical study

<p>Abstract</p> <p>Background</p> <p>Respiration-gated radiotherapy (RGRT) can decrease treatment toxicity by allowing for smaller treatment volumes for mobile tumors. RGRT is commonly performed using external surrogates of tumor motion. We describe the use of time-integrated electronic portal imaging (TI-EPI) to verify the position of internal structures during RGRT delivery</p> <p>Methods</p> <p>TI-EPI portals were generated by continuously collecting exit dose data (aSi500 EPID, Portal vision, Varian Medical Systems) when a respiratory motion phantom was irradiated during expiration, inspiration and free breathing phases. RGRT was delivered using the Varian RPM system, and grey value profile plots over a fixed trajectory were used to study object positions. Time-related positional information was derived by subtracting grey values from TI-EPI portals sharing the pixel matrix. TI-EPI portals were also collected in 2 patients undergoing RPM-triggered RGRT for a lung and hepatic tumor (with fiducial markers), and corresponding planning 4-dimensional CT (4DCT) scans were analyzed for motion amplitude.</p> <p>Results</p> <p>Integral grey values of phantom TI-EPI portals correlated well with mean object position in all respiratory phases. Cranio-caudal motion of internal structures ranged from 17.5–20.0 mm on planning 4DCT scans. TI-EPI of bronchial images reproduced with a mean value of 5.3 mm (1 SD 3.0 mm) located cranial to planned position. Mean hepatic fiducial markers reproduced with 3.2 mm (SD 2.2 mm) caudal to planned position. After bony alignment to exclude set-up errors, mean displacement in the two structures was 2.8 mm and 1.4 mm, respectively, and corresponding reproducibility in anatomy improved to 1.6 mm (1 SD).</p> <p>Conclusion</p> <p>TI-EPI appears to be a promising method for verifying delivery of RGRT. The RPM system was a good indirect surrogate of internal anatomy, but use of TI-EPI allowed for a direct link between anatomy and breathing patterns.</p

Analysis and reduction of 3D systematic and random setup errors during the simulation and treatment of lung cancer patients with CT-based external beam radiotherapy dose planning

Purpose: To determine the magnitude of the errors made in (a) the setup of patients with lung cancer on the simulator relative to their intended setup with respect to the planned treatment beams and (b) in the setup of these patients on the treatment unit. To investigate how the systematic component of the latter errors can be reduced with an off-line decision protocol for setup corrections. Methods and Materials: For 39 patients with CT planning, digitally-reconstructed radiographs (DRRs) were calculated for anterior-posterior and lateral beams. Retrospectively, the position of the visible anatomy relative to the planned isocenter was compared with the corresponding position on the digitized simulator radiographs using contour match software. The setup accuracy at the treatment unit relative to the simulator setup was measured for 40 patients for at least 5 fractions per patient in 2 orthogonal beams with the aid of an electronic portal imaging device (EPID). Setup corrections were applied, based on an off-line decision protocol, with parameters derived from knowledge of the random setup errors in the studied patient group. Results: The standard deviations (SD) of the simulator setup errors relative to the CT planning setup in the lateral, longitudinal, and anterior-posterior directions were 4.0, 2.8, and 2.5 mm, respectively. The SD of rotations around the anterior-posterior axis was 1.6° and around the left-right axis 1.3°. The setup error at the treatment unit had a small random component in all three directions (1 SD = 2 mm). The systematic components were larger, particularly in the longitudinal direction (1 SD = 3.6 mm), but were reduced with the decision protocol to 1 SD < 2 mm with, on average, 0.6 setup correction per patient. Conclusion: Setup errors at the simulator, which become systematic errors if the simulation defines the reference setup, were comparable to the systematic setup errors at the treatment unit in case no off-line protocol would have been applied. Hence, the omission of a separate simulation step can reduce systematic errors as efficiently as the application of an off-line correction protocol during treatment. The random errors were sufficiently small to make an off-line protocol feasible

Four-dimensional computed tomographic analysis of esophageal mobility during normal respiration

BACKGROUND: Chemo-radiotherapy for thoracic tumors can result in high-grade radiation esophagitis. Treatment planning to reduce esophageal irradiation requires organ motion to be accounted for. In this study, esophageal mobility was assessed using four-dimensional computed tomography (4DCT). METHODS AND MATERIALS: Thoracic 4DCT scans were acquired on a 16-slice CT scanner in 29 patients. The outer esophageal wall was contoured in two extreme phases of respiration in 9 patients with nonesophageal malignancies. The displacement of the center of contour was measured at 2-cm intervals. In 20 additional patients with Stage I lung cancer, the esophagus was contoured in all 10 phases of each 4DCT at five defined anatomic levels. Both approaches were then applied to 4DCT scans of 4 patients who each had two repeat scans performed. A linear mixed effects model was constructed with fixed effects: measurement direction, measurement type, and measurement location along the cranio-caudal axis. RESULTS: Measurement location and direction were significant descriptive parameters (Wald F-tests, p <0.001), and the interaction term between the two was significant (p = 0.02). Medio-lateral mobility exceeded dorso-ventral mobility in the lower half of the esophagus but was of a similar magnitude in the upper half. Margins that would have incorporated all movement in medio-lateral and dorso-ventral directions were 5 mm proximally, 7 mm and 6 mm respectively in the mid-esophagus, and 9 mm and 8 mm respectively in the distal esophagus. CONCLUSIONS: The distal esophagus shows more mobility. Margins for mobility that can encompass all movement were derived for use in treatment planning, particularly for stereotactic radiotherap

Reproducibility of target volumes generated using uncoached 4-dimensional CT scans for peripheral lung cancer

Background: 4-dimensional CT (4DCT) scans are increasingly used to account for mobility during radiotherapy planning. As variations in respiratory patterns can alter observed motion, with consequent changes in the generated target volumes, we evaluated the reproducibility of 4D target volumes generated during repeat uncoached quiet respiration. Methods: A retrospective analysis was performed on two successive scans (4DCT1 and 4DCT2) generated at the same scanning session for 26 patients with peripheral lung cancer treated with stereotactic radiotherapy (SRT). The volume and position of planning target volumes (PTV4DCT1 and PTV4DCT2) contoured on both scans were compared, and a dosimetric analysis performed. A SRT plan optimized for each PTV was sequentially applied to the other PTV, and coverage by the 80% isodose was evaluated. Color intensity projections (CIP) were used to evaluate regions of underdosage. Results: No significant volumetric differences were observed between the two PTVs (t-Test p = 0.60). The average displacement of the center of mass between corresponding PTVs was 1.4 ± 1.0 mm, but differences in position were 2.0 mm or greater in 5 cases (19%). Coverage of both PTVs by the 80% prescription isodose exceeded 90% for all but one patient. For the latter, the prescription isodose covered only 82.5% of PTV4DCT1. CIP analysis revealed that the region of underdosage was an end-inspiratory position occupied by the tumor for only 10-20% of the respiratory cycle. Conclusion: In nearly all patients with stage I lung cancer, the PTV derived from a single uncoached 4DCT achieves dosimetric coverage that is similar to that achieved using two such consecutive scans

MR-guided Gated Stereotactic Radiation Therapy Delivery for Lung, Adrenal, and Pancreatic Tumors: A Geometric Analysis

PURPOSE: We implemented magnetic resonance-guided breath-hold stereotactic body radiation therapy in combination with visual feedback using the MRIdian system. Both accuracy of gated delivery and reproducibility of tumor positions were studied. METHODS AND MATERIALS: Tumor tracking is realized through repeated magnetic resonance imaging in a single sagittal plane at 4 frames per second with deformable image registration. An in-room monitor allowed visualization of the tracked gross tumor volume (GTV) contour and the planning target volume (PTV) (GTV + 3 mm), which was the gating boundary. For each delivery, a predefined threshold-region of interest percentage (ROI%) allows a percentage of GTV area to be outside the gating boundary before a beam-hold is triggered. Accuracy of gated delivery and tumor position reproducibility during breath-holds was analyzed for 15 patients (87 fractions) with lung, adrenal, and pancreas tumors. For each fraction, we analyzed (1) reproducibility of system-tracked GTV centroid position within the PTV; (2) geometric coverage of GTV area within the PTV; (3) treatment duty cycle efficiency; (4) effects of threshold ROI% settings on treatment duty cycle efficiency and GTV area coverage; and (5) beam-off latency effect on mean GTV coverage. RESULTS: For lung, adrenal, and pancreatic tumors, grouped 5th to 95th percentile distributions of GTV centroid positions in the dorsoventral direction, relative to PTV-center of mass (COM), were, respectively, -3.3 mm to 2.8 mm, -2.5 mm to 3.7 mm, and -4.4 mm to 2.9 mm. Corresponding distributions in the craniocaudal direction were -2.6 mm to 4.6 mm, -4.1 mm to 4.4 mm, and -4.4 mm to 4.5 mm, respectively. Mean GTV areas encompassed during beam-on for all fractions were 94.6%, 94.3%, and 95.3% for lung, adrenal, and pancreas tumors, respectively. Mean treatment duty cycle efficiency ranged from 67% to 87% for these tumors. Use of higher threshold-ROI% resulted in increased duty cycle efficiency, at the cost of a small decrease in GTV area coverage. The beam-off latency had a marginal impact on the GTV coverage. CONCLUSIONS: Gated stereotactic body radiation therapy delivery during breath-hold, real-time magnetic resonance guidance resulted in at least 95% geometric GTV coverage in lung, adrenal, and pancreatic tumors

Delivery of magnetic resonance-guided single-fraction stereotactic lung radiotherapy

Background and purpose: Single-fraction stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage lung cancer, but concerns remain about the accurate delivery of SABR in a single session. We evaluated the delivery of single-fraction lung SABR using magnetic resonance (MR)-guidance. Materials and methods: An MR-simulation was performed in 17 patients, seven of whom were found to be unsuitable, largely due to unreliable tracking of small tumors. Ten patients underwent single-fraction SABR to 34 Gy on a 0.35 T MR-linac system, with online plan adaptation. Gated breath-hold SABR was delivered using a planning target volume (PTV) margin of 5 mm, and a 3 mm gating window. Continuous MR-tracking of the gross tumor volume (GTVt) was performed in sagittal plane, with visual patient feedback provided using an in-room monitor. The real-time MR images were analyzed to determine precision and efficiency of gated delivery. Results: All but one patient completed treatment in a single session. The median total in-room procedure was 120 min, with a median SABR delivery session of 39 min. Review of 7.4 h of cine-MR imaging revealed a mean GTVt coverage by the PTV during beam-on of 99.6%. Breath-hold patterns were variable, resulting in a mean duty cycle efficiency of 51%, but GTVt coverage was not influenced due to real-time MR-guidance. On-table adaptation improved PTV coverage, but had limited impact on GTV doses. Conclusions: Single-fraction gated SABR of lung tumors can be performed with high precision using MR-guidance. However, improvements are needed to ensure MR-tracking of small tumors, and to reduce treatment times