S Balik

Dose escalation for locally advanced lung cancer using adaptive radiation therapy with simultaneous integrated volume-adapted boost.

PURPOSE To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. METHODS AND MATERIALS Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). RESULTS The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. CONCLUSIONS The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

Evaluation of 4-dimensional Computed Tomography to 4-dimensional Cone-Beam Computed Tomography Deformable Image Registration for Lung Cancer Adaptive Radiation Therapy

PURPOSE To evaluate 2 deformable image registration (DIR) algorithms for the purpose of contour mapping to support image-guided adaptive radiation therapy with 4-dimensional cone-beam CT (4DCBCT). METHODS AND MATERIALS One planning 4D fan-beam CT (4DFBCT) and 7 weekly 4DCBCT scans were acquired for 10 locally advanced non-small cell lung cancer patients. The gross tumor volume was delineated by a physician in all 4D images. End-of-inspiration phase planning 4DFBCT was registered to the corresponding phase in weekly 4DCBCT images for day-to-day registrations. For phase-to-phase registration, the end-of-inspiration phase from each 4D image was registered to the end-of-expiration phase. Two DIR algorithms-small deformation inverse consistent linear elastic (SICLE) and Insight Toolkit diffeomorphic demons (DEMONS)-were evaluated. Physician-delineated contours were compared with the warped contours by using the Dice similarity coefficient (DSC), average symmetric distance, and false-positive and false-negative indices. The DIR results are compared with rigid registration of tumor. RESULTS For day-to-day registrations, the mean DSC was 0.75 ± 0.09 with SICLE, 0.70 ± 0.12 with DEMONS, 0.66 ± 0.12 with rigid-tumor registration, and 0.60 ± 0.14 with rigid-bone registration. Results were comparable to intraobserver variability calculated from phase-to-phase registrations as well as measured interobserver variation for 1 patient. SICLE and DEMONS, when compared with rigid-bone (4.1 mm) and rigid-tumor (3.6 mm) registration, respectively reduced the average symmetric distance to 2.6 and 3.3 mm. On average, SICLE and DEMONS increased the DSC to 0.80 and 0.79, respectively, compared with rigid-tumor (0.78) registrations for 4DCBCT phase-to-phase registrations. CONCLUSIONS Deformable image registration achieved comparable accuracy to reported interobserver delineation variability and higher accuracy than rigid-tumor registration. Deformable image registration performance varied with the algorithm and the patient.

Respiratory triggered 4D cone‐beam computed tomography: A novel method to reduce imaging dose

PURPOSE A novel method called respiratory triggered 4D cone-beam computed tomography (RT 4D CBCT) is described whereby imaging dose can be reduced without degrading image quality. RT 4D CBCT utilizes a respiratory signal to trigger projections such that only a single projection is assigned to a given respiratory bin for each breathing cycle. In contrast, commercial 4D CBCT does not actively use the respiratory signal to minimize image dose. METHODS To compare RT 4D CBCT with conventional 4D CBCT, 3600 CBCT projections of a thorax phantom were gathered and reconstructed to generate a ground truth CBCT dataset. Simulation pairs of conventional 4D CBCT acquisitions and RT 4D CBCT acquisitions were developed assuming a sinusoidal respiratory signal which governs the selection of projections from the pool of 3600 original projections. The RT 4D CBCT acquisition triggers a single projection when the respiratory signal enters a desired acquisition bin; the conventional acquisition does not use a respiratory trigger and projections are acquired at a constant frequency. Acquisition parameters studied were breathing period, acquisition time, and imager frequency. The performance of RT 4D CBCT using phase based and displacement based sorting was also studied. Image quality was quantified by calculating difference images of the test dataset from the ground truth dataset. Imaging dose was calculated by counting projections. RESULTS Using phase based sorting RT 4D CBCT results in 47% less imaging dose on average compared to conventional 4D CBCT. Image quality differences were less than 4% at worst. Using displacement based sorting RT 4D CBCT results in 57% less imaging dose on average, than conventional 4D CBCT methods; however, image quality was 26% worse with RT 4D CBCT. CONCLUSIONS Simulation studies have shown that RT 4D CBCT reduces imaging dose while maintaining comparable image quality for phase based 4D CBCT; image quality is degraded for displacement based RT 4D CBCT in its current implementation.

Interfraction displacement of primary tumor and involved lymph nodes relative to anatomic landmarks in image guided radiation therapy of locally advanced lung cancer.

PURPOSE To analyze primary tumor (PT) and lymph node (LN) position changes relative to each other and relative to anatomic landmarks during conventionally fractionated radiation therapy for patients with locally advanced lung cancer. METHODS AND MATERIALS In 12 patients with locally advanced non-small cell lung cancer PT, LN, carina, and 1 thoracic vertebra were manually contoured on weekly 4-dimensional fan-beam CT scans. Systematic and random interfraction displacements of all contoured structures were identified in the 3 cardinal directions, and resulting setup margins were calculated. Time trends and the effect of volume changes on displacements were analyzed. RESULTS Three-dimensional displacement vectors and systematic/random interfraction displacements were smaller for carina than for vertebra both for PT and LN. For PT, mean (SD) 3-dimensional displacement vectors with carina-based alignment were 7 (4) mm versus 9 (5) mm with bony anatomy (P<.0001). For LN, smaller displacements were found with carina- (5 [3] mm, P<.0001) and vertebra-based (6 [3] mm, P=.002) alignment compared with using PT for setup (8 [5] mm). Primary tumor and LN displacements relative to bone and carina were independent (P>.05). Displacements between PT and bone (P=.04) and between PT and LN (P=.01) were significantly correlated with PT volume regression. Displacements between LN and carina were correlated with LN volume change (P=.03). CONCLUSIONS Carina-based setup results in a more reproducible PT and LN alignment than bony anatomy setup. Considering the independence of PT and LN displacement and the impact of volume regression on displacements over time, repeated CT imaging even with PT-based alignment is recommended in locally advanced disease.

A longitudinal four‐dimensional computed tomography and cone beam computed tomography dataset for image‐guided radiation therapy research in lung cancer

Purpose: To describe in detail a dataset consisting of serial four‐dimensional computed tomography (4DCT) and 4D cone beam CT (4DCBCT) images acquired during chemoradiotherapy of 20 locally advanced, nonsmall cell lung cancer patients we have collected at our institution and shared publicly with the research community. Acquisition and validation methods: As part of an NCI‐sponsored research study 82 4DCT and 507 4DCBCT images were acquired in a population of 20 locally advanced nonsmall cell lung cancer patients undergoing radiation therapy. All subjects underwent concurrent radiochemotherapy to a total dose of 59.4–70.2 Gy using daily 1.8 or 2 Gy fractions. Audio‐visual biofeedback was used to minimize breathing irregularity during all fractions, including acquisition of all 4DCT and 4DCBCT acquisitions in all subjects. Target, organs at risk, and implanted fiducial markers were delineated by a physician in the 4DCT images. Image coordinate system origins between 4DCT and 4DCBCT were manipulated in such a way that the images can be used to simulate initial patient setup in the treatment position. 4DCT images were acquired on a 16‐slice helical CT simulator with 10 breathing phases and 3 mm slice thickness during simulation. In 13 of the 20 subjects, 4DCTs were also acquired on the same scanner weekly during therapy. Every day, 4DCBCT images were acquired on a commercial onboard CBCT scanner. An optically tracked external surrogate was synchronized with CBCT acquisition so that each CBCT projection was time stamped with the surrogate respiratory signal through in‐house software and hardware tools. Approximately 2500 projections were acquired over a period of 8–10 minutes in half‐fan mode with the half bow‐tie filter. Using the external surrogate, the CBCT projections were sorted into 10 breathing phases and reconstructed with an in‐house FDK reconstruction algorithm. Errors in respiration sorting, reconstruction, and acquisition were carefully identified and corrected. Data format and usage notes: 4DCT and 4DCBCT images are available in DICOM format and structures through DICOM‐RT RTSTRUCT format. All data are stored in the Cancer Imaging Archive (TCIA, http://www.cancerimagingarchive.net/) as collection 4D‐Lung and are publicly available. Discussion: Due to high temporal frequency sampling, redundant (4DCT and 4DCBCT) data at similar timepoints, oversampled 4DCBCT, and fiducial markers, this dataset can support studies in image‐guided and image‐guided adaptive radiotherapy, assessment of 4D voxel trajectory variability, and development and validation of new tools for image registration and motion management.

SU-F-BRF-07: Impact of Different Patient Setup Strategies in Adaptive Radiation Therapy with Simultaneous Integrated Volume-Adapted Boost of NSCLC

PURPOSE To evaluate the potential impact of several setup error correction strategies on a proposed image-guided adaptive radiotherapy strategy for locally advanced lung cancer. METHODS Daily 4D cone-beam CT and weekly 4D fan-beam CT images were acquired from 9 lung cancer patients undergoing concurrent chemoradiation therapy. Initial planning CT was deformably registered to daily CBCT images to generate synthetic treatment courses. An adaptive radiation therapy course was simulated using the weekly CT images with replanning twice and a hypofractionated, simultaneous integrated boost to a total dose of 66 Gy to the original PTV and either a 66 Gy (no boost) or 82 Gy (boost) dose to the boost PTV (ITV + 3mm) in 33 fractions with IMRT or VMAT. Lymph nodes (LN) were not boosted (prescribed to 66 Gy in both plans). Synthetic images were rigidly, bony (BN) or tumor and carina (TC), registered to the corresponding plan CT, dose was computed on these from adaptive replans (PLAN) and deformably accumulated back to the original planning CT. Cumulative D98% of CTV of PT (ITV for 82Gy) and LN, and normal tissue dose changes were analyzed. RESULTS Two patients were removed from the study due to large registration errors. For the remaining 7 patients, D98% for CTV-PT (ITV-PT for 82 Gy) and CTV-LN was within 1 Gy of PLAN for both 66 Gy and 82 Gy plans with both setup techniques. Overall, TC based setup provided better results, especially for LN coverage (p = 0.1 for 66Gy plan and p = 0.2 for 82 Gy plan, comparison of BN and TC), though not significant. Normal tissue dose constraints violated for some patients if constraint was barely achieved in PLAN. CONCLUSION The hypofractionated adaptive strategy appears to be deliverable with soft tissue alignment for the evaluated margins and planning parameters. Research was supported by NIH P01CA116602.

SU-F-T-42: MRI and TRUS Image Fusion as a Mode of Generating More Accurate Prostate Contours

PURPOSE Transrectal Ultrasound (TRUS) imaging is utilized intra-operatively for LDR permanent prostate seed implant treatment planning. Prostate contouring with TRUS can be challenging at the apex and base. This study attempts to improve accuracy of prostate contouring with MRI-TRUS fusion to prevent over- or under-estimation of the prostate volume. METHODS 14 patients with previous MRI guided prostate biopsy and undergone an LDR permanent prostate seed implant have been selected. The prostate was contoured on the MRI images (1 mm slice thickness) by a radiologist. The prostate was also contoured on TRUS images (5 mm slice thickness) during LDR procedure by a urologist. MRI and TRUS images were rigidly fused manually and the prostate contours from MRI and TRUS were compared using Dice similarity coefficient, percentage volume difference and length, height and width differences. RESULTS The prostate volume was overestimated by 8 ± 18% (range: 34% to -25%) in TRUS images compared to MRI. The mean Dice was 0.77 ± 0.09 (range: 0.53 to 0.88). The mean difference (TRUS-MRI) in the prostate width was 0 ± 4 mm (range: -11 to 5 mm), height was -3 ± 6 mm (range: -13 to 6 mm) and length was 6 ± 6 (range: -10 to 16 mm). Prostate was overestimated with TRUS imaging at the base for 6 cases (mean: 8 ± 4 mm and range: 5 to 14 mm), at the apex for 6 cases (mean: 11 ± 3 mm and range: 5 to 15 mm) and 1 case was underestimated at both base and apex by 4 mm. CONCLUSION Use of intra-operative TRUS and MRI image fusion can help to improve the accuracy of prostate contouring by accurately accounting for prostate over- or under-estimations, especially at the base and apex. The mean amount of discrepancy is within a range that is significant for LDR sources.

SU-F-J-108: TMR Correction Factor Based Online Adaptive Radiotherapy for Stereotactic Radiosurgery (SRS) of L-Spine Tumors Using Cone Beam CT

PURPOSE To investigate the feasibility of using TMR ratio correction factors for a fast online adaptive plan to compensate for anatomical changes in stereotactic radiosurgery (SRS) of L-spine tumors. METHODS Three coplanar treatment plans were made for 11 patients: Uniform (9 IMRT beams equally distributed around the patient); Posterior (IMRT with 9 posterior beams every 20 degree) and VMAT (2 360° arcs). For each patient, the external body and bowel gas were contoured on the planning CT and pre-treatment CBCT. After registering CBCT and the planning CT by aligning to the tumor, the CBCT contours were transferred to the planning CT. To estimate the actual delivered dose while considering patients anatomy of the treatment day, a hybrid CT was created by overriding densities in planning CT using the differences between CT and CBCT external and bowel gas contours. Correction factors (CF) were calculated using the effective depth information obtained from the planning system using the hybrid CT: CF = TMR (delivery)/TMR (planning). The adaptive plan was generated by multiplying the planned Monitor Units with the CFs. RESULTS The mean absolute difference (MAD) in V16Gy of the target between planned and estimated delivery with and without TMR correction was 0.8 ± 0.7% vs. 2.4 ± 1.3% for Uniform and 1.0 ± 0.9% vs. 2.6 ± 1.3% for VMAT plans(p<0.05), respectively. For V12Gy of cauda-equina with and without TMR correction, MAD was 0.24 ± 0.19% vs. 1.2 ± 1.02% for Uniform and 0.23 ± 0.20% vs. 0.78 ± 0.79% for VMAT plans(p<0.05), respectively. The differences between adaptive and original plans were not significant for posterior plans. CONCLUSION The online adaptive strategy using TMR ratios and pre-treatment CBCT information was feasible strategy to compensate for anatomical changes for the patients treated for L-spine tumors, particularly for equally spaced IMRT and VMAT plans.

SU-E-T-513: Investigating Dose of Internal Target Volume After Correcting for Tissue Heterogeneity in SBRT Lung Plans with Homogeneity Calculation

Purpose It was recommended to use the prescription of 54 Gy/3 with heterogeneity corrections for previously established dose scheme of 60 Gy/3 with homogeneity calculation. This study is to investigate dose coverage for the internal target volume (ITV) with and without heterogeneity correction. Methods Thirty patients who received stereotactic body radiotherapy (SBRT) to a dose of 60 Gy in 3 fractions with homogeneous planning for early stage non-small-cell lung cancer (NSCLC) were selected. ITV was created either from 4DCT scans or a fusion of multi-phase respiratory scans. Planning target volume (PTV) was a 5 mm expansion of the ITV. For this study, we recalculated homogeneous clinical plans using heterogeneity corrections with monitor units set as clinically delivered. All plans were calculated with 3 mm dose grids and collapsed cone convolution algorithm. To account for uncertainties from tumor delineation and image-guided radiotherapy, a structure ITV2mm was created by expanding ITV with 2 mm margins. Dose coverage to the PTV, ITV and ITV2mm were compared with a student paired t-test. Results With heterogeneity corrections, the PTV V60Gy decreased by 10.1% ± 18.4% (p<0.01) while the maximum dose to the PTV increased by 3.7 ± 4.3% (p<0.01). With and without corrections, D99% was 65.8 ± 4.0 Gy and 66.7 ± 4.8 Gy (p=0.15) for the ITV, and 63.9 ± 3.4 Gy and 62.9 ± 4.6 Gy for the ITV2mm (p=0.22), respectively. The mean dose to the ITV and ITV2mm increased 3.6% ± 4.7% (p<0.01) and 2.3% ± 5.2% (p=0.01) with heterogeneity corrections. Conclusion After heterogeneity correction, the peripheral coverage of the PTV decreased to approximately 54 Gy, but D99% of the ITV and ITV2mm was unchanged and the mean dose to the ITV and ITV2mm was increased. Clinical implication of these results requires more investigation.

SU-E-J-151: Dosimetric Evaluation of DIR Mapped Contours for Image Guided Adaptive Radiotherapy with 4D Cone-Beam CT

PURPOSE To estimate dosimetric errors resulting from using contours deformably mapped from planning CT to 4D cone beam CT (CBCT) images for image-guided adaptive radiotherapy of locally advanced non-small cell lung cancer (NSCLC). METHODS Ten locally advanced non-small cell lung cancer (NSCLC) patients underwent one planning 4D fan-beam CT (4DFBCT) and weekly 4DCBCT scans. Multiple physicians delineated the gross tumor volume (GTV) and normal structures in planning CT images and only GTV in CBCT images. Manual contours were mapped from planning CT to CBCTs using small deformation, inverse consistent linear elastic (SICLE) algorithm for two scans in each patient. Two physicians reviewed and rated the DIR-mapped (auto) and manual GTV contours as clinically acceptable (CA), clinically acceptable after minor modification (CAMM) and unacceptable (CU). Mapped normal structures were visually inspected and corrected if necessary, and used to override tissue density for dose calculation. CTV (6mm expansion of GTV) and PTV (5mm expansion of CTV) were created. VMAT plans were generated using the DIR-mapped contours to deliver 66 Gy in 33 fractions with 95% and 100% coverage (V66) to PTV and CTV, respectively. Plan evaluation for V66 was based on manual PTV and CTV contours. RESULTS Mean PTV V66 was 84% (range 75% - 95%) and mean CTV V66 was 97% (range 93% - 100%) for CAMM scored plans (12 plans); and was 90% (range 80% - 95%) and 99% (range 95% - 100%) for CA scored plans (7 plans). The difference in V66 between CAMM and CA was significant for PTV (p = 0.03) and approached significance for CTV (p = 0.07). CONCLUSION The quality of DIR-mapped contours directly impacted the plan quality for 4DCBCT-based adaptation. Larger safety margins may be needed when planning with auto contours for IGART with 4DCBCT images. Reseach was supported by NIH P01CA116602.