Purpose:Errors in displacement vector fields (DVFs) generated by Deformable Image Registration (DIR) algorithms can give rise to significant uncertainties in contour propagation and dose accumulation in Image‐Guided Adaptive Radiotherapy (IGART). The purpose of this work is to assess the accuracy of two DIR algorithms using a variety of quality metrics for prostate IGART.Methods:Pelvic CT images were selected from an anonymized database of nineteen prostate patients who underwent 8–12 serial scans during radiotherapy. Prostate, bladder, and rectum were contoured on 34 image‐sets for three patients by the same physician. The planning CT was deformably‐registered to daily CT using three variants of the Small deformation Inverse Consistent Linear Elastic (SICLE) algorithm: Grayscale‐driven (G), Contour‐driven (C, which utilizes segmented structures to drive DIR), combined (G+C); and also grayscale ITK demons (Gd). The accuracy of G, C, G+C SICLE and Gd registrations were evaluated using a new metric Edge Gradient Distance to Agreement (EGDTA) and other commonly‐used metrics such as Pearson Correlation Coefficient (PCC), Dice Similarity Index (DSI) and Hausdorff Distance (HD).Results:C and G+C demonstrated much better performance at organ boundaries, revealing the lowest HD and highest DSI, in prostate, bladder and rectum. G+C demonstrated the lowest mean EGDTA (1.14 mm), which corresponds to highest registration quality, compared to G and C DVFs (1.16 and 2.34 mm). However, demons DIR showed the best overall performance, revealing lowest EGDTA (0.73 mm) and highest PCC (0.85).Conclusion:As expected, both C‐ and C+G SICLE more accurately reproduce manually‐contoured target datasets than G‐SICLE or Gd using HD and DSI metrics. In general, the Gd appears to have difficulty reproducing large daily position and shape changes in the rectum and bladder. However, Gd outperforms SICLE in terms of EGDTA and PCC metrics, possibly at the expense of topological quality of the estimated DVFs.

Purpose:Use deformable registration to map more complex anatomies that include changes associated with both different body positions and breathing, and evaluate the resultant respiratory excursions for tumors and relevant organs at risk.Methods:Same‐day exhale and inhale datasets from prone and supine 4D CT scans of lung cancer patients have been registered using the Elastix software package through a 3 step process: (1) rigid registration for bony alignment (2) deformable multiresolution B‐Spline registration of entire anatomy (3) deformable multiresolution B‐Spline registration of lung parenchyma (to improve lung vasculature alignment).Manual contours were propagated from the supine‐inhale phase to supine‐exhale, prone‐exhale and prone‐inhale, via the resulting registration transformations. Motion excursions between exhale and inhale for both body orientations were computed for tumors, heart, esophagus, vertebrae (T2, T5, T12).Results:The registration accuracy was evaluated by visual inspection of the deformed contours by physicians and minimal contour adjustments were made where deemed appropriate. The average supine [mm] / prone [mm] motion amplitudes for the initial 5‐patient sample are as follows: Tumor – 5.8/6.5, T5 – 1.4/2.0, T2 – 0.5/1.6, T12 – 1.7/2.9, Heart– 4.9/9.0, Upper esophagus – 1.6/3.8, Middle esophagus – 3.8/5.0, Lower esophagus – 4.1/6.7. Differences between prone and supine excursions for heart, esophagus, T2 and T12 were significant at 95% level (one‐sided Wilcoxon Mann‐Whitney test).On average, the right and left lung volumes increased by 10% at inhale prone and by 5% at exhale prone from their respective values in supine position.Conclusion:A multi‐step deformable registration sequence was implemented and successfully used for supine‐prone image registration of thorax. In prone position, lungs are larger, likely owing to increased pulmonary compliance and decreased compressive force of the heart on lungs when prone. Breathing motion excursion is enhanced in prone, possible consequence of rib cage stabilization and increased diaphragmatic motion.Elisabeth Weiss: Research support from Philips Healthcare and National Institutes of Health; Licensing agreement with Varian Medical Systems, UpToDate royalties.

Local recurrence (LR) is common in locally advanced lung cancer. Predictive models of LR may allow risk based treatment paradigms and treatment adaptation. We hypothesized that primary tumor (PT) volume change during radiation therapy (RT) may be predictive of local recurrence. Thirty-four patients with inoperable locally advanced (stage II or III) non-small cell lung cancer treated with definitive fractionated RT ± chemotherapy were retrospectively reviewed on an IRB approved protocol. All patients underwent diagnostic PET/CT for staging and repeated fan beam CT scans during radiation therapy. The primary tumor (PT) was contoured on all CT scans. Clinical data including local recurrence of the PT based on CT RESIST criteria or as determined by PET/CT any time before death was recorded. A competing risk model was used to determine if there was a relationship between PT recurrence and percent reduction in tumor size per day. A secondary analysis assessed the relationship between distant recurrence and percent reduction in tumor size per day, with death considered an additional endpoint in each model. Fifteen (44%) patients had LR at the PT and nineteen (56%) patients developed DM. Median survival was 18.6 months. Sixteen patients (47%) had SCC, with remainder of non-squamous histology. Dose ranged from 52-67 Gy, with median dose of 66 Gy. Twenty-nine patients received chemotherapy. Median follow-up of living patients was 36 months. Average initial PET SUV max of PT was 16.20 (range 6-34). Median initial PT size was 81 cc (range 5-570 cc). Average percent reduction of tumor per day was 1.22 (range -0.78-3.07%, SD 0.83%). For every 0.25% decrease in the rate of tumor volume change per day, the likelihood of PT recurrence increased by a factor of 1.16 (95% CI: 1.01, 1.34; P=0.04). DM and survival were not associated with change in PT size. Neither initial tumor size (R2=0.04, p=0.26) nor initial SUV max (R2=0.04, p=0.28) correlated with percent tumor reduction per day. Larger initial tumor size was associated with increased risk of PT recurrence (p=0.02). Increased rate of tumor volume change based on repeated fan beam CT during RT is associated with a significantly lower rate of primary tumor recurrence and may provide an efficient and easily accessible early measure of RT response.

Purpose: Atelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position. Methods and materials: Twelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT. Results: The mean initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (−7 to 131 cm3) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was ≥0.5 cm in all patients and >1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P < .01), and the correlation was smaller with COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P = .002). Conclusions: Changes in AT and PT volumes during radiation treatment were significantly associated with PT displacements that often exceeded standard setup margins. Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for PT displacements during treatment.

Purpose: Adaptive Radiotherapy (ART) with frequent CT imaging has been used to improve dosimetric accuracy by accounting for anatomical variations, such as primary tumor shrinkage and/or body weight loss, in Head and Neck (H&N) patients. In most ART strategies, the difference between the planned and the delivered dose is estimated by generating new plans on repeated CT scans using dose-volume constraints used with the initial planning CT without considering already delivered dose. The aim of this study was to assess the dosimetric gains achieved by re-planning based on prior dose by comparing them to re-planning not based-on prior dose for H&N patients. Methods: Ten locally-advanced H&N cancer patients were selected for this study. For each patient, six weekly CT imaging were acquired during the course of radiotherapy. PTVs, parotids, cord, brainstem, and esophagus were contoured on both planning and six weekly CT images. ART with weekly re-plans were done by two strategies: 1) Generating a new optimized IMRT plan without including prior dose from previous fractions (NoPriorDose) and 2) Generating a new optimized IMRT plan based on the prior dose given from previous fractions (PriorDose). Deformable image registration was used to accumulate the dose distributions between planning and six weekly CT scans. The differences in accumulated doses for both strategies were evaluated using the DVH constraints for all structures. Results: On average, the differences in accumulated doses for PTV1, PTV2 and PTV3 for NoPriorDose and PriorDose strategies were <2%. The differences in Dmean to the cord and brainstem were within 3%. The esophagus Dmean was reduced by 2% using PriorDose. PriorDose strategy, however, reduced the left parotid D50 and Dmean by 15% and 14% respectively. Conclusion: This study demonstrated significant parotid sparing, potentially reducing xerostomia, by using ART with IMRT optimization based on prior dose for weekly re-planning of H&N cancer patients.

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