N Shusharina

Correlation of 18F-FDG Avid Volumes on Pre–Radiation Therapy and Post–Radiation Therapy FDG PET Scans in Recurrent Lung Cancer

PURPOSE To investigate the spatial correlation between high uptake regions of 2-deoxy-2-[(18)F]-fluoro-D-glucose positron emission tomography ((18)F-FDG PET) before and after therapy in recurrent lung cancer. METHODS AND MATERIALS We enrolled 106 patients with inoperable lung cancer into a prospective study whose primary objectives were to determine first, the earliest time point when the maximum decrease in FDG uptake representing the maximum metabolic response (MMR) is attainable and second, the optimum cutoff value of MMR based on its predicted tumor control probability, sensitivity, and specificity. Of those patients, 61 completed the required 4 serial (18)F-FDG PET examinations after therapy. Nineteen of 61 patients experienced local recurrence at the primary tumor and underwent analysis. The volumes of interest (VOI) on pretherapy FDG-PET were defined by use of an isocontour at ≥50% of maximum standard uptake value (SUVmax) (≥50% of SUVmax) with correction for heterogeneity. The VOI on posttherapy images were defined at ≥80% of SUVmax. The VOI of pretherapy and posttherapy (18)F-FDG PET images were correlated for the extent of overlap. RESULTS The size of VOI at pretherapy images was on average 25.7% (range, 8.8%-56.3%) of the pretherapy primary gross tumor volume (GTV), and their overlap fractions were 0.8 (95% confidence interval [CI]: 0.7-0.9), 0.63 (95% CI: 0.49-0.77), and 0.38 (95% CI: 0.19-0.57) of VOI of posttherapy FDG PET images at 10 days, 3 months, and 6 months, respectively. The residual uptake originated from the pretherapy VOI in 15 of 17 cases. CONCLUSIONS VOI defined by the SUVmax-≥50% isocontour may be a biological target volume for escalated radiation dose.

Analytic regularization of uniform cubic b-spline deformation fields

Image registration is inherently ill-posed, and lacks a unique solution. In the context of medical applications, it is desirable to avoid solutions that describe physically unsound deformations within the patient anatomy. Among the accepted methods of regularizing non-rigid image registration to provide solutions applicable to medical practice is the penalty of thin-plate bending energy. In this paper, we develop an exact, analytic method for computing the bending energy of a three-dimensional B-spline deformation field as a quadratic matrix operation on the spline coefficient values. Results presented on ten thoracic case studies indicate the analytic solution is between 61-1371x faster than a numerical central differencing solution.

TH‐C‐WAB‐03: A Robust Intensity Similarity Measure for Multi‐Atlas Segmentation

PURPOSE Atlas-based segmentation is a general approach to automatic segmentation that labels regions of an image based on their alignment to existing structures in an atlas image. The atlas-based approach can be improved by aligning multiple atlases with the target image, and fusing their results. A typical strategy for multi-atlas segmentation is weighted voting that combines structure distance with intensity similarity. This abstract investigates the use of a robust measure for penalizing the similarity of voxel intensities when voting. METHODS Experiments were performed comparing the robust measure, a truncated quadratic penalty, with the more commonly used quadratic penalty. An atlas database of 20 subjects with structures segmented on head and neck CT were evaluated. Training parameters were tuned using leave-one-out cross validation. RESULTS Automatic segmentation results were evaluated using the Dice similarity coefficient. The average Dice scores for segmentations produced with a quadratic penalty were 0.78 for brainstem; 0.78 and 0.77 for left and right eye balls; 0.66 and 0.64 for left and right parotids. The average Dice scores for segmentations produced with the truncated quadratic penalty were 0.82 for brainstem; 0.85 and 0.84 for left and right eye balls; 0.74 and 0.73 for left and right parotids. CONCLUSION A robust intensity similarity measure, such as a truncated quadratic penalty, can be an effective approach for improving overall segmentation quality for multi-atlas methods. National Institutes of Health.

Differences in lung injury after IMRT or proton therapy assessed by 18FDG PET imaging

BACKGROUND AND PURPOSE To compare lung injury among non-small cell lung cancer (NSCLC) patients treated with IMRT or proton therapy as revealed by 18F-FDG post-treatment uptake and to determine factors predictive for clinically symptomatic radiation pneumonitis. MATERIAL AND METHODS For 83 patients treated with IMRT or proton therapy, planning CT and follow up 18F-FDG PET-CT were analyzed. Post-treatment PET-CT was aligned with planning CT to establish a voxel-to-voxel correspondence between PET and planning dose images. 18F-FDG uptake as a function of radiation dose to normal lung was obtained for each patient. PET image-derived parameters as well as demographic, clinical, treatment and dosimetric patient characteristics were correlated with clinical symptoms of pneumonitis. RESULTS The dose distributions for the two modalities were significantly different; V5 was higher for IMRT, whereas V60 was higher for protons. The mean lung dose (MLD) was similar for the two modalities. The slope of linear 18F-FDG-uptake - dose response did not differ significantly between the two modalities. The MLD, slope, and 95th percentile of SUV were identified as three major factors associated with radiation pneumonitis. CONCLUSIONS Despite significantly different dose distributions for IMRT and for protons, the slope of the SUV-dose linear regression line previously shown to be associated with RP did not differ between IMRT and protons. Patients who developed radiation pneumonitis had statistically significantly higher MLD and higher slope regardless of treatment modality.

The clinical target distribution: a probabilistic alternative to the clinical target volume

Definition of the clinical target volume (CTV) is one of the weakest links in the radiation therapy chain. In particular, inability to account for uncertainties is a severe limitation in the traditional CTV delineation approach. Here, we introduce and test a new concept for tumor target definition, the clinical target distribution (CTD). The CTD is a continuous distribution of the probability of voxels to be tumorous. We describe an approach to incorporate the CTD in treatment plan optimization algorithms, and implement it in a commercial treatment planning system. We test the approach in two synthetic and two clinical cases, a sarcoma and a glioblastoma case. The CTD is straightforward to implement in treatment planning and comes with several advantages. It allows one to find the most suitable tradeoff between target coverage and sparing of surrounding healthy organs at the treatment planning stage, without having to modify or redraw a CTV. Owing to the variable probabilities afforded by the CTD, a more flexible and more clinically meaningful sparing of critical structure becomes possible. Finally, the CTD is expected to reduce the inter-user variability of defining the traditional CTV.

SU‐C‐207A‐07: Cumulative 18F‐FDG Uptake Histogram Relative to Radiation Dose Volume Histogram of Lung After IMRT Or PSPT and Their Association with Radiation Pneumonitis

PURPOSE To determine whether the difference in cumulative 18F-FDG uptake histogram of lung treated with either IMRT or PSPT is associated with radiation pneumonitis (RP) in patients with inoperable stage II and III NSCLC. METHODS We analyzed 24 patients from a prospective randomized trial to compare IMRT (n=12) with vs. PSPT (n=12) for inoperable NSCLC. All patients underwent PET-CT imaging between 35 and 88 days post-therapy. Post-treatment PET-CT was aligned with planning 4D CT to establish a voxel-to-voxel correspondence between post-treatment PET and planning dose images. 18F-FDG uptake as a function of radiation dose to normal lung was obtained for each patient. Distribution of the standard uptake value (SUV) was analyzed using a volume histogram method. The image quantitative characteristics and DVH measures were correlated with clinical symptoms of pneumonitis. RESULTS Patients with RP were present in both groups: 5 in the IMRT and 6 in the PSPT. The analysis of cumulative SUV histograms showed significantly higher relative volumes of the normal lung having higher SUV uptake in the PSPT patients for both symptomatic and asymptomatic cases (VSUV=2: 10% for IMRT vs 16% for proton RT and VSUV=1: 10% for IMRT vs 23% for proton RT). In addition, the SUV histograms for symptomatic cases in PSPT patients exhibited a significantly longer tail at the highest SUV. The absolute volume of the lung receiving the dose >70 Gy was larger in the PSPT patients. CONCLUSION 18F-FDG uptake - radiation dose response correlates with RP in both groups of patients by means of the linear regression slope. SUV is higher for the PSPT patients for both symptomatic and asymptomatic cases. Higher uptake after PSPT patients is explained by larger volumes of the lung receiving high radiation dose.

SU-G-BRC-12: Isotoxic Dose Escalation for Advanced Lung Cancer: Comparison of Different Boosting Strategiesfor Patients with Recurrent Disease

PURPOSE To determine the dose level and timing of the boost in locally advanced lung cancer patients with confirmed tumor recurrence by comparing different boosting strategies by an impact of dose escalation in improvement of the therapeutic ratio. METHODS We selected eighteen patients with advanced NSCLC and confirmed recurrence. For each patient, a base IMRT plan to 60 Gy prescribed to PTV was created. Then we compared three dose escalation strategies: a uniform escalation to the original PTV, an escalation to a PET-defined target planned sequentially and concurrently. The PET-defined targets were delineated by biologically-weighed regions on a pre-treatment 18F-FDG PET. The maximal achievable dose, without violating the OAR constraints, was identified for each boosting method. The EUD for the target, spinal cord, combined lung, and esophagus was compared for each plan. RESULTS The average prescribed dose was 70.4±13.9 Gy for the uniform boost, 88.5±15.9 Gy for the sequential boost and 89.1±16.5 Gy for concurrent boost. The size of the boost planning volume was 12.8% (range: 1.4 - 27.9%) of the PTV. The most prescription-limiting dose constraints was the V70 of the esophagus. The EUD within the target increased by 10.6 Gy for the uniform boost, by 31.4 Gy for the sequential boost and by 38.2 for the concurrent boost. The EUD for OARs increased by the following amounts: spinal cord, 3.1 Gy for uniform boost, 2.8 Gy for sequential boost, 5.8 Gy for concurrent boost; combined lung, 1.6 Gy for uniform, 1.1 Gy for sequential, 2.8 Gy for concurrent; esophagus, 4.2 Gy for uniform, 1.3 Gy for sequential, 5.6 Gy for concurrent. CONCLUSION Dose escalation to a biologically-weighed gross tumor volume defined on a pre-treatment 18F-FDG PET may provide improved therapeutic ratio without breaching predefined OAR constraints. Sequential boost provides better sparing of OARs as compared with concurrent boost.

SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition.

PURPOSE Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. METHODS 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. RESULTS Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. CONCLUSION It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

SU‐E‐J‐85: Landmark‐Driven Interactive Deformable Image Registration

Purpose: To build a framework for deformable B‐spline image registration with user controlled accuracy by using the positions of point landmarks as guidance. Methods: Manually identified point landmarks are placed on the reference image and their corresponding locations on the test image. An intensity‐based similarity measure is optimized under the constraint of minimizing the distance between the corresponding landmarks. After the Result of registration is visually inspected, the positions of the landmarks may be manually adjusted to improve matching accuracy. Each landmark adjustment operation triggers a re‐optimization routine, which can be repeated until the desired accuracy is reached. Results: We have tested the method on medical use cases to register CT images of the upper body, common in radiotherapy of head and neck cancer. The registration of these images compensates for position error, including pitch and yaw of the head, and flexion of the spine. Deformable registration of these images is very challenging when there is a large spatial shift of the head position. Placing landmarks on a single cross‐section and running optimization one or two times leads to a satisfactory Result. Conclusion: We have developed a practical method of interactive, intuitive correction of deformable registration of medical images. The method integrates both intensity and landmark matching. Our results prove the feasibility of the method and demonstrate potential of the tool for clinical applications.

TH‐A‐BRA‐10: The Role of Treatment Plan Adaptation during the Course of Proton Radiotherapy for Patients with Head and Neck Cancer

Purpose: To evaluate the advantages of adaptive replanning associated with protonradiotherapytreatment of patients with head and neck cancer.Methods: Six patients with tumors in the base of skull were treated with protonradiotherapy. Two CTs of the same patient, planning and repeat, were first registered rigidly in relation to bony structures of the skull to remove the setup error. A deformable B‐spline based registration was performed between the two CTs. The resulting deformation field was used to automatically transfer structure contours from the planning‐CT to the repeat‐CT. The original treatment plan was applied to the repeat‐CT and the dose distribution was recalculated. The differences between new and original dose distributions were evaluated by comparing isodose lines and by performing distance‐to‐agreement dose distribution analysis. The automatically transferred contours were used to compute dose‐volume histograms for the repeat‐CT and these were compared to the original DVHs. Results: Autotransferred contours were investigated by a physician and found satisfactory for the most critical structures. The targets were delineated manually. Anatomic changes caused by patient response to the treatment were primarily due to tumor shrinkage in the nasal cavity and in the paranasal sinuses. As a result the areas around target became highly heterogeneous with respect to density distribution. In 2 cases these heterogeneities resulted in hot spots within the tumor larger than 1 cm3 with a dose increase of 6%. In one case a cold spot with a dose decrease of 7% was observed. Conclusions: Evaluation of six cases shows no significant dosimetric changes that can favor adaptive replanning at the mid‐course of protonradiotherapy of head and neck cancer. Analysis of a larger patient set is needed to establish robust patterns of tissue deformation and dosimetric changes, with a focus on variations of the dose distribution in the presence of heterogeneities.