M. Rosu

Advances in 4D radiation therapy for managing respiration: Part II – 4D treatment planning

The development of 4D CT imaging technology made possible the creation of patient models that are reflective of respiration-induced anatomical changes by adding a temporal dimension to the conventional 3D, spatial-only, patient description. This had opened a new venue for treatment planning and radiation delivery, aimed at creating a comprehensive 4D radiation therapy process for moving targets. Unlike other breathing motion compensation strategies (e.g. breath-hold and gating techniques), 4D radiotherapy assumes treatment delivery over the entire respiratory cycle - an added bonus for both patient comfort and treatment time efficiency. The time-dependent positional and volumetric information holds the promise for optimal, highly conformal, radiotherapy for targets experiencing movements caused by respiration, with potentially elevated dose prescriptions and therefore higher cure rates, while avoiding the uninvolved nearby structures. In this paper, the current state of the 4D treatment planning is reviewed, from theory to the established practical routine. While the fundamental principles of 4D radiotherapy are well defined, the development of a complete, robust and clinically feasible process still remains a challenge, imposed by limitations in the available treatment planning and radiation delivery systems.

Lovastatin may reduce the risk of erectile dysfunction following radiation therapy for prostate cancer

reported. Yoshida et al. developed and validated the UBTAT-tool and correlated it to radiation-induced morbidity by RTOG score [3]. UBTAT measurements correlated with late toxicity grades. Skin and subcutaneous endpoints were pooled, and it is unknown if the UBTAT-tool can distinguish between these endpoints. Zhou et al. found two US measures from subcutaneous tissue in women treated with RT for early breast cancer being significantly different between irradiated and contralateral breast. Findings were not correlated to a clinical assessment of radiation-induced morbidity [5]. To our knowledge, our pilot study is the first to consider both induration and edema, but has a small sample size and an inadequate protocol for data acquisition of density measures in edematous patients. We found the largest difference in dermis thickness of 1.61 mm in patients with grade 2 induration combined with edema, whereas the lowest of 0.35 mm was for patients with grade 1 induration and without edema, although the latter was not statistically significant. Regression analysis showed a significant effect of edema, increasing dermis thickness with a mean 1.01 mm when present versus not present. The effect of induration alone remains inconclusive. Presently, we do not see US/HFUS evaluation of the skin as a part of large-scale follow-up routines in the assessment of radiation-induced morbidity. Data from the present study and the literature confirm a measurable skin (dermis ± epidermis) thickness difference present between irradiated and nonirradiated breast after RT, which is partly caused by edema. What we still seek is a reliable discriminative quality between radiation-induced morbidity endpoints and their grades. This would enable inter-individual and -institutional quality assurance and serve as an objective marker in future trials testing new regimens in treatment of radiation-induced morbidity of the skin.

Effect of variations in atelectasis on tumor displacement during radiation therapy for locally advanced lung cancer

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.

Variations of the Tumor Position in Frameless Lung Sbrt: Assessment of Predictive Factors Including Tumor Volume Changes

Purpose: To quantify inter- and intrafractional variations of tumor position and analyze the relationship between these changes and respiratory motion amplitude, volume changes and tumor location, in frameless stereotactic body radiotherapy (SBRT) of lung tumors. Materials and methods: Tumor volumes and bony landmarks were contoured manually by a single physician on 174 pre- and under treatment cone-beam computed tomographies (CBCTs) of 17 patients. The interfraction variation of the tumor position was measured by comparing the centroid position of the tumor relative to bony anatomy of each fraction to the pretreatment CBCT scans. The intrafraction variation was measured by comparing the pretreatment tumor location to under treatment CBCTs for every fraction. Respiratory motion was analyzed on planning 4D fan beam CTs for all patients. The change in tumor volume was determined by comparing the contoured tumor volumes on sequential pretreatment CBCTs. Results: The average interfraction/intrafraction tumor displacementrelative to bony landmark in mm was 0.6 (SD 2.3) /-0.3 (SD 0.7) in mediolateral, -0.7 (SD 3.8) /0.0 (SD 2.1) in anteroposterior, and -0.6 (SD 5.9) /-0.2 (SD 2.3) in craniocaudal direction. Inter-/intrafraction tumor-to-bone variations >3 mm were observed in 60%/14% of scans respectively. On the initial CBCT, the average tumor volume was 9 cm3 (range 1-37 cm3) with a mean volume reduction over the treatment course of 12% (range, +14% to -54%). Patients with a pretreatment motion amplitude > 9 mm (p=0.002), peripheral tumor location (p=0.04), and volume change >12% (p=0.009) had larger interfraction displacement in lateral direction. Conclusions: Frameless set up is comparable to patient positioning with more elaborate fixation devices. Tumor position variations relative to bony anatomy are an important source of geometric uncertainty providing a rationale for repeated soft tissue-based image guidance, particularly in patients identified in this study to be at higher risk for variations.

SU-F-J-120: Evaluation of the Combined Effect of Body Orientation and Breathing On Organ Movement in Thorax Using Multi-Step Deformable Image Registration

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.

SU-F-T-250: What Does It Take to Correctly Assess the High Failure Modes of an Advanced Radiotherapy Procedure Such as Stereotactic Body Radiation Therapy?

PURPOSE Assess the correct implementation of risk-based methodology of TG 100 to optimize quality management and patient safety procedures for Stereotactic Body Radiation Therapy. METHODS A detailed process map of SBRT treatment procedure was generated by a team of three physicists with varying clinical experience at our institution to assess the potential high-risk failure modes. The probabilities of occurrence (O), severity (S) and detectability (D) for potential failure mode in each step of the process map were assigned by these individuals independently on the scale from1 to 10. The risk priority numbers (RPN) were computed and analyzed. The highest 30 potential modes from each physicists analysis were then compared. RESULTS The RPN values assessed by the three physicists ranged from 30 to 300. The magnitudes of the RPN values from each physicist were different, and there was no concordance in the highest RPN values recorded by three physicists independently. The 10 highest RPN values belonged to sub steps of CT simulation, contouring and delivery in the SBRT process map. For these 10 highest RPN values, at least two physicists, irrespective of their length of experience had concordance but no general conclusions emerged. CONCLUSION This study clearly shows that the risk-based assessment of a clinical process map requires great deal of preparation, group discussions, and participation by all stakeholders. One group albeit physicists cannot effectively implement risk-based methodology proposed by TG100. It should be a team effort in which the physicists can certainly play the leading role. This also corroborates TG100 recommendation that risk-based assessment of clinical processes is a multidisciplinary team effort.

SU-E-T-538: Does Abdominal Compression Through Prone Patient Position Reduce Respiratory Motion in Lung Cancer Radiotherapy?

PURPOSE This study assesses the effect of physiological abdominal compression from prone positioning by comparing respiratory-induced tumor movements in supine and prone positions. METHODS 19 lung cancer patients underwent repeated supine and prone free-breathing 4DCT scans. The effect of patient position on motion magnitude was investigated for tumors, lymph nodes (9 cases), and subgroups of central (11 cases), peripheral (8 cases) and small peripheral tumors (5 cases), by evaluating the population average excursions, absolute and relative to a carina-point. RESULTS Absolute motion analysis: In prone, motion increased by ~20% for tumors and ~25% for lymph nodes. Central tumors moved more compared to peripheral tumors in both supine and prone (~22%, and ~4% respectively). Central tumors movement increased by ~12% in prone. For peripheral tumors the increase in prone position was ~25% (~40% and 29% changes on along RL and AP directions). Motion relative to carina-point analysis: Overall, tumor excursions relative to carina-point increased by ~17% in prone. Lymph node relative magnitudes were lower by ~4%. Likewise, the central tumors moved ~7% less in prone. The subgroup of peripheral tumors exhibited increased amplitudes by ~44%; the small peripheral tumors had even larger relative displacements in prone (~46%). CONCLUSION Tumor and lymph node movement in the patient population from this study averaged to be higher in prone than in supine position. Results from carina analysis also suggest that peripheral tissues have more physiologic freedom of motility when placed in the prone position, regardless of size. From these observations we should continue to avoid prone positioning for all types of primary lung tumor, suggesting that patients should receive radiotherapy for primary lung cancer in supine position to minimize target tissue mobility during normal respiratory effort. Further investigation will include more patients with peripheral tumors to validate our observations.

SU-E-J-227: Breathing Pattern Consistency and Reproducibility: Comparative Analysis for Supine and Prone Body Positioning

PURPOSE Evaluate and compare the cycle-to-cycle consistency of breathing patterns and their reproducibility over the course of treatment, for supine and prone positioning. METHODS Respiratory traces from 25 patients were recorded for sequential supine/prone 4DCT scans acquired prior to treatment, and during the course of the treatment (weekly or bi-weekly). For each breathing cycle, the average(AVE), end-of-exhale(EoE) and end-of-inhale(EoI) locations were identified using in-house developed software. In addition, the mean values and variations for the above quantities were computed for each breathing trace. F-tests were used to compare the cycle-to-cycle consistency of all pairs of sequential supine and prone scans. Analysis of variances was also performed using population means for AVE, EoE and EoI to quantify differences between the reproducibility of prone and supine respiration traces over the treatment course. RESULTS Consistency: Cycle-to-cycle variations are less in prone than supine in the pre-treatment and during-treatment scans for AVE, EoE and EoI points, for the majority of patients (differences significant at p<0.05). The few cases where the respiratory pattern had more variability in prone appeared to be random events. Reproducibility: The reproducibility of breathing patterns (supine and prone) improved as treatment progressed, perhaps due to patients becoming more comfortable with the procedure. However, variability in supine position continued to remain significantly larger than in prone (p<0.05), as indicated by the variance analysis of population means for the pretreatment and subsequent during-treatment scans. CONCLUSIONS Prone positioning stabilizes breathing patterns in most subjects investigated in this study. Importantly, a parallel analysis of the same group of patients revealed a tendency towards increasing motion amplitude of tumor targets in prone position regardless of their size or location; thus, the choice for body positioning during radiation therapy will have to consider the clinical relevance of the two opposing trends - breathing consistency and motion amplitude.

SU‐E‐J‐120: Reduction in Breathing Motion Intra‐Fraction Variability through Prone Body Positioning

Purpose: Simplicity in treatment is preferable, whenever possible: it reduces errors, execution time and effort, and increases patient confidence. We aim at this benefit by using a natural body compression approach through positioning the patient prone, instead of the habitual (albeit unsubstantiated) supine positioning. The innovative premise tested in this work is that prone positioning can moderate the respiratory‐induced motion and make it more consistent from cycle‐to‐cycle, compared to supine positioning. Methods: Breathing traces from 8 patients positioned supine, then prone, were used to evaluate cycle‐to‐cycle variances in end‐of‐exhale(EoE), end‐of‐inhale(EoI) and average(AVE) locations, and to quantify the statistical significance at a p‐value=0.05. Population variances were also evaluated for these locations. Results: Prone positioning has improved EoE‐location consistency for all patients, and was superior in all but one case for AVE‐location. EoI reproducibility was poorer (improved in 5 out of 8 cases). Data analysis for the entire population reveals an overall improvement through prone positioning for all locations of interest. Variance reduction implies a corresponding reduction in the random component of the respiratory motion. Conclusions: Our analysis demonstrates statistically significant improvements in breathing pattern consistency in prone position. This conclusion can be extended to the tumor motion as well, under the assumption that the RPM traces and the tumor trajectories exhibit similar motion pattern characteristics, a condition often fulfilled. Radiotherapy with prone body positioning is straightforward and non‐invasive, and can be implemented without using complex respirationcontrol technology (therefore could become widespread available). The reduction in breathing variability through prone positioning offers the potential for 4DCT image acquisition with even fewer motion artifacts and for radiation delivery under anatomical conditions resembling more closely those from the pre‐treatment CT scans, while enabling the possibility of tumordose escalation at similar or reduced normal tissuedoses compared to the conventional supine treatment position.