310 Accounting for lung tumor motion

$140 Wednesday, October 27, 2004

Time: the fourth dimension in radiotherapy 3O8

4D imaging and treatment planning E. Rietzel1"2, G. T. Y. Chen 1, N. C. Choi 1, C. G. Wlllett 3 ~Massachusetts General Hospital, Radiation Oncology, Boston, USA 2Gesellschaft fQr Schwerionenforschung, Abteilung Biophysik, Darmstadt, Germany 3Duke University, Radiation Oncology, Durham, USA Respiratory motion can introduce significant errors in radiotherapy imaging, treatment planning, and treatment delivery. 4D Computed Tomography provides time-resolved, spatio-temporal coherent volumetric data sets of patient anatomy [1]. Target volumes can be designed incorporating patient specific tumor motion. Furthermore, the impact of internal motion on dose distributions and organs at risk can be assessed. Patients are CT scanned in axial cine mode. At each couch position data are acquired for the duration of the patient's respiratory cycle. From such data, multiple images are reconstructed per couch position, each representing a different respiratory state. Images are sorted retrospectively into temporal coherent volumes by selecting images at the same respiratory phase for each slice. The 4DCT data acquisition protocol was improved and validated in several phantom studies. Typical motion artifacts are significantly reduced. For lung cancer patients, composite target volumes are used for treatment planning at MGH. Internal motion can be inspected visually by movie loops. To ensure adequate dose coverage throughout the respiratory cycle, the union of targets contoured on volumes at different respiratory phases is generated for treatment planning. For proton therapy of liver tumors, composite target volumes are treated. Sufficient proton penetration to the distal edge of the target is guaranteed by incorporating respiration induced density variations into treatment planning. Full dose coverage under respiration can be validated by recalculation of dose distributions for 4DCT volumes at all resorted respiratory phases. To calculate total effective dose distributions under respiratory motion, CT volumes have to be registered non-rigidly to maintain the dose-to-voxel relation. This has been accomplished using a free form deformation algorithm based on B-splines [2]. Dose distributions can be mapped to CTs at different respiratory phases by applying transformations obtained for non-rigid CT-CT registration. 4DCT data represents a snapshot of respiratory motion only and does not include possible daily variations. Therefore expansions from CTV to PTV have not significantly been reduced. To validate internal motion patient specifically, fluoroscopic studies and daily gated x-ray acquisition for patient set-up have been performed for some patients. [1] Pan et al, Med Phys 2004;31:333-40. [2] Rueckert et al, IEEE Trans Med Imaging 1999;18:712-21. 309

Four-dimensional radiotherapy planning P. Keall Medical College of Virginia Hospitals, VA Commonwealth Univ, Richmond, USA Four-dimensional (4D) radiotherapy isthe explicit inclusion of the temporal changes in anatomy during the imaging, planning and delivery of radiotherapy. High precision radiation therapy

Symposia

of moving targets is becoming increasingly important in this era of image-guided therapy. We have always known that humans are four-dimensional, though our current treatment techniques are predominantly three-dimensional. Anatomy and physiology of cancerous and healthy tissues changes with time, both within and between treatments. For radiotherapy patients, the additional effects of radiation, potentially with concomitant chemotherapy and or/hormone therapy can also cause anatomical changes during treatment. Though we have known about these anatomy changes with time, due to recent technological developments in both 4D imaging (as described in the previous presentation) and 4D radiation delivery, we are in an era where anatomical changes can be explicitly accounted for. Temporal anatomic changes can occur for many reasons, though the focus of this presentation is respiration motion for lung tumors. The rationale for 4D radiotherapy is increased targeting accuracy, allowing target dose escalation and/or normal tissue dose reduction, potential leading to higher tumor control with lower treatment-related toxicity. This presentation will describe 4D radiotherapy treatment-planning methodology based on a 4D CT image set, which typically contains 8-10 complete 3D CT image sets. There are several ways to use 4D CT for planning. In the absence of any treatment methods that explicitly account for respiratory motion, the GTV for each respiratory phase can be combined to form a respiratoryintegrated tumor volume (RTV), from which margins can be added to obtain the 3D PTV used for treatment. If respiratorygated radiotherapy is available, one of the constituent 4D CT image sets could be used for planning. If motion track(ng is available (the ability to move the beam with respect to the patient in near real-time) 4D treatment planning, both 4D CRT and 4D IMRT, can occur for each constituent 4D CT image sets, provided motion constraints of the delivery system are not exceeded. 4D radiotherapy can potentially reduce the magnitude of the internal margin applied to the CTV to create the PTV. However, additional geometric uncertainties introduced in the 4D radiotherapy process, including (1) limitations of the deformable image registration algorithm, (2) the correlation between the respiration signal and tumor position and (3) the response time of the motion tracking system, should also be taken into account during margin creation. As the 4D CT image set contains an order of magnitude more data than currently used for radiotherapy, automation of 4D planning processes isclearly necessary. 4D radiotherapy planning requires additional tools not available on existing treatment planning systems. These tools include (1) deformable image registration, (2) automated planning, (3) dose calculation on multiple datasets and (4) constrained optimization (for 4D IMRT). 310

Accounting for lung tumor motion C. Stevens 1, G. Starkschall 2, Z. Liao ~, T. Guerrero ~, J. Chang ~, R. Komakf, J. Cox ~, M. Jeeter~, K. Forster3 ~U.T. M.D. Anderson Cancer Center, Department of Radiation Oncology, Houston, TX, U.S.A. 2U. T. M.D. Anderson Cancer Center, Department of Radiation Physics, Houston, TX, U.S.A. 3U. T. Southwestern, Department of Radiation Oncology, Dallas, TX, U.S.A. We measured lung tumor motion in twenty-five patients. All patients had pathologically proven lung cancer, were be able to be trained to use the spirometer, and had a planned treatment course of at least 6 weeks. Patients with more than segmental atelectasis were excluded. CT images over the entire lung volume were acquired at 100% tidal volume (normal inspiration) and at 0% tidal volume (end expiration) using computerassisted occlusion spirometry. For each CT data set, the GTV

Symposia

was contoured and reviewed by two physicians. CT image sets were registered using the vertebral bodies. Lung motion was not uniform. Generally, the diaphragm moved anteriorly and inferiorly with inspiration, while the anterior chest wall moves slightly anteriorly. The carina can also move, usually anteriorly and inferiorly. The mediastinum generally narrows with inspiration, and the heart rotates. The mean tumor motion was 9.3 mm (_+4.3 mm). Mean motion of lower lobe lesions was 12.5 mm while for an upper lobe the mean was 7.8 mm. However, the standard deviation was quite large (30-50%). GTV volume, T stage, or tumor location did not predict tumor motion direction or magnitude. Tumors adjacent to the mediastinum tended to move medially with inspiration but standard deviations were large. Using this data, we determined if "standard" margins could be constructed to account for tumor motion. Tumors were contoured on the free breathing treatment planning CT scans. CTV expansion of 8mm was as was 7mm for setup uncertainty. If this volume was then expanded uniformly by 5mm, both the inspiration and expiration target volumes were within the free breathing PTV in only 10/25 cases. If this volume were expanded by 10 mm, only 20/25 cases were adequately covered. This would be an expansion of (8mm CTV + 7mm SU + 10mm motion) 25 mm from GTV. We concluded that tumor motion should be measured in each patient, and the margins individualized. A motion study was also repeated at the end of treatment in ten patients. Tumor motion changed significantly over the course of treatment with both the direction and' magnitude of tumor motion changing in all cases. In two cases, the final ITV was outside of the initial ITV by more than lcm, though the others were adequately covered. These data suggest that 3D-tumor motion should be assessed in each patient. Following the guidelines of ICRU 62, we now explicitly account for the tumor motion. The internal target volume (ITV) represents the volume occupied by the clinical target volume (CTV) during normal quiet respiration. In order to determine this volume, computed tomography (CT) image data sets at normal expiration (0% tidal volume) and at normal inspiration (100% tidal volume) as well as quiet-breathing image sets need to be acquired. Planning for all curatively treated patients uses ITV.

Lung cancer (RTT) 311 Improving therapeutic ratios in NSCLC: gating and/or IMRT? R. Underbercl, J. van S6msen de Koste, F. Lagerwaard, B. Slotman, S. Senan Vrije Universiteit Medical Centre, Department of Radiotherapy, Amsterdam, The Netherlands Background: With the use of conventional radiotherapy techniques, poor local control and/or excessive toxicity remain important problems in non-small cell lung cancer (NSCLC). Both intensity modulated radiotherapy (IMRT) and respiratory gating have considered potential solutions for these problems. This abstract addresses the merits of both the above approaches for stage I and stage III NSCLC. Stage I disease: Local control achieved with surgery serve as a reference goal for radiotherapy, and post-surgical 5 year survival rates range from 63-79% (stage IA; T1NoM0) to 44-60% (stage IB; T2NoM0). After conventional radiotherapy, however, overall survival rate at 5 years are only 21+8%, and the corresponding cause-specific survival is 25+9%. Factors contributing to these suboptimal results include the selection of an unfavourable patient population and geographic miss due to

Wednesday, October 27, 2004

$141

tumor mobility. Stereotactic radiotherapy (SRT) has been shown to be an excellent technique for delivering high biological tumor doses, with minimal normal tissue toxicity. At the VU medical centre, SRT is the standard treatment for stage I NSCLC. Our approach differs from the published literature in that we routinely perform respiration-correlated (4D) CT scans in order to derive internal target volumes (ITV, ICRU 62). This technique fully characterises all tumor mobility during the respiratory cycle, and mobility is subsequently into 10-20 phase 'bins'. 4D datasets offer the opportunity to accurately characterize mobility, and thereby identify patients in whom gating would be of benefit. As local control rates in excess of 85% have been reported with the use of SRT, and significant toxicity was not observed, the need for additional measures (e.g. gating) that may prolong treatment planning and delivery must carefully be evaluated. An analysis in 7 patients revealed that the average ITV's and planning target volumes could be reduced by 53% and 46%, respectively, when only three 'gating-bins' were selected [Underberg submitted]. Reductions of this magnitude are clinically significant for larger T2 tumors, and for trials of concurrent chemo-radiotherapy. A possible indication for the Use of IMRT are larger, less mobile tumors that are located in 'high-risk' areas, such as the hilum, thoracic wall and mediastinum. Even if pre-treatment mobility is fully characterised using 4D CT scans, inter-fractional changes may be a problem with IMRT as an increase in the PTV in 25% of patients with stage I NSCLC has been observed [Underberg submitted]. In these cases IMRT delivery may be considered risky unless onboard imaging (real-time tumor tracking) is available. Stage III disease: In stage III NSCLC, high local recurrences and toxicity remain major problems despite the survival advantage seen with 3D treatment planning. However, a major recent advance in non-surgical treatment was the comparable survival reported in stage Ill-N2 disease with either definitive chemo-radiotherapy (61 Gy), or induction chemo-radiotherapy followed by surgery [Turrisi 03]. The incidence of grade 3 or higher treatment-related toxicity was 22% with definitive chemoradiotherapy, thereby indicating that further approaches for reducing toxicity are needed. The benefits of IMRT for stage I11 NSCLC are still unclear as the steep dose gradients characterizing IMRT can lead to both geographic misses and unexpected toxicity can arise due to mobility of the tumor and normal organs. Measures other than IMRT, e.g. the omission of elective nodal irradiation already result in a lower incidence of toxicity. Data from 4D CT scans reveal that mediastinal nodes exhibit significant mobility, both the magnitude and direction of which may differ from that of the primary tumor [Underberg submitted]. Other problems related to use of IMRT are (i) the complexity of mobility in the thorax, (ii) limitations of commonly used dose-calculation algorithms, and (iii) the need for real-time tumor tracking. Our preliminary data indicates that, in carefully selected patients, gating (without IMRT) results in significant reductions in the irradiated volume versus approaches where all mobility is captured in an ITV. Gating has the advantage of being less complex and easier to implement. Examples showing mobility of different target volumes in the same patient, variations in planning volumes for normal organs at risk, consequences of mobility on IMRT plans and the relative benefits of RGRT will be used in order to illustrate why an individualized approach to treatment planning and delivery is needed for such patients. Conclusion: Excellent results can be achieved in stage I NSCLC using SRT, and respiratory gating can further reduce normal tissue irradiation, In stage III NSCLC, the first aim should be the reduction of treatment-related toxicity, especially of concurrent chemo-radiotherapy. Gating can considerably