X Qi

TH‐C‐224C‐07: EUD‐Assessed Impacts of Respiratory Motion On Breast Irradiation

Purpose:Respiration results in intrafractional motion and anatomic changes for both target and normal structures (e.g., lung,heart) during the radiation treatment for breast cancer. The purpose of this work is to quantify the dosimetric and radiobiological impacts using the concept of equivalent uniform dose (EUD). Method and Materials: Intrafractional variations were assessed based on 4DCT datasets acquired using a GE LightSpeed‐RT scanner and Varian RPM‐respiratory‐gating system. The 4DCT datasets along with the conventional 3DCT images for 10 patients were analyzed retrospectively. Each set of 4DCT consisted of 10 CT image sets at a phase between 0–90% during one respiration cycle. For each case, a 3D dosimetric plan of two tangential beams irradiating the whole breast was generated based on the 3DCT images using Xio (CMS) planning system. The parameters for this dosimetric plan (e.g., energy, beam angles, beam shape, wedge, weighting, isocenter location) were copied to each phase image set of the 4DCT to generated 3D dose distribution. DVHs for each phase image set were generated and were used for EUD calculation based on LQ model for breast tumor and Lyman model for lung.Results: 4DCT showed breast position/shape and lung position/shape/volume are changed with respiration. For example, lung volume changed up to 20% for the cases studied. These changes result in significant intrafractional variations in dose distributions/DVHs. Our calculations show that, compared to the planned EUD (based on the 3DCT), the breast EUD was lowered by an average of 5% (when including all 10 breathing phases) and up to 10% (at a particular phase). Lung EUD varied by ±3% during respiration.Conclusion: Respiratory motion in breast radiation treatment can potentially result in decreased target coverage and normal structure sparing. This effect that can be assessed using EUD, and decreased EUD may be an indicator for gated breast irradiation.

SU‐FF‐J‐35: Severe Inter‐Fractional Anatomic Changes and Their Dosimetric Impact in Abdominal Irradiation, An Indication for Adaptive Re‐Planning

Purpose: To study the dosimetric impact of inter‐fractional anatomic changes in the abdominal region during the course of radiation therapy and to determine the frequency of adaptive re‐planning. Methods and material: Daily CTimages acquired for selected abdominal cancer patients treated on a helical Tomotherapy unit were analyzed. The targets and organs at risk (OAR), such as kidneys,liver, cord and stomach, were delineated based on daily CT registered with the planning CT. The 3D dose distribution and dose volume histograms (DVHs) delivered to the patient on the day were reconstructed based on the CT of the day and the shifts performed (verification dose) using the Planned Adaptive software in the Tomotherapy planning system. The daily patient anatomy including body weight and locations, volumes and shapes of targets and OARs, as well as dose volume parameters including DVHs, maximum, minimum and mean doses and equivalent uniform dose (EUD) were compared to those from the planning CT.Results: Significant interfractional anatomic changes were observed for a patient with severe weight loss. In this patient with a suprarenal tumor, significant weight loss was observed during the second week (day 8) of radiotherapy, which led to 6.2%, 10.3% and 7% increases in maximum doses for PTV, the cord and unspecified tissue, respectively, from their values in the original plan. Compared to the original plan, the EUD changed by 24.6%, 11.3% and 14.6% respectively, for the right kidney,liver and stomach. In a cholangiocarcinoma case, dramatically organ volumetric and/or geometric changes for the liver and stomach were observed, resulting in changes in EUD of 16%, 22% and 46% for the liver, stomach and left‐kidney, respectively. Conclusion: Dramatic inter‐fractional anatomic changes in abdominal region, which can result in significant dosimetric impact and therefore, should be accounted for by an adaptive strategy, such as re‐planning.

MO‐FF‐A2‐02: Respiration Induced Heart Motion and Indications of Gated Delivery for Left‐Sided Breast Irradiation

Purpose: To study dosimetric gain of respiratory gating to account for heart motion during left‐sided breast irradiation and to determine indications for gating treatment during treatment planning.Methods and materials: The 4DCT data acquired with free breathing for 13 (out of 68) left‐sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Contours of the targets, lung and heart from the planning CT, selected to be the CT at 20% phase, were populated to 0‐ and 50%‐phase CT using deformable registration. The 3D dose distributions were reconstructed in these three phases (0, 20 and 50%). The heart dislocation between the breathing phases was measured in three selected transverse CT slices for the three phases by the changes of DLAD [the distance from left ascending aorta (LAD) to a fixed line drawn on each slice], and maximal heart depth (MDH, the distance of the forefront of the heart to the line). These distances were correlated with the changes of mean heart dose (MHD) and V25.2 for heart between the breathing phases. Results: Significant respiration induced heart displacement was seen, which resulted in substantial variations in dose delivered to the heart. In particular, the heart appeared to move towards to the chest wall during respiration, DLAD changed up to 9 mm, and MDH changed 10.4 mm, 11.0 mm and 10.7mm, respectively, on the three transverse CT slices from superior to inferior. The MHD and V25.2 varied up to 38% and 39%, respectively. These variations were reduced substantially with gating. Conclusion: The respiration induced heart displacement can result in significant variation in heart dose during left‐sided breast irradiation. A large variation in the distances: MDH and/or DLAD, can be used as an indicator to trigger respiratory management, such as gating prior to the treatment delivery.

SU-FF-J-74: Image-Guided Radiation Therapy for Large Soft Tissue Sarcoma: Tumor Volume Changes and Dosimetric Impacts

Purpose: To report our initial experience with image‐guidedradiation therapy for large soft tissuesarcoma with emphases on inter‐fractional tumor volume changes and their dosimetric impacts during the course of treatment.Methods and Materials: Twelve patients with large soft tissuesarcoma were treated with a Helical Tomotherapy unit. Daily MVCT images were acquired to guide patient positioning as well as monitoring the anatomical changes in clinical target volumes (CTVs) and other structures. The CTVs and normal structures were contoured on a series of daily MVCT sets, and were compared with the planning CTV and the planning target volume (PTV) obtained from planning KVCT. The 3D dose distributions and dose volume histograms (DVHs) the patient actually received were computed retrospectively based on the MVCT images using the Planned Adaptive software in the Tomotherapy planning system. These daily verification dose distributions and DVHs were compared to those from the original plan. Results: Daily pre‐treatment MVCT images demonstrated significant daily target shifts and allowed accurate localization of target volumes prior to each treatment. The significant tumor volume changes, both increases and decreases, were observed during the course of treatment. For a sample patient, the CTV (in the middle of the treatment) was found to be approximately doubled from the planning CTV, resulting in the original PTV smaller than the enlarged daily CTVs. The daily CTV coverage by the prescription dose varied from 30–95% during the course of treatment, which suggested significant underdosing in the CTVs. Conclusion: Dramatic inter‐fractional changes (increases and decreases) in gross tumor volume were observed during the radiation therapy of these large soft tissuesarcomas. Such changes can result in significant underdosing for tumor target(s) and/or overdosing for adjacent normal tissues, indicating that the image‐guided adaptive treatment with re‐planning can potentially improve tumor control and/or normal tissue sparing.

TH-C-224C-04: Radiobiological Concerns On Prolonged IMRT Delivery for Head-And-Neck Carcinoma

Purpose: Radiobiological effect of the prolonged IMRT delivery time on head‐and‐neck cancer has remain to be defined. The purpose of this work is to estimate a plausible set of radiobiological parameters (α/β, sublethal damage repair halftime, potential doubling time) for squamous cell carcinomas of head‐and‐neck (SCCHN) based on in vitro measurement and clinical data, and to examine the potential radiobiological influence due to the prolonged delivery time using the newly estimated parameters of SCCHN. Methods and Materials: In vitro cell survival measurements were performed for two cell lines of SCCHN irradiated by a series of specially‐designed single and split dose regimens using a 6 MV machine. The obtained survival data were fitted to the Linear‐Quadratic (LQ) model using the least χ2 technique. Other radiobiological models, such as equivalent uniformly dose (EUD) and tumor control probability (TCP), were used to analyze published clinical outcome to validate the parameters estimated from the in vitro data. Results: Based on the present in vitro measurements, we have estimated a set of radiobiological parameters for SCCHN: repair half‐time Tr = 16 ± 21 min, the potential doubling time Td = 48 ± 10 hours, radiosensitivity parameters α/β = 7.9 ± 4.5 Gy, α = 0.22 ± 0.08 Gy. This set of parameters was found to be able to fit the available clinical data. The calculation based on these parameters indicated that prolonged delivery time, if comparable/longer with the repair half‐time, would result in noticeable reduction in treatment effectiveness. For example, an IMRT delivery time of 30 minutes would result in a reduction of 11% in tumor EUD (compared to a 5‐minute fraction). Conclusions: The present measurement and analysis show that the repair half‐time and potential doubling time for head‐and‐neck cancer are relatively short, indicating that optimal IMRT delivery time needs to be clinically considered.

SU‐FF‐J‐122: Systematic Study of Inter‐Fractional Variations for Anatomic Sites From Head to Feet

Purpose: Inter‐fractional variations in patient set‐up and anatomic changes are usually site specific. This work aims to systematically study these inter‐fractional variations for anatomic sites from head to feet based on the daily MV CTimages collected using helical tomotherapy. Methods and Materials: A total of first 51 patients treated at various anatomic sites using a helical tomotherapy system (Hi‐Art, Tomotherapy Inc.) were analyzed. Daily Tomotherapy MV CT acquired prior to each treatment were used to correct for daily setup error online. A total of 6120 translational shifts and rotational corrections were performed for the 51 patients. The daily serial MV CT and the planning CT were also used to determine inter‐fractional anatomic changes off‐line. The data for three representative patient cases, pancreas, uterus, and soft tissuesarcoma, are presented. Results: Inter‐fractional set up errors in skull, brain, and head and neck are significantly smaller than those in chest, abdomen/pelvic, and extremity. The translational shifts are mostly within 3 mm in skull, brain, and head and neck, while they are within 6 mm for other sites. The inter‐fractional anatomic changes were significant. For example, during the course of treatment, the pancreas moved up to ±20 mm, and volumes of the uterus and sarcoma varied up to 30% and 100%, respectively. Conclusions: The inter‐fractional variations in patient setup and in shapes, sizes and positions of both targets and normal structures can be significant and are site specific. The helical Tomotherapy technology has the capability of quantifying and addressing these variations. The data presented in this work dealing with several anatomic sites may be useful in developing adaptive radiotherapy.

SU‐FF‐T‐382: Planning Non‐Uniform Dose Distributions for Brain Tumor

Purpose: Inhomogeneous radiobiology exists within tumor volume of malignant gliomas as shown by biological imaging. The purpose of this project is to plan non-uniform dose distributions to account for inhomogeneous radiosensitivity using IMRT. Method and Materials: Sample tumor volumes were divided into several sub-regions of different radiosensitivity that may be considered to correspond to different tumor grade. A pooled clinical and in-vitro data for gliomas were analyzed to determine radiosensitivity parameters for different tumor grades. LQ model and equivalent uniform dose (EUD) were used to calculate the required radiation dose to account for different tumor grade in different sub-region. While the required dose in each sub-region is uniform, the dose distribution within the entire tumor volume is non-uniform. The Xio/CMS IMRT planning system was used to plan the required non-uniform dose distributions and also the conventional 60Gy uniform dose. The EUDs for both uniform and non-uniform distributions were compared. Results: Using the parameters determined from clinical data the required dose (EUD in 2Gy fractions) was found to be >55Gy for grade 1 or 2, >60Gy for grade 3 and >65Gy for grade 4. Considering low tumor grade (thus low dose) existing in periphery region, IMRT can deliver the required non-uniform distributions while keeping or improving normal-tissue sparing compared to the conventional uniform dose delivery. The dose can be escalated even higher than the required value in a high-grade region. The non-uniform dose plans yield higher tumor EUD and lower or the same normal-tissue EUD as compared to the conventional plan, indicating that the non-uniform doses are more effective. Conclusion: It is dosimetrically feasible to plan non-uniform dose distributions to account for inhomogeneous radiosensitivity. This prepares a framework for biological imaging guided radiotherapy of malignant gliomas, a leading cause of cancer mortality in people with young ages.

SU‐FF‐T‐369: An Estimation of Radiobiological Parameters From Clinical Outcomes for Radiation Treatment Planning of Brain Tumor

Purpose: Appropriate organ‐specific radiobiological parameters are crucial for biologically‐based treatment planning. The purpose of this work is to derive a plausible set of such radiobiological parameters for malignant gliomas (MG) based on clinical outcomes. Method and Materials: Several radiobiological models, including the linear quadratic formalism with consideration of repopulation and repair, tumorcontrol probability and equivalent uniform dose, were used to analyze a series of published clinical data for MG involving different regimens of radiation therapy. The least chi‐square χ2 fitting technique was employed to estimate the LQ parameters. Results: A plausible set of LQ parameters: α = 0.08 ± 0.02 Gy−1, α/β = 11.4 ± 8.6 Gy, the tumor cell doubling time Td = 50 ± 30 days, with the repair halftime of 0.5 h was obtained for gliomas. The presently estimated biological parameters reasonably predict the effectiveness of the most of recently reported clinical results employing either single or combined RT modalities. In addiation, the radiosensitivity for grade III and VI astrocytoma was found to be: α = 0.18 ± 0.03 Gy−1, α/β = 6.0 ± 4.1 Gy and α = 0.09 ± 0.04 Gy−1, α/β = 9.0 ± 9.8 Gy respectively. For Grade III, our result agreed with the published in vitro data, while for Grade 4, the α and α/β values estimated presently based on clinical data are smaller than those from in vitro measurements, indicating lower radiosensitivity occurred in vivo as compared to in vitro. The derived α and α/β values demonstrated that GBM is quite radioresistant as known from clinical practice. Conclusion: The radiobiological parameters derived presently for MG can reasonably predict the most of the recently reported clinical results employing either single or combined RT modalities. These parameters can be potentially useful in evaluating, optimizing, and designing biological/functional image guided IMRT strategies.