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At least 1,261 records · Page 70
All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

Consensus Guidelines for Delineation of Clinical Target Volume for Intensity-Modulated Pelvic Radiotherapy for the Definitive Treatment of Cervix Cancer

Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Reirradiation of Large-Volume Recurrent Glioma With Pulsed Reduced-Dose-Rate Radiotherapy

Purpose: Pulsed reduced-dose-rate radiotherapy (PRDR) is a reirradiation technique that reduces the effective dose rate and increases the treatment time, allowing sublethal damage repair during irradiation. Patients and Methods: A total of 103 patients with recurrent glioma underwent reirradiation using PRDR (86 considered to have Grade 4 at PRDR). PRDR was delivered using a series of 0.2-Gy pulses at 3-min intervals, creating an apparent dose rate of 0.0667 Gy/min to a median dose of 50 Gy (range, 20-60) delivered in 1.8-2.0-Gy fractions. The mean treatment volume was 403.5 {+-} 189.4 cm{sup 3} according to T{sub 2}-weighted magnetic resonance imaging and a 2-cm margin. Results: For the initial or upgraded Grade 4 cohort (n = 86), the median interval from the first irradiation to PRDR was 14 months. Patients undergoing PRDR within 14 months of the first irradiation (n = 43) had a median survival of 21 weeks. Those treated {>=}14 months after radiotherapy had a median survival of 28 weeks (n = 43; p = 0.004 and HR = 1.82 with a 95% CI ranging from 1.25 to 3.10). These data compared favorably to historical data sets, because only 16% of the patients were treated at first relapse (with 46% treated at the second relapse, 32% at the third or fourth relapse, and 4% at the fourth or fifth relapse). The median survival since diagnosis and retreatment was 6.3 years and 11.4 months for low-grade, 4.1 years and 5.6 months for Grade 3, and 1.6 years and 5.1 months for Grade 4 tumors, respectively, according to the initial histologic findings. Multivariate analysis revealed age at the initial diagnosis, initial low-grade disease, and Karnofsky performance score of {>=}80 to be significant predictors of survival after initiation of PRDR. Conclusion: PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Assessment of Planning Target Volume Margins for Intensity-Modulated Radiotherapy of the Prostate Gland: Role of Daily Inter- and Intrafraction Motion

Purpose: To determine planning target volume margins for prostate intensity-modulated radiotherapy based on inter- and intrafraction motion using four daily localization techniques: three-point skin mark alignment, volumetric imaging with bony landmark registration, volumetric imaging with implanted fiducial marker registration, and implanted electromagnetic transponders (beacons) detection. Methods and Materials: Fourteen patients who underwent definitive intensity-modulated radiotherapy for prostate cancer formed the basis of this study. Each patient was implanted with three electromagnetic transponders and underwent a course of 39 treatment fractions. Daily localization was based on three-point skin mark alignment followed by transponder detection and patient repositioning. Transponder positioning was verified by volumetric imaging with cone-beam computed tomography of the pelvis. Relative motion between the prostate gland and bony anatomy was quantified by offline analyses of daily cone-beam computed tomography. Intratreatment organ motion was monitored continuously by the Calypso (registered) System for quantification of intrafraction setup error. Results: As expected, setup error (that is, inter- plus intrafraction motion, unless otherwise stated) was largest with skin mark alignment, requiring margins of 7.5 mm, 11.4 mm, and 16.3 mm, in the lateral (LR), longitudinal (SI), and vertical (AP) directions, respectively. Margin requirements accounting for intrafraction motion were smallest for transponder detection localization techniques, requiring margins of 1.4 mm (LR), 2.6 mm (SI), and 2.3 mm (AP). Bony anatomy alignment required 2.1 mm (LR), 9.4 mm (SI), and 10.5 mm (AP), whereas image-guided marker alignment required 2.8 mm (LR), 3.7 mm (SI), and 3.2 mm (AP). No marker migration was observed in the cohort. Conclusion: Clinically feasible, rapid, and reliable tools such as the electromagnetic transponder detection system for pretreatment target localization and, subsequently, intratreatment target location monitoring allow clinicians to reduce irradiated volumes and facilitate safe dose escalation, where appropriate.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Dose-Volume Histogram Parameters and Clinical Factors Associated With Pleural Effusion After Chemoradiotherapy in Esophageal Cancer Patients

Purpose: To investigate the dose-volume histogram parameters and clinical factors as predictors of pleural effusion in esophageal cancer patients treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Forty-three esophageal cancer patients treated with definitive CRT from January 2001 to March 2007 were reviewed retrospectively on the basis of the following criteria: pathologically confirmed esophageal cancer, available computed tomography scan for treatment planning, 6-month follow-up after CRT, and radiation dose {>=}50 Gy. Exclusion criteria were lung metastasis, malignant pleural effusion, and surgery. Mean heart dose, mean total lung dose, and percentages of heart or total lung volume receiving {>=}10-60 Gy (Heart-V{sub 10} to V{sub 60} and Lung-V{sub 10} to V{sub 60}, respectively) were analyzed in relation to pleural effusion. Results: The median follow-up time was 26.9 months (range, 6.7-70.2) after CRT. Of the 43 patients, 15 (35%) developed pleural effusion. By univariate analysis, mean heart dose, Heart-V{sub 10} to V{sub 60}, and Lung-V{sub 50} to V{sub 60} were significantly associated with pleural effusion. Poor performance status, primary tumor of the distal esophagus, and age {>=}65 years were significantly related with pleural effusion. Multivariate analysis identified Heart-V{sub 50} as the strongest predictive factor for pleural effusion (p = 0.01). Patients with Heart-V{sub 50} <20%, 20%{<=} Heart-V{sub 50} <40%, and Heart-V{sub 50} {>=}40% had 6%, 44%, and 64% of pleural effusion, respectively (p < 0.01). Conclusion: Heart-V{sub 50} is a useful parameter for assessing the risk of pleural effusion and should be reduced to avoid pleural effusion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Evaluation of the Planning Target Volume in the Treatment of Head and Neck Cancer With Intensity-Modulated Radiotherapy: What Is the Appropriate Expansion Margin in the Setting of Daily Image Guidance?

Purpose: To compare patterns of disease failure among patients treated with intensity-modulated radiotherapy (IMRT) in conjunction with daily image-guided radiotherapy (IGRT) for head and neck cancer, according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV). Methods and Materials: Two-hundred and twenty-five patients were treated with IMRT for squamous cell carcinoma of the head and neck. Daily IGRT scans were acquired using either kilovoltage or megavoltage volumetric imaging prior to each delivered fraction. The first 95 patients were treated with IMRT with 5-mm CTV-to-PTV margins. The subsequent 130 patients were treated using 3-mm PTV expansion margins. Results: Two-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 76%, 78%, and 81%, respectively. There were no differences with respect to any of these endpoints among patients treated with 5-mm and 3-mm PTV expansion margins (p > 0.05, all). The 2-year local-regional control rate for patients treated with IMRT with 5-mm and 3-mm PTV margins was 78% and 78%, respectively (p = 0.96). Spatial evaluation revealed no differences in the incidences of marginal failures among those treated with 5-mm and 3-mm PTV margins. Conclusions: The use of 3-mm PTV expansion margins appears adequate and did not increase local-regional failures among patients treated with IMRT for head and neck cancer. These data demonstrate the safety of PTV reduction of less than 5 mm and support current protocols recommending this approach in the setting of daily IGRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Dose-Volume Analysis of Radiation Pneumonitis in Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

Purpose: To examine the rates and risk factors of radiation pneumonitis (RP) in non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Methods and Materials: Dosimetry records for 251 patients with lymph node-negative Stage I-IIB NSCLC and no prior chest radiation therapy (RT) treated with SBRT were reviewed. Patients were coded on the basis of the presence of at least Grade (G) 2 RP using the Common Toxicity Criteria version 2 criteria. Radiation doses, V5, V10, V20, and mean lung dose (MLD) data points were extracted from the dose-volume histogram (DVH). Results: Median PTV volume was 48 cc. Median prescribed radiation dose was 60 Gy delivered in three fractions to the 80% isodose line. Median age at treatment was 74 years. Median follow-up was 17 months. RP was reported after treatment of 42 lesions: G1 in 19 (8%), G2 in 17 (7%), G3 in 5 (2%), and G4 in 1 (0.4%). Total lung DVHs were available for 143 patients. For evaluable patients, median MLD, V5, V10, and V20 were 4.1 Gy, 20%, 12%, and 4%, respectively. Median MLDs were 4 Gy and 5 Gy for G0-1 and G2-4 groups, respectively (p = 0.14); median V5 was 20% for G0-1 and 24% for G2-4 (p = 0.70); median V10 was 12% in G0-1 and 16% in G2-4 (p = 0.08), and median V20 was 4% in G0-1 and 6.6% in G2-4 (p = 0.05). G2-4 RP was noted in 4.3% of patients with MLD {<=}4 Gy compared with 17.6% of patients with MLD >4 Gy (p = 0.02), and in 4.3% of patients with V20 {<=}4% compared with 16.4% of patients with V20 >4% (p = 0.03). Conclusion: Overall rate of G2-4 RP in our population treated with SBRT was 9.4%. Development of symptomatic RP in this series correlated with MLD and V20.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Differences in Effective Target Volume Between Various Techniques of Accelerated Partial Breast Irradiation

Purpose: Different cavity expansions are used to define the clinical target volume (CTV) for accelerated partial breast irradiation (APBI) delivered via balloon brachytherapy (1 cm) vs. three-dimensional conformal radiotherapy (3D-CRT) (1.5 cm). Previous studies have argued that the CTVs generated by these different margins are effectively equivalent. In this study, we use deformable registration to assess the effective CTV treated by balloon brachytherapy on clinically representative 3D-CRT planning images. Methods and Materials: Ten patients previously treated with the MammoSite were studied. Each patient had two computed tomography (CT) scans, one acquired before and one after balloon implantation. In-house deformable registration software was used to deform the MammoSite CTV onto the balloonless CT set. The deformed CTV was validated using anatomical landmarks common to both CT scans. Results: The effective CTV treated by the MammoSite was on average 7% {+-} 10% larger and 38% {+-} 4% smaller than 3D-CRT CTVs created using uniform expansions of 1 and 1.5 cm, respectively. The average effective CTV margin was 1.0 cm, the same as the actual MammoSite CTV margin. However, the effective CTV margin was nonuniform and could range from 5 to 15 mm in any given direction. Effective margins <1 cm were attributable to poor cavity-balloon conformance. Balloon size relative to the cavity did not significantly correlate with the effective margin. Conclusion: In this study, the 1.0-cm MammoSite CTV margin treated an effective volume that was significantly smaller than the 3D-CRT CTV based on a 1.5-cm margin.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose-Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Accurate Analysis of the Change in Volume, Location, and Shape of Metastatic Cervical Lymph Nodes During Radiotherapy

Purpose: To establish a method for the accurate acquisition and analysis of the variations in tumor volume, location, and three-dimensional (3D) shape of tumors during radiotherapy in the era of image-guided radiotherapy. Methods and Materials: Finite element models of lymph nodes were developed based on computed tomography (CT) images taken before the start of treatment and every week during the treatment period. A surface geometry map with a volumetric scale was adopted and used for the analysis. Six metastatic cervical lymph nodes, 3.5 to 55.1 cm{sup 3} before treatment, in 6 patients with head and neck carcinomas were analyzed in this study. Three fiducial markers implanted in mouthpieces were used for the fusion of CT images. Changes in the location of the lymph nodes were measured on the basis of these fiducial markers. Results: The surface geometry maps showed convex regions in red and concave regions in blue to ensure that the characteristics of the 3D tumor geometries are simply understood visually. After the irradiation of 66 to 70 Gy in 2 Gy daily doses, the patterns of the colors had not changed significantly, and the maps before and during treatment were strongly correlated (average correlation coefficient was 0.808), suggesting that the tumors shrank uniformly, maintaining the original characteristics of the shapes in all 6 patients. The movement of the gravitational center of the lymph nodes during the treatment period was everywhere less than {+-}5 mm except in 1 patient, in whom the change reached nearly 10 mm. Conclusions: The surface geometry map was useful for an accurate evaluation of the changes in volume and 3D shapes of metastatic lymph nodes. The fusion of the initial and follow-up CT images based on fiducial markers enabled an analysis of changes in the location of the targets. Metastatic cervical lymph nodes in patients were suggested to decrease in size without significant changes in the 3D shape during radiotherapy. The movements of the gravitational center of the lymph nodes were almost all less than {+-}5 mm.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Investigation of the Relationship Between Gross Tumor Volume Location and Pneumonitis Rates Using a Large Clinical Database of Non-Small-Cell Lung Cancer Patients

Purpose: Studies have suggested that function may vary throughout the lung, and that patients who have tumors located in the base of the lung are more susceptible to radiation pneumonitis. The purpose of our study was to investigate the relationship between gross tumor volume (GTV) location and pneumonitis rates using a large clinical database of 547 patients with non-small-cell lung cancer. Methods and Materials: The GTV centroids of all patients were mapped onto one common coordinate system, in which the boundaries of the coordinate system were defined by the extreme points of each individual patient lung. The data were qualitatively analyzed by graphing all centroids and displaying the data according to the presence of severe pneumonitis, tumor stage, and smoking status. The centroids were grouped according to superior-inferior segments, and the pneumonitis rates were analyzed. In addition, we incorporated the GTV centroid information into a Lyman-Kutcher-Burman normal tissue complication probability model and tested whether adding spatial information significantly improved the fit of the model. Results: Of the 547 patients analyzed, 111 (20.3%) experienced severe radiation pneumonitis. The pneumonitis incidence rates were 16%, 23%, and 21% for the superior, middle, and inferior thirds of the lung, respectively. Qualitatively, the GTV centroids of nonsmokers were notably absent from the superior portion of the lung. In addition, the GTV centroids of patients who had Stage III and IV clinical staging were concentrated toward the medial edge of the lung. The comparison between the GTV centroid model and the conventional dose-volume model did not yield a statistically significant difference in model fit. Conclusions: Lower pneumonitis rates were noted for the superior portion of the lung; however the differences were not statistically significant. For our patient cohort, incorporating GTV centroid information did not lead to a statistically significant improvement in the fit of the pneumonitis model.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Rectal Bleeding After High-Dose-Rate Brachytherapy Combined With Hypofractionated External-Beam Radiotherapy for Localized Prostate Cancer: The Relationship Between Dose-Volume Histogram Parameters and the Occurrence Rate

Purpose: To determine the predictive risk factors for Grade 2 or worse rectal bleeding after high-dose-rate brachytherapy (HDR-BT) combined with hypofractionated external-beam radiotherapy (EBRT) for prostate cancer using dose-volume histogram analysis. Methods and Materials: The records of 216 patients treated with HDR-BT combined with EBRT were analyzed. The treatment protocols for HDR-BT were 5 Gy Multiplication-Sign five times in 3 days or 7 Gy Multiplication-Sign three, 10.5 Gy Multiplication-Sign two, or 9 Gy Multiplication-Sign two in 2 days. The EBRT doses ranged from 45 to 51 Gy with a fractional dose of 3 Gy. Results: In 20 patients Grade 2 or worse rectal bleeding developed, and the cumulative incidence rate was 9% at 5 years. By converting the HDR-BT and EBRT radiation doses into biologic effective doses (BED), the BED{sub 3} at rectal volumes of 5% and 10% in the patients who experienced bleeding were significantly higher than those in the remaining 196 patients. Univariate analysis showed that a higher rectal BED{sub 3-5%} and the use of fewer needles in brachytherapy were correlated with the incidence of bleeding, but BED{sub 3-5%} was found to be the only significant factor on multivariate analysis. Conclusions: The radiation dose delivered to small rectal lesions as 5% is important for predicting Grade 2 or worse rectal bleeding after HDR-BT combined with EBRT for prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Beam-Specific Planning Target Volume (PTV) Design for Proton Therapy to Account for Setup and Range Uncertainties

Purpose: To report a method for explicitly designing a planning target volume (PTV) for treatment planning and evaluation in heterogeneous media for passively scattered proton therapy and scanning beam proton therapy using single-field optimization (SFO). Methods and Materials: A beam-specific PTV (bsPTV) for proton beams was derived by ray-tracing and shifting ray lines to account for tissue misalignment in the presence of setup error or organ motion. Range uncertainties resulting from inaccuracies in computed tomography-based range estimation were calculated for proximal and distal surfaces of the target in the beam direction. The bsPTV was then constructed based on local heterogeneity. The bsPTV thus can be used directly as a planning target as if it were in photon therapy. To test the robustness of the bsPTV, we generated a single-field proton plan in a virtual phantom. Intentional setup and range errors were introduced. Dose coverage to the clinical target volume (CTV) under various simulation conditions was compared between plans designed based on the bsPTV and a conventional PTV. Results: The simulated treatment using the bsPTV design performed significantly better than the plan using the conventional PTV in maintaining dose coverage to the CTV. With conventional PTV plans, the minimum coverage to the CTV dropped from 99% to 67% in the presence of setup error, internal motion, and range uncertainty. However, plans using the bsPTV showed minimal drop of target coverage from 99% to 94%. Conclusions: The conventional geometry-based PTV concept used in photon therapy does not work well for proton therapy. We investigated and validated a beam-specific PTV method for designing and evaluating proton plans.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Prognostic Value of Metabolic Tumor Volume and Velocity in Predicting Head-and-Neck Cancer Outcomes

Purpose: We previously showed that metabolic tumor volume (MTV) on positron emission tomography-computed tomography (PET-CT) predicts for disease recurrence and death in head-and-neck cancer (HNC). We hypothesized that increases in MTV over time would correlate with tumor growth and biology, and would predict outcome. We sought to examine tumor growth over time in serial pretreatment PET-CT scans. Methods and Materials: From 2006 to 2009, 51 patients had two PET-CT scans before receiving HNC treatment. MTV was defined as the tumor volume {>=}50% of maximum SUV (SUV{sub max}). MTV was calculated for the primary tumor, nodal disease, and composite (primary tumor + nodes). MTV and SUV velocity were defined as the change in MTV or SUV{sub max} over time, respectively. Cox regression analyses were used to examine correlations between SUV, MTV velocity, and outcome (disease progression and overall survival). Results: The median follow-up time was 17.5 months. The median time between PET-CT scans was 3 weeks. Unexpectedly, 51% of cases demonstrated a decrease in SUV{sub max} (average, -0.1 cc/week) and MTV (average, -0.3 cc/week) over time. Despite the variability in MTV, primary tumor MTV velocity predicted disease progression (hazard ratio 2.94; p = 0.01) and overall survival (hazard ratio 1.85; p = 0.03). Conclusions: Primary tumor MTV velocity appears to be a better prognostic indicator of disease progression and survival in comparison to nodal MTV velocity. However, substantial variability was found in PET-CT biomarkers between serial scans. Caution should be used when PET-CT biomarkers are integrated into clinical protocols for HNC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Setup Variations in Radiotherapy of Anal Cancer: Advantages of Target Volume Reduction Using Image-Guided Radiation Treatment

Purpose: To define setup variations in the radiation treatment (RT) of anal cancer and to report the advantages of image-guided RT (IGRT) in terms of reduction of target volume and treatment-related side effects. Methods and Materials: Twelve consecutive patients with anal cancer treated by combined chemoradiation by use of helical tomotherapy from March 2007 to November 2008 were selected. With patients immobilized and positioned in place, megavoltage computed tomography (MVCT) scans were performed before each treatment and were automatically registered to planning CT scans. Patients were shifted per the registration data and treated. A total of 365 MVCT scans were analyzed. The primary site received a median dose of 55 Gy. To evaluate the potential dosimetric advantage(s) of IGRT, cases were replanned according to Radiation Therapy Oncology Group 0529, with and without adding recommended setup variations from the current study. Results: Significant setup variations were observed throughout the course of RT. The standard deviations for systematic setup correction in the anterior-posterior (AP), lateral, and superior-inferior (SI) directions and roll rotation were 1.1, 3.6, and 3.2 mm, and 0.3 Degree-Sign , respectively. The average random setup variations were 3.8, 5.5, and 2.9 mm, and 0.5 Degree-Sign , respectively. Without daily IGRT, margins of 4.9, 11.1, and 8.5 mm in the AP, lateral, and SI directions would have been needed to ensure that the planning target volume (PTV) received {>=}95% of the prescribed dose. Conversely, daily IGRT required no extra margins on PTV and resulted in a significant reduction of V15 and V45 of intestine and V10 of pelvic bone marrow. Favorable toxicities were observed, except for acute hematologic toxicity. Conclusions: Daily MVCT scans before each treatment can effectively detect setup variations and thereby reduce PTV margins in the treatment of anal cancer. The use of concurrent chemotherapy and IGRT provided favorable toxicities, except for acute hematologic toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Toward Semi-automated Assessment of Target Volume Delineation in Radiotherapy Trials: The SCOPE 1 Pretrial Test Case

Purpose: To evaluate different conformity indices (CIs) for use in the analysis of outlining consistency within the pretrial quality assurance (Radiotherapy Trials Quality Assurance [RTTQA]) program of a multicenter chemoradiation trial of esophageal cancer and to make recommendations for their use in future trials. Methods and Materials: The National Cancer Research Institute SCOPE 1 trial is an ongoing Cancer Research UK-funded phase II/III randomized controlled trial of chemoradiation with capecitabine and cisplatin with or without cetuximab for esophageal cancer. The pretrial RTTQA program included a detailed radiotherapy protocol, an educational package, and a single mid-esophageal tumor test case that were sent to each investigator to outline. Investigator gross tumor volumes (GTVs) were received from 50 investigators in 34 UK centers, and CERR (Computational Environment for Radiotherapy Research) was used to perform an assessment of each investigator GTV against a predefined gold-standard GTV using different CIs. A new metric, the local conformity index (l-CI), that can localize areas of maximal discordance was developed. Results: The median Jaccard conformity index (JCI) was 0.69 (interquartile range, 0.62-0.70), with 14 of 50 investigators (28%) achieving a JCI of 0.7 or greater. The median geographical miss index was 0.09 (interquartile range, 0.06-0.16), and the mean discordance index was 0.27 (95% confidence interval, 0.25-0.30). The l-CI was highest in the middle section of the volume, where the tumor was bulky and more easily definable, and identified 4 slices where fewer than 20% of investigators achieved an l-CI of 0.7 or greater. Conclusions: The available CIs analyze different aspects of a gold standard-observer variation, with JCI being the most useful as a single metric. Additional information is provided by the l-CI and can focus the efforts of the RTTQA team in these areas, possibly leading to semi-automated outlining assessment.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Prospective Pathologic Study to Define the Clinical Target Volume for Partial Breast Radiation Therapy in Women With Early Breast Cancer

Purpose: To determine an appropriate clinical target volume for partial breast radiation therapy (PBRT) based on the spatial distribution of residual invasive and in situ carcinoma after wide local excision (WLE) for early breast cancer or ductal carcinoma in situ (DCIS). Methods and Materials: We performed a prospective pathologic study of women potentially eligible for PBRT who had re-excision and/or completion mastectomy after WLE for early breast cancer or DCIS. A pathologic assessment protocol was used to determine the maximum radial extension (MRE) of residual carcinoma from the margin of the initial surgical cavity. Women were stratified by the closest initial radial margin width: negative (>1 mm), close (>0 mm and {<=}1 mm), or involved. Results: The study population was composed of 133 women with a median age of 59 years (range, 27-82 years) and the following stage groups: 0 (13.5%), I (40.6%), II (38.3%), and III (7.5%). The histologic subtypes of the primary tumor were invasive ductal carcinoma (74.4%), invasive lobular carcinoma (12.0%), and DCIS alone (13.5%). Residual carcinoma was present in the re-excision and completion mastectomy specimens in 55.4%, 14.3%, and 7.2% of women with an involved, close, and negative margin, respectively. In the 77 women with a noninvolved radial margin, the MRE of residual disease, if present, was {<=}10 mm in 97.4% (95% confidence interval 91.6-99.5) of cases. Larger MRE measurements were significantly associated with an involved margin (P<.001), tumor size >30 mm (P=.03), premenopausal status (P=.03), and negative progesterone receptor status (P=.05). Conclusions: A clinical target volume margin of 10 mm would encompass microscopic residual disease in >90% of women potentially eligible for PBRT after WLE with noninvolved resection margins.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Distance-to-Agreement Investigation of Tomotherapy's Bony Anatomy-Based Autoregistration and Planning Target Volume Contour-Based Optimization

Purpose: To compare Tomotherapy's megavoltage computed tomography bony anatomy autoregistration with the best achievable registration, assuming no deformation and perfect knowledge of planning target volume (PTV) location. Methods and Materials: Distance-to-agreement (DTA) of the PTV was determined by applying a rigid-body shift to the PTV region of interest of the prostate from its reference position, assuming no deformations. Planning target volume region of interest of the prostate was extracted from the patient archives. The reference position was set by the 6 degrees of freedom (dof)—x, y, z, roll, pitch, and yaw—optimization results from the previous study at this institution. The DTA and the compensating parameters were calculated by the shift of the PTV from the reference 6-dof to the 4-dof—x, y, z, and roll—optimization. In this study, the effectiveness of Tomotherapy's 4-dof bony anatomy–based autoregistration was compared with the idealized 4-dof PTV contour-based optimization. Results: The maximum DTA (maxDTA) of the bony anatomy-based autoregistration was 3.2 ± 1.9 mm, with the maximum value of 8.0 mm. The maxDTA of the contour-based optimization was 1.8 ± 1.3 mm, with the maximum value of 5.7 mm. Comparison of Pearson correlation of the compensating parameters between the 2 4-dof optimization algorithms shows that there is a small but statistically significant correlation in y and z (0.236 and 0.300, respectively), whereas there is very weak correlation in x and roll (0.062 and 0.025, respectively). Conclusions: We find that there is an average improvement of approximately 1 mm in terms of maxDTA on the PTV going from 4-dof bony anatomy-based autoregistration to the 4-dof contour-based optimization. Pearson correlation analysis of the 2 4-dof optimizations suggests that uncertainties due to deformation and inadequate resolution account for much of the compensating parameters, but pitch variation also makes a statistically significant contribution.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Residual Tumor After Neoadjuvant Chemoradiation Outside the Radiation Therapy Target Volume: A New Prognostic Factor for Survival in Esophageal Cancer

Purpose/Objective(s): The aim of this study was to analyze the accuracy of gross tumor volume (GTV) delineation and clinical target volume (CTV) margins for neoadjuvant chemoradiation therapy (neo-CRT) in esophageal carcinoma at pathologic examination and to determine the impact on survival. Methods and Materials: The study population consisted of 63 esophageal cancer patients treated with neo-CRT. GTV and CTV borders were demarcated in situ during surgery on the esophagus, using anatomical reference points to provide accurate information regarding tumor location at pathologic evaluation. To identify prognostic factors for disease-free survival (DFS) and overall survival (OS), a Cox regression analysis was performed. Results: After resection, macroscopic residual tumor was found outside the GTV in 7 patients (11%). Microscopic residual tumor was located outside the CTV in 9 patients (14%). The median follow-up was 15.6 months. With multivariate analysis, only microscopic tumor outside the CTV (hazard ratio [HR], 4.96; 95% confidence interval [CI], 1.03-15.36), and perineural growth (HR, 5.77; 95% CI, 1.27-26.13) were identified as independent prognostic factors for OS. The 1-year OS was 20% for patients with tumor outside the CTV and 86% for those without (P<.01). For DFS, microscopic tumor outside the CTV (HR, 5.92; 95% CI, 1.89-18.54) and ypN+ (HR, 3.36; 95% CI, 1.33-8.48) were identified as independent adverse prognostic factors. The 1-year DFS was 23% versus 77% for patients with or without tumor outside the CTV (P<.01). Conclusions: Microscopic tumor outside the CTV is associated with markedly worse OS after neo-CRT. This may either stress the importance of accurate tumor delineation or reflect aggressive tumor behavior requiring new adjuvant treatment modalities.

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