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At least 19 records

TU-F-CAMPUS-J-04: Setup Uncertainties in the Mediastinum Area for IMRT Treatment of Lymphoma Patients

Purpose: Despite daily image guidance setup uncertainties can be high when treating large areas of the body. The aim of this study was to measure local uncertainties inside the PTV for patients receiving IMRT to the mediastinum region. Methods: Eleven lymphoma patients that received radiotherapy (breath-hold) to the mediastinum were included in this study. The treated region could range all the way from the neck to the diaphragm. Each patient had a CT scan with a CT-on-rails system prior to every treatment. The entire PTV region was matched to the planning CT using automatic rigid registration. The PTV was then split into 5 regions: neck, supraclavicular, superior mediastinum, upper heart, lower heart. Additional auto-registrations for each of the 5 local PTV regions were performed. The residual local setup errors were calculated as the difference between the final global PTV position and the individual final local PTV positions for the AP, SI and RL directions. For each patient 4 CT scans were analyzed (1 per week of treatment). Results: The residual mean group error (M) and standard deviation of the inter-patient (or systematic) error (Σ) were lowest in the RL direction of the superior mediastinum (0.0mm and 0.5mm) and highest in the RL direction of the lower heart (3.5mm and 2.9mm). The standard deviation of the inter-fraction (or random) error (σ) was lowest in the RL direction of the superior mediastinum (0.5mm) and highest in the SI direction of the lower heart (3.9mm) The directionality of local uncertainties is important; a superior residual error in the lower heart for example keeps it in the global PTV. Conclusion: There is a complex relationship between breath-holding and positioning uncertainties that needs further investigation. Residual setup uncertainties can be significant even under daily CT image guidance when treating large regions of the body.

60 APPLIED LIFE SCIENCES↗

Automated characterization of perceptual quality of clinical chest radiographs: Validation and calibration to observer preference

Purpose: The authors previously proposed an image-based technique [Y. Lin et al. Med. Phys. 39, 7019–7031 (2012)] to assess the perceptual quality of clinical chest radiographs. In this study, an observer study was designed and conducted to validate the output of the program against rankings by expert radiologists and to establish the ranges of the output values that reflect the acceptable image appearance so the program output can be used for image quality optimization and tracking. Methods: Using an IRB-approved protocol, 2500 clinical chest radiographs (PA/AP) were collected from our clinical operation. The images were processed through our perceptual quality assessment program to measure their appearance in terms of ten metrics of perceptual image quality: lung gray level, lung detail, lung noise, rib–lung contrast, rib sharpness, mediastinum detail, mediastinum noise, mediastinum alignment, subdiaphragm–lung contrast, and subdiaphragm area. From the results, for each targeted appearance attribute/metric, 18 images were selected such that the images presented a relatively constant appearance with respect to all metrics except the targeted one. The images were then incorporated into a graphical user interface, which displayed them into three panels of six in a random order. Using a DICOM calibrated diagnostic display workstation and under low ambient lighting conditions, each of five participating attending chest radiologists was tasked to spatially order the images based only on the targeted appearance attribute regardless of the other qualities. Once ordered, the observer also indicated the range of image appearances that he/she considered clinically acceptable. The observer data were analyzed in terms of the correlations between the observer and algorithmic rankings and interobserver variability. An observer-averaged acceptable image appearance was also statistically derived for each quality attribute based on the collected individual acceptable ranges. Results: The observer study indicated that, for each image quality attribute, the averaged observer ranking strongly correlated with the algorithmic ranking (linear correlation coefficient R > 0.92), with highest correlation (R = 1) for lung gray level and the lowest (R = 0.92) for mediastinum noise. There was a strong concordance between the observers in terms of their rankings (i.e., Kendall’s tau agreement > 0.84). The observers also generally indicated similar tolerance and preference levels in terms of acceptable ranges, as 85% of the values were close to the overall tolerance or preference levels and the differences were smaller than 0.15. Conclusions: The observer study indicates that the previously proposed technique provides a robust reflection of the perceptual image quality in clinical images. The results established the range of algorithmic outputs for each metric that can be used to quantitatively assess and qualify the appearance quality of clinical chest radiographs.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Optimized Volumetric Modulated Arc Therapy Versus 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma Without Axillary Involvement: A Comparison of Second Cancers and Heart Disease Risk

Purpose: The purpose of this study was to evaluate the risks of second cancers and cardiovascular diseases associated with an optimized volumetric modulated arc therapy (VMAT) planning solution in a selected cohort of stage I/II Hodgkin lymphoma (HL) patients treated with either involved-node or involved-site radiation therapy in comparison with 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials: Thirty-eight patients (13 males and 25 females) were included. Disease extent was mediastinum alone (n=8, 21.1%); mediastinum plus unilateral neck (n=19, 50%); mediastinum plus bilateral neck (n=11, 29.9%). Prescription dose was 30 Gy in 2-Gy fractions. Only 5 patients had mediastinal bulky disease at diagnosis (13.1%). Anteroposterior 3D-CRT was compared with a multiarc optimized VMAT solution. Lung, breast, and thyroid cancer risks were estimated by calculating a lifetime attributable risk (LAR), with a LAR ratio (LAR{sub VMAT}-to-LAR{sub 3D-CRT}) as a comparative measure. Cardiac toxicity risks were estimated by calculating absolute excess risk (AER). Results: The LAR ratio favored 3D-CRT for lung cancer induction risk in mediastinal alone (P=.004) and mediastinal plus unilateral neck (P=.02) presentations. LAR ratio for breast cancer was lower for VMAT in mediastinal plus bilateral neck presentations (P=.02), without differences for other sites. For thyroid cancer, no significant differences were observed, regardless of anatomical presentation. A significantly lower AER of cardiac (P=.038) and valvular diseases (P<.0001) was observed for VMAT regardless of disease extent. Conclusions: In a cohort of patients with favorable characteristics in terms of disease extent at diagnosis (large prevalence of nonbulky presentations without axillary involvement), optimized VMAT reduced heart disease risk with comparable risks of thyroid and breast cancer, with an increase in lung cancer induction probability. The results are however strongly influenced by the different anatomical presentations, supporting an individualized approach.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

TU-H-CAMPUS-JeP2-02: Interobserver Variability of CT, PET-CT and MRI Based Primary Tumor Delineation for Lung Cancer

Purpose: Target delineation in lung cancer radiotherapy has, in general, large variability. MRI has so far not been investigated in detail for lung cancer delineation variability. The purpose of this study is to investigate delineation variability for lung tumors using MRI and compare it to CT alone and PET-CT based delineations. Methods: Seven physicians delineated the primary tumor volumes of nine patients for the following scenarios: (1) CT only; (2) post-contrast T1-weighted MRI registered with diffusion-weighted MRI; and (3) PET-CT fusion images. To compute interobserver variability, the median surface was generated from all observers’ contours and used as the reference surface. A single physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest-wall) on the median surface. Volume variation (normalized to PET-CT volume), minimum distance (MD), and bidirectional local distance (BLD) between individual observers’ contours and the reference contour were measured. Results: CT- and MRI-based normalized volumes were 1.61±0.76 (mean±SD) and 1.38±0.44, respectively, both significantly larger than PET-CT (p<0.05, paired t-test). The overall uncertainty (root mean square of SD values over all points) of both BLD and MD measures of the observers for the interfaces were not significantly different (p>0.05, two-samples t-test) for all imaging modalities except between tumor-mediastinum and tumor-atelectasis in PET-CT. The largest mean overall uncertainty was observed for tumor-atelectasis interface, the smallest for tumor-mediastinum and tumor-lung interfaces for all modalities. The whole tumor uncertainties for both BLD and MD were not significantly different between any two modalities (p>0.05, paired t-test). Overall uncertainties for the interfaces using BLD were similar to using MD. Conclusion: Large volume variations were observed between the three imaging modalities. Contouring variability appeared to depend on the interface type. This study will be useful for understanding the delineation uncertainty for radiotherapy planning of lung cancer using different imaging modalities. Disclosures: Research agreement with Phillips Healthcare (GH and EW), National Institutes of Health Licensing agreement with Varian Medical Systems (GH and EW), research grants from the National Institute of Health (GH and EW), UpToDate royalties (EW), and none (others). Authors have no potential conflicts of interest to disclose.

60 APPLIED LIFE SCIENCES↗

Reliability of the {sup 123}I-mIBG heart/mediastinum ratio: Results of a multicenter test–retest reproducibility study

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of {sup 123}I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test–retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test–retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m{sup 2}. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test–retest difference was 0.055 to 0.076. Bland–Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to {sup 123}I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of {sup 123}I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

SU-F-T-356: DosimetricComparison of VMAT Vs Step and Shoot IMRT Plans for Stage III Lung CancerPatients with Mediastinal Involvement

Purpose: For Stage III lung cancers that entail treatment of some or all of the mediastinum, anterior-posterior focused Step and Shoot IMRT (SS-IMRT) and VMAT plans have been clinically used to deliver the prescribed dose while working to minimize lung dose and avoid other critical structures. A comparison between the two planning methods was completed to see which treatment method is superior and minimizes dose to healthy lung tissue. Methods: Ten patients who were recently treated with SS-IMRT or VMAT plans for Stage III lung cancer with mediastinal involvement were selected. All patients received a simulation CT for treatment planning, as well as a 4D CT and PET/CT fusion for target delineation. Plans were prescribed 6250 cGy in 25 fractions and normalized such that 100% of the prescription dose covered 95% of the PTV. Clinically approved SS-IMRT or VMAT plans were then copied and planned using the alternative modality with identical optimization criteria. SS-IMRT plans utilized seven to nine beams distributed around the patient while the VMAT plans consisted of two full 360 degree arcs. Plans were compared for the lung volume receiving 20 Gy (V20). Results: Both SS-IMRT and VMAT can be used to achieve clinical treatment plans for patients with Stage III Lung cancer with targets encompassing the mediastinum. VMAT plans produced an average V20 of 23.0+/−8.3% and SS-IMRT produced an average of 24.2+/−10.0%. Conclusion: Results indicate that either method can achieve comparable dose distributions, however, VMAT can allow the optimizer to distribute dose over paths of minimal lung tissue and reduce the V20. Therefore, creating a VMAT with constraints identical to an SS-IMRT plan could help to reduce the V20 in clinical treatment plans.

60 APPLIED LIFE SCIENCES↗

MRI-Guided Percutaneous Biopsy of Mediastinal Masses Using a Large Bore Magnet: Technical Feasibility

ObjectiveTo evaluate the diagnostic accuracy and safety of magnetic resonance imaging (MRI)-guided percutaneous biopsy of mediastinal masses performed using a wide-bore high-field scanner.Materials and MethodsThis is a retrospective study of 16 consecutive patients (8 male, 8 female; mean age 74 years) who underwent MRI-guided core needle biopsy of a mediastinal mass between February 2010 and January 2014. Size and location of lesion, approach taken, time for needle placement, overall duration of procedure, and post-procedural complications were evaluated. Technical success rates and correlation with surgical pathology (where available) were assessed.ResultsTarget lesions were located in the anterior (n = 13), middle (n = 2), and posterior mediastinum (n = 1), respectively. Mean size was 7.2 cm (range 3.6–11 cm). Average time for needle placement was 9.4 min (range 3–18 min); average duration of entire procedure was 42 min (range 27–62 min). 2–5 core samples were obtained from each lesion (mean 2.6). Technical success rate was 100 %, with specimens successfully obtained in all 16 patients. There were no immediate complications. Histopathology revealed malignancy in 12 cases (4 of which were surgically confirmed), benign lesions in 3 cases (1 of which was false negative following surgical resection), and one inconclusive specimen (treated as inaccurate since repeat CT-guided biopsy demonstrated thymic hyperplasia). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in our study were 92.3, 100, 100, 66.7, and 87.5 %, respectively.ConclusionMRI-guided mediastinal biopsy is a safe procedure with high diagnostic accuracy, which may offer a non-ionizing alternative to CT guidance.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Imaging cardiac innervation in amyloidosis

Cardiac amyloidosis is a form of restrictive cardiomyopathy resulting in heart failure and potential risk on arrhythmia, due to amyloid infiltration of the nerve conduction system and the myocardial tissue. The prognosis in this progressive disease is poor, probably due the development of cardiac arrhythmias. Early detection of cardiac sympathetic innervation disturbances has become of major clinical interest, because its occurrence and severity limits the choice of treatment. The use of iodine-123 labelled metaiodobenzylguanidine ([I-123]MIBG), a chemical modified analogue of norepinephrine, is well established in patients with heart failure and plays an important role in evaluation of sympathetic innervation in cardiac amyloidosis. [I-123]MIBG is stored in vesicles in the sympathetic nerve terminals and is not catabolized like norepinephrine. Decreased heart-to-mediastinum ratios on late planar images and increased wash-out rates indicate cardiac sympathetic denervation and are associated with poor prognosis. Single photon emission computed tomography provides additional information and has advantages for evaluating abnormalities in regional distribution in the myocardium. [I-123]MIBG is mainly useful in patients with hereditary and wild-type ATTR cardiac amyloidosis, not in AA and AL amyloidosis. The potential role of positron emission tomography for cardiac sympathetic innervation in amyloidosis has not yet been identified.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Relationship of left ventricular global longitudinal strain with cardiac autonomic denervation as assessed by {sup 123}I-mIBG scintigraphy in patients with heart failure with reduced ejection fraction submitted to cardiac resynchronization therapy

Background: Heart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by {sup 123}I-metaiodobenzylguanidine ({sup 123}I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by {sup 123}I-mIBG scintigraphy in advanced HF. Methods/Results: BETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of − 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). Conclusion: Myocardial contractility as assessed by GLS is moderately correlated with AD as assessed by {sup 123}I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Role of cardiac {sup 123}I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD

Background: Despite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients. Methods: 170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, {sup 123}I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy. Results: During a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. {sup 123}I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a “bell-shaped” relation between {sup 123}I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate {sup 123}I-mIBG abnormalities tended to be at higher risk of events. Conclusion: Although SPECT {sup 123}I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between {sup 123}I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Patterns of Local-Regional Failure in Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer Cases: Implications for Postoperative Radiation Therapy Clinical Target Volume Design

Purpose: To analyze patterns of local-regional failure (LRF) for completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients treated in our hospital and to propose a clinical target volume (CTV) for postoperative radiation therapy (PORT) in these patients. Methods and Materials: From 2005 to 2011, consecutive patients with pT1-3N2 NSCLC who underwent complete resection in our hospital but who did not receive PORT were identified. The patterns of first LRF were assessed and evaluated as to whether these areas would be encompassed by our proposed PORT CTV. Results: With a median follow-up of 24 months, 173 of 250 patients (69.2%) experienced disease recurrence. Of the 54 patients with LRF as the first event, 48 (89%) had recurrence within the proposed PORT CTV, and 6 (11%) had failures occurring both within and outside the proposed CTV (all of which occurred in patients with right-lung cancer). Ninety-three percent of failure sites (104 of 112) would have been contained within the proposed PORT CTV. For left-sided lung cancer, the most common lymph node station failure site was 4R, followed by 7, 4L, 6, 10L, and 5. For right-sided lung cancer, the most common site was station 2R, followed by 10R, 4R, and 7. Conclusions: LRF following complete surgery was an important and potentially preventable pattern of failure in stage IIIA(N2) patients. Ipsilateral superior mediastinal recurrences dominated for right-sided tumors, whereas left-sided tumors frequently involved the bilateral superior mediastinum. Most of the LRF sites would have been covered by the proposed PORT CTV. A prospective investigation of patterns of failure after PORT (following our proposed CTV delineation guideline) is presently underway and will be reported in a separate analysis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. Methods and Materials: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. Results: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). Conclusions: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete response after ABVD-based chemotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Salvage Stereotactic Body Radiation Therapy (SBRT) for Local Failure After Primary Lung SBRT

Purpose: Local failure after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) is uncommon. We report the safety and efficacy of SBRT for salvage of local failure after previous SBRT with a biologically effective dose (BED) of ≥100 Gy{sub 10}. Methods and Materials: Using an institutional review board–approved lung SBRT registry, we identified all patients initially treated for early-stage NSCLC between August 2004 and January 2012 who received salvage SBRT for isolated local failure. Failure was defined radiographically and confirmed histologically unless contraindicated. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance, and received a BED of ≥100 Gy{sub 10} for each SBRT course. Tumor motion control involved a Bodyfix vacuum system for immobilization along with abdominal compression. Results: Of 436 patients treated from August 2004 through January 2012, we identified 22 patients with isolated local failure, 10 of whom received SBRT for salvage. The median length of follow-up was 13.8 months from salvage SBRT (range 5.3-43.5 months). Median tumor size was 3.4 cm (range 1.7-4.8 cm). Two of the 10 lesions were “central” by proximity to the mediastinum, but were outside the zone of the proximal bronchial tree. Since completing salvage, 3 patients are alive and without evidence of disease. A fourth patient died of medical comorbidities without recurrence 13.0 months after salvage SBRT. Two patients developed distant disease only. Four patients had local failure. Toxicity included grade 1-2 fatigue (3 patients) and grade 1-2 chest wall pain (5 patients). There was no grade 3-5 toxicity. Conclusions: Repeat SBRT with a BED of ≥100 Gy{sub 10} after local failure in patients with early-stage medically inoperable NSCLC was well tolerated in this series and may represent a viable salvage strategy in select patients with peripheral tumors ≤5 cm.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Local Control and Toxicity in a Large Cohort of Central Lung Tumors Treated With Stereotactic Body Radiation Therapy

Purpose: Stereotactic body radiation therapy (SBRT) in central lung tumors has been associated with higher rates of severe toxicity. We sought to evaluate toxicity and local control in a large cohort and to identify predictive dosimetric parameters. Methods and Materials: We identified patients who received SBRT for central tumors according to either of 2 definitions. Local failure (LF) was estimated using a competing risks model, and multivariate analysis (MVA) was used to assess factors associated with LF. We reviewed patient toxicity and applied Cox proportional hazard analysis and log-rank tests to assess whether dose-volume metrics of normal structures correlated with pulmonary toxicity. Results: One hundred twenty-five patients received SBRT for non-small cell lung cancer (n=103) or metastatic lesions (n=22), using intensity modulated radiation therapy. The most common dose was 45 Gy in 5 fractions. Median follow-up was 17.4 months. Incidence of toxicity ≥ grade 3 was 8.0%, including 5.6% pulmonary toxicity. Sixteen patients (12.8%) experienced esophageal toxicity ≥ grade 2, including 50% of patients in whom PTV overlapped the esophagus. There were 2 treatment-related deaths. Among patients receiving biologically effective dose (BED) ≥80 Gy (n=108), 2-year LF was 21%. On MVA, gross tumor volume (GTV) was significantly associated with LF. None of the studied dose-volume metrics of the lungs, heart, proximal bronchial tree (PBT), or 2 cm expansion of the PBT (“no-fly-zone” [NFZ]) correlated with pulmonary toxicity ≥grade 2. There were no differences in pulmonary toxicity between central tumors located inside the NFZ and those outside the NFZ but with planning target volume (PTV) intersecting the mediastinum. Conclusions: Using moderate doses, SBRT for central lung tumors achieves acceptable local control with low rates of severe toxicity. Dosimetric analysis showed no significant correlation between dose to the lungs, heart, or NFZ and severe pulmonary toxicity. Esophageal toxicity may be an underappreciated risk, particularly when PTV overlaps the esophagus.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Toxicity After Central versus Peripheral Lung Stereotactic Body Radiation Therapy: A Propensity Score Matched-Pair Analysis

Purpose: To compare toxicity after stereotactic body radiation therapy (SBRT) for “central” tumors—within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum—versus noncentral (“peripheral”) lung tumors. Methods and Materials: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non–small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/β=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ{sup 2} and 2-tailed t tests, adverse events with χ{sup 2} test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). Results: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. Conclusion: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP.

62 RADIOLOGY AND NUCLEAR MEDICINE↗