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Purpose To evaluate low- vs high-dose plaque brachytherapy for juxtapapillary choroidal melanoma. Design Retrospective interventional case series. Methods Setting: Single institution. Study Population: Forty-seven patients with juxtapapillary choroidal melanoma. Intervention: Iodine-125 plaque brachytherapy. Eyes were divided into apex low-dose (LD) and high-dose (HD) groups (≤ or > median apex dose 84.35 Gy). Main outcome measures were time to distant failure, local failure, death, enucleation, radiation retinopathy, optic neuropathy, and best-corrected visual acuity (BCVA). Results Freedom from distant failure rates were 96% and 95% in apex LD and HD groups at 5 years and 77% and 95% at 10 years, respectively ( P = .84). Freedom from local failure rates were 90% in the apex LD group vs 89% in the HD group at 5 and 10 years ( P = .96). Apex LD and HD groups did not differ for time to death or enucleation. Five- and 10-year freedom from radiation retinopathy and optic neuropathy rates were higher in the apex LD than HD group. Loss of ≥3 BCVA lines, final BCVA 20/40 or better, and final BCVA 20/200 or worse were more favorable in the 5 mm LD compared to HD group. Visual acuity outcomes did not differ between apex LD and HD groups. Conclusions Low-dose iodine-125 plaque brachytherapy (67.5–81 Gy at tumor apex) provides safe and effective tumor control for juxtapapillary choroidal melanoma and may be associated with reduced radiation toxicity. Larger trials are needed to determine the optimal therapeutic dose for juxtapapillary choroidal melanoma.

The aim of this study was to quantitatively compare dosimetric criteria between intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans for patients undergoing radiation treatment of gynecologic carcinoma with a simultaneous integrated boost (SIB) technique. IMRT and VMAT plans were retrospectively analyzed for 20 patients. The elective volume was planned to receive 45 Gy in 25 fractions of 1.8 Gy, with the integrated boost volume (involved nodes) receiving 55 Gy simultaneously. The same dose constraints were employed during the optimization of both techniques. IMRT plans consisted of 9 to 11 fields at equally spaced gantry angles. VMAT plans consisted of 3 full arcs of 360°. A large variety of dose metrics across planning target volume (PTV)45, PTV55, bladder, rectum, sigmoid, bowel, kidneys, and femoral heads were extracted per patient, per plan. Conformity and homogeneity indices were also calculated and compared for each target volume. The total number of monitor units as well as the integral dose was also compared between IMRT and VMAT. The Wilcoxon signed rank test was performed to evaluate any significant differences between parameters, with an applied Bonferroni correction to account for multiple testing (significance level, p < 0.0006). The results demonstrate the equivalence of the 2 planning techniques across all studied parameters, with the exception of the expected decrease in monitor units that VMAT is capable of achieving. The findings of this study suggest that IMRT and VMAT are both acceptable options for applying simultaneous integrated boost techniques for the treatment of gynecologic cancers. The technique of choice will be dependent on departmental resources and should be considered on a case-by-case basis.

Several series evaluating external-beam partial breast irradiation (PBI) have linked negative cosmetic outcomes to large normal tissue treatment volumes. We compared patients treated with PBI whose treatment plans included only photons to those whose plans incorporated electrons. Twenty-seven patients were identified: median age 67 years, pT1 82%, pN0 56%, margin negative 100%. All received 38.5 Gy using 3-5 noncoplanar photon beams (6-15X). Electrons (9-20 MeV) were included in 59%. Median follow-up was 22 months. Ninety percent experienced good/excellent cosmetic outcomes. Two patients had fair cosmesis, and both were treated with a mixed photon/electron approach. Median conformity index for photon-only treatment plans was 1.7 (range, 0.9-2.0) and for photon/electron plans, 1.0 (0.3-1.4). Median percent ipsilateral breast volume receiving 100% and 50% of prescription dose was 19 and 50 for photon-only plans vs. 10 and 38 for photon/electron plans (p0.05). Median percent target volume receiving 100% and 95% of prescription dose was 93 and 98 for photon-only plans vs. 75 and 94 for photon/electron plans (p0.05). A mixed photon/electron, noncoplanar technique decreases the volume of treated normal breast tissue at the cost of slightly decreased tumor bed coverage. Further study is needed to determine whether this results in a more favorable therapeutic ratio than photon-only approaches.

Purpose: Traditional treatment beams for non-small cell lung cancer are limited to the axial plane. For many tumor geometries non-axial orientations appear to reduce the dose to normal tissues (e.g. heart, liver). We hypothesize that non-axial beams provide a significant reduction in incidental irradiation of the heart and liver, while maintaining adequate target coverage. Materials and Methods: CT scans of twenty-four consecutive patients with lower lobe lung cancers were studied. For each patient, an opposed oblique axial beam pair and a competing non-axial opposed oblique pair were generated. The competing plans delivered comparable doses/margins to the GTV. DVHs and integral doses were computed for all structures of interest for the two competing plans. The integral dose was compared for axial and non-axial beams for each contoured organ using a paired t-test. Results: Dose to the heart was significantly lower for the non-axial plans (p=.0001). For 20/24 patients the integral heart dose was reduced by using non-axial beams. In those patients with tumors located in the inferior right lower lobe, a lower dose to the liver was achieved when non-axial beams were used. There were no meaningful differences in dose to the GTV, lungs, or skin between axial and non-axial beams. Conclusion: Non-axial beams can reduce the dose to the heart and liver in patients with lower lobe lung cancers. Non-axial beams may be clinically beneficial in these patients and should be considered as an option during planning.

A prospective study was performed to formally relate dose-dependent radiologically defined changes in normal brain induced by radiotherapy (RT) to neurocognitive dysfunction in subjects with primary brain tumors.Adult patients receiving three-dimensional RT for central nervous system (CNS) tumors were enrolled. Positron emission tomography (PET) scanning and neuropsychological testing were performed before RT and 3 weeks and 6 months after treatment. Analyses were performed for correlations between changes in 2-deoxy-2-[(18)F]-fluoro-d-glucose (FDG)-PET (metabolism), (15)O-PET (relative blood flow), regional radiation dose, follow-up time, and neuropsychological test scores.Eleven subjects were enrolled and 6 completed follow-up studies. The PET data showed reduced FDG uptake, with average decreases of 2-6% in regions of the brain receiving greater than 40 Gy at 3 weeks' and 6 months' follow-up. The (15)O-H(2)O PET showed increases (10%) at 3 weeks in relative regional blood flow in brain receiving greater than 30 Gy, but less at the 6-month follow-up studies. There were significant correlations between decreases in FDG uptake and increased scores from the Symptom Checklist-90-R, with an average increase in T score of 2 (p0.0001). The Wisconsin Card Sorting Test showed a significant correlation of decreased FDG uptake with increased errors and perseveration in test performance, with an average decrease in T score of 11 (p = 0.037).A dose-dependent response of CNS tissue was detected using FDG PET in this small number of patients. Decreases in CNS metabolism correlated with decreased performance on neuropsychological tests for problem solving, cognitive flexibility, and global measures of psychopathology. Additional research is needed to verify and define these findings.

Purpose To assess the impact of new technologies on deviation rates in radiation therapy (RT). Methods and Materials Treatment delivery deviations in RT were prospectively monitored during a time of technology upgrade. In January 2003, our department had three accelerators, none with "modern" technologies (e.g., without multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new accelerators, four with MLC, and associated advanced capabilities. The deviation rates among patients treated on "high-technology" versus "low-technology" machines (defined as those with vs. without MLC) were compared over time using the two-tailed Fisher's exact test. Results In 2003, there was no significant difference between the deviation rate in the "high-technology" versus "low-technology" groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation rate for the "high-technology" groups was lower than the "low-technology" (0.083% vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on the "high-technology" machines over time ( p = 0.053), as well as an unexpected trend toward an increase in deviations over time on the "low-technology" machines ( p = 0.15). Conclusions Advances in RT delivery systems appear to reduce the rate of treatment deviations. Deviation rates on "high-technology" machines with MLC decline over time, suggesting a learning curve after the introduction of new technologies. Associated with the adoption of "high-technology" was an unexpected increase in the deviation rate with "low-technology" approaches, which may reflect an over-reliance on tools inherent to "high-technology" machines. With the introduction of new technologies, continued diligence is needed to ensure that staff remain proficient with "low-technology" approaches.

Purpose: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post–radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. Methods and Materials: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board–approved prospective study and had pre- and serial post-RT (6–60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. Results: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate ( p = 0.0005 to 0.0058) and multivariate analysis ( p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate ( p = 0.0005 to 0.022) and multivariate analysis ( p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up "too deep" (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI ≥25 kg/m 2 compared with patients of normal weight (47% vs. 28%, p = 0.068). Conclusions: BMI ≥25 kg/m 2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.

The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-beta1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed gradeor =1 RP, and 27 (22.3%) developed gradeor =2 RP. For the endpoint of gradeor =1 RP, those with V3030% and an end-RT/baseline TGF-beta1 ratioor =1 had a significantly higher incidence of RP than did those with V3030% and an end-RT/baseline TGF-beta1 ratio1. For most other patient groups, there were no clear associations between TGF-beta1 values and rates of RP. These findings suggest that TGF-beta1 is generally not predictive for RP except for the group of patients with a high V30.

Purpose: To analyze local-regional patterns of failure after surgical resection of non–small-cell lung cancer (NSCLC). Methods and Materials: This retrospective analysis included 61 patients who underwent resection of NSCLC at Duke University Medical Center. Inclusion into the study required the following: margin-negative resection, no neoadjuvant/adjuvant radiation therapy (RT), first recurrence involving a local-regional site, and imaging studies available for review. Sites of intrathoracic disease recurrence were documented. Diagrams were constructed that illustrated sites of failure on the basis of lobe of primary tumor. Failure rates were compared by application of a two-tailed Fisher's exact test. Results: All patients had CT imaging for review, and 54% also had PET imaging. The median number of local-regional recurrent sites was two (range, 1–6). For all patients, the most common site of failure was the bronchial stump/staple line (44%), which was present more often in those who had a wedge resection than in those who had a more radical procedure (79% vs. 34%, p = 0.005). Patients with initial nodal involvement (pN1-2) were not more likely to have involvement of the mediastinum than were patients with pN0 disease (64% vs. 72%, p = 0.72), but were more likely to have involvement of the supraclavicular fossa (27% vs. 4%, p = 0.04). Mediastinal involvement, without overt evidence of hilar involvement, occurred in 59% of patients. Left-sided tumors tended to involve the contralateral mediastinum more frequently than did right-sided tumors. Patterns of failure after resection are diagrammed and follow a fairly predictable pattern on the basis of involved lobe. Conclusions: These data may help clinicians construct postoperative RT volumes that are smaller than ones traditionally utilized, which may improve the therapeutic ratio.

UNLABELLED Tangential radiotherapy for left-sided breast cancer may be cardiotoxic. Shaping the field with a heart block reduces cardiac exposure but may under-dose the breast and/or chest wall. We compared the incidence and location of local recurrences in patients irradiated with and without a heart block. METHODS AND MATERIALS Between 1994 and 1998, 180 patients irradiated to the left breast and/or chest wall were retrospectively reviewed. The local recurrence rates in patients treated with and without a heart block were compared using a 2-tailed Fisher exact test. An in-depth dosimetric analysis was performed in 23 patients to assess the percentage of breast tissue under-dosed by inclusion of the heart block. RESULTS Overall, the local recurrence rates in patients with or without a heart block were similar. In postlumpectomy patients with inferiorly located tumors, the rates of local recurrence with and without a heart block were 2 of 6 patients versus 0 of 19 patients, respectively. In the dosimetric analysis, the average percentage of breast tissue under-dosed by the inclusion of a heart block was 2.8% (range, 0%-11%). DISCUSSION A heart block is a reasonable method to limit cardiac dose but should be used cautiously following a lumpectomy in patients with inferiorly located tumors. Additional study with larger numbers of patients is warranted.

The aim of this retrospective review of patients with gynecologic malignancies treated with external beam radiotherapy (EBRT) and interstitial brachytherapy was to determine the rate of Gradeor =2 rectovaginal fistula and Gradeor =4 small bowel obstruction as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0.Thirty-six patients with primary and recurrent gynecologic cancers were treated with EBRT and interstitial brachytherapy. Median doses to tumor, bladder, and rectum were 75 Gy, 61 Gy, and 61 Gy, respectively. A univariate analysis was performed to identify variables that correlated with toxicity.At median follow-up of 19 months, the 3-year risk of small bowel obstruction was 6%. Those patients with prior abdomino-pelvic surgery who received EBRT with antero-posterior fields had higher rates of obstruction than patients without prior abdomino-pelvic surgery or those who received EBRT with four fields (50% vs. 0%, p0.0001). The 3-year risk of rectovaginal fistula was 18% and was significantly higher in patients who received76 Gy to the rectum compared with those who receivedor =76 Gy (100% vs. 7%, p = 0.009).Patients treated with EBRT and interstitial brachytherapy after abdomino-pelvic surgery should receive EBRT with four fields and the cumulative rectal dose should beor =76 Gy.

Purpose: To assess the 6-minute walk test (6MWT) as a predictor of radiation therapy–induced lung injury (RTLI). Methods and Materials: The 6MWT is a simple, economical, and reproducible test that measures both how far a person can walk in 6 min and any associated changes in vital signs. As part of a prospective trial to study RTLI, a pre-RT 6MWT was performed in 41 patients. The predictive capacities of pre-RT 6MWT, forced expiratory volume in 1 s (FEV1), and single-breath diffusing capacity for carbon monoxide (DLCO) for the development of RTLI were assessed with receiver operating curve (ROC) techniques. To evaluate the 6MWT, alone or with mean lung dose (MLD) of radiation, as a predictor of RTLI, the rates of RTLI in patient subgroups defined by 6MWT results were compared by using Fisher's exact test. Results: Thirty-one patients with ≥3 months' follow-up were evaluable. The median baseline 6MWT result was 1400 ft. Of 31 patients, 7 developed Grade ≥2 RTLI. Of 15 patients with an MLD >18 Gy (the median), 5 developed RTLI, compared with 2 of 16 with MLD ≤18 Gy ( p = 0.22). Among those with an MLD ≤18 Gy, the RTLI rates were 0 of 8 and 2 of 8 for 6MWT results ≥1400 ft or p = 0.46. The ROC area under the curve for individual metrics was as follows: FEV1 0.66, MLD 0.70, DLCO 0.61, and 6MWT 0.47. Combining FEV1 with 6MWT increased the ROC to 0.71, suggesting that the ratio might be a better predictor than the individual values. Patients with a high 6MWT/FEV1 ratio had a lower rate of RTLI than those with a relatively low ratio. Conclusions: The 6MWT might provide prognostic information beyond pulmonary function tests and dosimetric parameters in predicting RTLI. Additional work is needed to better assess the utility of these functional metrics.

A method to predict radiation-induced pneumonitis (RP) using an artificial neural network (ANN) was investigated. A retrospective study was applied to the clinical data from 142 patients who have been treated with three-dimensional conformal radiotherapy for tumors in the thoracic region. These data were classified, based on their treatment outcome, into two patient clusters: with RP ( N p = 26 ) and without RP ( N p = 116 ) . An ANN was designed as a classifier. To perform the classification, a patient-treatment outcome with RP was assigned a value of 1, and a patient treatment outcome without RP was assigned a value of −1. The input of the ANN was limited to the patient lungdose-volume data only. A volume vector ( V D ) that describes patient lung subvolumes receiving more than a set of threshold doses was used as the network input variable. A zero value was used as the threshold to set the output value into −1 or 1. Three ANNs (ANN_1, ANN_2, and ANN_3), each with three layers, were trained to perform this classification function and to show the effect of training data on the ANN performance. Radial basis function was applied as the hidden layer neuron activation function and a sigmoid function was selected as the output layer neuron function. Backpropagation with a conjugate gradient algorithm was used to train the network. ANN_1 was trained and tested by using the leave-one-out method. ANN_2 was trained by randomly selecting 2/3 of the patient data, and tested by the remaining 1/3 of the data. ANN_3 was trained by a user selecting 2/3 of the patient data, and tested by the remaining 1/3 of the data. The predictive accuracy was verified as the area under a receiver operator characteristic (ROC) curve. The correct classification rates of 73% for RP cases, and 99% for non-RP cases were obtained from ANN_1. The corresponding correct classification rates of 44% for RP cases, and 89% for non-RP cases were obtained from ANN_2. From the ANN_3 test phase, the corresponding correct classification rates of 55% for RP cases, and 95% non-RP cases were achieved. The area under ROC curve was 0 .85 ± 0 .05 , 0.68 ± 0.10 , and 0.81 ± 0.09 for ANN_1, ANN_2, and ANN_3, respectively, within its asymmetric 95% confidence interval. The sensitivity was 95%, 57%, and 71%, and the specificity was 94%, 88%, and 90% for ANN_1, ANN_2, and ANN_3, respectively. Preliminary results suggest that the ANN approach provides a useful tool for the prediction of radiation-induced lung pneumonitis, using the patient lungdose-volume information.

The purpose of this work is to compare the efficacy of mathematical models in predicting the occurrence of radiotherapy-induced left ventricular perfusion defects assessed using single-photon emission computed tomography(SPECT). The basis of this study is data from 73 left-sided breast/chestwall patients treated with tangential photon fields. The mathematical models compared were three commonly used parametric models [Lyman normal tissue complication probability (LNTCP), relative serialty (RS), generalized equivalent uniform dose (gEUD)] and a nonparametric model (Linear discriminant analysis—LDA). Data used by the models were the left ventricular dose—volume histograms, or SPECT-based dose–function histograms, and the presence/absence of SPECT perfusion defects 6 months postradiation therapy (21 patients developed defects). For the parametric models, maximum likelihood estimation and F-tests were used to fit the model parameters. The nonparametric LDAmodel step-wise selected features (volumes/function above dose levels) using a method based on receiver operating characteristics (ROC) analysis to best separate the groups with and without defects. Optimistic (upper bound) and pessimistic (lower bound) estimates of each model’s predictive capability were generated using ROC curves. A higher area under the ROC curve indicates a more accurate model (a model that is always accurate has area = 1 ). The areas under these curves for different models were used to statistically test for differences between them. Pessimistic estimates of areas under the ROC curve using dose–volume histogram/dose–function histogram inputs, in order of increasing prediction accuracy, were LNTCP ( 0.79 ∕ 0.75 ) , RS ( 0.80 ∕ 0.77 ) , gEUD ( 0.81 ∕ 0.78 ) , and LDA ( 0.84 ∕ 0.86 ) . Only the LDAmodel benefited from SPECT-based regional functional information. In general, the LDAmodel was statistically superior to the parametric models. The LDAmodel selected as features the left ventricular volumes above approximately 23 Gy ( V 23 ) , essentially volume in field, and 33 Gy ( V 33 ) , as best separating the groups with and without defects. In conclusion, the nonparametric LDAmodel appears to be a more accurate predictor of radiotherapy-induced left ventricular perfusion defects than commonly used parametric models.

To evaluate postradiation regional heart perfusion changes with single photon emission tomography (SPECT) myocardial perfusion imaging in 69 patients treated with tangential photon beams radiation therapy (RT) for left-sided breast cancer. To correlate SPECT changes with percent irradiated left ventricle (LV) volume and risk factors for coronary artery disease (CAD).Rest SPECT of the LV was acquired pre-RT and at 6-month intervals post-RT. The extent of defects (%) with a severity1.5 standard deviations below the mean was quantitatively analyzed for the distributions of the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) based on computer assisted polar map reconstruction (i.e., bull's-eye-view). Changes in perfusion were correlated with percent irradiated LV receiving25 Gy (range 0-32%). Data on patient- and treatment-related factors were collected prospectively (e.g., cardiac premorbidity, risk factors for CAD, chemotherapy, and hormonal treatment).In the LAD distribution, there were increased perfusion defects at 6 months (median 11%; interquartile range 2-23) compared with baseline (median 5%; interquartile range 1-14) (p0.001). There were no increases in perfusion defects in the LCX or RCA distributions. In multivariate analysis, the SPECT perfusion changes in the LAD distribution at 6 months were independently associated with percent irradiated LV (p0.001), hormonal therapy (p = 0.005), and pre-RT hypercholesterolemia (p = 0.006). The SPECT defects in the LAD distribution at 12 and 18 months were not statistically different from those at 6 months. The perfusion defects in the LAD distribution were limited essentially to the regions of irradiated myocardium.Tangential photon beam RT in patients with left-sided breast cancer was associated with short-term SPECT defects in the vascular distribution corresponding to the radiation portals. Factors related to the extent of perfusion defects included the percent irradiated LV, hormonal treatment, and pre-RT hypercholesterolemia.

In tubular structures, spatial aspects of the dose distribution may be important in determining the normal tissue response. Conventional dose-volume-histograms (DVHs) and dose-surface-histograms (DSHs) lack spatial information and may not be adequate to represent the three-dimensional (3D) dose data. A new 3D dose distribution data reduction scheme which preserves its longitudinal and circumferential character is presented. Dose distributions were generated at each axial level for esophagus or rectum in 123 patients with lung cancer or prostate cancer. Dose distribution histograms at each axial level were independently analyzed along the esophageal or rectal circumference to generate dose-circumference-histogram (DCH) sheets. Two types of plots were then generated from the DCH sheet. The first considered the percentage of the circumference at each axial level receiving various doses. The second considered the minimum dose delivered to any percentage of the circumference at each axial level. The DCH as a treatment planning tool can be easily implemented in a 3D planing system and is potentially useful for the study of the relationship between the complication risk and the longitudinal and circumferential dose distributions.

Purpose: To evaluate the incidence, severity, and clinical/dosimetric predictors of acute and chronic esophageal toxicities in patients with non-small cell lung cancer (NSCLC) treated with high-dose conformal thoracic radiation. Methods and Materials: Ninety-one patients with localized NSCLC treated definitively with high-dose conformal radiation therapy (RT) at Duke University Medical Center (DUMC) were reviewed. Patient characteristics were as follows: 53 males and 38 females; median age 64 yr (range 46–82); stage I—16, II—3, IIIa—40, IIIb—30, X—2; dysphagia pre-RT—6 (7%). Treatment parameters included: median corrected dose—78.8 Gy (range 64.2–85.6); BID fractionation—58 (64%); chemotherapy—43 (47%). Acute and late esophageal toxicities were graded by RTOG criteria. Using 3D treatment planning tools, the esophagus was contoured in a uniform fashion, the 3D dose distribution calculated (with lung density correction), and the dose–volume (DVH) and dose–surface histograms (DSH) generated. At each axial level, the percentage of the esophageal circumference at each dose level was calculated. The length of circumferential esophagus and the maximum circumference treated to doses >50 Gy were assessed. Patient and treatment factors were correlated with acute and chronic esophageal dysfunction using univariate and multivariate logistic regression analyses. Results: There were no acute or late grade 4 or 5 esophageal toxicities. Ten of 91 patients (11%) developed grade 3 acute toxicity. On univariate analysis of clinical parameters, both dysphagia pre-RT ( p = 0.10) and BID fractionation ( p = 0.11) tended toward significantly predicting grade 3 acute esophagitis. None of the dosimetric parameters analyzed significantly predicted for grade 3 acute esophagitis. Twelve of 66 assessable patients (18%) developed late esophageal toxicity. Of the clinical parameters analyzed, only dysphagia pre-RT ( p = 0.06) tended toward significantly predicting late esophageal toxicity. On univariate analyses, the effects of percent organ volume treated >50 Gy ( p = 0.05), percent surface area treated >50 Gy ( p = 0.05), length of 100% circumference treated >50 Gy ( p = 0.04), and maximum percent of circumference treated >80 Gy ( p = 0.01) significantly predicted for late toxicity of all grades. On multivariate analysis, percent organ volume treated >50 Gy ( p = 0.02) and maximum percent of circumference treated >80 Gy ( p = 0.02) predicted for late toxicity. Conclusions: Late esophageal toxicity following aggressive, high-dose conformal radiotherapy is common but rarely severe. Dosimetric variables addressing the longitudinal and circumferential character of the esophagus have biologic rationale and are predictive of late toxicity. Further studies are needed to assess whether these parameters are better predictors than those derived from traditional DVHs.

This article reviews radiation techniques including field arrangements, anatomic borders, and doses for the treatment of Hodgkin's disease when radiotherapy is being used as the sole treatment and when it is part of a planned combined modality program with chemotherapy. We describe the techniques currently in use at Duke University Medical Center. Particular emphasis is placed on the evidence regarding the appropriate extent of the treatment field and the doses of radiation necessary to achieve local control. These issues assume increasing importance as we attempt to maintain high cure rates for Hodgkin's disease but lower the frequency of serious long-term complications.

Purpose: To develop a clinical procedure to treat field within a field (concomitant boost) portals with a single compensated field. Methods and Materials: An ordinary manual cerrobend block former was used to produce styrofoam molds from simulator film data. A special gypsum compound was poured into the molds. The compensator block is independently mounted to the treatment machine via a custom-made compensator holder. Results: Measurements confirm that the inhomogeneous dose distribution has been reliably delivered via this technique. The accuracy of placement of the high dose region is sufficient for clinical use. Conclusion: The procedure enables the concomitant boost effect to be easily implemented in the clinic without increasing clinical setup time.

A case study is presented. Craniospinal radiotherapy and a three-field pineal boost for trilateral retinoblastoma were delivered to a patient previously irradiated for ocular retinoblastoma. The availability of CT-based three-dimensional treatment planning provided the capability of identifying the previously irradiated volume as a three-dimensional anatomic structure and of designing a highly customized set of treatment beams that minimized reirradiation of that volume.

The treatment of extremity soft-tissue sarcoma has evolved considerably over the years. Previously, the preferred treatment was radical resection or amputation. Recently, radiation therapy combined with conservative resection has been shown to provide adequate tumor control while preserving a functional limb. Often, a large volume of tissue is irradiated in a manner that requires the patient to be in a reproducible position. Minimizing patient movement is imperative to ensure that the prescribed dose is delivered to the designated target volume. At our institution, Alpha Cradles® * have been routinely used for eight years to aid in positioning extremity sarcoma patients. The positioning of the patient for tumors at different locations in the extremity and the Alpha Cradle® fabrication is described. The positioning device is comfortable for the patient and the accuracy is verified by comparison of simulation films with weekly port films.

Purpose To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Methods and Materials Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Results Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20–0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. Conclusion We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

To study the temporal nature of regional lung density changes and to assess whether the dose-dependent nature of these changes is associated with patient- and treatment-associated factors.Between 1991 and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT) chest computed tomography (CT) scans were evaluated. Changes in regional lung density were related to regional dose to define a dose-response curve (DRC) for RT-induced lung injury using three-dimensional planning tools and image fusion. Multiple post-RT follow-up CT scans were evaluated by fitting linear-quadratic models of density changes on dose with time as the covariate. Various patient- and treatment-related factors were examined as well.There was a dose-dependent increase in regional lung density at nearly all post-RT follow-up intervals. The population volume-weighted changes evolved over the initial 6-month period after RT and reached a plateau thereafter (p0.001). On univariate analysis, patient age greater than 65 years (p = 0.003) and/or the use of pre-RT surgery (p0.001) were associated with significantly greater changes in CT density at both 6 and 12 months after RT, but the magnitude of this effect was modest.There appears to be a temporal nature for the dose-dependent increases in lung density. Nondosimetric clinical factors tend to have no, or a modest, impact on these changes.

Purpose: To compare PET extracted metrics and investigate the role of a gradient-based PET segmentation tool, PET Edge (MIM Software Inc., Cleveland, OH), in the context of an adaptive PET protocol for node positive gynecologic cancer patients. Methods: An IRB approved protocol enrolled women with gynecological, PET visible malignancies. A PET-CT was obtained for treatment planning prescribed to 45–50.4Gy with a 55– 70Gy boost to the PET positive nodes. An intra-treatment PET-CT was obtained between 30–36Gy, and all volumes re-contoured. Standard uptake values (SUVmax, SUVmean, SUVmedian) and GTV volumes were extracted from the clinician contoured GTVs on the pre- and intra-treament PET-CT for primaries and nodes and compared with a two tailed Wilcoxon signed-rank test. The differences between primary and node GTV volumes contoured in the treatment planning system and those volumes generated using PET Edge were also investigated. Bland-Altman plots were used to describe significant differences between the two contouring methods. Results: Thirteen women were enrolled in this study. The median baseline/intra-treatment primary (SUVmax, mean, median) were (30.5, 9.09, 7.83)/( 16.6, 4.35, 3.74), and nodes were (20.1, 4.64, 3.93)/( 6.78, 3.13, 3.26). The p values were all < 0.001. The clinical contours were all larger than the PET Edge generated ones, with mean difference of +20.6 ml for primary, and +23.5 ml for nodes. The Bland-Altman revealed changes between clinician/PET Edge contours to be mostly within the margins of the coefficient of variability. However, there was a proportional trend, i.e. the larger the GTV, the larger the clinical contours as compared to PET Edge contours. Conclusion: Primary and node SUV values taken from the intratreament PET-CT can be used to assess the disease response and to design an adaptive plan. The PET Edge tool can streamline the contouring process and lead to smaller, less user-dependent contours.

PURPOSE: To assess results with twice-daily high-dose radiotherapy (RT) for non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between 1991 and 1998, 94 patients with unresectable NSCLC were prescribed ≥ 73.6 Gy via accelerated fractionation. Fifty were on a phase II protocol (P group); 44 were similarly treated off-protocol (NP group). The clinical target volume received 45 Gy at 1.25 Gy bid (6-hour interval). The gross target volume received 1.6 Gy bid to 73.6 to 80 Gy over 4.5 to 5 weeks using a concurrent boost technique. Overall survival (OS) and local progression-free survival (LPFS) were calculated by the Kaplan-Meier method. Median follow-up durations for surviving P and NP patients were 67 and 16 months, respectively. RESULTS: Total doses received were ≥ 72 Gy in 97% of patients. The median OS by stage was 34, 13, and 12 months for stages I/II, IIIa, and IIIb, respectively. LPFS was significantly longer for patients with T1 lesions (median, 43 months) versus T2-4 (median, 7 to 10 months; P = .01). Results were similar in the P and NP groups. Acute grade ≥ 3 toxicity included esophagus (14 patients; 15%), lung (three patients; 3% [one grade 5]), and skin (four patients; 4%). Grade ≥ 3 late toxicity in 86 assessable patients included esophagus (three patients; 3%), lung (15 patients; 17% [three grade 5]), skin (five patients; 6%), heart (two patients; 2%), and nerve (one patient; 1%). CONCLUSION: This regimen yielded favorable survival results, particularly for T1 lesions. Acute grade ≥ 3 toxicity seems greater than for conventional RT, though most patients recovered. Late grade ≥ 3 pulmonary toxicity occurred in 17%. Because of continued locoregional recurrences, we are currently using doses ≥ 86 Gy.

Purpose : Compare dose distributions of traditional versus conformal beam orientations in paranasal sinus malignancies. Materials and methods : Maximum normal tissue doses, dose volume histograms (DVH), normal tissue complication probabilities (NTCP), and the percentage of each normal tissue receiving > 80% of the average target dose (V80) were calculated. Results/Conclusions : Conformal planning reduced the V80 to the optic nerves and chiasm as well as the normal tissue maximum doses to the ipsilateral and contralateral optic nerves and chiasm, and mean NTCPs.

Purpose: To evaluate the dosimetric improvement of IMRT treatment plans generated with patient‐specific margins compared to uniform margins for prostate cancer patients. Methods and Materials: For 13 prostate cancer patients who underwent IMRT treatment, daily cone‐beam computed tomography(CBCT) scans were acquired during the first week, followed by weekly scans (total of 85 scans) for the remainder of the treatment. Both prostate and seminal vesicles were retrospectively segmented on all CBCTs. The patient‐specific planning target volume (PTVPS) was defined based on a composite volume of both prostate and seminal vesicles from the first four daily CBCTs and the planning CT. A 3‐mm margin was added around the composite volume to obtain PTVPS. As a comparison, we also generated a PTV in the planning CT with a uniform margin (PTVUni) of 10‐mm in all directions, except 5‐mm posteriorly, around the prostate and seminal vesicles. An IMRT plan for each PTV was generated for each patient. Evaluation plans based on each of weekly CBCT were generated to gauge the DVHs resulting from these IMRT plans to the patient volumes segmented on weekly CBCTs.Results: Evaluation plans generated with PTVPS in place of PTVUni resulted in average improvements of 1.4% and 2.8% for V95 of prostate and seminal vesicles, respectively, and average reduction of 7.0% and 4.7% for V50 of bladder and rectum, respectively. Out of 85 weekly CBCT evaluation plans for each PTV, 7.1% of cases showed improvement for V95 of prostate with PTVUni, 40.0% for V95 of seminal vesicles, 28.2% for V50 of bladder and 29.4% for V50 of rectum. Conclusions: Patient‐specific margins, designed using multiple scans, appear to provide little dosimetric benefit with respect to target coverage over a standard uniform margin formulation; sparing critical structures is improved to a greater degree. “Partially supported by Varian Medical Systems”.

13543 Background: Radiation (RT)-induced lung injury is a common side effect following thoracic RT. The study of RT-induced lung injury is complicated by the multiple endpoints considered (e.g., ra...

Purpose: To assess whether body mass index (BMI) affects the rate of “deep” set‐up errors (i.e. those that increase the volume of heart irradiated), resulting in an increased risk of RT‐induced myocardial perfusion defects (PD) 6–60 months post‐RT. Materials and Methods: For 87 patients receiving RT for left‐sided breast cancer,treatment set‐up accuracy was determined by measuring the height of the lung shadow seen at the level of the central axis on simulation and serial medial tangent portal films. SPECT nuclear medicine scans were performed serially pre‐ and post‐RT to assess for cardiac PD. The interaction among BMI, set‐up error frequency, and the rate of PD was compared using a 1‐tailed Fisher's Exact Test. Results: The rates of deep set‐up deviations were 9/32 vs. 24/51 in patients with BMI 0% but ⩽1% LV in the field (i.e. patients who are generally predicted to be at very low risk for RT‐induced cardiac dysfunction). The rates of PD in these patients with deep vs. “shallow” set‐up errors (i.e. those that decrease the volume of heart irradiated) were 5/6 vs. 3/10 (p=0.059) (Fig 2). Conclusions: Patients with BMI⩾25 kg/m2 tend to have a higher incidence of deep set‐up errors, causing more heart to be irradiated than intended. In patients with very small volumes of heart in the RT field, those with deep set‐up errors are more likely to have PD post‐RT. Accurate patient set‐up on the treatment machine is critical to minimize the risk of RT‐induced cardiac injury, particularly in overweight and obese patients. Supported by grants 17‐98‐1‐8071 and BC010663 from the DOD.