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At least 451 records · Page 25
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Reirradiation Human Spinal Cord Tolerance for Stereotactic Body Radiotherapy

Purpose: We reviewed the treatment for patients with spine metastases who initially received conventional external beam radiation (EBRT) and were reirradiated with 1-5 fractions of stereotactic body radiotherapy (SBRT) who did or did not subsequently develop radiation myelopathy (RM). Methods and Materials: Spinal cord dose-volume histograms (DVHs) for 5 RM patients (5 spinal segments) and 14 no-RM patients (16 spine segments) were based on thecal sac contours at retreatment. Dose to a point within the thecal sac that receives the maximum dose (P{sub max}), and doses to 0.1-, 1.0-, and 2.0-cc volumes within the thecal sac were reviewed. The biologically effective doses (BED) using {alpha}/{beta} = 2 Gy for late spinal cord toxicity were calculated and normalized to a 2-Gy equivalent dose (nBED = Gy{sub 2/2}). Results: The initial conventional radiotherapy nBED ranged from {approx}30 to 50 Gy{sub 2/2} (median {approx}40 Gy{sub 2/2}). The SBRT reirradiation thecal sac mean P{sub max} nBED in the no-RM group was 20.0 Gy{sub 2/2} (95% confidence interval [CI], 10.8-29.2), which was significantly lower than the corresponding 67.4 Gy{sub 2/2} (95% CI, 51.0-83.9) in the RM group. The mean total P{sub max} nBED in the no-RM group was 62.3 Gy{sub 2/2} (95% CI, 50.3-74.3), which was significantly lower than the corresponding 105.8 Gy{sub 2/2} (95% CI, 84.3-127.4) in the RM group. The fraction of the total P{sub max} nBED accounted for by the SBRT P{sub max} nBED for the RM patients ranged from 0.54 to 0.78 and that for the no-RM patients ranged from 0.04 to 0.53. Conclusions: SBRT given at least 5 months after conventional palliative radiotherapy with a reirradiation thecal sac P{sub max} nBED of 20-25 Gy{sub 2/2} appears to be safe provided the total P{sub max} nBED does not exceed approximately 70 Gy{sub 2/2}, and the SBRT thecal sac P{sub max} nBED comprises no more than approximately 50% of the total nBED.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

FDG-PET Assessment of the Effect of Head and Neck Radiotherapy on Parotid Gland Glucose Metabolism

Purpose: Functional imaging with [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) provides the opportunity to define the physiology of the major salivary glands before and after radiation therapy. The goal of this retrospective study was to identify the radiation dose-response relationship of parotid gland glucose metabolism in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods: Forty-nine adults with HNSCC were identified who had curative intent intensity-modulated radiation therapy (IMRT) and FDG-PET imaging before and after treatment. Using a graphical user interface, contours were delineated for the parotid glands on axial CT slices while all authors were blinded to paired PET slices. Average and maximal standard uptake values (SUV) were measured within these anatomic regions. Changes in SUV and volume after radiation therapy were correlated with parotid gland dose-volume histograms from IMRT plans. Results: The average parotid gland volume was 30.7 mL and contracted 3.9 {+-} 1.9% with every increase of 10 Gy in mean dose (p = 0.04). However, within the first 3 months after treatment, there was a uniform reduction of 16.5% {+-} 7.3% regardless of dose. The average SUV{sub mean} of the glands was 1.63 {+-} 0.48 pretreatment and declined by 5.2% {+-} 2.5% for every increase of 10 Gy in mean dose (p = 0.04). The average SUV{sub max} was 4.07 {+-} 2.85 pretreatment and decreased in a sigmoid manner with mean dose. A threshold of 32 Gy for mean dose existed, after which SUV{sub max} declined rapidly. Conclusion: Radiation dose responses of the parotid glands can be measured by integrated CT/FDG-PET scans. Retrospective analysis showed sigmoidal declines in the maximum metabolism but linear declines in the average metabolism of the glands with dose. Future studies should correlate this decline in FDG uptake with saliva production to improve treatment planning.

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

Should Patient Setup in Lung Cancer Be Based on the Primary Tumor? An Analysis of Tumor Coverage and Normal Tissue Dose Using Repeated Positron Emission Tomography/Computed Tomography Imaging

Purpose: Evaluation of the dose distribution for lung cancer patients using a patient setup procedure based on the bony anatomy or the primary tumor. Methods and materials: For 39 patients with non-small-cell lung cancer, the planning fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan was registered to a repeated FDG-PET/CT scan made in the second week of treatment. Two patient setup methods were analyzed based on the bony anatomy or the primary tumor. The original treatment plan was copied to the repeated scan, and target and normal tissue structures were delineated. Dose distributions were analyzed using dose-volume histograms for the primary tumor, lymph nodes, lungs, and spinal cord. Results: One patient showed decreased dose coverage of the primary tumor caused by progressive disease and required replanning to achieve adequate coverage. For the other patients, the minimum dose to the primary tumor did not significantly deviate from the planned dose: -0.2 {+-} 1.7% (p = 0.71) and -0.1 {+-} 1.7% (p = 0.85) for the bony anatomy setup and the primary tumor setup, respectively. For patients (n = 31) with nodal involvement, 10% showed a decrease in minimum dose larger than 5% for the bony anatomy setup and 13% for the primary tumor setup. The mean lung dose exceeded the maximum allowed 20 Gy in 21% of the patients for the bony anatomy setup and in 13% for the primary tumor setup, whereas for the spinal cord this occurred in 10% and 13% of the patients, respectively. Conclusions: In 10% and 13% of patients with nodal involvement, setup based on bony anatomy or primary tumor, respectively, led to important dose deviations in nodal target volumes. Overdosage of critical structures occurred in 10-20% of the patients. In cases of progressive disease, repeated imaging revealed underdosage of the primary tumor. Development of practical ways for setup procedures based on repeated high-quality imaging of all tumor sites during radiotherapy should therefore be an important research focus.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Dosimetric Comparison of Intensity-Modulated Radiotherapy Plans, With or Without Anterior Myocardial Territory and Left Ventricle as Organs at Risk, in Early-Stage Left-Sided Breast Cancer Patients

Purpose: We evaluated heart sparing using an intensity-modulated radiotherapy (IMRT) plan with the left ventricle (LV) and/or the anterior myocardial territory (AMT) as additional organs at risk (OARs). Methods and Materials: A total of 10 patients with left-sided breast cancer were selected for dosimetric planning. Both lungs, the right breast, heart, LV, and AMT were defined as OARs. We generated one tangential field plan and four IMRT plans for each patient. We examined the dose-volume histogram parameters of the planning target volume and OARs. Results: Compared with the tangential field plan, the mean dose to the heart in the IMRT plans did not show significant differences; however, the dose to the AMT and LV decreased by 18.7-45.4% and 10.8-37.4%, respectively. The maximal dose to the heart decreased by 18.6-35.3%, to the AMT by 22.0-45.1%, and to the LV by 23.5-45.0%, And the relative volumes of the heart (V{sub {>=}12}), AMT (V{sub >11}) and LV (V{sub >10}) decreased significantly with different levels, respectively. The volume of the heart, AMT, LV, both lungs, and right breast receiving {>=}5 Gy showed a significant increase. Compared with the IMRT (H) plan, the mean dose to the heart, AMT, and LV decreased by 17.5-21.5%, 25.2-29.8%, and 22.8-29.8% and the maximal dose by 13.6-20.6%, 23.1-29.6%, and 17.3-29.1%, respectively. The IMRT plans for both lungs and the right breast showed no significant differences. Conclusions: The IMRT plans with the addition of the AMT and/or LV as OARs considerably increased heart sparing. We recommend including the LV as an additional OAR in such plans.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Three-Dimensional Dose Addition of External Beam Radiotherapy and Brachytherapy for Oropharyngeal Patients Using Nonrigid Registration

Purpose: To develop and evaluate a method for adding dose distributions of combined external beam radiotherapy (EBRT) and brachytherapy (BT) for oropharyngeal patients. Methods and Materials: Two computed tomography (CT) scans were used for 5 patients: the EBRT CT, used for EBRT planning, and the BT CT, acquired after catheter implantation. For each scan, the salivary glands and the chewing and swallowing muscles were contoured, and a dose distribution was calculated. A nonrigid transformation was obtained by registering the organs' surfaces. Then the BT dose distribution was mapped onto the EBRT dose distribution by applying the transformation obtained. To account for differences in fractionation, the physical doses were converted to equivalent dose in 2 Gy (EQD{sub 2}), and the total dose was found by adding dose voxel by voxel. The robustness of the dose addition was investigated by varying delineations and input parameters of the registration method and by varying the {alpha}/{beta} parameter for EQD{sub 2}. The effect of the perturbations was quantified using dose-volume histograms (DVH) and gamma analyses (distance-to-agreement/dose-difference = 1 mm/1 Gy). Results: The variations in input parameters and delineations caused only small perturbations in the DVH of the added dose distributions. For most organs the gamma index was low, and it was moderately elevated for organs lying in areas with a steep gradient (median gamma index {<=}2.3 for constrictor muscles, {<=}0.7 for all other organs). Conclusions: The presented method allows adding dose distributions of combined EBRT and BT for oropharyngeal patients. In general, the method is reliable and robust with respect to uncertainties in organ delineation, perturbations in input parameters of the method, and {alpha}/{beta} values.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Variations in the Contouring of Organs at Risk: Test Case From a Patient With Oropharyngeal Cancer

Purpose: Anatomy contouring is critical in radiation therapy. Inaccuracy and variation in defining critical volumes will affect everything downstream: treatment planning, dose-volume histogram analysis, and contour-based visual guidance used in image-guided radiation therapy. This study quantified: (1) variation in the contouring of organs at risk (OAR) in a clinical test case and (2) corresponding effects on dosimetric metrics of highly conformal plans. Methods and Materials: A common CT data set with predefined targets from a patient with oropharyngeal cancer was provided to a population of clinics, which were asked to (1) contour OARs and (2) design an intensity-modulated radiation therapy plan. Thirty-two acceptable plans were submitted as DICOM RT data sets, each generated by a different clinical team. Using those data sets, we quantified: (1) the OAR contouring variation and (2) the impact this variation has on dosimetric metrics. New technologies were employed, including a software tool to quantify three-dimensional structure comparisons. Results: There was significant interclinician variation in OAR contouring. The degree of variation is organ-dependent. We found substantial dose differences resulting strictly from contouring variation (differences ranging from -289% to 56% for mean OAR dose; -22% to 35% for maximum dose). However, there appears to be a threshold in the OAR comparison metric beyond which the dose differences stabilize. Conclusions: The effects of interclinician variation in contouring organs-at-risk in the head and neck can be large and are organ-specific. Physicians need to be aware of the effect that variation in OAR contouring can play on the final treatment plan and not restrict their focus only to the target volumes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Validating the RTOG-Endorsed Brachial Plexus Contouring Atlas: An Evaluation of Reproducibility Among Patients Treated by Intensity-Modulated Radiotherapy for Head-and-Neck Cancer

Purpose: To evaluate interobserver variability for contouring the brachial plexus as an organ-at-risk (OAR) and to analyze its potential dosimetric consequences in patients treated with intensity-modulated radiotherapy (IMRT) for head-and-neck cancer. Methods and Materials: Using the Radiation Therapy Oncology Group (RTOG)-endorsed brachial plexus contouring atlas, three radiation oncologists independently delineated the OAR on treatment planning computed-tomography (CT) axial scans from 5 representative patients undergoing IMRT to a prescribed dose of 70 Gy for head-and-neck cancer. Dose-volume histograms for the brachial plexus were calculated, and interobserver differences were quantified by comparing various dosimetric statistics. Qualitative analysis was performed by visually assessing the overlapping contours on a single beam's eye view. Results: Brachial plexus volumes for the 5 patients across observers were 26 cc (18-35 cc), 25 cc (21-30 cc), 29 cc (28-32 cc), 29 cc (23-38 cc), and 29 cc (23-34 cc). On qualitative analysis, minimal variability existed except at the inferolateral portion of the OAR, where slight discrepancies were noted among the physicians. Maximum doses to the brachial plexus ranged from 71.6 to 72.6 Gy, 75.2 to 75.8 Gy, 69.1 to 71.0 Gy, 76.4 to 76.9 Gy, and 70.6 to 71.4 Gy. Respective volumes receiving doses greater than 60 Gy (V60) were 8.6 to 10.9 cc, 6.2 to 8.1 cc, 8.2 to 11.6 cc, 8.3 to 10.5 cc, and 5.6 to 9.8 cc. Conclusion: The RTOG-endorsed brachial plexus atlas provides a consistent set of guidelines for contouring this OAR with essentially no learning curve. Adoption of these contouring guidelines in the clinical setting is encouraged.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Helical Tomotherapy Versus Single-Arc Intensity-Modulated Arc Therapy: A Collaborative Dosimetric Comparison Between Two Institutions

Purpose: Both helical tomotherapy (HT) and single-arc intensity-modulated arc therapy (IMAT) deliver radiation using rotational beams with multileaf collimators. We report a dual-institution study comparing dosimetric aspects of these two modalities. Methods and Materials: Eight patients each were selected from the University of Maryland (UMM) and the University of Wisconsin Cancer Center Riverview (UWR), for a total of 16 cases. Four cancer sites including brain, head and neck (HN), lung, and prostate were selected. Single-arc IMAT plans were generated at UMM using Varian RapidArc (RA), and HT plans were generated at UWR using Hi-Art II TomoTherapy. All 16 cases were planned based on the identical anatomic contours, prescriptions, and planning objectives. All plans were swapped for analysis at the same time after final approval. Dose indices for targets and critical organs were compared based on dose-volume histograms, the beam-on time, monitor units, and estimated leakage dose. After the disclosure of comparison results, replanning was done for both techniques to minimize diversity in optimization focus from different operators. Results: For the 16 cases compared, the average beam-on time was 1.4 minutes for RA and 4.8 minutes for HT plans. HT provided better target dose homogeneity (7.6% for RA and 4.2% for HT) with a lower maximum dose (110% for RA and 105% for HT). Dose conformation numbers were comparable, with RA being superior to HT (0.67 vs. 0.60). The doses to normal tissues using these two techniques were comparable, with HT showing lower doses for more critical structures. After planning comparison results were exchanged, both techniques demonstrated improvements in dose distributions or treatment delivery times. Conclusions: Both techniques created highly conformal plans that met or exceeded the planning goals. The delivery time and total monitor units were lower in RA than in HT plans, whereas HT provided higher target dose uniformity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Helical Tomotherapy With Simultaneous Integrated Boost After Laparoscopic Staging in Patients With Cervical Cancer: Analysis of Feasibility and Early Toxicity

Purpose: To demonstrate the feasibility and safety of the simultaneous integrated boost technique for dose escalation in combination with helical tomotherapy in patients with cervical cancer. Methods and Materials: Forty patients (International Federation of Gynecology and Obstetrics Stage IB1 pN1-IVA) underwent primary chemoradiation with helical tomotherapy. Before therapy, 29/40 patients underwent laparoscopic pelvic and para-aortic lymphadenectomy. In 21%, 31%, and 3% of the patients, pelvic, pelvic and para-aortic, and skip metastases in the para-aortic region could be confirmed. All patients underwent radiation with 1.8-50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (planning target volume-A), and a simultaneous boost with 2.12-59.36 Gy to the boost region (planning target volume-B). The boost region was defined using titan clips during laparoscopic staging. In all other patients, standardized borders for the planning target volume-B were defined. High-dose-rate brachytherapy was performed in 39/40 patients. The mean biologic effective dose to the macroscopic tumor ranged from 87.5 to 97.5 Gy. Chemotherapy consisted of weekly cisplatin 40 mg/m{sup 2}. Dose-volume histograms and acute gastrointestinal, genitourinary, and hematologic toxicity were evaluated. Results: The mean treatment time was 45 days. The mean doses to the small bowel, rectum, and bladder were 28.5 {+-} 6.1 Gy, 47.9 {+-} 3.8 Gy, and 48 {+-} 3 Gy, respectively. Hematologic toxicity Grade 3 occurred in 20% of patients, diarrhea Grade 2 in 5%, and diarrhea Grade 3 in 2.5%. There was no Grade 3 genitourinary toxicity. All patients underwent curettage 3 months after chemoradiation, which confirmed complete pathologic response in 38/40 patients. Conclusions: The concept of simultaneous integrated boost for dose escalation in patients with cervical cancer is feasible, with a low rate of acute gastrointestinal and genitourinary toxicity. Whether dose escalation can be translated into improved outcome will be assessed after a longer follow-up time.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Dosimetric Comparison of Three-Dimensional Conformal Proton Radiotherapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Radiotherapy for Treatment of Pediatric Craniopharyngiomas

Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk-Operator }, 34.4%{sup Asterisk-Operator }) were recorded with the use of proton therapy. ({sup Asterisk-Operator }Differences were significant based on Friedman's test with Bonferroni-Dunn correction, {alpha} = 0.05) Conclusions: The current study found that proton therapy was able to avoid excess integral radiation dose to a variety of normal structures at all dose levels while maintaining equal target coverage. Future studies will examine the clinical benefits of these dosimetric advantages.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Radiation-Induced Middle Ear and Mastoid Opacification in Skull Base Tumors Treated With Radiotherapy

Purpose: To assess the incidence of middle ear (ME) pathology in patients treated with radiotherapy (RT) for skull base tumors. Methods and Materials: A retrospective analysis of 61 patients treated with RT between 2003 and 2008 for skull base tumors was conducted. Clinical outcomes and demographics were reviewed. Dose-volume histogram analysis was performed on the eustachian canal (EC), ME, mastoid air cells, vestibular apparatus, cochlea, internal auditory canal, lateral and posterior nasopharynx, and temporal lobes to relate doses to symptoms and radiographic change. Otomastoid opacification was rated 0 (none), 1 (mild), 2 (moderate), and 3 (severe) by a neuroradiologist blinded to clinical outcomes and doses. Results: The median prescribed dose was 50.4 Gy (range, 14-74 Gy). The ME mean dose was 14 Gy and 34 Gy for Grade 0-1 and 2-3 opacification, respectively (p < 0.0001). The mean mastoid dose was 10 Gy and 26 Gy for Grade 0-1 and 2-3, respectively (p < 0.0001). The mean EC dose was 17 Gy and 32 Gy for Grade 0-1 and 2-3, respectively (p = 0.0001). Otomastoid opacification resolved in 17 of 40 patients (42.5%), at a mean of 17 months after RT (range, 2-45 months). Otomastoid opacification persisted in 23 of 40 patients (57.5%), with a mean follow-up of 23 months (range, 2-55 months). Multivariate analysis showed that mastoid dose >30 Gy (odds ratio = 28.0, p < 0.001) and posterior nasopharynx dose of >30 Gy (odds ratio = 4.9, p = 0.009) were associated with Grade 2-3 effusions, whereas other factors including dose to EC and ME were not significant. Conclusions: A mean RT dose >30 Gy to the mastoid air cells or posterior nasopharynx is associated with increased risk of moderate to severe otomastoid opacification, which persisted in more than half of patients at 2-year follow-up.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Estimation of {alpha}/{beta} for Late Rectal Toxicity Based on RTOG 94-06

Purpose: To estimate {alpha}/{beta}, the parameter ratio from the linear-quadratic (LQ) model, for Grade {>=}2 late rectal toxicity among patients treated on Radiation Therapy Oncology Group (RTOG) protocol 94-06; and to determine whether correcting the rectal dose-volume histogram (DVH) for differences in dose per fraction, based on the LQ model, significantly improves the fit to these data of the Lyman-Kutcher-Burman (LKB) normal-tissue complication probability (NTCP) model. Methods and Materials: The generalized LKB model was fitted to the Grade {>=}2 late rectal toxicity data in two ways: by using DVHs representing physical dose to rectum, and by using a modified approach in which dose bins in the rectal DVH were corrected for differences in dose per fraction using the LQ model, with {alpha}/{beta} estimated as an additional unknown parameter. The analysis included only patients treated with the same treatment plan throughout radiotherapy, so that the dose per fraction to each voxel of rectum could be determined from the DVH. The likelihood ratio test was used to assess whether the fit of the LQ-corrected model was significantly better than the fit of the LKB model based on physical doses to rectum. Results: The analysis included 509 of the 1,084 patients enrolled on RTOG 94-06. The estimate of {alpha}/{beta} from the LQ-corrected LKB model was 4.8 Gy, with 68% confidence interval 0.6 Gy to 46 Gy. The fit was not significantly different from the fit of the LKB model based on physical dose to rectum (p = 0.236). Conclusions: The estimated fractionation sensitivity for Grade {>=}2 late rectal toxicity is consistent with values of {alpha}/{beta} for rectum found previously in human beings and in rodents. However, the confidence interval is large, and there is no evidence that LQ correction of the rectal DVH significantly changes the fit or predictions of the LKB model for this endpoint.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Dose Effect Relationship for Late Side Effects of the Rectum and Urinary Bladder in Magnetic Resonance Image-Guided Adaptive Cervix Cancer Brachytherapy

Purpose: To establish dose-response relationships for late side effects of the rectum and bladder in cervix cancer patients after magnetic resonance image-guided adaptive brachytherapy (IGABT). Methods and Materials: A cohort of 141 patients was treated with 45 to 50.4 Gy with or without cisplatin plus 4 fractions of 7 Gy IGABT. Doses for the most exposed 2, 1, and 0.1-cm{sup 3} (D{sub 2cc}, D{sub 1cc}, D{sub 0.1cc}) volumes of the rectum and bladder were converted into the equivalent dose in 2 Gy fractions (EQD2), using a linear quadratic model ({alpha}/{beta} = 3 Gy). Late side effects were prospectively assessed (using late effects in normal tissues subjective, objective, management and analytic [LENT SOMA]) scales. Dose-response relationships were determined by logit analyses. Results: Eleven patients developed rectal side effects, and 23 patients had urinary side effects. A significant dose effect was found for all rectal dose-volume histogram (DVH) parameters for patients with side effect grades of 1 to 4 but was only significant for D{sub 2cc} and D{sub 1cc} for grades {>=}2. The ED10 values for D{sub 2cc} were 73 Gy for grades 1 to 4 and 78 Gy for grades 2 to 4 rectal morbidity. For bladder side effects, a significant dose effect was shown for all DVH parameters for complication grades {>=}2; the respective ED10 was 101 Gy. Conclusions: Well-defined dose-response curves could be established for D{sub 2cc} in the rectum and the urinary bladder.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Development and Evaluation of Multiple Isocentric Volumetric Modulated Arc Therapy Technique for Craniospinal Axis Radiotherapy Planning

Purpose: To develop and compare a volumetric modulated arc therapy (VMAT) technique with conventional radiotherapy for craniospinal irradiation with respect to improved dose conformity and homogeneity in the planning target volume (PTV) and to reduced dose to organs at risk (OAR). Methods and Materials: Conventional craniospinal axis radiotherapy plans of 5 patients were acquired. The median (range) length of the PTV was 58.9 (48.1-83.7) cm. The 6-MV VMAT plans were inversely planned with one isocenter near the base of the brain and the minimum number of isocenters required for the specified lengths of spine. The plans were optimized with high weighting for PTV coverage and low weighting for OAR sparing. Conformity and heterogeneity indices, dose-volume histograms, mean doses, and non-PTV integral doses from the two plans (prescription dose 23.4 Gy in 13 fractions) were compared. Results: The median (range) conformity index of VMAT was 1.22 (1.09-1.45), compared with 1.69 (1.44-2.67) for conventional plans (p = 0.04). The median (range) heterogeneity index was also lower for VMAT compared with conventional plans: 1.04 (1.03-1.07) vs. 1.12 (1.09-1.19), respectively (p = 0.04). A significant reduction of mean and maximum doses was observed in the heart, thyroid, esophagus, optic nerves, and eyes with VMAT when compared with conventional plans. A decrease in body V{sub 10Gy} was observed, but for 4 of 5 patients non-PTV integral dose was increased with VMAT when compared with the conventional plans. Conclusions: A VMAT technique to treat the craniospinal axis significantly reduces OAR dose, potentially leading to lower late organ toxicity. However, this is achieved at the expense of increased low-dose volumes, which is inherent to the technique, carrying a potentially increased risk of secondary malignancies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Voxel-Based Dose Reconstruction for Total Body Irradiation With Helical TomoTherapy

Purpose: We have developed a megavoltage CT (MVCT)-based dose reconstruction strategy for total body irradiation (TBI) with helical TomoTherapy (HT) using a deformable registration model to account for the patient's interfraction changes. The proposed technique serves as an efficient tool for delivered dose verification and, potentially, plan adaptation. Methods and Materials: Four patients with acute myelogenous leukemia treated with TBI using HT were selected for this study. The prescription was 12 Gy, 2 Gy/fraction, twice per day, given at least 6 h apart. The original plan achieved coverage of 80% of the clinical target volume (CTV) by the 12 Gy isodose surface. MVCTs were acquired prior to each treatment. Regions of interest were contoured on each MVCT. The dose for each fraction was calculated based on the MVCT using the HT planned adaptive station. B-spline deformable registration was conducted to establish voxel-to-voxel correspondence between the MVCT and the planning CT. The resultant deformation vector was employed to map the reconstructed dose from each fraction to the same point as the plan dose, and a voxel-to-voxel summed dose from all six fractions was obtained. The reconstructed dose distribution and its dosimetric parameters were compared with those of the original treatment plan. Results: While changes in CTV contours occurred in all patients, the reconstructed dose distribution showed that the dose-volume histogram for CTV coverage was close (<1.5%) to that of the original plan. For sensitive structures, the differences between the reconstructed and the planned doses were less than 3.0%. Conclusion: Voxel-based dose reconstruction strategy that takes into account interfraction anatomical changes using MVCTs is a powerful tool for treatment verification of the delivered doses. This proposed technique can also be applied to adaptive TBI therapy using HT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Role of Principal Component Analysis in Predicting Toxicity in Prostate Cancer Patients Treated With Hypofractionated Intensity-Modulated Radiation Therapy

Purpose: To determine if principal component analysis (PCA) and standard parameters of rectal and bladder wall dose-volume histograms (DVHs) of prostate cancer patients treated with hypofractionated image-guided intensity-modulated radiotherapy (hypo-IMRT) can predict acute and late gastrointestinal (GI) toxicity. Methods and Materials: One hundred twenty-one patients underwent hypo-IMRT at 3 Gy/fraction, 5 days/week to either 60 Gy or 66 Gy, with daily online image guidance. Acute and late GI and genitourinary (GU) toxicity were recorded weekly during treatment and at each follow-up. All Radiation Therapy Oncology Group (RTOG) criteria toxicity scores were dichotomized as <2 and {>=}2. Standard dosimetric parameters and the first five to six principal components (PCs) of bladder and rectal wall DVHs were tested for association with the dichotomized toxicity outcomes, using logistic regression. Results: Median follow-up of all patients was 47 months (60 Gy cohort= 52 months; 66 Gy cohort= 31 months). The incidence rates of {>=}2 acute GI and GU toxicity were 14% and 29%, respectively, with no Grade {>=}3 acute GU toxicity. Late GI and GU toxicity scores {>=}2 were 16% and 15%, respectively. There was a significant difference in late GI toxicity {>=}2 when comparing the 66 Gy to the 60 Gy cohort (38% vs. 8%, respectively, p = 0.0003). The first PC of the rectal DVH was associated with late GI toxicity (odds ratio [OR], 6.91; p < 0.001), though it was not significantly stronger than standard DVH parameters such as Dmax (OR, 6.9; p < 0.001) or percentage of the organ receiving a 50% dose (V50) (OR, 5.95; p = 0 .001). Conclusions: Hypofractionated treatment with 60 Gy in 3 Gy fractions is well tolerated. There is a steep dose response curve between 60 Gy and 66 Gy for RTOG Grade {>=}2 GI effects with the dose constraints employed. Although PCA can predict late GI toxicity for patients treated with hypo-IMRT for prostate cancer, it provides no additional information over using more standard DVH parameters.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Dosimetric Comparison of Involved-Field Three-Dimensional Conformal Photon Radiotherapy and Breast-Sparing Proton Therapy for the Treatment of Hodgkin's Lymphoma in Female Pediatric Patients

Purpose: To assess the potential reduction in breast dose for young girls with Hodgkin's lymphoma (HL) treated with breast-sparing proton therapy (BS-PT) as compared with three-dimensional conformal involved-field photon radiotherapy (3D-CRT). Methods and Materials: The Clarian Health Cancer Registry was queried for female pediatric patients with the diagnosis of HL who received radiotherapy at the Indiana University Simon Cancer Center during 2006-2009. The original CT simulation images were obtained, and 3D-CRT and BS-PT plans delivering 21 Gy or cobalt gray equivalent (CGE) in 14 fractions were created for each patient. Dose-volume histogram data were collected for both 3D-CRT and BS-PT plans and compared by paired t test for correlated samples. Results: The cancer registry provided 10 female patients with Ann Arbor Stage II HL, aged 10-18 years at the time of treatment. Both mean and maximum breast dose were significantly less with BS-PT compared with 3D-CRT: 0.95 CGE vs. 4.70 Gy (p < 0.001) and 21.07 CGE vs. 23.11 Gy (p < 0.001), respectively. The volume of breast receiving 1.0 Gy/CGE and 5.0 Gy/CGE was also significantly less with BS-PT, 194 cm{sup 3} and 93 cm{sup 3}, respectively, compared with 790 cm{sup 3} and 360 cm{sup 3} with 3D-CRT (p = 0.009, 0.013). Conclusion: Breast-sparing proton therapy has the potential to reduce unnecessary breast dose in young girls with HL by as much as 80% relative to involved-field 3D-CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗