Comparative assessment of radiation therapy-induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy.

PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.

Pre-Chemoradiotherapy FDG PET/CT cannot Identify Residual Metabolically-Active Volumes within Individual Esophageal Tumors.

OBJECTIVE: To study whether subvolumes with a high pre-chemoradiotherapy (CRT) FDG uptake could identify residual metabolically-active volumes (MAVs) post-CRT within individual esophageal tumors. Accurate identification will allow simultaneous integrated boost to these subvolumes at higher risk to improve clinical outcomes. METHODS: Twenty patients with esophageal cancer were treated with CRT plus surgery and underwent FDG PET/CT scans before and after CRT. The two scans were rigidly registered. Seven MAVs pre-CRT and four MAVs post-CRT within a tumor were defined with various SUV thresholds. The similarity and proximity between the MAVs pre-CRT and post-CRT were quantified with three metrics: fraction of post-CRT MAV included in pre-CRT MAV, volume overlap and centroid distance. RESULTS: Eight patients had no residual MAV. Six patients had local residual MAV (SUV ≥2.5 post-CRT) within or adjoining the original MAV (SUV ≥2.5 pre-CRT). On average, less than 65% of any post-CRT MAVs was included in any pre-CRT MAVs, with a low volume overlap <45%, and large centroid distance >8.6 mm. In general, subvolumes with higher FDG-uptake pre-CRT or post-CRT had lower volume overlap and larger centroid distance. Six patients had new distant MAVs that were determined to be inflammation from radiation therapy. CONCLUSIONS: Pre-CRT PET/CT cannot reliably identify the residual MAVs within individual esophageal tumors. Simultaneous integrated boost to subvolumes with high FDG uptake pre-CRT may not be feasible.

SU-E-T-399: Dosimetric and Geometric Evaluation of a Novel Stereotactic Radiotherapy Device for Breast Cancer: The GammaPod.

PURPOSE: A dedicated stereotactic irradiation device, the GammaPodTM, was developed to treat early stage breast cancer. This study presents the first description of the dosimetric and geometric characteristics from the prototype unit. METHODS: The GammaPod stereotactic radiotherapy device is an assembly of a hemi-spherical source carrier containing 36 Co-60 sources, a tungsten collimator, a dynamically controlled treatment table and a breast immobilization cup embedded with a stereotactic coordinate system. The source carrier and the variable-size collimator rotate synchronously to form 36 non-coplanar, concentric arcs focused at the isocenter. The treatment table enables motion in three dimensions facilitating continuous dose painting in comparison to a sphere packing approach. Geometric and dosimetric evaluations and a method for absorbed dose calibration are provided. Dosimetric verifications of the dynamically delivered plans are performed for eight patients in hypothetical pre-op, post-op and dose painting treatment scenarios. RESULTS: Loaded with a cumulative activity of 4320 Ci, the GammaPod unit delivers 5.31 Gy/min at the isocenter. Due to non-coplanar beam arrangement and dynamic dose shaping features, the GammaPod delivers uniform doses to the targets with excellent conformity. The spatial accuracy of the device is less than 1 mm. Single shot profiles with the 25 mm collimator are measured with radiochromic film and found to be in good agreement with respect to the MC based calculations (congruence of FWHM less than 1 mm). Dosimetric verifications corresponding to all treatment plans corresponding to three target scenarios for each of the eight patients demonstrated Gamma index pass rates greater than 97%. CONCLUSIONS: The first description of the dosimetric and geometric evaluation of the GammaPod was performed. The observed level of agreement between the treatment planning system calculations and dosimetric measurements has confirmed that the system can deliver highly complex treatment plans with remarkable geometric and dosimetric accuracy. C Yu and J Zhang have commercial affiliations with Xcision Medical Systems.

SU-E-T-403: Delivery Efficiency of StereoArc Stereotactic Body Radiotherapy (SBRT).

PURPOSE: Traditional SBRT employs approximately 10 static beams with up to 20 Gy per fraction, requiring lengthy treatments which can be difficult for patients to tolerate, increasing the risk of movement, and causing discrepancies in the reproducibility of the breathing cycle. Commercial VMAT systems offer shorter treatment times with modulated beams; however, modulation is often not necessary or desired for small fields. Conformai arc therapy offers efficient beam delivery, but with only one aperture shape and constant beam weighting over all gantry angles. This study evaluates the efficiency of a new SBRT delivery Method: a conformai arc with multiple aperture shapes and variable dose rate. METHODS: Three clinical SBRT cases were chosen for this study. Each static field was converted into an arc segment to create a StereoArc plan. Gantry angle ranges were determined from the clinical monitor units, with the MU/degree chosen to maximize the dose rate. All segments were merged into a single arc with variable dose rate. Dose distributions from the StereoArc plans were compared to the clinical static field plans using Pinnacle. Delivery times were compared between the static SBRT plans, both with and without Beam Automation, and equivalent StereoArc plans. All plans were delivered on a Varian TrueBeam using a dose rate of 1000 MU/min. RESULTS: Dose differences between StereoArc and static plans were minimal. Delivery times for the static plans were 5-8 minutes, while delivery time with StereoArc was less than 3 minutes for all cases, which was equivalent to delivering the static plans with Beam Automation. CONCLUSIONS: Delivery efficiency was improved up to 60%: from 8 minutes for static fields, to less than 3 minutes for StereoArc. StereoArc appears to be both an effective and efficient way of delivering SBRT for centers not wishing to modulate SBRT and without access to Beam Automation. This study is partially supported by NIH grant 1R01CA133539-01A2.

SU-D-BRB-04: FDG-PET Histogram Distances: Novel Predictors of Tumor Response to Chemoradiotherapy.

PURPOSE: To examine the accuracy of FGD-PET histogram distances as predictors of pathologic tumor response to chemo-radiotherapy (CRT) in esophageal cancer. METHODS: Twenty patients were included. A rigid registration was used to align the post-CRT PET/CT with the pre-CRT PET/CT images. The primary tumor was delineated using a region-growing algorithm with a threshold of SUV = 2.5 on the pre-CRT PET. Two histograms of SUVs within the tumor were constructed on the pre-CRT PET and registered post-CRT PET, respectively. The differences between the two histograms reflected changes in the SUV distribution and were therefore potential predictors of tumor response. The differences were quantitatively measured by histogram distances using 12 bin-to-bin and 8 cross-bin algorithms. The accuracy of histogram distances in predicting pathologic tumor response to CRT was measured using the area under ROC curve (AUC), prediction accuracy, and the Mann-Whitney tests, in comparison with traditional PET response measures and texture features. RESULTS: Cross-bin histogram distances were shown to be significant (p<0.05) predictors of pathologic tumor response. They were more accurate than bin- to-bin histogram distances (not significant). The most accurate cross-bin histogram distances were: Quadratic-Chi distance (AUC=0.89, accuracy=80%, p=0.003), Earth Mover distance (AUC=0.83,accuracy=80%, p=0.014), diffusion distance (AUC = 0.82, accuracy=85%, p=0.02) and Match distance (AUC = 0.79, accuracy=80%, p=0.03). This family of novel predictors were more accurate than traditional PET response measures using SUVmax (AUC=0.76, accuracy=75%, p=0.05), SUVpeak (AUC=0.74, accuracy=70%, p=0.08), Total Glycolytic Volume (AUC=0.76, accuracy=70%, p=0.05), as well as texture features based on the cooccurrence matrix (Inertia: AUC=0.85, accuracy=80%, p=0.01). CONCLUSIONS: The cross-bin histogram distances characterized changes in the SUV distribution within a tumor and showed high accuracy for the prediction of pathologic response to CRT in esophageal cancer. This workwas supported in part by the National Cancer Institute Grant R21 CA131979.

Esophageal motion during radiotherapy: quantification and margin implications.

The purpose was to evaluate interfraction and intrafraction esophageal motion in the right-left (RL) and anterior-posterior (AP) directions using computed tomography (CT) in esophageal cancer patients. Eight patients underwent CT simulation and CT-on-rails imaging before and after radiotherapy. Interfraction displacement was defined as differences between pretreatment and simulation images. Intrafraction displacement was defined as differences between pretreatment and posttreatment images. Images were fused using bone registries, adjusted to the carina. The mean, average of the absolute, and range of esophageal motion were calculated in the RL and AP directions, above and below the carina. Thirty-one CT image sets were obtained. The incidence of esophageal interfraction motion > or =5 mm was 24% and > or =10 mm was 3%; intrafraction motion > or =5 mm was 13% and > or =10 mm was 4%. The average RL motion was 1.8 +/- 5.1 mm, favoring leftward movement, and the average AP motion was 0.6 +/- 4.8 mm, favoring posterior movement. Average absolute motion was 4.2 mm or less in the RL and AP directions. Motion was greatest in the RL direction above the carina. Coverage of 95% of esophageal mobility requires 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margins. In all directions, the average of the absolute interfraction and intrafraction displacement was 4.2 mm or less. These results support a 12 mm left, 8 mm right, 10 mm posterior, and 9 mm anterior margin for internal target volume (ITV) and can guide margins for future intensity modulated radiation therapy (IMRT) trials to account for organ motion and set up error in three-dimensional planning.

Investigation of optimal beam margins for stereotactic radiotherapy of lung-cancer using Monte Carlo dose calculations.

This work investigated the selection of beam margins in lung-cancer stereotactic body radiotherapy (SBRT) with 6 MV photon beams. Monte Carlo dose calculations were used to systematically and quantitatively study the dosimetric effects of beam margins for different lung densities (0.1, 0.15, 0.25, 0.35 and 0.5 g cm(-3)), planning target volumes (PTVs) (14.4, 22.1 and 55.3 cm3) and numbers of beam angles (three, six and seven) in lung-cancer SBRT in order to search for optimal beam margins for various clinical situations. First, a large number of treatment plans were generated in a commercial treatment planning system, and then recalculated using Monte Carlo simulations. All the plans were normalized to ensure that 95% of the PTV at least receives the prescription dose and compared quantitatively. Based on these plans, the relationships between the beam margin and quantities such as the lung toxicity (quantified by V20, the percentage volume of the two lungs receiving at least 20 Gy) and the maximum target (PTV) dose were established for different PTVs and lung densities. The impact of the number of beam angles on the relationship between V20 and the beam margin was assessed. Quantitative information about optimal beam margins for lung-cancer SBRT was obtained for clinical applications.

A method for repositioning of stereotactic brain patients with the aid of real-time CT image guidance.

This note presents a method that recalculates the coordinates of the isocentre for patients undergoing stereotactic radiotherapy to the brain with a relocatable head frame based on a pre-treatment CT scan. The method was evaluated by comparing initial stereotactic coordinates of the isocentre with the recalculated coordinates for eight single-fraction patients. These patients had the Brown-Roberts-Wells (BRW) frame fixed to the outer table of the skull, and therefore the coordinates of any anatomical point should be identical between the initial scan and the pre-treatment scan. The differences between the two sets of coordinates were attributed to errors in the method. The results showed that the systematic errors in the recalculated coordinates were less than 0.05 mm, and they were not statistically significant. The random errors (one standard deviation) were from 0.35 mm (lateral) to 0.58 mm (vertical). The average value of the combined 3D difference was 0.75 mm.

The treatment of non-metastatic prostate cancer with external beam radiation therapy.

Multiple treatment options exist for men with non-metastatic prostate cancer. For nearly 50 years, external beam radiation therapy (EBRT) has been an important means of treating men with this disease. Improvements in technology and better use of pre-treatment variables including prostate specific antigen (PSA), Gleason score and prediction nomograms have steadily improved biochemical and clinical outcomes. This article reviews the current status of EBRT in the treatment of prostate cancer. Differences in technique as well as clinical results using conventional, 3D conformal and intensity modulated radiation therapy are compared and contrasted. The appropriate use of adjuvant hormones as well as the complications of these treatments will also be discussed.

Stereotactic IMRT for prostate cancer: dosimetric impact of multileaf collimator leaf width in the treatment of prostate cancer with IMRT.

The focus of this work is the dosimetric impact of multileaf collimator (MLC) leaf width on the treatment of prostate cancer with intensity-modulated radiation therapy (IMRT). Ten patients with prostate cancer were planned for IMRT delivery using two different MLC leaf widths--4mm and 10mm--representing the Radionics micro-multileaf collimator (mMLC) and Siemens MLC, respectively. Treatment planning was performed on the XKnifeRT2 treatment-planning system (Radionics, Burlington, MA). All beams and optimization parameters were identical for the mMLC and MLC plans. All the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose. The differences in dose distribution between the two different plans were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. We specifically compared the volume of rectum receiving 40 Gy (V40), 50 Gy (V50), 60 Gy (V60), the dose received by 17% and 35% of rectum (D17 and D35), and the maximum dose to 1 cm3 of the rectum for a prescription dose of 74 Gy. For the urinary bladder, the dose received by 25% of bladder (D25), V40, and the maximum dose to 1 cm3 of the organ were recorded. For PTV we compared the maximum dose to the "hottest" 1 cm3 (Dmax1 cm3) and the dose to 99% of the PTV (D99). The dose inhomogeneity in the target, defined as the ratio of the difference in Dmax1 cm3 and D99 to the prescribed dose, was also compared between the two plans. In all cases studied, significant reductions in the volume of rectum receiving doses less than 65 Gy were seen using the mMLC. The average decrease in the volume of the rectum receiving 40 Gy, 50 Gy, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p < 0.0001 for V40 and V50 and p < 0.012 for V60. The mean dose reductions for D17 and D35 for the rectum using the mMLC were 20.4% (p < 0.0001) and 18.3% (p < 0.0002), respectively. There were consistent reductions in all dose indices studied for the bladder. The target dose inhomogeneity was improved in the mMLC plans by an average of 29%. In the high-dose range, there was no significant difference in the dose deposited in the "hottest" 1 cm3 of the rectum between the two plans for all cases (p > 0.78). In conclusion, the use of the mMLC for IMRT of the prostate resulted in significant improvement in the DVH parameters of the prostate and critical organs, which may improve the therapeutic ratio.

Megavoltage radiotherapy for aneurysmal bone cysts.

PURPOSE: An aneurysmal bone cyst (ABC) is a rapidly expansile and destructive benign tumor of bone that is usually treated by curettage and bone graft, with or without adjuvant treatment. For recurrent tumors, or tumors for which surgery would result in significant functional morbidity, does radiotherapy (RT) provide a safe and effective alternative for local control? PATIENTS AND METHODS: Nine patients with histologically diagnosed aneurysmal bone cysts without other associated benign or malignant tumors were treated at the University of Florida with megavoltage RT between February 1964 and June 1992. The patients received local radiotherapy doses between 20 and 60 Gy, with 6 patients receiving 26--30 Gy. In 6 patients the diagnosis was made by biopsy alone; 3 underwent intralesional curettage before RT. Minimum follow-up was 20 months; 7 of 9 patients (77%) had follow-up greater than 11 years. RESULTS: No patient experienced a local recurrence (median follow-up, 17 years). One patient required stabilization of the cervical spine 10 months after RT because of dorsal kyphosis from vertebral body collapse. No other significant side effects were experienced, and no patients developed secondary malignancies. Four patients were lost to follow-up: at 20 months, 11.5 years, 17 years, and 20 years after the initiation of treatment, none with any evidence of local recurrence. All of the patients who had significant pain before RT had relief of their symptoms within 2 weeks of completion of therapy. CONCLUSIONS: Using modern-day RT, patients with recurrent or inoperable aneurysmal bone cysts can be treated effectively (with minimal toxicity) using a prescribed tumor dose of 26--30 Gy.