Management of radiotherapy patients with implanted cardiac pacemakers and defibrillators: A Report of the AAPM TG-203†.

Managing radiotherapy patients with implanted cardiac devices (implantable cardiac pacemakers and implantable cardioverter-defibrillators) has been a great practical and procedural challenge in radiation oncology practice. Since the publication of the AAPM TG-34 in 1994, large bodies of literature and case reports have been published about different kinds of radiation effects on modern technology implantable cardiac devices and patient management before, during, and after radiotherapy. This task group report provides the framework that analyzes the potential failure modes of these devices and lays out the methodology for patient management in a comprehensive and concise way, in every step of the entire radiotherapy process.

Evaluation of intraoperative magnetic resonance imaging/ultrasound fusion optimization for low-dose-rate prostate brachytherapy.

PURPOSE: Intraoperative planning with transrectal ultrasound (US) is used for accurate seed placement and optimal dosimetry in prostate brachytherapy. However, prostate magnetic resonance imaging (MRI) has shown superiority in delineation of prostate anatomy. Accordingly, MRI/US fusion may be useful for accurate intraoperative planning. We analyzed planning with MRI/US fusion to compare differences in dosimetry and volume to that derived from the postoperative computed tomography (CT). MATERIAL AND METHODS: Twenty patients underwent preoperative prostate MRI, which was fused intraoperatively with US during prostate brachytherapy. Intraoperative 125I or 103Pd seed placement was modified by the use of MRI fusion when indicated. Following implantation, dose comparisons were made between data derived from MRI/US and that from post-operative CT scans. Plan parameters analyzed included the D90 (dose to 90% of the prostate), rectal D30, V30 (volume of the rectum receiving 30 percent of dose), and prostate V100. RESULTS: The median number of seeds implanted per patient was seventy-six. The MRI measured prostate volume, which was on average 4.47 cc larger than the CT measured prostate volume. In 9 patients, the apex of the prostate was better identified under MRI with the fusion protocol, and an average of 4 fewer seeds were required to be placed in the apex/urinary sphincter region. Both MRI and US individually showed a reduced intraoperative prostate D90 in comparison to the postoperative CT, with a larger mean difference for MRI in comparison with US (9.71 vs. 4.31 Gy, p = 0.007). This was also true for the prostate V100 (5.18 vs. 2.73 cc, p = 0.009). Post-operative CT underestimated rectal D30 and V30 in comparison to both MRI and US with MRI showing a larger mean difference than US for D30 (40.64 vs. 35.92 Gy, p = 0.04) and V30 (50.20 vs. 44.38 cc, p = 0.009). CONCLUSIONS: The MRI/US fusion demonstrated greater prostate volume compared to standard CT/US based planning likely due to the better resolution of the prostate apex. Furthermore, rectal dose was underestimated with CT vs. MRI based planning. Additional study is required to assess long-term clinical implications of disease control and effects on long-term toxicity, especially as related to the rectum and urinary sphincter. MRI/US intraoperative fusion may improve prostate dosimetry while sparing the rectum and urethra, potentially impacting disease control and late toxicity.

Megavoltage conebeam CT cine as final verification of treatment plan in lung stereotactic body radiotherapy.

INTRODUCTION: To analyse the clinical impact of megavoltage conebeam computed tomography (MV-CBCT) cine on internal target volume (ITV) coverage in lung stereotactic body radiotherapy (SBRT). METHODS: One hundred and six patients received lung SBRT. All underwent 4D computed tomography simulation followed by treatment via image guided 3D conformal or intensity modulated radiation. Prior to SBRT, all patients underwent MV-CBCT cine, in which raw projections are displayed as beam's-eye-view fluoroscopic series with the planning target volume (PTV) projected onto each image, enabling verification of tumour motion relative to the PTV and assessment of adequacy of treatment margin. RESULTS: Megavoltage conebeam computed tomography cine was completed 1-2 days prior to SBRT. Four patients (3.8%) had insufficient ITV coverage inferiorly at cine review. All four plans were changed by adding 5 mm on the PTV margin inferiorly. The mean change in PTV volumes was 3.9 cubic centimetres (cc) (range 1.85-6.32 cc). Repeat cine was performed after plan modification to ensure adequate PTV coverage in the modified plans. CONCLUSIONS: PTV margin was adequate in the majority of patients with this technique. MV-CBCT cine did show insufficient coverage in a small subset of patients. Insufficient PTV margins may be a function of 4D CT simulation inadequacies or deficiencies in visualizing the ITV inferior border in the full-inhale phase. MV-CBCT cine is a valuable tool for final verification of PTV margins.

Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors.

OBJECTIVES: We report single center experience on the outcome and toxicity of SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors between 2007 and 2014. PATIENTS AND METHODS: Patients with 1-4 hepatic lesions and tumor diameter ≤9 cm received SBRT at 46.8Gy ± 3.7 in 4-6 fractions. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. RESULTS: Eighty-seven assessable patients (114 lesions) completed liver SBRT for hepatoma (39) or isolated metastases (48) with a median followup of 20.3 months (range 1.9-64.1). Fourteen patients underwent liver transplant with SBRT as a bridging treatment or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤4 cm. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). No incidence of grade >2 treatment toxicity was observed. CONCLUSION: In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates.

Imaging a moving lung tumor with megavoltage cone beam computed tomography.

PURPOSE: Respiratory motion may affect the accuracy of image guidance of radiation treatment of lung cancer. A cone beam computed tomography (CBCT) image spans several breathing cycles, resulting in a blurred object with a theoretical size equal to the sum of tumor size and breathing motion. However, several factors may affect this theoretical relationship. The objective of this study was to analyze the effect of tumor motion on megavoltage (MV)-CBCT images, by comparing target sizes on simulation and pretreatment images of a large cohort of lung cancer patients. METHODS: Ninety-three MV-CBCT images from 17 patients were analyzed. Internal target volumes were contoured on each MV-CBCT dataset [internal target volume (ITVCB)]. Their extent in each dimension was compared to that of two volumes contoured on simulation 4-dimensional computed tomography (4D-CT) images: the combination of the tumor contours of each phase of the 4D-CT (ITV4D) and the volume contoured on the average CT calculated from the 4D-CT phases (ITVave). Tumor size and breathing amplitude were assessed by contouring the tumor on each CBCT raw projection where it could be unambiguously identified. The effect of breathing amplitude on the quality of the MV-CBCT image reconstruction was analyzed. RESULTS: The mean differences between the sizes of ITVCB and ITV4D were -1.6 ± 3.3 mm (p < 0.001), -2.4 ± 3.1 mm (p < 0.001), and -7.2 ± 5.3 mm (p < 0.001) in the anterior/posterior (AP), left/right (LR), and superior/inferior (SI) directions, respectively, showing that MV-CBCT underestimates the full target size. The corresponding mean differences between ITVCB and ITVave were 0.3 ± 2.6 mm (p = 0.307), 0.0 ± 2.4 mm (p = 0.86), and -4.0 ± 4.3 mm (p < 0.001), indicating that the average CT image is more representative of what is visible on MV-CBCT in the AP and LR directions. In the SI directions, differences between ITVCB and ITVave could be separated into two groups based on tumor motion: -3.2 ± 3.2 mm for tumor motion less than 15 mm and -10.9 ± 6.3 mm for tumor motion greater than 15 mm. Deviations of measured target extents from their theoretical values derived from tumor size and motion were correlated with motion amplitude similarly for both MV-CBCT and average CT images, suggesting that the two images were subject to similar motion artifacts for motion less than 15 mm. CONCLUSIONS: MV-CBCT images are affected by tumor motion and tend to under-represent the full target volume. For tumor motion up to 15 mm, the volume contoured on average CT is comparable to that contoured on the MV-CBCT. Therefore, the average CT should be used in image registration for localization purposes, and the standard 5 mm PTV margin seems adequate. For tumor motion greater than 15 mm, an additional setup margin may need to be used to account for the increased uncertainty in tumor localization.

Use of implanted gold fiducial markers with MV-CBCT image-guided IMRT for pancreatic tumours.

INTRODUCTION: Visualisation of soft tissues such as pancreatic tumours by mega-voltage cone beam CT (MV-CBCT) is frequently difficult and daily localisation is often based on more easily seen adjacent bony anatomy. Fiducial markers implanted into pancreatic tumours serve as surrogates for tumour position and may more accurately represent absolute tumour position. Differences in daily shifts based on alignment to implanted fiducial markers vs. alignment to adjacent bony anatomy were compared. METHODS: Gold fiducial markers were placed into the pancreatic tumour under endoscopic ultrasound (EUS) guidance in 12 patients. Patients subsequently received image-guided intensity-modulated radiation therapy (IG-IMRT). MV-CBCT was performed prior to each fraction and isocentre shifts were performed based on alignment to the fiducial markers. We retrospectively reviewed archived MV-CBCT datasets and calculated shift differences in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) axes relative to shifts based on alignment to adjacent bony anatomy. RESULTS: Two hundred forty-three fractions were analysed. The mean absolute difference in isocentre shifts between the fiducial markers and those aligned to bony anatomy was 3.4 mm (range 0-13 mm), 6.3 mm (range 0-21 mm) and 2.6 mm (range 0-12 mm), in LR, SI and AP directions, respectively. The mean three-dimensional vector shift difference between markers vs. bony anatomy alignment was 8.6 mm. CONCLUSIONS: These data suggest that fiducial markers used in conjunction with MV-CBCT improve the accuracy of daily target delineation compared with localisation using adjacent bony anatomy and that gold fiducial markers using MV-CBCT alignment are a viable option for target localisation during IG-IMRT.

Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure.

To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outside of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.

Flattening filter removal for improved image quality of megavoltage fluoroscopy.

PURPOSE: Removal of the linear accelerator (linac) flattening filter enables a high rate of dose deposition with reduced treatment time. When used for megavoltage imaging, an unflat beam has reduced primary beam scatter resulting in sharper images. In fluoroscopic imaging mode, the unflat beam has higher photon count per image frame yielding higher contrast-to-noise ratio. The authors' goal was to quantify the effects of an unflat beam on the image quality of megavoltage portal and fluoroscopic images. METHODS: 6 MV projection images were acquired in fluoroscopic and portal modes using an electronic flat-panel imager. The effects of the flattening filter on the relative modulation transfer function (MTF) and contrast-to-noise ratio were quantified using the QC3 phantom. The impact of FF removal on the contrast-to-noise ratio of gold fiducial markers also was studied under various scatter conditions. RESULTS: The unflat beam had improved contrast resolution, up to 40% increase in MTF contrast at the highest frequency measured (0.75 line pairs/mm). The contrast-to-noise ratio was increased as expected from the increased photon flux. The visualization of fiducial markers was markedly better using the unflat beam under all scatter conditions, enabling visualization of thin gold fiducial markers, the thinnest of which was not visible using the unflat beam. CONCLUSIONS: The removal of the flattening filter from a clinical linac leads to quantifiable improvements in the image quality of megavoltage projection images. These gains enable observers to more easily visualize thin fiducial markers and track their motion on fluoroscopic images.

A method for registration of single photon emission computed tomography (SPECT) and computed tomography (CT) images for liver stereotactic radiotherapy (SRT).

PURPOSE: To describe a simple method of coregistration of nonanatomic liver SPECT and CT images acquired in separate sessions for three-dimensional (3D)-CRT planning utilizing dual radiolabeled and radiopaque body surface markers, and evaluate the accuracy of the registration on the patient surface. METHODS: Ten patients treated for liver metastases or hepatocellular carcinoma with stereotactic body radiation therapy or 3D-CRT were selected for this study to evaluate the SPECT∕CT registration process. All patients were positioned in a custom-molded vacuum bag on the flat table top. Nine radiopaque markers were taped to the abdominal surface in three axial planes at the level of the liver. Following CT imaging, the nine radiopaque markers were then labeled with radioactive tags, each containing 10 µCi of (99m)Tc, and SPECT images were acquired. The metric used to evaluate the registration was the fiducial registration error (FRE), defined as the root mean square of the distance between pairs of homologous markers on the CT and SPECT images. The evaluation of the registration accuracy was performed in two steps: first the minimum number of markers necessary to obtain a robust registration was optimized; second the FRE was calculated on the remaining set of unused markers. Additionally, the deformation of the patient's abdominal surface between CT and SPECT acquisition sessions was evaluated using the distances between all possible unused marker pairs on the CT and SPECT images separately. The root mean square of the CT-to-SPECT difference between those distances was used to define the deformation index (DI). The registration method was evaluated on all ten patients in addition to an anthropomorphic phantom study. RESULTS: The minimum number of markers above which the registration was not improved by more than 1 mm was 4. The FRE, calculated over the 5 remaining markers, was 6.1 mm for the patient population and 1.8 mm for the phantom study. The DI was 5.0 mm on average over all 10 patients and correlated well with the FRE. The DI was 1.6 mm for the phantom study, which represented the imaging systems' resolution and the ability to place the CT and SPECT markers at the exact same location. CONCLUSIONS: It is feasible to use radiolabeled and radiopaque dual body surface markers for registration of SPECT and CT images acquired in separate sessions allowing conformal avoidance of SPECT-defined functional normal liver. Point-based rigid registration accuracy on the patient surface of 6.1 mm can be achieved using 4 dual body surface markers. The main contribution to the registration error is the deformation of the abdominal surface, arising from the inability to setup the patient in the exact same position at different times on two different imaging systems, and to properly account for breathing artifacts on the CT and SPECT images.

Influence of acquisition parameters on MV-CBCT image quality.

The production of high quality pretreatment images plays an increasing role in image-guided radiotherapy (IGRT) and adaptive radiation therapy (ART). Megavoltage cone-beam computed tomography (MV-CBCT) is the simplest solution of all the commercially available volumetric imaging systems for localization. It also suffers the most from relatively poor contrast due to the energy range of the imaging photons. Several avenues can be investigated to improve MV-CBCT image quality while maintaining an acceptable patient exposure: beam generation, detector technology, reconstruction parameters, and acquisition parameters. This article presents a study of the effects of the acquisition scan length and number of projections of a Siemens Artiste MV-CBCT system on image quality within the range provided by the manufacturer. It also discusses other aspects not related to image quality one should consider when selecting an acquisition protocol. Noise and uniformity were measured on the image of a cylindrical water phantom. Spatial resolution was measured using the same phantom half filled with water to provide a sharp water/air interface to derive the modulation transfer function (MTF). Contrast-to-noise ratio (CNR) was measured on a pelvis-shaped phantom with four inserts of different electron densities relative to water (1.043, 1.117, 1.513, and 0.459). Uniformity was independent of acquisition protocol. Noise decreased from 1.96% to 1.64% when the total number of projections was increased from 100 to 600 for a total exposure of 13.5 MU. The CNR showed a ± 5% dependence on the number of projections and 10% dependence on the scan length. However, these variations were not statistically significant. The spatial resolution was unaffected by the arc length or the sampling rate. Acquisition parameters have little to no effect on the image quality of the MV-CBCT system within the range of parameters available on the system. Considerations other than image quality, such as memory storage, acquisition speed, and individual projection image quality, speak in favor of the use of a coarse sampling rate on the short scan.

Mature follow-up for high-risk stage I non-small-cell lung carcinoma treated with sublobar resection and intraoperative iodine-125 brachytherapy.

PURPOSE: To update the Allegheny General Hospital experience of high-risk Stage I non-small-cell lung cancer patients treated with sublobar resection and intraoperative (125)I Vicryl mesh brachytherapy. METHODS AND MATERIALS: Between January 5, 1996 and February 19, 2008, 145 patients with Stage I non-small-cell lung cancer who were not lobectomy candidates because of cardiopulmonary compromise underwent sublobar resection and placement of (125)I seeds along the resection line. The (125)I seeds embedded in Vicryl suture were attached with surgical clips to a sheet of Vicryl mesh, inserted over the target area, and prescribed to a 0.5-cm planar margin. RESULTS: The mean target area, total activity, number of seeds implanted, and prescribed total dose was 33.3 cm(2) (range, 18.0-100.8), 20.2 mCi (range, 11.1-29.7), 46 (range, 30-100), and 117 Gy (range, 80-180), respectively. The median length of the surgical stay was 6 days (range, 1-111), with a perioperative mortality rate of 3.4%. At a median follow-up of 38.3 months (range, 1-133), 6 patients had developed local recurrence (4.1%), 9 had developed regional failure (6.2%), and 25 had distant failure (17.2%). On multivariate analysis, no patient- or tumor-specific factors or surgical or dosimetric factors were predictive of local recurrence. The overall median survival was 30.5 months with a 3- and 5-year overall survival rate of 65% and 35%, respectively. CONCLUSION: (125)I brachytherapy for high-risk, Stage I non-small-cell lung cancer after sublobar resection is well tolerated and associated with a low local failure rate.

Stereotactic radiosurgery boost to the resection bed for oligometastatic brain disease: challenging the tradition of adjuvant whole-brain radiotherapy.

OBJECT: Whole-brain radiation therapy (WBRT) has been the traditional approach to minimize the risk of intracranial recurrence following resection of brain metastases, despite its potential for late neurotoxicity. In 2007, the authors demonstrated an equivalent local recurrence rate to WBRT by using stereotactic radiosurgery (SRS) to the operative bed, sparing 72% of their patients WBRT. They now update their initial experience with additional patients and more mature follow-up. METHODS: The authors performed a retrospective review of all cases involving patients with limited intracranial metastatic disease (< or = 4 lesions) treated at their institution with SRS to the operative bed following resection. No patient had prior cranial radiation and WBRT was used only for salvage. RESULTS: From November 2000 to June 2009, 52 patients with a median age of 61 years met inclusion criteria. A single metastasis was resected in each patient. Thirty-four of the patients each had 1 lesion, 13 had 2 lesions, 3 had 3 lesions, and 2 had 4 lesions. A median dose of 1500 cGy (range 800-1800 cGy) was delivered to the resection bed targeting a median volume of 3.85 cm(3) (range 0.08-22 cm(3)). With a median follow-up of 13 months, the median survival was 15.0 months. Four patients (7.7%) had a local recurrence within the surgical site. Twenty-three patients (44%) ultimately developed distant brain recurrences at a median of 16 months postresection, and 16 (30.7%) received salvage WBRT (8 for diffuse disease [> 3 lesions], 4 for local recurrence, and 4 for diffuse progression following salvage SRS). The median time to WBRT administration postresection was 8.7 months (range 2-43 months). On univariate analysis, patient factors of a solitary tumor (19.0 vs 12 months, p = 0.02), a recursive partitioning analysis (RPA) Class I (21 vs 13 months, p = 0.03), and no extracranial disease on presentation (22 vs 13 months, p = 0.01) were significantly associated with longer survival. Cox multivariate analysis showed a significant association with longer survival for the patient factors of no extracranial disease on presentation (p = 0.01) and solitary intracranial metastasis (p = 0.02). Among patients with no extracranial disease, a solitary intracranial metastasis conferred significant additional survival advantage (43 vs 10.5 months, p = 0.05, log-rank test). No factor (age, RPA class, tumor size or histological type, disease burden, extent of resection, or SRS dose or volume) was related to the need for salvage WBRT. CONCLUSIONS: Adjuvant SRS to the metastatic intracranial operative bed results in a local recurrence rate equivalent to adjuvant WBRT. In combination with SRS for unresected lesions and routine imaging surveillance, this approach achieves robust overall survival (median 15 months) while sparing 70% of the patients WBRT and its potential acute and chronic toxicity.

Comparison of mega-voltage cone-beam computed tomography prostate localization with online ultrasound and fiducial markers methods.

The online image-guided localization data from 696 ultrasound (US), 598 mega-voltage cone-beam computed tomography (MV-CBCT), and 393 seed markers (SMs) couch alignments for patients undergoing intensity modulation radiotherapy of the prostate were analyzed. Daily US, MV-CBCT and SM images were acquired for 19, 17 and 12 patients, respectively, after each patient was immobilized in a vacuum cradle and setup to skin markers as the center of mass. The couch shifts applied in the lateral (left-right/LR), vertical (anterior-posterior/AP), and longitudinal (superior-inferior/SI) directions, along with the magnitude of the three-dimensional (3D) shift vector, were analyzed and compared for all three methods. The percentage of shifts larger than 5 mm in all directions was also compared. Clinical target volume-planning target volume (CTV-to-PTV) expansion margins were estimated based on the localization data with US, CB, and SM image guidance. Results show the US data have greater variability. Systematic and random shifts were -1.2 +/- 6.8 mm (LR), -2.8 +/- 5.1 mm (SI) and -1.0 +/- 5.9 mm (AP) for US, 1.0 +/- 3.9 mm (LR), -1.3 +/- 2.5 mm (SI) and -0.3 +/- 3.9 mm (AP) for CB, and -1.0 +/- 3.4 mm (LR), 0.0 +/- 3.4 mm (SI) and 0.5 +/- 4.1 mm (AP) for SM. The mean 3D shift distance was larger using US (8.8 +/- 6.2 mm) compared to CB and SM (5.3 +/- 3.4 mm and 5.2 +/- 3.7 mm, respectively). The percentage of US shifts larger than 5 mm were 34%, 31%, and 38% in the LR, SI, and AP directions, respectively, compared to 18%, 6%, and 16% for CB and 14%, 10%, and 20% for SM. MV-CBCT and SM localization data suggest a different distribution of prostate center-of-mass shifts with smaller variability, compared to US. The online MV-CBCT and SM image-guidance data show that for treatments that do not include daily prostate localization, one can use a CTV-to-PTV margin that is 4 mm smaller than the one suggested by US data, hence allowing more rectum and bladder sparing and potentially improving the therapeutic ratio.

Monitoring tumor motion with on-line mega-voltage cone-beam computed tomography imaging in a cine mode.

Accurate daily patient localization is becoming increasingly important in external-beam radiotherapy (RT). Mega-voltage cone-beam computed tomography (MV-CBCT) utilizing a therapy beam and an on-board electronic portal imager can be used to localize tumor volumes and verify the patient's position prior to treatment. MV-CBCT produces a static volumetric image and therefore can only account for inter-fractional changes. In this work, the feasibility of using the MV-CBCT raw data as a fluoroscopic series of portal images to monitor tumor changes due to e.g. respiratory motion was investigated. A method was developed to read and convert the CB raw data into a cine. To improve the contrast-to-noise ratio on the MV-CB projection data, image post-processing with filtering techniques was investigated. Volumes of interest from the planning CT were projected onto the MV-cine. Because of the small exposure and the varying thickness of the patient depending on the projection angle, soft-tissue contrast was limited. Tumor visibility as a function of tumor size and projection angle was studied. The method was well suited in the upper chest, where motion of the tumor as well as of the diaphragm could be clearly seen. In the cases of patients with non-small cell lung cancer with medium or large tumor masses, we verified that the tumor mass was always located within the PTV despite respiratory motion. However for small tumors the method is less applicable, because the visibility of those targets becomes marginal. Evaluation of motion in non-superior-inferior directions might also be limited for small tumor masses. Viewing MV-CBCT data in a cine mode adds to the utility of MV-CBCT for verification of tumor motion and for deriving individualized treatment margins.

A genetic algorithm for variable selection in logistic regression analysis of radiotherapy treatment outcomes.

A given outcome of radiotherapy treatment can be modeled by analyzing its correlation with a combination of dosimetric, physiological, biological, and clinical factors, through a logistic regression fit of a large patient population. The quality of the fit is measured by the combination of the predictive power of this particular set of factors and the statistical significance of the individual factors in the model. We developed a genetic algorithm (GA), in which a small sample of all the possible combinations of variables are fitted to the patient data. New models are derived from the best models, through crossover and mutation operations, and are in turn fitted. The process is repeated until the sample converges to the combination of factors that best predicts the outcome. The GA was tested on a data set that investigated the incidence of lung injury in NSCLC patients treated with 3DCRT. The GA identified a model with two variables as the best predictor of radiation pneumonitis: the V30 (p=0.048) and the ongoing use of tobacco at the time of referral (p=0.074). This two-variable model was confirmed as the best model by analyzing all possible combinations of factors. In conclusion, genetic algorithms provide a reliable and fast way to select significant factors in logistic regression analysis of large clinical studies.

IMRT planning and delivery incorporating daily dose from mega-voltage cone-beam computed tomography imaging.

The technology of online mega-voltage cone-beam (CB) computed tomography (MV-CBCT) imaging is currently used in many institutions to generate a 3D anatomical dataset of a patient in treatment position. It utilizes an accelerator therapy beam, delivered with 200 degrees gantry rotation, and captured by an electronic portal imager to account for organ motion and setup variations. Although the patient dose exposure from a single volumetric MV-CBCT imaging procedure is comparable to that from standard double-exposure orthogonal portal images, daily image localization procedures can result in a significant dose increase to healthy tissue. A technique to incorporate the daily dose, from a MV-CBCT imaging procedure, in the IMRT treatment planning optimization process was developed. A composite IMRT plan incorporating the total dose from the CB was optimized with the objective of ensuring uniform target coverage while sparing the surrounding normal tissue. One head and neck cancer patient and four prostate cancer patients were planned and treated using this technique. Dosimetric results from the prostate IMRT plans optimized with or without CB showed similar target coverage and comparable sparing of bladder and rectum volumes. Average mean doses were higher by 1.6 +/- 1.0 Gy for the bladder and comparable for the rectum (-0.3 +/- 1.4 Gy). In addition, an average mean dose increase of 1.9 +/- 0.8 Gy in the femoral heads and 1.7 +/- 0.6 Gy in irradiated tissue was observed. However, the V65 and V70 values for bladder and rectum were lower by 2.3 +/- 1.5% and 2.4 +/- 2.1% indicating better volume sparing at high doses with the optimized plans incorporating CB. For the head and neck case, identical target coverage was achieved, while a comparable sparing of the brain stem, optic chiasm, and optic nerves was observed. The technique of optimized planning incorporating doses from daily online MV-CBCT procedures provides an alternative method for imaging IMRT patients. It allows for daily treatment modifications where other volumetric tomographic imaging techniques may not be feasible and/or available and where accurate patient localization with a high degree of precision is required.

Commissioning and clinical implementation of a mega-voltage cone beam CT system for treatment localization.

The improvement in conformal radiotherapy techniques with steep dose gradients has allowed for the delivery of higher doses to a tumor volume while maintaining the sparing of surrounding normal tissue. In this situation, verification of patient setup and evaluation of internal organ motion just prior to radiation delivery is a crucial step. To this end, several volumetric image-guided techniques have been developed for patient localization, such as the Siemens MVision mega-voltage cone beam CT (MV-CBCT) system. In this work, the commissioning and clinical implementation of the MVision system is presented. The geometry and gain calibration procedures for the system are described, and guidelines for quality assurance procedures are provided. Different MV-CBCT clinical protocols, ranging from daily to weekly image-guidance, which includes image acquisition, reconstruction, registration with planning CT, and treatment couch offsets corrections, were commissioned. The image quality characteristics of the MVision system were measured and assessed qualitatively and quantitatively, including the image noise and uniformity, low-contrast resolution, and spatial resolution. Furthermore, the image reconstruction and registration software was evaluated. Data show that a 2 cm large object with 1% electron density contrast can be detected with the MVision system with 10 cGy at isocenter and that the registration software is accurate within 2 mm in the anterior-posterior, left-right, and superior-inferior directions.

EUCLID: an outcome analysis tool for high-dimensional clinical studies.

Treatment management decisions in three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) are usually made based on the dose distributions in the target and surrounding normal tissue. These decisions may include, for example, the choice of one treatment over another and the level of tumour dose escalation. Furthermore, biological predictors such as tumour control probability (TCP) and normal tissue complication probability (NTCP), whose parameters available in the literature are only population-based estimates, are often used to assess and compare plans. However, a number of other clinical, biological and physiological factors also affect the outcome of radiotherapy treatment and are often not considered in the treatment planning and evaluation process. A statistical outcome analysis tool, EUCLID, for direct use by radiation oncologists and medical physicists was developed. The tool builds a mathematical model to predict an outcome probability based on a large number of clinical, biological, physiological and dosimetric factors. EUCLID can first analyse a large set of patients, such as from a clinical trial, to derive regression correlation coefficients between these factors and a given outcome. It can then apply such a model to an individual patient at the time of treatment to derive the probability of that outcome, allowing the physician to individualize the treatment based on medical evidence that encompasses a wide range of factors. The software's flexibility allows the clinicians to explore several avenues to select the best predictors of a given outcome. Its link to record-and-verify systems and data spreadsheets allows for a rapid and practical data collection and manipulation. A wide range of statistical information about the study population, including demographics and correlations between different factors, is available. A large number of one- and two-dimensional plots, histograms and survival curves allow for an easy visual analysis of the population. Several visual and analytical methods are available to quantify the predictive power of the multivariate regression model. The EUCLID tool can be readily integrated with treatment planning and record-and-verify systems.

Patient dose and image quality from mega-voltage cone beam computed tomography imaging.

The evolution of ever more conformal radiation delivery techniques makes the subject of accurate localization of increasing importance in radiotherapy. Several systems can be utilized including kilo-voltage and mega-voltage cone-beam computed tomography (MV-CBCT), CT on rail or helical tomography. One of the attractive aspects of mega-voltage cone-beam CT is that it uses the therapy beam along with an electronic portal imaging device to image the patient prior to the delivery of treatment. However, the use of a photon beam energy in the mega-voltage range for volumetric imaging degrades the image quality and increases the patient radiation dose. To optimize image quality and patient dose in MV-CBCT imaging procedures, a series of dose measurements in cylindrical and anthropomorphic phantoms using an ionization chamber, radiographic films, and thermoluminescent dosimeters was performed. Furthermore, the dependence of the contrast to noise ratio and spatial resolution of the image upon the dose delivered for a 20-cm-diam cylindrical phantom was evaluated. Depending on the anatomical site and patient thickness, we found that the minimum dose deposited in the irradiated volume was 5-9 cGy and the maximum dose was between 9 and 17 cGy for our clinical MV-CBCT imaging protocols. Results also demonstrated that for high contrast areas such as bony anatomy, low doses are sufficient for image registration and visualization of the three-dimensional boundaries between soft tissue and bony structures. However, as the difference in tissue density decreased, the dose required to identify soft tissue boundaries increased. Finally, the dose delivered by MV-CBCT was simulated using a treatment planning system (TPS), thereby allowing the incorporation of MV-CBCT dose in the treatment planning process. The TPS-calculated doses agreed well with measurements for a wide range of imaging protocols.