Late Toxicity of Prostate Ultrahypofractionated Radiation Therapy Compared With Moderate Hypofractionation in a Randomized Trial.

PURPOSE: We report late toxicity, quality of life (QOL), and urinary symptom score with prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation and ultrahypofrationation. METHODS AND MATERIALS: Patients with intermediate and high-risk prostate cancer were randomized to either Arm 1 (70 Gy/28 fractions) or Arm 2 (36.25 Gy/5 weekly fractions). Late toxicity was evaluated using the Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytical scales. QOL was assessed with the Expanded Prostate Inventory Composite-26 Short Form and urinary function with the International Prostate Symptom Score. RESULTS: Eighty participants were randomized. Two from Arm 1 withdrew, leaving 36 patients in Arm 1 and 42 in Arm 2. There were no significant differences in baseline characteristics, except for worse International Prostate Symptom Score in Arm 2. No difference was observed in freedom from grade 3 or worse toxicity between treatments (P = .921), with only a single grade 3 event in each arm. There was no significant difference in freedom from grade 2 or worse toxicity (P = .280). No difference was observed in freedom from grade 2 or worse genitorurinary toxicity, with cumulative probabilities of 69.0% and 87.0% at 5 years for Arms 1 and 2, respectively (0.132). No difference was observed in freedom from grade 2 or worse gastrointestinal toxicity, with cumulative probabilities of 74.0% in Arm 1 and 80.0% in Arm 2 (P = .430). There were no significant differences in Expanded Prostate Inventory Composite-26 Short Form QOL between arms. CONCLUSIONS: Ultrahypofrationation, delivered weekly, is well tolerated with no significant differences in freedom from late toxicity compared with moderate hypofractionation.

Acute Toxicity of Ultrahypofractionation Compared With Moderate Hypofractionation in Prostate Cancer Treatment: A Randomized Trial.

PURPOSE: We report on the early toxic effects and quality of life of localized prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation (MHF) with ultrahypofractionation (UHF). METHODS AND MATERIALS: We randomized patients with intermediate- to high-risk localized prostate cancer to radiation therapy with MHF (70 Gy in 28 daily fractions) or UHF (36.25 Gy in 5 weekly fractions). We analyzed early toxic effects (using Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytic scales) and patient-reported quality of life (using the Expanded Prostate Inventory Composite questionnaire) when all patients had at least 6 months of follow-up. RESULTS: We randomized 80 participants. Two patients withdrew from radiation therapy. We ran analysis on results for 78 patients. The 2 arms were balanced in key patient and disease characteristics, except for a statistically worse baseline urinary function in the UHF arm (International Prostate Symptom Score >7: 68% vs 36%, P = .004). There were no statistically significant differences between the 2 arms in grade 3 or grade 2 toxic effects: grade ≥3 MHF 8%, UHF 2% (P = .235); grade ≥2 MHF 36%, UHF 24% (P = .235). There were also no significant differences in percentages of patients with a "minimal important change" of quality of life in the Incontinence (MHF 36%, UHF 33%; P = .746), Irritative/Obstructive (MHF 56%, UHF 74%; P = .074), or Bowel domains (MHF 58%, UHF 52%; P = .508) on the Expanded Prostate Inventory Composite questionnaire. CONCLUSIONS: UHF radiation therapy for prostate cancer is well tolerated, and there were no significant differences in toxic effects and quality of life changes between UHF and MHF up to 6 months after treatment in the current trial.

Determining Planning Priorities for SABR for Oligometastatic Disease: A Secondary Analysis of the SABR-COMET Phase II Randomized Trial.

PURPOSE: SABR may improve survival in patients with oligometastases, but for some lesions, safe delivery of SABR may require a reduction in delivered dose or target coverage. This study assessed the association between target coverage compromise and oncologic and survival outcomes. METHODS AND MATERIALS: Patients with a controlled primary malignancy and 1 to 5 oligometastases were randomized (1:2) between standard of care (SOC) treatment and SOC plus SABR. In patients receiving SABR, the target dose coverage was reduced to meet organ at risk (OAR) constraints, if necessary. The D99 value (minimum dose received by the hottest 99% of the planning target volume [PTV]) was used as a measure of PTV coverage for each treatment plan, and the relationship between the coverage compromise index (CCI, defined as D99/prescription dose) and patient outcomes was assessed. RESULTS: Sixty-two patients in the SABR arm had dosimetric information available and a total of 109 lesions were evaluated. The mean CCI per lesion was 0.96 (95% CI, 0.56-1.61). Of the 109 lesions evaluated, 29.4% (n = 32) required coverage compromise (CCI <0.9). Adrenal metastases required coverage compromise in 100% of analyzed lesions (n = 7). CCI was not significantly associated with lesional control, adverse events, overall survival (OS), or progression-free survival (PFS). CONCLUSIONS: Target compromise was required in a substantial minority of cases, but PTV coverage was not associated with OS, progression-free survival, or lesional control. This suggests that OAR constraints used for SABR treatments in the oligometastatic setting should continue to be prioritized during planning.

SpaceOAR© hydrogel rectal dose reduction prediction model: a decision support tool.

Prostate cancer external beam radiation therapy can result in toxicity due to organ at risk (OAR) dose, potentially impairing quality of life. A polyethylene glycol-based spacer, SpaceOAR© hydrogel (SOH), implanted between prostate gland and rectum may significantly reduce dose received by the rectum and hence risk of rectal toxicity. SOH implant is not equally effective in all patients. Determining patients in which the implant will offer most benefit, in terms of rectal dose reduction, allows for effective management of SOH resources. Several factors have been shown to be correlated with reduction in rectal dose including distance between rectum and planning treatment volume (PTV), volume of rectum in the PTV, and change in rectum volume pre- to post-SOH. Several of these factors along with other pre-SOH CT metrics were able to predict reduction in rectal dose associated with SOH implant. Rectal V55Gy metric, was selected as the dose level of interest in the context of 60 Gy in 20 fraction treatment plans. Models were produced to predict change in RV55Gy and pre-SOH hydrogel RV55Gy. These models offered R-squared between 0.81 and 0.88 with statistical significance in each model. Applying an ω 1  = 3% lower limit of pre-SOH RV55 Gy and an ω 2  = 3.5% lower limit on change in RV55 Gy, retained 60% of patients experiencing the largest rectal dose reduction from the hydrogel. This may offer a clinically useful tool in deciding which patients should receive SOH implant given limited resources. Predictive models, nomograms, and a workflow diagram were produced for clinical management of SOH implant.

Maximizing rectal dose sparing with hydrogel: A retrospective planning study.

External beam radiation therapy for prostate cancer can result in urinary, sexual, and rectal side effects, often impairing quality of life. A polyethylene glycol-based product, SpaceOAR© hydrogel (SOH), implanted into the connective tissue between the prostate gland and rectum can significantly reduce the dose received by the rectum and hence risk of rectal toxicity. The optimal way to manage the hydrogel and rectal structures for plan optimization is therefore of interest. In 13 patients, computerized tomography (CT) scans were taken pre- and post-SpaceOAR© implant. A prescription of 60 Gy in 20 fractions was planned on both scans. Six treatment plans were produced per anonymized dataset using either a structure of rectum plus the hydrogel, termed composite rectum wall (CRW), or rectal wall (RW) as an inverse optimization structure and intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) as a treatment technique. Dose-volume histogram metrics were compared between plans to determine which optimization structure and treatment technique offered the maximum rectal dose sparing. RW structures offered a statistically significant decrease in rectal dose over CRW structures, whereas the treatment technique (IMRT vs VMAT) did not significantly affect the rectal dose. There was improvement seen in bladder and penile bulb dose when VMAT was used as a treatment technique. Overall, treatment plans using the RW optimization structure offered the lowest rectal dose while VMAT treatment technique offered the lowest bladder and penile bulb dose.

Measured and Monte Carlo simulated electron backscatter to the monitor chamber for the Varian TrueBeam Linac.

To accurately simulate therapeutic electron beams using Monte Carlo methods, backscatter from jaws into the monitor chamber must be accounted for via the backscatter factor, S b. Measured and simulated values of S b for the TrueBeam are investigated. Two approaches for measuring S b are presented. Both require service mode operation with the dose and pulse forming networking servos turned off in order to assess changes in dose rate with field size. The first approach samples an instantaneous dose rate, while the second approach times the delivery of a fixed number of monitor units to assess dose rate. Dose rates were measured for 6, 12 and 20 MeV electrons for jaw- or MLC-shaped apertures between [Formula: see text] and [Formula: see text] cm2. The measurement techniques resulted in values of S b that agreed within 0.21% for square and asymmetric fields collimated by the jaws. Measured values of S b were used to calculate the forward dose component in a virtual monitor chamber using BEAMnrc. Based on this forward component, simulated values of S b were calculated and compared to measurement and Varian's VirtuaLinac simulations. BEAMnrc results for jaw-shaped fields agreed with measurements and with VirtuaLinac simulations within 0.2%. For MLC-shaped fields, the respective measurement techniques differed by as much as 0.41% and BEAMnrc results differed with measurement by as much as 0.4%, however, all measured and simulated values agreed within experimental uncertainty. Measurement sensitivity was not sufficient to capture the small backscatter effect due to the MLC, and Monte Carlo predicted backscatter from the MLC to be no more than 0.3%. Backscatter from the jaws changed the electron dose rate by up to 2.6%. This reinforces the importance of including a backscatter factor in simulations of electron fields shaped with secondary collimating jaws, but presents the option of ignoring it when jaws are retracted and collimation is done with the MLC.

Validation of Varian TrueBeam electron phase-spaces for Monte Carlo simulation of MLC-shaped fields.

PURPOSE: This work evaluates Varian's electron phase-space sources for Monte Carlo simulation of the TrueBeam for modulated electron radiation therapy (MERT) and combined, modulated photon and electron radiation therapy (MPERT) where fields are shaped by the photon multileaf collimator (MLC) and delivered at 70 cm SSD. METHODS: Monte Carlo simulations performed with EGSnrc-based BEAMnrc/DOSXYZnrc and penelope-based PRIMO are compared against diode measurements for 5 × 5, 10 × 10, and 20 × 20 cm(2) MLC-shaped fields delivered with 6, 12, and 20 MeV electrons at 70 cm SSD (jaws set to 40 × 40 cm(2)). Depth dose curves and profiles are examined. In addition, EGSnrc-based simulations of relative output as a function of MLC-field size and jaw-position are compared against ion chamber measurements for MLC-shaped fields between 3 × 3 and 25 × 25 cm(2) and jaw positions that range from the MLC-field size to 40 × 40 cm(2). RESULTS: Percent depth dose curves generated by BEAMnrc/DOSXYZnrc and PRIMO agree with measurement within 2%, 2 mm except for PRIMO's 12 MeV, 20 × 20 cm(2) field where 90% of dose points agree within 2%, 2 mm. Without the distance to agreement, differences between measurement and simulation are as large as 7.3%. Characterization of simulated dose parameters such as FWHM, penumbra width and depths of 90%, 80%, 50%, and 20% dose agree within 2 mm of measurement for all fields except for the FWHM of the 6 MeV, 20 × 20 cm(2) field which falls within 2 mm distance to agreement. Differences between simulation and measurement exist in the profile shoulders and penumbra tails, in particular for 10 × 10 and 20 × 20 cm(2) fields of 20 MeV electrons, where both sets of simulated data fall short of measurement by as much as 3.5%. BEAMnrc/DOSXYZnrc simulated outputs agree with measurement within 2.3% except for 6 MeV MLC-shaped fields. Discrepancies here are as great as 5.5%. CONCLUSIONS: TrueBeam electron phase-spaces available from Varian have been implemented in two distinct Monte Carlo simulation packages to produce dose distributions and outputs that largely reflect measurement. Differences exist in the profile shoulders and penumbra tails for the 20 MeV phase-space off-axis and in the outputs for the 6 MeV phase-space.

Comparison of measured Varian Clinac 21EX and TrueBeam accelerator electron field characteristics.

Dosimetric comparisons of radiation fields produced by Varian's newest linear accelerator, the TrueBeam, with those produced by older Varian accelerators are of interest from both practical and research standpoints. While photon fields have been compared in the literature, similar comparisons of electron fields have not yet been reported. In this work, electron fields produced by the TrueBeam are compared with those produced by Varian's Clinac 21EX accelerator. Diode measurements were taken of fields shaped with electron applicators and delivered at 100 cm SSD, as well as those shaped with photon MLCs without applicators and delivered at 70 cm SSD for field sizes ranging from 5 × 5 to 25 × 25 cm² at energies between 6 and 20 MeV. Additionally, EBT2 and EBT3 radio-chromic film measurements were taken of an MLC-shaped aperture with closed leaf pairs delivered at 70 cm SSD using 6 and 20 MeV electrons. The 6 MeV fields produced by the TrueBeam and Clinac 21EX were found to be almost indistinguishable. At higher energies, TrueBeam fields shaped by electron applicators were generally flatter and had less photon contamination compared to the Clinac 21EX. Differences in PDDs and profiles fell within 3% and 3 mm for the majority of measurements. The most notable differences for open fields occurred in the profile shoulders for the largest applicator field sizes. In these cases, the TrueBeam and Clinac 21EX data differed by as much as 8%. Our data indicate that an accurate electron beam model of the Clinac 21EX could be used as a starting point to simulate electron fields that are dosimetrically equivalent to those produced by the TrueBeam. Given that the Clinac 21EX shares head geometry with Varian's iX, Trilogy, and Novalis TX accelerators, our findings should also be applicable to these machines.

Investigation of variability in image acquisition and contouring during 3D ultrasound guidance for partial breast irradiation.

BACKGROUND: Three-dimensional ultrasound (3DUS) at simulation compared to 3DUS at treatment is an image guidance option for partial breast irradiation (PBI). This study assessed if user dependence in acquiring and contouring 3DUS (operator variability) contributed to variation in seroma shifts calculated for breast IGRT. METHODS: Eligible patients met breast criteria for current randomized PBI studies. 5 Operators participated in this study. For each patient, 3 operators were involved in scan acquisitions and 5 were involved in contouring. At CT simulation (CT1), a 3DUS (US1) was performed by a single radiation therapist (RT). 7 to 14 days after CT1 a second CT (CT2) and 3 sequential 3DUS scans (US2a,b,c) were acquired by each of 3 RTs. Seroma shifts, between US1 and US2 scans were calculated by comparing geometric centers of the seromas (centroids). Operator contouring variability was determined by comparing 5 RT's contours for a single image set. Scanning variability was assessed by comparing shifts between multiple scans acquired at the same time point (US1-US2a,b,c). Shifts in seromas contoured on CT (CT1-CT2) were compared to US data. RESULTS: From an initial 28 patients, 15 had CT visible seromas, met PBI dosimetric constraints, had complete US data, and were analyzed. Operator variability contributed more to the overall variability in seroma localization than the variability associated with multiple scan acquisitions (95% confidence mean uncertainty of 6.2 mm vs. 1.1 mm). The mean standard deviation in seroma shift was user dependent and ranged from 1.7 to 2.9 mm. Mean seroma shifts from simulation to treatment were comparable to CT. CONCLUSIONS: Variability in shifts due to different users acquiring and contouring 3DUS for PBI guidance were comparable to CT shifts. Substantial inter-observer effect needs to be considered during clinical implementation of 3DUS IGRT.

p16 expression: a marker of differentiation between childhood malignant melanomas and Spitz nevi.

BACKGROUND: Childhood malignant melanomas frequently present as nodular melanomas with Spitzoid features. Spitz nevus and Spitzoid melanoma overlap clinically and histopathologically and there have been many attempts to differentiate between them. Spitz nevi differ from melanomas by their immunohistochemical pattern of expression of cell cycle and apoptosis regulators such as the p16 protein. OBJECTIVE: The aim of this study was to evaluate in a childhood population the expression of p16 in nodular malignant melanoma of Spitzoid type, Spitz nevi, and a control group of benign compound melanocytic nevi. METHODS: We performed immunohistochemical studies for expression of p16 in 6 Spitzoid malignant melanomas, 18 Spitz nevi, and 12 compound melanocytic nevi in children younger than 18 years. Statistical analysis was used to compare p16 expression, mitotic count/mm(2), and Ki-67 index of childhood nodular malignant melanomas and Spitz nevi. RESULTS: All the childhood melanoma cases were associated with loss of p16 without any correlation with their Breslow thickness whereas all the Spitz nevi and benign melanocytic nevi had strong positive nuclear and cytoplasmic expression of p16 staining. We found a statistically significant difference in p16 expression, mitotic counts, and Ki-67 index when comparing the Spitzoid melanomas with the Spitz nevi. LIMITATIONS: This study is limited by the small number of malignant melanomas, which are known to be rare in childhood. CONCLUSION: p16 Expression in childhood nodular Spitzoid malignant melanomas and Spitz nevi, in conjunction with clinical and histopathological evaluation, may be a useful tool in differentiating between these two entities.

Clinical significance of multi-leaf collimator positional errors for volumetric modulated arc therapy.

BACKGROUND AND PURPOSE: Multi-leaf collimator (MLC) positional errors occur during intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) deliveries. The impact of such errors has been evaluated for IMRT but not VMAT. The purpose of this work is to understand how random and systematic VMAT MLC positional errors affect the patient dose distribution. MATERIALS AND METHODS: Eight head and neck single arc (360°) VMAT treatment plans were created. Random and two types of systematic MLC errors were simulated for error magnitudes of 0.25, 0.5, 1, 2 and 5mm. The two types of systematic MLC errors were: (1) MLC banks are shifted in the same direction (left or right) and (2) MLC banks are shifted in opposing directions resulting in smaller or larger field shapes. The MLC errors were simulated, for all control points, on both banks of active MLC leaves only. RESULTS: There is a linear correlation of MLC errors with gEUD for all error types. The gEUD dose sensitivities with MLC error for the PTV70 were -0.2, -0.9, -2.8 and 1.9 Gy/mm for random, systematic shift, systematic close and systematic open MLC errors, respectively. The sensitivity of VMAT plans to MLC positional errors was similar to those of IMRT plans with less than 50 segments but much less than those created for a step and shoot with more than 50 segments or sliding-window delivery technique. To maintain the PTV70 to within 2% would require that MLC open/close errors be within 0.6mm. CONCLUSIONS: Radiation therapy centers should have adequate quality assurance programs in place to assess open/close MLC errors (i.e. leaf gap errors) as they tend to be more impactful than random or systematic MLC shift errors.

RapidArc treatment verification in 3D using polymer gel dosimetry and Monte Carlo simulation.

The aim of this study was to verify the advanced inhomogeneous dose distribution produced by a volumetric arc therapy technique (RapidArc) using 3D gel measurements and Monte Carlo (MC) simulations. The TPS (treatment planning system)-calculated dose distribution was compared with gel measurements and MC simulations, thus investigating any discrepancy between the planned dose delivery and the actual delivery. Additionally, the reproducibility of the delivery was investigated using repeated gel measurements. A prostate treatment plan was delivered to a 1.3 liter nPAG gel phantom using one single arc rotation and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using a 1.5 T scanner. The MC dose distributions were calculated using the VIMC-Arc code. The relative absorbed dose differences were calculated voxel-by-voxel, within the volume enclosed by the 90% isodose surface (VOI(90)), for the TPS versus gel and TPS versus MC. The differences between the verification methods, MC versus gel, and between two repeated gel measurements were investigated in the same way. For all volume comparisons, the mean value was within 1% and the standard deviation of the differences was within 2.5% (1SD). A 3D gamma analysis between the dose matrices were carried out using gamma criteria 3%/3 mm and 5%/5 mm (% dose difference and mm distance to agreement) within the volume enclosed by the 50% isodose surface (VOI(50)) and the 90% isodose surface (VOI(90)), respectively. All comparisons resulted in very high pass rates. More than 95% of the TPS points were within 3%/3 mm of both the gel measurement and MC simulation, both inside VOI(50) and VOI(90). Additionally, the repeated gel measurements showed excellent consistency, indicating reproducible delivery. Using MC simulations and gel measurements, this verification study successfully demonstrated that the RapidArc plan was both accurately calculated and delivered as planned.

Analysis of RapidArc optimization strategies using objective function values and dose-volume histograms.

RapidArc is a novel treatment planning and delivery system that has recently been made available for clinical use. Included within the Eclipse treatment planning system are a number of different optimization strategies that can be employed to improve the quality of the final treatment plan. The purpose of this study is to systematically assess three categories of strategies for four phantoms, and then apply proven strategies to clinical head and neck cases. Four phantoms were created within Eclipse with varying shapes and locations for the planning target volumes and organs at risk. A baseline optimization consisting of a single 359.8 degrees arc with collimator at 45 degrees was applied to all phantoms. Three categories of strategies were assessed and compared to the baseline strategy. They include changing the initialization parameters, increasing the total number of control points, and increasing the total optimization time. Optimization log files were extracted from the treatment planning system along with final dose-volume histograms for plan assessment. Treatment plans were also generated for four head and neck patients to determine whether the results for phantom plans can be extended to clinical plans. The strategies that resulted in a significant difference from baseline were: changing the maximum leaf speed prior to optimization ( p < 0.05), increasing the total number of segments by adding an arc ( p < 0.05), and increasing the total optimization time by either continuing the optimization ( p < 0.01) or adding time to the optimization by pausing the optimization ( p < 0.01). The reductions in objective function values correlated with improvements in the dose-volume histogram (DVH). The addition of arcs and pausing strategies were applied to head and neck cancer cases, which demonstrated similar benefits with respect to the final objective function value and DVH. Analysis of the optimization log files is a useful way to intercompare treatment plans that have the same dose-volume objectives and importance values. The results for clinical head and neck plans were consistent with phantom plans.

Evaluation of the analytical anisotropic algorithm in an extreme water-lung interface phantom using Monte Carlo dose calculations.

Our study compares the performance of the analytical anisotropic algorithm (AAA), a new superposition-convolution algorithm recently implemented in the Eclipse (Varian Medical Systems, Palo Alto, CA) Integrated Treatment Planning System (TPS), to that of the pencil beam convolution (PBC) algorithm in an extreme (C-shaped, horizontal and vertical boundaries) water-lung interface phantom. Monte Carlo (MC) calculated dose distributions for a variety of clinical beam configurations at nominal energies of 6-MV and 18-MV are used as benchmarks in the comparison. Dose profiles extracted at three depths (4, 10, and 16 cm), two-dimensional (2D) maps of the dose differences, and dose difference statistics are used to quantify the accuracy of both photon-dose calculation algorithms. Results show that the AAA is considerably more accurate than the PBC, with the standard deviation of the dose differences within a region encompassing the lung block reduced by a factor of 2 and more. Confidence limits with the AAA were 4% or less for all beam configurations investigated; with the PBC, confidence limits ranged from 3.5% to 11.2%. Finally, AAA calculations for the small 4 x 4 18-MV beam, which is poorly modeled by PBC (dose differences as high as 16.1%), provided the same accuracy as the PBC model of the 6-MV beams commonly acceptable in clinical situations.

The use of phase sequence image sets to reconstruct the total volume occupied by a mobile lung tumor.

The use of phase sequence image (PSI) sets to reveal the total volume occupied by a mobile target is presented. Isocontrast composite clinical target volumes (CCTVs) may be constructed from PSI sets in order to reveal the total volume occupied by a mobile target during the course of its travel. The ability of the CCTV technique to properly account for target motion is demonstrated by comparison to contours of the true total volume occupied (TVO) for a number of experimental phantom geometries. Finally, using real patient data, the clinical utility of the CCTV technique to properly account for internal tumor motion while minimizing the volume of healthy lung tissue irradiated is assessed by comparison to the standard approach of applying safety margins. Results of the phantom study reveal that CCTV cross sections constructed at the 20% isocontrast level yield good agreement with the total cross sections (TXO) of mobile targets. These CCTVs conform well to the TVOs of the moving targets examined whereby the addition of small uniform margins ensures complete circumscription of the TVO with the inclusion of minimal amounts of surrounding external volumes. The CCTV technique is seen to be clearly superior to the common practice of the addition of safety margins to individual CTV contours in order to account for internal target motion. Margins required with the CCTV technique are eight to ten times smaller than those required with individual CTVs.

The use of phase sequence image sets to reconstruct the total volume occupied by a mobile lung tumor.

The use of phase sequence image (PSI) sets to reveal the total volume occupied by a mobile target is presented. Isocontrast composite clinical target volumes (CCTVs) may be constructed from PSI sets in order to reveal the total volume occupied by a mobile target during the course of its travel. The ability of the CCTV technique to properly account for target motion is demonstrated by comparison to contours of the true total volume occupied (TVO) for a number of experimental phantom geometries. Finally, using real patient data, the clinical utility of the CCTV technique to properly account for internal tumor motion while minimizing the volume of healthy lung tissue irradiated is assessed by comparison to the standard approach of applying safety margins. Results of the phantom study reveal that CCTV cross sections constructed at the 20% isocontrast level yield good agreement with the total cross sections (TXO) of mobile targets. These CCTVs conform well to the TVOs of the moving targets examined whereby the addition of small uniform margins ensures complete circumscription of the TVO with the inclusion of minimal amounts of surrounding external volumes. The CCTV technique is seen to be clearly superior to the common practice of the addition of safety margins to individual CTV contours in order to account for internal target motion. Margins required with the CCTV technique are eight to ten times smaller than those required with individual CTVs.

Metallic copper as a fiducial marker for both CT and PET.

There is great interest in augmenting computed tomography (CT) with information gained from other imaging modalities. Positron emission tomography (PET) provides valuable data related to patient physiology to aid in the delineation of tumor volumes. Combining the information provided by these imaging modalities requires accurate spatial registration of the two data sets. Fiducial based mapping provides straightforward registration based on corresponding landmark points or fiducials in the two image sets. When external fiducials are employed, consistent intermodality marker placement and centroid identification are essential to achieving an accurate and reliable registration. Similarity of marker design between modalities greatly aides in achieving this goal. Solid copper may serve as a fiducial marker in both CT and PET. Small spheres or wires of copper are readily visible in CT while neutron activation of these same markers produces positron emitting Copper-64 for detection by PET. The use of identical shaped markers in both imaging modalities greatly simplifies the task of intermodality centroid matching. Copper has excellent machining properties and, prior to activation, is easy and safe to handle. The feasibility of Cu as a marker for both CT and PET is demonstrated using imaging phantoms.

The impact of tumor motion upon CT image integrity and target delineation.

Accurate planning target volume delineation is vital to the success of conformal radiation techniques such as standard three-dimensional conformal radiotherapy and intensity modulated radiation therapy. With the exception of breath-hold schemes, all current approaches acquire images while the tumor is nonstationary and, as such, are subject to the presence of motion artifacts. In lung cancer sites where tumor mobility can be significant, the detrimental effect of these motion-induced distortions on image quality and subsequently target volume delineation cannot be ignored in the pursuit of improved treatment outcomes. To investigate the fundamental nature and functional dependence of computed tomography (CT) artifacts associated with lung tumor motion, and the implications for tumor delineation, a filtered backprojection algorithm was developed in MATLAB to generate transverse CT simulation images. In addition, a three-dimensional phantom capable of mimicking the essential motions of lung tumors was constructed for experimental verification. Results show that the spatial extent of a mobile object is distorted from its true shape and location and does not accurately reflect the volume occupied during the extent of motion captured. The presence of motion also negatively impacts image intensity (density) integrity rendering accurate volume delineation highly problematic and calling into question the use of such data in CT-based heterogeneity correction algorithms for dosimetric calculation.