Feasibility of postmastectomy treatment with helical TomoTherapy.

PURPOSE: To investigate the potential of helical tomotherapy for postmastectomy radiation therapy. METHODS AND MATERIALS: By use of the TomoTherapy Hi-Art II treatment-planning system (TomoTherapy Inc., Madison, WI), helical tomotherapy dose plans were developed for 5 patients and compared with the mixed-beam (electron-photon) plans with which they had been treated. The TomoTherapy plans were evaluated by use of dose-volume quantities, tumor control probability, normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). RESULTS: The TomoTherapy plans showed better dose homogeneity in the planning treatment volume containing the chest wall and internal mammary nodes (p = 0.001) and eliminated the need for abutting fields. For the normal tissues, the TomoTherapy plans showed a smaller fractional volume receiving 20 Gy or greater for the ipsilateral lung (p = 0.05), no change in NTCP for postradiation pneumonitis, increased SCCP for each lung and both lungs together (p < 0.02), no change in the volume of the heart receiving more than 15 Gy, no change in NTCP for excess cardiac mortality, and a larger mean dose and SCCP in the contralateral breast (p < 0.001). For nonspecific tissues, the volume receiving between 5 Gy and 25 Gy and SCCP were both larger for the TomoTherapy plans (p < 0.01). Total SCCP was larger for the TomoTherapy plans (p = 0.001). CONCLUSIONS: Overall, the TomoTherapy plans had comparable tumor control probability and NTCP to the mixed-beam plans and increased SCCP. The TomoTherapy plans showed significantly greater dose homogeneity in the chest wall, which offers the potential for improved cosmesis after treatment. These factors have resulted in TomoTherapy often being the treatment of choice for postmastectomy radiation therapy in our clinic.

Calculating percent depth dose with the electron pencil-beam redefinition algorithm.

In the present work, we investigated the accuracy of the electron pencil-beam redefinition algorithm (PBRA) in calculating central-axis percent depth dose in water for rectangular fields. The PBRA energy correction factor C(E) was determined so that PBRA-calculated percent depth dose best matched the percent depth dose measured in water. The hypothesis tested was that a method can be implemented into the PBRA that will enable the algorithm to calculate central-axis percent depth dose in water at a 100-cm source-to-surface distance (SSD) with an accuracy of 2% or 1-mm distance to agreement for rectangular field sizes > or = 2 x 2 cm. Preliminary investigations showed that C(E), determined using a single percent depth dose for a large field (that is, having side-scatter equilibrium), was insufficient for the PBRA to accurately calculate percent depth dose for all square fields > or = 2 x 2 cm. Therefore, two alternative methods for determining C(E) were investigated. In Method 1, C(E), modeled as a polynomial in energy, was determined by fitting the PBRA calculations to individual rectangular-field percent depth doses. In Method 2, C(E) for square fields, described by a polynomial in both energy and side of square W [that is, C = C(E,W)], was determined by fitting the PBRA calculations to measured percent depth dose for a small number of square fields. Using the function C(E,W), C(E) for other square fields was determined, and C(E) for rectangular field sizes was determined using the geometric mean of C(E) for the two measured square fields of the dimension of the rectangle (square root method). Using both methods, PBRA calculations were evaluated by comparison with measured square-field and derived rectangular-field percent depth doses at 100-cm SSD for the Siemens Primus radiotherapy accelerator equipped with a 25 x 25-cm applicator at 10 MeV and 15 MeV. To improve the fit of C(E) and C(E,W) to the electron component of percent depth dose, it was necessary to modify the PBRA's photon depth dose model to include dose buildup. Results showed that, using both methods, the PBRA was able to predict percent depth dose within criteria for all square and rectangular fields. Results showed that second- or third-order polynomials in energy (Methods 1 and 2) and in field size (Method 2) were typically required. Although the time for dose calculation using Method 1 is approximately twice that using Method 2, we recommend that Method 1 be used for clinical implementation of the PBRA because it is more accurate (most measured depth doses predicted within approximately 1%) and simpler to implement.

Improvement of field matching in segmented-field electron conformal therapy using a variable-SCD applicator.

The purpose of the present study is to demonstrate that the use of an electron applicator with energy-dependent source-to-collimator distances (SCDs) will significantly improve the dose homogeneity for abutted electron fields in segmented-field electron conformal therapy (ECT). Multiple Coulomb scattering theory was used to calculate and study the P(80-20) penumbra width of off-axis dose profiles as a function of air gap and depth. Collimating insert locations with air gaps (collimator-to-isocenter distance) of 5.0, 7.5, 11.5, 17.5 and 19.5 cm were selected to provide equal P(80-20) at a depth of 1.5 cm in water for energies of 6, 9, 12, 16 and 20 MeV, respectively, for a Varian 2100EX radiation therapy accelerator. A 15 x 15 cm(2) applicator was modified accordingly, and collimating inserts used in the variable-SCD applicator for segmented-field ECT were constructed with diverging edges using a computer-controlled hot-wire cutter, which resulted in 0.27 mm accuracy in the abutted edges. The resulting electron beams were commissioned for the pencil-beam algorithm (PBA) on the Pinnacle(3) treatment planning system. Four hypothetical planning target volumes (PTVs) and one patient were planned for segmented-field ECT using the new variable-SCD applicator, and the resulting dose distributions were compared with those calculated for the identical plans using the conventional 95 cm SCD applicator. Also, a method for quality assurance of segmented-field ECT dose plans using the variable-SCD applicator was evaluated by irradiating a polystyrene phantom using the treatment plans for the hypothetical PTVs. Treatment plans for all four of the hypothetical PTVs using the variable-SCD applicator showed significantly improved dose homogeneity in the abutment regions of the segmented-field ECT plans. This resulted in the dose spread (maximum dose-minimum dose), sigma, and D(90-10) in the PTV being reduced by an average of 32%, 29% and 32%, respectively. Reductions were most significant for abutted fields of nonadjacent energies. Planning segmented-field ECT using the variable-SCD applicator for a patient with recurrent squamous cell carcinoma of the left ear showed the dose spread, sigma, and D(90-10) of the dose distribution in the PTV being reduced by an average of 38%, 22% and 22%, respectively. The measured and calculated dose in a polystyrene phantom resulting from the variable-SCD, segmented-field ECT plans for the hypothetical PTVs showed good agreement; however, isolated differences between dose calculation and measurement indicated the need for a more accurate dose algorithm than the PBA for segmented-field ECT. These results confirmed our hypothesis that using the variable-SCD applicator for segmented-field ECT results in the PTV dose distribution becoming more homogenous and being within the range of 85-105% of the 'given dose'. Clinical implementation of this method requires variable-SCD applicators, and the design used in the present work should be acceptable, as should our methods for construction of the inserts. Dose verification measurements in a polystyrene phantom and the recommended improvements in dose calculation should be appropriate for quality assurance of segmented-field ECT.

Application of the electron pencil beam redefinition algorithm to electron arc therapy.

This project investigated the potential of summing fixed-beam dose distributions calculated using the pencil-beam redefinition algorithm (PBRA) at small angular steps (1 degree) to model an electron arc therapy beam. The PRBA, previously modified to model skin collimation, was modified further by incorporating two correction factors. One correction factor that is energy, SSD (source-to-surface distance), and field-width dependent constrained the calculated dose output to be the same as the measured dose output for fixed-beam geometries within the range of field widths and SSDs encountered in arc therapy. Another correction factor (single field-width correction factor for each energy) compensated for large-angle scattering not being modeled, allowing a more accurate calculation of dose output at mid arc. The PBRA was commissioned to accurately calculate dose in a water phantom for fixed-beam geometries typical of electron arc therapy. Calculated central-axis depth doses agreed with measured doses to within 2% in the low-dose gradient regions and within 1-mm in the high-dose gradient regions. Off-axis doses agreed to within 2 mm in the high-dose gradient regions and within 3% in the low-dose gradient regions. Arced-beam calculations of dose output and depth dose at mid arc were evaluated by comparing to data measured using two cylindrical water phantoms with radii of 12 and 15 cm at 10 and 15 MeV. Dose output was measured for all combinations of phantom radii of curvature, collimator widths (4, 5, and 6 cm), and arc angles (0 degrees, 20 degrees, 40 degrees, 60 degrees, 80 degrees, and 90 degrees) for both beam energies. Results showed the calculated mid-arc dose output to agree within 2% of measurement for all combinations. For a 90 degree arc angle and 5 x 20 cm2 field size, the calculated mid-arc depth dose in the low-dose gradient region agreed to within 2% of measurement for all depths at 10 MeV and for depths greater than depth of dose maximum R100 at 15 MeV. For depths in the buildup region at 15 MeV the calculations overestimated the measured dose by as much as 3.4%. Mid-arc depth dose in the high-dose gradient region agreed to within 2.2 mm of measured dose. Calculated two-dimensional relative dose distributions in the plane of rotation were compared to dose measurements using film in a cylindrical polystyrene phantom for a 90 degree arc angle and field widths of 4, 5, and 6 cm at 10 and 15 MeV. Results showed that off-axis dose at the ends of arc (without skin collimation) agreed to within 2% in the low-dose gradient region and to within 1.2 mm in the high-dose gradient region. This work showed that the accuracy of the PBRA arced-beam dose model met the criteria specified by Van Dyk et al. [Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)] with the exception of the buildup region of the 15 MeV beam. Based on the present results, results of a previous study showing acceptable accuracy in the presence of skin collimation, and results of a previous study showing acceptable accuracy in the presence of internal heterogeneities, it is concluded that the PBRA arced-beam dose model should be adequate for planning electron arc therapy.

Modeling skin collimation using the electron pencil beam redefinition algorithm.

Skin collimation is an important tool for electron beam therapy that is used to minimize the penumbra when treating near critical structures, at extended treatment distances, with bolus, or using arc therapy. It is usually made of lead or lead alloy material that conforms to and is placed on patient surface. Presently, commercially available treatment-planning systems lack the ability to model skin collimation and to accurately calculate dose in its presence. The purpose of the present work was to evaluate the use of the pencil beam redefinition algorithm (PBRA) in calculating dose in the presence of skin collimation. Skin collimation was incorporated into the PBRA by terminating the transport of electrons once they enter the skin collimator. Both fixed- and arced-beam dose calculations for arced-beam geometries were evaluated by comparing them with measured dose distributions for 10- and 15-MeV beams. Fixed-beam dose distributions were measured in water at 88-cm source-to-surface distance with an air gap of 32 cm. The 6 x 20-cm2 field (dimensions projected to isocenter) had a 10-mm thick lead collimator placed on the surface of the water with its edge 5 cm inside the field's edge located at +10 cm. Arced-beam dose distributions were measured in a 13.5-cm radius polystyrene circular phantom. The beam was arced 90 degrees (-45 degrees to +45 degrees), and 10-mm thick lead collimation was placed at +/- 30 degrees. For the fixed beam at 10 MeV, the PBRA- calculated dose agreed with measured dose to within 2.0-mm distance to agreement (DTA) in the regions of high-dose gradient and 2.0% in regions of low dose gradient. At 15 MeV, the PBRA agreed to within a 2.0-mm DTA in the regions of high-dose gradient; however, the PBRA underestimated the dose by as much as 5.3% over small regions at depths less than 2 cm because it did not model electrons scattered from the edge of the skin collimation. For arced beams at 10 MeV, the agreement was 1-mm DTA in the high-dose gradient regions, and 2% in the low-dose gradient regions. For arced beams at 15 MeV, the agreement was 1 mm in the high-dose gradient regions, and in the low-dose gradient region at depth less than 2 cm, as much as 5% dose difference was observed. This study demonstrated the ease with which skin collimation can be incorporated into the PBRA. The good agreement of PBRA calculated with measured dose shows that the PBRA is likely sufficiently accurate for clinical use in the presence of skin collimation for electron arc therapy. To further improve the accuracy of the PBRA in regions having significant electrons scattered from the edge of the skin collimation would require transporting the electrons through the lead skin collimation near its edges.

Dosimetry of a prototype retractable eMLC for fixed-beam electron therapy.

An electron multileaf collimator (eMLC) has been designed that is unique in that it retracts to 37 cm from the isocenter [63-cm source-to-collimator distance (SCD)] and can be deployed to distances of 20 and 10 cm from the isocenter (80 and 90 cm SCD, respectively). It is expected to be capable of arc therapy at 63 cm SCD; isocentric, fixed-beam therapy at 80 cm SCD; and source-to-surface distance (SSD), fixed-beam therapy at 90 cm SCD. In all positions, its leaves could be used for unmodulated or intensity-modulated therapy. Our goal in the present work is to describe the general characteristics of the eMLC and to demonstrate that its leakage characteristics and dosimetry are adequate for SSD, fixed-beam therapy as an alternative to Cerrobend cutouts with applicators once the prototype's leaves are motorized. Our eMLC data showed interleaf electron leakage at 15 MeV to be less than 0.1% based on a 0.0025 cm manufacturing tolerance, and lateral electron leakage at 5 and 15 MeV to be less than 2%. X-ray leakage through the leaves was 1.6% at 15 MeV. Our data showed that beam penumbra was independent of direction and leaf position. The dosimetric properties of square fields formed by the eMLC were very consistent with those formed by Cerrobend inserts in the 20 x 20 cm2 applicator. Output factors exhibited similar field-size dependence. Airgap factors exhibited almost identical field-size dependence at two SSDs (105 and 110 cm), consistent with the common assumption that airgap factors are applicator independent. Percent depth-dose curves were similar, but showed variations up to 3% in the buildup region. The pencil-beam algorithm (PBA) fit measured data from the eMLC and applicator-cutout systems equally well, and the resulting two-dimensional (2-D) dose distributions, as predicted by the PBA, agreed well at common airgap distance. Simulating patient setups for breast and head and neck treatments showed that almost all fields could be treated using similar SSDs as when using applicators, although head and neck treatments require placing the patient's head on a head-holder treatment table extension. The results of this work confirmed our design goals and support the potential use of the eMLC design in the clinical setting. The eMLC should allow the same treatments as are typically delivered with the electron applicator-cutout system currently used for fixed-beam therapy.

Development of a method for the direct analysis of peptide AM336 in monkey cerebrospinal fluid using liquid chromatography/electrospray ionization mass spectrometry with a mixed-function column.

A liquid chromatography/mass spectrometry (LC/MS) analytical procedure, using a single column for sample clean-up, enrichment and separation, has been developed for the determination of the peptide AM336 in monkey cerebrospinal fluid (CSF). CSF samples were injected and analyzed using a polymer-coated mixed-function high-performance liquid chromatography (HPLC) column with gradient elution and application of a timed valve-switching event. The mass spectrometer was operated in the positive electrospray ionization (ESI(+)) mode with single ion recording (SIR) at m/z 920. The method was validated, yielding calibration curves with correlation coefficients greater than 0.9892. Assay precision and accuracy were evaluated by direct injection of AM336-fortified CSF samples at three concentration levels. Analyzed concentrations ranged from 99.93 to 113.1% of their respective theoretical concentrations with coefficients of variation below 9.0%. An evaluation of the signal-to-noise (S/N) ratio for a 200 ng/mL calibration standard, considered to be the lower limit of quantitation (LLOQ), resulted in an estimated limit of detection (LOD) of 31.2 ng/mL. Preliminary data suggest the possibility of using this method to analyze AM336 also in plasma samples, pending the successful outcome of additional investigations.

The use of an extra-focal electron source to model collimator-scattered electrons using the pencil-beam redefinition algorithm.

Currently, the pencil-beam redefinition algorithm (PBRA) utilizes a single electron source to model clinical electron beams. In the single-source model, the electrons appear to originate from a virtual source located near the scattering foils. Although this approach may be acceptable for most treatment machines, previous studies have shown dose differences as high as 8% relative to the given dose for small fields for some machines such as the Varian Clinac 1800. In such machines collimation-scattered electrons originating from the photon jaws and the applicator give rise to extra-focal electron sources. In this study, we examined the impact of modeling an additional electron source to better account for the collimator-scattered electrons. The desired dose calculation accuracy in water throughout the dose distribution is 3% or better relative to the given dose. We present here a methodology for determining the electron-source parameters for the dual-source model using a minimal set of data, that is, two central-axis depth-dose curves and two off-axis profiles. A Varian Clinac 1800 accelerator was modeled for beam energies of 20 and 9 MeV and applicator sizes of 15 x 15 and 6 x 6 cm2. The improvement in the accuracy of PBRA-calculated dose, evaluated using measured two-dimensional dose distributions in water, was characterized using the figure of merit, FA3%, which represents the fractional area containing dose differences greater than 3%. For the 15 x 15 cm2 field the evaluation was restricted to the penumbral region, and for the 6 x 6 cm2 field the central region of the beam was included as it was impacted by the penumbra. The greatest improvement in dose accuracy was for the 6 x 6 cm2 applicator. At 9 MeV, FA3% decreased from 15% to 0% at 100 cm SSD and from 34% to 4% at 110 cm SSD. At 20 MeV, FA3% decreased from 17% to 2% at 100 cm SSD and from 41% to 10% at 110 cm SSD. In the penumbra of the 15 x 15 cm2 applicator, the improvement was less, but still significant. At 9 MeV, FA3% changed from 11% to 1% at 100 cm SSD and from 10% to 12% at 110 cm SSD. At 20 MeV, FA3% decreased from 12% to 8% at 100 cm SSD and from 14% to 5% at 110 cm SSD. Results demonstrate that use of a dual-source beam model can provide significantly improved accuracy in the PBRA-calculated dose distribution that was not achievable with a single-source beam model when modeling the Varian Clinac 1800 electron beams. Time of PBRA dose calculation was approximately doubled; however, dual-source beam modeling of newer accelerators (e.g., the Varian Clinac 2100) may not be necessary because of less impact of collimator-scattered electrons on dosimetry.

Electron conformal radiotherapy using bolus and intensity modulation.

PURPOSE: Conformal electron beam therapy can be delivered using shaped bolus, which varies the penetration of the electrons across the incident beam so that the 90% isodose surface conforms to the distal surface of the planning target volume (PTV). Previous use of this modality has shown that the irregular proximal surface of the bolus causes the dose heterogeneity in the PTV to increase from 10%, the typical dose spread of a flat-water surface to approximately 20%. The present work evaluates the ability to restore dose homogeneity by varying the incident electron intensity. METHODS AND MATERIALS: Three patients, one each with chest wall, thorax, and head-and-neck cancer, were planned using electron conformal therapy with bolus, with and without intensity modulation. Resulting dose distributions and dose-volume histograms were compared with non-intensity-modulated bolus plans. RESULTS: In all cases, the DeltaD(90%-10%) for the PTV was reduced; for example, for the head-and-neck case, the DeltaD(90%-10%) for the PTV was reduced from 14.9% to 9.2%. This reduction in dose spread is a direct result of intensity modulation. CONCLUSIONS: The results showed that intensity-modulated electron beams could significantly improve the dose homogeneity in the PTV for patients treated with electron conformal therapy using shaped bolus.