Development of generalized time-dependent TCP model and the investigation of the effect of repopulation and weekend breaks in fractionated external beam therapy.

We developed a tumor control probability (TCP) model that incorporates variable time intervals between fractions and a kick-off time (Tk) for radiation-induced accelerated tumor proliferation. The resulting Lee-Rosen model, TCPLR, was used to compute TCPs for treatment courses with and without weekend treatment for tumors with different proliferation rates - slow (prostate), moderate (breast), and rapid (head and neck). TCPs were computed using ideal uniform dose distributions and actual patient plans. The doses for the uniform plans were the mean doses for the prostate and breast cases and the minimum tumor dose for the head and neck case. The TCPLR model predictions agreed with expectations that TCP increases with increasing Tk in all cases. For standard fractionation, as Tk increased from 0 to 4 weeks, TCP increased for the patient distributions by 74.7% for the head and neck cancer, by 6.2% for the breast cancer, and by 2.4% for the prostate cancers. For the uniform dose distributions, the increases were 79.2%, 5.7%, and 2.3%, respectively. TCP increased as the number of weekend breaks decreased. The effect of weekend breaks decreased as the tumor proliferation rate decreased. For the head and neck tumor, notable decreases in TCP of 6.0% (uniform dose distribution) and 6.8% (actual plan dose distribution) were observed with Friday starts compared to Monday starts for the standard 5 fx/wk schedule (Tk = 4 wk). The 7 fx/wk schedule produced increases in TCP of 17.0% and 20.5% for the uniform and patient dose distributions, respectively, compared to the standard schedule. For the breast cancer, starting the 5 fx/wk schedule on Friday decreased the TCP by 0.2% (Tk = 4 wk) compared to a Monday start. The 7 fx/wk schedule produced increases of 0.3% and 0.4% in TCP compared to the standard schedule for the uniform and patient dose distributions, respectively (Tk = 4 wk). For the prostate cancer, the change in TCP for 5 fx/wk schedules starting on different days was 0.1%. The 7 fx/wk schedule increased TCP by 0.8% compared to the standard schedule (Tk = 4 wk). TCP values for the uniform dose distributions for the standard schedule (Tk = 4 wk) agreed with the TCP values for the actual dose distributions within 4.5% for the head and neck tumor and within 0.2% for the breast and prostate tumors. This good agreement suggests that the doses chosen for the uniform dose distributions were good approximations to the clinical doses. The results for head and neck tumors support, in part, the current practice of hyperfractionated/accelerated radiotherapy. They also suggest that shortening the overall treatment time for conventional fractions by eliminating weekend breaks might be beneficial. The predicted effect on TCP of the various schedules studied was insignificant for prostate and breast tumors, suggesting that a weekend treatment might not be necessary for patients starting radiotherapy on a Friday. There is significant uncertainty in the values of the model parameters chosen for these calculations, and no consideration was given to the potential effects of these various schedules on normal tissues.

Identifying surgeon and institutional drivers of cost in total shoulder arthroplasty: a multicenter study.

BACKGROUND: Despite rapid increases in the demand for total shoulder arthroplasty, data describing cost trends are scarce. We aim to (1) describe variation in the cost of shoulder arthroplasty performed by different surgeons at multiple hospitals and (2) determine the driving factors of such variation. METHODS: A standardized, highly accurate cost accounting method, time-driven activity-based costing, was used to determine the cost of 1571 shoulder arthroplasties performed by 12 surgeons at 4 high-volume institutions between 2016 and 2018. Costs were broken down into supply costs (including implant price and consumables) and personnel costs, including physician fees. Cost parameters were compared with total cost for surgical episodes and case volume. RESULTS: Across 4 institutions and 12 surgeons, surgeon volume and hospital volume did not correlate with episode-of-care cost. Average cost per case of each institution varied by factors of 1.6 (P = .47) and 1.7 (P = .06) for anatomic total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RSA), respectively. Implant (56% and 62%, respectively) and personnel costs from check-in through the operating room (21% and 17%, respectively) represented the highest percentages of cost and highly correlated with the cost of the episode of care for TSA and RSA. CONCLUSIONS: Variation in episode-of-care total costs for both TSA and RSA had no association with hospital or surgeon case volume at 4 high-volume institutions but was driven primarily by variation in implant and personnel costs through the operating room. This analysis does not address medium- or long-term costs.

Designing a large field-of-view two-photon microscope using optical invariant analysis.

Conventional two-photon microscopy (TPM) is capable of imaging neural dynamics with subcellular resolution, but it is limited to a field-of-view (FOV) diameter [Formula: see text]. Although there has been recent progress in extending the FOV in TPM, a principled design approach for developing large FOV TPM (LF-TPM) with off-the-shelf components has yet to be established. Therefore, we present a design strategy that depends on analyzing the optical invariant of commercially available objectives, relay lenses, mirror scanners, and emission collection systems in isolation. Components are then selected to maximize the space-bandwidth product of the integrated microscope. In comparison with other LF-TPM systems, our strategy simplifies the sequence of design decisions and is applicable to extending the FOV in any microscope with an optical relay. The microscope we constructed with this design approach can image [Formula: see text] lateral and [Formula: see text] axial resolution over a 7-mm diameter FOV, which is a 100-fold increase in FOV compared with conventional TPM. As a demonstration of the potential that LF-TPM has on understanding the microarchitecture of the mouse brain across interhemispheric regions, we performed in vivo imaging of both the cerebral vasculature and microglia cell bodies over the mouse cortex.

Abnormal synaptic Ca(2+) homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice.

OBJECTIVE: Migraine is among the most common and debilitating neurological conditions. Familial hemiplegic migraine type 1 (FHM1), a monogenic migraine subtype, is caused by gain-of-function of voltage-gated CaV 2.1 calcium channels. FHM1 mice carry human pathogenic mutations in the α1A subunit of CaV 2.1 channels and are highly susceptible to cortical spreading depression (CSD), the electrophysiologic event underlying migraine aura. To date, however, the mechanism underlying increased CSD/migraine susceptibility remains unclear. METHODS: We employed in vivo multiphoton microscopy of the genetically encoded Ca(2+)-indicator yellow cameleon to investigate synaptic morphology and [Ca(2+)]i in FHM1 mice. To study CSD-induced cerebral oligemia, we used in vivo laser speckle flowmetry and multimodal imaging. With electrophysiologic recordings, we investigated the effect of the CaV 2.1 gating modifier tert-butyl dihydroquinone on CSD in vivo. RESULTS: FHM1 mutations elevate neuronal [Ca(2+)]i and alter synaptic morphology as a mechanism for enhanced CSD susceptibility that we were able to normalize with a CaV 2.1 gating modifier in hyperexcitable FHM1 mice. At the synaptic level, axonal boutons were larger, and dendritic spines were predominantly of the mushroom type, which both provide a structural correlate for enhanced neuronal excitability. Resting neuronal [Ca(2+)]i was elevated in FHM1, with loss of compartmentalization between synapses and neuronal shafts. The percentage of calcium-overloaded neurons was increased. Neuronal [Ca(2+)]i surge during CSD was faster and larger, and post-CSD oligemia and hemoglobin desaturation were more severe in FHM1 brains. INTERPRETATION: Our findings provide a mechanism for enhanced CSD susceptibility in hemiplegic migraine. Abnormal synaptic Ca(2+) homeostasis and morphology may contribute to chronic neurodegenerative changes as well as enhanced vulnerability to ischemia in migraineurs.

Target localization accuracy in a respiratory phantom using BrainLAB ExacTrac and 4DCT imaging.

This study evaluated the accuracy of measuring the motion of an internal target using four-dimensional computed tomography (4DCT) scanning and the BrainLAB ExacTrac X-ray imaging system. Displacements of a metal coil implanted in a commercial respiratory phantom were measured in each system and compared to the known motion. A commercial respiratory motion phantom containing a metal coil as a surrogate target was used. Phantom longitudinal motions were sinusoidal with a 4.0 second period and amplitudes ranging from 5-25 mm. We acquired 4DCT and ExacTrac images of the coil at specified respiratory phases and recorded the coordinates of the coil ends. Coil displacement relative to the 0% phase (full-inhale) position were computed for the ExacTrac and 4DCT imaging systems. Coil displacements were compared to known displacements based on the phantom's sinusoidal motion. Coil length distortion due to 4DCT phase binning was compared to the known physical length of the coil (31 mm). The maximum localization error for both coil endpoints for all motion settings was 3.5 mm for the 4DCT and 0.8 mm for the ExacTrac gating system. Coil length errors measured on the 4DCT were less than 0.8 mm at end inhale/exhale phases, but up to 8.3 mm at mid-inhalation phases at the largest motion amplitude (25 mm). Due to the fast image acquisition time (100 ms), no coil distortion was observable in the ExacTrac system. 4DCT showed problems imaging the coil during mid-respiratory phases of higher velocity (phases 20%-30% and 70%-80%) due to distortion caused by residual motion within the 4DCT phase bin. The ExacTrac imaging system was able to accurately localize the coil in the respiratory phantom over all phases of respiration. For our clinic, where end-respiration phases from 4DCT may be used for treatment planning calculations, the ExacTrac system is used to measure internal target motion. With the ExacTrac system, planning target size and motion uncertainties are minimized, potentially reducing internal target volume margins in gated radiotherapy.

Investigation of pitch and jaw width to decrease delivery time of helical tomotherapy treatments for head and neck cancer.

Helical tomotherapy plans using a combination of pitch and jaw width settings were developed for 3 patients previously treated for head and neck cancer. Three jaw widths (5, 2.5, and 1 cm) and 4 pitches (0.86, 0.43, 0.287, and 0.215) were used with a (maximum) modulation factor setting of 4. Twelve plans were generated for each patient using an identical optimization procedure (e.g., number of iterations, objective weights, and penalties, etc.), based on recommendations from TomoTherapy (Madison, WI). The plans were compared using isodose plots, dose volume histograms, dose homogeneity indexes, conformity indexes, radiobiological models, and treatment times. Smaller pitches and jaw widths showed better target dose homogeneity and sparing of normal tissue, as expected. However, the treatment time increased inversely proportional to the jaw width, resulting in delivery times of 24 ± 1.9 min for the 1-cm jaw width. Although treatment plans produced with the 2.5-cm jaw were dosimetrically superior to plans produced with the 5-cm jaw, subsequent calculations of tumor control probabilities and normal tissue complication probabilities suggest that these differences may not be radiobiologically meaningful. Because treatment plans produced with the 5-cm jaw can be delivered in approximately half the time of plans produced with the 2.5-cm jaw (5.1 ± 0.6 min vs. 9.5 ± 1.1 min), use of the 5-cm jaw in routine treatment planning may be a viable approach to decreasing treatment delivery times from helical tomotherapy units.

Evaluation of a commercial flatbed document scanner and radiographic film scanner for radiochromic EBT film dosimetry.

The purpose of this study was to quantify the performance and assess the utility of two different types of scanners for radiochromic EBT film dosimetry: a commercial flatbed document scanner and a widely used radiographic film scanner. We evaluated the Epson Perfection V700 Photo flatbed scanner and the Vidar VXR Dosimetry Pro Advantage scanner as measurement devices for radiochromic EBT film. Measurements were made of scan orientation effects, response uniformity, and scanner noise. Scanners were tested using films irradiated with eight separate 3x3cm2 fields to doses ranging from 0.115-5.119 Gy. ImageJ and RIT software was used for analyzing the Epson and Vidar scans, respectively. For repeated scans of a single film, the measurements in each dose region were reproducible to within +/- 0.3% standard deviation (SD) with both scanners. Film-to-film variations for corresponding doses were measured to be within +/- 0.4% SD for both Epson scanner and Vidar scanners. Overall, the Epson scanner showed a 10% smaller range of pixel value compared to the Vidar scanner. Scanner noise was small: +/- 0.3% SD for the Epson and +/- 0.2% for the Vidar. Overall measurement uniformity for blank film in both systems was better than +/- 2%, provided that the leading and trailing 2 cm film edges were neglected in the Vidar system. In this region artifacts are attributed to the film rollers. Neither system demonstrated a clear measurement advantage. The Epson scanner is a relatively inexpensive method for analyzing radiochromic film, but there is a lack of commercially available software. For a clinic already using a Vidar scanner, applying it to radiochromic film is attractive because commercial software is available. However, care must be taken to avoid using the leading and trailing film edges.

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.

Independent calculation of dose from a helical TomoTherapy unit.

A new calculation algorithm has been developed for independently verifying doses calculated by the TomoTherapy Hi.Art treatment planning system (TPS). The algorithm is designed to confirm the dose to a point in a high dose, low dose-gradient region. Patient data used by the algorithm include the radiological depth to the point for each projection angle and the treatment sinogram file controlling the leaf opening time for each projection. The algorithm uses common dosimetric functions [tissue phantom ratio (TPR) and output factor (Scp)] for the central axis combined with lateral and longitudinal beam profile data to quantify the off-axis dose dependence. Machine data for the dosimetric functions were measured on the Hi.Art machine and simulated using the TPS. Point dose calculations were made for several test phantoms and for 97 patient treatment plans using the simulated machine data. Comparisons with TPS-predicted point doses for the phantom treatment plans demonstrated agreement within 2% for both on-axis and off-axis planning target volumes (PTVs). Comparisons with TPS-predicted point doses for the patient treatment plans also showed good agreement. For calculations at sites other than lung and superficial PTVs, agreement between the calculations was within 2% for 94% of the patient calculations (64 of 68). Calculations within lung and superficial PTVs overestimated the dose by an average of 3.1% (sigma=2.4%) and 3.2% (sigma=2.2%), respectively. Systematic errors within lung are probably due to the weakness of the algorithm in correcting for missing tissue and/or tissue density heterogeneities. Errors encountered within superficial PTVs probably result from the algorithm overestimating the scatter dose within the patient. Our results demonstrate that for the majority of cases, the algorithm could be used without further refinement to independently verify patient treatment plans.

Accuracy of TomoTherapy treatments for superficial target volumes.

Helical tomotherapy is a technique for delivering intensity modulated radiation therapy treatments using a continuously rotating linac. In this approach, fan beams exiting the linac are dynamically modulated in synchrony with the motion of the gantry and couch. Helical IMRT deliveries have been applied to treating surface lesions, and the purpose of this study was to evaluate the accuracy of dose calculated by the TomoTherapy HiArt treatment planning system for superficial planning target volumes (PTVs). TomoTherapy treatment plans were developed for three superficial PTVs (2-, 4-, and 6-cm deep radially by 90 degrees azimuthally by 4-cm longitudinally) contoured on a 27-cm diameter cylindrical white opaque, high-impact polystyrene phantom. The phantom included removable transverse and sagittal film cassettes that contained bare Kodak EDR2 films cut such that their edges matched the phantom surface (+/-0.05 cm). The phantom was aligned to the machine's isocenter (+/-0.05 cm) and was irradiated according to the treatment plans. Films were scanned with a Vidar film digitizer, and optical densities were converted to dose using a calibration determined from a 6 MV perpendicular film exposure. This perpendicular calibration required that axial film doses (parallel irradiation) be scaled by 1.02 so that mid-arc depth doses matched those measured in the sagittal plane (perpendicular irradiation). All film readings were scaled by 0.935 to correct for over-response due to phantom Cerenkov light. Measured dose distributions were registered to calculated ones and compared. Calculated doses overpredicted measured doses by as much as 9.5% of the prescribed dose at depths less than 1 cm. At depths greater than 1 cm, calculated dose distributions showed agreement to measurement within 5% in the high-dose region and within 0.2 cm distance-to-agreement in the dose falloff regions. In the low-dose region posterior to the PTVs (<10% of the prescribed dose), the dose algorithm underpredicted the dose by 1%-2% of the prescribed dose. Clinically, it is recommended that 1 cm of bolus be used on the surface to ensure that cancerous tissues less than 1 cm depth are not underdosed.

Comparison of breath-hold and free-breathing positions of an external fiducial by analysis of respiratory traces.

An internal target volume (ITV) accounting for respiratory-induced tumor motion is best obtained using 4DCT. However, when 4DCT is not available, inspiratory/expiratory breath-hold (BH insp, BH exp) CT images have been suggested as an alternative. In such cases, an external fiducial on the abdomen can be used as a substitute for tumor motion and CT images are acquired when the marker position matches - as judged by the therapist/physicist - its positions at previously determined free-breathing (FB) respiratory extrema (FB insp, FB exp). In this study we retrospectively determined the accuracy of these matches. Free breathing 4DCT images were acquired, followed by BH insp and BH exp CT images for 25 patients with non-small-cell lung cancer. Respiration was monitored using a commercial external fiducial system, which generates positional information while CT studies are conducted. Software was written for statistically analyzing the displacement of the external fiducial during BH insp and BH exp CT acquisition and comparing these displacements with corresponding mean FB extrema positions (FB insp and FB exp, respectively) using a Student's t-test. In 72% of patients, mean positions at BH insp differed significantly from mean positions at FB insp (p < 0.05: 0.13 - 1.40 cm). In 92% of patients, mean positions at BH exp differed significantly from mean positions at FB exp (p < 0.05: 0.03 - 0.70 cm), although this difference was smaller than 0.5 cm in many cases (median = 0.34 cm). Our findings indicate that relying solely on abdominal external markers for accurate BH CT imaging in order to accurately estimate FB extrema positions may be subject to significant error.

Evaluation of MVCT images with skin collimation for electron beam treatment planning.

This study assessed the potential of using megavoltage CT (MVCT) images taken with high density skin collimation in place for electron beam treatment planning. MVCT images were taken using the TomoTherapy Hi-Art system (TomoTherapy Inc., Madison, WI), and the CT numbers were converted to density by calibrating the Hi-Art system using an electron density phantom. Doses were computed using MVCT images and kVCT images and compared by calculating dose differences in the uniform dose region ( > 90%, excluding buildup region) and calculating distance-to-agreement (DTA) in high dose-gradient regions (penumbra and distal falloff, 90%-10%). For 9 and 16 MeV electron beams of 10 x 10 cm calculated on a homogeneous CIRS Plastic Water (Computerized Imaging Research Systems Inc., Norfolk, VA) phantom without skin collimation, the maximum dose differences were 2.3% and the maximum DTAs were 2.0 mm for both beams. The same phantom was then MVCT scanned nine times with square skin collimators of Cerrobend on its surface - field sizes of 3 x 3, 6 x 6, and 10 x 10 cm and thicknesses of 6, 8, and 10 mm. Using the Philips Pinnacle 3 treatment planning system (Philips Medical Systems, N.A., Bothwell, WA), a treatment plan was created for combinations of electron energies of 6, 9, 12, and 16 MeV and each field size. The same treatment plans were calculated using kVCT images of the phantom with regions-of-interest (ROI) manually drawn to duplicate the sizes, shapes, and density of the skin collimators. With few exceptions, the maximum dose differences exceeded +/-5% and the DTAs exceeded 2 mm. We determined that the dose differences were due to small distortions in the MVCT images created by the high density material and manifested as errors in the phantom CT numbers and in the shape of the skin collimator edges. These results suggest that MVCT images without skin collimation have potential for use in patient electron beam treatment planning. However, the small distortion in images with skin collimation makes them unsuitable for clinical use.

Helical tomotherapy for parotid gland tumors.

PURPOSE: To investigate helical tomotherapy (HT) intensity-modulated radiotherapy (IMRT) as a postoperative treatment for parotid gland tumors. METHODS AND MATERIALS: Helical tomotherapy plans were developed for 4 patients previously treated with segmental multileaf collimator (SMLC) IMRT. A primary planning target volume (PTV64) and two secondary PTVs (PTV60, PTV54) were defined. The clinical goals from the SMLC plans were applied as closely as possible to the HT planning. The SMLC plans included bolus, whereas HT plans did not. RESULTS: In general, the HT plans showed better target coverage and target dose homogeneity. The minimum doses to the desired coverage volume were greater, on average, in the HT plans for all the targets. Minimum PTV doses were larger, on average, in the HT plans by 4.6 Gy (p = 0.03), 4.8 Gy (p = 0.06), and 4.9 Gy (p = 0.06) for PTV64, PTV60, and PTV54, respectively. Maximum PTV doses were smaller, on average, by 2.9 Gy (p = 0.23), 3.2 Gy (p = 0.02), and 3.6 Gy (p = 0.03) for PTV64, PTV60, and PTV54, respectively. Average dose homogeneity index was statistically smaller in the HT plans, and conformity index was larger for PTV64 in 3 patients. Tumor control probabilities were higher for 3 of the 4 patients. Sparing of normal structures was comparable for the two techniques. There were no significant differences between the normal tissue complication probabilities for the HT and SMLC plans. CONCLUSIONS: Helical tomotherapy treatment plans were comparable to or slightly better than SMLC plans. Helical tomotherapy is an effective alternative to SMLC IMRT for treatment of parotid tumors.

Assessing respiration-induced tumor motion and internal target volume using four-dimensional computed tomography for radiotherapy of lung cancer.

PURPOSE: To assess three-dimensional tumor motion caused by respiration and internal target volume (ITV) for radiotherapy of lung cancer. METHODS AND MATERIALS: Respiration-induced tumor motion was analyzed for 166 tumors from 152 lung cancer patients, 57.2% of whom had Stage III or IV non-small-cell lung cancer. All patients underwent four-dimensional computed tomography (4DCT) during normal breathing before treatment. The expiratory phase of 4DCT images was used as the reference set to delineate gross tumor volume (GTV). Gross tumor volumes on other respiratory phases and resulting ITVs were determined using rigid-body registration of 4DCT images. The association of GTV motion with various clinical and anatomic factors was analyzed statistically. RESULTS: The proportions of tumors that moved >0.5 cm along the superior-inferior (SI), lateral, and anterior-posterior (AP) axes during normal breathing were 39.2%, 1.8%, and 5.4%, respectively. For 95% of the tumors, the magnitude of motion was less than 1.34 cm, 0.40 cm, and 0.59 cm along the SI, lateral, and AP directions. The principal component of tumor motion was in the SI direction, with only 10.8% of tumors moving >1.0 cm. The tumor motion was found to be associated with diaphragm motion, the SI tumor location in the lung, size of the GTV, and disease T stage. CONCLUSIONS: Lung tumor motion is primarily driven by diaphragm motion. The motion of locally advanced lung tumors is unlikely to exceed 1.0 cm during quiet normal breathing except for small lesions located in the lower half of the lung.

The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy.

PURPOSE: Out-of-field radiation doses to normal tissues may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Step-and-shoot intensity-modulated radiation therapy (IMRT), an increasingly popular treatment modality, yields higher out-of-field doses than do conventional treatments, because of an increase in required monitor units (beam-on time). METHODS: We used published risk coefficients (NRCP Report 116) and out-of-field dose equivalents to multiple organ sites to estimate a conservative maximal risk of fatal secondary malignancy associated with 6 IMRT approaches and 1 conventional external-beam approach for prostate cancer. RESULTS: Depending on treatment energy, the IMRT treatments required 3.5-4.9 times as many monitor units to deliver as did the conventional treatment. The conservative maximum risk of fatal second malignancy was 1.7% for conventional radiation, 2.1% for IMRT using 10-MV X-rays, and 5.1% for IMRT using 18-MV X-rays. Intermediate risks were associated with IMRT using 6-MV X-rays: 2.9% for treatment with the Varian accelerator and 3.7% for treatment with the Siemens accelerator, as well as using 15-MV X-rays: 3.4% (Varian) and 4.0% (Siemens). CONCLUSION: The risk of fatal secondary malignancy differed substantially between IMRT and conventional radiation therapy for prostate cancer, as well as between different IMRT approaches. Perhaps this risk should be considered when choosing the optimal treatment technique and delivery system for patients who will undergo prostate radiation.

Out-of-field photon and neutron dose equivalents from step-and-shoot intensity-modulated radiation therapy.

PURPOSE: To measure the photon and neutron out-of-treatment-field dose equivalents to various organs from different treatment strategies (conventional vs. intensity-modulated radiation therapy [IMRT]) at different treatment energies and delivered by different accelerators. METHODS AND MATERIALS: Independent measurements were made of the photon and neutron out-of-field dose equivalents resulting from one conventional and six IMRT treatments for prostate cancer. The conventional treatment used an 18-MV beam from a Clinac 2100; the IMRT treatments used 6-MV, 10-MV, 15-MV, and 18-MV beams from a Varian Clinac 2100 accelerator and 6-MV and 15-MV beams from a Siemens Primus accelerator. Photon doses were measured with thermoluminescent dosimeters in a Rando phantom, and neutron fluence was measured with gold foils. Dose equivalents to the colon, liver, stomach, lung, esophagus, thyroid, and active bone marrow were determined for each treatment approach. RESULTS: For each treatment approach, the relationship between dose equivalent per MU, distance from the treatment field, and depth in the patient was examined. Photon dose equivalents decreased approximately exponentially with distance from the treatment field. Neutron dose equivalents were independent of distance from the treatment field and decreased with increasing tissue depth. Neutrons were a significant contributor to the out-of field dose equivalent for beam energies > or =15 MV. CONCLUSIONS: Out-of-field photon and neutron dose equivalents can be estimated to any point in a patient undergoing a similar treatment approach from the distance of that point to the central axis and from the tissue depth. This information is useful in determining the dose to critical structures and in evaluating the risk of associated carcinogenesis.

Intensity-modulated radiation therapy (IMRT) of cancers of the head and neck: comparison of split-field and whole-field techniques.

BACKGROUND: Oropharynx cancers treated with intensity-modulated radiation (IMRT) are often treated with a monoisocentric or half-beam technique (HB). IMRT is delivered to the primary tumor and upper neck alone, while the lower neck is treated with a matching anterior beam. Because IMRT can treat the entire volume or whole field (WF), the primary aim of the study was to test the ability to plan cases using WF-IMRT while obtaining an optimal plan and acceptable dose distribution and also respecting normal critical structures. METHODS AND MATERIALS: Thirteen patients with early-stage oropharynx cancers had treatment plans created with HB-IMRT and WF-IMRT techniques. Plans were deemed acceptable if they met the planning guidelines (as defined or with minor violations) of the Radiation Therapy Oncology Group protocol H0022. Comparisons included coverage to the planning target volume (PTV) of the primary (PTV66) and subclinical disease (PTV54). We also compared the ability of both techniques to respect the tolerance of critical structures. RESULTS: The volume of PTV66 treated to >110% was less in 9 of the 13 patients in the WF-IMRT plan as compared to the HB-IMRT plan. The calculated mean volume receiving >110% for all patients planned with WF-IMRT was 9.3% (0.8%-25%) compared to 13.7% (2.7%-23.7%) with HB-IMRT (p = 0.09). The PTV54 volume receiving >110% of dose was less in 10 of the 13 patients planned with WF-IMRT compared to HB-IMRT. The mean doses to all critical structures except the larynx were comparable with each plan. The mean dose to the larynx was significantly less (p = 0.001), 18.7 Gy, with HB-IMRT compared to 47 Gy with WF-IMRT. CONCLUSIONS: Regarding target volumes, acceptable plans can be generated with either WF-IMRT or HB-IMRT. WF-IMRT has an advantage if uncertainty at the match line is a concern, whereas HB-IMRT, particularly in cases not involving the base of tongue, can achieve much lower doses to the larynx.

Retrospective analysis of 2D patient-specific IMRT verifications.

We performed 858 two-dimensional (2D) patient-specific intensity modulated radiotherapy verifications over a period of 18 months. Multifield, composite treatment plans were measured in phantom using calibrated Kodak EDR2 film and compared with the calculated dose extracted from two treatment planning systems. This research summarizes our findings using the normalized agreement test (NAT) index and the percent of pixels failing the gamma index as metrics to represent the agreement between measured and computed dose distributions. An in-house dose comparison software package was used to register and compare all verifications. We found it was important to use an automatic positioning algorithm to achieve maximum registration accuracy, and that our automatic algorithm agreed well with anticipated results from known phantom geometries. We also measured absolute dose for each case using an ion chamber. Because the computed distributions agreed with ion chamber measurements better than the EDR2 film doses, we normalized EDR2 data to the computed distributions. The distributions of both the NAT indices and the percentage of pixels failing the gamma index were found to be exponential distributions. We continue to use both the NAT index and percent of pixels failing gamma with 5%/3 mm criteria to evaluate future verifications, as these two metrics were found to be complementary. Our data showed that using 2%/2 mm or 3%/3 mm criteria produces results similar to those using 5%/3 mm criteria. Normalized comparisons that have a NAT index greater than 45 and/or more than 20% of the pixels failing gamma for 5%/3 mm criteria represent outliers from our clinical data set and require further analysis. Because our QA verification results were exponentially distributed, rather than a tight grouping of similar results, we continue to perform patient-specific QA in order to identify and correct outliers in our verifications. The data from this work could be useful as a reference for other clinics to indicate anticipated trends in 2D verifications under various conditions.

Dosimetric accuracy of Kodak EDR2 film for IMRT verifications.

Patient-specific intensity-modulated radiotherapy (IMRT) verifications require an accurate two-dimensional dosimeter that is not labor-intensive. We assessed the precision and reproducibility of film calibrations over time, measured the elemental composition of the film, measured the intermittency effect, and measured the dosimetric accuracy and reproducibility of calibrated Kodak EDR2 film for single-beam verifications in a solid water phantom and for full-plan verifications in a Rexolite phantom. Repeated measurements of the film sensitometric curve in a single experiment yielded overall uncertainties in dose of 2.1% local and 0.8% relative to 300 cGy. 547 film calibrations over an 18-month period, exposed to a range of doses from 0 to a maximum of 240 MU or 360 MU and using 6 MV or 18 MV energies, had optical density (OD) standard deviations that were 7%-15% of their average values. This indicates that daily film calibrations are essential when EDR2 film is used to obtain absolute dose results. An elemental analysis of EDR2 film revealed that it contains 60% as much silver and 20% as much bromine as Kodak XV2 film. EDR2 film also has an unusual 1.69:1 silver:halide molar ratio, compared with the XV2 film's 1.02:1 ratio, which may affect its chemical reactions. To test EDR2's intermittency effect, the OD generated by a single 300 MU exposure was compared to the ODs generated by exposing the film 1 MU, 2 MU, and 4 MU at a time to a total of 300 MU. An ion chamber recorded the relative dose of all intermittency measurements to account for machine output variations. Using small MU bursts to expose the film resulted in delivery times of 4 to 14 minutes and lowered the film's OD by approximately 2% for both 6 and 18 MV beams. This effect may result in EDR2 film underestimating absolute doses for patient verifications that require long delivery times. After using a calibration to convert EDR2 film's OD to dose values, film measurements agreed within 2% relative difference and 2 mm criteria to ion chamber measurements for both sliding window and step-and-shoot fluence map verifications. Calibrated film results agreed with ion chamber measurements to within 5 % /2 mm criteria for transverse-plane full-plan verifications, but were consistently low. When properly calibrated, EDR2 film can be an adequate two-dimensional dosimeter for IMRT verifications, although it may underestimate doses in regions with long exposure times.

Detection of IMRT delivery errors using a quantitative 2D dosimetric verification system.

We investigated the feasibility of detecting intensity modulated radiotherapy delivery errors automatically using a scalar evaluation of two-dimensional (2D) transverse dose measurement of the complete treatment delivery. Techniques using the gamma index and the normalized agreement test (NAT) index were used to parametrize the agreement between measured and computed dose distributions to seven different scalar metrics. Simulated verifications with delivery errors calculated using a commercially available treatment planning system for 9 prostate and 7 paranasal sinus cases were compared to 433 clinical verifications. The NAT index with 5% and 3 mm criteria that included cold areas outside the planning target volume detected the largest percent of delivery errors. Assuming a false positive rate of 5%, it was able to detect 88% of beam energy changes, 94% of a different patient's plan being delivered, 25% of plans with one beam's collimator rotated by 90 degrees, 81% of rotating one beam's gantry angle by 10 degrees, and 100% of omitting the delivery of one beam. However, no instances of changing one beam's monitor unit setting by 10% or shifting the isocenter by 5 mm were detected. Although the phantom shift could not be detected by the small change it made in the dose distribution, our autopositioning algorithm clearly identified the spatial anomaly. Using tighter 3 %/2 mm criteria or combining dose and distance disagreements in an either/or fashion resulted in poorer delivery error detection. The mean value of the 2D gamma index distribution was less sensitive to delivery errors than the other scalar metrics studied. Although we found that scalar metrics do not have sufficient delivery error detection rates to be used as the sole clinical analysis technique, manually examining 2D dose comparison images would result in a near 100% detection rate while performing an ion chamber measurement alone would only detect 54% of these errors.