Feasibility of CBCT-based dose with a patient-specific stepwise HU-to-density curve to determine time of replanning.

PURPOSE: (a) To investigate the accuracy of cone-beam computed tomography (CBCT)-derived dose distributions relative to fanbeam-based simulation CT-derived dose distributions; and (b) to study the feasibility of CBCT dosimetry for guiding the appropriateness of replanning. METHODS AND MATERIALS: Image data corresponding to 40 patients (10 head and neck [HN], 10 lung, 10 pancreas, 10 pelvis) who underwent radiation therapy were randomly selected. Each patient had both intensity-modulated radiation therapy and volumetric-modulated arc therapy plans; these 80 plans were subsequently recomputed on the CBCT images using a patient-specific stepwise curve (Hounsfield units-to-density). Planning target volumes (PTVs; D98%, D95%, D2%), mean dose, and V95% were compared between simulation-CT-derived treatment plans and CBCT-based plans. Gamma analyses were performed using criterion of 3%/3 mm for three dose zones (>90%, 70%~90%, and 30%~70% of maximum dose). CBCT-derived doses were then used to evaluate the appropriateness of replanning decisions in 12 additional HN patients whose plans were previously revised during radiation therapy because of anatomic changes; replanning in these cases was guided by the conventional observed source-to-skin-distance change-derived approach. RESULTS: For all disease sites, the difference in PTV mean dose was 0.1% ± 1.1%, D2% was 0.7% ± 0.1%, D95% was 0.2% ± 1.1%, D98% was 0.2% ± 1.0%, and V95% was 0.3% ± 0.8%; For 3D dose comparison, 99.0% ± 1.9%, 97.6% ± 4.4%, and 95.3% ± 6.0% of points passed the 3%/3 mm criterion of gamma analysis in high-, medium-, and low-dose zones, respectively. The CBCT images achieved comparable dose distributions. In the 12 previously replanned 12 HN patients, CBCT-based dose predicted well changes in PTV D2% (Pearson linear correlation coefficient = 0.93; P < 0.001). If 3% of change is used as the replanning criteria, 7/12 patients could avoid replanning. CONCLUSIONS: CBCT-based dose calculations produced accuracy comparable to that of simulation CT. CBCT-based dosimetry can guide the decision to replan during the course of treatment.

Optimizing the MLC model parameters for IMRT in the RayStation treatment planning system.

Unlike other commercial treatment planning systems (TPS) which model the rounded leaf end differently (such as the MLC dosimetric leaf gap (DLG) or rounded leaf-tip radius), the RayStation TPS (RaySearch Laboratories, Stockholm, Sweden) models transmission through the rounded leaf end of the MLC with a step function, in which the radiation transmission through the leaf end is the square root of the average MLC transmission factor. We report on the optimization of MLC model parameters for the RayStation planning system. This (TPS) models the rounded leaf end of the MLC with the following parameters: eaf-tip offset, leaf-tip width, average transmission factor, and tongue and groove. We optimized the MLC model parameters for IMRT in the RayStation v. 4.0 planning system and for a Varian C-series linac with a 120-leaf Millennium MLC, and validated the model using measured data. The leaf-tip offset is the geometric offset due to the rounded leaf-end design and resulting divergence of the light/radiation field. The offset value is a function of the leaf-tip position, and tabulated data are available from the vendor. The leaf-tip width was iteratively evaluated by comparing computed and measured transverse dose profiles of MLC defined fields at dmax in water. In-water profile comparisons were also used to verify the MLC leaf position (leaf-tip offset). The average transmission factor and leaf tongue-and-groove width were derived iteratively by maximizing the agreement between measurements and RayStation TPS calculations for five clinical IMRT QA plans. Plan verifications were performed by comparing MapCHECK2 measurements and Monte Carlo calculations. The MLC model was validated using five test IMRT cases from the AAPM Task Group 119 report. Absolute gamma analyses (3 mm/3% and 2 mm/2%) were applied. In addition, computed output factors for MLC-defined small fields (2 × 2, 3 × 3, 4 × 4, 6× 6cm2) of both 6 MV and 18 MV photons were compared to those independently measured by the Imaging and Radiation Oncology Core (IROC), Houston, TX. 6MV and 18 MV models were both determined to have the same MLC parameters: leaf-tip offset = 0.3 cm, 2.5% transmission, and leaf tongue-and-groove width = 0.05 cm. IMRT QA analysis for five test cases in TG-119 resulted in a 100% passing rate with 3 mm/3% gamma analysis for 6 MV, and > 97.5% for 18 MV. The passing rate was > 94.6% for 6 MV and > 90.9% for 18 MV when the 2 mm/2% gamma analysis criteria was applied. These results compared favorably with those published in AAPM Task Group 119. The reported MLC model parameters serve as a reference for other users.

Pegfilgrastim Improves Survival of Lethally Irradiated Nonhuman Primates.

Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 µg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/µL, ANC ≥1,000/µL and platelet (PLT) count ≥20,000/µL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data demonstrate that pegfilgrastim is an additional medical countermeasure capable of increasing survival and neutrophil-related parameters when administered in an abbreviated schedule to a NHP model of lethal H-ARS.

An analytical formalism to calculate phantom scatter factors for flattening filter free (FFF) mode photon beams.

Phantom Scatter Factors, Sp in the Khan formalism (Khan et al 1980 J. Radiat. Oncol. Biol. Phys. 6 745-51) describe medium-induced changes in photon-beam intensity as a function of size of the beam. According to the British Journal of Radiology, Supplement 25, megavoltage phantom scatter factors are invariant as a function of photon-beam energy. However, during the commissioning of an accelerator with flattening filter free (FFF) photon beams (Varian TrueBeam(TM) 6-MV FFF and 10-MV FFF), differences were noted in phantom scatter between the filtered beams and FFF-mode beams. The purpose of this work was to evaluate this difference and provide an analytical formalism to explain the phantom scatter differences between FFF-mode and the filtered mode. An analytical formalism was devised to demonstrate the source of phantom scatter differences between the filtered and the FFF-mode beams. The reason for the differences in the phantom scatter factors between the filtered and the FFF-mode beams is hypothesized to be the non-uniform beam profiles of the FFF-mode beams. The analytical formalism proposed here is based on this idea, taking the product of the filtered phantom scatter factors and the ratio of the off-axis ratio between the FFF-mode and the filtered beams. All measurements were performed using a Varian TrueBeam(TM) linear accelerator with photon energies of 6-MV and 10-MV in both filtered and FFF-modes. For all measurements, a PTW Farmer type chamber and a Scanditronix CC04 cylindrical ionization were used. The in-water measurements were made at depth dose maximum and 100 cm source-to-axis distance. The in-air measurements were done at 100 cm source-to-axis distance with appropriate build-up cap. From these measurements, the phantom scatter factors were derived for the filtered beams and the FFF-mode beams for both energies to be evaluated against the phantoms scatter factors calculated using the proposed algorithm. For 6-MV, the difference between the measured and the calculated FFF-mode phantom scatter factors ranged from -0.34% to 0.73%. The average per cent difference was -0.17% (1σ = 0.25%). For 10-MV, the difference ranged from -0.19% to 0.24%. The average per cent difference was -0.17% (1σ = 0.13%). An analytical formalism was presented to calculate the phantom scatter factors for FFF-mode beams using filtered phantom scatter factors as a basis. The overall differences between measurements and calculations were within ± 0.5% for 6-MV and ± 0.25% for 10-MV.

The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 µg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells µL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage.

The objective of this pilot study was to explore whether administration of a catalytic antioxidant, AEOL 10150 (C48H56C15MnN12), could reduce radiation-induced lung injury and improve overall survival when administered after 11.5 Gy of whole thorax lung irradiation in a non-human primate model. Thirteen animals were irradiated with a single exposure of 11.5 Gy, prescribed to midplane, and delivered with 6 MV photons at a dose rate of 0.8 Gy min. Beginning at 24 h post irradiation, the AEOL 10150 cohort (n = 7) received daily subcutaneous injections of the catalytic antioxidant at a concentration of 5 mg kg for a total of 4 wk. All animals received medical management, including dexamethasone, based on clinical signs during the planned 180-d in-life phase of the study. All decedent study animals were euthanized for failure to maintain saturation of peripheral oxygen > 88% on room air. Exposure of the whole thorax to 11.5 Gy resulted in radiation-induced lung injury in all animals. AEOL 10150, as administered in this pilot study, demonstrated potential efficacy as a mitigator against fatal radiation-induced lung injury. Treatment with the drug resulted in 28.6% survival following exposure to a radiation dose that proved to be 100% fatal in the control cohort (n = 6). Computed tomography scans demonstrated less quantitative radiographic injury (pneumonitis, fibrosis, effusions) in the AEOL 10150-treated cohort at day 60 post-exposure, and AEOL 10150-treated animals required less dexamethasone support during the in-life phase of the study. Analysis of serial plasma samples suggested that AEOL 10150 treatment led to lower relative transforming growth factor-Beta-1 levels when compared with the control animals. The results of this pilot study demonstrate that treatment with AEOL 10150 results in reduced clinical, radiographic, anatomic, and molecular evidence of radiation-induced lung injury and merits further study as a medical countermeasure against radiation-induced pulmonary injury.

The MCART radiation physics core: the quest for radiation dosimetry standardization.

Dose-related radiobiological research results can only be compared meaningfully when radiation dosimetry is standardized. To this purpose, the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Medical Countermeasures Against Radiological Threats (MCART) consortium recently created a Radiation Physics Core (RPC) as an entity to assume responsibility of standardizing radiation dosimetry practices among its member laboratories. The animal research activities in these laboratories use a variety of ionizing photon beams from several irradiators such as 250-320 kVp x-ray generators, Cs irradiators, Co teletherapy machines, and medical linear accelerators (LINACs). In addition to this variety of sources, these centers use a range of irradiation techniques and make use of different dose calculation schemes to conduct their experiments. An extremely important objective in these research activities is to obtain a Dose Response Relationship (DRR) appropriate to their respective organ-specific models of acute and delayed radiation effects. A clear and unambiguous definition of the DRR is essential for the development of medical countermeasures. It is imperative that these DRRs are transparent between centers. The MCART RPC has initiated the establishment of standard dosimetry practices among member centers and is introducing a Remote Dosimetry Monitoring Service (RDMS) to ascertain ongoing quality assurance. This paper will describe the initial activities of the MCART RPC toward implementing these standardization goals. It is appropriate to report a summary of initial activities with the intent of reporting the full implementation at a later date.

Protons offer reduced normal-tissue exposure for patients receiving postoperative radiotherapy for resected pancreatic head cancer.

PURPOSE: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. METHODS AND MATERIALS: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. RESULTS: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). CONCLUSIONS: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

Use of a matchline dosimetry analysis tool (MDAT) to quantify dose homogeneity in the region between abutting tangential and supraclavicular radiation fields.

In this work, we develop and test a matchline dosimetry analysis tool (MDAT) to examine the dose distribution within the abutment region of two or more adjoining radiotherapy fields that employ different blocking mechanisms and geometries in forming a match. This objective and quantitative tool uses calibrated radiographic film to measure the dose in the abutment region, and uses a frequency distribution of area versus dose (a dose-area histogram) to visualize the spatial dose distribution. We tested the MDAT's clinical applicability and parameters by evaluating the dose between adjacent photon fields incident on a flat phantom using field-matching techniques employing collimator-jaw and multileaf collimator (MLC) configurations. Additionally, we evaluated the dose in the abutment regions of four different clinical tangential-breast and supraclavicular matching techniques using various combinations of collimator and MLC matches. Using the MDAT tool, it was deter-mined that a 1 cm abutment region width (centered about the theoretical matchline between fields) is the most appropriate width to determine dose homogeneity in a field matching region. Using the MDAT, both subtle and large differences were seen between fields that used MLCs to form the match, compared to flat edge devices such as collimators and external cerrobend blocks. We conclude that the MDAT facilitates a more precise evaluation of the distribution of dose within the region of abutment of radiotherapy fields.

Optimal acquisition parameter selection for CT simulators in radiation oncology.

The purpose of this study was to identify optimal CT acquisition parameter settings for each make and model of scanners used in a large Radiation Oncology (RO) Department, considering the special requirements of CT simulation. Two CT phantoms were used to evaluate the image quality of the five different multi-channel CT scanners using helical scan mode. We compared the effects of various pitch, detector configurations, and rotation time parameters on image artifacts, and on spatial and contrast resolution. We found that helical artifact was closely related to pitch and detector configuration settings. This artifact was scanner-specific and generally more obvious when the channel width or detector collimation was equal to the image thickness. Different acquisition parameter settings produced slight differences in observed high- and low-contrast resolution. Short rotation time degraded image quality for certain scanners, but only slightly, while other rotation times, such as 0.75 sec/rotation and above, had no obvious effect on resolution. An optimized combination of acquisition parameters was determined for each scanner make and model, based on phantom image quality and other considerations for clinical applications. This information may be directly useful for physicists whose CT simulation scanners match one of the five examined in this study. If not, the strategy reported here may be used as a guide to perform a similar evaluation of the scanner.

Accuracy of two heterogeneity dose calculation algorithms for IMRT in treatment plans designed using an anthropomorphic thorax phantom.

With the advent of intensity-modulated radiation therapy (IMRT), the inclusion of heterogeneity corrections is further complicated by the conformal delivery of many small beams forming steep dose gradients. Radiation treatment planning has evolved to take into account even small changes in tissue density so that the dose to tumor can be further optimized. However, different treatment planning systems incorporate different heterogeneity correction algorithms, and it is unclear whether any of these algorithms are superior to others in terms of accurately predicting delivered radiation doses relative to measurement in a clinical setting. The purpose of this study was to determine the accuracy of heterogeneity dose calculations from two widely used IMRT treatment planning systems (Pinnacle and Corvus) against measurement. These two systems handle heterogeneity dose corrections by means of a collapsed-cone convolution superposition algorithm and a finite-size pencil-beam algorithm with one-dimensional depth scaling correction, respectively. Treatment plans were generated by each system using an anthropomorphic thorax phantom, routine clinical lung tumor constraints, and a common prescribed dose. Dose measurements made by thermoluminescent detectors (TLDs) and radiochromic film positioned within the phantom's lung and offset tumor insert were then compared with the calculated values. The collapsed cone convolution superposition dose calculation algorithm provided clinically acceptable results (+/-5% of the normalization dose or 3 mm distance to agreement) in the designed treatment plan and delivery. The pencil-beam algorithm with an effective pathlength correction showed reasonable agreement within the gross tumor volume, overestimated dose within a majority of the planning target volume, and underestimated the extent of the penumbral broadening, yielding only about 60% accuracy when judged by the above criterion. Even judged by a more generous criterion (+/-7% /7 mm), the results were clinically unfavorable (at only about 80% accuracy). To ascertain the dose in heterogeneous regions such as the tumor-lung interface and the peripheral lung dose near the tumor, the superposition convolution algorithm that accounts for lateral scatter and electron transport should be used. The use of the pencil-beam algorithm with only an effective pathlength correction may result in the dose to the target being overestimated. As a result, a full understanding of any treatment planning system's heterogeneity algorithm is required prior to clinical implementation.

Clinical implications of incorporating heterogeneity corrections in mantle field irradiation.

PURPOSE: Patient dose calculations for mantle-field irradiation have traditionally been performed using homogeneous, water phantom data. The advent of computed tomography (CT)-based treatment planning now permits dose calculations to be corrected for actual patient density. Incorporation of full heterogeneity corrections is desirable, because calculations performed in this fashion more closely represent the actual dose delivered to the patient. In preparation for full clinical implementation of heterogeneity corrections in mantle irradiation, an evaluation of possible changes in dosimetry when transitioning from treatment plans generated without heterogeneity corrections to treatment plans that incorporated full heterogeneity corrections is presented. MATERIALS AND METHODS: A retrospective analysis was performed of treatment plans with and without heterogeneity corrections for 15 consecutive patients who had undergone full mantle-field irradiation. Comparisons were made of the absolute delivered doses (in cGy per monitor unit) and the absolute volume (in cubic centimeters) enclosed by the isodose surface of the 30.6 Gy prescription line and the surface representing 90% of the prescribed dose. Dose-volume histograms (DVHs) were generated and studied to evaluate differences in the doses received by the lungs, heart, and spinal cord between corrected and uncorrected plans. Comparisons were made of the volumes of lung receiving at least 20 Gy, the volumes of heart receiving at least 25.2 Gy, and the maximum cord dose. RESULTS: Dosimetric differences between heterogeneity-corrected and heterogeneity-uncorrected calculations were small. The mean total ratio of corrected-to-uncorrected dose per monitor unit was 1.01, with a standard deviation (SD) of 0.02. The mean corrected-to-uncorrected treated volume ratio (30.6 Gy) was 0.97, SD 0.14, and the mean corrected-to-uncorrected volume ratio of the 90% isodose surface was 0.99, SD 0.02. The ratio of the volume of lung receiving at least 20 Gy was 1.03, SD 0.02; the ratio of the volume of heart receiving at least 25.2 Gy was 1.01, SD 0.03; and the maximum spinal cord dose ratio was 1.02, SD 0.02. CONCLUSIONS: In all patient treatment plans evaluated, no significant dosimetric differences were observed between heterogeneity-corrected and heterogeneity-uncorrected treatment plans. However, unpredictable differences in the prescription isodose (30.6 Gy) were observed. The differences in coverage at the 90% isodose volume were negligible. The dose administered to lung in heterogeneity-corrected plans demonstrates a higher dose overall, with the greatest increase occurring at volumes receiving at least 20 Gy. In light of these small dosimetric differences, we believe that heterogeneity corrections can be incorporated into full mantle-field treatment planning.

Corrections to traditional methods of verifying tangential-breast 3D monitor-unit calculations: use of an equivalent triangle to estimate effective fields.

This paper describes an innovative method for correctly estimating the effective field size of tangential-breast fields. The method uses an "equivalent triangle" to verify intact breast tangential field monitor-unit settings calculated by a 3D planning system to within 2%. The effects on verification calculations of loss of full scatter due to beam oblique incidence, proximity to field boundaries, and reduced scattering volumes are handled properly. The methodology is validated by comparing calculations performed by the 3D planning system with the respective verification estimates. The accuracy of this technique is established for dose calculations both with and without heterogeneity corrections.