Single-field Plan Research Articles

Markerless dynamic tumor tracking (MDTT) radiotherapy using diaphragm as a surrogate for liver targets.

To assess the feasibility of using the diaphragm as a surrogate for liver targets during MDTT. Diaphragm as surrogate for markers: a dome-shaped phantom with implanted markers was fabricated and underwent dual-orthogonal fluoroscopy sequences on the Vero4DRT linac. Ten patients participated in an IRB-approved, feasibility study to assess the MDTT workflow. All images were analyzed using an in-house program to back-project the diaphragm/markers position to the isocenter plane. ExacTrac imager log files were analyzed. Diaphragm as tracking structure for MDTT: The phantom "diaphragm" was contoured as a markerless tracking structure (MTS) and exported to Vero4DRT/ExacTrac. A single field plan was delivered to the phantom film plane under static and MDTT conditions. In the patient study, the diaphragm tracking structure was contoured on CT breath-hold-exhale datasets. The MDTT workflow was applied until just prior to MV beam-on. Diaphragm as surrogate for markers: phantom data confirmed the in-house 3D back-projection program was functioning as intended. In patients, the diaphragm/marker relative positions had a mean±RMS difference of 0.70±0.89, 1.08±1.26, and 0.96±1.06mm in ML, SI, and AP directions. Diaphragm as tracking structure for MDTT: Building a respiratory-correlation model using the diaphragm as surrogate for the implanted markers was successful in phantom/patients. During the tracking verification imaging step, the phantom mean±SD difference between the image-detected and predicted "diaphragm" position was 0.52±0.18mm. The 2D film gamma (2%/2mm) comparison (static to MDTT deliveries) was 98.2%. In patients, the mean difference between the image-detected and predicted diaphragm position was 2.02±0.92mm. The planning target margin contribution from MDTT diaphragm tracking is 2.2, 5.0, and 4.7mm in the ML, SI, and AP directions. In phantom/patients, the diaphragm motion correlated well with markers' motion and could be used as a surrogate. MDTT workflows using the diaphragm as the MTS is feasible using the Vero4DRT linac and could replace the need for implanted markers for liver radiotherapy.

Treatment planning of carbon ion radiotherapy for prostate cancer based on cellular experiments with PC3 human prostate cancer cells

[Purpose] Treatment plans for carbon ion radiotherapy (CIRT) in Japan are designed to uniformly deliver the prescribed clinical dose based on the radiosensitivity of human salivary gland (HSG) cells to the planning target volume (PTV). However, sensitivity to carbon beams varies between cell lines, that is, it should be checked that the clinical dose distribution based on the cell radiosensitivity of the treatment site is uniform within the PTV.[Methods] We modeled the linear energy transfer (LET) dependence of the linear-quadratic (LQ) coefficients specific to prostate cancer, which accounts for the majority of CIRT. This was achieved by irradiating prostate cancer cells (PC3) with X-rays from a 4 MV-Linac and carbon beams with different LETs of 11.1–214.3 keV/μm. By using the radiosensitivity of PC3 cells derived from cellular experiments, we reconstructed prostate-cancer-specific clinical dose distributions on patient computed tomography (CT).[Results] The LQ coefficient, α, of PC3 cells was larger than that of HSG cells at low (<50 keV/μm) LET and smaller at high (>50 keV/μm) LET, which was validated by cellular experiments performed on rectangular SOBPs. The reconstructed dose distribution on patient CT was sloped when 1 fraction incident from the one side of the patient was considered, but remained uniform from the sum of 12 fractions of the left–right opposing beams (as is used in clinical practice).[Conclusion] Our study reveals the inhomogeneity of clinical doses in single-field plans calculated using the PC3 radiosensitivity data. However, this inhomogeneity is compensated by using the combination of left–right opposing beams.

Universal and dynamic ridge filter for pencil beam scanning particle therapy: a novel concept for ultra-fast treatment delivery

Objective. In pencil beam scanning particle therapy, a short treatment delivery time is paramount for the efficient treatment of moving targets with motion mitigation techniques (such as breath-hold, rescanning, and gating). Energy and spot position change time are limiting factors in reducing treatment time. In this study, we designed a universal and dynamic energy modulator (ridge filter, RF) to broaden the Bragg peak, to reduce the number of energies and spots required to cover the target volume, thus lowering the treatment time. Approach. Our RF unit comprises two identical RFs placed just before the isocenter. Both RFs move relative to each other, changing the Bragg peak’s characteristics dynamically. We simulated different Bragg peak shapes with the RF in Monte Carlo simulation code (TOPAS) and validated them experimentally. We then delivered single-field plans with 1 Gy/fraction to different geometrical targets in water, to measure the dose delivery time using the RF and compare it with the clinical settings. Main results. Aligning the RFs in different positions produces different broadening in the Bragg peak; we achieved a maximum broadening of 2.5 cm. With RF we reduced the number of energies in a field by more than 60%, and the dose delivery time by 50%, for all geometrical targets investigated, without compromising the dose distribution transverse and distal fall-off. Significance. Our novel universal and dynamic RF allows for the adaptation of the Bragg peak broadening for a spot and/or energy layer based on the requirement of dose shaping in the target volume. It significantly reduces the number of energy layers and spots to cover the target volume, and thus the treatment time. This RF design is ideal for ultra-fast treatment delivery within a single breath-hold (5–10 s), efficient delivery of motion mitigation techniques, and small animal irradiation with ultra-high dose rates (FLASH).

Impact of a spatially dependent dose delivery time structure on the biological effectiveness of scanning proton therapy.

In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. This research aimed to evaluate the spatially dependent biological effectiveness of protracted irradiation in scanning proton therapy. One and two parallel opposed fields plans were created in water phantom with the prescribed dose of 2 Gy. Three scenarios (instantaneous, continuous, and layered scans) were used with the corresponding beam delivery models. The biological dose (physical dose × relative biological effectiveness) was calculated using the linear quadratic model and the theory of dual radiation action to quantitatively evaluate the dose delivery time effect. In addition, simulations using clinical plans (postoperative seminoma and prostate tumor cases) were conducted to assess the impact of the effects on the dose volume histogram parameters and homogeneity coefficient (HC) in targets. In a single-field plan of water phantom, when the treatment time was 19 min, the layered-scan scenario showed a decrease of<0.2% (almost 3.3%) in the biological dose from the plan on the distal (proximal) side because of the high (low) dose rate. This is in contrast to the continuous scenario, where the biological dose was almost uniformly decreased over the target by approximately 3.3%. The simulation with clinical geometry showed that the decrease rates in D99% were 0.9% and 1.5% for every 10 min of treatment time prolongation for postoperative seminoma and prostate tumor cases, respectively, whereas the increase rates in HC were 0.7% and 0.2%. In protracted irradiation in scanning proton therapy, the spatially dependent dose delivery time structure in scanning beam delivery can be an important factor for accurate evaluation of biological effectiveness.

How can scanned proton beam treatment planning for low-grade glioma cope with increased distal RBE and locally increased radiosensitivity for late MR-detected brain lesions?

A novel risk model has recently been proposed for the occurrence of late contrast-enhancing brain lesions (CEBLs) after proton irradiation of low-grade glioma (LGG) patients. It predicts a strong dependence on dose-weighted linear-energy transfer (LETd effect) and an increased radiosensitivity of the ventricular proximity, a 4-mm fringe surrounding the ventricular system (VP4mm effect). On this basis, we investigated (A) how these two risk factors and patient-specific anatomical and treatment plan (TP) features contribute to normal tissue complication probability (NTCP) and (B) if conventional LETd -reduction techniques like multiple-field TP are able to reduce NTCP. (A) The LGG model cohort (N=110) was stratified with respect to prescribed dose, tumor grade, and treatment field configuration. NTCP predictions and CEBL occurrence rates per strata were analyzed. (B) The effect of multiple-field TP was investigated in two patient groups: (i) nine high-risk subjects with extended lateral target volumes who had developed CEBLs after single-beam treatments were retrospectively replanned with a clinical standard two-field setting using almost orthogonal fields and strictly opposing fields, (ii) single-field treatments were simulated for seven low-risk patients with small central target volumes clinically treated with two strictly opposing fields. (A) In the model cohort, we identified the exposure of the radiosensitive VP4mm fringe with proton field components of increased biological effectiveness as dominant NTCP driving factor. We observed that larger target volumes and location lateral to the main ventricles, both being characteristic for WHO°II tumors, presented with the highest complication risks. Among subjects of an equal dose prescription of 54Gy(RBE), the highest median NTCP was obtained for the WHO°II group treated with two fields using sharp angles. (B) Regarding the effect of multiple-field plans, we found that an NTCP reduction was only achievable in the low-risk group where the LETd effect dominates and the VP4mm effect is small. NTCP of the single-field plans was 23% higher compared to the clinical opposing field plan. In the high-risk group, where the VP4mm effect dominates the risk, both two-field scenarios yielded 44% higher NTCP predictions compared to the clinical single-field plans. The interplay of an increased radiosensitivity in the VP4mm fringe with proton field components of increased biological effectiveness creates a geometric complexity that can hardly be managed by current clinical TP. Our results underline that advanced biologically guided TP approaches become crucial for an effective risk minimization in proton therapy of LGG.

Assessing the advantages of CFR-PEEK over titanium spinal stabilization implants in proton therapy—a phantom study

High-density materials, such as titanium, used for spinal stabilization, introduces several critical issues in proton therapy (PT). Artefacts affect both contouring and dose calculation. Subsequently, artefacts need to be corrected which is a time-consuming process. Besides, titanium causes proton interactions that are unaccounted for in dose calculation. The result is a suboptimal treatment plan, and indeed decreased local controls have been reported for these patients. Carbon fiber reinforced polyetheretherketone (CFR-PEEK) implant material, which is of low density, potentially solves these issues. For this study, we designed a unique phantom to compare the effects of titanium and CFR-PEEK implants in PT. The phantom contains four interchangeable spinal inserts representing a native spine, and three different spinal stabilizations consisting of titanium only, CFR-PEEK only, and a combination of titanium and CFR-PEEK. All phantom scenarios received the standard treatment workup. Two planning approaches were investigated: a single field plan and a multi-field optimized plan with spinal cord sparing. For both plans we analyzed the following aspects: total volume of artefacts on CT images, time required for artefact correction, effect of planning CT correction on dose calculation, plan robustness to range and set up uncertainties, and finally the discrepancy between the calculated dose and the delivered dose with Gafchromic® film. The CFR-PEEK implant had a 90% reduction of artefacts on CT images and subsequently severely reduced the time for artefact correction with respect to the titanium-only implant. Furthermore, the CFR-PEEK as opposed to titanium did not influence the robustness of the plan. Finally, the titanium implants led to hardware-related discrepancies between the planned and the measured dose while the CFR-PEEK implant showed good agreement. As opposed to titanium, CFR-PEEK has none to minor effects on PT. The use of CFR-PEEK is expected to optimize treatment and possibly improve outcomes for patients that require spinal stabilization.

P204] Proton pencil beam scanning with motion emulated as spot shifts: Dose reconstruction for lung cancer

Purpose Respiratory motion impairs delivered dose in proton pencil beam scanning for lung cancer radiotherapy. These uncertainties can be estimated by splitting the treatment plan into phase-specific plans (based on 4DCT) and summing the dose by deformable image registration (DIR), which is labor intensive and susceptible to DIR-errors. A faster spot shift method (SSM), applicable to any motion observed during treatment, is an alternative. Methods The SSM emulates beam’s-eye-view target motion as proton spot-shifts and in-depth motion as energy changes. Dose is calculated in the end-expiration phase. The method was tested for a challenging case, with a primary 1.5 ml tumor (T) in the lower left lobe, a 4.8 ml lymph node (LN) in station 8 and large respiratory motion (T: 20 mm, LN: 6 mm). We simulated treatment delivery in end-inspiration with dose evaluation in end-expiration. A test plan had two spots hitting the center of each target in the end-inspiration. The dose in the end-expiration anatomy was estimated by warping the end-inspiration dose to the end-expiration and by calculating the dose directly in the end-expiration by the SSM using different spot shifts for T and LN. Next, a full single field plan was calculated in the end-inspiration and the dose was again estimated in the end-expiration by dose warping and SSM calculation. Target doses were compared between methods. Results The warped dose in end-expiration represented rib and tumor doses well, while the lung entrance dose was wrong (DIR’s insufficient modelling of the pleura motion). Although the SSM used a wrong entrance path through the ribs, the target doses agreed well with the original end-inspiration doses. The Dice index between warped and SSM end-expiration dose was 0.77 and 0.71 for the 50% and 95% isodoses. DVH parameters of the full plan agreed for LN, but had discrepancies for T. Conclusions The SSM dose reconstruction agreed with the warped dose for the single spot plan. For the full plan, the agreement was good for the LN, but only fair for the T, probably due to volume changes and lung deformations near the tumor. In larger tumors with smaller motion, the SSM is likely to perform better.

Experimental validation of a deforming grid 4D dose calculation for PBS proton therapy

The aim of this study was to verify the temporal accuracy of the estimated dose distribution by a 4D dose calculation (4DDC) in comparison to measurements. A single-field plan (0.6 Gy), optimised for a liver patient case (CTV volume: 403cc), was delivered to a homogeneous PMMA phantom and measured by a high resolution scintillating-CCD system at two water equivalent depths. Various motion scenarios (no motion and motions with amplitude of 10 mm and two periods: 3.7 s and 4.4 s) were simulated using a 4D Quasar phantom and logged by an optical tracking system in real-time. Three motion mitigation approaches (single delivery, 6 layered and volumetric rescanning) were applied, resulting in 10 individual measurements. 4D dose distributions were retrospectively calculated in water by taking into account the delivery log files (retrospective) containing information on the actually delivered spot positions, fluences, and time stamps. Moreover, in order to evaluate the sensitivity of the 4DDC inputs, the corresponding prospective 4DDCs were performed as a comparison, using the estimated time stamps of the spot delivery and repeated periodical motion patterns. 2D gamma analyses and dose-difference-histograms were used to quantify the agreement between measurements and calculations for all pixels with 5% of the maximum calculated dose. The results show that a mean gamma score of 99.2% with standard deviation 1.0% can be achieved for 3%/3 mm criteria and all scenarios can reach a score of more than 95%. The average area with more than 5% dose difference was 6.2%. Deviations due to input uncertainties were obvious for single scan deliveries but could be smeared out once rescanning was applied. Thus, the deforming grid 4DDC has been demonstrated to be able to predict the complex patterns of 4D dose distributions for PBS proton therapy with high dosimetric and geometric accuracy, and it can be used as a valid clinical tool for 4D treatment planning, motion mitigation selection, and eventually 4D optimisation applications if the correct temporal information is available.

Effect of 16-bit computed tomography imaging of metallic implants on dose distribution in radiotherapy

Objective To reconstruct 16-bit images of metal implants using the extended function of computed tomography (CT) imaging, and to analyze the effect of the metal CT value on calculation of dose distribution by evaluation of metal CT values in different scanning conditions. Methods A stainless steel rod and a titanium rod were inserted in a phantom. The 12-and 16-bit images and CT value distribution of metal implants were obtained by scanning the phantom using 120 kV tube voltage and 230 mA tube current. The 16-bit images and CT value distribution of metal implants were obtained by scanning the phantom using fixed tube current (230 mA) with varied tube voltage (100, 120, and 140 kV) or fixed tube voltage (120 kV) with varied tube current (180, 230, and 280 mA). In the Varian treatment planning system, a single-field plan and a parallel-opposed field plan were designed based on the CT images. The dose distribution was calculated and compared by the paired t test. Results The CT values of the stainless steel rod and the titanium rod were both 3071 HU in 12-bit CT images. In 16-bit CT images; however, the CT value of the stainless steel rod was significantly larger than that of the titanium rod. There were no significant differences in CT value of 16-bit image and dose distribution in radiotherapy plan between three scanning conditions with different tube currents. Under three scanning conditions with different tube voltages, the maximum CT values were 13568, 13127, and 12295 HU for the stainless steel rod and 8420, 7140, and 6310 HU for the titanium rod, respectively. Conclusions High-density metal implants cannot be distinguished by 12-bit images, while the distribution of metal CT value can be obtained by 16-bit images. The dose distribution of metal implants based on 12-bit images is different from that based on 16-bit images. Changes in tube voltage cause substantial changes in the CT value for metal implants, leading to changes in dose distribution in radiotherapy. Variation of tube current within a certain range causes slight changes in metal CT value and dose distribution. Key words: Metallic implants; Tomography; X-ray computed; Scanning condition; Radiotherapy dose distribution

Nanodosimetry-Based Plan Optimization for Particle Therapy

Treatment planning for particle therapy is currently an active field of research due uncertainty in how to modify physical dose in order to create a uniform biological dose response in the target. A novel treatment plan optimization strategy based on measurable nanodosimetric quantities rather than biophysical models is proposed in this work. Simplified proton and carbon treatment plans were simulated in a water phantom to investigate the optimization feasibility. Track structures of the mixed radiation field produced at different depths in the target volume were simulated with Geant4-DNA and nanodosimetric descriptors were calculated. The fluences of the treatment field pencil beams were optimized in order to create a mixed field with equal nanodosimetric descriptors at each of the multiple positions in spread-out particle Bragg peaks. For both proton and carbon ion plans, a uniform spatial distribution of nanodosimetric descriptors could be obtained by optimizing opposing-field but not single-field plans. The results obtained indicate that uniform nanodosimetrically weighted plans, which may also be radiobiologically uniform, can be obtained with this approach. Future investigations need to demonstrate that this approach is also feasible for more complicated beam arrangements and that it leads to biologically uniform response in tumor cells and tissues.

SU-E-T-218: Investigating the Differences in Out-Of-Field Dose Between An Inherently Uniform Beam and a Flattening Filter Free Beam Made Uniform Through Inverse Modulation

Purpose: To characterize with physical measurements the out-of-field dose for flattening filter free (FFF) and IMRT flattened FFF photon beams less than 10 MV from a Siemens Artiste LINAC, field size dependence, thereof, and comparison with the Pinnacle planning system calculation. Methods: Single field plans were developed for 5×5cm^2 and 20×20cm^2 field sizes for 6MV and 7MV-FFF. An additional 7MV-FFF plan was developed for each field size with the purpose of delivering a uniform dose (7MV-FFFUniform), similar to 6MV, utilizing inverse modulation. The calculated and measured dose was normalized to achieve equivalence at 10cm depth in water. Out-of-field dose measurements were acquired with a farmer-type ionization chamber in solid water at incremental distances up to 90cm from the field edge at physical depths of 1.5cm and 5.0cm. The dose contribution from head leakage was determined by closing the jaws symmetrically and the MLC off-axis Results: Data collected show that the out-of-field dose for 6MV is generally greater than 7MV-FFF and 7MV-FFF-Uniform. The 7MV-FFF-Uniform dose is less than 7MV-FFF for the small field size, but similar for the larger field and may be attributed to the small IMRT segments of the 5x5 field developing narrow beam geometry with reduced scatter. The out-of-field dose from 7MV-FFF-Uniform for the 20×20 field was greater than 6MV and 7MV-FFF beyond 50cm from the field edge. Head leakage from the 7MV-FFF-Uniform segmental MU modulation was greater than the un-modulated beams. The calculated out-of-field dose was consistently −200% different than measured for a subset of points considered. Conclusion: The modulation required to deliver a uniform large field dose with 7MV-FFF will increase the peripheral dose to the patient in comparison to already physically flattened fields; however, the dose near the field edge will be reduced. If reliable out-of-field doses are needed physical measurements should be used.

SU-E-T-184: Feasibility of Superabsorbent Polymers as a Buildup Material

Purpose: To investigate the feasibility of superabsorbent polymers as a buildup material for radiation therapy Methods: A standard bolus, a layered damp towel, and a superabsorbent polymer (SAP) phantom were created and scanned to compare the Hounsfield units of each buildup material. A single field plan was developed on Eclipse TPS with AAA dose calculation algorithm to examine dose buildup. Relative film dosimetery (EBT3) was performed to evaluate the surface dose with each buildup material. Each buildup material had an approximate thickness of 0.5 cm and 100 monitor units with 6MV were delivered with solid water placed underneath film to simulate backscatter and more realistic surface dose. Results: The average HU units of the bolus, wet towel, and SAP phantom were 75 (SD=3), -378 (SD=113), -198 (SD=45) respectively. AAA dose calculation demonstrated sufficient dose buildup in all three materials. The relative surfaces doses to film were 23.7% without buildup, 87.5% with 0.5 cm bolus, 92.4% for the SAP phantom, and 87.1% for the damp towel. Conclusion: We demonstrate that superabsorbent polymers can provide sufficient dose buildup. Furthermore, due to the form in which SAPs are traditionally manufactured, this material is less expensive conforms more easily to irregular surfaces than standard sheets of bolus. Also, as a substance which is designed to absorb and retain water efficiently, SAPs are much more comfortable and more consistent than damp towels.

Modality comparison for small animal radiotherapy: A simulation study

Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. This paper presents a comparison of dose distributions generated by the three approaches-a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.

SU-E-T-49: Verification of the Monte Carlo Model in the BrainLAB IPlan System for Clinical Applications

Purpose: To verify the Monte Carlo (MC) model in the BrainLab iPlan treatment planning system (TPS) in homogeneous and inhomogeneous media for clinical applications and to evaluate the BL Imaging Couch Top (BICT) in the TPS. Methods: One 30×30×12 cm3 solid water phantom and one 30×30×18 cm3 inhomogeneous phantom made of solid water and cork board were CT scanned and the images were transferred to the iPlan TPS. Single field plans (from 2×2 to 15×15 cm2) were calculated on the two phantoms for AP, PA and oblique gantry angles. An IMRT and a dynamic arc plans were also calculated. Each plan was calculated using both the Pencil Beam Convolution (PBC) and the MC models and with insertion of the BICT. All plans were delivered at the Novalis TX and the isocenter doses were measured using the A‐14 ion chamber.Results: For the homogeneous phantom, planned doses from the PBC and the MC models agree within 2% and all the planned doses agree with the measured doseswithin 2%. For the inhomogeneous phantom, the planned doses from the PBC and the MC models differ from 1.6% to 4.8% depending on the field sizes. The measurements agree with the MC plans within 1.2%. The differences between the measurements and the PBC plans vary from −1.3% to −4.0%. With the BICT included in the plans, the measured doses for the single PA fields differ with the MC planned doses from 0.5% to 3.7%. However, for the six‐beam IMRT and the six‐dynamic arc plans, the measured total doses agree with the planned doses with in 2%. Conclusions: This work verified that the MC model in the BrainLab iPlan TPS is ready for clinical applications in both homogeneous and inhomogeneous media. The couch model in the TPS was evaluated and is acceptable.

Dose calculation accuracy using cone-beam CT (CBCT) for pelvic adaptive radiotherapy

This study is to evaluate the dose calculation accuracy using Varian's cone-beam CT (CBCT) for pelvic adaptive radiotherapy. We first calibrated the Hounsfield Unit (HU) to electron density (ED) for CBCT using a mini CT QC phantom embedded into an IMRT QA phantom. We then used a Catphan 500 with an annulus around it to check the calibration. The combined CT QC and IMRT phantom provided correct HU calibration, but not Catphan with an annulus. For the latter, not only was the Teflon an incorrect substitute for bone, but the inserts were also too small to provide correct HUs for air and bone. For the former, three different scan ranges (6 cm, 12 cm and 20.8 cm) were used to investigate the HU dependence on the amount of scatter. To evaluate the dose calculation accuracy, CBCT and plan-CT for a pelvic phantom were acquired and registered. The single field plan, 3D conformal and IMRT plans were created on both CT sets. Without inhomogeneity correction, the two CT generated nearly the same plan. With inhomogeneity correction, the dosimetric difference between the two CT was mainly from the HU calibration difference. The dosimetric difference for 6 MV was found to be the largest for the single lateral field plan (maximum 6.7%), less for the 3D conformal plan (maximum 3.3%) and the least for the IMRT plan (maximum 2.5%). Differences for 18 MV were generally 1–2% less. For a single lateral field, calibration with 20.8 cm achieved the minimum dosimetric difference. For 3D and IMRT plans, calibration with a 12 cm range resulted in better accuracy. Because Catphan is the standard QA phantom for the on-board imager (OBI) device, we specifically recommend not using it for the HU calibration of CBCT.

A dosimetric comparison of different treatment plans of palliative spinal bone irradiation: analysis of dose coverage with respect to ICRU 50 report

BackgroundThis study aimed to analyze three-dimensional (3D) dosimetric data of conventional two-dimensional (2D) palliative spinal bone irradiation using different reference points and treatment plans with respect to the International Commission on Radiation Units and Measurements (ICRU) Report 50.MethodsForty-five simulation CT scans of 39 patients previously treated for thoraco-lumbar spinal bone metastases were used. Three different treatment plans were created: (1) single posterior field plans using the ICRU reference points (ICRUrps); (2) single posterior field plans using the International Bone Metastasis Consensus Working Party reference points (IBMCrps); (3) two opposed anterior-posterior (AP-PA) field plans using the ICRUrps. The intended dose range for planning target volume (PTV) was 90% to 110% of the prescribed dose for AP-PA field plans. Cumulative dose-volume histograms were generated for each plan, and minimum, maximum and mean doses to the PTV, medulla spinalis, esophagus and intestines were analyzed.ResultsThe mean percentages of minimum, maximum and mean PTV doses ± standard deviation were, respectively, 91 ± 1.3%, 108.8 ± 1.3% and 99.7 ± 1.3% in AP-PA field plans; 77.3 ± 2.6%, 122.2 ± 4.3% and 99.8 ± 2.6% in ICRUrp single field plans; and 83.7 ± 3.3%, 133.9 ± 7.1% and 108.8 ± 3.3% in IBMCrp single field plans. Minimum doses of both single field plans were significantly lower (p < 0.001) while maximum doses were significantly higher (p < 0.001) than AP-PA field plans. Minimum, maximum and mean doses were higher in IBMCrp single field plans than in ICRUrp single field plans (p < 0.001). The mean medulla spinalis doses were lower in AP-PA field plans than single posterior field plans (p < 0.001). Maximum doses for medulla spinalis were higher than 120% of the prescribed dose in 22 of 45 (49%) IBMCrp single field plans. Mean esophagus and intestinal doses were higher (p < 0.001) in AP-PA field plans than single field plans, however, less than 95% of the prescribed dose.ConclusionIn palliative spinal bone irradiation, 2D conventional single posterior field radiotherapy did not accomplish the ICRU Report 50 recommendations for PTV dose distribution, while the AP-PA field plans did achieve the intended dose ranges with a homogenous distribution and reasonable doses to the medulla spinalis, esophagus and intestines.

Significance and implementation of RBE variations in proton beam therapy.

Key to radiation therapy is to apply a high tumor-destroying dose while protecting healthy tissue, especially near organs at risk. To optimize treatment for ion therapy not the dose but the dose multiplied by the relative biological effectiveness (RBE) is decisive. Proton therapy has been based on the use of a generic RBE, which is applied to all treatments independent of dose/fraction, position in the spread-out Bragg peak (SOBP), initial beam energy or the particular tissue. Dependencies of the RBE on various physical and biological properties are disregarded. The variability of RBE in clinical situations is believed to be within 10-20%. This is in the same range of effects that receive high attention these days, i.e., patient set-up uncertainties, organ motion effects, and dose calculation accuracy all affecting proton as well as conventional radiation therapy. Elevated RBE values can be expected near the edges of the target, thus probably near critical structures. This is because the edges show lower doses and, depending on the treatment plan, may be identical with the beam's distal edge, where dose is deposited in part by high-LET protons. We assess the rationale for the continued use of a generic RBE and whether the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBE's. Two aspects have to be considered. Firstly, the available information from experimental studies and secondly, our ability to calculate RBE values for a given treatment plan based on parameters extracted from such experiments. We analyzed published RBE values for in vitro and in vivo endpoints. The values for cell survival in vitro indicate a substantial spread between the diverse cell lines. The average value at mid SOBP over all dose levels is approximately 1.2 in vitro and approximately 1.1 in vivo. Both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. The experimental in vivo data indicate that continued employment of a generic RBE value of 1.1 is reasonable. At present, there seems to be too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, etc. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in animal systems, especially as a function of dose in the range of 1-4 Gy. However, there is a measurable increase in RBE over the terminal few mm of the SOBP, which results in an extension of the bio-effective range of the beam of a few mm. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. To assess our ability to calculate RBE values we studied two approaches, which are both based on the track structure theory of radiation action. RBE calculations are difficult since both the physical input parameters, i.e., LET distributions, and, even more so, the biological input parameters, i.e., local cellular response, have to be known with high accuracy. Track structure theory provides a basis for predicting dose-response curves for particle irradiation. However, designed for heavy ion applications the models show weaknesses in the prediction of proton radiation effects. We conclude that, at present, RBE modeling in treatment planning involves significant uncertainties. To incorporate RBE variations in treatment planning there has to be a reliable biological model to calculate RBE values based on the physical characteristics of the radiation field and based on well-known biological input parameters. In order to do detailed model calculations more experimental data, in particular for in vivo endpoints, are needed

Relative biological effectiveness (RBE) values for proton beam therapy

Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs. As substantial clinical experience and additional experimental determinations of RBE have accumulated and the number of proton radiation therapy centers is projected to increase, it is appropriate to reassess the rationale for the continued use of a generic RBE and for that RBE to be 1.0–1.1.Methods and Materials: Results of experimental determinations of RBE of in vitro and in vivo systems are examined, and then several of the considerations critical to a decision to move from a generic to tissue-, dose/fraction-, and LET-specific RBE values are assessed. The impact of an error in the value assigned to RBE on normal tissue complication probability (NTCP) is discussed. The incidence of major morbidity in proton-treated patients at Massachusetts General Hospital (MGH) for malignant tumors of the skull base and of the prostate is reviewed. This is followed by an analysis of the magnitude of the experimental effort to exclude an error in RBE of ≥10% using in vivo systems.Results: The published RBE values, using colony formation as the measure of cell survival, from in vitro studies indicate a substantial spread between the diverse cell lines. The average value at mid SOBP (Spread Out Bragg Peak) over all dose levels is ≈1.2, ranging from 0.9 to 2.1. The average RBE value at mid SOBP in vivo is ≈1.1, ranging from 0.7 to 1.6. Overall, both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. There is agreement that there is a measurable increase in RBE over the terminal few millimeters of the SOBP, which results in an extension of the bioeffective range of the beam in the range of 1–2 mm. There is no published report to indicate that the RBE of 1.1 is low. However, a substantial proportion of patients treated at ≈2 cobalt Gray equivalent (CGE)/fraction 5 or more years ago were treated by a combination of both proton and photon beams. Were the RBE to be erroneously underestimated by ≈10%, the increase in complication frequency would be quite serious were the complication incidence for the reference treatment ≥3% and the slope of the dose response curves steep, e.g., a γ50 ≈ 4. To exclude ≥1.2 as the correct RBE for a specific condition or tissue at the 95% confidence limit would require relatively large and multiple assays.Conclusions: At present, there is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc. The experimental in vivo and clinical data indicate that continued employment of a generic RBE value and for that value to be 1.1 is reasonable. However, there is a local “hot region” over the terminal few millimeters of the SOBP and an extension of the biologically effective range. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in laboratory animal systems, especially as a function of dose/fraction in the range of 1–4 Gy.