The elimination of an artifact in the FLURZnrc-derived electron-fluence spectrum close to the Spencer-Attix-Nahum cut-offΔ.

Objective. An artifact in the electron fluence, differential in energy,ΦE, computed by the EGSnrc Monte-Carlo user-code FLURZnrc, was identified and a methodology has been developed to eliminate it. This artifact manifests itself as an 'unphysical' increase inΦEat energies close to the production threshold for knock-on electrons,AE; this in turn causes an over-estimation of the Spencer-Attix-Nahum (SAN) 'track-end' dose by a factor ∼1.5, thereby inflating the dose derived from the SAN cavity integral. For SAN cut-offΔSAN =1 keV for 1 MeV and 10 MeV photons in water, aluminium and copper, withmaximum fractional energy loss per step ESTEPE= 0.25 (default value), this anomalous increase in the SAN cavity-integral dose is of the order of 0.5%-0.7%.Approach. The dependence ofΦEon the value ofAE(the maximum energy loss involved in the restricted electronic stopping power (dE/ds)AE) at or close toΔSANwas investigated; this was done for different values ofESTEPE.Main results.The error in the electron-fluence spectrum occurs whenΔSANis setclose toorequal to AE; this error disappears (at the 0.1% level or better) ifAEis set ≤ 0.5 ×ΔSAN. However, ifESTEPE≤ 0.04 the error in the electron-fluence spectrum is negligible even whenΔSAN=AE.Significance. An artifact in the FLURZnrc-derived electron fluence, differential in energy, at or close to electron energyAEhas been identified. It is shown how this artifact can be avoided, thereby ensuring the accurate evaluation of the SAN cavity integral.

The use and QA of biologically related models for treatment planning: short report of the TG-166 of the therapy physics committee of the AAPM.

Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS.

Analysis of tumour dose-response data from animal experiments via two TCP models accounting for tumor hypoxia and resensitization.

To treat animal dose-response data exhibiting inverse dose-response behavior with two tumor control probability (TCP) models accounting for tumor hypoxia and re-oxygenation leading to resensitization of the tumor. One of the tested TCP models uses a modified linear-quadratic (LQ) model of cell survival where both α and ß radiosensitivities increase in time during the treatment due to re-oxygenation of the hypoxic tumor sub-population. The other TCP model deals with two types of hypoxia-chronic and acute-and accounts for tumor re-sensitization via oxygenation of the chronically hypoxic and fluctuating oxygenation of the acutely hypoxic sub-populations. The two models are fit using the maximum likelihood method to the data of Fowler et al. on mice mammary tumors irradiated to different doses using different fractionated schedules. These data are chosen since as many as five of the dose-response curves show an inverse dose behavior, which is interpreted as due to re-sensitization. The p-values of the fits of both models to the data render them statistically acceptable. A performed comparison test shows that both models describe the data equally well. It is also demonstrated that the most sensitive (oxic) tumor component has no impact on the treatment outcome. The ability of the tested models to predict and describe the impact of re-sensitization on the treatment outcome is thus proven. It is also demonstrated that prolonged treatment schedules can be more beneficial than shorter ones. However, this may be true only for schedules with small number of fractions, i.e. for hypo-fractionated treatments only.

The Impact of Different Timing Schedules on Prostate HDR-Mono-Brachytherapy. A TCP Modeling Investigation.

BACKGROUND: Mechanistic TCP (tumor control probability) models exist that account for possible re-sensitization of an initially hypoxic tumor during treatment. This phenomenon potentially explains the better outcome of a 28-day vs 14-day treatment schedule of HDR (high dose rate) brachytherapy of low- to intermediate-risk prostate cancer as recently reported. METHODS: A TCP model accounting for tumor re-sensitization developed earlier is used to analyze the reported clinical data. In order to analyze clinical data using individual TCP model, TCP distributions are constructed assuming inter-individual spread in radio-sensitivity. RESULTS: Population radio-sensitivity parameter values are found that result in TCP population values which are close to the reported ones. Using the estimated population parameters, two hypothetical regimens are investigated that are shorter than the ones used clinically. The impact of the re-sensitization rate on the calculated treatment outcome is also investigated as is the anti-hypothesis that there is no re-sensitization during treatment. CONCLUSIONS: The carried out investigation shows that the observed clinical data cannot be described without assuming an initially hypoxic state of the tumor followed by re-oxygenation and, hence, re-sensitization. This phenomenon explains the better outcome of the prolonged treatment schedule compared to shorter regimens based on the fact that prostate cancer is a slowly repopulating tumor.

Analysis of a cohort of prostate patients treated with HDR mono-brachytherapy.

The aim of this study is to perform volumetric and basic radiobiological analyses using the database on prostate patients treated by HDR brachytherapy in our institution during the period 2011-2016. Real-time ultrasound based technique was used, with Oncentra Prostate planning software. The whole period was divided into two sub-periods, according to the 100% dose per fraction, which was 10.5 Gy during the first period (2011-2012), and 11 Gy during the second period (2013-2016), for each of the three fractions. The follow up time varied from 19 to 81 months, with a median of 45 months and a mean of 47 months. The uniformity of the treatment technique for both periods is investigated. Tumour Control Probability (TCP) values for the expected local control are calculated according to a population phenomenological TCP model for different values of the α/ß ratio. The calculations are based on the obtained averaged Dose Volume Histograms for the two investigated sub-periods. 74 patients were treated in total. Local control failure is observed in 5 cases, which corresponds to an observed TCP = 93.2%. The comparison of the calculated population average DVH with the DVHs of the cases with local control failure shows that in 4 of them, doses higher than average were delivered to the prostate. It is shown that the uniformity of the treatment was improved during the second sub-period. A possible explanation of the observed failures may be that these cases exhibit inherent tumour cell radio-resistance higher than average. Our radiobiological analysis indicates a α/ß ratio value somewhat higher than the one currently accepted. The value of the prostate α/ß ratio is estimated to be in the range of [3.5-6] Gy.

Theoretical investigation of the impact of different timing schemes in hypofractionated radiotherapy.

PURPOSE: This study compares the effectiveness of three fractionation schemes of equal fraction size, comprising five fractions of SBRT over 5 days, 10 days, or 15 days, respectively. METHOD: This comparative study is based on two tumor-control-probability (TCP) models that take into account tumor cell re-sensitization and repopulation during treatment; the Zaider-Minerbo-Stavreva (ZMS) and the Ruggieri-Nahum (RN) models. The ZMS model is further modified to include also re-sensitization according to the ß mechanism of the linear-quadratic (LQ) model of cell killing. The modified version of the ZMS model is verified through fitting to the experimental data set of Fisher and Moulder. The study applies an idea used in a plan ranking methodology developed for the case when the specific values of the model parameters are not known. RESULTS: The TCPs of the compared regimens are calculated for various values of the model parameters and for two different values of the dose per fraction. The TCPs are presented as 2-D functions of two of the model parameters for each model correspondingly. The differences between the TCPs of each of the prolonged regimens and the TCP of the every week day regimen are also calculated for each model. CONCLUSIONS: Both models predict that the prolonged regimens are superior in terms of TCP to the every week-day one for most of the studied cases; however this is shown to exist to a different degree by the two models. It is shown again to a different degree that reversed situations where the every week day schedule is better than the prolonged regimens are also possible. It is concluded that a 30% TCP difference observed in a clinical study in favor of the fifteen-day regimen is theoretically possible. However, the fifteen-day regimen is outperformed in terms of TCP by the every week day regimen in more cases than the regimen lasting ten days. Therefore the choice of a prolongation in time must be made with care.

Tumor Control Probability Modeling and Systematic Review of the Literature of Stereotactic Body Radiation Therapy for Prostate Cancer.

PURPOSE: Dose escalation improves localized prostate cancer disease control, and moderately hypofractionated external beam radiation is noninferior to conventional fractionation. The evolving treatment approach of ultrahypofractionation with stereotactic body radiation therapy (SBRT) allows possible further biological dose escalation (biologically equivalent dose [BED]) and shortened treatment time. METHODS AND MATERIALS: The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiation Therapy/SBRT included a subgroup to study the prostate tumor control probability (TCP) with SBRT. We performed a systematic review of the available literature and created a dose-response TCP model for the endpoint of freedom from biochemical relapse. Results were stratified by prostate cancer risk group. RESULTS: Twenty-five published cohorts were identified for inclusion, with a total of 4821 patients (2235 with low-risk, 1894 with intermediate-risk, and 446 with high-risk disease, when reported) treated with a variety of dose/fractionation schemes, permitting dose-response modeling. Five studies had a median follow-up of more than 5 years. Dosing regimens ranged from 32 to 50 Gy in 4 to 5 fractions, with total BED (α/ß = 1.5 Gy) between 183.1 and 383.3 Gy. At 5 years, we found that in patients with low-intermediate risk disease, an equivalent doses of 2 Gy per fraction (EQD2) of 71 Gy (31.7 Gy in 5 fractions) achieved a TCP of 90% and an EQD2 of 90 Gy (36.1 Gy in 5 fractions) achieved a TCP of 95%. In patients with high-risk disease, an EQD2 of 97 Gy (37.6 Gy in 5 fractions) can achieve a TCP of 90% and an EQD2 of 102 Gy (38.7 Gy in 5 fractions) can achieve a TCP of 95%. CONCLUSIONS: We found significant variation in the published literature on target delineation, margins used, dose/fractionation, and treatment schedule. Despite this variation, TCP was excellent. Most prescription doses range from 35 to 40 Gy, delivered in 4 to 5 fractions. The literature did not provide detailed dose-volume data, and our dosimetric analysis was constrained to prescription doses. There are many areas in need of continued research as SBRT continues to evolve as a treatment modality for prostate cancer, including the durability of local control with longer follow-up across risk groups, the efficacy and safety of SBRT as a boost to intensity modulated radiation therapy (IMRT), and the impact of incorporating novel imaging techniques into treatment planning.

Dosimetric verification of IMAT delivery with a conventional EPID system and a commercial portal dose image prediction tool.

PURPOSE: The electronic portal imaging device (EPID) is a system for checking the patient setup; as a result of its integration with the linear accelerator and software customized for dosimetry, it is increasingly used for verification of the delivery of fixed-field intensity-modulated radiation therapy (IMRT). In order to extend such an approach to intensity-modulated arc therapy (IMAT), the combined use of an EPID system and a portal dose image prediction (PDIP) tool has been investigated. METHODS: The dosimetric behavior of an EPID system, mechanically reinforced to maintain its positional stability during the accelerator gantry rotation, has been studied to assess its ability to measure portal dose distributions for IMAT treatment beams. In addition, the PDIP tool of a commercial treatment planning system, commonly used for static IMRT dosimetry, has been validated for simulating the PDIs of IMAT treatment fields. The method has been applied to the delivery verification of 23 treatment fields that were measured in their dual mode of IMRT and IMAT modalities. RESULTS: The EPID system has proved to be appropriate for measuring the PDIs of IMAT fields; additionally the PDIP tool was able to simulate these accurately. The results are quite similar to those obtained for static IMRT treatment verification, although it was necessary to investigate the dependence of the EPID signal and of the accelerator monitor chamber response on variable dose rate. CONCLUSIONS: Our initial tests indicate that the EPID system, together with the PDIP tool, is a suitable device for the verification of IMAT plan delivery; however, additional tests are necessary to confirm these results.

Severe hypofractionation: non-homogeneous tumour dose delivery can counteract tumour hypoxia.

BACKGROUND: The current rationale for severely hypofractionated schedules (3-5 fractions) used in stereotactic-body-radiotherapy (SBRT) of non-small-cell lung cancer (NSCLC) is the small size of the irradiated volumes. Being the dose prescribed to the 60-80% isodose line enclosing the PTV, a non-homogeneous tumour-dose-delivery results which might impact on tumour hypoxia. A comparison between homogeneous and SBRT-like non-homogeneous tumour-dose-delivery is then proposed here, using severe hypofractionation on large tumour volumes where both dose prescription strategies are applicable. MATERIALS AND METHODS: For iso-NTCP hypofractionated schedules (1f/d*5d/w) with respect to standard fractionation (d=2Gy), computed from the individual DVHs for lungs, oesophagus, heart and spinal cord (Lyman-Kutcher-Burman NTCP-model), TCP values were calculated (α-averaged Poissonian-LQ model) for homogeneous and SBRT-like non-homogeneous plans both with and without tumour hypoxia. Two different estimates of the oxygen-enhancement-ratio (OER) in combination with two distinct assumptions on the kinetics of reoxygenation were considered. Homogeneous and SBRT-like non-homogeneous plans were finally compared in terms of therapeutic ratio (TR), as the product of TCP and the four (1-NTCP(i)) values. RESULTS: For severe hypofractionation (3-5 fractions) and for any of the hypotheses on the kinetics of reoxygenation and the OER, there was a significant difference between the computed TRs with or without inclusion of tumour hypoxia (anova, p=0.01) for homogeneous tumour-dose-delivery, but no significant difference for the SBRT-like non-homogeneous one. Further, a significantly increased mean TR for the group of SBRT-like non-homogeneous plans resulted (t-test, p=0.05) with respect to the group with homogeneous target-dose-coverage. CONCLUSIONS: SBRT-like dose-boosting seems to counterbalance the loss of reoxygenation within a few fractions. For SBRT it then seems that, in addition to the high level of dose-sparing to the adjacent normal tissues, when severe hypofractionation is adopted it is probably the intrinsic ability of stereotactic techniques to perform intra-tumour simultaneous dose-boosting which yields the reported high clinical efficacy.

Monte-Carlo-computed dose, kerma and fluence distributions in heterogeneous slab geometries irradiated by small megavoltage photon fields.

Small-field dosimetry is central to the planning and delivery of radiotherapy to patients with cancer. Small-field dosimetry is beset by complex issues, such as loss of charged-particle equilibrium (CPE), source occlusion and electron-scattering effects in low-density tissues. The purpose of the present research is the elucidation of the fundamental physics of small fields through the computation of absorbed dose, kerma and fluence distributions in heterogeneous media using the Monte-Carlo (MC) method. Absorbed dose and kerma were computed using the DOSRZnrc MC user-code for beams with square field sizes ranging from 0.25 × 0.25 to 7 × 7 cm2 (for 6 MV 'full linac' geometry) and 0.25 × 0.25 to 16 × 16 cm2 (for 15 MV 'full linac' geometry). In the bone inhomogeneity the dose increases (vs. homogeneous water) for field sizes <1 × 1 cm2 at 6 MV and ⩽3 × 3 cm2 at 15 MV and decreases (vs. homogeneous water) for field sizes ⩾3 × 3 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV. In the lung inhomogeneity there is negligible decrease in dose compared to in uniform water for field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV, consistent with the Fano theorem. The near-unity value of the absorbed-dose to collision-kerma ratio, D/K col, at the centre of the bone and lung slabs in the heterogeneous phantom demonstrates that CPE is achieved in bone for field sizes >1 × 1 cm2 at 6 MV and ⩾5 × 5 cm2 at 15 MV; CPE is achieved in lung at field sizes >5 × 5 cm2 at 6 MV and ⩾16 × 16 cm2 at 15 MV. Electron-fluence perturbation factors for the 0.25 × 0.25 cm2 field were 1.231 and 1.403 for bone-to-water and 0.454 and 0.333 for lung-to-water at 6 and 15 MV, respectively. For field sizes large enough for quasi-CPE, the MC-derived dose-perturbation factors, lung-to-water, [Formula: see text] were close to unity; electron-fluence perturbation factors, lung-to-water, [Formula: see text] were ∼1.0, consistent with the Fano theorem. At 15 MV in the lung inhomogeneity the magnitude and also the 'shape' of the primary electron-fluence spectrum differ significantly from that in water. Beam penumbrae relative to water are narrower in the bone inhomogeneity and broader in the lung inhomogeneity for all field sizes.

Monte Carlo modeling of small photon fields: quantifying the impact of focal spot size on source occlusion and output factors, and exploring miniphantom design for small-field measurements.

The accuracy with which Monte Carlo models of photon beams generated by linear accelerators (linacs) can describe small-field dose distributions depends on the modeled width of the electron beam profile incident on the linac target. It is known that the electron focal spot width affects penumbra and cross-field profiles; here, the authors explore the extent to which source occlusion reduces linac output for smaller fields and larger spot sizes. A BEAMnrc Monte Carlo linac model has been used to investigate the variation in penumbra widths and small-field output factors with electron spot size. A formalism is developed separating head scatter factors into source occlusion and flattening filter factors. Differences between head scatter factors defined in terms of in-air energy fluence, collision kerma, and terma are explored using Monte Carlo calculations. Estimates of changes in kerma-based source occlusion and flattening filter factors with field size and focal spot width are obtained by calculating doses deposited in a narrow 2 mm wide virtual "milliphantom" geometry. The impact of focal spot size on phantom scatter is also explored. Modeled electron spot sizes of 0.4-0.7 mm FWHM generate acceptable matches to measured penumbra widths. However the 0.5 cm field output factor is quite sensitive to electron spot width, the measured output only being matched by calculations for a 0.7 mm spot width. Because the spectra of the unscattered primary (psi(pi)) and head-scattered (psi(sigma)) photon energy fluences differ, miniphantom-based collision kerma measurements do not scale precisely with total in-air energy fluence psi = (psi(pi) + psi(sigma) but with (psi(pi)+ 1.2psi(sigma)). For most field sizes, on-axis collision kerma is independent of the focal spot size; but for a 0.5 cm field size and 1.0 mm spot width, it is reduced by around 7% mostly due to source occlusion. The phantom scatter factor of the 0.5 cm field also shows some spot size dependence, decreasing by 6% (relative) as spot size is increased from 0.1 to 1.0 mm. The dependence of small-field source occlusion and output factors on the focal spot size makes this a significant factor in Monte Carlo modeling of small (< 1 cm) fields. Changes in penumbra width with spot size are not sufficiently large to accurately pinpoint spot widths. Consequently, while Monte Carlo models based exclusively on large-field data can quite accurately predict small-field profiles and PDDs, in the absence of experimental methods of determining incident electron beam profiles it will remain necessary to measure small-field output factors, fine-tuning modeled spot sizes to ensure good matching between the Monte Carlo and the measured output factors.

Early mucosal reactions during and after head-and-neck radiotherapy: dependence of treatment tolerance on radiation dose and schedule duration.

PURPOSE: To more precisely localize the dose-time boundary between head-and-neck radiotherapy schedules inducing tolerable and intolerable early mucosal reactions. METHODS AND MATERIALS: Total cell-kill biologically effective doses (BED(CK)) have been calculated for 84 schedules, including incomplete repair effects, but making no other corrections for the effect of schedule duration T. [BED(CK),T] scatterplots are graphed, overlying BED(CKboundary)(T) curves on the plots and using discriminant analysis to optimize BED(CKboundary)(T) to best represent the boundary between the tolerable and intolerable schedules. RESULTS: More overlap than expected is seen between the tolerable and intolerable treatments in the 84-schedule [BED(CK),T] scatterplot, but this was largely eliminated by removing gap and tolerated accelerating schedules from the plot. For the remaining 57 predominantly regular schedules, the BED(CKboundary)(T) boundary increases with increasing T (p = 0.0001), curving upwards significantly nonlinearly (p = 0.00007) and continuing to curve beyond 15 days (p = 0.035). The regular schedule BED(CKboundary)(T) boundary does not describe tolerability well for accelerating schedules (p = 0.002), with several tolerated accelerating schedules lying above the boundary where regular schedules would be intolerable. Gap schedule tolerability also is not adequately described by the regular schedule boundary (p = 0.04), although no systematic offset exists between the regular boundary and the overall gap schedule tolerability pattern. CONCLUSIONS: All schedules analyzed (regular, gap, and accelerating) with BED(CK) values below BED(CKboundary)(T)=69.5x(T/32.2)/sin((T/32.2)((radians)))-3.5Gy(10)(forT< or =50 days) are tolerable, and many lying above the boundary are intolerable. The accelerating schedules analyzed were tolerated better overall than are the regular schedules with similar [BED(CK),T] values.

Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours.

BACKGROUND AND PURPOSE: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. MATERIALS AND METHODS: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. RESULTS: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP=5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. CONCLUSIONS: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT.

Using a Monte Carlo model to predict dosimetric properties of small radiotherapy photon fields.

Accurate characterization of small-field dosimetry requires measurements to be made with precisely aligned specialized detectors and is thus time consuming and error prone. This work explores measurement differences between detectors by using a Monte Carlo model matched to large-field data to predict properties of smaller fields. Measurements made with a variety of detectors have been compared with calculated results to assess their validity and explore reasons for differences. Unshielded diodes are expected to produce some of the most useful data, as their small sensitive cross sections give good resolution whilst their energy dependence is shown to vary little with depth in a 15 MV linac beam. Their response is shown to be constant with field size over the range 1-10 cm, with a correction of 3% needed for a field size of 0.5 cm. BEAMnrc has been used to create a 15 MV beam model, matched to dosimetric data for square fields larger than 3 cm, and producing small-field profiles and percentage depth doses (PDDs) that agree well with unshielded diode data for field sizes down to 0.5 cm. For fields sizes of 1.5 cm and above, little detector-to-detector variation exists in measured output factors, however for a 0.5 cm field a relative spread of 18% is seen between output factors measured with different detectors-values measured with the diamond and pinpoint detectors lying below that of the unshielded diode, with the shielded diode value being higher. Relative to the corrected unshielded diode measurement, the Monte Carlo modeled output factor is 4.5% low, a discrepancy that is probably due to the focal spot fluence profile and source occlusion modeling. The large-field Monte Carlo model can, therefore, currently be used to predict small-field profiles and PDDs measured with an unshielded diode. However, determination of output factors for the smallest fields requires a more detailed model of focal spot fluence and source occlusion.

Origins of the changing detector response in small megavoltage photon radiation fields.

Differences in detector response between measured small fields, f clin, and wider reference fields, f msr , can be overcome by using correction factors [Formula: see text] or by designing detectors with field-size invariant responses. The changing response in small fields is caused by perturbations of the electron fluence within the detector sensitive volume. For solid-state detectors, it has recently been suggested that these perturbations might be caused by the non-water-equivalent effective atomic numbers Z of detector materials, rather than by their non-water-like densities. Using the EGSnrc Monte Carlo code we have analyzed the response of a PTW 60017 diode detector in a 6 MV beam, calculating the [Formula: see text] correction factor from computed doses absorbed by water and by the detector sensitive volume in 0.5 × 0.5 and 4 × 4 cm2 fields. In addition to the 'real' detector, fully modelled according to the manufacturer's blue-prints, we calculated doses and [Formula: see text] factors for a 'Z → water' detector variant in which mass stopping-powers and microscopic interaction coefficients were set to those of water while preserving real material densities, and for a 'density → 1' variant in which densities were set to 1 g cm-3, leaving mass stopping-powers and interaction coefficients at real levels. [Formula: see text] equalled 0.910 ± 0.005 (2 standard deviations) for the real detector, was insignificantly different at 0.912 ± 0.005 for the 'Z → H2O' variant, but equalled 1.012 ± 0.006 for the 'density → 1' variant. For the 60017 diode in a 6 MV beam, then, [Formula: see text] was determined primarily by the detector's density rather than its atomic composition. Further calculations showed this remained the case in a 15 MV beam. Interestingly, the sensitive volume electron fluence was perturbed more by detector atomic composition than by density; however, the density-dependent perturbation varied with field-size, whereas the Z-dependent perturbation was relatively constant, little affecting [Formula: see text].

IMAT-SIM: a new method for the clinical dosimetry of intensity-modulated arc therapy (IMAT).

Dynamic-gantry multi-leaf collimator (MLC)-based, intensity-modulated radiotherapy (IMAT) has been proposed as an alternative to tomotherapy. In contrast to fixed-gantry, MLC-based intensity-modulated radiotherapy (IMRT), where commercial treatment planning systems (TPS) or dosimetric analysis software currently provide many automatic tools enabling two-dimensional (2D) detectors (matrix or electronic portal imaging devices) to be used as measurement systems, for the planning and delivery of IMAT these tools are generally not available. A new dosimetric method is proposed to overcome some of these limitations. By converting the MLC files of IMAT beams from arc to fixed gantry-angle modality, while keeping the leaf trajectories equal, IMAT plans can be both simulated in the TPS and executed as fixed-gantry, sliding-window DMLC treatments. In support of this idea, measurements of six IMAT plans, in their double form of original arcs and converted fixed-gantry DMLC beams (IMAT-SIM), have been compared among themselves and with their corresponding IMAT-SIM TPS calculations. Radiographic films and a 2D matrix ionization chamber detector rigidly attached to the accelerator gantry and set into a cubic plastic phantom have been used for these measurements. Finally, the TPS calculation-algorithm implementations of both conformal dynamic MLC arc (CD-ARC) modalities, used for clinical IMAT calculations, and DMLC modalities (IMAT-SIM), proposed as references for validating IMAT plan dose-distributions, have been compared. The comparisons between IMAT and IMAT-SIM delivered beams have shown very good agreement with similar shapes of the measured dose profiles which can achieve a mean deviation (+/-2sigma) of (0.35+/-0.16) mm and (0.37+/-0.14)%, with maximum deviations of 1.5 mm and 3%. Matching the IMAT measurements with their corresponding IMAT-SIM data calculated by the TPS, these deviations remain in the range of (1.01+/-0.28) mm and (-1.76+/-0.42)%, with maximums of 3 mm and 5%, limits generally accepted for IMRT plan dose validation. Differences in the algorithm implementations have been found, but by correcting CD-ARC calculations for the leaf-end transmission offset (LTO) effect the IMAT and IMAT-SIM simulations agree well in terms of final dose distributions. The differences found between IMAT and the IMAT-SIM beam measurements are due to the different controls of leaf motion (via electron gun delay in the latter) that cannot be used in the former to correct possible speed variations in the rotation of the gantry. As the IMAT delivered beams are identical to what the patient will receive during the treatment, and the IMAT-SIM beam calculations made by the TPS reproduce exactly the treatment plans of that patient, the accuracy of this new dosimetric method is comparable to that which is currently used for static IMRT. This new approach of 2D-detector dosimetry, together with the commissioning, quality-assurance, and preclinical dosimetric procedures currently used for IMRT techniques, can be applied and extended to any kind of dynamic-gantry MLC-based treatment modality either CD-ARC or IMAT.

Optimal dose and fraction number in SBRT of lung tumours: A radiobiological analysis.

The efficacy of Stereotactic Body Radiation Therapy (SBRT) in early-stage non-small cell lung cancer for severely hypofractionated schedules is clinically proven. Tumour control probability (TCP) modelling might further optimize prescription dose and number of treatment fractions (n). To this end, we will discuss the following controversial questions. Which is the most plausible cell-survival model at doses per fraction (d) as high as 20Gy? Do clinical data support a dose-response relationship with saturation over some threshold-dose? Given the reduced re-oxygenation for severe hypofractionation, is the inclusion of tumour hypoxia in TCP modelling relevant? Can iso-effective schedules be derived by assuming a homogeneous tumour-cell population with α/ß≈10Gy, or should distinct cell subpopulations, with different α/ß values, be taken into account? Is there scope for patient-specific individualization of n? Despite the difficulty of providing definite answers to the above questions, reasonable suggestions for lung SBRT can be derived from the literature. The LQ model appears to be the best-fitting model of cell-survival even at such large d, and is therefore the preferred choice for TCP modelling. TCP increases with dose, reaching saturation above 90% local control, but there is still uncertainty on the threshold-dose. In silico simulations accounting for variations in tumour oxygenation are consistent with an improved therapeutic ratio at 5-8 fractions instead of the current 3-fraction reference schedules. Tumour hypoxia modelling might also explain how α/ß changes with n, identifying the clonogen subpopulation which determines tumour response. Finally, an optimal patient-specific n can be derived from the planned lung dose distribution.

The impact of hypofractionation on simultaneous dose-boosting to hypoxic tumor subvolumes.

In a previous study, the dependence of the therapeutic ratio on the number of fractions (n), including both acute and chronic hypoxia, was investigated for homogeneously irradiated tumors. The present study further develops the model to include simultaneous dose-boosting to the hypoxic tumour subvolumes. The acutely hypoxic (ah) tumor subvolume was partitioned into a large number (10(2)-10(3)) of oxygenation subvolumes, modelled through rectangular pO2(t) waves all with the same frequency and fractional time spent below the hypoxic threshold, but with randomly distributed phases. Three quite different assumptions were considered for the effect of prolonged hypoxia on the radiosensitivity (alpha) of the chronically hypoxic (ch) clonogens, ranging from equal radiosensitivity to that of the ah-cells to an even greater radiosensitivity than that of the well-oxygenated (ox) cells. The linear-quadratic model, including tumor repopulation, intertumor alpha-heterogeneity, and dependence of the oxygen enhancement ratio on the dose per fraction, was adopted for tumor control probability (TCP) computation. To include a consideration of therapeutic ratio, lung irradiation was considered and the mean normalized total lung dose (NTD(L)) was used as a risk indicator. For those 1(fr/d) x 5(d/w) schedules yielding 50% TCP with homogeneous irradiation (our reference benchmark), we estimated the gain in TCP and the corresponding NTD(L) from dose boosting only the ch-subvolume, both the ah- and the ch-subvolumes, or 50% of the pretreatment tumor volume without specific targeting to tumor hypoxia. For two of the three assumptions for the radiosensitivity of the ch-clonogens, dose-boosting the ch-subvolume was associated with a substantial gain in TCP, and with a trend including minima in NTD(L), for severely hypofractionated schedules only, whereas when dose-boosting both the ah- and the ch-subvolumes a substantial gain in TCP was always obtained for multifractionated schedules. By contrast, the "blind" dose-boosting strategy was generally inferior, although an appreciable gain in TCP for severely hypofractionated schedules was obtained. In conclusion, a strategy of dose-boosting tumor hypoxia, guided by nuclear medicine techniques that substantially map chronic hypoxia, is expected to yield optimal gains in TCP via severely hypofractionated delivery.

Secondary bremsstrahlung and the energy-conservation aspects of kerma in photon-irradiated media.

Kerma, collision kerma and absorbed dose in media irradiated by megavoltage photons are analysed with respect to energy conservation. The user-code DOSRZnrc was employed to compute absorbed dose D, kerma K and a special form of kerma, K ncpt, obtained by setting the charged-particle transport energy cut-off very high, thereby preventing the generation of 'secondary bremsstrahlung' along the charged-particle paths. The user-code FLURZnrc was employed to compute photon fluence, differential in energy, from which collision kerma, K col and K were derived. The ratios K/D, K ncpt/D and K col/D have thereby been determined over a very large volumes of water, aluminium and copper irradiated by broad, parallel beams of 0.1 to 25 MeV monoenergetic photons, and 6, 10 and 15 MV 'clinical' radiotherapy qualities. Concerning depth-dependence, the 'area under the kerma, K, curve' exceeded that under the dose curve, demonstrating that kerma does not conserve energy when computed over a large volume. This is due to the 'double counting' of the energy of the secondary bremsstrahlung photons, this energy being (implicitly) included in the kerma 'liberated' in the irradiated medium, at the same time as this secondary bremsstrahlung is included in the photon fluence which gives rise to kerma elsewhere in the medium. For 25 MeV photons this 'violation' amounts to 8.6%, 14.2% and 25.5% in large volumes of water, aluminium and copper respectively but only 0.6% for a 'clinical' 6 MV beam in water. By contrast, K col/D and K ncpt/D, also computed over very large phantoms of the same three media, for the same beam qualities, are equal to unity within (very low) statistical uncertainties, demonstrating that collision kerma and the special type of kerma, K ncpt, do conserve energy over a large volume. A comparison of photon fluence spectra for the 25 MeV beam at a depth of ≈51 g cm−2 for both very high and very low charged-particle transport cut-offs reveals the considerable contribution to the total photon fluence by secondary bremsstrahlung in the latter case. Finally, a correction to the 'kerma integral' has been formulated to account for the energy transferred to charged particles by photons with initial energies below the Monte-Carlo photon transport cut-off PCUT; for 25 MeV photons this 'photon track end' correction is negligible for all PCUT below 10 keV.