Prostate Dose-painting Radiotherapy and Radiobiological Guided Optimisation Enhances the Therapeutic Ratio.

AIMS: To describe the treatment of 11 patients with radiobiologically guided dose-painting radiotherapy and report on toxicity. MATERIALS AND METHODS: Boost volumes were identified with functional magnetic resonance imaging scans in 11 patients with high-risk prostate cancer. Patients were treated using a dose-painting approach; the boost dose was limited to 86 Gy in 37 fractions, while keeping the rectal normal tissue complication probability to 5-6%. Rotational intensity-modulated radiotherapy was used with daily image guidance and fiducial markers. RESULTS: The median dose to the prostate (outside the boost volume) and urethra was 75.4 Gy/37 fractions (range 75.1-75.8 Gy), whereas the median boost dose was 83.4 Gy (range 79.0-87.4 Gy). The tumour control probability (TCP) (Marsden model) increased from 71% for the standard plans to 83.6% [76.6-86.8%] for the dose-painting boost plans. The mean (Lyman-Kutcher-Burman) normal tissue complication probability for rectal bleeding was 5.2% (range 3.3-6.2%) and 5.2% for faecal incontinence (range 3.6-7.8%). All patients tolerated the treatment well, with a low acute toxicity profile. At a median follow-up of 36 months (range 24-50) there was no grade 3 late toxicity. Two patients had grade 2 late urinary toxicity (urethral stricture, urinary frequency and urgency), one patient had grade 1 and one grade 2 late rectal toxicity. The mean prostate-specific antigen at follow-up was 0.81 ng/ml after stopping hormone therapy; one patient relapsed biochemically at 32 months (2.70 ng/ml). CONCLUSIONS: The toxicity for this radiobiological guided dose-painting protocol was low, but we have only treated a small cohort with limited follow-up time. The advantages of this treatment approach should be established in a clinical trial.

Mechanistic modelling of radiotherapy-induced lung toxicity.

OBJECTIVE: This work explores the biological basis of a mechanistic model of radiation-induced lung damage; uniquely, the model makes a connection between the cellular radiobiology involved in lung irradiation and the full three-dimensional distribution of radiation dose. METHODS: Local tissue damage and loss of global organ function, in terms of radiation pneumonitis (RP), were modelled as different levels of radiation injury. Parameters relating to the former could be derived from the local dose-response function, and the latter from the volume effect of the organ. The literature was consulted to derive information on a threshold dose and volume-effect mechanisms. RESULTS: Simulations of local tissue damage supported the alveolus as a functional subunit (FSU) which can be regenerated from a single surviving stem cell. A moderate interpatient variation in stem cell radiosensitivity (15%) resulted in a great variation in tissue response between 8 and 20 Gy. The threshold of FSU inactivation within a critical functioning volume leading to RP was found to be approximately 47% and the degree of health status variation (influencing the volume effect) in a population was estimated at 25%. CONCLUSION: This work has shown that it is possible to make sense of the way the lung responds to radiation by modelling RP mechanistically, from cell death to tissue damage to loss of organ function. ADVANCES IN KNOWLEDGE: Simulations were able to provide parameter values, currently not available in the literature, related to the response of the lung to irradiation.

Radiobiologically guided optimisation of the prescription dose and fractionation scheme in radiotherapy using BioSuite.

OBJECTIVE: Radiobiological models provide a means of evaluating treatment plans. Keeping in mind their inherent limitations, they can also be used prospectively to design new treatment strategies which maximise therapeutic ratio. We propose here a new method to customise fractionation and prescription dose. METHODS: To illustrate our new approach, two non-small cell lung cancer treatment plans and one prostate plan from our archive are analysed using the in-house software tool BioSuite. BioSuite computes normal tissue complication probability and tumour control probability using various radiobiological models and can suggest radiobiologically optimal prescription doses and fractionation schemes with limited toxicity. RESULTS: Dose-response curves present varied aspects depending on the nature of each case. The optimisation process suggests doses and fractionation schemes differing from the original ones. Patterns of optimisation depend on the degree of conformality, the behaviour of the normal tissue (i.e. "serial" or "parallel"), the volume of the tumour and the parameters of clonogen proliferation. CONCLUSION: Individualising the prescription dose and number of fractions with the help of BioSuite results in improved therapeutic ratios as evaluated by radiobiological models.

An NTCP Analysis of Urethral Complications from Low Doserate Mono- and Bi-Radionuclide Brachytherapy.

Urethral NTCP has been determined for three prostates implanted with seeds based on (125)I (145 Gy), (103)Pd (125 Gy), (131)Cs (115 Gy), (103)Pd-(125)I (145 Gy), or (103)Pd-(131)Cs (115 Gy or 130 Gy). First, DU(20), meaning that 20% of the urhral volume receive a dose of at least DU(20), is converted into an I-125 LDR equivalent DU(20) in order to use the urethral NTCP model. Second, the propagation of uncertainties through the steps in the NTCP calculation was assessed in order to identify the parameters responsible for large data uncertainties. Two sets of radiobiological parameters were studied. The NTCP results all fall in the 19%-23% range and are associated with large uncertainties, making the comparison difficult. Depending on the dataset chosen, the ranking of NTCP values among the six seed implants studied changes. Moreover, the large uncertainties on the fitting parameters of the urethral NTCP model result in large uncertainty on the NTCP value. In conclusion, the use of NTCP model for permanent brachytherapy is feasible but it is essential that the uncertainties on the parameters in the model be reduced.

Escalation and intensification of radiotherapy for stage III non-small cell lung cancer: opportunities for treatment improvement.

In this overview we review and model how radiotherapy tumour control and complication rates vary with dose, fractionation, schedule duration, irradiated volume and use of chemotherapy for stage III non-small cell lung cancer (NSCLC), and use the modelling to study the effectiveness of different NSCLC dose-escalation approaches being developed in the UK. Data have been collated for pneumonitis, lung fibrosis, early and late oesophagitis, cord and cardiac complications, and local progression-free survival at 30 months. Dependences of the various end points on treatment-related factors are catalogued and analysed using the linear-quadratic incomplete repair model to account for dose and fractionation effects, making linear corrections for differences in schedule duration, and loosely characterising volume effects using parallel- and series-type concepts. Tolerance limits are calculated for the different end points and distilled into ranges of prescribed dose likely to be tolerable when delivered in 2.5 and 4 week radiation and 6 week chemoirradiation schedules using conformal techniques. Worthwhile ( approximately 20%) gains in 30 month local progression-free survival should be achievable at safely deliverable levels of dose escalation. The analysis suggests that longer schedules may be more beneficial than shorter ones, but this finding is governed by the relative rates of tumour and oesophageal accelerated proliferation, which are quite imprecisely known. Consequently escalated 2.5, 4 and 6 week schedules are being developed; each should lead to useful improvements in local control but it is not yet known which schedule will be most effective.

Addendum to the IPEMB code of practice for the determination of absorbed dose for x-rays below 300 kV generating potential (0.035 mm Al-4 mm Cu HVL).

This addendum to the code of practice for the determination of absorbed dose for x-rays below 300 kV has recently been approved by the IPEM and introduces three main changes: (i) Due to a lack of available data the original code recommended a value of unity for k(ch) in the very-low-energy range (0.035-1.0 mm Al HVL). A single table of k(ch) values, ranging from 1.01 to 1.07, applicable to both designated chamber types is now presented. (ii) For medium-energy x-rays (0.5-4 mm Cu HVL) methods are given to determine the absorbed dose to water either at 2 cm depth or at the surface of a phantom depending on clinical needs. Determination of the dose at the phantom surface is derived from an in-air measurement and by extending the low-energy range up to 4 mm Cu HVL. Relevant backscatter factors and ratios of mass energy absorption coefficients are given in the addendum. (iii) Relative dosimetry: although not normally forming part of a dosimetry code of practice a brief review of the current literature on this topic has been added as an appendix. This encompasses advice on techniques for measuring depth doses, applicator factors for small field sizes, dose fall off with increasing SSD and choice of appropriate phantom materials and ionization chambers.

The IPEM code of practice for electron dosimetry for radiotherapy beams of initial energy from 4 to 25 MeV based on an absorbed dose to water calibration.

This report contains the recommendations of the Electron Dosimetry Working Party of the UK Institute of Physics and Engineering in Medicine (IPEM). The recommendations consist of a code of practice for electron dosimetry for radiotherapy beams of initial energy from 4 to 25 MeV. The code is based on the absorbed dose to water calibration service for electron beams provided by the UK standards laboratory, the National Physical Laboratory (NPL). This supplies direct N(D,w) calibration factors, traceable to a calorimetric primary standard, at specified reference depths over a range of electron energies up to approximately 20 MeV. Electron beam quality is specified in terms of R(50,D), the depth in water along the beam central axis at which the dose is 50% of the maximum. The reference depth for any given beam at the NPL for chamber calibration and also for measurements for calibration of clinical beams is 0.6R(50.D) - 0.1 cm in water. Designated chambers are graphite-walled Farmer-type cylindrical chambers and the NACP- and Roos-type parallel-plate chambers. The practical code provides methods to determine the absorbed dose to water under reference conditions and also guidance on methods to transfer this dose to non-reference points and to other irradiation conditions. It also gives procedures and data for extending up to higher energies above the range where direct calibration factors are currently available. The practical procedures are supplemented by comprehensive appendices giving discussion of the background to the formalism and the sources and values of any data required. The electron dosimetry code improves consistency with the similar UK approach to megavoltage photon dosimetry, in use since 1990. It provides reduced uncertainties, approaching 1% standard uncertainty in optimal conditions, and a simpler formalism than previous air kerma calibration based recommendations for electron dosimetry.

Optimization of accelerator target and detector for portal imaging using Monte Carlo simulation and experiment.

Megavoltage portal images suffer from poor quality compared to those produced with kilovoltage x-rays. Several authors have shown that the image quality can be improved by modifying the linear accelerator to generate more low-energy photons. This work addresses the problem of using Monte Carlo simulation and experiment to optimize the beam and detector combination to maximize image quality for a given patient thickness. A simple model of the whole imaging chain was developed for investigation of the effect of the target parameters on the quality of the image. The optimum targets (6 mm thick aluminium and 1.6 mm copper) were installed in an Elekta SL25 accelerator. The first beam will be referred to as A16 and the second as Cu1.6. A tissue-equivalent contrast phantom was imaged with the 6 MV standard photon beam and the experimental beams with standard radiotherapy and mammography film/screen systems. The arrangement with a thin Al target/mammography system improved the contrast from 1.4 cm bone in 5 cm water to 19% compared with 2% for the standard arrangement of a thick, high-Z target/radiotherapy verification system. The linac/phantom/detector system was simulated with the BEAM/EGS4 Monte Carlo code. Contrast calculated from the predicted images was in good agreement with the experiment (to within 2.5%). The use of MC techniques to predict images accurately, taking into account the whole imaging system, is a powerful new method for portal imaging system design optimization.

Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

PURPOSE: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. METHODS AND MATERIALS: Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. RESULTS: In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. CONCLUSIONS: A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

Series model volume effects in a population of non-identical patients: how low is low?

Working with several mechanisms of critical local tissue damage, formulae are analytically derived that describe normal tissue complication probabilities (ntcps) for series-type radiotherapy complications arising in heterogeneous patient populations. Using the formulae, values are calculated for deltaD50(10)-the increase in dose leading to a 50% series-type complication rate (D50) when irradiated organ volume is reduced tenfold. From the structure of the ntcp formulae derived, it follows that dose-levels leading to clinically relevant serious complication rates (less than 5%) will change less with irradiated volume than will D50. Calculated values of deltaD50(10) for the heterogeneous series model are low-generally less than 6 Gy; such values are much lower than those calculated for the non-heterogeneous series model (27-37 Gy). These results suggest that if the dose-limiting toxicity of a radiotherapy treatment is a series-type complication with a local damage mechanism similar to any of those studied in this work, then even very substantial improvements in technique-leading to large reductions in highly dosed normal tissue volumes-would be unlikely to allow a useful degree of escalation of the dose delivered to the tumour, unless highly dosed normal tissue volumes can be reduced below the length-scale of a functional subunit.

Monte Carlo calculation of output factors for circular, rectangular, and square fields of electron accelerators (6-20 MeV).

Monte Carlo (MC) techniques can be used to build a simulation model of an electron accelerator to calculate output factors for electron fields. This can be useful during commissioning of electron beams from a linac and in clinical practice where irregular fields are also encountered. The Monte Carlo code BEAM/EGS4 was used to model electron beams (6-20 MeV) from a Varian 2100C linear accelerator. After optimization of the Monte Carlo simulation model, agreement within 1% to 2% was obtained between calculated and measured (with a Si diode) lateral and depth dose distributions or within 1 mm in the penumbral regions. Output factors for square, rectangular, and circular fields were measured using two different plane-parallel ion chambers (Markus and NACP) and compared to MC simulations. The agreement was usually within 1% to 2%. This study was not primarily concerned with minimizing the simulation time required to obtain output factors but some considerations with respect to this are presented. It would be particularly useful if the MC model could also be used to calculate output factors for other, similar linacs. To see if this was possible, the primary electron energies in the MC model were retuned to model a recently commissioned similar linac. Good agreement between calculated and measured output factors was obtained for most field sizes for this second accelerator.

Impact of dose-distribution uncertainties on rectal ntcp modeling. I: Uncertainty estimates.

A trial of nonescalated conformal versus conventional radiotherapy treatment of prostate cancer has been carried out at the Royal Marsden NHS Trust (RMH) and Institute of Cancer Research (ICR), demonstrating a significant reduction in the rate of rectal bleeding reported for patients treated using the conformal technique. The relationship between planned rectal dose-distributions and incidences of bleeding has been analyzed, showing that the rate of bleeding falls significantly as the extent of the rectal wall receiving a planned dose-level of more than 57 Gy is reduced. Dose-distributions delivered to the rectal wall over the course of radiotherapy treatment inevitably differ from planned distributions, due to sources of uncertainty such as patient setup error, rectal wall movement and variation in the absolute rectal wall surface area. In this paper estimates of the differences between planned and treated rectal dose-distribution parameters are obtained for the RMH/ICR nonescalated conformal technique, working from a distribution of setup errors observed during the RMH/ICR trial, movement data supplied by Lebesque and colleagues derived from repeat CT scans, and estimates of rectal circumference variations extracted from the literature. Setup errors and wall movement are found to cause only limited systematic differences between mean treated and planned rectal dose-distribution parameter values, but introduce considerable uncertainties into the treated values of some dose-distribution parameters: setup errors lead to 22% and 9% relative uncertainties in the highly dosed fraction of the rectal wall and the wall average dose, respectively, with wall movement leading to 21% and 9% relative uncertainties. Estimates obtained from the literature of the uncertainty in the absolute surface area of the distensible rectal wall are of the order of 13%-18%. In a subsequent paper the impact of these uncertainties on analyses of the relationship between incidences of bleeding and planned rectal dose-distributions is explored.

Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling.

PURPOSE: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure. METHODS AND MATERIALS: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids of different diameters. Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the tcp model. RESULTS: Hypoxia was seen only for spheroids greater than 500 microm in diameter. For small spheroids tcp estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the tcp estimates of the number of clonogenic cells agreeing with measured values. CONCLUSIONS: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not limit directly the success of radiation therapy.

Correlations between dose-surface histograms and the incidence of long-term rectal bleeding following conformal or conventional radiotherapy treatment of prostate cancer.

BACKGROUND AND PURPOSE: In a randomized trial, the incidence of rectal bleeding among patients treated for prostate cancer using conformal radiotherapy was significantly lower (p = 0.002) than that among those treated conventionally. Here the relationship between rectal dose distributions and incidences of bleeding is assessed. METHODS AND MATERIALS: Rectal dose-surface histograms (DSHs) have been calculated for 79 trial patients. The relationship between the DSHs and incidences of Grade 1-3 bleeding has been explored using both semiempiric and biologic (parallel) model-based approaches. RESULTS: Semiempiric analysis of the trial data suggests that it is more useful to work with DSH fractional surface areas multiplied by outlined rectal lengths than with either raw DSH fractional areas or fractional areas multiplied by absolute total outlined rectal surface area. Fitting the parallel model to length-multiplied rectal DSHs and complication data reveals the existence of a significant volume effect, the rate of Grade 1-3 bleeding falling by 1.1% (95% confidence interval [0.04, 2.2]%) for each 1% decrease in the fraction of rectal wall (outlined over an 11-cm length) receiving a dose of more than 57 Gy. CONCLUSION: The existence of this volume effect suggests that dose escalation can be achieved using conformal techniques, although the extent to which doses may be safely escalated cannot be reliably estimated from the trial data.

Individualization of dose prescription based on normal-tissue dose-volume and radiosensitivity data.

PURPOSE: The aim of this paper is to illustrate the potential gain in tumor control probability (TCP) of prostate cancer patients by individualizing the prescription dose according to both normal-tissue (N-T) dose-volume and radiosensitivity data. METHODS AND MATERIALS: Two exercises have been carried out. Firstly, patients' dose prescriptions were individualised on the basis of N-T dose-volume histograms (DVHs) alone and secondly modeling potential differences in N-T sensitivity as well. In both cases, the change in tumor control that may be achieved by individualizing patients' dose was estimated assuming that after the dose adjustments, every patient had (1) the same value of normal tissue complication probability (NTCP) (5%) and (2) NTCP equal to the average NTCP before individualization (i.e., without increasing the average NTCP). The Lyman-Kutcher-Burman NTCP model was used to predict the N-T response curves with two different sets of parameters. The first exercise, based only on individual NT DVHs (i.e., assuming all patient equally radiosensitive), was over a real population of 50 prostate cancer patients. The second exercise modeled a 10,000-prostate-cancer patient population with varying NT dose-volume distributions and radiosensitivity (through allowing TD(50) to vary). RESULTS: A gain of more than 9% in TCP was predicted when doses were individualized based only on DVHs so that every patient had 5% NTCP after dose adjustments. By adding the estimate of radiosensitivity, the gain increased to more than 15%. When the individualisation was performed without increasing the mean NTCP, then the potential gain in TCP was almost 5% (for adjustment based on DVH distribution solely) increasing to 7% with the additional consideration of radiosensitivity. CONCLUSIONS: There is a potential gain (increase in local tumor control) from dose individualisation strategies based on both N-T dose-volume data and radiosensitivity (assuming that this is available). Dose prescription individualization based only on dose-volume data can be exploited provided that reliable N-T response models are available. There will be additional gains if some estimate of N-T radiosensitivity is available to allow further patient stratification, identification of patients with high radiosensitivity being particularly important.

Backscatter towards the monitor ion chamber in high-energy photon and electron beams: charge integration versus Monte Carlo simulation.

In some linear accelerators, the charge collected by the monitor ion chamber is partly caused by backscattered particles from accelerator components downstream from the chamber. This influences the output of the accelerator and also has to be taken into account when output factors are derived from Monte Carlo simulations. In this work, the contribution of backscattered particles to the monitor ion chamber response of a Varian 2100C linac was determined for photon beams (6, 10 MV) and for electron beams (6, 12, 20 MeV). The experimental procedure consisted of charge integration from the target in a photon beam or from the monitor ion chamber in electron beams. The Monte Carlo code EGS4/BEAM was used to study the contribution of backscattered particles to the dose deposited in the monitor ion chamber. Both measurements and simulations showed a linear increase in backscatter fraction with decreasing field size for photon and electron beams. For 6 MV and 10 MV photon beams, a 2-3% increase in backscatter was obtained for a 0.5 x 0.5 cm2 field compared to a 40 x 40 cm2 field. The results for the 6 MV beam were slightly higher than for the 10 MV beam. For electron beams (6, 12, 20 MeV), an increase of similar magnitude was obtained from measurements and simulations for 6 MeV electrons. For higher energy electron beams a smaller increase in backscatter fraction was found. The problem is of less importance for electron beams since large variations of field size for a single electron energy usually do not occur.

Monte Carlo dose calculations and radiobiological modelling: analysis of the effect of the statistical noise of the dose distribution on the probability of tumour control.

The aim of this work is to investigate the influence of the statistical fluctuations of Monte Carlo (MC) dose distributions on the dose volume histograms (DVHs) and radiobiological models, in particular the Poisson model for tumour control probability (tcp). The MC matrix is characterized by a mean dose in each scoring voxel, d, and a statistical error on the mean dose, sigma(d); whilst the quantities d and sigma(d) depend on many statistical and physical parameters, here we consider only their dependence on the phantom voxel size and the number of histories from the radiation source. Dose distributions from high-energy photon beams have been analysed. It has been found that the DVH broadens when increasing the statistical noise of the dose distribution, and the tcp calculation systematically underestimates the real tumour control value, defined here as the value of tumour control when the statistical error of the dose distribution tends to zero. When increasing the number of energy deposition events, either by increasing the voxel dimensions or increasing the number of histories from the source, the DVH broadening decreases and tcp converges to the 'correct' value. It is shown that the underestimation of the tcp due to the noise in the dose distribution depends on the degree of heterogeneity of the radiobiological parameters over the population; in particular this error decreases with increasing the biological heterogeneity, whereas it becomes significant in the hypothesis of a radiosensitivity assay for single patients, or for subgroups of patients. It has been found, for example, that when the voxel dimension is changed from a cube with sides of 0.5 cm to a cube with sides of 0.25 cm (with a fixed number of histories of 10(8) from the source), the systematic error in the tcp calculation is about 75% in the homogeneous hypothesis, and it decreases to a minimum value of about 15% in a case of high radiobiological heterogeneity. The possibility of using the error on the tcp to decide how many histories to run for a given voxel size is also discussed.

An analysis of the relationship between radiosensitivity and volume effects in tumor control probability modeling.

The dependence of local tumor control probability (tcp) on tumor volume is analyzed and discussed with the help of radiobiological modeling; in particular the impact of possible correlations between mean tumor radiosensitivity and tumor dimensions on the tcp volume dependence is explored. The linear-quadratic Poissonian tumor control probability (tcp) model was modified to account for the possible dependence of clonogenic cell density and radiosensitivity parameters on tumor volume; then the original and modified versions of the model were fitted to published clinical and laboratory tumor control data. These different versions of the tcp model often fitted tumor control data equally well, because of the high degree of correlation between the parameters. Nevertheless the results were very different from a physical point of view and we suggest that sometimes it is possible to choose between equally good fits on the basis of physical considerations. Possible links between the volume dependence of the mean radiosensitivity and the degree of tumor hypoxia were also analyzed through a comparison of the results of the tcp fit to published measurements of oxygen tension in tumors.

BIOPLAN: software for the biological evaluation of. Radiotherapy treatment plans.

Distributions of absorbed dose do not provide information on the biological response of tissues (either tumor or organs at risk [OAR]) to irradiation. BIOPLAN (BiOlogical evaluation of PLANs) has been conceived and developed as a PC-based user-friendly software that allows the user to evaluate a treatment plan from the (more objective) point of view of the biological response of the irradiated tissues, and at the same time, provides flexibility in the use of models and parameters. It requires information on dose-volume histograms (DVHs) and can accept a number of different formats (including DVH files from commercial treatment planning systems). BIOPLAN provides a variety of tools, such as tumor control probability (TCP) calculations (using the Poisson model), normal tissue complication probability (NTCP) calculations (using either the Lyman-Kutcher-Burman or the relative seriality models), the ATCP method, DVH subtraction, plots of NTCP/TCP as a function of prescription dose, tumor and OAR dose statistics, equivalent uniform dose (EUD), individualized dose prescription, and parametric sensitivity analysis of the TCP/NTCP models employed.

Converting absorbed dose to medium to absorbed dose to water for Monte Carlo based photon beam dose calculations.

Current clinical experience in radiation therapy is based upon dose computations that report the absorbed dose to water, even though the patient is not made of water but of many different types of tissue. While Monte Carlo dose calculation algorithms have the potential for higher dose accuracy, they usually transport particles in and compute the absorbed dose to the patient media such as soft tissue, lung or bone. Therefore, for dose calculation algorithm comparisons, or to report dose to water or tissue contained within a bone matrix for example, a method to convert dose to the medium to dose to water is required. This conversion has been developed here by applying Bragg-Gray cavity theory. The dose ratio for 6 and 18 MV photon beams was determined by computing the average stopping power ratio for the primary electron spectrum in the transport media. For soft tissue, the difference between dose to medium and dose to water is approximately 1.0%, while for cortical bone the dose difference exceeds 10%. The variation in the dose ratio as a function of depth and position in the field indicates that for photon beams a single correction factor can be used for each particular material throughout the field for a given photon beam energy. The only exception to this would be for the clinically non-relevant dose to air. Pre-computed energy spectra for 60Co to 24 MV are used to compute the dose ratios for these photon beams and to determine an effective energy for evaluation of the dose ratio.