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In light-ion radiation therapy, both the dose and the local energy spectrum, which is often characterized with the linear energy transfer (LET), must be considered. In treatment optimization, it is advantageous to use a radiobiological model that analytically accounts for both dose and LET for the ion type of interest. With such a model the biological effect can also be estimated for dose and LET combinations for which there are no observations in the underlying experimental data. In this study, the repairable-conditionally repairable (RCR) damage model was extended by expressing its parameters as functions of LET to provide a radiobiological model that accounts for both the dose and the LET for a given ion type and cell line. This LET-parameterized RCR model was fitted to published cell survival data for HSG and V79 cells irradiated with carbon ions and for T1 cells irradiated with helium ions. To test the robustness of the model, fittings to only a subset of the data were performed. Good agreement with the cell survival data was obtained, including survival data for LET values not used for model fitting, opening up the possibility of using the model in treatment planning for light ions.

New radiobiological models are used to describe tumour and normal tissue reactions and to account for their dependence on the irradiated volume and inhomogeneities of the delivered dose distribution and cell sensitivity. The probability of accomplishing complication-free tumour control is maximized by an iterative algorithm. The algorithm is demonstrated by applying it to a one-dimensional (1D) tumour model but also to a more clinically relevant 2D case. The new algorithm is n-dimensional so it could simultaneously optimize the dose delivery in a 3D volume and in principle also select the ideal beam orientations, beam modalities (photons, electrons, neutrons, etc) and optimal spectral distributions of the corresponding modalities. To make calculation time reasonable, 2D-3D problems are most practical, and suitable beam orientations are preselected by the choice of irradiation kernel. The energy deposition kernel should therefore be selected in order to avoid irradiation through organs at risk. Clinically established dose response parameters for the tissues of interest are used to make the optimization as relevant as possible to the clinical problems at hand. The algorithm can be used even with a poorly selected kernel because it will always, as far as possible, avoid irradiating organs at risk. The generated dose distribution will be optimal with respect to the spatial distribution and assumed radiobiological properties of the tumour and normal tissues at risk for the kernel chosen. More specifically the probability of achieving tumour control without fatal complications in normal tissues is maximized. In the clinical examples a reduced tumour dose is seen at the border to sensitive organs at risk, but instead an increased dose just inside the tumour border is generated. The increased tumour dose has the effect that the dose fall-off is as steep as possible at the border to organs at risk.

The problem of choosing radiation quantities and units for energy deposition kernels and their associated kernel densities is treated with the aim of making them consistent with related classical radiation quantities and units such as restricted mass stopping powers and mass attenuation coefficients. It is shown that it is very useful to define the kernels h(r), in terms of the quotient of the mean specific energy imparted to the medium by the radiant energy incident on a volume element centred at the origin of the kernel. The basic building block used to generate these kernels is the point energy deposition kernel, h(p), describing the spatial distribution of the energy imparted by a photon interacting at a point in a medium. This will allow the kernels to be regarded as generalizations of the traditional mass stopping and attenuation coefficients, which in detail describe the spatial distribution of the mean energy deposition around an interaction site. As a consequence, the irradiation or kernel density, f(r) should be expressed in terms of the radiant energy incident per unit volume of the medium. It is shown that the kernel density is equal to minus the divergence of the incident unattenuated vectorial energy fluence, and it therefore acts as an irradiation density for the incident vectorial energy fluence. The microscopic kernels or the irradiation density may thus be viewed as a perfect 'sink' distribution to the required incident photon energy fluence which is totally absorbed at f(r), and instead replaced by the kernels which describe the detailed energy deposition in the medium in coordinates centred at the sinks. From these definitions the required incident energy fluence from an external radiation source used for treatment realization can be determined directly by projecting the irradiation density on the relevant positions of the radiation source. This procedure has the valuable property that maximal calculational accuracy is achieved in the tumour because the irradiation density has non-zero values only in the tumour, and the accuracy of the kernel is highest at its origin.

Object Radiation treatment of large arteriovenous malformations (AVMs) remains difficult and not very effective, even though seemingly promising methods such as staged volume treatments have been proposed by some radiation treatment centers. In symptomatic patients harboring large intracranial AVMs not amenable to embolization or resection, single-session high-dose stereotactic radiation therapy is a viable option, and the special characteristics of high-ionization-density light-ion beams offer several treatment advantages over photon and proton beams. These advantages include a more favorable depth-dose distribution in tissue, an almost negligible lateral scatter of the beam, a sharper penumbra, a steep dose falloff beyond the Bragg peak, and a higher probability of vascular response due to high ionization density and associated induction of endothelial cell proliferation and/or apoptosis. Carbon ions were recently shown to be an effective treatment for skull-base tumors. Bearing that in mind, the authors postulate that the unique physical and biological characteristics of light-ion beams should convey considerable clinical advantages in the treatment of large AVMs. In the present meta-analysis the authors present a comparison between light-ion beam therapy and more conventional modalities of radiation treatment with respect to these lesions. Methods Dose-volume histograms and data on peripheral radiation doses for treatment of large AVMs were collected from various radiation treatment centers. Dose-response parameters were then derived by applying a maximum likelihood fitting of a binomial model to these data. The present binomial model was needed because the effective number of crucial blood vessels in AVMs (the number of vessels that must be obliterated to effect a cure, such as large fistulous nidus vessels) is low, making the Poisson model less suitable. In this study the authors also focused on radiobiological differences between various radiation treatments. Results Light-ion Bragg-peak dose delivery has the precision required for treating very large AVMs as well as for delivering extremely sharp, focused beams to irregular lesions. Stereotactic light-ion radiosurgery resulted in better angiographically defined obliteration rates, less white-matter necrosis, lower complication rates, and more favorable clinical outcomes. In addition, in patients treated by He ion beams, a sharper dose-response gradient was observed, probably due to a more homogeneous radiosensitivity of the AVM nidus to light-ion beam radiation than that seen when low-ionization-density radiation modalities, such as photons and protons, are used. Conclusions Bragg-peak radiosurgery can be recommended for most large and irregular AVMs and for the treatment of lesions located in front of or adjacent to sensitive and functionally important brain structures. The unique physical and biological characteristics of light-ion beams are of considerable advantage for the treatment of AVMs: the densely ionizing beams of light ions create a better dose and biological effect distribution than conventional radiation modalities such as photons and protons. Using light ions, greater flexibility can be achieved while avoiding healthy critical structures such as diencephalic and brainstem nuclei and tracts. Treatment with the light ion He or Li is more suitable for AVMs ≤ 10 cm3, whereas treatment with the light ion Li, Be, or C may be more appropriate for larger AVMs. A binomial model based on the effective number of crucial vessels in the AVM may be used quite well to predict AVM obliteration probabilities for both small and large AVMs when therapies involving either photons or light ions are used.

Risk factors for development of a stricture of the upper esophagus after radiotherapy for head and neck cancer are poorly defined.This was a retrospective case-control study of patients diagnosed and treated for esophageal stricture after radiotherapy for head and neck cancer.The incidence of esophageal stricture after external beam radiation therapy (EBRT) was 3.3%. Seventy patients with stricture and 66 patients without stricture were identified. A multivariate analysis showed that there was increased risk of stricture in receiving enteral feeding during EBRT or in receiving a mean dose of45 Gy to the upper esophagus.Enteral feeding during EBRT is strongly associated with the development of stricture of the esophagus, as is a mean dose of45 Gy to the upper esophagus. Treatment of the stricture with Savary-Gilliard bougienage or through scope balloon dilatation is safe and successful but often has to be repeated.

Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D(50)) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D(50) value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the convolution process. The assumption of an effective FSU size is consistent with most of the effects seen when different portions of the rat spinal cord are irradiated to different doses. The effective FSU length from these experiments is about 8.5 +/- 0.5 mm. This length could be interpreted as an effective size of the functional subunits in a rat spinal cord, where multiple myelin sheaths are connected by a single oligodendrocyte and repair is limited by the range of oligodendrocyte progenitor cell diffusion. It was even possible to suggest a more likely than uniform effective FSU sensitivity distribution from the experimental data.

The spinal cord, known for its strongly serial character and high sensitivity to radiation even when a small segment is irradiated, is one of the most critical organs at risk to be spared during radiation therapy. To compare the sensitivity of different parts of the spinal cord, data for radiation myelopathy have been used.In the present study, the relative seriality model was fitted to two different datasets of clinical radiation myelitis concerning cervical spinal cord after treating 248 patients for head and neck cancer and thoracic spinal cord after treating 43 patients with lung carcinoma. The maximum likelihood method was applied to fit the clinical data. The model parameters and their 68% confidence intervals were calculated for each dataset. The alpha/beta ratio for the thoracic cord was also was also found to be 0.9 (0-3.0) Gy.The dose-response curve for the more sensitive cervical myelopathy is well described by the parameters D(50)=55.9 (54.8-57.1) Gy, gamma=6.9 (5.0-9.2), s=0.13 (0.07-0.24), whereas the thoracic myelopathy is described by the parameters D(50)=75.5 (70.5-80.8) Gy, gamma=1.1 (0.6-1.6), s=36 (3.3-infinity).Large differences in radiation response between the cervical and thoracic region of spinal cord are thus observed: cervical myelopathy seems to be characterized by medium seriality, while thoracic spinal cord is characterized by a highly serial dose-response. The much steeper dose-response curve for cervical spinal cord myelopathy can be interpreted as a higher number of functional subunits consistent with a higher amount of white matter close to the brain.

Introduction. In SRT/SRS, dedicated treatment planning systems are used for the calculation of the dose distribution. The majority of these systems utilize the standard TMR/OAR formalism for dose calculation as well as they usually neglect any perturbation due to head heterogeneities. The aim of this study is to examine the errors due to head heterogeneities for both absolute and relative dose distributions in stereotactic radiotherapy. Materials and methods. Dosimetric measurements in phantoms have been made for linac stereotactic irradiation. CT-based phantoms have been used for Monte Carlo simulations for both linac-based stereotactic system and Gamma Knife unit. Absolute and relative dose distributions have been compared between homogeneous and heterogeneous media. DVH and TCP results are presented for all cases. Results. The maximum absolute dose difference at the isocenter was 2.2% and 6.9% for the linac and Gamma Knife respectively. The impact of heterogeneity in the target DVH was minor for the linac technique whereas considerable difference was observed for the Gamma Knife treatment. This was reflected also to the radiobiological evaluation, where the maximum TCP difference for the linac system was 2.7% and for the Gamma Knife was 4%. Discussion and conclusions. The errors rising from the existence of head heterogeneities are not negligible especially for the Gamma Knife which uses lower energy beams. The errors of the absolute dose calculation could be easily eliminated by implementing a simple heterogeneity correction algorithm at the TPS. Nevertheless, the errors for not taking into account the lateral electron transport would require a more sophisticated approach and even direct Monte Carlo calculation.

The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose (D) is applied together with the complication-free tumour control probability (P(+)). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using D as the common prescription point of the treatment plans and plotting the tissue response probabilities versus D for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome P(+) of 62.2% and 46.0%, D to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P(+) of 66.9% and 72.9%, D to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P(+) of 68.7% and 72.2%, D to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose-response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of P(+)--D diagrams to effectively evaluate and compare treatment plans.

To speed up dose calculation, an analytical pencil-beam method has been developed to calculate the mean radial dose distributions due to secondary electrons that are set in motion by light ions in water. For comparison, radial dose profiles calculated using a Monte Carlo technique have also been determined. An accurate comparison of the resulting radial dose profiles of the Bragg peak for (1)H(+), (4)He(2+) and (6)Li(3+) ions has been performed. The double differential cross sections for secondary electron production were calculated using the continuous distorted wave-eikonal initial state method (CDW-EIS). For the secondary electrons that are generated, the radial dose distribution for the analytical case is based on the generalized Gaussian pencil-beam method and the central axis depth-dose distributions are calculated using the Monte Carlo code PENELOPE. In the Monte Carlo case, the PENELOPE code was used to calculate the whole radial dose profile based on CDW data. The present pencil-beam and Monte Carlo calculations agree well at all radii. A radial dose profile that is shallower at small radii and steeper at large radii than the conventional 1/r(2) is clearly seen with both the Monte Carlo and pencil-beam methods. As expected, since the projectile velocities are the same, the dose profiles of Bragg-peak ions of 0.5 MeV (1)H(+), 2 MeV (4)He(2+) and 3 MeV (6)Li(3+) are almost the same, with about 30% more delta electrons in the sub keV range from (4)He(2+)and (6)Li(3+) compared to (1)H(+). A similar behavior is also seen for 1 MeV (1)H(+), 4 MeV (4)He(2+) and 6 MeV (6)Li(3+), all classically expected to have the same secondary electron cross sections. The results are promising and indicate a fast and accurate way of calculating the mean radial dose profile.

In a recently published paper (Nioutsikou et al 2005 Phys. Med. Biol. 50 L17) the authors showed that the use of the dose-mass histogram (DMH) concept is a more accurate descriptor of the dose delivered to lung than the traditionally used dose-volume histogram (DVH) concept. Furthermore, they state that if a functional imaging modality could also be registered to the anatomical imaging modality providing a functional weighting across the organ (functional mass) then the more general and realistic concept of the dose-functioning mass histogram (D[F]MH) could be an even more appropriate descriptor. The comments of the present letter to the editor are in line with the basic arguments of that work since their general conclusions appear to be supported by the comparison of the DMH and DVH concepts using radiobiological measures. In this study, it is examined whether the dose-mass histogram (DMH) concept deviated significantly from the widely used dose-volume histogram (DVH) concept regarding the expected lung complications and if there are clinical indications supporting these results. The problem was investigated theoretically by applying two hypothetical dose distributions (Gaussian and semi-Gaussian shaped) on two lungs of uniform and varying densities. The influence of the deviation between DVHs and DMHs on the treatment outcome was estimated by using the relative seriality and LKB models using the Gagliardi et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 46 373) and Seppenwoolde et al (2003 Int. J. Radiat. Oncol. Biol. Phys. 55 724) parameter sets for radiation pneumonitis, respectively. Furthermore, the biological equivalent of their difference was estimated by the biologically effective uniform dose (D) and equivalent uniform dose (EUD) concepts, respectively. It is shown that the relation between the DVHs and DMHs varies depending on the underlying cell density distribution and the applied dose distribution. However, the range of their deviation in terms of the expected clinical outcome was proven to be very large. Concluding, the effectiveness of the dose distribution delivered to the patients seems to be more closely related to the radiation effects when using the DMH concept.

Heterogeneous tumors often have a wide spectrum of radiation sensitivities due to factors like their genetic make up, clonal distribution and degree of genetic instability, as well as gradients of oxygen and nutrients. Recent studies demonstrate that the radiation response of heterogeneous tumors can be rather well described by a single effective clonogen compartment when the dose-response relation at high doses is of main interest. When a correct description of the clonogen survival is important at both low and high doses, a description based on one sensitive and one resistant clonogen compartment will be necessary and generally sufficient and surprisingly accurate. Such a description is valuable for example when in vivo PET-CT data are acquired early in the treatment to predict the required curative radiation dose. Methods are given for derivation of the sensitive and resistant cell compartments based on clinically observed dose-response relations and the degree of hypoxia. Principal characteristics of heterogeneous tumors are derived, such as the dose D(t) describing the transition when sensitive cells are lost and resistant cells start to dominate the response resulting in a fast change in slope of the cell survival curve. Since the effective compartments are based on the whole spectrum of radiation resistance, they will take both low intermediate and high sensitivity values into account, thus providing an accurate description of the radiation response over the entire range of clinically relevant doses.

Aims Because of the highly conformal distributions that can be obtained with intensity-modulated radiotherapy (IMRT), any discrepancy between the intended and delivered distributions would probably affect the clinical outcome. Consequently, there is a need for a measure that would quantify those differences in terms of a change in the expected clinical outcome. Materials and methods To evaluate such a measure, cancer of the cervix was used, where the bladder and rectum are proximal and partially overlapping with the internal target volume. A solid phantom simulating the pelvic anatomy was fabricated and a treatment plan was developed to deliver the prescribed dose to the phantom. The phantom was then irradiated with films positioned in several transverse planes. The racetrack microtron at 50MV was used in the treatment planning and delivery processes. The dose distribution delivered was analysed based on the film measurements and compared against the treatment plan. The differences in the measurements were evaluated using both physical and biological criteria. Whereas the physical comparison of dose distributions can assess the geometric accuracy of delivery, it does not reflect the clinical effect of any measured dose discrepancies. Results It is shown how small inaccuracies in delivered dose can affect the treatment outcome in terms of complication-free tumour cure. Conclusions With highly conformal IMRT, the accuracy of the patient set-up and treatment delivery are critical for the success of the treatment. A method is proposed to evaluate the precision of the delivered plan based on changes in complication and control rates as they relate to uncertainties in dose delivery.

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.

The aim of the study was to examine the influence of overall treatment time (OTT) on the value of calculated biological effective doses (BEDs) for different biological variables. These variables were: tumour proliferation rate, different cell radiosensitivity (alpha=0.2, 0.3, and 0.4 /Gy), and different start time for repopulation (Tk=21, 28, and 35 days). Also the influence of age (/= 50 years), Hb level (/= 116 g/l), tumor proliferation rate (bromodeoxyuridine labelling index; BrdUrdLI), and DNA ploidy on survival after shorter (/= 60 days) or longer (60 days) OTT was investigated. The study included 229 patients with cervix carcinoma treated entirely by standard radiotherapy (RT) (external beam RT plus low-medium dose-rate (LDR/MDR) brachytherapy (BT) at the Center of Oncology in Krakow. The linear quadratic equation was used to calculate BED, which is proportional to log cell kill. BEDs 10 (for tumours) were calculated with consideration of OTT for each patient and tumour proliferation rate (standardized potential doubling time; standardized Tpot) based on BrdUrdLI assessed on biopsy material before RT. Median OTT was 90 days (range 30-210). The mean calculated total BED for point A for tumour and 'early reactions' was equal to 103.0 Gy10. The longest median survival time--52 months--was seen for patients treated with OTT/= 60 days. If OTT exceeded 90 days to more than 120 days, loss in BED10 for relatively radiosensitive tumours (alpha=0.3-0.4/Gy and Tk=28 days) was equal to 0.37-0.26 Gy/day. However, for radioresistant tumours (alpha=0.2/Gy) it was 0.6 Gy/day. For fast proliferating tumours (BrdUrdLI8.8%) BED loss was 1.4 Gy/day and for slowly proliferating tumours (BrdUrdLI/= 8.8%) it was 0.2 Gy/day. Assuming shorter (21 days) or longer (35 days) periods for Tk and relatively radiosensitive tumours similar BED loss of 0.38 Gy/day was observed. Kaplan-Meier analysis revealed that OTT/= 60 days was a significant prognostic factor for overall survival (OS) (p=0.019), disease-free survival (DFS) (p=0.0173), and local control (LC) (p=0.011). BED10 had significant influence on survival (p=0.047). Cox multivariate analysis revealed that for OTT shorter than 60 days the only favourable significant parameters were: age50 years (p=0.003) and high Hb level (116 g/l) (p=0.041). For longer treatments (OTT60 days) the unfavourable parameters were: age/= 50 years (p=0.037), BrdUrdLI/= 8.8% (p=0.003), tumour aneuploidy (p=0.043), and BED10/= 103 Gy (p=0.017). The examined tumour biological parameters should be taken into account for RT and provide a basis for adjuvant RT.

Background: The estimation of the parameters that describe the dose-response relations of anal sphincter regarding the clinical endpoints of fecal leakage and blood or phlegm in stools is important in the optimization of prostate cancer radiotherapy. Also, the validity of the relative seriality model for this clinical case needs to be examined by associating the clinical follow-up results with the predicted complication rates. Patients and Methods: In this study, 65 patients who received radiation therapy for clinically localized prostate adenocarcinoma are analyzed. The clinical treatment outcome and the three-dimensional dose distribution delivered to anal sphincter were available for each patient. A questionnaire was used for assessing the clinical bowel and urinary symptoms. A maximum likelihood fitting was performed to calculate the best estimates of the parameters used by the relative seriality model. The clinical utilization of the calculated parameters in predicting anal sphincter complication probabilities was illustrated by applying the best estimate of the parameters to a subset of the patient population. Results: The estimated values of the parameters for the two clinical endpoints are D 50 = 70.2 Gy, γ = 1.22, s = 0.35 for fecal leakage and D 50 = 74.0 Gy, γ = 0.75, s ≈ 0 for blood or phlegm in stools. The standard deviations of the parameters were also calculated together with the confidence intervals of the dose-response curves. The analysis proved that the treatment outcome pattern of the patient material can suitably be reproduced by the relative seriality model (probability of finding a worse fit = 60.2%, the area under the receiver operating characteristic curve = 0.72 and 0.69 and χ2-test = 0.97 and 0.86, respectively). Conclusion: Fecal leakage is characterized by a medium relative seriality whereas blood or phlegm in stools was found to have strong volume dependence (low relative seriality). Diminishing the biologically effective uniform dose to anal sphincter < 40–45 Gy may significantly reduce the risk of fecal leakage or blood or phlegm in stools for patients irradiated for prostate cancer.

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D50 = 68.4 Gy, gamma = 6.55, s = 0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit = 61.0%, the area under the ROC curve = 0.84 and chi2 test = 0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve.

To investigate dysfunction caused by unwanted radiation to the anal-sphincter region and the rectum.A questionnaire assessing bowel symptoms, sexual function, and urinary symptoms was sent to 72 patients with clinically localized prostatic adenocarcinoma treated by external beam radiation therapy at the Radiumhemmet, Karolinska Hospital, in Stockholm, Sweden, 2-4 years after treatment. The mean percentage dose-volume histograms for patients with and without the specific symptom were calculated.Of the 65 patients providing information, 9 reported fecal leakage, 10 blood and mucus in stools, 10 defecation urgency, and 7 diarrhea or loose stools. None of the 19 and 13 patients who received, respectively, a dose ofor =35 Gy toor =60% oror =40 Gy toor =40% of the anal-sphincter region volume reported fecal leakage (p0.05). In dose-volume histograms, a statistically significant correlation was found between radiation to the anal-sphincter region and the risk of fecal leakage in the interval 45-55 Gy. There was also a statistically significant correlation between radiation to the rectum and the risk of defecation urgency and diarrhea or loose stools in the interval 25-42 Gy. No relationship was found between anatomic rectal wall volume and the investigated late effects.Although the limited data in this study prevent the definition of a conclusive threshold regarding volume and dose to the anal-sphincter region and untoward morbidity, it seems that careful monitoring of unnecessary irradiation to this area should be done because it can potentially help reduce the risk of adverse effects, such as fecal leakage. Future studies should pay more attention to the anal-sphincter region and help to more rigorously define its radiotherapeutic tolerance.

BACKGROUND It is well recognized that many patients with head and neck carcinoma have problems with food intake and malnutrition. The objective of the current study was to determine the clinical pattern of patients with nonneoplastic stricture of the upper esophagus after radiotherapy for head and neck carcinoma. METHODS A retrospective chart study of 22 patients with stricture of the proximal esophagus diagnosed between 1993 and 1999 at Karolinska Hospital was performed. The dose volume histograms of the first 2 cm and 5 cm, respectively, of the proximal esophagus were calculated. RESULTS Five of the patients (23%) had total obliteration. The first 2 cm of the esophagus received at least 60 grays (Gy) in > 80% of the volume. Radiation injury was not reported to occur at doses < 60 Gy. There was a correlation found between dysphagia during radiotherapy and the development of proximal esophageal stricture. Stricture was diagnosed 1–60 months (median, 6 months) after radiotherapy. In 18 patients, the stricture was treated with single or repeated endoscopic dilation. These treatments allowed a nearly normal diet in 78% of the patients. CONCLUSIONS Stricture of the upper esophagus is one deglutition disorder that is reported to occur after radiotherapy for head and neck carcinoma. In the current study, the authors emphasize the importance of knowing the tolerance of the normal esophagus to irradiation as well as early diagnosis of stricture of the proximal esophagus because this condition may lead to physical and emotional distress. Cancer 2003;97:1693–700. © 2003 American Cancer Society. DOI 10.1002/cncr.11236

The quality of the radiation therapy delivered in the treatment of breast cancer is susceptible to setup errors and organ motion uncertainties. For 60 breast cancer patients (24 resected with negative node involvement, 13 resected with positive node involvement and 23 ablated) who were treated with three different irradiation techniques. these uncertainties are simulated. The delivered dose distributions in the lung were recalculated taking positioning uncertainty and breathing effects into account. In this way the real dose distributions delivered to the patients are more closely determined. The positioning uncertainties in the anteroposterior (AP) and the craniocaudal (CC) directions are approximated by Gaussian distributions based on the fact that setup errors are random. Breathing is assumed to have a linear behavior because of the chest wall movement during expiration and inspiration. The combined frequency distribution of the positioning and breathing distributions is obtained by convolution. By integrating the convolved distribution over a number of intervals, the positions and the weights of the fields that simulate the original 'effective fields' are calculated. Opposed tangential fields are simulated by a set of 5 pairs of fields in the AP direction and 3 such sets in the CC direction. Opposed AP + PA fields are simulated by a set of 3 pairs of fields in the AP direction and 3 such sets in the CC direction. Single frontal fields are simulated by a set of 5 fields. In radiotherapy for breast cancer, the lung is often partly within the irradiated volume even though it is a sensitive organ at risk. The influence of the deviation in the dose delivered by the original and the adjusted treatment plans on the clinical outcome is estimated by using the relative seriality model and the biologically effective uniform dose concept. Radiation pneumonitis is used as the clinical endpoint for lung complications. The adjusted treatment plans show larger lung complication probabilities than the original plans. This means that the true expected complications are often underestimated in clinical practice. The lung density variation during breathing is calculated from the maximal change in average density during tidal breathing. The change in density in the lung due to breathing is shown to have almost no influence on the dose distribution in the lung. The proposed treatment-plan adjustments taking positioning uncertainty and breathing effects into account indicate significant deviations in the dose delivery and the predicted lung complications.

The prognostic significance of intratumour microvessel density (IMD) and haemoglobin (Hb) level was studied in 152 (FIGO stage IB-IIIB) cervical cancer patients before radiotherapy. Patients' age and tumour stage, grade and degree of keratinization were also studied. IMD measurement expressed as the mean vessel count per 1 mm2 was performed on formalin-fixed, paraffin-embedded tumour biopsies stained with anti-factor VIII antibody (DAKO Ltd.) using immunohistochemistry and the vascular hot-spot technique. The median age of patients was 55 years (29-80). Median values for IMD and Hb level were: 142.5 (range 56.3-476.6) vessels/mm2 and 129 (range 81-160) gil, respectively. The median time of follow-up was 26 months, with a range of 2-145 months. Tumour stage (p = 0.7009), grade (p = 0.6660) and degree of keratinization (0.2669) were not significant in the Kaplan-Meier univariate analysis. However, patients' age50 years (p = 0.0079). high vascularity (IMD190.0 vessels/mm2, minimal cut-off point, p = 0.0503) and Hb concentration116 g/l (p = 0.0213) were favourable prognostic factors for cervical cancer treated with radiotherapy. In the Cox multivariate analysis only higher vascularity (IMD190/mm2 and Hb concentration116 g/l were favourable prognostic factors in terms of patients' survival. However, when a Cox analysis was done separately for keratinizing and non-keratinizing tumours, it was found that higher vascularity was significant only for keratinizing, and higher Hb level only for non-keratinizing cancers.

This study was carried out in order to derive the radiobiological parameters of the dose–response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose–response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose–response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.

In order to compare the biological effectiveness of a 50 MV scanned bremsstrahlung beam to (60)Co and 6 MV photons, the survival of Chinese hamster cells (V79-379A), human normal fibroblasts cells (GSH(+/+)) and human small cell lung cancer cells (U-1690) were analysed.Cells were irradiated in vitro under aerobic conditions in a plastic phantom. Dose to the cells was determined using ferrous sulphate and ionization chamber dosimetry. A number of cell survival models were fitted to the experimental data, including the standard LQ model with and without the induced repair. In particular, a new model treating damage and repair separately was used in combination with a new technique for accurate RBE determination.The measured RBE for the three cell lines were 0.988 (0.984-0.992), 0.999 (0.996-1.002) and 1.013 (1.009-1.016) for V79-379A, GSH(+/+) and U-1690 respectively and thus 50 MV scanned beams did not differ more than a fraction of a per cent from conventional therapy beams.The present study gives RBE consistent with previously calculated RBEs based on photonuclear reaction cross-sections of high-energy photons.

Radiation therapy is today in a state of very rapid development with new intensity modulated treatment techniques continuously being developed. This has made intensity modulated electron and photon beams almost as powerful as conventional uniform beam proton therapy. To be able to cure also the most advanced hypoxic and radiation resistant tumors of complex local spread, intensity modulated light ion beams are really the ultimate tool and only slightly more expensive than proton therapy. The aim of the new center for ion therapy and tumor diagnostics in Stockholm is to develop radiobiologically optimized 3-dimensional pencil beam scanning techniques. Beside the “classical” approaches using low ionization density hydrogen ions (protons, but also deuterons and tritium nuclei) and high ionization density carbon ions, two new approaches will be developed. In the first one lithium or beryllium ions, that induce the least detrimental biological effect to normal tissues for a given biological effect in a small v...

A new object oriented optimization code dedicated to radiotherapy optimization problems, has been developed. The philosophy of the program is to provide a framework for solving the very wide range of optimization problems encountered in treatment planning. The main design objectives has been to create a code that is possible maintain over a longer time span and that is easily extendible when new scientific problems need to be solved. Orbit is capable of handling complex optimization problems such as simultaneous optimization of intensity modulation and beam directions.

Purpose: BioSuite is a program developed to help clinicians to identify cases eligible for dose escalation and/or altered fractionation and to quantify this potential using biological models of normal tissue and tumour response to EBRT. Materials: BioSuite consists in a single executable file developed in C++. The input data are DVHs from a TPS (Philips Pinnacle) as well as a more general DVH format. Plans are defined by parameters such as the number of fractions or a default prescription dose. These DVHs are in turn associated with an endpoint defined by a biological model and a set of parameters. From these models (LKB, Relative Seriality and enhanced LQ Poisson TCP), evaluation of NTCP or TCP can be performed forwardly or inversely. The forward evaluation is made in real-time as the operator modifies plan or endpoint parameters. The inverse evaluation (or optimisation) finds the "dose multiplication factor" (DMP) rescaling the DVH or number of fractions of a given size which take the complication risk to a prior set level. An "isotoxic optimisation" can also be done, which consists of computing for a fraction-number range the highest DMP (and thus TCP) for a constant NTCP. An upper TCP limit can be set (e.g. 99%) to avoid excessive doses in particular cases. The operator can finally generate dose-response curves to visually assess plan quality. Isotoxic optimisation was applied to 33 plans from our institution whose DVHs were exported to BIOSUITE. Results: For most of these plans, scope for dose escalation and/or altered fractionation was found, suggesting these patients were "undertreated". In cases with a very small tumour and consequently small volume of irradiated normal tissue, the models implemented in BioSuite suggested treatments very similar to those currently done in SBRT i.e. TCP close to 100% for as low as 3 fractions. Serial organ DVHs in the plan can drastically affect the BIOSUITE fractionation strategy, making hypofractionation no longer viable.

During the past decade, tumor and normal tissue reactions after radiotherapy have been increasingly quantified in radiobiological terms. For this purpose, response models describing the dependence of tumor and normal tissue reactions on the irradiated volume, heterogeneity of the delivered dose distribution and cell sensitivity variations can be taken into account. The probability of achieving a good treatment outcome can be increased by using an objective function such as P+, the probability of complication-free tumor control. A new procedure is presented, which quantifies P+ from the dose delivery on 2D surfaces and 3D volumes and helps the user of any treatment planning system (TPS) to select the best beam orientations, the best beam modalities and the most suitable beam energies. The final step of selecting the prescribed dose level is made by a renormalization of the entire dose plan until the value of P+ is maximized. The index P+ makes use of clinically established dose-response parameters, for tumors and normal tissues of interest, in order to improve its clinical relevance. The results, using P+, are compared against the assessments of experienced medical physicists and radiation oncologists for two clinical cases. It is observed that when the absorbed dose level for a given treatment plan is increased, the treatment outcome first improves rapidly. As the dose approaches the tolerance of normal tissues the complication-free cure begins to drop. The optimal dose level is often just below this point and it depends on the geometry of each patient and target volume. Furthermore, a more conformal dose delivery to the target results in a higher control rate for the same complication level. This effect can be quantified by the increased value of the P+ parameter.

Not until the last decade has flexible intensity modulated three-dimensional dose delivery techniques with photon beams become a clinical reality, first in the form of heavy metal transmission blocks and other beam compensators, then in dynamic and segmented multileaf collimation, and most recently by scanning high-energy narrow electron and photon beams. The merits of various treatment unit and bremsstrahlung target designs for high-energy photon therapy are investigated theoretically for two clinically relevant target sites, a cervix and a larynx cancer both in late stages. With an optimized bremsstrahlung target it is possible to generate photon beams with a half-width of about 3 cm at a source to axis distance (SAD) of 100 cm and an initial electron energy of 50 MeV. By making a more compact treatment head and shortening the SAD, it is possible to reduce the half-width even further to about 2 cm at a SAD of 70 cm and still have sufficient clearance between the collimator head and the patient. One advantage of a reduced SAD is that the divergence of the beam for a given field size on the patient is increased, and thus the exit dose is lowered by as much as 1%/cm of the patient cross section. A second advantage of a reduced SAD is that the electron beam on the patient surface will be only about 8 mm wide and very suitable for precision spot beam scanning. It may also be possible to reduce the beamwidth further by increasing the electron energy up to about 60 MeV to get a photon beam of around 15 mm half-width and an electron beam as narrow as 5 mm. The compact machine will be more efficient and easy to work with, due to the small gantry and the reduced isocentric height. For a given target volume and optimally selected static multileaf collimator, it is no surprise that the narrowest possible scanned elementary bremsstrahlung beam generates the best possible treatment outcome. In fact, by delivering a few static field segments with individually optimized scan patterns, it is possible to combine the advantage of being able to fine tune the fluence distribution by the scanning system with the steeper dose gradients that can be delivered by a few static multileaf collimator segments. It is demonstrated that in most cases a few collimator segments are sufficient and often a single segment per beam portal may suffice when narrow scanned photon beams are employed, and they can be delivered sequentially with a negligible time delay. A further advantage is the increase of therapeutically useful photons and improved patient protection, since the pencil beam is only scanned where the leaf collimator is open. Consequently, some of the problems associated with dynamic multileaf collimation such as the tongue and groove and edge leakage effects are significantly reduced. Fast scanning beam techniques combined with good treatment verification systems allow interesting future possibilities to counteract patient and internal organ motions in real time.

Purpose: To investigate the clinical efficacy and effectiveness of 3D‐Conformal radiotherapy,Intensity Modulated Radiotherapy(IMRT) using Multileaf Collimators(MLC) and Helical Tomotherapy (HT), by evaluating dosimetric and radiobiological measures of a lungcancer case. Method and Materials: A typical case of lungcancer has been investigated by developing a 3D‐Conformal treatment plan, a linac MLC‐based step‐and‐shoot IMRT plan and a Helical Tomotherapy plan. The treatment plans of the 3D‐Conformal and the MLC‐based IMRT were developed on the Philips treatment planning station using the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment planning station was used for the HT plan. With the use of the complication‐free tumorcontrol probability, P + and the biologically effective uniform dose,D concept as the common prescription point of the plans, the three different treatment plans were compared based on radiobiological measures. Results: The applied plan evaluation method shows that in this lungcancer case the MLC‐based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range, whereas the 3D‐Conformal plan appears to be quite inferior than the other two modalities. More specifically, the 3D‐Conformal, MLC‐based IMRT and HT treatment plans give a P + of 55.4%, 72.9% and 66.9%, for a D to the target volume of 57.0Gy, 66.9Gy and 64.0Gy, respectively. If a higher than 5% risk for complications could be allowed, the complication‐free tumorcontrol could be increased by almost 5% compared to the initial dose prescription. Conclusion: In comparison to 3D‐Conformal radiotherapy, both the MLC based‐IMRT and HT can better encompass the often large ITV while minimizing the volume of the OARs receiving high dose. The use of P ‐ D diagrams can compliment the traditional tools of evaluation such as DVHs, in order to compare and effectively evaluate different treatment plans.

(1996). Current Status of Conformal Radiotherapy. Acta Oncologica: Vol. 35, No. sup8, pp. 41-57.

From the Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, (M. al-Abany, A´ .R. Helgason, G. Steineck), the Stockholm Center for Public Health (A´ .R. Helgason), Department ofMedical Hospital Radiation Physics, So¨der Hospital (A.-K. A˚ gren Cronqvist), Department of Medical RadiationPhysics, Karolinska Institutet (B. Lind, P. Mavroidis), Uro-oncology, Radiumhemmet, Karolinska Hospital (P.Wersa¨ll), Department of Oncology, Radiumhemmet, Karolinska Hospital (H. Lind) and the Department ofRadiology, Karolinska Hospital (E. Qvanta), Stockholm, SwedenCorrespondence to: Professor Gunnar Steineck, Clinical Cancer Epidemiology, Karolinska Hospital Z6:01, SE-17176 Stockholm, Sweden. Tel

A very flexible iterative method for simultaneous optimization of dynamic multileaf collimation, scanning patterns and compensation filters has been developed. The algorithm can account for and optimize almost all the degrees of freedom available in a modern radiation therapy clinic. The method has been implemented for three dimensional treatment planning. The algorithm has been tested for a number of cases where both traditional wedge filters and block collimators, and modern equipment such as scanned beams and multileaf collimators are available. It is shown that the algorithm can improve heavily on traditional uniform dose plans with respect to the probability of achieving tumor control without causing severe complications (P +) simply by finding the optimal beam weights and block collimator settings. By allowing more complex equipment to deliver the dose and by accounting for their increased flexibility during the optimization, the dose plan can be substantially improved with respect to the applied objective functions. It is demonstrated that flexible lateral collimation combined with compensators or scanned beams in most cases allow close to optimal dose delivery. Here both the calculation time and the amount of primary computer memory needed has been reduced by performing the dose calculations in a cone beam coordinate system allowing the use of approximately spatially invariant energy deposition kernels. A typical calculation time for optimization of a two‐field technique in a three dimensional volume is about 20 s per iteration step on a Hewlett‐Packard 735 workstation. A well converged solution is normally obtained within about 50–100 iterations or within 15–30 min.

An iterative pencil beam algorithm for optimization of multidimensional radiation therapy dose plans has been developed. The algorithm allows the use of both physical and radiobiological treatment objective functions and allows arbitrary sampling such as straight Cartesian grids with linear or nonlinear sampling functions or random sampling. The algorithm can account for and optimally combine almost all the degrees of freedom at an advanced radiotherapy clinic, such as different beam modalities and spectra, beam directions, beam fluence distributions, and time-dose fractionations. The algorithm allows for external charged and neutral beams as well as intracavitary and interstitial sources to be optimally combined. A quantity termed the generalized fluence vector is introduced, combining fluences and energy fluences from external beams as well as the radiation source densities of intracavitary and interstitial sources or external source distributions. The positivity constraint on the generalized fluence can therefore be applied directly during the optimization procedure. The convergence properties and the required iteration time of the algorithm are discussed. Several examples with combinations of photon and electron beams of different energies and directions of incidence are presented. The optimization has been made with the treatment objective to maximize the probability of achieving tumor control without causing severe complications in healthy normal tissues.

Purpose: Proton's physical properties offer the maximum radiationdose to the target volume, which is an advantage in the radiotherapy development. The aim of this study is the clinical derivation of the dose‐response relations regarding urinary complications from combined photon and proton prostate radiotherapy.Material and Methods: 189 patients were treated for prostate cancer at Uppsala's Academic Hospital, Sweden from 2002 to 2006. The patients were treated with a proton boost of 20 Gy given in 5 Gy, followed by a X‐ray treatment of 50 Gy in 2 Gy fractions. The dose distribution delivered to the organs of interest and the clinical treatment outcomes (24 months follow‐up time) were available for 72 patients. The delineated regions of interest were the urinary bladder and the region of the lower 3 cm part of the bladder. The photon and protondoses were calculated with the BED (biologically effective dose) concept. Additionally, an RBE of 1.1 was used for protons. The radiobiological parameter acquisition of D 50 and γ was performed for the Poisson, Binomial and Probit models applying the Maximum Likelihood method. Results: Of the 72 patients, 15 (21%) showed urinary complications, whereas 57 (79%) didn't. The best estimated values of the parameters for the whole bladder and bladder 3 cm are D 50=104.0 Gy, γ =0.7 and D 50=88.4 Gy, γ =1.3 for Poisson,D 50=108.0 Gy, γ=0.6 and D 50=88.6 Gy, γ=1.3 for Binomial, whereas for Probit are D 50=97.0 Gy, γ=1.0 and D 50=85.6 Gy, γ=1.8, respectively. The analysis of the mean cumulative DVHs proves that the urinary complications were mainly due to the photontreatment.Conclusions: The dose‐response relations are described well by the estimated parameters of the Poisson, Binomial and Probit models. The results are necessary for a prospective estimation of the clinical effectiveness of radiation therapy using combinations of different radiation modalities.