A 5- to 8-year randomized study on the treatment of cervical radiculopathy: anterior cervical decompression and fusion plus physiotherapy versus physiotherapy alone.

OBJECTIVE The aim of this study was to evaluate the 5- to 8-year outcome of anterior cervical decompression and fusion (ACDF) combined with a structured physiotherapy program as compared with that following the same physiotherapy program alone in patients with cervical radiculopathy. No previous prospective randomized studies with a follow-up of more than 2 years have compared outcomes of surgical versus nonsurgical intervention for cervical radiculopathy. METHODS Fifty-nine patients were randomized to ACDF surgery with postoperative physiotherapy (30 patients) or to structured physiotherapy alone (29 patients). The physiotherapy program included general and specific exercises as well as pain coping strategies. Outcome measures included neck disability (Neck Disability Index [NDI]), neck and arm pain intensity (visual analog scale [VAS]), health state (EQ-5D questionnaire), and a patient global assessment. Patients were followed up for 5-8 years. RESULTS After 5-8 years, the NDI was reduced by a mean score% of 21 (95% CI 14-28) in the surgical group and 11% (95% CI 4%-18%) in the nonsurgical group (p = 0.03). Neck pain was reduced by a mean score of 39 mm (95% CI 26-53 mm) compared with 19 mm (95% CI 7-30 mm; p = 0.01), and arm pain was reduced by a mean score of 33 mm (95% CI 18-49 mm) compared with 19 mm (95% CI 7-32 mm; p = 0.1), respectively. The EQ-5D had a mean respective increase of 0.29 (95% CI 0.13-0.45) compared with 0.14 (95% CI 0.01-0.27; p = 0.12). Ninety-three percent of patients in the surgical group rated their symptoms as "better" or "much better" compared with 62% in the nonsurgical group (p = 0.005). Both treatment groups experienced significant improvement over baseline for all outcome measures. CONCLUSIONS In this prospective randomized study of 5- to 8-year outcomes of surgical versus nonsurgical treatment in patients with cervical radiculopathy, ACDF combined with physiotherapy reduced neck disability and neck pain more effectively than physiotherapy alone. Self-rating by patients as regards treatment outcome was also superior in the surgery group. No significant differences were seen between the 2 patient groups as regards arm pain and health outcome.

Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy.

BACKGROUND AND PURPOSE: To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom 'absence of vaginal elasticity' and how time to follow-up influences this relation. MATERIAL AND METHODS: The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patient's age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. RESULTS: The dose-response parameters for 'absence of vaginal elasticity' according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL=-39.8, D50=49.7 (47.2-52.4) Gy, γ50=1.40 (1.12-1.70) and LL=-37.4, D50=46.9 (43.5-50.9) Gy, γ50=1.81 (1.17-2.51) respectively. CONCLUSIONS: The proposed model, which describes the influence of time to follow-up on the dose-response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom 'absence of vaginal elasticity' increases with time to follow-up, while D50 decreases.

Factors Affecting the Outcome of Surgical Versus Nonsurgical Treatment of Cervical Radiculopathy: A Randomized, Controlled Study.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To analyze factors that may influence the outcome of anterior cervical decompression and fusion (ACDF) followed by physiotherapy versus physiotherapy alone for treatment of patients with cervical radiculopathy. SUMMARY OF BACKGROUND DATA: An understanding of patient-related factors affecting the outcome of ACDF is important for preoperative patient selection. No previous prospective, randomized study of treatment effect modifiers relating to outcome of ACDF compared with physiotherapy has been carried out. METHODS: 60 patients with cervical radiculopathy were randomized to ACDF followed by physiotherapy or physiotherapy alone. Data for possible modifiers of treatment outcome at 1 year, such as sex, age, duration of pain, pain intensity, disability (Neck Disability Index, NDI), patient expectations of treatment, anxiety due to neck/arm pain, distress (Distress and Risk Assessment Method), self-efficacy (Self-Efficacy Scale) health status (EQ-5D), and magnetic resonance imaging findings were collected. A multivariate analysis was performed to find treatment effect modifiers affecting the outcome regarding arm/neck pain intensity and NDI. RESULTS: Factors that significantly altered the treatment effect between treatment groups in favor of surgery were: duration of neck pain less than 12 months (P = 0.007), duration of arm pain less than 12 months (P = 0.01) and female sex (P = 0.007) (outcome: arm pain), low EQ-5D index (outcome: neck pain, P = 0.02), high levels of anxiety due to neck/arm pain (outcome: neck pain, P = 0.02 and NDI, P = 0.02), low Self-Efficacy Scale score (P = 0.05), and high Distress and Risk Assessment Method score (P = 0.04) (outcome: NDI). No factors were found to be associated with better outcome with physiotherapy alone. CONCLUSION: In this prospective, randomized study of patients with cervical radiculopathy, short duration of pain, female sex, low health quality, high levels of anxiety due to neck/arm pain, low self-efficacy, and a high level of distress before treatment were associated with better outcome from surgery. No factors were found to be associated with better outcome from physiotherapy alone.

Impact of dose and sensitivity heterogeneity on TCP.

This present paper presents an analytical description and numerical simulations of the influence of macroscopic intercell dose variations and intercell sensitivity variations on the probability of controlling the tumour. Computer simulations of tumour control probability accounting for heterogeneity in dose and radiation sensitivity were performed. An analytical expression for tumor control probability accounting for heterogeneity in sensitivity was also proposed and validated against simulations. The results show good agreement between numerical simulations and the calculated TCP using the proposed analytical expression for the case of a heterogeneous dose and sensitivity distributions. When the intratumour variations of dose and sensitivity are taken into account, the total dose required for achieving the same level of control as for the case of homogeneous distribution is only slightly higher, the influence of the variations in the two factors taken into account being additive. The results of this study show that the interplay between cell or tumour variation in the sensitivity to radiation and the inherent heterogeneity in dose distribution is highly complex and therefore should be taken into account when predicting the outcome of a given treatment in terms of tumor control probability.

Predicting the sensitivity to ion therapy based on the response to photon irradiation--experimental evidence and mathematical modelling.

BACKGROUND/AIM: The use of ion radiation therapy is growing due to the continuously increasing positive clinical experience obtained. Therefore, there is a high interest in radio-biological experiments comparing the relative efficiency in cell killing of ions and photons as photons are currently the main radiation modality used for cancer treatment. This comparison is particularly important since the treatment planning systems (TPSs) used at the main ion therapy Centers make use of parameters describing the cellular response to photons, respectively ions, determined in vitro. It was, therefore, the aim of this article to compare the effects of high linear energy transfer (LET) ion radiation with low LET photons and determine whether the cellular response to low LET could predict the response to high LET irradiation. MATERIALS AND METHODS: Clonogenic cell survival data of five tumor cell lines irradiated with different ion beams of similar, clinically-relevant, LET were studied in relation to response to low LET photons. Two mathematical models were used to fit the data, the repairable-conditionally repairable damage (RCR) model and the linear quadratic (LQ) model. RESULTS: The results indicate that the relative biological efficiency of the high LET radiation assessed with the RCR model could be predicted based only on the response to the low LET irradiation. CONCLUSION: The particular features of the RCR model indicate that tumor cells showing a large capacity for repairing the damage will have the larger benefit from radiation therapy with ion beams.

Surgery versus nonsurgical treatment of cervical radiculopathy: a prospective, randomized study comparing surgery plus physiotherapy with physiotherapy alone with a 2-year follow-up.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To study the outcome of anterior cervical decompression and fusion combined with a structured physiotherapy program compared with the same physiotherapy program alone for patients with cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Knowledge concerning the effects of interventions for patients with cervical radiculopathy is scarce due to a lack of randomized studies. METHODS: Sixty-three patients were randomized to surgery with postoperative physiotherapy (n = 31) or physiotherapy alone (n = 32). The surgical group was treated with anterior cervical decompression and fusion. The physiotherapy program included general/specific exercises and pain-coping strategies. The outcome measures were disability (Neck Disability Index), neck and arm pain intensity (visual analogue scale), and the patient's global assessment. Patients were followed for 24 months. RESULTS: The result from the repeated-measures analysis of variance showed no significant between-group difference for Neck Disability Index (P = 0.23). For neck pain intensity, the repeated-measures analysis of variance showed a significant between-group difference during the study period in favor of the surgical group (P = 0.039). For arm pain intensity, no significant between-group differences were found according to the repeated-measures analysis of variance (P = 0.580). Eighty-seven percent of the patients in the surgical group rated their symptoms as "better/much better" at the 12-month follow-up compared with 62% in the nonsurgical group (P < 0.05). At 24 months, the corresponding figures were 81% and 69% (P = 0.28). The difference was significant only at the 12-month follow-up in favor of the surgical group. Significant reduction in Neck Disability Index, neck pain, and arm pain compared with baseline was seen in both groups (P < 0.001). CONCLUSION: In this prospective, randomized study of patients with cervical radiculopathy, it was shown that surgery with physiotherapy resulted in a more rapid improvement during the first postoperative year, with significantly greater improvement in neck pain and the patient's global assessment than physiotherapy alone, but the differences between the groups decreased after 2 years. Structured physiotherapy should be tried before surgery is chosen. LEVEL OF EVIDENCE: 2.

Investigation of the dose- and time-dependence of the induction of different types of cell death in a small­cell lung cancer cell line: Implementation of the repairable-conditionally repairable model.

The purpose of this study was to quantify and model various types of cell death for a small-cell lung cancer (SCLC) cell line (U1690) after exposure to a 137Cs source and as well as to compare the linear-quadratic (LQ) and repairable-conditionally repairable model (RCR). This study is based on four different experiments that were taken place at Cancer Centrum Karolinska (CCK). A human small-cell lung cancer (SCLC) cell line after the exposure to a 137Cs source was used for the extraction of the clonogenic cell survival curve. Additionally, for the determination and quantification of various modes of cell death the method of fluorescence staining was implemented, where the cell deaths were categorized based on morphological characteristics. The percentage of cells in each phase of the cell cycle was investigated with flow cytometry analysis. The quantification of senescent cells was performed by staining the samples with senescence-associated ß-galactosidase (SA-ß-Gal) solution and then scoring as senescent cells those that had incorporated the substance. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the examined model. In this model, the modes of cell death are divided into three categories: apoptotic, senescent and other types of cell death (necrotic/apoptotic, necrotic, micronuclei and giant). In the clonogenic cell survival assay, the fitting of the RCR model gives a χ(2)-value of 6.10 whereas for the LQ model became 9.61. In the fluorescence microscopy and senescence assay, the probability of the three different modes of cell death on day 2 seems to increases with a dose up to about 10 Gy where there is saturation. On day 7 a significant induction of apoptosis in a dose- and time-dependent manner was evident, whereas senescence was slightly increased in response to dose but not to time. As for the 'other types of cell death' mode on day 7 showed a higher probability than the one on day 2 and as well as a prominent dose-dependence. The RCR model fits better to the experimental data than the LQ model. On day 2 there is a slight increase of the apoptotic and senescent probability with dose. On the other hand, on day 7 the shape of the curve of apoptosis differs and a sigmoidal increase with dose is observed. At both time-points, the present model fits the data reasonably well. Due to the fact that the clonogenic survival does not coincide with the one extracted from the fluorescence microscopy, a more accurate way to quantify cell death needs to be used, e.g. computerized video time-lapse (CVTL).

Physical function outcome in cervical radiculopathy patients after physiotherapy alone compared with anterior surgery followed by physiotherapy: a prospective randomized study with a 2-year follow-up.

STUDY DESIGN: Prospective randomized study. OBJECTIVE: To investigate differences in physical functional outcome in patients with radiculopathy due to cervical disc disease, after structured physiotherapy alone (consisting of neck-specific exercises with a cognitive-behavioral approach) versus after anterior cervical decompression and fusion (ACDF) followed by the same structured physiotherapy program. SUMMARY OF BACKGROUND DATA: No earlier studies have evaluated the effectiveness of a structured physiotherapy program or postoperative physical rehabilitation after ACDF for patients with magnetic resonance imaging-verified nerve compression due to cervical disc disease. METHODS: Our prospective randomized study included 63 patients with radiculopathy and magnetic resonance imaging-verified nerve root compression, who were randomized to receive either ACDF in combination with physiotherapy or physiotherapy alone. For 49 of these patients, an independent examiner measured functional outcomes, including active range of neck motion, neck muscle endurance, and hand-related functioning before treatment and at 3-, 6-, 12-, and 24-month follow-ups. RESULTS: There were no significant differences between the 2 treatment alternatives in any of the measurements performed (P = 0.17-0.91). Both groups showed improvements over time in neck muscle endurance (P ≤ 0.01), manual dexterity (P ≤ 0.03), and right-handgrip strength (P = 0.01). CONCLUSION: Compared with a structured physiotherapy program alone, ACDF followed by physiotherapy did not result in additional improvements in neck active range of motion, neck muscle endurance, or hand-related function in patients with radiculopathy. We suggest that a structured physiotherapy program should precede a decision for ACDF intervention in patients with radiculopathy, to reduce the need for surgery. LEVEL OF EVIDENCE: 2.

A model for the relative biological effectiveness of protons: the tissue specific parameter α/ß of photons is a predictor for the sensitivity to LET changes.

BACKGROUND: The biological effects of particles are often expressed in relation to that of photons through the concept of relative biological effectiveness, RBE. In proton radiotherapy, a constant RBE of 1.1 is usually assumed. However, there is experimental evidence that RBE depends on various factors. The aim of this study is to develop a model to predict the RBE based on linear energy transfer (LET), dose, and the tissue specific parameter α/ß of the linear-quadratic model for the reference radiation. Moreover, the model should capture the basic features of the RBE using a minimum of assumptions, each supported by experimental data. MATERIAL AND METHODS: The α and ß parameters for protons were studied with respect to their dependence on LET. An RBE model was proposed where the dependence of LET is affected by the (α/ß)phot ratio of photons. Published cell survival data with a range of well-defined LETs and cell types were selected for model evaluation rendering a total of 10 cell lines and 24 RBE values. RESULTS AND CONCLUSION: A statistically significant relation was found between α for protons and LET. Moreover, the strength of that relation varied significantly with (α/ß)phot. In contrast, no significant relation between ß and LET was found. On the whole, the resulting RBE model provided a significantly improved fit (p-value < 0.01) to the experimental data compared to the standard constant RBE. By accounting for the α/ß ratio of photons, clearer trends between RBE and LET of protons were found, and our results suggest that late responding tissues are more sensitive to LET changes than early responding tissues and most tumors. An advantage with the proposed RBE model in optimization and evaluation of treatment plans is that it only requires dose, LET, and (α/ß)phot as input parameters. Hence, no proton specific biological parameters are needed.

Dose-response relationships for an atomized symptom of fecal incontinence after gynecological radiotherapy.

PURPOSE: The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future. MATERIAL AND METHODS: Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model. RESULTS: The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs. CONCLUSIONS: In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.

Limitations (and merits) of PENELOPE as a track-structure code.

PURPOSE: To outline the limitations of PENELOPE (acronym of PENetration and Energy LOss of Positrons and Electrons) as a track-structure code, and to comment on modifications that enable its fruitful use in certain microdosimetry and nanodosimetry applications. METHODS: Attention is paid to the way in which inelastic collisions of electrons are modelled and to the ensuing implications for microdosimetry analysis. RESULTS: Inelastic mean free paths and collision stopping powers calculated with PENELOPE and two well-known optical-data models are compared. An ad hoc modification of PENELOPE is summarized where ionization and excitation of liquid water by electron impact is simulated using tables of realistic differential and total cross sections. CONCLUSIONS: PENELOPE can be employed advantageously in some track-structure applications provided that the default model for inelastic interactions of electrons is replaced by suitable tables of differential and total cross sections.

The influence of dose heterogeneity on tumour control probability in fractionated radiation therapy.

Theoretical modelling of tumour control probability (TCP) with respect to non-uniformity in the dose to the tumour, alternate fractionation schemes and tumour kinetics is a very useful tool for assessment of the influence of changes in dosimetric or radiobiological factors on the outcome of the treatment. Various attempts have been made to also include effects from non-uniform dose to the tumour volume, but the problem has not been fully solved and many factors were totally neglected or not accurately taken into account. This paper presents derivations of analytical expressions of TCP for macroscopic inter-cell dose variations and for random inter-fractional variations in average tumour dose, based on binomial statistics for the TCP and the well-known linear quadratic model for the cell survival. Numerical calculations have been performed to validate the analytical expressions. An analysis of the influence of the deterministic and stochastic heterogeneity in dose delivery on the TCP was performed. The precision requirements in dose delivery are discussed briefly with the support of the presented results. The main finding of this paper is that it is primarily the shape of the cell survival curve that governs how the response is affected by macroscopic dose variations. The analytical expressions for TCP accounting for heterogeneity in dose can quite well describe the TCP for varying dose from cell to cell and random dose in each fraction. An increased TCP is seen when a large number of fractions are used and the variations in dose to the cells are rather high for tissues with low α/ß.

A Monte Carlo program for the analysis of low-energy electron tracks in liquid water.

A Monte Carlo code for the event-by-event simulation of electron transport in liquid water is presented. The code, written in C++, can accommodate different interaction models. Currently it implements cross sections for ionizing collisions calculated with the model developed by Dingfelder et al (1998 Radiat. Phys. Chem. 53 1-18, 2008 Radiat. Res. 169 584-94) and cross sections for elastic scattering computed within the static-exchange approximation (Salvat et al 2005 Comput. Phys. Commun. 165 157-90). The latter cross sections coincide with those recommended in ICRU Report 77 (2007). Other included interaction mechanisms are excitation by electron impact and dissociative attachment. The main characteristics of the code are summarized. Various track penetration parameters, including the detour factor, are defined as useful tools to quantify the geometrical extent of electron tracks in liquid water. Results obtained with the present microdosimetry code are given in the form of probability density functions for initial electron kinetic energies ranging from 0.1 to 10 keV. The sensitivity of the simulated distributions to the choice of alternative physics models has been briefly explored. The discrepancies with equivalent simulations reported by Wilson et al (2004 Radiat. Res. 161 591-6) stem from the adopted cross sections for elastic scattering, which determine largely the spatial evolution of low-energy electron tracks.

Health-related quality of life in patients with surgically treated lumbar disc herniation: 2- and 7-year follow-up of 117 patients.

BACKGROUND AND PURPOSE: Health-related quality of life (HRQoL) instruments have been of increasing interest for evaluation of medical treatments over the past 10-15 years. In this prospective, long-term follow-up study we investigated the influence of preoperative factors and the change in HRQoL over time after lumbar disc herniation surgery. METHODS: 117 patients surgically treated for lumbar disc herniation (L4-L5 or L5-S1) were evaluated with a self-completion HRQoL instrument (EQ-5D) preoperatively, after 2 years (96 patients) and after 7 years (89 patients). Baseline data (age, sex, duration of leg pain, surgical level) and degree of leg and back pain (VAS) were obtained preoperatively. The mean age was 39 (18-66) years, 54% were men, and the surgical level was L5-S1 in 58% of the patients. The change in EQ-5D score at the 2-year follow-up was analyzed by testing for correlation and by using a multiple regression model including all baseline factors (age, sex, duration of pain, degree of leg and back pain, and baseline EQ-5D score) as potential predictors. RESULTS: 85% of the patients reported improvement in EQ-5D two years after surgery and this result remained at the long-term follow-up. The mean difference (change) between the preoperative EQ-5D score and the 2-year and 7-year scores was 0.59 (p < 0.001) and 0.62 (p < 0.001), respectively. However, the HRQoL for this patient group did not reach the mean level of previously reported values for a normal population of the same age range at any of the follow-ups. The changes in EQ-5D score between the 2- and 7-year follow-ups were not statistically significant (mean change 0.03, p = 0.2). There was a correlation between baseline leg pain and the change in EQ-5D at the 2-year (r = 0.33, p = 0.002) and 7-year follow-up (r = 0.23, p = 0.04). However, when using regression analysis the only statistically significant predictor for change in EQ-5D was baseline EQ-5D score. INTERPRETATION: Our findings suggest that HRQoL (as measured by EQ-5D) improved 2 years after lumbar disc herniation surgery, but there was no further improvement after 5 more years. Low quality of life and severe leg pain at baseline are important predictors of improvement in quality of life after lumbar disc herniation surgery.

Comparison of dose response models for predicting normal tissue complications from cancer radiotherapy: application in rat spinal cord.

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ2-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

Toolkit for determination of dose-response relations, validation of radiobiological parameters and treatment plan optimization based on radiobiological measures.

Accurately determined dose-response relations of the different tumors and normal tissues should be estimated and used in the clinic. The aim of this study is to demonstrate developed tools that are necessary for determining the dose-response parameters of tumors and normal tissues, for clinically verifying already published parameter sets using local patient materials and for making use of all this information in the optimization and comparison of different treatment plans and radiation techniques. One of the software modules (the Parameter Determination Module) is designed to determine the dose-response parameters of tumors and normal tissues. This is accomplished by performing a maximum likelihood fitting to calculate the best estimates and confidence intervals of the parameters used by different radiobiological models. Another module of this software (the Parameter Validation Module) concerns the validation and compatibility of external or reported dose-response parameters describing tumor control and normal tissue complications. This is accomplished by associating the expected response rates, which are calculated using different models and published parameter sets, with the clinical follow-up records of the local patient population. Finally, the last module of the software (the Radiobiological Plan Evaluation Module) is used for estimating and optimizing the effectiveness a treatment plan in terms of complication-free tumor control, P(+). The use of the Parameter Determination Module is demonstrated by deriving the dose-response relation of proximal esophagus from head and neck cancer radiotherapy. The application of the Parameter Validation Module is illustrated by verifying the clinical compatibility of those dose-response parameters with the examined treatment methodologies. The Radiobiological Plan Evaluation Module is demonstrated by evaluating and optimizing the effectiveness of head and neck cancer treatment plans. The results of the radiobiological evaluation are compared against dosimetric criteria. The presented toolkit appears to be very convenient and efficient for clinical implementation of radiobiological modeling. It can also be used for the development of a clinical data and health information database for assisting the performance of epidemiological studies and the collaboration between different institutions within research and clinical frameworks.

Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy.

BACKGROUND AND PURPOSE: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. MATERIAL AND METHODS: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. RESULTS: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D(50)=61.5 Gy (52.9-84.9 Gy), γ=1.4 (0.8-2.6) and s=0.1 (0.01-0.3). CONCLUSIONS: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.

Vascular structure and binomial statistics for response modeling in radiosurgery of cerebral arteriovenous malformations.

Radiation treatment of arteriovenous malformations (AVMs) has a slow and progressive vaso-occlusive effect. Some studies suggested the possible role of vascular structure in this process. A detailed biomathematical model has been used, where the morphological, biophysical and hemodynamic characteristics of intracranial AVM vessels are faithfully reproduced. The effect of radiation on plexiform and fistulous AVM nidus vessels was simulated using this theoretical model. The similarities between vascular and electrical networks were used to construct this biomathematical AVM model and provide an accurate rendering of transnidal and intranidal hemodynamics. The response of different vessels to radiation and their obliteration probability as a function of different angiostructures were simulated and total obliteration was defined as the probability of obliteration of all possible vascular pathways. The dose response of the whole AVM is observed to depend on the vascular structure of the intra-nidus AVM. Furthermore, a plexiform AVM appears to be more prone to obliteration compared with an AVM of the same size but having more arteriovenous fistulas. Finally, a binomial model was introduced, which considers the number of crucial vessels and is able to predict the dose response behavior of AVMs with a complex vascular structure.