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Background and purpose The FiGaRO trial assessed the feasibility and safety of using an FDG-PET-based dose-painting technique to deliver a radiotherapy (RT) boost to the FDG-avid primary tumour in patients with locally advanced high and intermediate risk oropharyngeal cancer. Materials and method Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5 Gy in30 fractions delivered using a simultaneous integrated boost Intensity Modulated RT (SIB-IMRT) technique. RT was delivered with concomitant Cisplatin following 2 cycles of induction chemotherapy. The primary outcome was the incidence of grade ≥ 3 late mucosal toxicity 12 months post-treatment, with an excess rate of >10% regarded as unacceptable. Results Twenty-nine patients were included and twenty-four were treated between 2014 and 2018, in two UK centres. Median follow-up was 36 months (range 4–56 months). Pre-defined planning target volume objectives and organ at risk dose constraints were met in all cases. There were no incidents of acute grade 4 toxicity. There were 4 cases of grade ≥ 3 mucosal toxicity at 12 months post-treatment (19.1%). There were no cases of persistent mucosal ulceration at 12 months. Overall survival at 3-years was 87.5%, 92.9% for intermediate and 70.0% for high risk patients. Conclusion Late toxicity rates, although higher than anticipated, are comparable to contemporary published data for standard dose chemo-IMRT. Results suggest improved 3y survival rates for high risk patients. This approach merits further investigation. ClinicalTrials.gov Identifier: NCT02953197.

There is a growing interest in the use of flattening filter free (FFF) beams due to the shorter treatment times. The reduction of head scatter suggests a better radiation protection to radiotherapy patients, considering the expected decrease in peripheral surface dose (PSD). In this work, PSD of flattened (FF) and FFF-photon beams was compared. A radiochromic film calibration method to reduce energy dependence was used. PSD was measured at distances from 2 to 50 cm to the field border for different square field sizes, modifying relevant clinical parameters. Also, clinical breast and prostate stereotactic body radiotherapy (SBRT) plans were studied. For square beams, FFF PSD is lower compared with FF PSD (differences ranging from 3 to 64%) and 10 MV FFF yields to the lowest value, for distances greater than 5 cm. For SBRT plans, near and far away from the field border, there is a reduction of PSD for FFF-beams, but the behavior at intermediate distances should be checked depending on the case.

Background and purpose The objective of this work is to evaluate the risk of carcinogenesis of low dose ionizing radiation therapy (LDRT), for treatment of immune-related pneumonia following COVID-19 infection, through the estimation of effective dose and the lifetime attributable risk of cancer (LAR). Material and methods LDRT treatment was planned in male and female computational phantoms. Equivalent doses in organs were estimated using both treatment planning system calculations and a peripheral dose model (based on ionization chamber measurements). Skin dose was estimated using radiochromic films. Later, effective dose and LAR were calculated following radiation protection procedures. Results Equivalent doses to organs per unit of prescription dose range from 10 mSv/cGy to 0.0051 mSv/cGy. Effective doses range from 204 mSv to 426 mSv, for prescription doses ranging from 50 cGy to 100 cGy. Total LAR for a prescription dose of 50 cGy ranges from 1.7 to 0.29% for male and from 4.9 to 0.54% for female, for ages ranging from 20 to 80 years old. Conclusions The organs that mainly contribute to risk are lung and breast. Risk for out-of-field organs is low, less than 0.06 cases per 10000. Female LAR is on average 2.2 times that of a male of the same age. Effective doses are of the same order of magnitude as the higher-dose interventional radiology techniques. For a 60 year-old male, LAR is 8 times that from a cardiac CT, when prescription dose is 50 cGy.

Purpose Biological treatment plan evaluation does not currently consider second cancer induction from peripheral doses associated to photon radiotherapy. The aim is to propose a methodology to characterize the therapeutic window by means of an integral radiobiological approach, which considers not only Tumour Control Probability ( TCP ) and Normal Tissue Complication Probability ( NTCP ) but also Secondary Cancer Probability ( SCP ). Methods Uncomplicated and Cancer-Free Control Probability ( UCFCP ) function has been proposed assuming a statistically uncorrelated response for tumour and normal tissues. The Poisson’s and Lyman’s models were chosen for TCP and NTCP calculations, respectively. SCP was modelled as the summation of risks associated to photon and neutron irradiation of radiosensitive organs. For the medium (>4 Gy) and low dose regions, mechanistic and linear secondary cancer risks models were used, respectively. Two conformal and intensity-modulated prostate plans at 15 MV (same prescription dose) were selected to illustrate the UCFCP features. Results UCFCP exhibits a bell-shaped behaviour with its maximum inside the therapeutic window. SCP values were not different for the plans analysed (∼2.4%) and agreed with published epidemiological results. Therefore, main differences in UCFCP came from differences in rectal NTCP (18% vs 9% for 3D-CRT and IMRT, respectively). According to UCFCP values, the evaluated IMRT plan ranked first. Conclusions The level of SCP was found to be similar to that of NTCP complications which reinforces the importance of considering second cancer risks as part of the possible late sequelae due to treatment. Previous concerns about the effect of peripheral radiation, especially neutrons, in the induction of secondary cancers can be evaluated by quantifying the UCFCP .

Purpose Neutron peripheral contamination in high-energy radiotherapy implies an increase of secondary radiation-induced cancer risk. Although peripheral neutron dose (PND) has been evaluated in organs, few studies have been performed regarding patient size. This work aims to improve an existing methodology for adult patient PND estimations to generalize it to young and children, for its implementation in treatment planning systems (TPS). Methods As a first step, we aimed to generalize the previous model to be usable with any thermal neutron detector. Then, taking into account total neutron spectra and dose-to-point thermal neutron fluence measurements for three phantom sizes (adult, teen and child) and two common treatment locations (H&N and abdomen), the new model was proposed. It represents an upgraded parameterization and extension of the existing one, including patient anatomy. Finally, comparison between estimations and measurements, as well as validation against the original model, was carried out for 510 measured patients. Results Concordance found between experimental and theoretical estimations makes us confident about later implementation in treatment planning systems. Comparison among the previous and upgraded models shows no significant differences for the adult case. However, an important underestimation (34.1% on average) can be observed regarding child case for the original one. Conclusions An improved generalization of an existing PND model, considering patient anatomy has been validated and used in real patients. The final methodology is easily implementable in clinical routine and TPS thanks to the ready availability of input parameters (patient height and weight, high-energy MU and facility characterization).

One of the major causes of secondary malignancies after radiotherapy treatments are peripheral doses, known to increase for some newer techniques (such as IMRT or VMAT). For accelerators operating above 10MV, neutrons can represent important contribution to peripheral doses. This neutron contamination can be measured using different passive or active techniques, available in the literature. As far as active (or direct-reading) procedures are concerned, a major issue is represented by their parasitic photon sensitivity, which can significantly affect the measurement when the point of test is located near to the field-edge. This work proposes a simple method to estimate the unwanted photon contribution to these neutrons. As a relevant case study, the use of a recently neutron sensor for "in-phantom" measurements in high-energy machines was considered. The method, called "Dual Energy Photon Subtraction" (DEPS), requires pairs of measurements performed for the same treatment, in low-energy (6MV) and high energy (e.g. 15MV) fields. It assumes that the peripheral photon dose (PPD) at a fixed point in a phantom, normalized to the unit photon dose at the isocenter, does not depend on the treatment energy. Measurements with ionization chamber and Monte Carlo simulations were used to evaluate the validity of this hypothesis. DEPS method was compared to already published correction methods, such as the use of neutron absorber materials. In addition to its simplicity, an advantage of DEPs procedure is that it can be applied to any radiotherapy machine.

Purpose An accurate assessment of out-of-field dose is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. Although treatment planning systems (TPSs) calculate dose distributions outside the treatment field, little is known about the accuracy of these calculations. The aim of this work is to thoroughly compare the out-of-field dose distributions given by two algorithms implemented in the Monaco TPS, with measurements and full Monte Carlo simulations. Methods Out-of-field dose distributions predicted by the collapsed cone convolution (CCC) and Monte Carlo (MCMonaco ) algorithms, built into the commercially available Monaco version 5.11 TPS, are compared with measurements carried out on an Elekta Axesse linear accelerator. For the measurements, ion chambers, thermoluminescent dosimeters, and EBT3 film are used. The BEAMnrc code, built on the EGSnrc system, is used to create a model of the Elekta Axesse with the Agility collimation system, and the space phase file generated is scored by DOSXYZnrc to generate the dose distributions (MCEGSnrc ). Three different irradiation scenarios are considered: (a) a 10 × 10 cm2 field, (b) an IMRT prostate plan, and (c) a three-field lung plan. Monaco's calculations, experimental measurements, and Monte Carlo simulations are carried out in water and/or in an ICRP110 phantom. Results For the 10 × 10 cm2 field case, CCC underestimated the dose, compared to ion chamber measurements, by 13% (differences relative to the algorithm) on average between the 5% and the ≈2% isodoses. MCMonaco underestimated the dose only from approximately the 2% isodose for this case. Qualitatively similar results were observed for the studied IMRT case when compared to film dosimetry. For the three-field lung plan, dose underestimations of up to ≈90% for MCMonaco and ≈60% for CCC, relative to MCEGSnrc simulations, were observed in mean dose to organs located beyond the 2% isodose. Conclusions This work shows that Monaco underestimates out-of-field doses in almost all the cases considered. Thus, it does not describe dose distribution beyond the border of the field accurately. This is in agreement with previously published works reporting similar results for other TPSs. Analytical models for out-of-field dose assessment, MC simulations or experimental measurements may be an adequate alternative for this purpose.

[Purpose] To perform a systematic and thorough assessment, using the Uncomplicated and Cancer-Free Control Probability (UCFCP) function, of a broad range of photon prostate cancer RT treatments, on the same scenario (a unique pelvic CT set). UCFCP considers, together with the probabilities of local tumour control (TCP) and deterministic (late) sequelae (NTCP), the second primary cancer risk (SPCR) due to photon and neutron peripheral doses., [Methods and materials] Thirty-six radiotherapy plans were produced for the same CT. 6, 10, 15 and 18 MV 3DCRT, IMRT and VMAT (77.4 Gy in 43 fractions) and 6 and 10 MV SBRT (36.25 Gy in 5 fractions with flattened and FFF beams) for Elekta, Siemens and Varian Linacs plans were included. DVH and peripheral organ dosimetry were used to compute TCP, NTCP, and SPCR (the competition and LNT models) for further plan ranking., [Results] Biological models (and parameters) used predicted an outcome which is in agreement with epidemiological findings. SBRT plans showed the lowest SPCR and a below average NTCPrectal. High energy plans did not rank worse than the low energy ones. Intensity modulated plans were ranked above the 3D conformal techniques., [Conclusions] According to UCFCP, the best plans were the10 MV SBRTs. SPCR rates were low and did not show a substantial impact on plan ranking. High energy intensity-modulated plans did not increase in excess the average of SPCR. Even more, they ranked among the best, provided that MU were efficiently managed., BSN acknowledges the support of Conicyt FONDECYT Regular 2018 (N1181133) and of Pontificia Universidad Católica de Chile [EPB2016, P1702/2017 and “Concurso de Apoyo a Sabáticos Internacionales 2017”]. MRE would like to thank Banco Santander for its support through the grant program ‘‘Becas Iberoamérica. Jóvenes Profesores e Investigadores y Alumnos de Doctorado Santander Universidad”.

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D‐CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.

Intra-tumor variability of oxygenation and clonogenic cell density causes tumor non-uniform spatial response to radiation. Strategies like dose redistribution/boosting, whose impact should be quantified in terms of tumor control probability (TCP), have been proposed to improve treatment outcome. In 1999, Sanchez-Nieto et al. developed a tool to evaluate the impact of dose distribution inhomogeneities, compared to a reference homogeneous dose distribution, in terms of TCP. DVH data were used to calculate the so-called ∆TCP, defined as the difference in TCP arising from dose variations in individual DVH-bins. In this work, we develop an open source tool to calculate volumetric ∆TCP and evaluate the impact on TCP of: (i) Spatial dose distribution variations with respect to a reference dose; (ii) Spatial radiosensitivity variations with respect to a reference radiosensitivity; (iii) Simultaneous variation in dose distribution and radiosensitivity. ∆TCP calculations can be evaluated voxel-by-voxel, or in a user defined subvolume basis. The tool capabilities are shown with 2 examples of H&N RT treatments and subvolume contours data providing information about tumor oxygenation status. ΔTCP values are computed for a homogeneous dose to a well oxygenated tumor volume (with a homogeneous 5% vascular fraction), as reference condition, with respect to the same dose now considering 3 oxygenation levels and 3 cell density values (104, 106 and 107 cells/mm3, respectively). ΔTCP values are also computed for the comparison of a homogenous dose distribution vs a redistributed dose distribution delivered to the non-homogeneous tumor.

Motivated by the capabilities of modern radiotherapy techniques and by the recent developments of functional imaging techniques, dose painting by numbers (DPBN) was proposed to treat tumors with heterogeneous biological characteristics. This work studies different DPBN optimization techniques for virtual head and neck tumors assessing tumor response in terms of cell survival and tumor control probability with a previously published tumor response model (TRM). Uniform doses of 2 Gy are redistributed according to the microscopic oxygen distribution and the density distribution of tumor cells in four virtual tumors with different biological characteristics. In addition, two different optimization objective functions are investigated, which: i) minimize tumor cell survival (OFsurv) or; ii) maximize the homogeneity of the density of surviving tumor cells (OFstd). Several adaptive schemes, ranging from single to daily dose optimization, are studied and the treatment response is compared to that of the uniform dose. The results show that the benefit of DPBN treatments depends on the tumor reoxygenation capability, which strongly differed among the set of virtual tumors investigated. The difference between daily (fraction by fraction) and three weekly optimizations (at the beginning of weeks 1, 3 and 4) was found to be small, and higher benefit was observed for the treatments optimized using OFsurv. This in silico study corroborates the hypothesis that DPBN may be beneficial for treatments of tumors which show reoxygenation during treatment, and that a few optimizations may be sufficient to achieve this therapeutic benefit.

et al., Active thermal neutron detectors are used in a wide range of measuring devices in medicine, industry and research. For many applications, the long-term stability of these devices is crucial, so that very well controlled neutron fields are needed to perform calibrations and repeatability tests. A way to achieve such reference neutron fields, relying on a 3 MV Tandem Pelletron accelerator available at the CNA (Seville, Spain), is reported here. This paper shows thermal neutron field production and reproducibility characteristics over few days., This work would not be possible without the financial support of the CSN (Consejo de Seguridad Nuclear), Junta de Andalucía (FQM-8229), Mineco (FPA2013-47327-C2-1-R) and CEI-Biotic Granada (P-BS-64).

The aim of this work was to estimate peripheral neutron and photon doses associated with the conventional 3D conformal radiotherapy techniques in comparison to modern ones such as Intensity modulated radiation therapy and volumetric modulated arc therapy. Assessment in terms of second cancer incidence ought to peripheral doses was also considered. For that, a dosimetric methodology proposed by the authors has been applied beyond the region where there is no CT information and, thus, treatment planning systems do not calculate and where, nonetheless, about one third of second primary cancers occurs.

Purpose: Knowing the contribution of neutron to collateral effects in treatments is both a complex and a mandatory task. This work aims to present an operative procedure for neutron estimates in any facility using a neutron digital detector. Methods: The authors’ previous work established a linear relationship between the total second cancer risk due to neutrons (TR{sup n}) and the number of MU of the treatment. Given that the digital detector also presents linearity with MU, its response can be used to determine the TR{sup n} per unit MU, denoted as m, normally associated to a generic Linac model and radiotherapy facility. Thus, from the number of MU of each patient treatment, the associated risk can be estimated. The feasibility of the procedure was tested by applying it in eight facilities; patients were evaluated as well. Results: From the reading of the detector under selected irradiation conditions, m values were obtained for different machines, ranging from 0.25 × 10{sup −4}% per MU for an Elekta Axesse at 10 MV to 6.5 × 10{sup −4}% per MU for a Varian Clinac at 18 MV. Using these values, TR{sup n} of patients was estimated in each facility and compared to that frommore » the individual evaluation. Differences were within the range of uncertainty of the authors’ methodology of equivalent dose and risk estimations. Conclusions: The procedure presented here allows an easy estimation of the second cancer risk due to neutrons for any patient, given the number of MU of the treatment. It will enable the consideration of this information when selecting the optimal treatment for a patient by its implementation in the treatment planning system.« less

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

The increasing interest of the medical community to radioinduced second malignancies due to photoneutrons in patients undergoing high-energy radiotherapy, has stimulated in recent years the study of peripheral doses, including the development of some dedicated active detectors. Although these devices are designed to respond to neutrons only, their parasitic photon response is usually not identically zero and anisotropic. The impact of these facts on measurement accuracy can be important, especially in points close to the photon field-edge. A simple method to estimate the photon contribution to detector readings is to cover it with a thermal neutron absorber with reduced secondary photon emission, such as a borated rubber. This technique was applied to the TNRD (Thermal Neutron Rate Detector), recently validated for thermal neutron measurements in high-energy photon radiotherapy. The positive results, together with the accessibility of the method, encourage its application to other detectors and different clinical scenarios.

Neutron peripheral contamination in patients undergoing high-energy photon radiotherapy is considered as a risk factor for secondary cancer induction. Organ-specific neutron-equivalent dose estimation is therefore essential for a reasonable assessment of these associated risks. This work aimed to develop a method to estimate neutron-equivalent doses in multiple organs of radiotherapy patients. The method involved the convolution, at 16 reference points in an anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy spectra with the kerma and energy-dependent radiation weighting factor. This was then scaled with the total neutron fluence measured with passive detectors, at the same reference points, in order to obtain the equivalent doses in organs. The latter were correlated with the readings of a neutron digital detector located inside the treatment room during phantom irradiation. This digital detector, designed and developed by our group, integrates the thermal neutron fluence. The correlation model, applied to the digital detector readings during patient irradiation, enables the online estimation of neutron-equivalent doses in organs. The model takes into account the specific irradiation site, the field parameters (energy, field size, angle incidence, etc) and the installation (linac and bunker geometry). This method, which is suitable for routine clinical use, will help to systematically generate the dosimetric data essential for the improvement of current risk-estimation models.

The resistance of hypoxic cells to radiation, due to the oxygen dependence of radiosensitivity, is well known and must be taken into account to accurately calculate the radiation induced cell death. A proper modelling of the response of tumours to radiation requires deriving the distribution of oxygen at a microscopic scale. This usually involves solving the reaction-diffusion equation in tumour voxels using a vascularization distribution model. Moreover, re-oxygenation arises during the course of radiotherapy, one reason being the increase of available oxygen caused by cell killing, which can turn hypoxic tumours into oxic. In this work we study the effect of cell death kinetics in tumour oxygenation modelling, analysing how it affects the timing of re-oxygenation, surviving fraction and tumour control. Two models of cell death are compared, an instantaneous cell killing, mimicking early apoptosis, and a delayed cell death scenario in which cells can die shortly after being damaged, as well as long after irradiation. For each of these scenarios, the decrease in oxygen consumption due to cell death can be computed globally (macroscopic voxel average) or locally (microscopic). A re-oxygenation model already used in the literature, the so called full re-oxygenation, is also considered. The impact of cell death kinetics and re-oxygenation on tumour responses is illustrated for two radiotherapy fractionation schemes: a conventional schedule, and a hypofractionated treatment. The results show large differences in the doses needed to achieve 50% tumour control for the investigated cell death models. Moreover, the models affect the tumour responses differently depending on the treatment schedule. This corroborates the complex nature of re-oxygenation, showing the need to take into account the kinetics of cell death in radiation response models.

A newly TPS algorithm, implemented in Pinnacle3, has been developed for peripheral neutron dose estimation for radiotherapy patients. The script gives doses in several organs according to gender, treatment location and delivered high energy monitor units. In order to validate these estimations, doses for a total of 119 patients were calculated with Pinnacle3 TPS script, and compared to the experimental measurements with the new Thermal Neutron Digital Detector (TNRD). The studied patients, cover a wide range of pathologies for three different linacs. The comparison shows that with the implemented script we obtain a good correlation between measurement and theoretical values. On the other hand, periodic neutron characterization of the facility should be considered for better estimations.

A new thermal neutron detector (TNRD), developed for nuclear research, has shown to be effective for clinical use in peripheral neutron dose estimation, either in patient and ‘in-phantom’ measurements. This work shows some TNRD difficulties when adapting it to radiotherapy environments, mainly due to the fact that it has shown structural limitations. Two problems have been studied: (1) the influence of cable lengthening, necessary to be operative in a radiotherapy environment and (2) cable irradiation during the measurements. As we are measuring very small signals, we have to take into account not only these two facts but also the quality of the materials and connectors used. Thus, we studied cable elongation and irradiation influences in conventional and extreme situations once the setup was improved, in order to avoid uncertainties which could be of the order of the signal. Mean deviations of -0.15% from the original TNRD cable extension have been noticed. For the wide variety of conditions tested, in terms of both dose delivered and setup of the radiotherapy exposure, uncertainties smaller than 1.2% have been estimated.

Individualization of dose prescription based on normal-tissue dose-volume and radiosensitivity data. Purpose: The aim of this paper is to illustrate the potential gain in tumor control probability (TCP) of prostate ranter patients by individualizing the prescription dose according to both normal-tissue (N-T) dose-volume and radiosensitivity data. Methods and Materials: Two exercises have been carried out. Firstly, patients' dose prescriptions were individualised on the basis of N-T dose-volume histograms (DVHs) alone and secondly modeling potential differences in N-T sensitivity as well. In both cases, the change in tumor control that may be achieved by individualizing patients' dose was estimated assuming that after the dose adjustments, every patient had (1) the same value of normal tissue complication probability (NTCP) (5%) and (2) NTCP equal to the average NTCP before Individualization (i,e,, without increasing the average NTCP). The Lyman-Kutcher-Burman NTCP model was used to predict the N-T response curves with two different sets of parameters. The first exercise, based only on individual NT DVHs (i,e,, assuming all patient equally radiosensitive), was over a real population of 50 prostate cancer patients, The second exercise modeled a 10,000-prostate-cancer patient population with varying NT dose-volume distributions and radiosensitivity (through allowing TD50 to vary). Results: A gain of more than 9% in TCP was predicted when doses were individualized based only on DVHs so that every patient had 5% NTCP after dose adjustments. BY adding the estimate of radiosensitivity, the gain increased to more than 15%. When the individualisation was performed without increasing the mean NTCP, then the potential gain in TCP was almost 5% (for adjustment based on DVH distribution solely) increasing to 7% with the additional consideration of radiosensitivity. Conclusions: There is a potential gain (increase in local tumor control) from dose individualisation strategies based on both N-T dose-volume data and radiosensitivity (assuming that this is available). Dose prescription Individualization based only on dose-volume data can be exploited provided that reliable N-T response models are available. There will be additional gains if some estimate of N-T radiosensitivity is available to allow further patient stratification, identification of patients with high radiosensitivity being particularly important.

Purpose: Differences between radiotherapy techniques and energies, can offer improvements in tumor coverage and organs at risk preservation. However, a more complete decision should include peripheral doses delivered to the patient. The purpose of this work is the balance of photon and neutron peripheral doses for a prostate case solved with 6 different treatment modalities. Methods: Inverse and Forward IMRT and 3D-CRT in 6 and 15 MV for a Siemens Primus linac, using the same CT data set and contours. The methodology described in [1], was used with the TNRD thermal neutron detector [2] for neutron peripheral dose estimation at 7 relevant organs (colon, esophagus, stomach, liver, lung, thyroid and skin). Photon doses were estimated for these organs by terms of the algorithm proposed in [3]. Plans were optimized with the same restrictions and limited to 30 segments in the Inverse case. Results: A similar photon peripheral dose was found comparing 6 and 15 MV cases with slightly higher values of (1.9 ± 1.6) % in mean, for the 6 MV cases. Neutron presence when using 15 MV, represents an increase in peripheral dose of (18 ± 17) % in average. Due to the higher number of MU used in Inverse IMRT, an increasing of (22 ± 3) % in neutron dose is found related to Forward and 3D-CRT plans. This corresponds to photon doses within 44 and 255 mSv along the organs, for a dose prescription of 68 Gy at the isocenter. Conclusion: Neutron and photon peripheral doses for a prostate treatment planified in 6 different techniques have been analyzed. 6 MV plans are slightly more demanding in terms of photon peripheral doses. Inverse technique in 15 MV has Result to be the most demanding one in terms of total peripheral doses, including neutrons and photons. [1]Phys.Med.Biol,2012;57:6167–6191.[2]Med.Phys.,2014;41(112105)1–5.[3]Phys.Medica,2014;30:e33.

Differences between the scatter conditions of dosimetry and treatment situation are more important in the case of large-field photon beams than in standard ones. In the former, the scattering volume is defined by the phantom cross section; in the latter, the radiation field size. Two factors should be considered: the thickness and the cross section of the phantom. Both of them have an effect on the Percentage Depth Dose (PDD) distribution. In a previous study we addressed the influence of backscatter thickness on dose delivered. The aim of this work is to measure the effect of cross section phantom on the PDD curves under our TBI treatment conditions. Results showed a strong dependence of the PDDs on this parameter. A semi-empirical expression has also been derived to calculate (within 0.5% uncertainty) the Lateral scatter Correction Factor (LCF). The model of LCF states a linear dependence on depth whilst slope of these curves depends exponentially on distance to the lateral surface. The algorithm is being applied to our practical Total Body Irradiation (TBI) procedure.

For total body irradiation (TBI) dose calculation requirements, anatomical information about the whole body is needed. Despite the fact that video image grabbing techniques are used by some treatment planning systems for standard radiotherapy, there are no such systems designed to generate anatomical parameters for TBI planning. The paper describes an anthropometrical computerised system based on video image grabbing which was purpose-built to provide anatomical data for a PC-based TBI planning system. Using software, the system controls the acquisition and digitalisation of the images (external images of the patient in treatment position) and the measurement procedure itself (on the external images or the digital CT information). An ASCII file, readable by the TBI planning system, is generated to store the required parameters of the dose calculation points, i.e. depth, backscatter tissue thickness, thickness of inhomogeneity, off-axis distance (OAD) and source to skin distance (SSD).

Background and purpose : As for conventional radiotherapy, one of the basic requirements in Total Body Irradiation (TBI) is to know accurately the dose delivered to the entire body. Both the dosimetry and the treatment planning need to be improved. Physical, technical and dosimetrical aspects of TBI have been widely discussed in the literature. However, to our knowledge, no planning systems specifically designed for TBI are commercially available. This article describes a CT-aided PC-based planning system (TBI- Plansys ) and its dose calculation algorithm, which applies scatter and inhomogeneity corrections, developed for the TBI technique currently in use at our centre (AP/PA irradiation with patient positioned on his side). Material and method : A description of the material and method followed in the dosimetrical procedure is included as it constitutes the basis of the proposed dose calculation algorithm (more than 2D). A Windows programming environment has been used to develop the software. Results : TBI- Plansys uses patient CT data and indicates absolute and relative dose distributions along midline (at reference points), the transversal axis at the specification point and on transverse sections. The system also calculates the appropriate thicknesses of bolus and shielding to modify undesired dose distributions. TBI- Plansys has been checked against two other well-established systems (beam-zone method and our in vivo semiconductor probe-based system). The checks showed good accuracy with dose differences less than 1% and 3% for homogeneous and inhomogeneous tissues, respectively. Conclusions : CT calculations by TBI- Plansys allow us to detect undesired distributions which may go unnoticed by calculations at only some specific points. The system has shown clear advantages for routine clinical use as it generates more detailed and accurate information than manual calculations and diminishes the time requirements.

Total skin electron irradiation (TSEI) has been used as a treatment for mycosis fungoides. Our center has implemented a modified Stanford technique with six pairs of 6 MeV adjacent electron beams, incident perpendicularly on the patient who remains lying on a translational platform, at 200 cm from the source. The purpose of this study is to perform a dosimetric characterization of this technique and to investigate its optimization in terms of energy characteristics, extension, and uniformity of the treatment field. In order to improve the homogeneity of the distribution, a custom-made polyester filter of variable thickness and a uniform PMMA degrader plate were used. It was found that the characteristics of a 9 MeV beam with an 8 mm thick degrader were similar to those of the 6 MeV beam without filter, but with an increased surface dose. The combination of the degrader and the polyester filter improved the uniformity of the distribution along the dual field (180cm long), increasing the dose at the borders of field by 43%. The optimum angles for the pair of beams were ± 27°. This configuration avoided displacement of the patient, and reduced the treatment time and the positioning problems related to the abutting superior and inferior fields. Dose distributions in the transversal plane were measured for the six incidences of the Stanford technique with film dosimetry in an anthropomorphic pelvic phantom. This was performed for the optimized treatment and compared with the previously implemented technique. The comparison showed an increased superficial dose and improved uniformity of the 85% isodose curve coverage for the optimized technique.

Neutrons have a high biological effectiveness. Therefore, patient exposition to them represents a relevant issue and consequences to this exposure, regarding secondary cancer induction, must be clarified. The aim of this work was to make a complete study on the production of photoneutrons in radiotherapy facilities. Detailed Monte Carlo simulation, using MCNPX code, was performed to characterize the neutron generation in a Siemens PRIMUS linac operating at 15 MV and to determine the fluence energy distributions inside the treatment room. This information is mandatory to understand the response, under radiotherapy conditions, of a new neutron digital detector developed by our group.

Nowadays, neutron contamination in high energy photon beams normally used in radiotherapy treatments is an issue of interest from the radioprotection point of view. However, neutron production when using electron beams to treat superficial tumors has usually been ignored. The aim of this paper was to study such contamination and its effect on patients. In order to do that, experimental measurements in a radiotherapy environment were carried out using a digital device sensitive to thermal neutrons. Besides, Monte Carlo simulations were performed to estimate the difference in number of particles between photon and electron operational modes, required to deposit the same dose at a certain depth. Results show that neutron production is lower for electron beams than photon ones but not as low as previously expected.

The characteristics of the thermoluminescence glow curve and dosimetric peak of LiF:Mg,Ti (TLD-100) crystals are studied, with emphasis on the evaluation of the influence of the irradiation dose and heating rate on the dosimetric peak (peak 5) trapping parameters. These parameters were obtained using a computerized deconvolution routine that assumed first-order kinetics for each peak composing the glow curve. This routine was able to fit accurately (1.2% < FOM < 3.4%) all measured glow curves. It was found that for the evaluated range of photon doses (0.2 to 20 cGy) and heating rates (7 to 25 K/s), the behavior of the dosimetric peak was consistent with the predictions of the Randall-Wilkins first-order kinetic model. In particular, it was confirmed that the activation energy of the dosimetric peak is independent of the heating rate and irradiation dose, as expected from this model. The mean activation energy obtained for peak 5 was 2.27 ± 0.08 eV. The area under the experimental glow curves for the same dose remained stable regardless of the heating rate used, indicating that the thermal quenching effect did not have a significant influence within the studied range. By fixing the heating rate and varying the dose, it was found that the integral was proportional to the irradiation dose, as expected.

Introduction Peripheral doses are directly related to second cancer risk after radiotherapy. Our group developed a methodology to estimate neutron contribution to peripheral organ doses by terms of two general models, namely abdomen and head and neck [PMB-2012;57:6167–6191]. Purpose This work aims to verify the validity of these models in real treatments, in order to evaluate the need of further improvements for specific locations beside the two generic ones. Materials and methods Neutron doses were calculated in 12 representative organs from measured thermal neutron fluences with TNRD detectors at 16 points inside the phantom [MedPhys-2014;41:112105], for two high energy (15 MV) treatments (lung and prostate). Following the methodology described in [RO107:234–241], these neutron doses were estimated by terms of number of delivered MU and facility characterization. Abdomen model was used for the prostate case while both (abdomen and headn42:276–281]. Results Values generally agreed within the 30% uncertainty range established for the models and the 15% for the measurement. Abdomen model has shown to fit better for the lung. Further studies should be needed to improve generic models in some specific locations such as skin or organs close to the field-edge. Conclusion The generic model has shown to be good enough to cover frequent high-energy specific treatments as those studied here. It seems to be no need of more specific models, while some improvements have to bee done for particular points.

Purpose Second cancer, as a consequence of a curative intent radiotherapy (RT), represents a growing concern nowadays. The unwanted neutron exposure is an important contributor to this risk in patients irradiated with high energy photon beams. The design and development by our group of a neutron digital detector, together with the methodology to estimate, from the detector readings, the neutron equivalent dose in organs, made possible the unprecedented clinical implementation of an online and systematic neutron dosimetry system. The aim of this study was to systematically estimate neutron equivalent dose in organs of a large patient group treated in different installations. Patients and methods Neutron dosimetry was carried out in 1377 adult patients at more than 30 different institutions using the new neutron digital detector located inside the RT room. Second cancer risk estimates were performed applying ICRP risk coefficients. Results Averaged equivalent dose in organs ranges between 0.5mSv and 129mSv depending on the type of treatment (dose and beam-on time), the distance to isocenter and the linac model. The mean value of the second cancer risk for our patient group is 1.2%. Reference values are proposed for an overall estimation of the risks in 15 linac models (from 2.8×10 −5 to 62.7×10 −5 %/MU). Conclusions The therapeutic benefit of RT must outweigh the second cancer risk. Thus, these results should be taken into account when taking clinical decisions regarding treatment strategy choice during RT planning.

Purpose To propose multivariate predictive models for changes in pulmonary function tests (ΔPFTs) with respect to preradiotherapy (pre-RT) values in patients undergoing RT for breast cancer and lymphoma. Methods and Materials A prospective study was designed to measure ΔPFTs of patients undergoing RT. Sixty-six patients were included. Spirometry, lung capacity (measured by helium dilution), and diffusing capacity of carbon monoxide tests were used to measure lung function. Two lung definitions were considered: paired lung vs . irradiated lung (IL). Correlation analysis of dosimetric parameters (mean lung dose and the percentage of lung volume receiving more than a threshold dose) and ΔPFTs was carried out to find the best dosimetric predictor. Chemotherapy, age, smoking, and the selected dose-volume parameter were considered as single and interaction terms in a multivariate analysis. Stability of results was checked by bootstrapping. Results Both lung definitions proved to be similar. Modeling was carried out for IL. Acute and late damage showed the highest correlations with volumes irradiated above ∼20 Gy (maximum R 2 = 0.28) and ∼40 Gy (maximum R 2 = 0.21), respectively. RT alone induced a minor and transitory restrictive defect ( p = 0.013). Doxorubicin-cyclophosphamide-paclitaxel (Taxol), when administered pre-RT, induced a late, large restrictive effect, independent of RT ( p = 0.031). Bootstrap values confirmed the results. Conclusions None of the dose-volume parameters was a perfect predictor of outcome. Thus, different predictor models for ΔPFTs were derived for the IL, which incorporated other nondosimetric parameters mainly through interaction terms. Late ΔPFTs seem to behave more serially than early ones. Large restrictive defects were demonstrated in patients pretreated with doxorubicin-cyclophosphamide-paclitaxel.

PURPOSE: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>/=50 Gy). Evidence is emerging that lower doses could also be important. METHODS AND MATERIALS: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. RESULTS: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30