B. Sánchez-Nieto

BIOPLAN: SOFTWARE FOR THE BIOLOGICAL EVALUATION OF RADIOTHERAPY TREATMENT PLANS

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

DOSE-VOLUME CONSTRAINTS TO REDUCE RECTAL SIDE EFFECTS FROM PROSTATE RADIOTHERAPY: EVIDENCE FROM MRC RT01 TRIAL ISRCTN 47772397

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<or=80%, V40<or=65%, V50<or=55%, V60<or=40%, V65<or=30%, V70<or=15%, and V75<or=3%. CONCLUSION Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

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

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

Estimation of neutron-equivalent dose in organs of patients undergoing radiotherapy by the use of a novel online digital detector

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.

A CT-aided PC-based physical treatment planning of TBI: a method for dose calculation.

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.

Neutron contamination in radiotherapy: Estimation of second cancers based on measurements in 1377 patients

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 0.5 mSv and 129 mSv 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.

Midline Dose Algorithm for in Vivo Dosimetry

The high level of accuracy required in radiotherapy treatment dosimetry makes necessary good treatment quality control. The common way is the use of in vivo dosimetry equipment that allows the direct measurement of dose delivered to the patient. Control of homogeneity and constancy of the incident beam on the patient can be achieved directly by means of entrance dose measurement; however, control of dose delivered to tumours and internal organs is difficult because of the impossibility of a direct measurement. In this case calculations are made using external measurements (entrance and exit sides of the patient) to obtain the dose delivered. In this work, an algorithm that allows the real-time knowledge of midline dose as a function of thickness and entrance and exit doses coming from semiconductor detectors is presented. By having the electrometer connected to the computer, these three values (entrance, midline, and exit dose) are displayed instantaneously when the algorithm is included in the acquisition program. The model has been developed both for standard (source to surface distance = 100 cm) and special treatment techniques such as total body irradiation (SSD = 314 cm). There is a good agreement of experimental and calculated values with differences below 0.04%.

A new online detector for estimation of peripheral neutron equivalent dose in organ.

PURPOSE Peripheral dose in radiotherapy treatments represents a potential source of secondary neoplasic processes. As in the last few years, there has been a fast-growing concern on neutron collateral effects, this work focuses on this component. A previous established methodology to estimate peripheral neutron equivalent doses relied on passive (TLD, CR39) neutron detectors exposed in-phantom, in parallel to an active [static random access memory (SRAMnd)] thermal neutron detector exposed ex-phantom. A newly miniaturized, quick, and reliable active thermal neutron detector (TNRD, Thermal Neutron Rate Detector) was validated for both procedures. This first miniaturized active system eliminates the long postprocessing, required for passive detectors, giving thermal neutron fluences in real time. METHODS To validate TNRD for the established methodology, intrinsic characteristics, characterization of 4 facilities [to correlate monitor value (MU) with risk], and a cohort of 200 real patients (for second cancer risk estimates) were evaluated and compared with the well-established SRAMnd device. Finally, TNRD was compared to TLD pairs for 3 generic radiotherapy treatments through 16 strategic points inside an anthropomorphic phantom. RESULTS The performed tests indicate similar linear dependence with dose for both detectors, TNRD and SRAMnd, while a slightly better reproducibility has been obtained for TNRD (1.7% vs 2.2%). Risk estimates when delivering 1000 MU are in good agreement between both detectors (mean deviation of TNRD measurements with respect to the ones of SRAMnd is 0.07 cases per 1000, with differences always smaller than 0.08 cases per 1000). As far as the in-phantom measurements are concerned, a mean deviation smaller than 1.7% was obtained. CONCLUSIONS The results obtained indicate that direct evaluation of equivalent dose estimation in organs, both in phantom and patients, is perfectly feasible with this new detector. This will open the door to an easy implementation of specific peripheral neutron dose models for any type of treatment and facility.

Analytical model for photon peripheral dose estimation in radiotherapy treatments

This work aims to generate a simple analytical model that allows estimation of peripheral photon equivalent dose to organs of individual patients, valid for any isocentric technique. Photon radiation scattered in the LINAC head has been simulated as a virtual source of radiation emitting isotropically so that, before reaching a point inside the patient, it decreases with the square law and with attenuation due to air and tissue. Leakage has been simulated as a constant background dose along the patient. Firstly, a dose-to-points basic model was proposed and parameterized by fitting it to absorbed doses measured with TLD-700 in a humanoid phantom. Secondly, this model was generalized to any other situation involving intensity-modulated beams of any size and shape. Validation of this general model, usable beyond 10 cm from the field edge, was carried out by comparing estimation with TLD-100 doses for VMAT and IMRT treatments as well as with experimental data and models existing in the bibliography. Finally, an equivalent dose-to-organs model has been proposed by rescaling individual anatomical dimensions onto a mathematical phantom in order to make an estimation of organ length for dose calculation. The parameterized extended model, accounting for intensity-modulated beams of any shape, predicts measurements with a maximum relative uncertainty of ±25%. This general model, easy to apply in a clinical routine thanks to the ready availability of input parameters, has been proposed and validated for estimation of photon equivalent doses to peripheral organs. Finally, as a first step, it has been implemented into a piece of software termed PERIPHOCAL (PERIpheral PHOton CALculation), which is easily transferred to a commercial treatment planning system (TPS).

Backscatter Correction Algorithm for TBI Treatment Conditions.

The accuracy requirements in target dose delivery is, according to ICRU, +/- 5%. This is so not only in standard radiotherapy but also in total body irradiation (TBI). Physical dosimetry plays an important role in achieving this recommended level. The semi-infinite phantoms, customarily used for dosimetry purposes, give scatter conditions different to those of the finite thickness of the patient. So dose calculated in patients points close to beam exit surface may be overestimated. It is then necessary to quantify the backscatter factor in order to decrease the uncertainty in this dose calculation. The backward scatter has been well studied at standard distances. The present work intends to evaluate the backscatter phenomenon under our particular TBI treatment conditions. As a consequence of this study, a semi-empirical expression has been derived to calculate (within 0.3% uncertainty) the backscatter factor. This factor depends lineally on the depth and exponentially on the underlying tissue. Differences found in the qualitative behavior with respect to standard distances are due to scatter in the bunker wall close to the measurement point.