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Proper understanding of the risk of radiation-induced late effects for patients receiving external photon beam radiotherapy requires the determination of reliable dose-response relationships. Although significant efforts have been devoted to improving dose estimates for the study of late effects, the most often questioned explanatory variable is still the dose. In this work, based on a literature review, we provide an in-depth description of the radiotherapy dose reconstruction process for the study of late effects. In particular, we focus on the identification of the main sources of dose uncertainty involved in this process and summarise their impacts on the dose-response relationship for radiotherapy late effects. We provide a number of recommendations for making progress in estimating the uncertainties in current studies of radiotherapy late effects and reducing these uncertainties in future studies.

The purpose of this work was to experimentally investigate the out-of-field dose in a water phantom, with several high energy electron beams used in external beam radiotherapy (RT). The study was carried out for 6, 9, 12, and 18 MeV electron beams, on three different linear accelerators, each equipped with a specific applicator. Measurements were performed in a water phantom, at different depths, for different applicator sizes, and off-axis distances up to 70 cm from beam central axis (CAX). Thermoluminescent powder dosimeters (TLD-700) were used. For given cases, TLD measurements were compared to EBT3 films and parallel-plane ionization chamber measurements. Also, out-of-field doses at 10 cm depth, with and without applicator, were evaluated. With the Siemens applicators, a peak dose appears at about 12-15 cm out of the field edge, at 1 cm depth, for all field sizes and energies. For the Siemens Primus, with a 10 × 10 cm(²) applicator, this peak reaches 2.3%, 1%, 0.9% and 1.3% of the maximum central axis dose (Dmax) for 6, 9, 12 and 18 MeV electron beams, respectively. For the Siemens Oncor, with a 10 × 10 cm(²) applicator, this peak dose reaches 0.8%, 1%, 1.4%, and 1.6% of Dmax for 6, 9, 12, and 14 MeV, respectively, and these values increase with applicator size. For the Varian 2300C/D, the doses at 12.5 cm out of the field edge are 0.3%, 0.6%, 0.5%, and 1.1% of Dmax for 6, 9, 12, and 18 MeV, respectively, and increase with applicator size. No peak dose is evidenced for the Varian applicator for these energies. In summary, the out-of-field dose from electron beams increases with the beam energy and the applicator size, and decreases with the distance from the beam central axis and the depth in water. It also considerably depends on the applicator types. Our results can be of interest for the dose estimations delivered in healthy tissues outside the treatment field for the RT patient, as well as in studies exploring RT long-term effects.

Purpose: The implementation of image-guided brachytherapy in cervical cancer raises the problem of adapting the experience acquired with 2D brachytherapy to this technique. The GEC-ESTRO (Groupe européen de curiethérapie - European Society for Radiotherapy and Oncology) has recommended reporting the dose delivered to the rectum in the maximally exposed 2 cm(3) volume, but so far, the recommended dose constraints still rely on 2D data. The aim of this study was to evaluate the relationship between the doses evaluated at the ICRU rectal point and modern dosimetric parameters., Material and Methods: For each patient, dosimetric parameters were generated prospectively at the time of dosimetry and were reported. For analysis, they were converted in 2 Gy equivalent doses using an α/β ratio of 3 with a half-time of repair of 1.5 hours., Results: The dosimetric data from 229 consecutive patients treated for locally advanced cervical cancer was analyzed. The mean dose calculated at ICRU point (DICRU) was 55.75 Gy ± 4.15, while it was 59.27 Gy ± 6.16 in the maximally exposed 2 cm(3) of the rectum (P=0.0003). The D2 cm(3) was higher than the DICRU in 78% of the cases. The mean difference between D2 cm(3) and DICRU was 3.53 Gy ± 4.91. This difference represented 5.41% ± 7.40 of the total dose delivered to the rectum (EBRT and BT), and 15.49% ± 24.30 of the dose delivered when considering brachytherapy alone. The two parameters were significantly correlated (P=0.000001), and related by the equation: D2 cm(3)=0.902 × DICRU + 0.984. The r(2) coefficient was 0.369., Conclusion: In this large cohort of patients, the DICRU significantly underestimates the D2 cm(3). This difference probably results from the optimization process itself, which consists in increasing dwell times above the ICRU point in the cervix. Considering these findings, caution must be taken while implementing image-guided brachytherapy and dose escalation., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: After successful treatment of cancers in childhood, the occurrence of second malignant neoplasm (SMN) came to the fore. Few studies have considered the relationship between the radiation dose received and the risk of developing an SMN. To take into account the heterogeneity of the dose distribution so as to evaluate the overall risk of an SMN after a childhood cancer, we therefore focused on the integral dose restricted to the irradiated fields., Methods and Materials: The study was performed in a cohort of 4,401 patients who were 3-year survivors of all types of childhood cancer treated between 1947 and 1986 in France and Great Britain. For each patient, the integral dose was estimated for the volume inside the beam edges., Results: We found a significant dose-response relationship between the overall risk of an SMN and the estimated integral dose. The excess relative risk for each incremental unit of the integral dose was only 0.008 in a linear model and 0.017 when a negative exponential term was considered, when adjusted for chemotherapy. The risk of SMN occurrence was 2.6 times higher in the case of irradiation. However among patients who had received radiotherapy, only those who had received the highest integral dose actually had a higher risk., Conclusions: The integral dose in our study cannot be considered as a good predictor of later risks. However other studies with the same study design are obviously needed to evaluate the use of the integral dose as a tool for decision making concerning different radiotherapy techniques.

High-energy external radiotherapy has become one of the most common treatment in localized prostate cancer. We compared the difference of dose distribution, mainly at the 5-30 Gy dose level, in the irradiated pelvic volume among three modalities of radiotherapy for patients with prostate cancer: conventional, conformal and intensity-modulated radiotherapy (IMRT). We selected six patients with prostate cancer treated by conformal radiotherapy at the doses of 46 Gy to PTVN (prostate and seminal vesicles), and 70 Gy to PTV-T (prostate). The conventional technique": an 8-field arrangement was used; the conformal technique 4 fields with a boost through 6 fields. For IMRT, a five-beam arrangement was used. Dose-volume histograms (DVH) were analyzed and compared among the three techniques. The IMRT technique significantly increased the pelvic volume covered by the isodose surfaces below 15 Gy as compared with the conventional and conformal techniques. The mean absolute increase for the pelvic volume included between 5-30 Gy for the IMRT technique, was about 2 900 ml as compared with the conventional technique. However, IMRT significantly reduced the irradiated volume of the rectum in the dose range of 5 to 40 Gy, also significantly reduced the irradiated volume of bladder and femoral heads, and obtained a similar or improved isodose distribution in the PTVs. In addition, the use of IMRT slightly increased the relative dose delivered to the body volume outside the pelvis, as estimated by the use of specific software. A long-term follow-up will be needed to evaluate potential late treatment complications related to the use of IMRT and the low or moderate irradiation dose level obtained in the pelvis and in the whole body.

Purpose: The aim of this work was to establish the acquisition, calculation and 3D compensator manufacturing optimum parameters. This methodology is based on virtual simulation and 3D dosimetry., Materials and Methods: The material used is a helicoidal CT (PQ 5000-Marconi), a virtual simulation system (AcQsim version 4-Marconi), a Treatment Planning System (Dosigray), a linear accelerator Saturne 43 (Varian, CGR), an automated milling system for compensator filters (Autimo 2.5 D-HEK), a water tank phantom (wellhofer) and an homogeneous phantom with simple patterns in order to simulate the obliquity surface of patient body. The compensator was composed by granulate tin because this material ensures a good profile modulation. The compensation plane has been calculated at 80% to dose profile. The compensator thickness profile has been calculated with different acquisition (slice thickness, pitch factor), calculation (attenuation coefficient, bixel) and fabrication parameters (drill diameter, specification of milling system)., Results: After this preliminary study, we have defined the optimum parameters for the compensator realization. We have observed that the slice thickness, bixel size and drill diameter are the parameters that mainly affect the profiles homogeneity. The choice of parameters with smaller dimensions S = 3 mm; B = 3 mm, F = 3 mm, improve the profiles homogeneity. Though, for manufacture times compatible with the clinical routine, the selected parameters are S = 5 mm, B = 6 mm and F = 6 mm. Compensator can be used for any type of Linac. However, one must pay attention on their realization and their positioning on the beam central axis.

Purpose: To evaluate dosimetric consequences generated by the automatic definition based on lesion coverage of prescription isodose. A clinical series of 124 arteriovenous malformations was analysed. Plan quality was quantified by the standard deviation of the differential dose volume histogram calculated in the lesion., Material and Methods: We define two quantitative protocols based on lesion coverage for the automatic definition of prescription isodose using a volumetric definition of coverage (90% of lesion volume), and an isodose-based definition proposed by RTOG (prescription isodose equals minimum isodose in the lesion divided by 0.9)., Results: We have evaluated the plans obtained for these two protocols, calculating several dose-volume indices. These indices are presented as a function of dose-volume histogram standard deviation in order to quantify the consequences of their variations for this representative series of plans. The margin our team tolerates is such that the sum of underdosed lesion and overdosed healthy tissues factors remains lower than one. Protocol based on volumetric coverage gives results situated within this margin. Protocol based on RTOG definition produces conformation indices that could be greater than 1., Conclusion: The absolute dose would be decided taking into account examined dose-volume indices and clinical data. A protocol for automatic definition of prescription isodose using volumetric lesion coverage seems to be more judiciously adapted to arteriovenous malformation conformal plans in stereotactic conditions because of variations observed in the overdosage of healthy tissues.

An inverse planning algorithm for determining the intensity of modulated beams that generates conformal radiotherapy dose distributions is presented. This algorithm is based on the mathematical analysis of the singular values decomposition. It is integrated in the DOSIGRAY 3D treatment planning software. The dose is calculated by the separation of the primary and scattered radiation. We presented, for a prostate cancer, the modulated intensity profiles and the optimal dose distribution obtained by the inverse optimization software developed and integrated in the treatment planning system. We obtained a region with high doses which geometrically conforms the target volume and spares the neighboring critical structures. This preliminary study showed the feasibility and the managing of the singular value decomposition to generate conformal dose distribution in a clinical environment.

We began intracranial stereotactic irradiation under the direction of O Betti 11 years ago. At the present time, we believe it is interesting to present the methodologies of the SALT (Saint-Anne-Lariboisière-Tenon) group. Up to the present time we have irradiated 693 patients using a single fraction. Arteriovenous malformations (AVMs) represented the majority (90%) of treated lesions. Irradiation protocol has little changed since 1986, and the localization of the target volume was performed in the neurosurgery department of St Anne Hospital, France. The stereotactic images (computerized tomography [CT], angiography) were sent to the radiotherapy department of Tenon Hospital through the French public digital network NUMERIS. Protocol was realized using the stereotactic ARTEMIS-3D/Dosigray TPS. The lesion volume was filled by one or more spherical or elliptical subvolumes using the "Associated Target Methodology". The interactive adjustment of subvolumes was based on the 3D graphical representations of the lesion. The direct optimization of the irradiation space was performed by managing parameters provided by the DDB (Dosimetric Data Base) such as the number of arcs, their angular position, as well as the starting and the ending point of each arc. The evaluation of the calculated dose distribution was made using quantitative parameters. The second method of optimization was based on the minibeam intensity modulation using a mathematical theory of inverse problems and singular value decomposition (SVD) analysis. At the present time, due to technical reasons, linear accelerators do not permit the modulation of intensity of arctherapy. Thus we transformed the profiles of irregular forms into rectangular profiles of modulated ponderation, with each optimized plan being evaluated before its implementation. The criteria of evaluation were derived from the differential and cumulative dose volume histograms (DVH). The DVHs permitted the evaluation of the volumes of underdosage and overdosage inside the lesion and in the healthy tissue, respectively. Using DVHs, we have defined parameters such as the conform factor and the homogeneity index. We stress that the methodology of protocol optimization is valid for single or multiple fractions as well as for intra- and extra-cranial irradiation.

A new radiosurgical methodology, the "associated targets methodology" has been developed and tested by our group for the irradiation of complex cerebral arteriovenous malformations using our treatment planning system Artemis-3D. For the treatment of the arteriovenous malformations we used 15 MV photons generated by a Saturne 43 Linac, eight additional collimators (6-20 mm in diameter), the Betti fixation seat and the Talairach stereotactic frame. The successive steps of the associated targets' methodology are: -the prescription of a peripheral minimal therapeutic effective dose corresponding to the 60-70% cumulated isodose range; -the compartmentalization of the target volume into several sub-volumes, each of them having its own isocenter, collimator, irradiation space and isocenter dose weight; -the 3-dimensional computation and graphics requirements, and dose volume analysis; -the optimization evaluation criteria taking into account the dose inside and outside of the lesion. Two treatment planning software versions of Artemis-3D exist; the first one was developed for the sitting position and later for the supine treatment position, the second version is a multi-modalities imagery radiosurgical treatment planning system based on more powerful computers. Different types of stereotactic frames have been integrated. Three-dimensional visualization, stereotactic CT imaging, and angiography can be used for the sitting or supine position. We started using this methodology in 1990, and treated 44 patients during that year. For 26 single isocenter arteriovenous malformations, the obliteration rate was 22/26 (85%). In the 18 multi-isocenters irradiation cases, the overall obliteration rate was 11/18 = 61%. An example of successfully irradiated complex arteriovenous malformation is discussed to illustrate the methodology. With this three-dimensional methodology we have improved the results obtained during the first period (1986 to 1989) of our radiosurgical practice in which we used a two dimensional planification approach.