Jean-Claude Rosenwald

Evaluation of microscopic tumor extension in non-small-cell lung cancer for three-dimensional conformal radiotherapy planning.

PURPOSE One of the most difficult steps of the three-dimensional conformal radiotherapy (3DCRT) is to define the clinical target volume (CTV) according to the degree of local microscopic extension (ME). In this study, we tried to quantify this ME in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS Seventy NSCLC surgical resection specimens for which the border between tumor and adjacent lung parenchyma were examined on routine sections. This border was identified with the naked eye, outlined with a marker pen, and the value of the local ME outside of this border was measured with an eyepiece micrometer. The pattern of histologic spread was also determined. RESULTS A total of 354 slides were examined, corresponding to 176 slides for adenocarcinoma (ADC) and 178 slides for squamous cell carcinoma (SCC). The mean value of ME was 2.69 mm for ADC and 1.48 mm for SCC (p = 0.01). The usual 5-mm margin covers 80% of the ME for ADC and 91% for SCC. To take into account 95% of the ME, a margin of 8 mm and 6 mm must be chosen for ADC and SCC, respectively. Aerogenous dissemination was the most frequent pattern observed for all groups, followed by lymphatic invasion for ADC and interstitial extension for SCC. CONCLUSION The ME was different between ADC and SCC. The usual CTV margin of 5 mm appears inadequate to cover the ME for either group, and it must be increased to 8 mm and 6 mm for ADC and SCC, respectively, to cover 95% of the ME. This approach is obviously integrated into the overall 3DCRT procedure and with other margins.

Conformal radiotherapy (CRT) planning for lung cancer: analysis of intrathoracic organ motion during extreme phases of breathing

PURPOSE Conformal radiotherapy beams are defined on the basis of static computed tomography acquisitions by taking into account setup errors and organ/tumor motion during breathing. In the absence of precise data, the size of the margins is estimated arbitrarily. The objective of this study was to evaluate the amplitude of maximum intrathoracic organ motion during breathing. METHODS AND MATERIALS Twenty patients treated for non-small-cell lung cancer were included in the study: 10 patients at the Institut Curie with a personalized alpha cradle immobilization and 10 patients at Tenon Hospital with just the Posirest device below their arms. Three computed tomography acquisitions were performed in the treatment position: the first during free breathing and the other two during deep breath-hold inspiration and expiration. For each acquisition, the displacements of the various intrathoracic structures were measured in three dimensions. RESULTS Patients from the two centers were comparable in terms of age, weight, height, tumor site, and stage. In the overall population, the greatest displacements were observed for the diaphragm, and the smallest displacements were observed for the lung apices and carina. The relative amplitude of motion was comparable between the two centers. The use of a personalized immobilization device reduced lateral thoracic movements (p < 0.02) and lung apex movements (p < 0.02). CONCLUSION Intrathoracic organ movements during extreme phases of breathing are considerable. Quantification of organ motion is necessary for definition of the safety margins. A personalized immobilization device appears to effectively reduce apical and lateral displacement.

CT and 18F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers

PURPOSE To validate a computed tomography (CT) and (18)F-deoxyglucose (FDG) image fusion procedure and to evaluate its usefulness to facilitate target definition and treatment planning in three-dimensional conformal radiation therapy (3D-CRT) for non-small-cell lung cancer. METHODS AND MATERIALS Twelve patients were assessed by CT and FDG-coincidence mode dual-head gamma camera (CDET) before radiotherapy. The patients were placed in a similar position during CT and FDG-CDET. Matching was achieved by minimizing the cost function by 3D translation and rotation between four landmarks drawn on the patients skin. Virtual simulation was performed from image fusion and estimated dose-volume histograms (DVH) were calculated. RESULTS Quantitative analysis indicated that the matching error was < 5 mm. Fusion of anatomic and metabolic data corrected staging of lymph nodes (N) for 4 patients and staging of metastases for 1 patient. In these 5 patients, DVH revealed that the lung volume irradiated at 20 Gy (Vl(20)) was decreased by an average of 22.8%, and tumor volume irradiated at the 95% isodose (V(95)) was increased by 22% and 8% for 2 patients, respectively, and was decreased by an average of 59% for 3 patients after fusion. No difference in terms of Vl(20) and V(95) was observed for the other 7 patients. CONCLUSION We have validated CT and FDG-CDET lung image fusion to facilitate determination of lung cancer volumes, which improved the accuracy of 3D-CRT.

Variation of sensitometric curves of radiographic films in high energy photon beams

Film dosimetry is an important tool for the verification of irradiation techniques. The shape of the sensitometric curve depends on the type of film as well as on the irradiation and processing conditions. Existing data concerning the influence of irradiation geometry on the sensitometric curve are conflicting. In particular the variation of optical density, OD, with field size and depth in a phantom shows large differences in magnitude between various authors. This variation, as well as the effect of beam energy and film plane orientation on OD, was therefore investigated for two types of film, Kodak X-Omat V and Agfa Structurix D2. Films were positioned in a solid phantom, either perpendicular or (almost) parallel to the beam axis, and irradiated to different dose levels using various photon beams (Co-60, 6 MV, 15 MV, 18 MV, 45 MV). It was found that the sensitometric curves of the Kodak film derived at different depths are almost identical for the four x-ray beams. For the Kodak film the differences in OD with depth are less than 2%, except for the Co-60 beam, where the difference is about 4% at 10 cm depth for a 15 cm x 15 cm field. The slope of the sensitometric curve of the Agfa film is somewhat more dependent on photon beam energy, depth and field size. The sensitometric curves of both types of film are almost independent of the film plane orientation, except for shallow depths. For Co-60 and for the same dose, the Kodak and Agfa films gave at dose maximum an OD lower by 4% and 6%, respectively, for the parallel compared to the perpendicular geometry. Good dosimetric results can be obtained if films from the same batch are irradiated with small to moderate field sizes (up to about 15 cm x 15 cm), at moderate depths (up to about 15 cm), using a single calibration curve, e.g., for a 10 cm x 10 cm field.

Experimental determination and verification of the parameters used in a proton pencil beam algorithm

We present an experimental procedure for the determination and the verification under practical conditions of physical and computational parameters used in our proton pencil beam algorithm. The calculation of the dose delivered by a single pencil beam relies on a measured spread-out Bragg peak, and the description of its radial spread at depth features simple specific parameters accounting individually for the influence of the beam line as a whole, the beam energy modulation, the compensator, and the patient medium. For determining the experimental values of the physical parameters related to proton scattering, we utilized a simple relation between Gaussian radial spreads and the width of lateral penumbras. The contribution from the beam line has been extracted from lateral penumbra measurements in air: a linear variation with the distance collimator-point has been observed. Analytically predicted radial spreads within the patient were in good agreement with experimental values in water under various reference conditions. Results indicated no significant influence of the beam energy modulation. Using measurements in presence of Plexiglas slabs, a simple assumption on the effective source of scattering due to the compensator has been stated, leading to accurate radial spread calculations. Dose measurements in presence of complexly shaped compensators have been used to assess the performances of the algorithm supplied with the adequate physical parameters. One of these compensators has also been used, together with a reference configuration, for investigating a set of computational parameters decreasing the calculation time while maintaining a high level of accuracy. Faster dose computations have been performed for algorithm evaluation in the presence of geometrical and patient compensators, and have shown good agreement with the measured dose distributions.

Selecting Patients for Exclusive Permanent Implant Prostate Brachytherapy: The Experience of the Paris Institut Curie/Cochin Hospital/Necker Hospital Group on 809 Patients

PURPOSE The aim of this study was to analyze overall and relapse-free survival in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than American Brachytherapy Society (ABS) criteria. METHODS AND MATERIALS Between January 1999 and September 2004, 809 patients were treated with permanent loose 125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809 patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between 10 and 15, or a Gleason score of 7, or both (non-ABS group). RESULTS Overall 5-year survival was 98%, with no difference between the ABS group and the non-ABS patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS group; it was significantly lower (p = 0.001) in the non-ABS group but remained satisfactory at 94%. On subgroup analysis, the results appeared to be better for the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason score of 7. CONCLUSIONS Our results suggest that selected patients in the intermediate-risk group of localized prostate cancers can be safely proposed as recipients of permanent implant brachytherapy as monotherapy.

Breast irradiation in the lateral decubitus position: technique of the Institut Curie

Breast irradiation in the lateral decubitus (LD) position is a technique used at the Institut Curie for more than 30 years in the breast-conserving management of patient with breast cancer. This technique is described in detail in this article. The patients position allows the breast to flatten over a support, hence providing a rather homogeneous thickness throughout the treated volume. Dose at mid-thickness on the beam axis can be easily determined from entrance and exit dose measurements. Disadvantages and advantages of the LD technique are discussed. We presently recommend this technique for patients with large breasts (more than 6 cm thickness in LD position).

Assessment of organ absorbed doses and estimation of effective doses from pediatric anthropomorphic phantom measurements for multi-detector row CT with and without automatic exposure control.

This study was designed to measure organ absorbed doses from multi-detector row computed tomography (MDCT) on pediatric anthropomorphic phantoms, calculate the corresponding effective doses, and assess the influence of automatic exposure control (AEC) in terms of organ dose variations. Four anthropomorphic phantoms (phantoms represent the equivalent of a newborn, 1-, 5-, and 10-y-old child) were scanned with a four-channel MDCT coupled with a z-axis-based AEC system. Two CT torso protocols were compared: a first protocol without AEC and constant tube current-time product and a second protocol with AEC using age-adjusted noise indices. Organ absorbed doses were monitored by thermoluminescent dosimeters (LiF: Mg, Cu, P). Effective doses were calculated according to the tissue weighting factors of the International Commission on Radiological Protection (ICRP Publication 103). For fixed mA acquisitions, organ doses normalized to the volume CT dose index in a 16-cm head phantom (CTDIvol16) ranged from 0.6 to 1.5 and effective doses ranged from 8.4 to 13.5 mSv. For the newborn-equivalent phantom, the AEC-modulated scan showed almost no significant dose variation compared to the fixed mA scan. For the 1-, 5- and 10-y equivalent phantoms, the use of AEC induced a significant dose decrease on chest organs (ranging from 61 to 31% for thyroid, 37 to 21% for lung, 34 to 17% for esophagus, and 39 to 10% for breast). However, AEC also induced a significant dose increase (ranging from 28 to 48% for salivary glands, 22 to 51% for bladder, and 24 to 70% for ovaries) related to the high density of skull base and pelvic bones. These dose increases should be considered before using AEC as a dose optimization tool in children.

Automatic exposure control in multichannel CT with tube current modulation to achieve a constant level of image noise: Experimental assessment on pediatric phantoms

Automatic exposure control (AEC) systems have been developed by computed tomography (CT) manufacturers to improve the consistency of image quality among patients and to control the absorbed dose. Since a multichannel helical CT scan may easily increase individual radiation doses, this technical improvement is of special interest in children who are particularly sensitive to ionizing radiation, but little information is currently available regarding the precise performance of these systems on small patients. Our objective was to assess an AEC system on pediatric dose phantoms by studying the impact of phantom transmission and acquisition parameters on tube current modulation, on the resulting absorbed dose and on image quality. We used a four-channel CT scan working with a patient-size and z-axis-based AEC system designed to achieve a constant noise within the reconstructed images by automatically adjusting the tube current during acquisition. The study was performed with six cylindrical poly(methylmethacrylate) (PMMA) phantoms of variable diameters (10-32 cm) and one 5 years of age equivalent pediatric anthropomorphic phantom. After a single scan projection radiograph (SPR), helical acquisitions were performed and images were reconstructed with a standard convolution kernel. Tube current modulation was studied with variable SPR settings (tube angle, mA, kVp) and helical parameters (6-20 HU noise indices, 80-140 kVp tube potential, 0.8-4 s. tube rotation time, 5-20 mm x-ray beam thickness, 0.75-1.5 pitch, 1.25-10 mm image thickness, variable acquisition, and reconstruction fields of view). CT dose indices (CTDIvol) were measured, and the image quality criterion used was the standard deviation of the CT number measured in reconstructed images of PMMA material. Observed tube current levels were compared to the expected values from Brooks and Di Chiros [R.A. Brooks and G.D. Chiro, Med. Phys. 3, 237-240 (1976)] model and calculated values (product of a reference value multiplied by a dose ratio measured with thermoluminescent dosimeters). Our study demonstrates that this AEC system accurately modulates the tube current according to phantom size and transmission to achieve a stable image noise. The system accurately controls the tube current when changing tube rotation time, tube potential, or image thickness, with minimal variations of the resulting noise. Nevertheless, CT users should be aware of possible changes of tube current and resulting dose and quality according to several parameters: the tube angle and tube potential used for SPR, the x-ray beam thickness (tube current decreases and image noise increases when doubling x-ray beam thickness), the pitch value (a pitch decrease leads to a higher dose but also to a higher noise), and the acquisition field of view (FOV) (tube current is lower when using the small acquisition FOV compared to the large one, but the use of small acquisition FOV at 120 kVp leads to a peculiar increase of tube current and CTDIvol).

On‐axis and off‐axis primary dose component in high energy photon beams

The depth dose of the primary dose component, on axis and off axis of six different x-ray beams, has been determined from transmission measurements in narrow beam geometry with and without flattening filter using a Perspex column of a cross section large enough to ensure electronic equilibrium. In order to derive the primary photon fluence, a correction for the scatter from the column has been applied according to the following method: A number of spectra taken from the literature have been used for computing a scatter coefficient Sc at different depths by convolution of dose spread arrays. Using the relationship between Sc and the single attenuation coefficient mu i to represent each entire spectrum, it has been possible to correct the experimental transmission curves iteratively, until the corresponding values of mu were stabilized and representative of the primary. The measured attenuation coefficients were found to have a linear increase as a function of the distance from the central axis for all the energies and types of linear accelerators. For the same nominal energy, this increase is different from one accelerator to another. The same phenomenon was observed for the attenuation coefficients obtained without the flattening filter in the same experimental conditions. The results are tentatively interpreted considering the angular variation of bremsstrahlung energy spectra with and without a flattening filter as calculated by a Monte Carlo method and they are consistent and useful to take accurately into account the softening of the beam as the off-axis distance increases.