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.

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 Chiro's [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).

Application of the quality index methodology for dosimetric verification of build-up effect beyond air-tissue interface in treatment planning system algorithms.

We have designed a simple benchmark test for the user of a treatment planning system to check the calculation algorithm's ability to model the build up effect beyond an air/tissue interface. The expected result is expressed as an inhomogeneity correction factor CF derived from measurements and from Monte Carlo calculations for a full range of photon beam qualities. The linear regression lines obtained from plotting CF as a function of beam quality index form the basis for a quantitative check of the algorithm performance.

PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical failure: a study of 295 patients with a minimum 3-year followup.

PURPOSE: To assess the frequency and features of the PSA bounce phenomenon in a series of patients treated with permanent implant brachytherapy for prostate cancer, and to evaluate the percentage of cases in which this bounce could have mimicked a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology consensus criteria. METHODS AND MATERIALS: From January 1999 to December 2001, 295 patients were treated with a permanent prostate implantation (real-time technique, with free (125)I seeds) by the Paris Institut Curie/Hospital Cochin/Hospital Necker Paris group. Duration of followup is 40.3 months (9-66 months). PSA level was reported at intervals not exceeding 6 months. Bounce was defined by temporary elevation in PSA level, followed by a spontaneous decrease. RESULTS: In our series, 161 patients (55%) showed a transitory PSA increase (bounce) of at least 0.1 ng/mL; 145 patients (49%) a bounce of 0.2 ng/mL; 93 patients (32%) a bounce of 0.4 ng/mL; and 43 patients (15%) a bounce of at least 1 ng/mL. Mean PSA bounce was 0.8 ng/mL (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of total) presented three successive PSA increases, and therefore were to be considered as experiencing a biochemical relapse according to the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria. Among those 32 patients, 18 (56%) subsequently showed, without any treatment, a complete normalization of their PSA. In multivariate analysis, age <70 (p<0.0001) and D90>200Gy (p<0.003) were identified as independent factors for a PSA bounce of at least 0.4 ng/mL. CONCLUSIONS: The observed rate of 32% of patients showing a PSA bounce of at least 0.4 ng/mL in our series is in good agreement with what has been previously reported in the literature. Among 32 patients fulfilling the classical ASTRO criteria for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, questioning the ASTRO consensus for the biochemical followup of patients undergoing permanent implant prostate brachytherapy.

Initial evaluation of a four-dimensional computed tomography system using a programmable motor.

A dynamic lung tumor phantom was used to investigate the geometric reconstruction accuracy of a commercial four-dimensional computed tomography (4D-CT) system. A ball filled with resin, embedded in a cork cube, was placed on a moving platform. Various realistic antero-posterior (AP) motions were programmed to reproduce the respiratory motion of a lung tumor. Several three-dimensional (3D) CT and 4D-CT images of this moving object were acquired and compared using different acquisition parameters. Apparent volume and diameter of the ball were measured and compared to the real values. The position of two points (the AP limits of the ball) during the motion in the coordinate system of the CT scanner were also compared with the expected values. Volume error was shown to increase with object speed. However, although the volume error was associated with intraslice artifacts, it did not reflect large interslice inconstancies in object position and should not be used as an indicator of image accuracy. The 3D-CT gave a random position of the tumor along the phantom excursion; accuracy in the assessment of position by 4D-CT ranged from 0.4 mm to 2.6 mm during extreme phases of breathing. We used average projection (AVE) and maximum intensity projection (MIP) algorithms available on the commercial software to create internal target volumes (ITVs) by merging gross tumor volume (GTV) images at various respiratory phases. The ITVs were compared to a theoretical value computed from the programmed ball excursion. The ITVs created from the MIP algorithm were closer to the theoretical value (within 12%) than were those created from the AVE algorithm (within 40%).

Performance optimization of the Varian aS500 EPID system.

Today, electronic portal imaging devices (EPIDs) are widely used as a replacement to portal films for patient position verification, but the image quality is not always optimal. The general aim of this study was to optimize the acquisition parameters of an amorphous silicon EPID commercially available for clinical use in radiation therapy with the view to avoid saturation of the system. Special attention was paid to selection of the parameter corresponding to the number of rows acquired between accelerator pulses (NRP) for various beam energies and dose rates. The image acquisition system (IAS2) has been studied, and portal image acquisition was found to be strongly dependent on the accelerator pulse frequency. This frequency is set for each "energy - dose rate" combination of the linear accelerator. For all combinations, the image acquisition parameters were systematically changed to determine their influence on the performances of the Varian aS500 EPID system. New parameters such as the maximum number of rows (MNR) and the number of pulses per frame (NPF) were introduced to explain portal image acquisition theory. Theoretical and experimental values of MNR and NPF were compared, and they were in good agreement. Other results showed that NRP had a major influence on detector saturation and dose per image. A rule of thumb was established to determine the optimum NRP value to be used. This practical application was illustrated by a clinical example in which the saturation of the aSi EPID was avoided by NRP optimization. Moreover, an additional study showed that image quality was relatively insensitive to this parameter.

An inhomogeneity correction algorithm for irregular fields of high-energy photon beams based on Clarkson integration and the 3D beam subtraction method.

A number of treatment-planning systems still use conventional correction methods for body inhomogeneities. Most of these methods (power law method, tissue-air ratio (TAR), etc.) consider only on-axis points, rectangular fields, and inhomogeneous slabs covering the whole irradiating field. A new method is proposed that overcomes the above limitations. The new method uses the principle of the Clarkson method on sector integration to take into account the position and lateral extent of the inhomogeneity with respect to the point of calculation, as well as the shape of the irradiating field. The field is divided into angular sectors, and each sector is then treated separately for the presence of inhomogeneities using a conventional correction method. Applying this method, we can predict the correction factors for Co-60 and 6-MV photon beams for irregular fields that include inhomogeneities of lower or higher densities relative to water. Validation of the predicted corrections factors was made against Monte Carlo calculations for the same geometries. The agreement between the predicted correction factors and the Monte Carlo calculations was within 1.5%. In addition, the new method was able to predict the behavior of the correction factor when the point of calculation was approaching or moving away from the interface between two materials.

Lung volume assessment for a cross-comparison of two breathing-adapted techniques in radiotherapy.

PURPOSE: To assess the validity of gated radiotherapy of lung by using a cross-check methodology based on four-dimensional (4D)-computed tomography (CT) exams. Variations of volume of a breathing phantom was used as an indicator. METHODS AND MATERIALS: A balloon was periodically inflated and deflated by a medical ventilator. The volume variation (DeltaV) of the balloon was measured simultaneously by a spirometer, taken as reference, and by contouring 4D-CT series (10 phases) acquired by the real-time position management system (RPM). Similar cross-comparison was performed for 2 lung patients, 1 with free breathing (FB), the other with deep-inspiration breath-hold (DIBH) technique. RESULTS: During FB, DeltaV measured by the spirometer and from 4D-CT were in good agreement: the mean differences for all phases were 8.1 mL for the balloon and 10.5 mL for a patient-test. End-inspiration lung volume has been shown to be slightly underestimated by the 4D-CT. The discrepancy for DeltaV between DIBH and end-expiration, measured from CT and from spirometer, respectively, was less than 3%. CONCLUSIONS: Provided that each slice series is correctly associated with the proper breathing phase, 4D-CT allows an accurate assessment of lung volume during the whole breathing cycle (DeltaV error <3% compared with the spirometer signal). Taking the lung volume variation into account is a central issue in the evaluation and control of the toxicity for lung radiation treatments.

Breast radiotherapy in the lateral decubitus position: A technique to prevent lung and heart irradiation.

PURPOSE: To present an original technique for breast radiotherapy, with the aim of limiting lung and heart irradiation, satisfying quality assurance criteria. METHODS AND MATERIAL: An original radiotherapy technique for breast irradiation has been developed at the Institute Curie in January 1996. It consists of isocentric breast irradiation in the lateral decubitus position (isocentric lateral decubitus [ILD]). This technique is indicated for voluminous or pendulous breasts needing breast irradiation only. Thin carbon fiber supports and special patient positioning devices have been developed especially for this technique. In vivo measurements were performed to check the dose distribution before the routine use of the technique. RESULTS: ILD has been successfully implemented in routine practice, and 500 patients have been already treated. Breast radiotherapy is performed using a dose of 50 Gy at ICRU point in 25 fractions. ILD shows good homogeneity of the dose in breast treatment volume, treatment fields are perpendicular to the skin ensuring its protection, and extremely low dose is delivered to the underlying lung and heart. CONCLUSION: In cases of voluminous breasts or patients with a history of lung and heart disease, our technique provides several advantages over the conventional technique with opposing tangential fields. This technique improves the dose homogeneity according to the ICRU recommendations.

[A French survey on breast radiotherapy techniques for simulation and treatment]. / Enquête sur les techniques de préparation et de traitement utilisées pour la radiothérapie du sein en France.

Breast radiotherapy is still in progress. The target volumes - whole breast and lymph nodes - are usually located by clinical palpation and the use of bony landmarks. However computed tomography has allowed a better definition of the deep edge of the volumes and the calculation of 3D dose distributions. A survey of 194 centers has started in June 2005 in France. The questionnaire that was sent included questions about general techniques in breast radiotherapy. Preliminary results on 50 centers showed that patient anatomical data were in the vast majority acquired by a simulator-CT or a CT (for 92%). In the 50 departments, beam placement is done either directly at the simulator (20 centers), or on the TPS (16 centers). Virtual simulation software is used in 8 centers. In about 20% (11) radiotherapy departments, 3D target volumes are contoured and the beams adapted to their shapes.

Prostate cancer brachytherapy: is real-time ultrasound-based dosimetry predictive of subsequent CT-based dose distribution calculation? A study of 450 patients by the Institut Curie/Hospital Cochin (Paris) Group.

PURPOSE: Real-time ultrasound (US)-based dosimetry performed during (125)I loose seed implantation provides the radiation oncologist with an estimation of the dose distribution at seed insertion. However, for a number of reasons, this distribution may not reflect the real (reference) dosimetry as determined by subsequent CT, usually performed 1-2 months after implantation. The present study compared the two dosimetry data sets (US and CT) to evaluate how predictive extemporaneous US-based dosimetry can be of the real dose distribution. METHODS AND MATERIALS: A total of 450 patients with prostate cancer were treated with loose (125)I seed implantation between June 1999 and October 2002 by the Institut Curie/Hospital Cochin (Paris) Group. The mean patient age was 65 years. Most patients (74%) had Stage T1c; the stage did not exceed T2b for the others. All patients had a prostate-specific antigen level of <15 ng/mL and was <10 ng/mL for 72%; 84% had a Gleason score of < or =6 and did not exceed 7 for the others; and 56% were treated with neoadjuvant hormonal therapy for a mean of 4.3 months. All patients were treated with loose seed implantation. Real-time US-based dosimetry was performed intraoperatively for all patients. CT-based dosimetry was performed 2 months after implantation, using the VariSeed software. The minimal dose to 90% of the outlined volume (D(90)) and percentage of volume receiving at least 100% of the prescribed dose (V(100)) were calculated with the two methods and compared for all patients. RESULTS: On CT-based dosimetry, the D(90) was found to be > or =145 Gy (range, 115-240 Gy) in all patients except one. A large majority (86%) of patients showed a CT-based V(100) of >95%, and 48% had a V(100) of >98%. The mean CT-based D(90)/US-based D(90) ratio was 1.0 (range, 0.66-1.33). For 89% of the patients, the difference between the two values was <20% and for 62% was <10%. The mean CT-based V(100)/US-based V(100) ratio was 0.98 (range, 0-1.02), with 89% of patients showing a difference of <5%. CONCLUSION: Our results indicate that the D(90) and V(100) values obtained intraoperatively with our real-time US-based dosimetry are in reasonable agreement with the subsequent values obtained with CT-based dosimetry performed 2 months after implantation. Recent innovations in our dose planning software allowed better control of the longitudinal seed position and could still improve the correlation between real-time US-based dosimetry and the subsequent CT-based dose distribution.

Conformal radiotherapy for lung cancer: different delineation of the gross tumor volume (GTV) by radiologists and radiation oncologists.

PURPOSE: Delineation of the gross tumor volume (GTV) and organs at risk constitutes one of the most important phases of conformal radiotherapy (CRT) procedures. In the absence of a clear redefinition of the GTV, for a given pathology, complemented by detailed contouring procedures, the GTV are likely to be estimated rather arbitrarily with the risk of tumor underdosage or detriment to the surrounding healthy tissues. The objective of this study was to compare the delineation of the GTV of intrathoracic tumors by radiologists and radiation oncologists with experience in the field in various centers. MATERIALS AND METHODS: The computed tomography images of ten patients with nonoperated non-small cell lung cancer (NSCLC) eligible for CRT were reviewed. Nine radiologists and eight radiation oncologists working in five different centers, classified as either 'junior' or 'senior' according to their professional experience, had to delineate the GTV (primary tumor and involved lymph nodes) with predefined visualization parameters. A dedicated software was used to compare the delineated volumes in terms of intersection and union volumes and to calculate the 'concordance index' for each patient and each subgroup of physicians. RESULTS: Significant differences between physicians and between centers were observed. Compared to radiation oncologists, radiologists tended to delineate smaller volumes and encountered fewer difficulties to delineate 'difficult' cases. Junior physicians, regardless of their specialty, also tended to delineate smaller and more homogeneous volumes than senior physicians, especially for 'difficult' cases. CONCLUSIONS: Major discordances were observed between the radiation oncologists' and the radiologists' delineations, indicating that this step needs to be improved. A better training of radiation oncologists in thoracic imaging and collaboration between radiation oncologists and radiologists should decrease this variability. New imaging techniques (image fusion, positron emission tomography, magnetic resonance imaging spectroscopy, etc.) may also provide a useful contribution to this difficult delineation.

Practical use of Gafchromic(®) EBT films in electron beams for in-phantom dose distribution measurements and monitor units verification.

PURPOSE: The possibility of using the Gafchromic(®) EBT films parallel to incident electron beams was assessed in order to facilitate quality assurance tests for electron dose calculation algorithms. MATERIALS AND METHODS: Calibration curves were made for electron energies of 6, 9 and 12MeV. A set-up was suggested for EBT film irradiation parallel to the beam, and the dose measurements were compared to Ionization Chamber (IC) measurements in standard and small electrons beams. A more complex Quality Assurance (QA) set-up was performed with the cylindrical CARPET(®) phantom in order to test our Treatment Planning System (TPS) (Eclipse, Varian Medical Systems, Palo Alto, California) for the clinical situation of a chest wall electron beam therapy. Two dimensional dose distribution and gamma index results were compared to the calculated distribution given by the TPS. RESULTS: The reproducibility was found to be better than 1.5%. We found that applying strong pressure and aligning carefully the film edge with the phantom surface, as recommended for radiographic films, did not completely eliminate the air gap effect. Adding an ultrasound transmission gel and 2 complementary EBT films on the surface gave satisfactory results. The absolute dose for the reference 10×10cm(2) field was always within 1% of IC measurements and for smaller elongated fields (5×10, 4×10 and 3×10cm(2)) the mean difference was -1.4% for the three energies. The mean difference with the IC measurements in R(100), R(90) and R(50) was 0.9mm for all fields and for the three energies. The mean difference in the width of the 90% and the 50% isodoses at R(100) was 0.6mm. With the CARPET(®) phantom set-up very good agreement was found in the 2D dose distribution; 99% of the points satisfied the γ<1 criteria (3%-3mm). CONCLUSION: EBT films parallel to the beam axis could be used for absolute measurements of 2D dose distribution if ultrasound gel and overlying perpendicular films are added on the phantom surface.

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 (). 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.

Conformal radiotherapy planning for lung cancer: analysis of set-up uncertainties.

The objective of this study was to evaluate set-up uncertainties using a portal imaging system in a population of inoperable non-small cell lung cancer. Twenty-one patients were treated by a conformal radiotherapy technique with a personalized immobilization cast. The beam was verified by comparison with a corresponding digitally reconstructed radiograph by superimposition of anatomical structures. One thousand eight hundred eighty three images were analyzed. The mean intrafraction and interfraction errors (+/-SD) were 2.17 mm and 0.9 +/- 3.7 mm, 2.3 mm and 0.9 +/- 3.1 mm, 3 mm and 0.7 +/- 3 mm on the lateral (x), cranio-caudal (y) and anterior-posterior (z) axes, respectively. The mean systematic error was small, less than 1 mm, in all directions. The random errors were 2.5 mm, 2.4 mm, and 1.8 mm on the x, y, and z axes, respectively. No correlation between errors and the patient's height, weight, age, or sex was found. Set-up errors accuracy depending on practices, each institution should review their own treatments to quantify and reduce set-up errors in clinical practice.

[Respiratory gated radiotherapy: the 4D radiotherapy]. / La radiothérapie asservie à la respiration: la radiothérapie 4D.

Respiration-gated radiotherapy offers a significant potential for improvement in the irradiation of tumor sites affected by respiratory motion such as lung, breast and liver tumors. An increased conformality of irradiation fields leading to decreased complications rates of organs at risk (lung, heart...) is expected. Respiratory gating is in line with the need for improved precision required by radiotherapy techniques such as 3D conformal radiotherapy or intensity modulated radiotherapy. Reduction of respiratory motion can be achieved by using either breath hold techniques or respiration synchronized gating techniques. Breath hold techniques can be achieved with active, in which airflow of the patient is temporarily blocked by a valve, or passive techniques, in which the patient voluntarily breath-hold. Synchronized gating techniques use external devices (CCD camera for the GEMS/Varian system tested at Curie Institute) to predict the phase of the respiration cycle while the patient breaths freely. A new strategy is currently developed: the 4D Respiration correlated CT. It consists of retrospectively reconstruct CT slices at different phases of the breathing cycle allowing to measure residual movements and to choose the optimal patient's breathing phase where tumor movements are lower. These techniques presently investigated in several medical centers worldwide. The first results are very promising.