Image-guided IMRT for localized prostate cancer with daily repositioning: inferring the difference between planned dose and delivered dose distribution.

INTRODUCTION: To investigate the dosimetric impact of daily on-line repositioning during a full course of IMRT for prostate cancer. MATERIALS AND METHODS: Twenty patients were treated with image-guided IMRT. Each pre-treatment plan (Plan A) was compared with a post-treatment plan sum (Plan B) based on couch shifts measured. The delivered dose to the prostate without a daily repositioning was inferred by considering each daily couch shift during the whole course of image-guided IMRT (i.e., plan B). Dose metrics were compared for prostate CTV (P-CTV) and PTV (P-PTV) and for organs at risk. Ten patients were treated with a 5 mm margin and 10 patients with a 10 mm margin. RESULTS: For plan A vs. plan B: the average D95, D98, D50, D mean and EUD were: 76.4 Gy vs. 73.9 Gy (p = 0.0007), 75.4 Gy vs. 72.3 Gy (p = 0.001), 78.9 Gy vs. 78.4 Gy (p = 0.014), 78.7 Gy vs. 77.8 Gy (p = 0.003) and 78.1 Gy vs. 75.9 Gy (p = 0.002), respectively for P-CTV, and 73.2 Gy vs. 69.3 Gy (p = 0.0006), 70.7 Gy vs. 66.0 Gy (p = 0.0008), 78.3 Gy vs. 77.5 Gy (p = 0.001), 77.8 Gy vs. 76.4 Gy (p = 0.0002) and 74.4 Gy vs. 69.2 Gy (p = 0.003), respectively for P-PTV. Margin comparison showed no differences in dose metrics between the two plans except for D98 of the rectum in plan B which was significantly higher with a 10 mm margin. CONCLUSIONS: The absence of daily image-guided IMRT resulted in a significantly less uniform and less homogeneous dose distribution to the prostate. A reduction in PTV margin showed neither a lower target coverage nor a better spare of OAR with and without daily image-guided IMRT.

[Image-guided radiotherapy in prostate cancer: concepts and implications]. / Radiothérapie guidée par l'image des cancers prostatiques : concepts et implications.

Intensity modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are technological developments, which when applied in a model of prostate cancer, led to a significant reduction in the toxicity and digestive and urinary sequelae of 3D conformational radiotherapy. The major clinical benefits of these techniques with regard to reduced digestive and urinary toxicity are unequivocal since very few sequelae have been reported at 10 years (2% of grade 2 and 1% of grade 3 digestive toxicity; 11% of grade 2 and 5% of grade 3 urinary toxicity). Even when these two techniques are combined, IG-IMRT significantly diminishes late genitourinary toxicity. In the absence of adaptive radiotherapy, there are many IGRT protocols and repositioning techniques, and every step in the IGRT process must be carried out with extreme rigor: installing the patient and contention system, repositioning technique with or without fiduciary markers, type of repositioning imaging, definition of margins inherent in each technique (prostate, seminal vesicles and/or pelvic lymph nodes), frequency of repositioning during treatment, dietary constraints with or without rectal lavage. For these reasons, every centre that performs IGRT must carefully and rigorously assess the uncertainties of repositioning linked to the IGRT technique. In this review, we analyzed data from the literature based on dosimetric studies and the proven clinical impact in order to answer the different questions asked by radiation oncologists at every step of the IGRT process for cancer of the prostate. Recommendations are made for the repositioning protocols according to the most widely used repositioning techniques: fiduciary markers or soft tissues, kV-CBCT or MV-CBCT, 3D ultrasonography.

[High precision radiotherapy with ultrasonic imaging guidance]. / Radiothérapie de haute précision guidée par échographie.

Conformal radiation therapy with or without intensity modulation is the standard treatment of localized prostate cancer and facilitates dose escalation. The implementation of three-dimensional conformal radiotherapy necessitates focusing on target volume delineation, dosimetry, reproducibility of treatment and quality control. Recently, ultrasound systems that allow direct daily visualization of the prostate have become available. This non-invasive technique can be used to correct both prostate organ motion and set-up error and leads to increase treatment accuracy.

[Implementation of transabdominal ultrasound image guided conformal intensity modulated radiotherapy]. / Mise en oeuvre de la radiothérapie conformationnelle par modulation d'intensité guidée par échographie transabdominale.

PURPOSE: Optically guided ultrasound imaging has been used in our department since 2003 in order to implement an on line correction scheme in intensity modulated radiation therapy of prostate carcinoma. PATIENTS AND METHODS: The corrections observed during the initial time period of the system (17 patients) are compared to those observed more recently (10 patients). Treatment margins are calculated. RESULTS: Overall systematic errors decreased between 2003 and 2006, and are presently statistically not different from zero. Random errors remain the same (max 4.3 mm). Proposed margins are 7 mm both in lateral and longitudinal direction and 8.4 mm in anteroposterior. CONCLUSION: Ultrasound can be used for on line correction of both positioning and internal organs motion errors and allows reduction of the margins between clinical and planning volume.

[Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001)]. / Résultats préliminaires de l'évaluation de la radiothérapie conformationnelle avec modulation d'intensité (RCMI) pour le traitement des cancers prostatiques et ORL (STIC 2001).

INTRODUCTION: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results. PATIENTS AND METHODS: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations. RESULTS: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

[Secondary effects of brachytherapy in the treatment of coronary restenosis]. / Effets secondaires de la curiethérapie dans le traitement de la resténose coronaire.

Brachytherapy is proposed for the treatment or prevention of coronary restenosis with encouraging results, especially in intra-stent restenosis. The results of the first clinical studies show benefit, for example those of the American SCRIPPS trial with a 3 year follow-up. However, recent reports in the literature have described secondary effects associated with this technique: 1) stenoses occurring at the limits of the irradiated segments which are attributed to a proliferative effect of low doses on damaged tissue; 2) late occlusions at the irradiated site: their incidence is estimated at 9% at 6 months. The mechanisms of these thromboses are not understood but delayed re-endothelialisation probably plays a rôle; 3) finally, irradiation is associated with uncovered dissection probably related to delayed healing. Other long-term trials are necessary to provide a more complete assessment of the secondary effects of brachytherapy, especially with regards to their mechanisms, prevention and treatment.

Dose escalation with 3D-CRT in prostate cancer: French study of dose escalation with conformal 3D radiotherapy in prostate cancer-preliminary results.

PURPOSE: To evaluate the feasibility of dose escalation in a multi-institutional study in prostate cancer patients. METHODS AND MATERIALS: Between October 1995 and October 1998, 164 patients with localized adenocarcinoma of the prostate were treated with 3-dimensional conformal radiotherapy at one of five French institutions. The dose of radiation was escalated from 66 to 80 Gy (ICRU point). The maximum dose to the rectal wall was limited to 75 Gy. RESULTS: Results were compared in two groups, one (group 1) receiving the standard dose (n = 46 patients; 66 to 70 Gy) and the other (group 2) receiving the escalated dose (n = 118 patients; 74 to 80 Gy). There was no difference in the characteristics of patients between the two groups. The mean follow-up time was 32 months in group 1 and 17.5 months in group 2. No statistical difference between the two groups was observed in the incidence of late gastrointestinal and urinary toxicities. The probability of achieving a posttreatment prostate-specific antigen nadir of

[Evolution of the use of the portal imaging device: prospective study over three years]. / Evolution des concepts d'utilisation de l'imagerie électronique: étude prospective sur trois périodes.

PURPOSE: To describe the evolution of the use of the electronic portal imaging device (EPID) over three periods. MATERIAL AND METHODS: From 1990, as part of the quality assurance research programs, the radiotherapy department of the G.-F. Leclerc Centre of Dijon used EPID systems in a prospective fashion. During the first of the three periods (PER 1:1990-1993), the study consisted of analysis criteria determination, software efficiency improvement and a selection of patients who could benefit from the method. Eight hundred and forty-five images of 40 patients were analysed qualitatively and quantitatively. Two verifications per week were planned, and the action level for correction was 10 mm. Head and neck images were also displayed in 'cinema' presentation for internal movements analysis. From 1994 to 1995 (PER 2), off-line procedure (OLP) based upon early correction of the systematic error and the rules calculated from our previous experience were tested for checking the brain, head and neck (LOC 1: 396 images) and many of the pelvic irradiations (LOC 2: 260 images). A double-exposure procedure and/or movie loop presentation was reserved for other patients. During the last period (PER 3: 1996-1997), the OLP procedure was routinely performed in 54 patients (images: 321 LOC 1, 680 LOC 2). RESULTS: LOC 1: deviations of < 3 mm increased from 75.5% during PER 1 to 81% during PER 2 to 83% during PER3. Conversely, deviations of 3-5 mm dropped from 19.5 to 13%, while deviations of more than 5 mm remained stable, around 5%. The actual standard error of the mean deviation observed was 2 mm. LOC 2: deviations of < 5 mm were observed in 81% of the cases during PER 1 and in 91% during PER 3 (89.5% in PER 2). These good results led to a decrease in deviation of 5 to 7 mm (11 to 6%) and also to a significant drop in deviations of more than 7 mm, 8 to 3% respectively. The actual precision obtained was 2.5 mm +/- 3 mm SD. CONCLUSIONS: The OLP based upon the early correction of the systematic error led to a significant increase of setup accuracy of patients irradiated for the brain, head and neck, and especially for pelvic lesions.

Radiotherapy of advanced mycosis fungoides: indications and results of total skin electron beam and photon beam irradiation.

BACKGROUND: The goals of this retrospective study of advanced mycosis fungoides are (1) to describe the indications of a combination of total skin electron beam and photon beam irradiation and (2) to analyze the results of total body or segmental photon irradiation for patients with extension beyond the skin. METHODS: From January 1975 to December 1995, 45 patients with pathologically-confirmed mycosis fungoides or Sézary syndrome received a combination of TSEB and photon beam irradiation for advanced disease: 34 males and 11 females, mean age 61 years (range 27-87 years). The mean follow-up was 111 months (range 18-244 months, median 85 months). Whole-skin irradiation treatment to a depth of 3-5 mm with a 6-MeV electron beam was produced by a linear accelerator to a total dose of 24-30 Gy in 8-15 fractions, 3-4 times a week. In cases of thick plaques or tumors that were beyond the scope of low energy electron beams or for treating nodal areas (especially in the head and neck area or axilla involvement), regional irradiation (RRT) with Co-60 photon beams was followed by whole-skin electron beam irradiation (15 patients). In cases of diffuse erythrodermia, Sézary syndrome, nodal or visceral involvement, total body irradiation was delivered with a 25-MV photon beam using a split-course regimen to prevent hematological toxicity (22 patients). The first course consisted of 1.25 Gy delivered in ten fractions and 10 days. Subsequently, patients received TSEB. Four to 6 weeks after TSEB, they received a second course of 1.25 Gy. The cumulative TBI dose ranged from 2.5 to 3 Gy in about 3 months. Hemi-body irradiation (HB) with Co-60 (and a bolus) was given in cases of multiple regional tumors with large and thick infiltration of the skin to a dose of 9-12 Gy (using fractions of 1-1.5 Gy/day) which, once flattened, were boosted with whole-skin electron beam therapy (8 patients). RESULTS: At 3 months, the overall response rate was 75% with 23/45 (51%) patients in complete response and 24% in partial response; one patient had stable lesions and 1 patient presented progressive disease. The overall response rate was 81% for T3 patients, 61% for T4, 79% for N1 and 70% for N3. The complete response rate was 67% for T3 and 28% for T4. Sixty-four percent of N1 patients and 41% of N3 had a complete response. The 5-year actuarial overall survival was 37% for T3 and 44% for T4 (P = 0.84). Patients with clinically abnormal lymph nodes that were pathologically negative (N1) presented a 5-year survival of 63%. Patients with pathologically positive lymph nodes (N3) experienced a 5-year survival rate of 32% (P = 0.040). CONCLUSIONS: TSEB provides an excellent quality of life by reducing itching and discharge from the skin. Patients with more advanced disease may be treated and cured by the addition of photon beams in combination with TSEB. A selection of patients with advanced skin disease and regional extension may be cured by a combination of TSEB and photon beam irradiation. The regional treatment allows the use of electrons after the reduction of the plaques or thick tumors and a prophylactic irradiation of the adjacent nodal area.

[Assessment of the use of electronic portal imaging]. / Bilan de l'utilisation de l'imagerie électronique.

Improvement in the accuracy of the positioning of the patient during external irradiation is one of the most important issues of the last decades, due to the detrimental impact of the misplacements on treatment outcome. Since 1990, the evolution of the technologic environment has led to a full integration of the portal imaging devices into linac technology. It offers a real on-line verification tool for "high-dose, high-accuracy" treatments. This overview based upon data from the literature describes the different types of imaging devices, the strategies of use and the results obtained. It also considers the use of imaging devices as an in vivo dosimeter.

[Intraoperative radiotherapy. Preliminary results]. / La radiothérapie per-opératoire. Résultats préliminaires.

We report a series of 40 patients treated by intraoperative radiotherapy between 1988 and 1992 (18 primary tumors, 13 local recurrences and 9 nodal extensions). The doses delivered were 15 Gy to 25 Gy, completed by external radiotherapy (15 to 45 Gy) in 13 cases. The local tumor control rate was 61% for initial therapy in primary tumors (70% for adenocarcinoma of the stomach) and 80.9% after complete en bloc surgery. The local control rate after palliative surgery for local recurrences is 38% and 33% for nodal extension. Two patients died (5%) during the postoperative period. We observed 2 hemorrhages and 3 cases of stone-free cholecystitis. The value of this approach must be confirmed in rigorous indications in comparison with surgery alone in controlled and randomised clinical trials.

[Dose evaluation during radiographic examinations of the pelvis in pediatrics]. / Estimation des doses lors des examens radiographiques du bassin en pédiatrie.

Dosimetry studies, employing a model, were conducted under the technical conditions established by one of the authors for exploration of the infant and child pelvis during diagnosis and treatment of congenital dislocation of the hip. Based on this data, it was confirmed that the dose applied to the various organs of a patient can be evaluated by using a relation identical to that employed for calculating the dose during radiotherapy. The results measured experimentally or calculated from the proposed formula, were comparable to those in the published literature. This method of dose assessment is valid not only in pediatric radiology, and whatever the region explored, but also for radiodiagnosis in adults.

Biological and technical principles of total body irradiation for bone marrow graft conditioning.

The aims of total body irradiation, namely immunologic suppression of the hematopoietic tissues and eventually eradication of leukemia, require a large dose which may cause detrimental effects on healthy tissues. The main problem is raised by the interstitial pneumonitis and a relative protection of the lung is advisable. A partial reduction of the dose to the lung may cause an important increase of the number of surviving cells in the cell population the irradiation is aiming aiming at. Technical problems are raised to keep this increase to an acceptable value. A relative protection of the critical tissues can be achieved by a convenient time distribution of the dose, since the repair of sublethal injuries taking place between the sessions of a fractionated irradiation or during the course of low dose rate irradiation is larger for intestine, lung..., than for bone marrow and probably leukemic cells. Animal experiments have provided radiobiological data for estimating the therapeutic benefit related to the fraction number or to the dose rate.