Harmonization of practices between radiotherapy centres in the Nord and Pas-de-Calais regions (France): A three-year evaluation.

PURPOSE: The delineation of volumes of interest can be a source of significant interobserver variability. The purpose of this study was to improve the homogeneity of delineation between oncologist-radiotherapists in the territorial departments of Nord and Pas-de-Calais (France) through discussions of clinical cases and the adoption of common published reference documents. MATERIALS AND METHODS: All eleven radiotherapy centres in the Nord and Pas-de-Calais departments of France participated. The localizations assessed to date included prostate, head and neck, breast and brain cancers. For each localization, the junior or senior physician(s) in charge of pathology delineated the volumes of interest according to their usual practices. Validated indices, including the Dice similarity coefficient, were used to quantify the delineation differences. The anonymized results were presented at two to three annual meetings. A second delineation of the clinical cases was then carried out to quantify homogenization. An evaluation of dosimetry practices was also conducted for prostate cancer. Wilcoxon assay matched data were used. RESULTS: Our work showed either satisfactory delineation concordance after the initial assessment or improved delineation concordance. For prostate cancer, the Dice similarity coefficient values were greater than 0.6 initially in two of the three clinical cases. For head and neck cancers, a statistically significant improvement was observed for only one of the clinical target volumes. More than half of the Dice similarity coefficient values were greater than 0.6 in the first comparison. The study of clinical cases of breast cancer allowed a homogenization of the delineation of five of the six lymph node clinical target volumes. The dosimetry study of prostate cancer allowed for a homogenization of practices. CONCLUSION: This work makes it possible to harmonize the delineation practices around validated standards. An extension to the entire Hauts-de-France region is planned.

[Is adaptive intensity-modulated radiotherapy for uterine cervix carcinoma necessary?]. / La radiothérapie (conformationnelle avec modulation d'intensité) adaptative est-elle nécessaire pour les carcinomes du col utérin ?

PURPOSE: To observe on ten patients, the changes of different pelvic structures during a Stade IB2-IIB cervix cancer tomotherapy course delivering 60Gy over 5.5 weeks and evaluate the rationale of adaptive treatments. MATERIALS AND METHODS: Each of the six weekly mega voltage CT-scan (MVCT) exams performed the same day of the week were analyzed. The centro-pelvic CTV volume was contoured as well as the organs at risk (OAR). The dose delivered was recalculated while those to 2%, 50% and 98% of the centro-pelvic CTV as well as to 2 cm(3), 10 cm(3) and 50 cm(3) of the OAR were analyzed. RESULTS: The mean decrease in volume of the centro-pelvic CTV was 13% and non-significant (P>0.2). However four tumors decreased from 21% to 42%. This decrease was centripetal. Likewise, the fraction doses to 2%, 50% and 98% were respectively 2.14±0.08Gy, 2.02±0.14 Gy, 1.8±0.34Gy at week 1 and 2.13±0.1 Gy, 2.06±0.12Gy, 1.88±0.24Gy at week 6 (P>0.2). The doses delivered to 2 cm(3), 10 cm(3) and 50 cm(3) of the different OAR did not change at a significant level (P>0.05) too, except the dose to 50 cm(3) of non-sigmoid bowel moving from 1.69±0.16Gy at week 1 to 1.78±0.14Gy at week 6 (P=0.05). CONCLUSION: As a whole, adaptive therapy does not seem mandatory in this population of stages IB2-IIB cancers. A complementary study on more advanced stages is however necessary.

[Management of pregnant women with advanced cervical cancer: About five cases observed in Lille from 2002 till 2009. Evaluation of practices referring to the new French recommendations of 2008]. / Cancer du col utérin invasif et grossesse : cinq cas observés à Lille de 2002 à 2009. Évaluation des pratiques en référence aux recommandations françaises.

PURPOSE: An update on the management of invasive cervical cancer (from stage IB) diagnosed during pregnancy with reference to the recent French guidelines. PATIENTS AND METHODS: We retrospectively analyzed patients for whom invasive cervical cancer was diagnosed during pregnancy and managed jointly by Jeanne-de-Flandres and Roubaix maternity and by Oscar-Lambret cancer center between 2002 and 2009. RESULTS: Five patients were included: four stage IB1, and one stage IB2. Five pregnancies resulted in the birth of six alive children. Three patients received neoadjuvant chemotherapy during pregnancy. One patient had a laparoscopic pelvic lymphadenectomy in first trimester. Two laparoscopic extraperitoneal paraortic lymphadenectomy have been made. The mean time of survey is 47.5 months (12-94 months). One patient died of her cancer. CONCLUSION: The diagnosis of cervical cancer during pregnancy involves the same therapeutic guidelines in the absence of pregnancy. The laparoscopic pelvic lymphadenectomy (up to 20 to 24 weeks of gestation) is crucial in the therapeutic treatment for tumors less than 4cm. Neoadjuvant chemotherapy is used during pregnancy for patients refusing medical termination of pregnancy.

Results and special considerations when treating elderly patients with CyberKnife®: a review of 345 cases.

The relatively recent introduction of CyberKnife® in the field of radiotherapy has prompted the question of accessibility and usefulness of this technique for seniors. From June 2007 to June 2009, we treated 345 patients of all ages with CyberKnife as part of a single-center study. Median age was 61 years (range, 8-86 years). Ninety-eight patients were over 70 and 17 were older than 80. The treatment could not be completed with 2% (2/98) patients over 70 vs. 3.6% (9/247) among the younger (ns). Physiologic or psychologic problems in maintaining position for a long time were not more frequent among those over 70. The same was true with those over 80. Patients over 70 years old are able to tolerate CyberKnife treatment as efficiently as their younger counterparts. Elderly patients should not be restricted from access to CyberKnife radiosurgery with curative intent.

[Economic assessment of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution for cervix carcinoma]. / Evaluation économique de la curiethérapie de débit pulsé gynécologique (PDR) avec optimisation de la dose pour les cancers du col utérin.

PURPOSE: Our study aims at evaluating the cost of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution versus traditional treatments (iridium wires, cesium, non-optimized PDR). Issues surrounding reimbursement were also explored. MATERIALS AND METHODS: This prospective, multicentre, non-randomised study conducted in the framework of a project entitled "Support Program for Costly Diagnostic and Therapeutic Innovations" involved 21 hospitals. Patients with cervix carcinoma received either classical brachytherapy or the innovation. The direct medical costs of staff and equipment, as well as the costs of radioactive sources, consumables and building renovation were evaluated from a hospital point of view using a microcosting approach. Subsequent costs per brachytherapy were compared between the four strategies. RESULTS: The economic study included 463 patients over two years. The main resources categories associated with PDR brachytherapy (whether optimized or not) were radioactive sources (1053euro) and source projectors (735euro). Optimized PDR induced higher cost of imagery and dosimetry (respectively 130euro and 367euro) than non-optimized PDR (47euro and 75euro). Extra costs of innovation over the less costly strategy (iridium wires) reached more than 2100euro per treatment, but could be reduced by half in the hypothesis of 40 patients treated per year (instead of 24 in the study). CONCLUSION: Aside from staff, imaging and dosimetry, the current hospital reimbursements largely underestimated the cost of innovation related to equipment and sources.

[Repositioning accuracy of cerebral fractionated stereotactic radiotherapy using CT scanning]. / Evaluation par tomodensitométrie du repositionnement en radiothérapie stéréotaxique fractionnée cérébrale.

PURPOSE: To evaluate the accuracy of patient repositioning in fractionated cerebral stereotactic radiotherapy using a Brain Lab stereotactic cranial mask in conjunction with standard dental fixation. PATIENTS AND METHODS: Fifty planning and checking CT scans were performed in 25 patients. The check CT scan was performed before or after one of the three sessions of treatment. Coregistration to the planning CT scan was used to assess alignment of the isocentre to the reference markers. The relative position of the PTV with regard to isocentre allowed us to determine its total displacement (3D vector). RESULTS: Mean isocentre translations (+/-SD) taking into account direction were -0.01+/-0.7, -0.2+/-1.3 and 0.07+/-0.5mm in mediolateral, craniocaudal and anteroposterior directions respectively. Mean rotations (+/- SD) were -0.02+/-0.6, -0.08+/-0.3 and -0.1+/-0.3 degree in mediolateral, craniocaudal and anteroposterior axes respectively. Mean overall PTV displacement was 1.8+/-1.5mm. PTV displacement was smaller than 2 and 3mm in 19/25 and 23/25 patients respectively. CONCLUSION: The accuracy of patient positioning using a stereotactic cranial mask system is similar to those reported in the literature and shows a satisfactory reproducibility with a standard dental fixation.

[Laparoscopic management of occult cervical cancer discovered after simple hysterectomy]. / Prise en charge chirurgicale par voie d'abord coelioscopique du cancer du col utérin occulte découvert après hystérectomie simple.

OBJECTIVES: To assess the feasibility and morbidity of surgical management by combined laparoscopic and vaginal approach after cervical cancer diagnosed at the time of simple hysterectomy. PATIENTS AND METHODS: From 2000 to 2005, 10 patients were referred with occult cervical cancer discovered after simple hysterectomy. All these patients had laparoscopy for surgical staging. RESULTS: Eight on ten patients had complete laparoscopic staging: pelvic lymphadenectomy (N=8), radical colpectomy (N=5). Operative time, pelvic lymph nodes resected, postoperative stay were respectively 261.3 minutes (200-400), 27 (23-38), 4.4 days. There were 2 symptomatic lymphocysts. Pelvic lymph nodes were positive for 1 patient with negative paraaortic nodes. Residual disease was present in 2 cases: 1 parametrial and vaginal involvement, 1 ovarian metastasis. 5 patients had adjuvant treatment: 2 combined pelvic external radiotherapy and brachytherapy, 1 pelvic external radiotherapy, 1 pelvic concurrent chemoradiation and 1 brachytherapy only. Two on ten patients needed a laparoconversion, one for ovarian involvement and one for technical failure. With a median follow-up of 29.7 months (4-63), 3 patients recurred. 3 patients recurred above 5 patients with pelvic lymphadenectomy but without parametrectomy versus no recurrence above 5 patients with pelvic lymphadenectomy and parametrectomy. DISCUSSION AND CONCLUSION: Surgical staging of occult cervical cancer discovered after simple hysterectomy is necessary for indication of adjuvant treatment. Laparoscopy combined with vaginal surgery is feasible and safe, inducing fewer adhesions which is important for adjuvant radiotherapy. The realization of a radical parametrectomy seems to offer a local control of the disease and a decrease in the risk of recurrence, which need to be confirmed by conducting a study with more patients. This emphasize the necessity of creating a national record to register all women managed for occult cervical cancer.

Prospective evaluation of surgical staging of advanced cervical cancer via a laparoscopic extraperitoneal approach.

OBJECTIVES: To report on a large series of cervical cancer patients at risk for lymph node metastasis who underwent surgical staging by a novel technique. METHODS: Between 1/97 and 3/02, we identified 111 patients who underwent an infrarenal aortic and common iliac lymph node dissection via a laparoscopic extraperitoneal approach for either bulky or locally advanced cervical cancer. We reviewed the medical records and extracted pertinent information. RESULTS: There were no intraoperative complications. Mean patient age was 46 (+/- 9) years. Mean node count was 19 (+/- 12). Thirty (27%) patients had lymph node metastasis. The mean operative time was 157 (+/- 46) min, and mean postoperative stay was 2 days. The majority of complications in the early part of the series were symptomatic lymphoceles. Since 4/01, preventive peritoneal marsupialization has been performed without lymphocele occurrence (37 patients). Two patients (2%) required reoperation. In the node-positive group, extended-field radiation and chemotherapy were well tolerated, but prognosis was dismal (median survival, 27 months). In the node-negative group, the median survival after pelvic radiation limited to the lower level of the surgical dissection was not reached after an average follow-up of 16.6 months. CONCLUSIONS: This novel technique is feasible and combines the benefits of laparoscopy with those of a retroperitoneal approach. It can be used to tailor external radiation therapy. The benefits of extended-field radiation therapy remain unclear; however, this approach does not preclude later use of radiation therapy, whereas possibly minimizing associated toxicities secondary to adhesions.

[Endometrial cancer: what's new?]. / Controverses et nouveautés dans l'adénocarcinome de l'endomètre.

OBJECTIVES: New and much debated data of the endometrial cancer concerning the preoperative assessment of myometrial invasion, the surgical staging, and the adjuvant treatment. PATIENTS AND METHODS: Medline (1998-2002): searching for "endometrial carcinoma". RESULTS: The pap smears are useful when it is difficult to have a transvaginal ultrasonography or an MRI. We can perform the pap smears and the endometrial biopsy in the clinic. If a patient has pap smears with malignant cells or elevated preoperative CA 125, it probably is a cancer with poor prognostic factors. Surgical staging with abdominal and node evaluation is necessary. The MRI seems to be the best preoperative imaging because we have information about adnexal and abdominal metastases, pelvic or aortic nodes and the invasion of the myometrium. So it gives us information on the surgical route, and provides indication for a lymphadenectomy. The surgical staging is a part of the treatment of the endometrial cancer: an exploration of the peritoneal cavity, a pelvic lymphadenectomy, a para-aortic lymphadenectomy if the pelvic nodes are positive or if there are factors of bad prognosis (deep stage IC, grade 3, adnexal or abdominal involvement, serous carcinoma of the endometrium). It can be performed if technical conditions are correct. The adjuvant teletherapy in the documented stage IpN0 (surgical staging with pelvic lymphadenectomy) does not seem to be necessary. But we can perform an adjuvant brachytherapy (high-dose rate if it is possible) in patients with a high local recurrence (stage IC, stage I with grade 3, stage IB grade 2). CONCLUSION: The preoperative MRI is useful choosing the surgical approach, and the depth of the myometrial invasion, which can be an indication for a pelvic lymphadenectomy. The surgical staging must be a part of the treatment of the endometrial cancer. So the adjuvant teletherapy in patients with stage IpN0 documented should not be used.

[Pulse Dose Rate brachytherapy: optimization and place of imaging]. / La curiethérapie de débit pulsé: optimisation et place de l'imagerie.

Pulse Dose Rate (PDR) brachytherapy presents the potential radiobiological advantages of low dose rate and the technical and radiation protection advantages of high dose rate remote afterloading technology. The different algorithms provided by the treatment planning systems allow dose rate and isodose shape optimization regarding the volumes defined by the radiologist and the radiation oncologist. The contribution of imaging together with these new optimization tools should improve brachytherapy practice and the therapeutic ratio. These new evolutions of brachytherapy will be presented here.

[Radiation protectants of the crystalline lens]. / Les radioprotecteurs du cristallin.

During more than a half of century, numerous compounds have been tested in different models against radiation-induced cataract. In this report, we will review the radioprotectors that have been already tested for non-human crystalline lens protection. We will focus on the most important published studies in this topic and the mechanisms of cytoprotection reported in vitro and in vivo from animals. The most frequent mechanisms incriminated in the cytoprotective effect are: free radical scavenging, limitation of lipid peroxidation, modulation of cycle progression increase of intracellular reduced glutathion pool, reduction of DNA strand breaks and limitation of apoptotic cell death. Amifostine (or Ethyol) and anethole dithiolethione (or Sulfarlem), already used clinically as chemo- and radioprotectants, could be further tested for ocular radioprotection particularly for radiation-induced cataract.

[In vivo dosimetry and radiation therapy of breast cancer]. / Dosimétrie in vivo et radiothérapie des cancers du sein.

INTRODUCTION: Verification of absorbed dose in target volume is a key factor for quality assurance in radiotherapy. In vivo measurements allow evaluation of the variations in dose with time and variations between measured doses and calculated doses by TPS. The aim of this work were to evaluate reproducibility of patient positioning and to compare calculated doses by 2 different TPS. PATIENTS AND METHODS: Twenty patients were divided in 2 groups according to the thickness of their breast (mean SSD = 92.9 cm). In vivo measurement was performed within the first two sessions. RESULTS: Reproducibility of SSD evaluation was made on 12 beams between 2 fractions. With a tolerance margin of 0.5 cm, positioning errors were present in 33% (4/12). The 2 TPS were in agreement in 75% (30/40). CONCLUSION: In vivo dosimetry can be a very interesting tool to assess patients positioning variations and TPS dose calculation.

[Quality control of intensity modulated treatments in radiotherapy]. / Contrôle de qualité dans la mise en oeuvre de la modulation d'intensité en radiothérapie.

Since January 2001, radiotherapy treatments with modulated intensity beams (IMRT) have started at the Centre Oscar-Lambret. This paper presents the tests and measurements made before the clinical implementation as well the quality control performed before each routine treatment. We use the treatment planning system Helax-TMS (MDS-Nordion) and the Primus accelerator (Siemens) linked to the Lantis network with Primeview and Simtec modules (Siemens) allowing to deliver intensity modulated beams with Step-and-Shoot technique. A prostate case and a head and neck case have been studied and have permitted to evaluate the benefit of IMRT compared to a "classical" conformal radiotherapy. In a second time, we have tested the accelerator's capabilities to deliver these intensity modulated beams, id-est, the accuracy of the leaf positions and the linearity of the monitor chamber. The third step has been the verification of the dose distributions calculated by Helax-TMS, id-est, the dose for different segment sizes, the dose profiles for an intensity modulated beam and the dose distribution for all the traitment beams. The used phantom has been especially developed at the Centre Oscar-Lambret for IMRT. The results have allowed to start clinical treatments and to establish a quality control set for this technique. The next step is the real time dosimetry with a portal imager.

[Comparison of conventional and conformational dosimetry in radiotherapy of cerebral neoplasms]. / Comparaison entre dosimétries classique et conformationnelle dans l'irradiation de tumeurs cérébrales.

PURPOSE: We prospectively compared a conventional treatment planning (PT2D) and 3-dimensional conformal treatment planning (PT3D) for radiotherapy of cerebral tumours. PATIENTS AND METHODS: Patients treated between 1/10/98 and 1/4/99 by irradiation for cerebral tumours were analysed. For each case, we planned PT2D using conventional orthogonal x-ray films, and afterward, PT3D using CT scan. Gross tumor volume, planning target volume and normal tissue volumes were defined. Dose was prescribed according to report 50 of the International Commission on Radiation Units and Measurements (ICRU). We compared surfaces of sagittal view targets defined on PT2D and PT3D and called them S2D and S3D, respectively. Irradiated volumes by 90% isodoses (VE-90%) and normal tissue volumes irradiated by 20, 50, 90% isodoses were calculated and compared using Student's paired t-test. RESULTS: There was a concordance of 84% of target surfaces defined on PT2D and PT3D. Percentages of target surface under- or-over defined by PT2D were 16 and 13% respectively. VE-90% was decreased by 15% (p = 0.07) with PT3D. Normal brain volume irradiated by 90% isodose was decreased by 27% with PT3D (p = 0.04). CONCLUSION: For radiotherapy of cerebral tumors using only coplanar beams, PT3D leads to a reduction of normal brain tissue irradiated. We recommend PT3D for radiotherapy of cerebral tumors, particularly for low-grade or benign tumors (meningiomas, neuromas, etc.).

[Dosimetry with radiosensitive gels in radiotherapy. Methods]. / Dosimétrie par gels radiosensibles en radiothérapie. Intérêt et méthodes.

The goal of conformal radiotherapy is to concentrate the dose in a well-defined volume by avoiding the neighbouring healthy structures. This technique requires powerful treatment planning software and a rigorous control of estimated dosimetry. The usual dosimetric tools are not adapted to visualize and validate complex 3D treatment. Dosimetry by radiosensitive gel permits visualization and measurement of the three-dimensional dose distribution. The objective of this work is to report on current work in this field and, based on our results and our experience, to draw prospects for an optimal use of this technique. Further developments will relate to the realization of new radiosensitive gels satisfying, as well as possible, cost requirements, easy realization and use, magnetic resonance imagery (MRI) sensitivity, tissue equivalence, and stability. Other developments focus on scanning methods, especially in MRI to measure T1 and T2.

Pulsed dose rate brachytherapy in head and neck cancers. Feasibility study of a French cooperative group.

PURPOSE: To prospectively evaluate the feasibility of pulsed dose rate (PDR) brachytherapy to mimic the continuous low dose rate (cLDR) iridium wire technique in head and neck carcinomas. MATERIALS AND METHODS: A series of 30 patients were included from June 1995 to May 1998. The primaries were located in the oral cavity (four T1, seven T2 and two T3), the velotonsillar arch (eight T1 and eight T2) and the posterior wall (one T3). Thirteen were irradiated by exclusive brachytherapy (dose, > or =45 Gy). The PDR delivered 0.5 Gy/pulse, one pulse/h, day and night, to mimic cLDR irradiation. RESULTS: The implantation was feasible for all the patients, usually easy and of good quality. The mean duration/pulse was 13 min, with a mean source activity of 171 mCi. Patient tolerance was poor in nine cases. Sixteen patients could receive the whole PDR treatment with a total ranging from 30 to 120 pulses without any problem. Seven had short breakdowns (< or =6 h). Seven had definitive breakdowns, but could end the irradiation by manual afterloading of iridium 192 wires. The radioprotection was better (or complete), except for one patient. Most of the breakdowns were related to kinking or flattering of the tube. CONCLUSIONS: PDR is feasible in head and neck carcinomas, but necessitates improvement of the quality and control of the plastic tubes.

[Treatment of pelvic lymph node involvement in early stage cervical cancer]. / Le traitement de l'envahissement ganglionnaire pelvien dans les cancers du col utérin aux stades précoces.

OBJECTIVES: Results of a retrospective paired study comparing the outcome of patients irradiated for lymph node involvement according to the method of node assessment: laparotomy or laparoscopy. MATERIAL AND METHODS: Twenty-six patients with cervical cancer managed by postoperative radiation therapy for pelvic node involvement during the Wertheim-Meigs operation (historical group) were compared to 26 patients in whom lymph node involvement was discovered at the time of laparoscopy and managed by definitive radiation therapy without hysterectomy (laparoscopy group). The patients were matched according to age, stage, tumor histology and tumoral volume. RESULTS: No difference was observed in the five-year survivals. Although it was not significant there were more grade 3-4 radio-induced complications in the historical group. CONCLUSIONS: The introduction of laparoscopy and the absence of hysterectomy did not impair the outcome of our patients. Laparoscopic lymphadenectomy reduces the risk of radio-induced adverse effects.