Correlation between pelvic bone marrow radiation dose and acute hematological toxicity in cervical cancer patients treated with concurrent chemoradiation.

PURPOSE: To evaluate the association between pelvic bone marrow (BM) dose volume parameters and probability of acute hematological toxicity (HT), a cohort of cervical cancer patients receiving definitive chemoradiation (CRT) was assessed. MATERIALS AND METHODS: Medical records of patients treated by CRT (45 Gy in 25 fractions, without dose constraints applied to the BM) were reviewed. Baseline and weekly hematological parameters were collected. BM was retrospectively delineated and divided into sub-sites: iliac crests, lower pelvis, lumbosacral region. BM volumes (V) receiving 5, 10, 20, 30, 40 Gy (V5, V10, V20, V30, V40, respectively) and mean dose (Dm) were calculated. Logistic regression was used to analyze associations between HT and dose-volume histograms parameters. RESULTS: 114 patients were included. 75.4% were treated with 3D radiation therapy and 24.6% were receiving intensity modulated radiation therapy (IMRT). Neither age, chemotherapy regimen (cisplatin vs carboplatin), number of chemotherapy cycles, performance status, body mass index, or para-aortic irradiation were associated with HT. In univariate analysis, more frequent grade 3+ leukopenia was found in the IMRT group (odds ratio [OR]: 3.5; 95% CI, 1.4-9.1; p=0.007). In multivariate analysis, grade 4 HT was associated with lower pelvis V5>95% (OR 4.1; 95% CI, 1.6-14. p=0.02), lower pelvis V20>45% (OR 3.5; 95% CI, 1.1-13.4; p=0.05), total pelvic bone V20>65%, and iliac crests Dm >31 Gy (OR 4.5; 95% CI, 1.4-14.7; p=0.02). CONCLUSION: The following dose constraints could be proposed to decrease acute HT risk: lower pelvis V5<95%, lower pelvis V20≤45%, total pelvic bone V20<65%, and iliac crests Dm <31 Gy.

[Why is brachytherapy still essential in 2017?] / Pourquoi la curiethérapie reste-t-elle indispensable en 2017 ?

These recent years, brachytherapy has benefited from imaging modalities advances. A more systematic use of tomodensitometric, ultrasonographic and MRI images during brachytherapy procedures has allowed an improvement in target and organs at risk assessment as well as their relationship with the applicators. New concepts integrating tumor regression during treatment have been defined and have been clinically validated. New applicators have been developed and are commercially available. Optimization processes have been developed, integrating hypofractionation modalities leading to tumor control improvement. All these opportunities led to further development of brachytherapy, with indisputable ballistic advantages, especially compared to external irradiation.

[New calculation algorithms in brachytherapy for iridium 192 treatments]. / Nouveaux algorithmes de calcul en curiethérapie pour les traitements par iridium 192.

Since 1995, the brachytherapy dosimetry protocols follow the methodology recommended by the Task Group 43. This methodology, which has the advantage of being fast, is based on several approximations that are not always valid in clinical conditions. Model-based dose calculation algorithms have recently emerged in treatment planning stations and are considered as a major evolution by allowing for consideration of the patient's finite dimensions, tissue heterogeneities and the presence of high atomic number materials in applicators. In 2012, a report from the American Association of Physicists in Medicine Radiation Therapy Task Group 186 reviews these models and makes recommendations for their clinical implementation. This review focuses on the use of model-based dose calculation algorithms in the context of iridium 192 treatments. After a description of these algorithms and their clinical implementation, a summary of the main questions raised by these new methods is performed. Considerations regarding the choice of the medium used for the dose specification and the recommended methodology for assigning materials characteristics are especially described. In the last part, recent concrete examples from the literature illustrate the capabilities of these new algorithms on clinical cases.

45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims?

AIMS: In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. MATERIALS AND METHODS: The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. RESULTS: A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. CONCLUSION: The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions.

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.

PURPOSE: Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. METHODS: Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. RESULTS: Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3-4 toxicities were reported in 10.4% and urinary grades 3-4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (>55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P=0.021 and P=0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P=0.046, odds ratio=7.0). CONCLUSIONS: Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.

Clinical Experience with Pulse Dose Rate Brachytherapy for Conservative Treatment of Penile Carcinoma and Comparison with Historical Data of Low Dose Rate Brachytherapy.

AIMS: To assess the efficacy of pulse dose rate (PDR) interstitial brachytherapy in the treatment of carcinoma of the penis and to compare with historical data of low dose rate (LDR) brachytherapy. MATERIALS AND METHODS: We reviewed the clinical records of 27 consecutive patients treated in our institution with exclusive PDR brachytherapy for a squamous cell carcinoma of the penis. The median tumour greatest diameter was 20 mm (range: 10-50 mm). Twenty-three patients (85%) had tumours limited to the glans and/or prepuce and four patients (15%) also had inguinal lymph node metastases. Implantations were carried out according to the Paris system and treatments were delivered with PDR brachytherapy. RESULTS: The median brachytherapy dose was 60 Gy (range: 60-70 Gy). The median treated volume was 28 cm(3) (range: 8-62 cm(3)). The median reference isodose rate was 0.4 Gy/pulse/h (range: 0.4-0.5 Gy/pulse/h). The median number of pulses was 150 (range: 120-175 pulses). With a median follow-up of 33 months (range: 6-64 months), tumour relapses in the penis were reported in four patients (15%). All patients with only local relapse (n = 3) were successfully salvaged with partial amputation. The estimated overall survival rate at 3 years was 95% (95% confidence interval: 83-100%). No grade 3 or more acute reaction was observed. Delayed ulcerations and stenoses requiring at least one meatal dilatation were reported in two (9%) and five (22%) patients without local relapse. The treated volume was significantly correlated to the risk of clinically relevant delayed toxicity. CONCLUSIONS: The efficacy/toxicity results of PDR brachytherapy for the treatment of penile carcinoma are comparable with those obtained with LDR brachytherapy in historical cohorts.

Interstitial pulsed-dose-rate brachytherapy for the treatment of squamous cell anal carcinoma: A retrospective single institution analysis.

OBJECTIVE: To examine the outcome of patients receiving interstitial pulsed-dose-rate brachytherapy (PDR-BT) after pelvic radiation therapy for treatment of an anal squamous cell carcinoma. METHODS AND MATERIALS: Twenty-one patients were identified: 13, six, and two with stages I, II, and III tumors, respectively. After receiving received pelvic irradiation +/- concurrent chemotherapy, patients were delivered a PDR-BT boost to the residual tumor, with intention to deliver a minimal total dose of 60 Gy. The greatest dimension of residual tumor at the time of brachytherapy procedure was 12.5 mm (range: 0-20 mm). Brachytherapy implantation was performed according to the Paris system, only one plane implant being used. RESULTS: Median dose delivered through BT was 20 Gy (range: 10-30 Gy). Median number of pulses was 48 (range: 20-80 pulses). Median treated volume was 9 cm(3) (range: 5-16 cm(3)). Median dose per pulse was 40 cGy (range: 37.5-50 cGy). No Grade 3 or more acute toxicity was reported. No Grade 3 or more delayed toxicity was seen among 18 patients with more than 6 months follow-up. Median followup was 47 months (range: 6-73 months). Twenty patients (95%) were alive at last follow-up. Tumor relapses were experienced in four patients (19%), including local relapse in three patients (14%). CONCLUSION: With almost 4 years median followup, this study confirms previous data suggesting that PDR-BT is effective and safe in this indication. Local control rate and toxicity were in the range of what was seen with continuous low-dose-rate BT.

Implementation of the global risk analysis in pulsed-dose rate brachytherapy: methods and results.

PURPOSE: To report the application of the global risk analysis (GRA) in the pulsed-dose rate (PDR) brachytherapy workflow. MATERIAL AND METHODS: Analyses were led by a multidisciplinary working group established within the unit with the guidance of a quality engineer. First, a mapping of hazardous situations was developed as a result of interactions between the patient workflow for a treatment using PDR brachytherapy split into 51 sub-phases with a comprehensive list of the hazards that he/she faces (44). Interactions, when relevant, were sorted by level of priority: to be treated immediately, secondarily (the group is not entitled to treat the situation), or later (safe situation). Secondly, for each high priority dangerous situation, scenarios were developed to anticipate their potential consequences. Criticality was assessed, using likelihood and severity scales and a matrix, which allocated risks into categories: acceptable (C1), tolerable under control (C2) and unacceptable (C3). Then, corrective actions were proposed and planned when relevant, after assessment of their feasibility with a scale of effort. Finally, the criticality of the scenarios was reevaluated, taking into account the implementation of these actions, leading to a residual risk mapping, which could trigger additional proposals of actions. RESULTS: Two thousand one hundred and eighty-four potential interactions between the list of hazards and the workflow were analyzed. Mapping of dangerous situations identified 213 relevant interactions, from which 61 were considered with high priority. One hundred and twenty-six scenarios were generated: 68 with a low criticality (74.3%), 58 with an intermediate score (25.7%). No scenario with the highest criticality was individualized. Twenty-one corrective actions were planned. Mapping of residual risk resulted in the disappearance of most C2 risks, leaving 5 C2 scenarios (4%), for which four monitoring indicators were implemented in addition to the corrected actions decided on. CONCLUSION: The implementation of the GRA appeared feasible, and led to implement 21 corrective actions, based on scenarios and not on incidents.

[Pulsed-dose rate brachytherapy in cervical cancers: why, how?]. / Curiethérapie de débit de dose pulsé dans les cancers du col utérin : pourquoi, comment ?

The end of the production of 192 iridium wires terminates low dose rate brachytherapy and requires to move towards pulsed-dose rate or high-dose rate brachytherapy. In the case of gynecological cancers, technical alternatives exist, and many teams have already taken the step of pulsed-dose rate for scientific reasons. Using a projector source is indeed a prerequisite for 3D brachytherapy, which gradually installs as a standard treatment in the treatment of cervical cancers. For other centers, this change implies beyond investments in equipment and training, organizational consequences to ensure quality.

Comparison between the ICRU rectal point and modern volumetric parameters in brachytherapy for locally advanced cervical cancer.

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/ß 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.

[Intensity-modulated radiotherapy in cervical cancer: towards a new standard?]. / Radiothérapie conformationnelle avec modulation d'intensité dans les cancers du col : vers un nouveau standard ?

Intensity modulated radiation therapy has demonstrated its ability to prevent xerostomia in the treatment of head and neck cancers, as well as post-radiation related proctitis in prostate cancer. In the management of cervical carcinomas, many published dosimetric studies have shown its ability to limit the irradiation of organs at risk. However, clinical data remain limited to comparisons of cohorts, mostly retrospective, but promising. This review aims to update the current state of knowledge.

Volumetric evaluation of an alternative bladder point in brachytherapy for locally advanced cervical cancer.

PURPOSE: To evaluate an alternative dose point, so-called ALG (for Alain Gerbaulet), for the bladder in comparison to the International Commission on Radiation Units and Measurements (ICRU) point and D2cm(3) (minimal dose to maximally exposed 2 cm(3)) in a large cohort of patients with locally advanced cervical cancer treated with external beam radiotherapy followed by image-guided pulsed dose rate brachytherapy. METHODS AND MATERIALS: For each patient, the ALG point was constructed 1.5 cm above the ICRU bladder, parallel to the tandem (coronal and sagittal planes). The dosimetric data from 162 patients were reviewed. RESULTS: Average doses to ALG and bladder points were 19.40 Gy ± 7.93 and 17.14 ± 8.70, respectively (p=0.01). The 2 cm(3) bladder dose averaged 24.40 ± 6.77 Gy. Ratios between D2cm(3) and dose points were 1.37 ± 0.46 and 1.68 ± 0.74 (p<0.001) for ALG and ICRU points, respectively. Both dose points appeared correlated with D2cm(3) (p<0.001) with coefficients of determination (R(2)) of 0.331 and 0.399 respectively. The estimated dose to the ICRU point of the rectum was 12.77 ± 4.21 and 15.76 ± 5.94 for D2cm(3) (p<0.0001). Both values were significantly correlated (p<0.0001, R(2) = 0.485). CONCLUSION: The ALG point underestimates the D2cm(3), but its mean on a large cohort is closer to D2cm(3) than the dose to ICRU point. However, it shows great variability between cases and the weak strength of its correlation to D2cm(3) indicates that it is not a good surrogate for individual volumetric evaluation of the dose D2cm(3).

[Contribution of 3D imaging in brachytherapy: which kind of imaging for which localization?]. / Apport de l'imagerie 3D en curiethérapie : quel type d'imagerie pour quelle localisation ?

The use of image-guided brachytherapy has led to a significant change in application techniques and improvements in treatment planning. Today, 3D imaging has replaced orthogonal radiographs for a large number of treatments, providing a possibility of an optimization adapted to the anatomy of each patient. When properly selected and implemented, this imaging provides accurate 3D information of volumes and brachytherapy device, allowing moving from a dose to points assessment to a dose/volume evaluation. This article describes the contribution of different imaging modalities for the different brachytherapy techniques: gynecological brachytherapy, interstitial brachytherapy (breast, penis, etc.) and prostate brachytherapy. It reminds recommendations for the establishment of protocols of images acquisition and 3D reconstruction of brachytherapy devices (applicators, plastic tubes, needles, etc.).

Brachytherapy for isolated tongue metastasis of renal clear cell carcinoma.

INTRODUCTION: Tongue metastasis of renal cell carcinoma (RCC) is rare. Treatment is hindered by the proximity of anatomic structures involved in swallowing, speech and mastication. It is, moreover, radioresistant. CASE REPORT: We report a case of inaugural isolated tongue metastasis, where biopsy redirected diagnosis to RCC. To avoid potentially mutilating excision in a metastatic disease of poor prognosis, treatment was local, consisting in interstitial brachytherapy, enabling a high dose (65Gy) to be delivered. Despite initially complete response, recurrence at 10.5months required salvage surgery. DISCUSSION AND CONCLUSION: Brachytherapy allowed a higher dose to be delivered than with external beam radiation therapy, previously reported for similar cases. This dose, which can usually be expected to ensure local control in 90% of squamous cell carcinomas of the tongue, obtained 10months' response, insufficient to avoid salvage surgery.

[Impact on the indoor environment of allergic children of the medical counselor on indoor environment, after two successive visits at 6 months interval]. / Impact sur l'habitat de l'enfant atteint d'une affection respiratoire allergique du conseiller médical en environnement intérieur après deux visites successives à 6 mois d'intervalle.

BACKGROUND: The aim of this retrospective study was to assess the impact of a medical indoor environment counselor (MIEC) on the allergic child's indoor home environment, as well as the real-life experience of patients' families. METHODS: We enrolled 50 children (age, 4-18 years) with allergic respiratory illness (96 % asthmatics) from March 2011 to January 2012. During the first visit, the CMEI gave advice according to the results of the assessment. Home environmental exposures were assessed 6 months later. A satisfaction questionnaire was completed by the parents. RESULTS: We found a significant decrease in the presence of house dust mites (P = 0.0047), humidity, and molds (P = 0.0047) as well as volatile organic compounds (P = 0.0047). Smoking habits were not significantly changed (P = 0.083), nor was the presence of domestic pets (P = 0.3173). Over 74 % of the families were very satisfied with the CMEI's intervention. DISCUSSION: According to de Blay's study, a home visit by the MEIC increased compliance with mite reduction. The intervention to advise parents of asthmatic children on the risks of passive smoking was ineffective in reducing their children's exposure to environmental tobacco smoke. The advice given by the MEIC was better understood by the patients than that expressed by the medical teams. CONCLUSION: A targeted home-based environmental intervention increased the compliance to mite, humidity, and mold reduction. The role of the CMEI will undoubtedly develop: follow-up studies are necessary to justify their activity (cost-efficacy ratio of their intervention).

[Accelerated partial breast irradiation for early breast cancer]. / Irradiation partielle accélérée du cancer du sein : aspect théorique.

Hypofractionated and accelerated partial breast irradiation are more and more widely used for early breast cancer. Here, this short communication would expose the role of hypofractionated radiotherapy in adjuvant breast radiotherapy, rational, techniques and indications of accelerated partial breast irradiation.

[Outcome of cervical carcinoma with locoregional lymph node involvement by FDG-PET]. / Modalités d'évolution des cancers du col utérin avec atteinte ganglionnaire locorégionale à la TEP-FDG.

PURPOSE: To assess the outcome of cervical carcinoma with positive nodes on fluorodesoxyglucose positon emission tomography scans (FDG-PET). PATIENTS AND METHODS: Patients with cervical carcinoma who had pelvic and/or para-aortic lymph nodes involvement by FDG-PET and treated with a curative intent from 2003 to 2007 were retrospectively studied. All patients received pelvic (and possibly para-aortic) radiotherapy with chemotherapy, followed by brachytherapy, and possibly surgery. The first site of relapse was classified as follows: local, nodal (pelvic or para-aortic) or metastatic. RESULTS: Forty patients were included the study. Median age was 47 years (range: 28-78). Thirty patients had nodal involvement limited to pelvic area and ten had a para-aortic involvement. Median follow-up was 42.5 months (range: 11-85). There were 22 relapses and 20 deaths: 20 due to relapse and one due to late toxicity. Three-year survival is 50 % (95 % confidence interval [CI]: 36-65). First relapse was: metastatic for 33 % (13/40), local for 20 % (8/40) and isolated nodal for 5 % (2/40). Multivariate analysis has revealed that only staging according to International Federation of Gynecology and Obstetrics (FIGO) and para-aortic involvement had a significant impact on survival. Three-year survival was 58 % (CI: 39-74) and 24 % (CI: 7-57) (P=0.009) in patient without and with para-aortic involvement, respectively. CONCLUSION: Para-aortic involvement by FDG-PET is a significant prognostic factor for overall survival. Local control at primary site remains of paramount importance for patient with nodal involvement. Isolated nodal failures are scarce.

Role of anti-HSP 60/65 antibodies in atherogenesis in patients with type 2 diabetes and lower limb ischemia.

The role of heat shock proteins and anti-HSP 60/65 antibodies in atherogenesis has been widely described in the literature, but the participation of these molecules in the pathogenesis of diabetic macroangiopathy has not been extensively investigated. 30 patients with type 2 diabetes complicated with macroangiopathy of the lower extremities in the intermittent claudication stage. The control group (n=18) consisted of healthy volunteers of corresponding age. Levels of anti-HSP 60/65 antibodies, von Willebrand factor (vWF) and hsCRP in blood serum were measured. We also assessed static effort based on isometric contraction lasting until full fatigue. In patients with lower limb ischemia in diabetic macroangiopathy, a positive correlation between anti-HSP 60/65 antibodies and von Willebrand factor levels in blood serum was found (R=0.543, p<0.05). Concentrations of anti-HSP 60/65 antibodies were higher than in the control group, but not statistically significant (44.77±55.00 vs. 26.09±13.85; NS). The ongoing disease process contributed statistically significantly to the strength of the quadriceps muscle of the thigh (21.47 vs. 27.82 for the right limb, and 20.27 vs. 28.33 for the left limb; p<0.05). Increased concentrations of anti-HSP 60/65 antibodies in blood serum suggests their involvement in the pathogenesis of diabetic macroangiopathy and correlates with the parameters of endothelial cell damage. In patients with type 2 diabetes complicated with atherosclerotic changes, a statistically significant reduction in lower limb muscle strength was found compared with the control group.

[Locally advanced cervical cancer: Should intensity-modulated radiotherapy replace brachytherapy?]. / Complément d'irradiation dans le cancer du col de l'utérus localement évolué : curiethérapie utérovaginale ou radiothérapie conformationnelle avec modulation d'intensité ?

Intensity-modulated conformal radiotherapy (IMRT) is booming as treatment of locally advanced cervical cancer. This technique reduces the doses delivered to organs at risk and, by analogy to the irradiation of prostate cancer, opens the door to the possibility of dose escalation to levels close or similar to those achieved by brachytherapy. To date, several studies comparing IMRT with brachytherapy have been published, often methodologically flawed, concluding sometimes that both techniques are comparable. These results should be taken with extreme caution and should not overshadow the recent advances in brachytherapy with the use of 3D imaging and optimization. Preliminary works also showed that the combination of 3D optimized brachytherapy with IMRT could improve the management of the local disease especially for lesions poorly covered by intracavitary techniques.

[Three-dimensional brachytherapy optimization techniques in the treatment of patients with cervix cancer]. / Apport des techniques de curiethérapie optimisée grâce à l'imagerie tridimensionnelle dans la prise en charge des patientes atteintes d'un cancer du col utérin.

Traditionally, prescription and treatment planning in intracavitary brachytherapy for cervix cancer have used either reference points (mainly points A and B) or reference isodoses (60Gy according to ICRU recommendations) to report doses to the target volume. Doses to critical organs were reported at bladder and rectum ICRU points. This practice has been supported by a long-standing clinical experience that has yielded an acceptable therapeutic ratio. The recent development of imaging has contributed to the improvement in target and organs at risk knowledge. In 2005 and 2006, GEC-ESTRO recommendations publications on 3-D based image brachytherapy have defined the different volumes of interest. These recommendations have been validated with intercomparison delineation studies. With the concomitant development of remote after-loading projectors, provided with miniaturized sources, it is now possible to plan radiation doses by adjusting dwell positions and relative dwell time values. These procedures allow better coverage of the targets while sparing OAR. The recent literature data evidence a significant improvement in local control with no increase in complications. Further studies are needed to better define the dose recommended in both tumour and organs at risk. This is one of the goals of the European study on MRI-guided brachytherapy in locally advanced cervical cancer (EMBRACE) protocol.