Optimisation des techniques de radiothérapie dans le cadre de la prise en charge des patientes traitées par radiochimiothérapie d'un cancer du col de l'utérus

Contexte : En février 1999 la publication de 4 essais randomisés incite le NCI à recommander la radiochimiothérapie chez les patientes traitées pour un cancer du col utérin de stade avancé. Objectif : Le but de notre étude était de comparer nos résultats en terme de survie globale, de toxicité aiguë et tardive à ceux de la littérature, et de déterminer si l'augmentation du volume irradié en curiethérapie (V60) et en radiothérapie externe était prédictif de complications, chez les patientes de stade >= IB2 traitées par radiochimiothérapie. Matériels et Méthodes : 97 patientes d'âge moyen 49,4 ans atteintes de cancers du col utérin de stade >= IB2 (17 IB2, 12 IIA, 21 IIB, 1 IlIA, 34 IIIB, 4 IVA et 8 IVB), ont été incluses dans notre étude rétrospective. Toutes les patientes ont reçu une chimiothérapie à base de sel de platine (CDDP-5FU ou Carbo-5FU ou CDDP hebdo) de manière concomitante à la radiothérapie, 94 patientes ont eu une curiethérapie et 55 patientes ont bénéficié d'une chirurgie. Résultats : Le suivi moyen des patientes était de 34,2 mois. Les patientes dont la V60 était supérieur à 70 cm3, avaient plus de toxicités tardives (grade 2, 3,4) 61,7% que les patientes dont la V60 était inférieur à 70 cm3, 33,3% (p=0,02). La taille des champs de radiothérapie externe, ainsi que le protocole de chimiothérapie ne modifiaient pas le taux de complications tardives ni aiguës. La réalisation d'une chirurgie augmentait les toxicités tardives (grade 3, 4), 11,3% en cas de chirurgie vs 0% en l'absence de chirurgie (P=0,02). La survie actuarielle à 5 ans est de 63,6%. La survie sans événement est de 83% à 2 ans. Conclusion : Nos résultats sont comparables à ceux de la littérature en terme de survie sans récidive, de survie globale et de taux de complications aiguës et tardives. Notre étude met en évidence une relation entre le volume de curiethérapie et le taux de complications tardives. Des travaux récents ont montré une augmentation du contrôle local lorsque la dose de curiethérapie augmente, les curiethérapies devront à l'avenir être réalisées avec optimisation de la répartition de dose.The aim of our study was to compare our results in term of survival, acute and late toxicity to those of the literature, and to determine if increase in the volume irradiated in brachytherapy (V60) and in extemal radiotherapy were predictive complications, in the patients of stage >= IB2 treated by radiochemotherapy.Materials and Methods : 97 patients of average age 49,4 years reached of cancers of the cervix cancer of stage >= IB2 (17 IB2, 12 lIA, 21 IlB, 1 IlIA, 34 I1IB, 4 IV A and 8 IVB), were included in our retrospective study. All the patients received a chemotherapy containing platinum salt (CDDP-5FU or Carbo-5FU or CDDP weekly) in a concomitant way to the radiotherapy, 94 patients had brachytherapy and 55 patients profited from a surgery. Results : The average follow-up of the patients was 34,2 months. The patients whose V60 was higher than 70 Cm3, had more late toxicities (rank 2,3,4) 61,7% that the patients whose V60 was lower than 70 Cm3, 33,3% (p=0,02). Size of the fields of extemal radiotherapy, as weil as the protocol of chemotherapy did not modify the rate of late complications nor acute. The surgery increased late toxicities (rank 3, 4), II,3% in the event of surgery vs 0% in the absence of surgery (p=0,02). Survival at 2 years is 86%. Survival without event is 83% to 2 years. Conclusion: Our results are comparable with those of the literature in term of survival without repetition, total survival and rate of acute and late complications. Our study highlights a relation between the volume of brachytherapy and the rate of late complications. Recent work showed an increase in local control when the amount of c brachytherapy increases, the brachytherapy will have in the future to be completed with optimization of the distribution of amount.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Impact of dosimetric parameters on local control for patients treated with three-dimensional pulsed dose-rate brachytherapy for cervical cancer

International audienceTo investigate the impact of dose-volume histograms parameters on local control of three-dimensional (3D) image-based pulsed dose-rate brachytherapy (BT).METHODS AND MATERIALS:Within a French multicentric prospective study, the data of the 110 patients treated for cervical cancer with external beam radiotherapy followed by 3D image-based and optimized pulsed dose-rate BT were analyzed. Delineation procedures were performed on magnetic resonance imaging in a minority of cases and on CT for the majority of cases, adapted from the Gynaecological Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology recommendations. Optimization procedure was left to the discretion of the treating center.RESULTS:At 2 years, local control rate reached 78%. Dose to Point A, total reference air kerma, and intermediate-risk clinical target volume (IR-CTV) V60 were predictive factors for local control (p = 0.001, p = 0.001, and p = 0.013, respectively). Patients with IR-CTV V60 <75% had a relative risk of local recurrence of 3.8 (95% confidence interval, 1.4-11.1). There was no correlation found between the high-risk clinical target volume dosimetric parameters and local control.CONCLUSIONS:This multicentric study has shown that 3D image-based BT provides a high local control rate for cervical cancer patients. The V60 for IR-CTV was identified as an important predictive factor for local control

Expression of neurotensin receptor 1 in endometrial adenocarcinoma is correlated with histological grade and clinical outcome

International audienceThe promalignant effects of neurotensin (NTS) are sustained in many solid tumors, including hormone-dependent cancers. As the endometrium is also subjected to hormonal regulation, we evaluated the contribution of NTS to endometrial carcinogenesis. Neurotensin receptor 1 (NTSR1) expression and NTSR1 promoter methylation (HM450) were analyzed in 385 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Additionally, from a series of 100 endometrial carcinomas, and 66 benign endometrium samples, NTS and NTSR1 labeling was evaluated by immunohistochemistry. Using TCGA series, NTSR1 messenger RNA (mRNA) level was negatively correlated with overall survival (OS) and progression-free survival (PFS) (p = 0.0012 and p = 0.0116, respectively), and positively correlated with the grade (p = 0.0008). When including only endometrioid carcinomas, NTSR1 mRNA level continued to be negatively correlated with OS (log-rank: p < 0.0001) and PFS (log-rank: p = 0.002). A higher NTSR1 mRNA level was significantly associated with a loss of NTSR1 promoter methylation. Immunohistochemical expression of NTS and NTSR1 was significantly increased in adenocarcinoma (n = 100), as compared to benign endometrium (p < 0.001). NTSR1 expression was positively correlated with grade (p = 0.004). High immunohistochemical expression of cytoplasmic NTSR1 was significantly correlated with a shorter OS and PFS (p < 0.001 and p = 0.001, respectively). This correlation remained significant when excluding non-endometrioid subtypes (p = 0.04 and p = 0.02, respectively). In multivariate analysis, the expression of NTSR1 was an independent prognostic factor (p = 0.004). NTSR1 overexpression is a poor prognostic factor in endometrial cancer, highlighting the contribution of NTS in endometrial cancer progression and its uses as a prognostic marker, and as a potential therapeutic target

Identification of specific tumor markers in vulvar carcinoma through extensive human papillomavirus DNA characterization using next generation sequencing method

International audienceObjectives: A subset of vulvar carcinomas (VC) are associated with human papillomavirus (HPV) DNA. This trait can be used to identify tumor markers for patient's follow-up. A large diversity of HPV prevalence in VC has been reported, but no data are available concerning the insertional HPV status in this tumor type. Therefore, we have used an innovative next generation sequencing (NGS)-based CaptHPV method able to provide an extensive characterization of HPV DNA in tumors.Material and Methods: Tumor tissue specimens from 55 patients with VC were analyzed using p16 immunohistochemistry, in situ hybridization, polymerase chain reaction, and CaptHPV-NGS assays.Results: Our analyses showed that 8 (14.5%) of 55 cases were associated with HPV 16 DNA. No other HPV genotypes were identified. The HPV genome was in a free episomal state only in one case and both episomal and integrated into the tumor cell genome in 7. There was a single insertion in 5 cases and multiple sites, scattered at different chromosomal loci in two. ISH data suggest that some of these might reflect tumor heterogeneity. Viral integration targeted cellular genes among which were TP63, CCDC148, LOC100133091, PKP1, and POLA2. Viral integration at the PKP1 locus was associated with partial gene deletion, and no PKP1 protein was detected in tumor tissue.Conclusions: Using the NGS-based innovative capture-HPV approach, we established a cartography of HPV 16 DNA in 8 VC cases and identified novel genes targeted by integration that may be used as specific tumor markers. In addition, we established a rationale strategy for optimal characterization of HPV status in VC