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

Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial.

INTRODUCTION We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). METHODS Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cycle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed. RESULTS The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. placebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. placebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade ≥3 toxicities was similar across arms. CONCLUSIONS In this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN

Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial

Introduction: We report long-term efficacy and overall survival (OS) results from a randomised, double-blind, phase 2 study (NCT02022098) investigating xevinapant plus standard-of-care chemoradiotherapy (CRT) vs. placebo plus CRT in 96 patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).Methods: Patients were randomised 1:1 to xevinapant 200 mg/day (days 1-14 of a 21-day cycle for 3 cycles), or matched placebo, plus CRT (cisplatin 100 mg/m2 every 3 weeks for 3 cycles plus conventional fractionated high-dose intensity-modulated radiotherapy [70 Gy/35 F, 2 Gy/F, 5 days/week for 7 weeks]). Locoregional control, progression-free survival, and duration of response after 3 years, long-term safety, and 5-year OS were assessed.Results: The risk of locoregional failure was reduced by 54% for xevinapant plus CRT vs. placebo plus CRT but did not reach statistical significance (adjusted hazard ratio [HR] 0.46; 95% CI, 0.19-1.13; P = .0893). The risk of death or disease progression was reduced by 67% for xevinapant plus CRT (adjusted HR 0.33; 95% CI, 0.17-0.67; P = .0019). The risk of death was approximately halved in the xevinapant arm compared with placebo (adjusted HR 0.47; 95% CI, 0.27-0.84; P = .0101). OS was prolonged with xevinapant plus CRT vs. placebo plus CRT; median OS not reached (95% CI, 40.3-not evaluable) vs. 36.1 months (95% CI, 21.8-46.7). Incidence of late-onset grade ≥3 toxicities was similar across arms.Conclusions: In this randomised phase 2 study of 96 patients, xevinapant plus CRT demonstrated superior efficacy benefits, including markedly improved 5-year survival in patients with unresected LA SCCHN