Facteurs prédictifs de non réponse histologique après radiochimiothérapie néoadjuvante suivie de chirurgie pour cancers de l oesophage

Contexte : Le traitement du cancer de l'oesophage (CO) localement avancé comprend une radiochimiothérapie néoadjuvante (RCTN) suivie de chirurgie. Les données disponibles suggèrent que les patients présentant une réponse histologique auraient un meilleur pronostic. De plus, la RCTN n'apporterait pas de bénéfice sur la survie des patients non répondeurs, voire pourrait être délétère. Le but de ce travail était donc d'évaluer l'impact pronostique de la réponse histologique de la tumeur primitive évaluée selon le TRG de Mandard après RCTN suivie de chirurgie pour CO et d'identifier des facteurs prédictifs de réponse histologique complète et de non réponse histologique. Méthodes : Une étude rétrospective multicentrique a été menée chez 810 patients atteints de CO traités par RCTN suivie de chirurgie. L'analyse des facteurs pronostiques de survie a été réalisée par régression de Cox. L'étude de survie globale selon le grade TRG a permis de regrouper la population en 3 groupes : réponse complète (TRG 1), réponse partielle (TRG 2 et 3) et en non réponse (TRG 4 et 5). L'identification de facteurs prédictifs de réponse/non réponse a été faite par régression logistique. Résultats : La réponse histologique complète a été retrouvée comme facteur indépendant de bon pronostic dans la population étudiée (HR 0,524 ; IC95% 0,368 - 0,745). Les survies des groupes en réponse complète, en réponse partielle et en non réponse étaient statistiquement différentes deux à deux et globalement (p<0,001). Les facteurs prédictifs de réponse complète retrouvés (TRG 1) étaient la réponse morphologique complète (p<0,001), le type histologique carcinome épidermoïde (p<0,001) et la bonne différenciation tumorale (p<0,001). Les facteurs prédictifs de non réponse (TRG 4 et 5) retrouvés étaient l'absence de réponse morphologique (p=0,049), la différenciation tumorale faible (p<0,001) et le nombre de cycles de chimiothérapie inférieur ou égal à 2 (p=0.04). Conclusion : Le TRG selon Mandard simplifié en 3 grades a un impact pronostique sur la survie des patients atteints de CO traités par RCTN suivie de chirurgie. Des facteurs de réponse histologique complète et de non réponse ont été identifiés. Cependant, les facteurs de non réponse identifiés ne permettent pas de sélectionner les patients qui ne bénéficieront pas de la RCTN. Des études ultérieures à la recherche de facteurs prédictifs cliniques devraient être menées.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

High-Grade Toxicity to Neoadjuvant Treatment for Upper Gastrointestinal Carcinomas: What is the Impact on Perioperative and Oncologic Outcomes?

International audienceBACKGROUND:Perioperative oncologic treatments provide a survival benefit for junctional and gastric adenocarcinoma (JGA) and esophageal cancer (EC). Whether neoadjuvant therapy toxicity (NTT) correlates with increased perioperative risk remains unclear. We aimed to evaluate the impact of grade III/IV NTT on postoperative and oncologic outcomes in resected upper gastrointestinal malignancies.METHODS:A multicenter retrospective analysis was performed on consecutive patients who benefited from neoadjuvant chemo(radio)therapy followed by surgery between 1997 and 2010 for JGA (first cohort, n = 653) and for EC (second cohort, n = 640). Data between patients who experienced NTT were compared to those who did not.RESULTS:NTT was associated with higher postoperative mortality after resection of JGA (P = 0.001) and after esophagectomy (P < 0.001), more non-R0 resections (JGA P = 0.019, EC P = 0.024), a decreased administration of adjuvant treatment among the JGA cohort (P = 0.012), and higher surgical morbidity (JGA P = 0.005, EC P = 0.020). Median survival was reduced in patients who experienced NTT in both cohorts (JGA P = 0.018, EC P = 0.037). After adjustment on confounding variables, NTT was independently associated with postoperative mortality in both cohorts (P ≤ 0.007).CONCLUSIONS:NTT is a predictor of postoperative mortality, correlates with higher postoperative morbidity, and negatively affects oncologic outcomes for upper gastrointestinal carcinomas

Depletion of MUC5B mucin in gastrointestinal cancer cells alters their tumorigenic properties: implication of the Wnt/β-catenin pathway

International audienceSecreted mucins are large O-glycosylated proteins that participate in the protection/defence of underlying mucosae in normal adults. Alteration of their expression is a hallmark of numerous epithelial cancers and has often been correlated to bad prognosis of the tumour. The secreted mucin MUC5B is overexpressed in certain subtypes of gastric and intestinal cancers, but the consequences of this altered expression on the cancer cell behaviour are not known. To investigate the role of MUC5B in carcinogenesis, its expression was knocked-down in the human gastric cancer cell line KATO-III and in the colonic cancer cell line LS174T by using transient and stable approaches. Consequences of MUC5B knocking-down on cancer cells were studied with respect to in vitro proliferation, migration and invasion, and in vivo on tumour growth using a mouse subcutaneous xenograft model. Western blotting, luciferase assay and qRT-PCR were used to identify proteins and signalling pathways involved. In vitro MUC5B down-regulation leads to a decrease in proliferation, migration and invasion properties in both cell lines. Molecular mechanisms involved the alteration of β-catenin expression, localization and activity and decreased expression of several of its target genes. In vivo xenografts of MUC5B-deficient cells induced a decrease in tumour growth when compared with MUC5B-expressing Mock cells. Altogether, the present study shows that down-regulation of MUC5B profoundly alters proliferation, migration and invasion of human gastrointestinal cancer cells and that these alterations may be, in part, mediated by the Wnt/β-catenin pathway emphasizing the potential of MUC5B as an actor of gastrointestinal carcinogenesis

Non-occlusive Small Bowel Ischemia Related to Postoperative Feeding Jejunostomy Tube Use After Esophagectomy for Cancer: Propensity Score Analysis of the AFC-FREGAT Database

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Surgically treated oesophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes

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Impact of Neoadjuvant Chemoradiotherapy on Postoperative Outcomes After Esophageal Cancer Resection

International audienceObjectives: To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection.Background: Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL.Methods: Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n = 593) were compared with those treated by primary surgery (n = 1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics.Results: Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P = 0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P = 0.110) and 33.4% versus 32.1% (P = 0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P = 0.291), whereas chylothorax (2.5% vs 1.2%; P = 0.020), cardiovascular complications (8.6% vs 0.1%; P = 0.037), and thromboembolic events (8.6% vs 6.0%; P = 0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P = 0.228), with more chylothorax (2.5% vs 0.7%; P = 0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P = 0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT.Conclusions: Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection (NCT 01927016)

Role of neoadjuvant treatment in clinical T2N0M0 oesophageal cancer: results from a retrospective multi-center European study

International audienceAims: The aims of this study were to compare short-and long-term outcomes for clinical T2N0 oesophageal cancer with analysis of (i) primary surgery (S) versus neoadjuvant therapy plus surgery (NS), (ii) squamous cell carcinoma and adenocarcinoma subsets; and (iii) neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy.Methods: Data were collected from 30 European centres from 2000 to 2010. Among 2944 included patients, 355 patients (12.1%) had cT2N0 disease; 285 (S) and 70 (NS), were compared in terms of short-and long-term outcomes. Propensity score matching analyses were used to compensate for differences in baseline characteristics.Results: No significant differences between the groups were shown in terms of in hospital morbidity and mortality. Nodal disease was observed in 50% of S-group at the time of surgery, with 20% pN2/N3. Utilisation of neoadjuvant therapy was associated with significant tumour downstaging as reflected by increases in pT0, pN0 and pTNM stage 0 disease, this effect was further enhanced with neoadjuvant chemoradiotherapy. After adjustment on propensity score and confounding factors, for all patients and subset analysis of squamous cell and adenocarcinoma, neoadjuvant therapy had no significant effect upon survival or recurrence (overall, loco-regional, distant or mixed) compared to surgery alone. There were no significant differences between neoadjuvant chemotherapy and chemoradiotherapy in short-or long-term outcomes.Conclusion: The results of this study suggest that a surgery alone treatment approach should be recommended as the primary treatment approach for cT2N0 oesophageal cancer despite 50% of patients having nodal disease at the time of surgery

Incidence and Risk Factors Related to Symptomatic Venous Thromboembolic Events After Esophagectomy for Cancer

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