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

Significance of Microscopically Incomplete Resection Margin After Esophagectomy for Esophageal Cancer

International audienceOBJECTIVE:The objectives of this study were to establish if R1 resection margin after esophagectomy was (i) a poor prognostic factor independent of patient and tumor characteristics, (ii) a marker of tumor aggressiveness and (iii) to look at the impact of adjuvant treatment in this subpopulation.METHODS:Data were collected from 30 European centers from 2000 to 2010. Patients with an R1 resection margin (n = 242) were compared with those with an R0 margin (n = 2573) in terms of short- and long-term outcomes. Propensity score matching and multivariable analyses were used to compensate for differences in baseline characteristics.RESULTS:Independent factors significantly associated with an R1 resection margin included an upper third esophageal tumor location, preoperative malnutrition, and pathological stage III. There were significant differences between the groups in postoperative histology, with an increase in pathological stage III and TRG 4-5 in the R1 group. Total average lymph node harvests were similar between the groups; however, there was an increase in the number of positive lymph nodes seen in the R1 group. Propensity matched analysis confirmed that R1 resection margin was significantly associated with reduced overall survival and increased overall, locoregional, and mixed tumor recurrence. Similar observations were seen in the subgroup that received neoadjuvant chemoradiation. In R1 patients adjuvant therapy improved survival and reduced distant recurrence however failed to affect locoregional recurrence.CONCLUSIONS:This large multicenter European study provides evidence to support the notion that R1 resection margin is a prognostic indication of aggressive tumor biology with a poor long-term prognosis.TRIAL REGISTRATION:ClinicalTrials.gov NCT01927016

Self-Expanding Covered Metallic Stent as a Bridge to Surgery in Esophageal Cancer: Impact on Oncologic Outcomes

International audienceBACKGROUND:Self-expanding metallic stents (SEMSs) have been used as a bridge to surgery, relieving dysphagia and maintaining nutrition, in patients with operable but obstructive esophageal cancer (EC). However, the impact of SEMSs on oncologic outcomes is unknown. The aim of this study was to evaluate the impact of SEMS insertion before EC surgery on oncologic outcomes.STUDY DESIGN:From 2000 to 2010, two thousand nine hundred and forty-four patients who underwent an operation for EC with a curative intent were included in a multicenter European cohort. Through propensity score analysis, patients who underwent SEMS insertion (SEMS group, n = 38) were matched 1:4 to control patients who did not undergo SEMS insertion (control group, n = 152).RESULTS:The SEMS and control groups were comparable according to age, sex, tumor location, clinical stage, American Society of Anesthesiologists score, dysphagia, malnutrition, neoadjuvant treatment administration, histology, and surgical procedure. Self-expanding metallic stent insertion was complicated by tumoral perforation in 2 patients. The in-hospital postoperative mortality and morbidity rates for the SEMS vs control groups were 13.2% vs 8.6% (p = 0.370) and 63.2% vs 59.2% (p = 0.658), respectively. The R0 resection rate (71.0% vs 85.5%; p = 0.041), median time to recurrence (6.5 vs 9.0 months; p = 0.040), and 3-year overall survival (25% vs 44%; p = 0.023) were significantly reduced in the SEMS group, and the 3-year locoregional recurrence rate was increased (62% vs 34%; p = 0.049). The results remained significant after excluding SEMS-related esophageal perforations. After adjusting for confounding factors, SEMS insertion was a predictor of poor prognosis (hazard ratio = 1.6; p = 0.038).CONCLUSIONS:Self-expanding metallic stent insertion, as a bridge to surgery, has a negative impact on oncologic outcomes in EC. Clinicaltrials.gov ID: NCT 01927016

Salvage Surgery for Esophageal Cancer: How to Improve Outcomes?

International audienceBACKGROUND:Locoregional recurrence rates after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer (EC) are high. Salvage surgery (SALV) is considered the best treatment option in case of persistent or recurrent disease for operable patients, but SALV has been associated with increased morbidity and mortality. The aim of this study is to identify factors linked to outcomes after SALV to better select candidates and to optimize perioperative care.STUDY DESIGN:We retrospectively analyzed data from 308 consecutive SALV patients from a large multicenter European cohort. Univariate and multivariate analyses were performed to identify factors associated with in-hospital postoperative morbidity, anastomotic leakage (AL), and overall survival (OS).RESULTS:The in-hospital postoperative mortality and morbidity rates were 8.4 and 34.7%, respectively. Squamous cell histology (p = 0.040) and radiation dose ≥ 55 Gy (p = 0.047) were independently associated with major morbidity. The AL rate was 12.7%, and cervical anastomosis was independently associated with AL (p = 0.002). OS at 5 years was 34.0%. Radiation dose ≥ 55 Gy (p = 0.003), occurrence of postoperative complications (p = 0.006), ypTNM stage 3 (p = 0.019), and positive surgical margins (p < 0.001) were linked to poor prognosis.CONCLUSIONS:SALV is a valuable option for patients with persistent or recurrent disease after dCRT and offers long-term survival. Factors such as radiation dose and anastomosis location identified here will help to optimize outcomes after SALV, which may be considered a standard treatment in the EC therapeutic armamentarium

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)