scholarly journals Short-term outcome of Ivor Lewis esophagectomy following neoadjuvant chemoradiation versus perioperative chemotherapy in patients with locally advanced adenocarcinoma of the esophagus and gastroesophageal junction: a propensity score-matched analysis

2021 ◽  
Author(s):  
Patrick Sven Plum ◽  
Alexander Damanakis ◽  
Lisa Buschmann ◽  
Angela Ernst ◽  
Rabi Raj Datta ◽  
...  
Keyword(s):  
Propensity Score ◽  
Postoperative Morbidity ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiation ◽  
Perioperative Chemotherapy ◽  
Charlson Score ◽  
Ivor Lewis ◽  
Ivor Lewis Esophagectomy ◽  
Gastroesophageal Adenocarcinoma ◽  
Matching Criteria

Abstract Background Patients with locally advanced esophageal or gastroesophageal adenocarcinoma benefit from multimodal therapy concepts including neoadjuvant chemoradiation (nCRT), respectively, perioperative chemotherapy (pCT). However, it remains unclear which treatment is superior concerning postoperative morbidity. Methods In this study, we compared the postsurgical survival (30-day/90-day/1-year mortality) (primary endpoint), treatment response, and surgical complications (secondary endpoints) of patients who either received nCRT (CROSS protocol) or pCT (FLOT protocol) due to esophageal/gastroesophageal adenocarcinoma. Between January 2013 and December 2017, 873 patients underwent Ivor Lewis esophagectomy in our high-volume center. 339 patients received nCRT and 97 underwent pCT. After 1:1 propensity score matching (matching criteria: sex, age, BMI, ASA score, and Charlson score), 97 patients per subgroup were included for analysis. Results After matching, tumor response (ypT/ypN) did not differ significantly between nCRT and pCT (p = 0.118, respectively, p = 0.174). Residual nodal metastasis occurred more often after pCT (p = 0.001). Postsurgical mortality was comparable within both groups. No patient died within 30 or 90 days after surgery while the 1-year survival rate was 72.2% for nCRT and 68.0% for pCT (p = 0.47). Only grade 3a complications according to Clavien–Dindo were increased after pCT (p = 0.04). There was a trend towards a higher rate of pylorospasm within the pCT group (nCRT: 23.7% versus pCT: 37.1%) (p = 0.061). Multivariate analysis identified pCT, younger age, and Charlson score as independent variables for pylorospasm. Conclusion Both nCRT and pCT are safe and efficient within the multimodal treatment of esophageal/gastroesophageal adenocarcinoma. We did not observe differences in postoperative morbidity. However, functional aspects such as gastric emptying might be more frequent after pCT.

Phase II trial of perioperative chemotherapy + avelumab in locally advanced gastroesophageal adenocarcinoma: Preliminary results.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4046-4046
Author(s):  
Thierry Alcindor ◽  
Touhid Opu ◽  
Arielle Elkrief ◽  
Farzin Khosrow-Khavar ◽  
Carmen L. Mueller ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tumor Regression ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Daily Intake ◽  
Disease Free Survival ◽  
Type I ◽  
Perioperative Chemotherapy ◽  
Preliminary Results ◽  
Gastroesophageal Adenocarcinoma

4046 Background: Perioperative chemotherapy improves cure rate in locally advanced gastroesophageal adenocarcinoma (GEA), and immune checkpoint inhibitors are active at the metastatic stage. This trial tests the hypothesis that the addition of avelumab to perioperative chemotherapy will increase the major pathologic response (MPR) rate in comparison with historical controls. Methods: Phase II study of avelumab + chemotherapy (docetaxel, cisplatin and 5-FU or mDCF) given every 2 weeks for 4 cycles before and after surgery. Main inclusion criteria: GEA, cT3 and/or cN+, M0, WHO PS 0-1. Main exclusion criteria: use of immunosuppressants, serious autoimmune disease, daily intake >10 mg prednisone. Staging studies: CT, PET-CT, endoscopic ultrasound, diagnostic laparoscopy. Surgical resection: D2 lymphadenectomy, en-bloc esophagectomy for type I/II gastroesophageal junction (GEJ) tumors. Aim of the study: MPR as defined as tumor regression grades 0-1 (modified Ryan scheme); as per hypothesis, this experimental regimen will result in a 20% rate of MPR, compared with 7% with chemotherapy alone. Simon 2-stage design: if less than 2 MPR are seen in the first 16 patients, the study will be closed. The study hypothesis cannot be rejected if at least 6 MPR are seen in the first 50 patients. All adverse effects are prospectively recorded per CTCAE guidelines in patients who have received at least one treatment cycle. Survival rates are calculated with Kaplan-Meier method. Preliminary results are presented since the study has met its primary endpoint. Results: Feb 2018-Feb 2020: 28 patients enrolled (25 M/3 F, age 45-78). Location: GEJ (23), stomach (5). Staging: cT3 (25), cT4 (1), cN+ (20). Biomarkers expression: mismatch repair (MMR) protein loss (3/28); PD-L1(clone 73-10) expression in 1% (TPS) or more of tumor cells seen in 12/28 samples, and >10% in 6 patients. Grade 3 toxicity: stomatitis (2/28); nausea (2/28); vomiting (1/28); diarrhea (1/28); hypothyroidism (1/28); arthralgia (3/28); neutropenia (1/28). Grade 4 toxicity: pneumonia (1/28); neutropenia (2/28). Postoperative 30-day mortality: 0%. One patient was excluded from efficacy analyses for M1 staging; 27 patients underwent surgery, 26 with R0 (96%). Six cases (22%) show MPR: 3 grade 0 (11%) and 3 grade 1 (11%) tumor regressions. No correlation was seen between MMR proteins or PD-L1 expression and tumor regression. With a median follow-up of 1.5 years (range 0.4-2.5), the disease-free survival rate is projected to be 0.92 (95% CI 0.83-1.00) at 12 months and 0.77 (95% CI 0.58-1.00) at 24 months. Conclusions: The combination of mDCF chemotherapy with Avelumab demonstrates a promising safety and activity profile. Ongoing laboratory investigations are underway to correlate our findings with tumor molecular features before exposure to treatment. Clinical trial information: NCT03288350.

HER-2 overexpression in gastroesophageal junction (EGJ) adenocarcinoma as a predictor of prognosis in patients treated with perioperative chemotherapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 151-151
Author(s):  
Tiago Felismino ◽  
Audrey Oliveira ◽  
Ana Caroline Alves ◽  
Victor Hugo Fonseca Jesus ◽  
Wilson L. Costa ◽  
...  
Keyword(s):  
Cox Model ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Primary Site ◽  
Clinical Staging ◽  
Prognostic Impact ◽  
Perioperative Chemotherapy ◽  
Dismal Prognosis ◽  
Her 2 ◽  
Gastroesophageal Adenocarcinoma

151 Background: Approximately 15% of all gastroesophageal adenocarcinomas overexpress HER-2. This is more common in intestinal subtype and proximal tumors. HER-2 status is associated with poor prognosis in non-metastatic patients, but its prognostic impact on the outcomes of pts treated with perioperative chemotherapy (CT) is unclear. Methods: The aim of this study was to retrospectively analyze the influence of HER-2 status on the overall survival (OS) and Relapse Free Survival (RFS) of pts with locally advanced gastroesophageal adenocarcinoma treated with perioperative CT. HER-2 positive tumors were defined by 3+ immunohistochemical staining or fluorescence in situ hybridization positivity. Independent variables used in the Cox model were: Lauren's subtype, clinical staging, and a combination of primary site and HER-2 status. Results: A total of 97 patients were included: median age was 62y, 62 (63.9%) were male; N = 57 (58.8%) had cT3 tumors and 60 (60.1%) had cN+. Lauren’s subtype was intestinal in N = 35 (36.1%), and diffuse in N = 44 (45.4%). CT regimens were mainly FOLFOX (46.4%), EOX (23.7%) or DCF (13.4%). Regarding primary site and HER-2 status: gastric HER-2 negative N = 61, Gastric HER-2 positive N = 8, GEJ HER-2 negative N = 23, GEJ HER-2 positive N = 5. In a Cox multivariate analyses for OS and RFS, EGJ HER-2 positive pts had higher chance of recurrence (HR = 3.57, 1.08 – 11.77, p = 0.03) and death (HR = 6.14, 1.83 – 20.60, p = 0.003). EGJ HER-2+ 3y RFS was zero and 3y OS was 20%. Conclusions: EGJ HER-2+ tumors carried a dismal prognosis and had little benefit from conventional perioperative CT strategies. Although further studies are needed to confirm our data, we believe that a different approach, possible combining anti-HER-2 drugs, should be tested in this scenario.

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