scholarly journals Surgical Therapy of Esophageal Adenocarcinoma—Current Standards and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5834
Author(s):  
Wolfgang Schröder ◽  
Suzanne S. Gisbertz ◽  
Daan M. Voeten ◽  
Christian A. Gutschow ◽  
Hans F. Fuchs ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Postoperative Morbidity ◽  
Intraoperative Imaging ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Extent Of Resection ◽  
Surgical Reconstruction ◽  
Risk Patients ◽  
Resectable Esophageal ◽  
Locally Advanced Tumors

Transthoracic esophagectomy is currently the predominant curative treatment option for resectable esophageal adenocarcinoma. The majority of carcinomas present as locally advanced tumors requiring multimodal strategies with either neoadjuvant chemoradiotherapy or perioperative chemotherapy alone. Minimally invasive, including robotic, techniques are increasingly applied with a broad spectrum of technical variations existing for the oncological resection as well as gastric reconstruction. At the present, intrathoracic esophagogastrostomy is the preferred technique of reconstruction (Ivor Lewis esophagectomy). With standardized surgical procedures, a complete resection of the primary tumor can be achieved in almost 95% of patients. Even in expert centers, postoperative morbidity remains high, with an overall complication rate of 50–60%, whereas 30- and 90-day mortality are reported to be <2% and <6%, respectively. Due to the complexity of transthoracic esophagetomy and its associated morbidity, esophageal surgery is recommended to be performed in specialized centers with an appropriate caseload yet to be defined. In order to reduce postoperative morbidity, the selection of patients, preoperative rehabilitation and postoperative fast-track concepts are feasible strategies of perioperative management. Future directives aim to further centralize esophageal services, to individualize surgical treatment for high-risk patients and to implement intraoperative imaging modalities modifying the oncological extent of resection and facilitating surgical reconstruction.

Neoadjuvant Chemoradiotherapy Combined with Atezolizumab for Resectable Esophageal Adenocarcinoma: A Single Arm Phase II Feasibility Trial (PERFECT)

2021 ◽  
pp. clincanres.4443.2020
Author(s):  
Tom van den Ende ◽  
Nicolien de Clercq ◽  
Mark I. van Berge Henegouwen ◽  
Suzanne S Gisbertz ◽  
Debby Geijsen ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Neoadjuvant Chemoradiotherapy ◽  
Feasibility Trial ◽  
Resectable Esophageal

A More Extensive Lymphadenectomy Enhances Survival Following Neoadjuvant Chemoradiotherapy in Locally Advanced Esophageal Adenocarcinoma

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Smita Sihag ◽  
Tamar Nobel ◽  
Meier Hsu ◽  
Kay See Tan ◽  
Rebecca Carr ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Extensive Lymphadenectomy

scholarly journals A Phase II Study Demonstrates No Feasibility of Adjuvant Treatment with Six Cycles of S-1 and Oxaliplatin in Resectable Esophageal Adenocarcinoma, with ERCC1 as Biomarker for Response to SOX

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 839
Author(s):  
Charlotte I. Stroes ◽  
Sandor Schokker ◽  
Remco J. Molenaar ◽  
Ron A. A. Mathôt ◽  
Maarten F. Bijlsma ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Biomarker Discovery ◽  
Neoadjuvant Chemoradiotherapy ◽  
Area Under The Curve ◽  
Dose Intensity ◽  
Additional Treatment ◽  
Resectable Esophageal ◽  
Negative Tumor ◽  
Tumor Expression ◽  
Biomarker Research

We assessed the feasibility of adjuvant S-1 and oxaliplatin following neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Patients treated with nCRT (paclitaxel, carboplatin) and esophagectomy received six 21-day cycles with oxaliplatin (130 mg/m2) on day 1 and S-1 (25 mg/m2 twice daily) on days 1–14. The primary endpoint was feasibility, defined as ≥50% completing treatment. We performed exploratory propensity-score matching to compare survival, ERCC1 and Thymidylate Synthase (TS) immunohistochemistry analyses, proteomics biomarker discovery and 5-FU pharmacokinetic analyses. Forty patients were enrolled and 48% completed all adjuvant cycles. Median dose intensity was 98% for S-1 and 62% for oxaliplatin. The main reason for early discontinuation was toxicity (67%). The median recurrence-free and overall survival were 28.3 months and 40.8 months, respectively (median follow-up 29.1 months). Survival was not significantly prolonged compared to a matched cohort (p = 0.09). Patients with ERCC1 negative tumor expression had significantly better survival compared to ERCC1 positivity (p = 0.01). Our protein signature model was predictive of survival [p = 0.04; Area under the curve (AUC) 0.80]. Moreover, 5-FU pharmacokinetics significantly correlated with treatment-related toxicity. To conclude, six cycles adjuvant S-1 and oxaliplatin were not feasible in pretreated esophageal adenocarcinoma. Although the question remains whether additional treatment with chemotherapy should be provided in the adjuvant setting, subgroups such as patients with ERCC1 negativity could potentially benefit from adjuvant SOX based on our exploratory biomarker research.

A phase II feasibility trial of neoadjuvant chemoradiotherapy combined with atezolizumab for resectable esophageal adenocarcinoma: The PERFECT trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4045-4045 ◽  
Author(s):  
Tom van den Ende ◽  
Nicolien C. de Clercq ◽  
Mark I. van Berge Henegouwen ◽  
Suzanne S. Gisbertz ◽  
Sybren L. Meijer ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Feasibility Trial ◽  
R0 Resection ◽  
Resectable Esophageal ◽  
The Cross ◽  
Grade 3

4045 Background: The CROSS study demonstrated the superiority of neoadjuvant chemoradiotherapy (nCRT) over surgery alone (van Hagen et al. NEJM. 2012). However, for resectable esophageal adenocarcinoma (rEAC) 5y survival is only 43%. PD1/PDL1 checkpoint inhibitors have shown promising efficacy for several cancer types, including esophageal cancer. To further improve outcomes in rEAC, we performed a phase II trial of nCRT combined with atezolizumab, a PD-L1 inhibitor. Methods: Pts with rEAC received standard dose CROSS regimen (5 cycles of IV: carboplatin AUC2, paclitaxel 50 mg/m2 and concurrent 23 fractions of 1.8 Gy on weekdays) with atezolizumab (5 cycles: 1200 mg IV, 3 weekly). Primary endpoint was the percentage of pts completing treatment with atezolizumab. Secondary endpoints included: toxicity, post-operative complications (Clavien-Dindo), Mandard score, R0 resection rate, PFS and OS. In total 40 pts will be enrolled. Results: Since July 2017, 39 pts have been enrolled (87% males, median age 63). Neoadjuvant treatment was completed by 31 pts and is ongoing in 8 pts. All cycles/fractions of nCRT were administered in 29/31 pts; 26 pts completed all cycles of atezolizumab, 24 pts finished complete neoadjuvant treatment. Reasons for missing any cycle of chemotherapy/atezolizumab included: toxicity (6 pts, in 3/6 pts immune-related adverse events (irAE)) and progression (1 pt). Grade 3-4 toxicity was observed in 15/31 pts (6/31 irAEs of any grade) which did not delay surgery. Thus far 23/31 pts were resected, 3 pts are planned for surgery, 3 pts had interval metastases preoperatively, 1 pt died during treatment (pulmonary embolism), and 1 pt declined surgery. Clavien-Dindo grade 3-4 complications were seen in 11/23 pts with no surgery related mortality. A pathological complete response (pCR), Mandard 1 was seen in 9/23 (39%) pts. All patients underwent an R0 resection. Updated results will be presented at the meeting. Conclusions: Based on data thus far, atezolizumab added to nCRT is feasible. A pCR was observed in 39% of patients, which is promising compared to 23% in the CROSS study. Treatment is associated with irAE which are manageable. Biomarker research will be performed on blood (circulating tumor DNA), tissue (immune microenvironment) and feces (microbiome). Clinical trial information: NCT03087864.

A novel gene signature for predicting response to chemoradiotherapy in esophageal adenocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 445-445
Author(s):  
Souvik Ghatak ◽  
Ashten N. Omstead ◽  
Blair A Jobe ◽  
Rachael Kreft ◽  
Anastasia Gorbunova ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Biomarker Discovery ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Gene Signature ◽  
Post Treatment ◽  
Frequent Mutations ◽  
Immune Related Genes ◽  
Biomarker Signature

445 Background: While neoadjuvant chemoradiotherapy (CRT) has emerged as an important treatment modality in patients with locally advanced esophageal adenocarcinoma (EAC), ~60%-70% of patients do not respond to such treatments; but are exposed to their toxicity nonetheless. This highlights the clinical need for the development of biomarkers that can robustly predict response to CRT and spare others from the toxicity and expense associated with these treatments. Herein, we systematically identified a biomarker signature that predicts response to CRT in EAC patients. Methods: Using a clinical-trial driven cohort of 25 EAC patients treated with 5- fluorouracil plus carboplatin and concurrent radiation therapy, we performed whole-exome sequencing (WES) in paired biopsy specimens obtained at baseline and 3-6 weeks post-treatment. In addition, we also analyzed the predictive potential of a panel of immune-related genes (TIM3, LAG3, IDO1 and CXCL9) in these matched tissues. Results: In our cohort, based upon RECIST criteria, 14 EAC patients were categorized as non-responders, while 11 were deemed as responders to CRT. Among responders, the most frequently mutated genes were NOTCH1, NOTCH2, NOTCH3, and MLL2; and the overall tumor mutation burden (TMB) was significantly reduced for these genes in post-treatment specimens (P<0.001). In contrast, in non-responders, NFE2L2, KEAP1, FAT1, FAT2, FAT3 and PIK3CA, harbored frequent mutations. Similarly, all four immune-related genes were significantly up-regulated in post-treatment specimens (p<0.05-0.001). Interestingly, the progression-free survival was significantly greater in patients with lower TMB (64.1%, p=0.04) and increased immunogenic scoring (62.7%, p=0.01). We finally constructed a risk-stratification model that comprised of mutational scores from 10 most frequently mutated genes, together with 4 immune-related genes, which achieved an AUC of 0.83 in predicting response to CRT in EAC patients. Conclusions: Using a systematic biomarker discovery approach, we have developed a novel biomarker signature that robustly predicts response to CRT in EAC patients and has a significant potential for personalized management of EAC patients.

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