RAMIE vs OTE for Esophageal Cancer
(RAMIE vs OTE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: St. Joseph's Healthcare Hamilton
Disqualifiers: Pregnancy, Stage IV cancer, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
In Canada, the incidence of esophageal cancer has been increasing over time, while surgical standards for esophageal resections have remained unchanged. Currently, the standard of surgical care for this cancer is Open Transthoracic Esophagectomy (OTE), a highly morbid operation that is associated with a complication rate of 60-80%, and a recovery period of many months. While Minimally Invasive Esophagectomy (MIE) has been developed it has not been adopted because it is highly complex, technically demanding, and has a longer operative time than OTE. With the advent of robotic platforms, Robotic Assisted Minimally Invasive Esophagectomy (RAMIE) has recently emerged as a novel minimally invasive alternative to OTE. RAMIE utilizes the DaVinci Xi robotic surgical platform which offers superior dexterity, 3D-vision, and wristed surgical equipment. To date, case reports and small case series have demonstrated the safety of RAMIE, however it has not been performed yet in Canada, and there has been no randomized trial that has compared RAMIE to OTE. This study proposes to build the infrastructure for introducing RAMIE to Canada, while laying the foundations for a future randomized controlled trial which will compare it to OTE.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications.
What data supports the effectiveness of the treatment RAMIE vs OTE for Esophageal Cancer?
Research shows that robotic-assisted minimally invasive esophagectomy (RAMIE) has similar long-term survival and disease-free survival rates compared to open transthoracic esophagectomy (OTE) for esophageal cancer, with potentially better short-term outcomes like reduced blood loss and shorter ICU stays.12345
Is robotic-assisted minimally invasive esophagectomy (RAMIE) safe compared to open esophagectomy (OE) for esophageal cancer?
How does the RAMIE vs OTE treatment for esophageal cancer differ from other treatments?
The RAMIE (Robotic Assisted Minimally Invasive Esophagectomy) treatment is unique because it uses robotic assistance to perform the surgery, which can potentially offer more precision and less invasiveness compared to traditional open surgery methods like OTE (Open Transthoracic Esophagectomy). This approach may lead to quicker recovery times and fewer complications for patients.7891011
Eligibility Criteria
This trial is for adults with Stage I, II, or III esophageal cancer who are eligible for surgery. It's not open to pregnant or breastfeeding women, those not using birth control, people allergic to ICG/sodium iodide/iodine, or anyone unsuitable for minimally invasive surgery.Inclusion Criteria
I am 18 years old or older.
My surgeon has approved me for a less invasive surgery.
My esophageal cancer is in an early stage and I am a candidate for surgery.
Exclusion Criteria
I am not pregnant, breastfeeding, and if able to bear children, I am using effective birth control.
Hypersensitivity or allergy to ICG, sodium iodide, or iodine
My esophageal cancer is in stage IV.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase A: Learning Curve
40 patients undergo NIF-guided RAMIE using ICG dye to gain proficiency
Varies per patient
Phase B: Randomized Controlled Feasibility Trial
54 patients are randomized to either NIF-guided RAMIE using ICG dye or OTE
Varies per patient
Follow-up
Participants are monitored for safety and effectiveness after treatment
12 weeks
Postoperative Day 1, 3-Weeks Postoperative, 12-Weeks Postoperative
Treatment Details
Interventions
- Open Transthoracic Esophagectomy (OTE) (Procedure)
- Robotic Assisted Minimally Invasive Esophagectomy (RAMIE) (Procedure)
Trial OverviewThe study compares two surgical methods for esophageal cancer: a new robotic-assisted technique (RAMIE) and the standard open surgery (OTE). RAMIE uses advanced robotics aiming to reduce complications and recovery time.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: NIF-Guided RAMIE using ICG Dye (Experimental Arm)Experimental Treatment1 Intervention
The patient will undergo NIF-guided RAMIE using ICG dye using the standard Ivor-Lewis approach. This will be a two-stage operation involving a first stage through a 5-port robotic approach through the abdomen to achieve a proximal gastrectomy and D2 nodal dissection. A feeding jejunostomy would not be inserted, as per the enhanced recovery pathway for esophagectomy. In addition, the vascularization of the conduit can be confirmed using the near-infrared camera of the robot with the ICG dye. The second stage of the operation will involve a 4-port robotic approach through the right chest to achieve thoracic nodal dissection, esophagectomy, and a hand-sewn anastomosis between the residual esophagus and the gastric conduit at the level of the azygous vein. During this second stage of the operation, NIF with ICG dye will be used to visualize the vascular supply of the gastric conduit, and assess the gastric conduit for any perfusions to potentially reduce anastomotic leaks.
Group II: Open Transthoracic Esophagectomy (OTE)Active Control1 Intervention
The patient will undergo OTE using the standard Ivor-Lewis approach. This is a two-stage operation involving a first stage through laparotomy, proximal gastrectomy, D2 nodal dissection, and insertion of feeding jejunostomy. The second stage of the operation will involve a right thoracotomy, thoracic nodal dissection, esophagectomy, and a stapled anastomosis between the residual esophagus and the gastric conduit at the level of the azygous vein.
Open Transthoracic Esophagectomy (OTE) is already approved in Canada, European Union, United States for the following indications:
🇨🇦 Approved in Canada as Open Transthoracic Esophagectomy for:
- Esophageal cancer
🇪🇺 Approved in European Union as Open Transthoracic Esophagectomy for:
- Esophageal cancer
🇺🇸 Approved in United States as Open Transthoracic Esophagectomy for:
- Esophageal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
St. Joseph's Healthcare HamiltonHamilton, Canada
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Who Is Running the Clinical Trial?
St. Joseph's Healthcare HamiltonLead Sponsor
McMaster UniversityCollaborator
References
Two-Year Quality of Life Outcomes After Robotic-Assisted Minimally Invasive and Open Esophagectomy. [2022]Robotic-assisted minimally invasive esophagectomy (RAMIE) is a safe alternative to open esophagectomy (OE). However, differences in quality of life (QOL) after these procedures remain unclear. We previously reported short-term QOL outcomes after RAMIE and OE and describe here our results from 2 years of follow-up.
Oncologic Long-Term Results of Robot-Assisted Minimally Invasive Thoraco-Laparoscopic Esophagectomy with Two-Field Lymphadenectomy for Esophageal Cancer. [2022]Open transthoracic esophagectomy is the worldwide gold standard in the treatment of resectable esophageal cancer. Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RAMIE) for esophageal cancer may be associated with reduced blood loss, shorter intensive care unit (ICU) stay, and less cardiopulmonary morbidity; however, long-term oncologic results have not been reported to date.
Does the Approach Matter? Comparing Survival in Robotic, Minimally Invasive, and Open Esophagectomies. [2019]Our objective was to determine how surgical approach impacts overall survival and postoperative outcomes when comparing robotic-assisted minimally invasive esophagectomy (RAMIE), minimally invasive esophagectomy (MIE), and open esophagectomy (OE).
Survival After Esophagectomy: A Propensity-Matched Study of Different Surgical Approaches. [2022]Although open esophagectomy (OE) is considered the "gold standard" treatment for esophageal cancer, robotic-assisted minimally invasive esophagectomy (RAMIE), and laparoscopic/thoracoscopic minimally invasive esophagectomy (MIE) are becoming more common. This study aimed to compare short-term outcomes and overall survival of patients undergoing RAMIE, MIE, and OE.
Robot-assisted minimally invasive thoracolaparoscopic esophagectomy versus open esophagectomy: long-term follow-up of a randomized clinical trial. [2021]Initial results of the ROBOT, which randomized between robot-assisted minimally invasive esophagectomy (RAMIE) and open transthoracic esophagectomy (OTE), showed significantly better short-term postoperative outcomes in favor of RAMIE. However, it is not yet clarified if RAMIE is equivalent to OTE regarding long-term outcomes. The aim of this study was to report the long-term oncological results of the ROBOT trial in terms of survival and disease-free survival. This study is a follow-up study of the ROBOT trial, which was a randomized controlled trial comparing RAMIE to OTE in 112 patients with intrathoracic esophageal cancer. Both the trial protocol and short-term results were previously published. The primary outcome of the current study was 5-year overall survival. Secondary outcomes were disease-free survival and recurrence patterns. Analysis was by intention to treat. During the recruitment period, 109 patients were included in the survival analysis (RAMIE n = 54, OTE n = 55). Majority of patients had clinical stage III or IV (RAMIE 63%, OTE 55%) and received neoadjuvant chemoradiotherapy (80%). Median follow-up was 60 months (range 31-60). The combined 5-year overall survival rates for RAMIE and OTE were 41% (95% CI 27-55) and 40% (95% CI 26-53), respectively (log rank test P = 0.827). The 5-year disease-free survival rate was 42% (95% CI 28-55) in the RAMIE group and 43% (95% CI 29-57) in the OTE group (log rank test P = 0.749). Out of 104 patients, 57 (55%) developed recurrent disease detected at a median of 10 months (range 0-56) after surgery. No statistically difference in recurrence rate nor recurrence pattern was observed between both groups. Overall survival and disease-free survival of RAMIE are comparable to OTE. These results continue to support the use of robotic surgery for esophageal cancer.
Long-term survival outcomes associated with robotic-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer. [2023]Minimally Invasive esophagectomy for esophageal cancer is associated with less morbidity compared to open approach. Whether robotic-assisted minimally invasive esophagectomy (RAMIE) results in better long-term survival compared with open esophagectomy (OE) and minimally invasive esophagectomy (MIE) is unclear.
12-lipoxygenase promotes tumor progress by TGF-β1-mediated epithelial to mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma. [2022]To clarify the effect of 12-lipoxygenase/12-hydroxyeicosatetraeonic acid (12-LOX/12-HETE) on progress of esophageal squamous cell carcinoma (ESCC) and the possible mechanism.
Prognostic role of PGE2 receptor EP2 in esophageal squamous cell carcinoma. [2022]Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, has been shown to affect numerous tumorigenic processes. PGE2 acts through G-protein-coupled receptors designated as EPs. Recently it has been documented that PGE2 promotes colon cancer cell growth via EP2. However, the expression and the prognostic role of EP2 in esophageal squamous cell carcinoma (ESCC) remained unknown. From January 1995 to January 2001, tissue samples from 226 patients with ESCC who underwent esophagectomies at our institutions were collected and made into tissue core arrays for study. EP2 expression was examined by immunohistochemical staining and confirmed by Western blot. The clinicopathologic data were then analyzed. EP2 overexpression was observed in 43.4% (98/226) of ESCC. Overexpression of EP2 correlated positively with depth of tumor invasion (T status) (P = 0.016) and was associated with worse overall survival (P = 0.047). In patients without regional or distant lymph node metastasis (N0 or M0), EP2 overexpression was associated with worse overall survival (P = 0.033 and P = 0.003, respectively). Using Cox regression analysis, T status, N status, and M status were the independent factors of overall survival, but EP2 expression was not. However, when focusing on patients with T1-3N0M0 status, EP2 expression became an independent factor of overall survival (P = 0.048). Our results show that EP2 overexpression was associated with worse prognosis, and correlated positively with T status in ESCC. Meanwhile, among those patients at earlier stages, EP2 overexpression significantly disclosed patients at high risks for poor prognosis.
Prostaglandin EP2 receptor expression is increased in Barrett's oesophagus and oesophageal adenocarcinoma. [2010]Accumulating evidence suggests that cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) is involved in oesophageal adenocarcinogenesis. PGE2 exerts its biological action by binding to specific receptors (EP1, EP2, EP3 and EP4).
Effects of selective PGE2 receptor antagonists in esophageal adenocarcinoma cells derived from Barrett's esophagus. [2013]Accumulating evidence suggests that COX-2-derived prostaglandin E(2) (PGE(2)) plays an important role in esophageal adenocarcinogenesis. Recently, PGE(2) receptors (EP) have been shown to be involved in colon cancer development. Since it is not known which receptors regulate PGE(2) signals in esophageal adenocarcinoma, we investigated the role of EP receptors using a human Barrett's-derived esophageal adenocarcinoma cell line (OE33). OE33 cells expressed COX-1, COX-2, EP(1), EP(2) and EP(4) but not EP(3) receptors as determined by real time RT-PCR and Western-blot. Treatment with 5-aza-dC restored expression, suggesting that hypermethylation is involved in EP(3) downregulation. Endogenous PGE(2) production was mainly due to COX-2, since this was significantly suppressed with COX-2 inhibitors (NS-398 and SC-58125), but not COX-1 inhibitors (SC-560). Cell proliferation ((3)H-thymidine uptake) was significantly inhibited by NS-398 and SC-58125, the EP(1) antagonist SC-51322, AH6809 (EP(1)/EP(2) antagonist), and the EP(4) antagonist AH23848B, but was not affected by exogenous PGE(2). However, treatment with the selective EP(2) agonist Butaprost or 16,16-dimethylPGE(2) significantly inhibited butyrate-induced apoptosis and stimulated OE33 cell migration. The effect of exogenous PGE(2) on migration was attenuated when cells were first treated with EP(1) and EP(4) antagonists. These findings suggest a potential role for EP selective antagonists in the treatment of esophageal adenocarcinoma.
Characterization of the prostaglandin E2 pathway in a rat model of esophageal adenocarcinoma. [2019]Accumulating evidence indicates that the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays a key role in esophageal carcinogenesis. A better understanding of the pathway downstream of COX-2 may reveal novel targets for the prevention of esophageal adenocarcinoma (EAC). The objective of this study was to characterize the profile of genes involved in PGE2 metabolism and signaling in an experimental model of EAC. Esophagojejunostomy with gastric preservation was performed in wistar rats to induce gastroduodenal reflux. Rats were sacrificed 2 or 4 months after surgery. Nine non-operated rats were used to obtain normal (control) esophageal tissues.