Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Stomach Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Stomach Cancer

Patients underwent gastric surgery through the use of a robotic system.

Patients underwent gastric surgery with laparoscopic procedures.

Gastrectomy performed with a robotic system.

Robot-Assisted Gastrectomy

Gastrectomy performed with conventional laparoscopic approach.

Laparoscopic Gastrectomy

Mª Asunción Acosta Mérida, MD. PhD.

In recent years there has been a rapid incursion of robotic technology applied to almost all fields of surgery. In gastric cancer, whose mainstay of treatment is still surgical resection, gastrectomy with robotic lymphadenectomy is growing faster than the scientific evidence supporting its results.

The "National Multicenter Cohort Study of ROBOT-Assisted Gastrectomy Versus Laparoscopy in Gastric Cancer" (ROBOTAG study) is proposed as a prospective multicenter Spanish nationwide study, comparing robotic gastrectomy versus conventional laparoscopic gastrectomy for the treatment of gastric cancer. This study aims to provide evidence on the feasibility, safety and complications, possible technical advantages, short and long term surgical and oncological results, as well as aspects related to quality of life, which can support the increase in cost and the important technological effort that underlies robotic surgery with respect to conventional laparoscopic access.

The relevance of this project is doubled by directing the objectives, on the one hand, on a new and expensive technology that is reaching hospitals still surrounded by controversy about its real benefits; and on the other hand, by acting on a pathology for which most of the available studies come from Eastern countries, sometimes not very applicable to the Western context.

RELEVANCE OF THE STUDY

The project presented here is a pioneering study in Spain, which aims to provide scientific evidence on robot-assisted gastrectomy in gastric cancer. The feasibility, oncologic outcomes, potential benefits, complications and limitations will be investigated. Few hospitals in the country have robotic technology and also perform this surgical procedure. The aim is to include as many centers as possible in this study, which will involve an important effort, but also the search for answers of great scientific value and repercussion in the applicability of this innovation in western environment. It is hoped to be able to provide, both at the management level of the Spanish Health System and extensively in other countries, a basis for decision making to audit and, if necessary, endorse the development and diffusion of this technology in hospitals, in order to offer patients the best surgical option in the treatment of gastric cancer.

OBJECTIVES

The main objective of this study is to compare Robot-Assisted Gastrectomy (RAG) with conventional Laparoscopic Gastrectomy (LG), from the point of view of clinical and oncological safety.

In addition, possible differences between patients undergoing each technique will be analyzed in other aspects, both intraoperatively and postoperatively.

Primary objective The main objective of this study is to compare the clinical and oncological safety of robot-assisted gastrectomy (RAG) with conventional laparoscopic gastrectomy (LG).

For this purpose the investigators will analyze in both groups (robot and laparoscopy):

1. as a measure of clinical safety:

   * Intraoperative blood loss
   * Perioperative complications
2. and as a measure of oncologic safety:

   * Nodal count (Number of lymph nodes retrieved)
   * R0 resection margin

   Secondary objectives

   To assess the differences between the groups (RAG vs LG) in intraoperative outcomes:
   * Operative time
   * Number of surgeons per procedure
   * Need for conversion to open surgery
   * Surgeon comfort
   * Learning curve

   To assess the differences between groups (RAG vs LG) in postoperative recovery course and physical status:
   * Onset of oral tolerance
   * Onset of mobilization
   * Hospital stay
   * Readmission
   * Mortality.

   To assess the differences between groups (RAG vs LG) in oncological outcomes:
   * Overall and disease-free survival
   * Local and systemic recurrence To assess the differences between the groups (RAG vs LG) cost utility measured in QALYs.

   HYPOTHESIS

   Robot-assisted laparoscopic gastrectomy with lymphadenectomy (RAG) offers at least the same results as gastrectomy with lymphadenectomy using a conventional laparoscopic (LG) approach in the treatment of gastric cancer, in terms of feasibility, safety, complications, and oncological outcomes.

   MATERIAL AND METHODS
   * Type of study: National, multicenter, prospective follow-up cohort study in patients undergoing minimally invasive gastric cancer surgery, using robot-assisted laparoscopic gastrectomy with lymphadenectomy (RAG) versus conventional laparoscopy (LG).
   * Study population: Patients diagnosed with gastric adenocarcinoma, in whom surgical treatment with curative intent by minimally invasive gastrectomy (RAG or LG) has been indicated.

   The protocol will follow standard clinical practice, without being modified by the present study.

   Patients who agree to participate in the study will have signed the informed consent form.

   • Primary outcome variable:
   * As a clinical safety measure, intraoperative blood loss and perioperative complications at 30 and 90 days will be analyzed.
   * As an oncological safety measure, the number of resected lymph nodes and the R0 resection margin will be analyzed.
   * Other intraoperative and postoperative, oncologic and quality of life parameters will be analyzed secondarily.

     * Sample size:

   This study aims to involve the largest number of centers nationwide and recruit the largest possible number of patients that these centers can provide. Taking into account the annual incidence of cases in each center, an approximate number of 20 cases per year per center is estimated. With the participation of at least 20 hospital centers, the investigators hope to obtain a sample of at least 400 patients for analysis.
   * Inclusion criteria:

     - Histologically confirmed primary gastric adenocarcinoma

     - Clinical stages Ib, II and III of gastric cancer (8th edition of the TNM classification)

     - Patients with ECOG performance status 0, 1 or 2

     - Patients who sign the informed consent to participate in the study

     - Patients over 18 years old

     - Patients treated by surgery with curative intent
   * Exclusion criteria:

     - Any histology other than adenocarcinoma

     - Stage Ia and IV

     - Unresectability criteria (tumor factors): distant metastasis, peritoneal carcinomatosis, positive cytology of ascitic fluid, invasion or tumor entrapment of large vessels (aorta, liver, celiac trunk), infiltration of the root of the mesentery, para-aortic lymphadenopathy or levels \>3, linitis plastica, involvement of other organs

     - Inoperability criteria (patient factors): serious concomitant systemic disorders incompatible with surgery or the study (at the discretion of the investigator)

     - Non-compliance with any of the inclusion criteria
     * Patients undergoing surgery for gastric cancer with open approach at the beginning
     * Palliative surgery cases
   * Recruitment:

   All the centers included in the study must have the human and technical means necessary to guarantee the quality of the surgical treatment of gastric cancer, following current standards.

   The surgery will be performed in a hospital that has a specialized Esophagogastric Surgery Unit that performs advanced minimally invasive, laparoscopic and robotic surgery on a regular basis, as well as a Multidisciplinary Tumor Committee.

   All surgeons included must have previous experience of at least 20 gastrectomies with laparoscopic lymphadenectomies and an annual caseload of at least 10 cases; in addition to having accreditation as a robot console surgeon, having previously performed at least 3 gastrectomies with robot-assisted oncologic lymphadenectomy.

   Patients who are candidates for inclusion by the participating centers, who meet the inclusion criteria and who wish to participate, must sign the informed consent for the study. Access codes will be assigned to the center's investigators for the anonymized introduction of the study data. The confidentiality of the information handling of this study will be guaranteed, following national and international regulations.

   • Duration of study: Each collaborating researcher will provide patients who meet the inclusion criteria, recruiting them for 1 year. The minimum follow-up of all patients will be 1 year, after which the global analysis of the data and the corresponding study will be carried out. The final objective would be to achieve follow-up of all patients for at least 5 years, after which a new global analysis of the sample would be carried out to obtain the results after this period.

   • Follow-up: All patients included in the study must have at least a 1-year follow-up.

   The study will end when all enrolled patients have been followed for five years, died, withdrew consent or were lost to follow-up. A preliminary analysis of results will be performed when all patients enrolled in the study have been followed for the first year.

   • Data collection:

   In this study it is planned to obtain information from the collection of preoperative, intraoperative and postoperative data:

   - Patient's affiliation data

   - Medical history

   - Analytical and complementary test data

   - Patient and tumor characteristics

   - Surgical procedure parameters
   * Postoperative results
   * Follow-up data and quality of life

   The patient will be followed up throughout the study, and the status of the postoperative variables will be collected at each medical appointment.

   • Statistical analysis: Descriptive analysis of the data will be performed. Qualitative variables will be presented by frequency distribution and quantitative variables will be measured by indicators of central tendency (mean or median) and dispersion (standard deviation or interquartile range, respectively).

   Hypothesis contrast tests will be performed, with comparison of proportions when both variables are qualitative (Chi-square, Fisher's exact test) and comparisons of means for independent samples when one of them is quantitative (Student's t test if normal distribution or Mann-Whitney U test for variables that do not comply with normality). Survival will be estimated using the Kaplan-Meier method and survival curves will be compared using the Log-Rank test to analyze the effect of the different factors that may influence survival. The results of the study will be analyzed by intention-to-treat. After recruitment of half of the patients, an intermediate data analysis will be performed.

   The final analysis will be performed in two phases, one on the morbidity-mortality results at the end of recruitment, and another at the end of the study with the definitive data on recurrence and survival.

   A logistic regression model will be performed to evaluate the effect of representative covariates on the LRS. For this purpose, those that are significant in the univariate analysis (p\<0.2) or clinically relevant will be included.

   A value of p\<0.05 will be considered statistically significant.

National Multicenter Cohort Study of Robot-Assisted Gastrectomy Versus Laparoscopy in Gastric Cancer

Intraoperative blood loss and perioperative complications (types of complications, Clavien Dindo classification, Comprehensive Complication Index (CCI®))

Nodal count (number of lymph nodes retrieved) and R0 resection margin.

* Operative time (duration of the surgical procedure measured in minutes)
* Number of surgeons who have participated in the operation (1 to 5)
* Need for conversion to open surgery (conversion to open surgery vs non-conversion)
* Comfort of the surgeon during the intervention, using an analog scale of 0-5 (0 is no comfort, 1 is little comfort, 2 is moderate comfort, 3 is quite a bit of comfort, 4 is a lot of comfort and 5 is extreme comfort)
* Learning curve (number of robotic versus laparoscopic gastrectomies performed by the surgeon before the registered case)

* Onset of oral tolerance (measured in number of days from the intervention to the first oral intake)
* Onset of mobilization (measured in number of days from the operation to the start of the patient's ambulation)
* Hospital stay (number of days of hospital admission, counted from the day of the intervention until discharge)
* Readmission (yes /no) (need for hospital admission after discharge, related to the operation, over 1 year postoperatively)
* Mortality (yes /no) (procedure-related death, within 1 year postoperatively) In case of death: time in days since surgery.

* Overall survival (OS): time between the date of intervention and the date of death (from any cause).
* Recurrence-free survival (RFS): time from the date of intervention to locoregional recurrence, distant recurrence or death, whichever occurred first. The date of biopsy will be the date of recurrence (or date of death).
* Local recurrence: surgical site of gastrectomy and lymphadenectomy (anastomosis or perianastomosis nodes).
* Distant or systemic recurrence: extra-regional lymph nodes (N3 and/or more distant lymph node levels), metastases in laparoscopic ports, parenchymal organ, carcinomatosis or bone metastases.

Dr. Negrin University Hospital

Principal Investigator

Symptoms and General Pathology

Neoplasm Metastasis

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Cisplatin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

In the intervention arm, conventional pressurized intraperitoneal chemotherapy (PIPAC) with cisplatin (10.5 mg/m2 body surface in 150ml saline) and doxorubicin (2.1 mg/m2 body surface in 50ml saline) is performed through Medical Device Regulation (MDR) class IIb the CE-certified nebuliser by certified PIPAC surgeons directly after the completion of the minimally invasive gastric resection and reconstruction using the remaining relevant ports. Chemotherapy is administered through a CE-certified nebulizer according to the manufacturer's manual and followed by 30 minutes of simple diffusion. The carbondioxide is evacuated through a closed system, and the abdominal wall is closed according to local surgical standards.

The same procedure is repeated, incorporating the same compounds and dose regimens six to eight weeks postoperatively and before the start of the adjuvant part of the perioperative systemic chemotherapy.

In the control arm, patients will undergo minimally invasive D2 gastrectomy

Jonas Sanberg, PhD

Martin Graversen, PhD

Yanghee Woo, PhD

Clarisse Eveno, PhD

Beate Rau, PhD

Michael Bau Mortensen, DMSci, PhD

The goal of this randomized clinical trial is to investigate whether pressurized intraperitoneal chemotherapy (PIPAC), delivered immediately after minimally invasive D2 gastrectomy and repeated 6-8 weeks later, improves 12-month peritoneal disease-free survival in patients with high-risk gastric adenocarcinoma when compared to standard treatment.

Despite declining incidence, gastric adenocarcinoma (GAC) is considered the fifth most common cancer worldwide and the third leading cause of cancer death globally. Its incidence varies across different parts of the globe, with a low incidence in the West. In East Asia, especially Japan and Korea, the incidence of distal GAC remains high, whereas proximal GAC tends to dominate in the West. Gastroesophageal junction (GEJ) adenocarcinomas that have the epicentre in the proximal 2 to 5 cm of the stomach (Siewert type III) should be staged and treated as GAC.

The consensus in most Western countries is that medically fit GAC patients should undergo D2 gastrectomy, carried out in specialised, high-volume centres with perioperative outcomes in terms of morbidity and mortality rates comparable to those presented in Japan and South Korea. A minimally invasive D2 gastrectomy has emerged as a valid and preferable alternative to open surgery.

Despite significant progress in implementing preventive strategies and curative treatment of premalignant and early neoplastic gastric lesions, most GAC patients still present with advanced stages of the disease, leading to a dismal prognosis even after treatments with curative intent. Given that many patients relapse following surgery, various multimodal treatment strategies have been studied to improve survival rates, mainly by combining surgery with systemic treatment in the form of perioperative chemotherapy. Clinical research has explored and documented the concept of perioperative chemotherapy in GAC and cancers originating in the distal esophagus and GEJ. Noteworthy is that some of these have suggested that the tumours with the most obvious responses to corresponding regimens originate in the esophagus and GEJ. Moreover, GACs of poorly differentiated tubular type or poorly cohesive cancer, regardless the presence of signet-ring cells type has been reported to be more resistant to chemotherapy regimens. Another observation with clinical implications is that GAC patients with malignant cells retrieved from peritoneal lavage before surgery have an extremely poor prognosis. Hence, laparoscopy with peritoneal lavage for malignant cells is recommended in all stage IB-III gastric cancers, otherwise considered potentially resectable, to exclude radiologically occult metastatic disease. The true value of this information may be even greater for patients with T3/T4 disease. Considering the above-mentioned challenges, it is critically important to explore novel multimodal therapeutic concepts in GAC since current therapeutic strategies offer these patients a limited option for cure.

The occurrence of peritoneal metastases (PM) has a significant negative impact on the overall prognosis, with a median survival of three to four months without treatment. None of the available chemotherapy regimens has reduced or prevented the risk of PM. It is commonly believed that PM occur through the deposition of tumour cells either by the direct extension and subsequent cellular exfoliation or through the traumatic dissemination of cancer cells during surgery. Clinical validation of the concept of direct spread is also provided by observing the higher rate of PM seen with increasing tumour stages (T-stages) and serosal involvement. This is also supported by the association of between positive peritoneal cytology and a higher tumour stage.

Sixty percent of lavage cytology-negative patients will convert to a cytology-positive state immediately after gastrectomy. Accordingly, it can be argued that during gastrectomy, cancer cells within the dissected lymphatic channels and blood vessels are released to and disseminated throughout the abdominal cavity. Free cancer cells can then attach to the peritoneal surface, a process facilitated by the action of cytokines and the deposition of fibrin layers, allowing for the entrapment of those cells. This new restrictive-peritoneal environment is thought to hinder the penetrance of cytotoxic drugs delivered systemically and provides grounds for the launch of intraperitoneal treatments.

Based on the minimal effects of traditional regimens on GAC, exploring alternative perioperative therapeutic concepts appears of the highest clinical significance. Since only a fraction of the systemically administered chemotherapy reaches the peritoneum, the effect of intraperitoneal chemotherapy has been extensively studied. A new aerosol technique, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC), improves intraperitoneal delivery and subsequent uptake of chemotherapy. It has shown promising results in patients with PM from colorectal, ovarian, pancreatic, and gastric cancer. Furthermore, PIPAC is feasible, safe, and well tolerated by many patients when administered in the palliative setting.

Randomised studies on prophylactic treatment of high-risk GAC patients (serosal invasion) using intraperitoneal chemotherapy or hyperthermic intraperitoneal chemotherapy (HIPEC) are mainly from Asian institutions. The risk of postoperative morbidity and mortality did not seem to be negatively influenced by intraoperative, intraperitoneal chemotherapy, contrasting to western non-randomized trials reporting considerable morbidity and mortality after these combined procedures. Thus, the use of prophylactic HIPEC in non-metastatic high-risk GAC is still debated.

Data from Odense PIPAC Centre on the outcome of PIPAC with low-dose cisplatin and doxorubicin in GAC patients with chemotherapy-resistant PM revealed objective tumour response in 40% of the patients after three PIPAC directed therapies. An additional 20% had no further tumour progression. These observations in GAC patients deliver further evidence suggesting that PIPAC can induce regression of resistant PMs in several cancer types and carries the potential to meet the clinical need for new and better therapies. Our results also provide evidence that low-dose PIPAC therapy might effectively treat patients with recurrent, chemo-resistant gastric PMs, including the poorly differentiated tubular type or poorly cohesive cancer.

The pivotal question is whether PIPAC delivered immediately after a laparoscopic D2 gastrectomy for GAC can reduce the risk of recurrent PM. Our institutions' recent phase I trial has shown this therapeutic concept to be feasible and safe. Hence, a randomised phase-II clinical trial must be conducted to assess the impact of PIPAC on disease-free survival in patients with high-risk GAC who are offered surgical treatment with curative intent.

The Efficacy of PIPAC and Minimally Invasive Radical Resection in High-risk Gastric Cancer Patients.

The Efficacy of Pressurised Intraperitoneal Aerosol Chemotherapy (PIPAC) Combined With CURativE Intent Minimally Invasive Radical Resection in High-risk Gastric Cancer Patients. A Multicentre, Randomised, Open-label Phase-II Study

Peritoneal disease-free survival (P-DFS) defined as no signs of peritoneal recurrence on (PET) CT and/or control laparoscopy with at least 12 months follow-up after minimally invasive D2-gastrectomy

Rate of disease-free survival (DFS) with at least 12 months of follow-up

Rate of overall survival with at least 12 months of follow-up

Rate of patients with 30 days postoperative toxicity (CTCAE)

Rate of patients with 30 days postoperative complications (Dindo-Clavien)

Rate of patients with 90 days postoperative mortality

Rate of positive peritoneal lavage at surgery

European Organisation for Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

European Organisation for Treatment of Cancer Quality of Life Questionnaire Gastric Cancer (EORTC QLC-STO22)

Number of patients not receiving adjuvant chemotherapy as planned due to PIPAC related complications.

Karolinska University Hospital

Odense University Hospital

Exercise program is scheduled to be conducted in three phases. Phase I is in-hospital exercise program. This program will be conducted in hospital during 1 week after surgery. Phase II is home-exercise program that will be performed at home during 1 week after discharge. Phase III is main-exercise program that will be conducted the fitness center nearby hospital during 8 weeks after phase II program. Main-exercise program is focused on the functional recovery.

physical activity intervention

Gastric cancer is a major health issue and one of the most common malignance in Korea. With the popularization of cancer screenings and increasing the average lifespan, the number of gastric cancer patients is increased. In the past, most of the research were concerned with survival and recovery after cancer surgery. However, as the medical technology had been developed and recovery rate and survival rate of cancer patients had risen, the patients wanted to return to a daily life and desire for participation for leisure. In other words, the patients who underwent surgery wants to maintain a high quality of life(QOL) level as like prior to cancer surgery.

There are many reports on the effect of the exercise program after cancer surgery. In addition, exercise program was associated with improving the QOL and functional recovery, decreasing a mood of depression, maintaining a muscle mass and improving the survival rate.

However, the subject patients of previous studies were Western people. Therefore, The results were not disclosed whether the exercise program suited to the body characteristics of Korean people. Furthermore there was no exercise program studies for the gastric cancer patients.

Medical service for cancer patients care should include not only diagnosis, treatment as like surgery but efforts on enhancing the quality of life. In other words, post-management education and management program as like exercise program are necessary for the cancer patients after surgery. Thus, the investigators have done the pilot study about how to practice the exercise program and how to evaluate the effect on the recovery. Based on the result of pilot study which could identify the safety and the feasibility , the investigators would like to do a prospective randomized controlled study to prove the effect of exercise program after surgery

An Effect of an Individualized Physical Activity Intervention for Gastric Cancer Patient Undergoing Minimally Invasive Gastrectomy: a Phase III, Prospective Randomized Controlled Trial

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
National Multicenter Cohort Study of Robot-Assisted Gastrectomy Versus Laparoscopy in Gastric Cancer	NCT06242613	Gastric Cancer	Robot-Assisted ... Laparoscopic Ga...	18 Years -	Dr. Negrin University Hospital
The Efficacy of PIPAC and Minimally Invasive Radical Resection in High-risk Gastric Cancer Patients.	NCT06295094	Gastric Cancer Chemotherapy, A... Peritoneal Meta... Minimally Invas...	Cisplatin Doxorubicin	18 Years - 80 Years	Odense University Hospital
National Multicenter Cohort Study of Robot-Assisted Gastrectomy Versus Laparoscopy in Gastric Cancer	NCT06242613	Gastric Cancer	Robot-Assisted ... Laparoscopic Ga...	18 Years -	Dr. Negrin University Hospital
An Effect of an Individualized Physical Activity Intervention for Gastric Cancer Patient Undergoing Minimally Invasive Gastrectomy: a Phase III, Prospective Randomized Controlled Trial	NCT02120885	Gastric Cancer	physical activi...	20 Years - 70 Years	Yonsei University
The Efficacy of PIPAC and Minimally Invasive Radical Resection in High-risk Gastric Cancer Patients.	NCT06295094	Gastric Cancer Chemotherapy, A... Peritoneal Meta... Minimally Invas...	Cisplatin Doxorubicin	18 Years - 80 Years	Odense University Hospital

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