Gastroesophageal-junction Cancer Clinical Trial
Official title:
Significance of Peritoneal Washing Cytology Before and After Neoadjuvant Chemotherapy in Patients With Esophagogastric-junction Cancer
Background:
The prevalence of gastroesophageal-junction cancer (cancer between the distal part of the
oesophagus, and proximal part of the stomach/GEJ-cancer) is increasing in Denmark with more
than 400 patients per year. The 5-year overall survival is less than 10% for the 2/3 of the
patients, which are not considered resectable. Even for the 1/3, which is treated with
surgical intervention and neoadjuvant chemotherapy the overall-survival is approximately
30%.
The current Danish intended curative treatment consists of esophagectomy (surgical resection
of the oesophagus with extended lymphadenectomy in abdomen and thorax (removal of
lymphnodes)). Furthermore, perioperative chemotherapy consists of 6 series neoadjuvant
chemotherapy (3 series before, and 3 series after operation).
Unresectable patients receive palliative chemotherapy and no resection. Peritoneal washing
cytology (PWC) is a recommended prediagnostic modality in gastric cancer patients. The
method is used to detect free peritoneal cancer cells in the abdominal cavity even when
macroscopic carcinomatosis is not present (i.e. the cancer has spread to other parts of the
abdomen).
Carcinomatosis can be found in up to 19% in gastric cancer patients often in the peritoneum.
Positive peritoneal cytology (C1) can be identified in up to 7% of gastric cancer patients
without metastases (C1M0), i.e. malignant cells can be identified in the peritoneal washing,
but tumor spread has not been identified.
Lots of studies indicate that C1-disease is an independent prognostic predictor for
decreased survival, and increased recurrence rate, comparable with M1 patients (i.e.
patients with distant metastases).
The American Joint Committee on cancer recommends that C1 patients should be treated
non-surgically - even when M1 disease has not been identified.
On the basis of the above, PWC can be used to identify patients at greater risk for
recurrence, and thereby not candidates for intended curative treatment.
It is a fact, though, that C1M0 patients have a better survival than C1M1 patients.
Currently, there is no level-1 evidence for specific treatment of C1M0 patients, why further
research is required to approach this patient group in the most comprehensive way. The focus
group of our study is therefore C1M0 patients, because of the difference in opinions.
Furthermore most evidence is based on gastric carcinomas, why GEJ-cancer patients are the
group, we will examine.
Purpose:
Peritoneal washing cytology (PWC) is performed as a standard prediagnostic modality at
Rigshospitalet, for patients with gastric- and GEJ cancer, considered resectable at
preceding multidisciplinary conference. Most studies in the past 20-years have focused on
gastric cancer, and not specifically GEJ-cancer.
This study will determine the usefulness of peritoneal washing cytology, and thereby
verifying our own standard regarding GEJ-cancer. Furthermore, we will determine the effect
of neoadjuvant chemotherapy on free peritoneal tumor cells and its correlation with overall
survival.
This study is intended as a validation of our own standard.
1. Background:
The prevalence of gastroesophageal-junction cancer is increasing in Denmark with more
than 400 patients per year. The 5-year overall survival is less than 10% for the 2/3 of
the patients, which are not considered resectable. Even for the 1/3, which is treated
with surgical intervention and neoadjuvant chemotherapy, the overall-survival is
approximately 30%.
The current Danish intended curative treatment consist of esophagectomy a.m. Ivor Lewis
with extended lymphadenectomy in the abdomen and thorax. Furthermore, perioperative
chemotherapy consists of 6 series neoadjuvant chemotherapy.
Unresectable patients receive palliative chemotherapy and no resection.
Peritoneal washing cytology is a recommended prediagnostic modality in gastric cancer.
The method is used to detect free peritoneal cancer cells in the abdominal cavity, even
when macroscopic carcinomatosis is not present.
Carcinomatosis can be found in up to 19% in gastric cancer patients, often in the
peritoneum. Positive peritoneal cytology (C1) can be identified in up to 7% of gastric
cancer patients without metastases (C1M0). Lots of studies indicate that C1-disease is
an independent prognostic predictor for decreased survival, and increased recurrence
rate, comparable with M1 patients (i.e. patients with distant metastases).
The American Joint Committee on cancer recommends that C1 patients should be treated
non-surgically - even when M1 disease is not identified.
On the basis of the above, PWC can be used to identify patients at greater risk for
recurrence, and thereby not candidates for intended curative treatment.
It is a fact, though, that C1M0 patients have a better survival than C1M1 patients.
Currently, there is no level-1 evidence supporting specific treatment of C1M0 patients,
why further research is required to approach this patient group in the most
comprehensive way. Therefore, the focus group of our study is C1M0 patients, because of
the differences in opinions. Furthermore, most evidence is based on gastric carcinomas,
why GEJ-cancer patients are the group, we will examine.
Results from other investigators regarding treatment of C1M0 patients:
Lee et al. found a median survival of 21 months and 4 months in gastrectomized versus
non-gastrectomized patients. Lorentzen et al. found a median 5-year survival of 71,4%
and 25% in gastrectomized patients, who had C1 at staging laparoscopy and converted
after preoperative chemotherapy versus persistent C1-disease after preoperative
chemotherapy.
Another interesting treatment modality for C1M0 patients is extensive intraperitoneal
lavage (EIPL) examined by a Japanese study group. 88 C1M0 patients were randomized into
three group; 1. Gastrectomy only, 2. Gastrectomy + intraperitoneal chemotherapy (IPC),
and 3. Gastrectomy + IPC + EIPL. Group 3 compared to group 2 had a significant better 5
year overall survival of 43,8% versus 4,6% (p<0,0001).
Further research is required to establish specific guideline for C1M0 patients.
2. Purpose:
Peritoneal washing cytology (PWC) is performed as a standard prediagnostic modality at
Rigshospitalet for patients, with gastric- and GEJ cancer, considered resectable at
preceding multidisciplinary conference. Most studies in the past 20-years have focused
on gastric cancer, and not specifically GEJ-cancer.
This study will determine the usefulness of peritoneal washing cytology, and thereby,
verify our own standard regarding GEJ-cancer. Furthermore, we will determine the effect
of neoadjuvant chemotherapy on free peritoneal tumor cells, correlated with overall
survival.
See outcome measures for more detailed description. This study is intended as a
validation of our own standard.
3. Methods
Our current algorithm includes peritoneal washings performed at two different time
points:
A. Staging laparoscopy using one port technique
o After pneumoperitoneum and oversight of the abdomen is established, a puncture is
created subhepatically in the midclavicular line with a pigtail catheter ch. 10.
- 500ml of sterile 37°C NaCl is injected through the catheter and manually dispersed
throughout the abdomen by positioning the operating table in different positions.
- At least 200ml of fluid is aspirated subhepatically through the catheter.
- 100ml is analysed by an experienced pathologist for any malignant cancer cells.
B. Initially, before operation (transthoracic esophagectomy): either open operation or
robot assisted o Robot assisted: same technique as above o Open operation: • After
abdominal incision and exploration 500ml °C of sterile NaCl is manually dispersed in
the abdominal cavity.
- Peritoneal washings is aspirated subhepatically
- Further algorithm as described above
4. Recruiting of patients:
90 consecutive patients with biopsy verified GEJ-cancer will be included. Because PWC is
already a standard guideline for this group of patients at Rigshospitalet, there will be no
direct inclusion of patients.
5. Study design: Prospective feasibility study. Patients considered candidates for intented
curative therapy, according to The Danish Esophagus-,GEJ- and Gastric Cancer Association
(DECV), is included. Furthermore, patients must have undergone evaluation of a
multidisciplinary panel of specialist including the specialties surgical gastroenterology,
thoracic surgery, oncology, pathology, radiology, and clinical nuclear medicine.
6. Data: Patient data will be obtained from internal systems of Rigshospitalet including
OPUS, LABKA, PatologiWEB, and ORBIT.
The following preoperative data will be obtained:
- age, sex, initial symptoms, tumour staging (TNM version 7) and histology characteristics,
disease anamnesis, chemotherapy treatment, medicine anamnesis, comorbidity, postoperative
complications, mortality, specifics regarding PWC such as injected volume of NaCl, procedure
time, aspirated amount of fluid, and cytology findings.
7. Approval: Authorization of data retreatment is approved by The Danish Data Protection
Agency.
Approval of The Danish Ethics Committee has not been applied, because the study is a
validation of our own standard guideline.
8. Finances:
The following contributors have financed the study:
The Danish Cancer Society Research Center, Mogens Andreasen Fonden, Familien Erichsens
familiefond, and Rigshospitalet.
All expenses have been covered.
9. Results Both negative and positive results will be published in a national and/or
international journal.
10. Practical feasibility The relevant patients and the medical expertise are to find at the
surgical gastroenterology department of Rigshospitalet. 120 staging laparoscopies are being
performed per year in the handling of gastric cancer patients. Persons and departments
involved in the study have agreed to allocate time and resources to the study. Furthermore,
our department has a technician affiliated with our institution on full time basis, who is
going to provide development, optimization, and assistance of projects associated with
GEJ-cancer.
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Observational Model: Cohort, Time Perspective: Prospective
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