Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04947020 |
| Other study ID # |
BARO Trial |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2021 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Jagiellonian University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The data will be obtained from 10 tertiary centers located in Poland (Cracow - coordinating
center, Warsaw - 3 centers, Sosnowiec, Szczecin, Bydgoszcz, Lublin, Gdansk, Poznan) and 5
foreign centers.
The analyses will include patients with rectal cancer operated on between 2013-2019. A
database in MS Excel is prepared that consists of following data:
- Type of neoadjuvant treatment (if any)
- Time-interval between the end of neoadjuvant treatment and surgery
- Type of surgery
- Staging of rectal cancer i.e. (y)pTNM
- Number of retrieved lymph nodes
- Number of lymph nodes with metastases
- R classification (R0, R1, R2)
- Preoperative medications (metformin, statins, NSAIDs, anticoagulants)
- Recurrence date and type (local, systemic, both diagnosed at the same time)
- Date of death or date of last follow-up visit
The aims of the study are following:
1. Establishing whether neoadjuvant treatment (PSCR or chemoradiotherapy) influences number
of retrieved lymph nodes in rectal cancer
2. Establishing whether time-interval between the end of PSCR and surgery influences lymph
node yield
3. Establishing the prognostic value of lymph node ratio - validation of the previously
calculated cutoff point at the level of 0.41
4. Determining independent prognostic factors in rectal cancer - in particular related to
medications taken before the operation, metformin and anti diabetic drugs in the first
place
Description:
Previously published studies showed that preoperative treatment of rectal cancer is
associated with a lower number of lymph nodes retrieved during resection that is often lower
than the recommended number of 12 nodes necessary for proper establishing of ypN category. A
few studies revealed that lymph node ratio (LNR) is a more precise prognostic factor than pN
category. The analysis conducted at the 1st Department of Surgery (Jagiellonian University,
Cracow, Poland) based on patients' data from 1999 - 2006 year indicated that the median
number of harvested lymph nodes after preoperative short course radiotherapy 5x5 Gy (PSCR)
was 16. Therefore, PSCR did not seem to influence the number of lymph nodes in the operative
specimen. Time-interval between radiotherapy and surgery (7-10 days versus 4-5 weeks) was not
associated with lymph node yield, either.
Medication taken by the patients before operation may influence the treatment results as
well. In a couple of studies metformin was identified as inhibitor of carcinogenesis
according to antiangiogenic and antimetabolic effects and as a potential radiosensitizer. The
anticancer property of metformin is largely attributed to its capability in modulating
signaling pathways involved in cellular proliferation, apoptosis, and metabolism. In the last
decade, mounting evidence supports the use of metformin in the prevention and treatment of
colorectal cancer. Moreover, the use of metformin as monotherapy or as an adjuvant in
colorectal cancer patients has led to further dose reduction and increased
radio-chemosensitivity which lead to minimal gastrointestinal side effects and reduced
toxicity. The use of metformin was associated with improved survival among colorectal cancer
patients with type 2 diabetes mellitus compared to sulfonylureas and insulin. The effect of
metformin in nondiabetic patients has not been evaluated so far. Based on the aforementioned
results, it seems well-grounded to establish the influence of other medications (statins,
nonsteroidal anti-inflammatory drugs, anticoagulants) on the results of combined treatment of
rectal cancer with the assessment whether they are independent prognostic factors in
comparison with such parameters as (y)pT, (y)pN or LNR.
After study initiation, a template of MS Excel database with manual will be sent to the
Principal Investigators in every participating center. After obtaining the filled sheets from
all participating centers, a central database will be prepared. No personal data of the
patients (name, surname, personal ID numbers) will be collected and data in the central
database will be anonymized.
Number of harvested lymph nodes will be compared in patients who underwent neoadjuvant
chemoradiotherapy, PSCR, or surgery alone. In addition, number of retrieved lymph nodes and
lymph node ratio will be compared in patients operated on after different time-intervals
between PSCR and surgery (< 7 days and > 4 weeks). Kaplan-Meier curves will be drawn to
established influence of number and ratio of harvested lymph nodes on overall survival and
disease-free survival. Local and systemic recurrence rate will be established and compared in
analysed patients. Statistical analysis will be performed with SPSS 27 for Mac. Variables
without normal distribution will be compared by means of Mann Whitney U and Chi-square tests.
Cumulative proportions of surviving will be compared with the use of log-rank test.
Univariate and multivariate Cox regression will be performed to establish prognostic factors
in analysed population.
The study is academic and non-commercial. The participating centers will not have to cover
any additional cost as the treatment options analysed constitute standard clinical practice.
No financial support is granted for investigators nor study participants.
