Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:24 PM
Study NCT ID:
NCT06325423
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-03-26
First Post:
2024-03-16
Brief Title:
Predicting Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
The Impact of Tumor Microenvironment and Clinicopathological Features in Predicting Response to Neoadjuvant Chemotherapy in Muscle Invasive Bladder Cancer
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Bladder cancer BC is the 10th most commonly diagnosed cancer worldwide and the second most common cancer among Egyptian males
The mainstay of treatment of muscle-invasive BC MIBC is neoadjuvant chemotherapy NAC followed by radical cystectomy RC or bladder preservationBP using maximal transurethral resection of the bladder tumor followed by chemoradiation The rationale to use NAC before RC or BP is to eradicate micro-metastasis and to downstage the primary tumor
The 5-year cancer-specific survival for responders to NAC is 90 in contrast to 30-40 for those not obtaining an objective response Drawbacks of NAC are disappointing delay of surgery in non-responders and the potential toxicity So predictors of response to NAC are necessary to identify patients who may achieve pathologic complete response and will benefit from BP and the others who may not respond to NAC and spare them NAC toxicity and RC delay
Tumor microenvironment TME including neutrophil extracellular traps NETs and CD8 T lymphocytes is a promising predictor of response to NAC in MIBC
NETs are reticulated DNA structures decorated with various protein substances eg histones myeloperoxidase neutrophil elastaseNETs are involved in tumor growth metastasis and treatment resistance Moreover NETs can inhibit T cell responses thereby promoting tumor growth
On the other hand immune cells that are present in the TME play a major role in slowing down tumor progression CD8T lymphocytes play a central role in immune-mediated control of cancer Also they have been found to be a prognostic tool for advanced BC
The mainstay of treatment of muscle-invasive BC MIBC is neoadjuvant chemotherapy NAC followed by radical cystectomy RC or bladder preservationBP using maximal transurethral resection of the bladder tumor followed by chemoradiation The rationale to use NAC before RC or BP is to eradicate micro-metastasis and to downstage the primary tumor
The 5-year cancer-specific survival for responders to NAC is 90 in contrast to 30-40 for those not obtaining an objective response Drawbacks of NAC are disappointing delay of surgery in non-responders and the potential toxicity So predictors of response to NAC are necessary to identify patients who may achieve pathologic complete response and will benefit from BP and the others who may not respond to NAC and spare them NAC toxicity and RC delay
Tumor microenvironment TME including neutrophil extracellular traps NETs and CD8 T lymphocytes is a promising predictor of response to NAC in MIBC
NETs are reticulated DNA structures decorated with various protein substances eg histones myeloperoxidase neutrophil elastaseNETs are involved in tumor growth metastasis and treatment resistance Moreover NETs can inhibit T cell responses thereby promoting tumor growth
On the other hand immune cells that are present in the TME play a major role in slowing down tumor progression CD8T lymphocytes play a central role in immune-mediated control of cancer Also they have been found to be a prognostic tool for advanced BC
Detailed Description:
Formalin fixed paraffin embedded tissue specimen of the baseline TUR of MIBC will be obtained from pathology laboratory Pathology Department Assiut University
Histological diagnosis of HE stained sections will be confirmed
Immunohistochemical staining for Citrullinated histone H3 H3Cit antibody as a hallmark of NETs and CD8 antibody to quantity density of NETs and CD8 expression then calculate NETsCD8 ratio
Baseline clinicopathological features of MIBC patients who received neoadjuvant chemotherapy will be collected from patients records
Correlation between NETs expression CD8 expression NETsCD8 ratio and the baseline clinicopathological features with the response to neoadjuvant chemotherapy
develop a risk score based on the significant predictors of response to identify patients who may achieve pathologic complete response and will benefit from BP and the others who may not respond to NAC and spare them NAC toxicity and RC delay
Histological diagnosis of HE stained sections will be confirmed
Immunohistochemical staining for Citrullinated histone H3 H3Cit antibody as a hallmark of NETs and CD8 antibody to quantity density of NETs and CD8 expression then calculate NETsCD8 ratio
Baseline clinicopathological features of MIBC patients who received neoadjuvant chemotherapy will be collected from patients records
Correlation between NETs expression CD8 expression NETsCD8 ratio and the baseline clinicopathological features with the response to neoadjuvant chemotherapy
develop a risk score based on the significant predictors of response to identify patients who may achieve pathologic complete response and will benefit from BP and the others who may not respond to NAC and spare them NAC toxicity and RC delay
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None