Neores Study: Evaluating Systemic chemotherapy efficacy in colorectal peritoneal metastases
Ansvarig forskare:
Peter Cashin Akademiska sjukhuset / Uppsala universitet
Research plan Background The effectiveness of systemic chemotherapy on peritoneal metastases is still rather poorly investigated. It is clear from randomized medical oncology trials that patients with peritoneal metastases from colorectal cancer do more poorly than other metastatic colorectal cancer. Currently, many countries use neoadjuvant therapy as a downstaging treatment or a test of tumor biology prior to selecting patients for CRS and HIPEC. However, very little is published concerning this treatment modality and its downstaging ability.
Purpose and aims The main aim of this research project is to evaluate the efficacy of systemic chemotherapy on isolated peritoneal metastases from colorectal cancer. Here are some specific aims.
Upfront systemic conversion chemotherapy:
1\. What is the response rate of preoperative systemic conversion chemotherapy? 2. How many patients go on to CRS+HIPEC? 3. Those who do not come to surgery, what is their prognosis? Open/close laparotomy
1. How many patients have a successful FMCA test on chemotherapy sensitivity?
2. How many patients receive as first line chemotherapy a treatment that is sensitive vs resistant to given chemotherapy? Prognosis difference? Methods This will be a retrospective hospital charting study. The cohort will consist av two distinct populations - those that start with upfront systemic chemotherapy and those that come after an open/close laparotomy.
MDT pathway
1. Inclusion criteria HIPEC MDK where extensive isolated peritoneal metastases are noted Colorectal cancer Decision during HIPEC MDT to start systemic conversion chemotherapy
2. Exclusion criteria Appendiceal cancer Retroperitoneal lymph node metastases Other systemic metastases (e.g. liver, lung, brain, bone etc) Open-close surgery pathway
1\. Inclusion criteria Colorectal cancer with isolated peritoneal metastases Going for upfront surgery, but resulting in an open/close laparotomy Successful FMCA analysis 2. Exclusion criteria Appendiceal cancer Retroperitoneal lymph node metastases Other systemic metastases (e.g. liver, lung, brain, bone etc) The first pathway will be evaluated by reviewing all HIPEC MDT conferences between 2004-2021. All patients with isolated peritoneal metastases from colorectal cancer that were sent for neoadjuvant conversion therapy will be identified. The clinical outcomes will be reviewed. The endpoints will be response to therapy and conversion rate to CRS+HIPEC.
The second pathway will be evaluated by reviewing all open/close patients with isolated peritoneal metastases from colorectal cancer. All patients with a successful FMCA analysis will be included for evaluation. The endpoint will be progression-free survival and overall survival.
Data will be taken from the Uppsala University Hospital charting as well as from the Swedish patient registry and from the "Nationella Patientöversikten" (a Swedish national digital charting service). If data on what chemotherapy was administered is not found through these sources, requests will be made to each respective referral hospital to send the oncology department charting in order to have complete data on what chemotherapy has been administered to each patient. Only the first and second-line therapies will be registered and the response to these therapies. Overall survival will also be registered.
Statistics Descriptive statistics, Kaplan-Meier curves and Cox proportional hazard modelling will be used to evaluate the respective endpoints.
Clinical significance Due to the paucity of published articles evaluating systemic chemotherapy in isolated peritoneal metastases, it is pertinent to investigate its use. Considering the fact that neoadjuvant treatment in the relatively chemotherapy sensitive ovarian cancer has not been proven to improve overall or recurrence-free survival, it seems logical that it may not have a relevant clinical use in the colorectal cancer situation. Despite this, neoadjuvant therapy is still widely used in colorectal cancer with peritoneal metastases. Furthermore, as the Uppsala institution has had the FMCA analysis available for chemotherapy sensitivity analyses for many years, this provides an opportunity to evaluate its predictive abilities for treatment outcome.
Publications Two papers are planned. The first paper will evaluate the neoadjuvant conversion chemotherapy use and the second paper will evaluate the FMCA analysis and its ability to predict response to systemic chemotherapy.
Updated research plan 2024 The aims have been added and updated in order to allow for immunotherapy evaluation.
1. Evaluate preoperative immunotherapy for colorectal cancer with peritoneal metastases (dMMR subtype)
2. Evaluate first-line palliative immunotherapy treatment of colorectal peritoneal metastases Inclusion criteria have been updated.
1: Simultaneous resectable liver, resectable para-aortal and resectable lung metastases are allowed.
Methods have been updated.
1: The project includes requisitioning data from the Swedish Colorectal Cancer Registry (SCRCR) in order to have more complete data on KRAS, NRAS, BRAF, PIK3CA, and MMR status. Also getting data on first-line treatment of colorectal cancer with peritoneal metastases is more complete from the SCRCR.
