Neoadjuvant chemoradiotherapy alters the peritumoral environment. I would be grateful if anyone could provide evidence (or share experience) that the presence of elements of inflammation-fibrosis in otherwise clear margins is associated with higher recurrence risk. Please feel free to comment on any type of solid malignancy according to your expertise.
Neoadjuvant CRT invariably induces some degree of inflammation and/or fibrosis. To my knowledge there is no evidence that the degree of these changes is associated with the risk of local recurrence. What should be kept in mind is that tumours may react to CRT by either shrinkage or fragmentation; in the latter case the margin width will be unaffected compared to the pre-CRT situation.
I don't think we really know. The response seen is due to the cancer and also the treatment. Different studies have suggested a fibrotic reaction offers a good and a poor prognosis. What is key is the immune response to the cancers, with the presence of a rich lymphocyte infiltrate crucial to a better outcome.
Our work suggests this matrix is a poor prognostic factor in pancreatic and colorectal cancer, but we feel the changes within the tumour microenvironment in terms of the immune response and inflammatory infiltrate is crucial and an area of on-going study.
Well in my opinion n experience after a real meticulous n well resection of the tumor , should not b worries about reappearance of tumoral cells in the past tumoral zone! N the CRT regular changes in ttmt area is not directly related with new tumor cells in the margins of the resection zone.
Thank you all for your valuable comments.
My rationale is that inflammatory/fibrotic changes after neoadjuvant CRT at the peritumoral environment may hide elements of residual disease, which could remain undetectable during the histopathological examination, suggesting a false negative complete removal of the cancerous lesion. Moreover, the excessive deposition of fibrin could act as a scaffold that facilitates local spread of cancer cells beyond the margins of the initial site.
I absolutely agree that the local immuno-reaction is the key factor changing the final outcome. Recently, there are many studies evaluating the prognostic significance of easily accessible biomarkers, like neutrophil-to-lymphocyte ratio, but it is important to know if this local balance of immune cell subtypes is in allignment with the systematic balance. It also highlights the promising era of immunoregulation in confronting cancer.
To put in a nutshell, would it be of any value to revise the definition of resection margins after neoadjuvant CRT in the future based on local/systematic profile of immune system reaction to cancer? Would that enable us to perform tailored surgery in an oncologically safer way?
In rectal cancer, the presence of a fibroinfiammatory response to neoadjuvant RT-CHT is associated with a trend versus better DFS and OS, as shown by the work of Debucquoy et al (Europ J Can 4 4 ( 2 0 0 8 ) 7 9 1 –797) By analysing variations in the resection specimen of 95 patients included in the EORTC trial 22921, the authors observed a significantly more prominent inflammatory component in patients with T-downstaging compared with non responders. They concluded that patients with a marked inflammatory component in the stroma have a lower chance of recurrence.
Only morphological investigation can give the answer about the purity of resection margins. Therefore the resection should be carried out according to oncology standards despite of neoadjuvant chemotherapy
- Badges
- Science topic