Short summary

The WW approach in rectal cancer seems promising, but up to 25-30% relapse after treatment. The existing methods are not efficient in selecting candidates for the WW approach; therefore news tools are required. Tumor infiltrating lymphocytes have proven to be an excellent predictive marker in colon cancer, even in early tumors. It is of great interest to clarify the role of TILs in rectal cancer. It is conceivable that increased knowledge about TILs will lead to a more individualized treatment.

Rationale

Cancer in the distal part of the rectum is a major therapeutic challenge. The traditional surgical approach is a mutilating procedure with serious long term consequences.

Several studies have demonstrated that neoadjuvant treatment reduces the rate of local regrowth, but it does not affect overall survival. It seems that treatment of rectal cancer has reached a plateau in terms of oncological outcome.

Neoadjuvant chemoradiotherapy (nCRT) results in tumor shrinkage in a large proportion of patients and in a small subgroup treatment results in total tumor regression. Consequently, high interest has arisen in the last two decades as to whether some patients can be managed with chemoradiotherapy (CRT) alone.

Current data suggest that the watch and wait (WW) strategy is safe in a selected group of patients and with less morbidity than that of standard treatment. However, with a regrowth rate of 25-30%, current methods are not sufficient in selecting patients for the non-operative strategy. Therefore, there is an obvious need for other markers to identify candidates who will benefit from the WW strategy.

The role of the immune system in cancer has gained more interest during the last two decades. High density of effector memory T cells in tumour tissue is an independent prognostic factor associated with longer disease-free and overall survival (DFS and OS) in colorectal cancer. The immunoscore (algorithm combining CD3+ and CD8+ densities in the center of the tumour and invasive margins) has been developed to asses T cells in tumour tissue. The assay has been validated in a large international study in colon cancer. Data demonstrates that the immunoscore is an independent predictor of recurrence, and it seems as a stronger predictor of survival than the well-known parameters such as T and N stage, differentiation, MSI status, and micrometastatic disease (vascular emboli, lymphatic invasion, and perineural invasion). Although the results seem promising in colon cancer, the role of T-cells in rectal cancer is less known and current data is sparse and contradictive.

We hypothesize that TILs in rectal tumor biopsies may predict response to CRT, recurrence, and overall survival.

Primary endpoint

• Complete clinical remission

Secondary endpoint

• Rate of local regrowth

• Overall survival

Description of the cohort

Tissue from patients (N=42) with low rectal cancer treated according to the WW1 protocol, but not eligible for inclusion in the protocol.

Data and biological material

Biopsies are done at diagnosis. All data is obtained from the patients journal and treatment forms.

Collaborating researchers and departments

Department of Oncology, Vejle Hospital, Torben Frøstrup Hansen, associate professor, MD, PhD.

Department of Clinical Pathology, Vejle Hospital. Jan Lindebjerg, associate professor, MD, Ph.D.

Hôpital Europeen Georges Pompidou, Service D'Immunologie Biologique 20-40 Rue LeBlanc, 75908 Paris Cedex 15