DOI: 10.25934/pr00009817
title: To determine whether Programmed Cell Death Ligand 1 (PDL1) expression in oesophago-gastric cancer differs depending on the tumour site from which the biopsy was taken from.

description: Oesophago-gastric cancers (those affecting the gullet and the stomach) are the fourth leading cause of cancer deaths worldwide and are aggressive cancers that are hard to treat. Adenocarcinoma is the name of the most common (>90%) type that affects the stomach and gastro-oesophageal junction (this is the junction between the gullet and the stomach) and is the diagnosis for approximately 40% of oesophageal cancer cases in Europe.  Patients can present with symptoms such as weight loss, difficulty swallowing, bleeding and pain. Patients may be diagnosed when the cancer has already spread to other parts of the body (metastisized) and in these cases the treatment offered is a combination of chemotherapy (a type of drug that stops the growth of cancer cells) and immunotherapy (a treatment that uses the patients immune system to help fight the disease).

Research has shown that there are markers on cancer cells, that if present, can determine how likely a patient is to respond to some of these treatments. One such marker is called programmed cell death ligant 1 (PDL1). However, it has also been shown that these markers can be present in different amounts depending on where the tissue sample has been taken from, the amount can also vary in different areas of the tumour itself, in response to treatment the patient has received and where in the disease course the patient is. 

Checkmate 649 was a international clinical trial whose aim was to find out if the combination of nivolumab (a type of immunotherapy drug) and chemotherapy would help patients with advanced or metastatic gastroesophageal adenocarcinoma to live longer and without their cancer getting worse. It measured a score for PDL1 expression (a cancer marker). 

Our study would like to look at a score collected in the trial, called the PDL1 combined positive score (CPS), more closely and analyse where the tissue came from in the body, for example was it from tissue of the original tumour or was it from tissue taken from one of the sites or organs to where it had spread, and do these scores demonstrate any differences or patterns? 

We will conduct a statistical analysis to see if there is an association or relationship between the different features of the patients included in the trial and their cancer to see if we can gain a better understanding of what the scores mean for an individual patient. Various statistical methods will be used to make comparisons.

Only patients whose tumour has a PDL1 combined positive score (CPS) of 5 or more are eligible to have immunotherapy added to chemotherapy in many countries. Many medical centres, including our own, find a much lower proportion of tumours have a PDL1 CPS of 5 or more than that reported in the Checkmate 649 trial. This means that fewer patients are eligible for the addition of nivolumab to chemotherapy than anticipated based on the trial results. If we can show that PDL1 scores are systematically higher if biopsies were taken from metastases, then this would support a change in clinical practice so that biopsies in routine clinical care are also taken from metastatic sites. This would mean that more patients would be eligible for immunotherapy.