Phase II Feasibility Study of Lipidiol Markers for Radiation Therapy Localisation and Response Assessment in the Multi-Disciplinary Team Management of Oesophageal-Gastric Cancer

Lipiodol is a stable fatty acid ethyl ester which is a derivative of poppy seed oil which has a wide range of applications in current medical practice which include localisation of hepatocellular carcinoma. Endoscopically inserted lipiodol is currently utilized for the treatment of bleeding gastric varices in combination with Histoacryl (n-butyl cyanoacrylate) which acts as a glue in order to prevent extravasation of the lipiodol. Currently surrogate markers exist in the form of standard surgical heamaclips have been routinely used in neurosurgery, thoracic surgery, breast surgery and abdominal surgery for 50+ years. Radiotherapy fields can be more accurately marked and treatment delivered using surgical clips. At present only one study utilizing lipiodol injection as a surrogate marker for localization prior to radiotherapy planning exists. This study utilized trans-rectal ultrasound guidance to inject lipiodol into the prostate. However there has been extensive experience in the use of lipiodol and histoacryl in the treatment of gastric varices where it has been shown to be a safe and effective therapy with minimal complications. Whilst the combination of lipiodol/histoacryl are not yet standard therapy for localization of tumours, however given the promise of the initial pilot study the Urology unit at Austin health are also further investigating the utility of lipiodol marking of prostate cancers. Further more at Austin Health it is standard practice for patients who require radiotherapy for prostate cancer to have gold seed fiducials as surrogate markers inserted into their prostate glands before treatment. This helps to track the location of the prostate during radiotherapy. It is standard practice for patients who require radiotherapy for breast cancer to have titanium heamaclip fiducials inserted in the breast at surgery before radiotherapy. The use of lipiodol markers for the purpose of assessing tumour response in oesophageal cancer is something that has not been published previously. One previous pilot study has demonstrated the feasibility and safety of using metal fiducials in oesophageal cancer, gastric and pancreatic cancers for surgical pathologic correlation and/or image guided radiotherapy. This has been supported by our own recent experience with gold fiducial insertion in gastro-oesophageal cancers. Endoscopic tattooing is standard of care in gastrointestinal tract tumours (oesophageal, gastric, colonic). At present carbon particles (SPOT), Indocyanine green and India ink are currently used to mark these lesions. However they are radiolucent whereas lipiodol which is radio-opaque and therefore should act as a marker for radiotherapy as seen in the previous study performed in the prostate. A submucosal injection into normal muocsa adjacent to the tumour will be performed through the gastroscope with 1.4mls of saline, followed by 0.4mls of lipiodol:0.4mls of histoacryl solution to prevent extravasation of the lipiodol. This procedure will be performed 4 x to outline the superior/inferior and lateral margins of the tumour. This will be performed as a once off procedure. The duration of the markers will be dictated by the patient's treatment pathway (eg. if curative then will be resected in surgical specimen at time of the operation). Whether a patient proceeds to radiotherapy, its duration, intensity etc will be discussed for each participant at the multi disclipinary meeting prior to marker insertion. The markers have no impact on the type or duration of the radiotherapy involved and each patient will receive current standard of care treatment.