EPeOnc

Enhanced Perioperative
Oncology (EPeOnc)
Consortium

About

The aim of the enhanced perioperative oncology (EPEONC) consortium is to integrate principles of optimized surgical, anesthesiological and oncological treatments in order to improve the short- and long-term outcomes of patients undergoing cancer surgery. The project includes proof of concept clinical studies determining the most effective combination for reducing post-operative stress and maximizing the immune system stimulation. In parallel, in vitro and in vivo experiments as well as epidemiological studies will be carried out, to gain insight into cellular mechanisms and global co-factors affecting these processes.

Project Planning

We will identify the negative effects, the surgical stress response has on the adaptive and cellular immune system, and the stimulating effects it has on cancer cells. By using human and in vitro scientific methods, we identify and validate the optimal methods for measuring outcomes to use in our future proof of concept studies designed to explore potential interventions to alter long-term oncological outcomes. Thus, data from this WP will be utilized in several of the following WP’s.

Beyond the expected beneficial effect on cardiopulmonary function by prehabilitation, there
is also an increase in the attention towards the immunomodulatory effects of prehabilitation. In addition to reducing complications in the immediate postoperative period, muscular excise and dietary interventions may also result in improved immune system function leading to reduced relapse rate and prolonged survival. This may be also benefit non-frail patients in the future

Clearance of micrometastatic disease has previously proven difficult with conventional nontargeted chemotherapeutic treatment strategies. However, activation of immune responses through immunogenic local treatment directed towards the primary tumor in the bowel wall, may facilitate the recognition and elimination of tumor cells in the primary tumor lesion, as well as systemic micrometastatic lesions, leading to reduced postoperative disease recurrence.

The transmuscular quadratus lumborum nerve block can modify the surgical stress response by inhibiting somatosensory, visceral sensory and autonomous nerve impulses from the abdomen. It remains to be explored in patients undergoing laparoscopic colorectal cancer surgery if this effect will have clinical benefits and if it will reduce opioid use. This new analgesic modality may result in improved pain control in relation to surgery, enhanced recovery and reduction of the systemic stress response leading to improved immune function. The epidemiological studies in this WP will be able to show associations that may affect clinical practice.

The conventional technique for right-sided colectomy involves an externalization of the intestines through an upper abdominal incision and confectioning of the anastomosis extracorporeally. In recent years, a new surgical technique where the intestines are kept inside the abdomen and the anastomosis is performed intracorporeally has been established. The new technique makes it possible to perform specimen extraction trough a small pfannenstiel incision instead of an upper abdominal incision. We hypothesize that the new technique reduces the surgical stress response, resulting in reduced postoperative pain, and faster recovery leading to earlier start of adjuvant chemotherapy.

There is a need for research into interventions in the perioperative period that may both reduce postoperative morbidity, improve recovery and ultimately reduce recurrence by improving the immune system. Two promising medical interventions, interferon alfa and metformin, have been chosen for proof of concept phase II randomized clinical trials.

A delay in chemotherapy results in reduced survival after colorectal cancer surgery. The specific reason for the delay in oncological treatment has not been investigated in detail. The hypothesis is that there are both patient and organizational/administrative delays in the start of oncological treatment after colorectal cancer surgery and that this delay is modifiable.

The pathophysiology of disease processes in the perioperative setting is multifactorial involving both effects of anesthesia and surgery and effects of postoperative recovery and morbidity and what is worse – many of these factors affect the others. Hence, looking at one variable at a time is at best simplistic, but in some cases even counterproductive in terms of understanding the real etiology. The use of “omics” in medical research promises to give a more comprehensive view on complex problems measuring many features simultaneously. The use of certain big data processing approaches will enable us to get new insights based on an integrated analysis of thousands of biochemical variables at the same time through the use of adequate multivariate data analysis methods.

Funding

The consortium has received funding of 10 mio DKK from the Zealand University Hospital for 5 years and was launched in June 2018.