In 2015, 3500 patients were diagnosed with colon cancer in Denmark (DCCG Arsrapport 2015, www.dccg.dk). Despite curative intended surgery and perioperative chemotherapy in colon cancers, relapse is often encountered, and across tumor stage recurrence is found in 18-26% of the resected patients. Eighty-six percent of the recurrences are diagnosed within three years after resection, and 36% of the recurrences are diagnosed within the first year regardless of tumor stage. The route of dissemination varies with different cancer types, but a common denominator is the risk of peritoneal metastases (PM). PM is the second most common site of recurrence in colon cancer patients, and accounts for 25-35% of all recurrences. Patients with PM - both in the synchronous and metachronous setting - will often have a very short life expectancy and traditionally, treatment have been nihilistic due to poor performance status and response rates, and most patients with recurrence to the peritoneum will only be treated with best supportive care. During the last two decades, more aggressive treatment strategies have been implemented, including extensive surgery (Cytoreductive surgery, CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). However, CRS and HIPEC are only used in selected patients with limited PM. High risk factors for relapse with PM have been identified, and patients with T4 colon cancers have a risk of relapse with metachronous PM between 12-50%, while patients with intraperitoneally perforated colorectal cancers relapse with PM in 14-58% of the cases. The risk of metachronous PM in perforated or T4 colorectal cancers has been validated and this is widely recognized in the ongoing trials around Europe, where adjuvant HIPEC is being investigated in patients with high-risk colon tumors to prevent metachronous PM (www.clinicaltrials.gov NCT02231086, NCT02965248, NCT02614534, NCT02974556, NCT01226394).
In addition to tumor stage, free intraperitoneal tumor cells (FITC) are perceived as a precursor of PM, and it is expected, that patients with perforated/T4 colon cancers will have FITC prior to visible recurrence with PM. However, despite the reported impact on the risk of recurrence and poor survival data, the presence of FITC is not routinely investigated, and this may be due to the lack of treatment options regarding the eradication of free tumor cells. In a systematic review of resected patients with stage I-IV colorectal cancer, 13.7% had FITC detected during perioperative peritoneal lavage. The rate of FITC increased with increasing T-stage and the patients with FITC had a significantly increased risk of both local and overall recurrence, plus a significantly increased mortality risk.
Based on the above-mentioned rate of recurrences after resection of high-risk colon cancers and the limited treatment options, new treatment strategies are needed. A German research group has invented a new intraperitoneal chemotherapy delivery method, where the chemotherapy is nebulized within the pressurized abdominal cavity - Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC).
As PIPAC seems to have an effect on visible PM in colon cancer patients, we hypothesize that
PIPAC can minimize the risk of PM recurrence in resected high risk colon cancer patients.
Furthermore, we expect that PIPAC can eradicate FITC in these patients.
Description of the cohort
Danish patients with colon cancer are eligible candidates according to the inclusion criteria. The patients will be included after resection and, if indicated, adjuvant systemic chemotherapy. While expected accrual is based on the number of resected patients at Odense University Hospital, this study will include patients nationwide. In 2015, 284 patients were resected due to colon cancer at Odense University Hospital (OUH). Ninety-three percent of the resections were with curative intent (n=264), and eighteen percent had T4 tumors (DCCG Arsrapport 2015, www.dccg.dk). Based on these data and according to the inclusion criteria, 47 patients are eligible candidates per year, and the expected accrual of 60 patients (see below) is two years.
Collaborating researchers and departments
Department of Surgery, Odense University Hospital
- Martin Graversen, MD, Upper GI and HPB Section
- Professor Michael Bau Mortensen, MD, DMSc, PhD, Upper GI and HPB Section
- Consultant Claus Fristrup, MD, PhD, Upper GI and HPB Section
- Consultant Soren Salomon, MD, PhD
- Consultant Per Vadgaard Andersen MD
Department of Oncology, Odense University Hospital
- Professor Per Pfeiffer, MD, PhD
Department of Pathology, Odense University Hospital
- Consultant Sonke Detlefsen, MD, PhD