Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay. Methods/Design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 degrees C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA. Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival

Subclassification of Multivisceral Resections for T4b Colon Cancer with Relevance for Postoperative Complications and Oncological Risks

BACKGROUND: Multivisceral resection for T4b colon cancer constitutes a heterogeneous group of surgical procedures. The purpose of this study was to explore clinically distinct categories of multivisceral resection, with subsequent correlation to postoperative complications and oncological outcomes. METHODS: In this multicenter cohort study, all consecutive patients without metastases who underwent multivisceral resection for pT4bN0-2M0 colon cancer between 2000 and 2014 were included. Multivisceral resection was divided into four categories: (i) gastrointestinal (including the stomach), (ii) urologic ((partial) bladder and ureter), (iii) solid organ (spleen, kidney, liver, pancreas, and uterus), and (iv) abdominal wall/omentum/ovaries. The primary outcome was surgical complications and secondary outcomes were 5-year intra-abdominal recurrence, disease-free survival, and overall survival. RESULTS: In total, 130 patients who underwent curative intent resection of pT4 colon cancer were included. Patients who underwent multivisceral resection within multiple categories were assigned to one of the categories based on hierarchy of clinical impact after exploratory analysis. For the primary endpoint, 55 patients were assigned to gastrointestinal, 14 to urologic, 14 to solid organ, and 47 to abdominal wall/omentum/ovaries multivisceral resection. Gastrointestinal multivisceral resection was independently associated with surgical complications (HR 3.9, 95% CI 1.4-10.6). Abdominal wall/omentum/ovaries multivisceral resection was significantly related with intra-abdominal recurrence (HR 7.8, 95% CI 1.0-57.8). The 5-year disease-free survival and overall survival showed no significant differences per multivisceral resection category. CONCLUSIONS: Multivisceral resections for T4b colon cancer are heterogeneous procedures considering risk profiles. The proposed multivisceral resection subclassification needs validation, but might improve comparability between studies and hospitals (auditing).status: publishe

Postoperative abdominal infections after resection of T4 colon cancer increase the risk of intra-abdominal recurrence

INTRODUCTION: Patients with pT4 colon cancer are at risk of developing intra-abdominal recurrence. Infectious complications have shown to negatively influence disease free survival (DFS) and overall survival (OS) in stage I-III colon cancer. The aim of this study was to determine whether surgical site infections (SSIs) also increase the risk of intra-abdominal recurrence in pT4 colon cancer patients. METHODS: All consecutive patients with pT4N0-2M0 colon cancer from four centres between January 2000 and December 2014 were included. Patients were categorized into 2 groups; with and without a postoperative (<30 days) SSIs. SSIs included both deep incisional as well as organ/space SSIs. The primary outcome was intra-abdominal recurrence (including local/incisional recurrence, peritoneal metastases) and was assessed using Kaplan-Meier and Cox regression analyses. Secondary outcome measures were DFS and OS. RESULTS: Out of 420 patients, 62 (15%) developed a SSI. The 5-year intra-abdominal recurrence rates were 44% and 27% for patients with and without a SSI, respectively (p = 0.011). After multivariate analysis, SSI was independently associated with intra-abdominal recurrence (HR 1.807 (1.091-2.992)), worse DFS (HR 1.788 (1.226-2.607)), and worse OS (HR 1.837 (1.135-2.973)). Other independent risk factors for intra-abdominal recurrence were a R1 resection (HR 2.616 (1.264-5.415)) and N2-stage (HR 2.096 (1.318-3.332)). CONCLUSION: SSIs after resection of a pT4N0-2M0 colon cancer are associated with an increased risk of intra-abdominal recurrence and worse survival. This finding supports the hypothesis that infection-based immunologic pathways play a role in colon cancer cell dissemination and outgrowth.status: publishe