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

Trends in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of synchronous peritoneal carcinomatosis of colorectal origin in the Netherlands

Background: Population-based data on the percentage of colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis (PC) being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently lacking. The current population-based study describes trends in the use of CRS-HIPEC in the Netherlands, one of the first countries where CRS and HIPEC was introduced. Methods: All patients diagnosed with synchronous PC of CRC between 2005 and 2012 were extracted from the Netherlands Cancer Registry (n = 4623). Patients with primary appendiceal cancer were excluded resulting in a study population of 4430 patients. Trends in the use of CRS-HIPEC over time were analyzed by means of a Cochrane-Armitage trend test. Survival proportions were calculated as the time between diagnosis and date of death or last follow-up (January 2014). Results: Of the total 4430 patients with synchronous PC, 297 (6.4%) underwent treatment with CRS HIPEC. The proportion of colorectal PC patients receiving CRS HIPEC increased significantly over time from 3.6% in 2005-2006 to 9.7% in 2011-2012 (p < 0.0001). Overall median survival (MS) for patients treated with CRS HIPEC was 32.3 months, whereas MS rates were respectively 12.6, 6.1 and 1.5 for months palliative chemotherapy with/without surgery, palliative surgery and best supportive care. Conclusion: The proportion of patients diagnosed with synchronous PC from CRC treated with CRS HIPEC has increased significantly over time and currently almost 10% of PC patients are treated with CRS HIPEC. Median survival in this population based group is 32.3 months. (C) 2015 Elsevier Ltd. All rights reserved

Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer

Background: Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Patients and methods: Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: 64, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. Results: 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus = 75 versus <65 years 1.6 (1.25-1.94)), emergency resection (OR 1.8 (1.41-2.32)), anastomotic leakage (OR 8.1 (6.14-10.62)), referral to another hospital for adjuvant chemotherapy (OR 1.9 (1.36-2.57)) and prolonged postoperative hospital admission (OR 4.7 (3.30-6.68)). Starting 5-8 weeks post-surgery showed no decrease in OS compared to initiation within 4 weeks (Hazard ratio (HR) 5-6 weeks 0.9 (0.79-1.11); HR 7-8 weeks 1.1 (0.91-1.30)). However, commencing beyond 8 weeks was associated with decreased OS compared to initiation within 8 weeks (HR 9-10 weeks 1.4 (1.21-1.68); HR 11-12 weeks 1.3 (1.06-1.59); HR 13-16 weeks 1.7 (1.23-2.23)). Conclusion: Our data support initiating adjuvant chemotherapy in stage III colon cancer patients within 8 weeks post-surgery. (C) 2015 Elsevier Ltd. All rights reserved

Pancreatic cancer surgery in elderly patients: Balancing between short-term harm and long-term benefit. A population-based study in the Netherlands

Background: At a national level, it is unknown to what degree elderly patients with pancreatic or periampullary carcinoma benefit from surgical treatment compared to their younger counterparts. We investigated resection rates and outcomes after surgical treatment among elderly patients. Methods: From the Netherlands Cancer Registry, 20 005 patients diagnosed with primary pancreatic or periampullary cancer in 2005-2013 were selected. The associations between age (= 80 years) and resection rates were investigated using chi(2) tests, and surgical outcomes (30-, 90-day mortality) were evaluated using logistic regression analysis. Overall survival after resection was investigated by means of Kaplan-Meier and Cox proportional hazard regression analysis. Results: During the study period, resection rates increased in all age groups (= 80 years: 2-8%, p = 80 vs. <70 years) = 1.21, 95% confidence interval (0.99-1.47), p = 0.07]. Conclusion: Despite higher short-term mortality, octogenarians who underwent pancreatic resection showed long-term survival similar to younger patients. With careful patient screening and counselling of elderly patients, a further increase of resection rates may be combined with improved outcomes

Hospital of diagnosis and likelihood of surgical treatment for pancreatic cancer

Surgical resection for pancreatic cancer offers the only chance of cure. Assessment of the resectability of a pancreatic tumour is therefore of great importance. The aim of the study was to investigate whether centre of diagnosis influences the likelihood of surgery and whether this affects long-term survival. Patients diagnosed with non-metastasized pancreatic cancer (M0) between 2005 and 2013 in the Netherlands were selected from the Netherlands Cancer Registry. Hospitals were classified as a pancreatic centre (at least 20 resections/year) or a non-pancreatic centre (fewer than 20 resections/year). The relationship between centre of diagnosis and likelihood of surgery was analysed by multivariable logistic regression. Influence of centre on overall survival was assessed by means of multivariable Cox regression analysis. Some 8141 patients were diagnosed with non-metastasized pancreatic cancer, of whom 3123 (38·4 per cent) underwent surgery. Of the 2712 patients diagnosed in one of 19 pancreatic centres, 52·4 per cent had exploratory laparotomy compared with 31·4 per cent of 5429 patients diagnosed in one of 74 non-pancreatic centres (P  < 0·001). A pancreatectomy was performed in 42·8 and 24·6 per cent of the patients respectively (P  < 0·001). Multivariable analysis revealed that patients diagnosed in a pancreatic centre had a higher chance of undergoing surgery (odds ratio 2·21, 95 per cent c.i. 1·98 to 2·47). Centre of diagnosis was not associated with improved long-term survival (hazard ratio 0·95, 95 per cent c.i. 0·91 to 1·00). Patients with non-metastasized pancreatic cancer had a greater likelihood of having surgical treatment when the diagnosis was established in a pancreatic centr

The Hospital de Câncer de Barretos Registry: an analysis of cancer survival at a single institution in Brazil over a 10-year period

Epidemiological studies that describe cancer survival statistics at specific hospitals are scarce. Cancer registries, which are collections of cancer patient characteristics, treatment and outcome data, help determine quality of care and treatment indicators.Research and Education Institute, Hospital de Câncer de Barretos, Barretos, Brazi