... Thus, RIGS surgery can lead to a non-randomized more rational approach when selecting radical... more ... Thus, RIGS surgery can lead to a non-randomized more rational approach when selecting radical or non-radical surgery for colorectal cancer. ... FIRST RESULTS OF A PHASE III STUDY ] Zalcberq, D. Cunningham, U. Rath, I. Olver, D. Kerr, E. Vim Cutsem, C. Svenson,].F. Seitz, E ...
From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized ... more From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy. Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone. At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 "curatively" operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01). Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group.
The Stockholm II trial is a population-based prospective randomized trial on preoperative radioth... more The Stockholm II trial is a population-based prospective randomized trial on preoperative radiotherapy in rectal carcinoma. Eligibility criteria were age younger than 80 years and biopsy-proven adenocarcinoma of the rectum judged resectable for cure with an abdominal procedure. Between 1987 and 1993, 557 patients were included. Patients were randomized to preoperative radiotherapy (RT+) followed by surgery within a week (n = 272) or surgery alone (RT-; n = 285). Radiotherapy was given with 25 grays in 1 week to the rectum and pararectal tissues. Curative resection was performed in 481 patients (86%). Median follow-up was 8.8 years. Among patients who underwent curative surgery, the incidence of pelvic recurrence was 12% (RT+) and 25% (RT-), respectively (P < 0.001). The overall survival rate in irradiated patients who underwent curative surgery was improved (46%) versus (39%; P < 0.03). For all included patients, the difference was 39% (RT+) compared with 36% (RT-; P = 0.2). Within 6 months of surgery, 13 of 272 (5%) of the irradiated patients died of intercurrent disease versus 4 of 285 (1%) of the nonirradiated (P = 0.02). Cardiovascular death was the main cause of intercurrent death and occurred in 35 of 272 (13%) of the irradiated patients compared with 20 of 285 (7%) among the nonirradiated (P = 0.07). Preoperative short-term radiotherapy reduces the risk of pelvic recurrence and can improve survival after curative surgery for rectal carcinoma. An increased risk of intercurrent death may reduce the benefit especially in elderly patients.
Despite radiotherapy and improved surgical techniques, local recurrence rates after treatment of ... more Despite radiotherapy and improved surgical techniques, local recurrence rates after treatment of rectal cancer still vary between 3 and 30 per cent. Tumour involvement of the circumferential resection margin (CRM) predicts a high risk of local recurrence. Magnetic resonance imaging (MRI) allows accurate description of the tumour and its spread within the mesorectum. The aim of this study was to assess the prognostic impact of an involved CRM identified at preoperative MRI in patients with rectal cancer. Preoperative MRI was performed in 115 patients with rectal cancer between 1995 and 1999. The images were evaluated retrospectively. The shortest distance from the tumour to the CRM was measured, correlated with patient outcome and compared with histopathological findings. The risk of any recurrence in patients with or without a tumour-involved margin on MRI was nine of 29 and nine of 57 respectively (P = 0.036). Overall survival at 5 years was 43 and 77 per cent (P = 0.012) respectively. Twenty-four of 30 patients who had an involved CRM on histopathology were correctly identified by MRI. Patients with a potentially involved CRM identified by MRI had a significantly higher risk of recurrence and cancer-related death. Preoperative MRI may be of prognostic value in rectal cancer and may be used to select patients for neoadjuvant radiochemotherapy and/or more radical surgery.
To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rect... more To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. Some 303 patients were randomized to either short-course RT (5 x 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long-course RT (25 x 2 Gy) and surgery after 4-8 weeks (group 3). Demographic data were similar between groups and there were few protocol violations (5.0-6 per cent). Eight patients (2.6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46.6, 40.0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0.164). Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37). Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. NCT00904813 (http://www.clinicaltrials.gov).
Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatm... more Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatment of rectal cancer that have emerged in the past 20 years. The aim of this study was to evaluate the effects of an initiative to teach the TME technique on outcomes at 5 years after surgery. TME-based surgery was introduced in Stockholm in 1994. The study population comprised all 447 patients who underwent abdominal operations for rectal cancer in Stockholm County during 1995 and 1996. Outcomes were compared with those in the Stockholm I (790 patients) and Stockholm II (542 patients) radiotherapy trials. The permanent stoma rate was reduced from 60.3 and 55.3 per cent in the Stockholm I and II trials respectively to 26.5 per cent in the TME project (P < 0.001). Five-year local recurrence rates decreased from 21.9 and 19.1 per cent to 8.2 per cent respectively (P < 0.001). Five-year cancer-specific survival rates increased from 66.0 and 65.7 per cent in the Stockholm trials to 77.3 per cent in the TME project (hazard ratio 0.62 (95 per cent confidence interval 0.49 to 0.80); P < 0.001). A surgical teaching programme had a major impact on rectal cancer outcome.
... Thus, RIGS surgery can lead to a non-randomized more rational approach when selecting radical... more ... Thus, RIGS surgery can lead to a non-randomized more rational approach when selecting radical or non-radical surgery for colorectal cancer. ... FIRST RESULTS OF A PHASE III STUDY ] Zalcberq, D. Cunningham, U. Rath, I. Olver, D. Kerr, E. Vim Cutsem, C. Svenson,].F. Seitz, E ...
From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized ... more From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial to evaluate the role of preoperative radiotherapy. Patients were given either 25 Gy during 5 to 7 days before surgery or underwent surgery alone. At a median follow-up time of 107 months (range, 62-144 months) the incidence of pelvic recurrence among 684 "curatively" operated patients was significantly lower among those who also received radiotherapy (P < 0.001) in all Dukes' stages. No significant difference was observed between the treatment groups with regard to frequency of distant metastases or overall survival. The time to local recurrence or distant metastasis and survival was significantly prolonged in the irradiated group. However, the postoperative mortality was 8% in the radiotherapy group compared with 2% in the surgery only group (P = 0.01). Preoperative short term radiotherapy reduced the incidence of pelvic recurrences and prolonged survival related to rectal cancer compared with surgery alone. The postoperative morbidity was significantly higher in the irradiated group.
The Stockholm II trial is a population-based prospective randomized trial on preoperative radioth... more The Stockholm II trial is a population-based prospective randomized trial on preoperative radiotherapy in rectal carcinoma. Eligibility criteria were age younger than 80 years and biopsy-proven adenocarcinoma of the rectum judged resectable for cure with an abdominal procedure. Between 1987 and 1993, 557 patients were included. Patients were randomized to preoperative radiotherapy (RT+) followed by surgery within a week (n = 272) or surgery alone (RT-; n = 285). Radiotherapy was given with 25 grays in 1 week to the rectum and pararectal tissues. Curative resection was performed in 481 patients (86%). Median follow-up was 8.8 years. Among patients who underwent curative surgery, the incidence of pelvic recurrence was 12% (RT+) and 25% (RT-), respectively (P < 0.001). The overall survival rate in irradiated patients who underwent curative surgery was improved (46%) versus (39%; P < 0.03). For all included patients, the difference was 39% (RT+) compared with 36% (RT-; P = 0.2). Within 6 months of surgery, 13 of 272 (5%) of the irradiated patients died of intercurrent disease versus 4 of 285 (1%) of the nonirradiated (P = 0.02). Cardiovascular death was the main cause of intercurrent death and occurred in 35 of 272 (13%) of the irradiated patients compared with 20 of 285 (7%) among the nonirradiated (P = 0.07). Preoperative short-term radiotherapy reduces the risk of pelvic recurrence and can improve survival after curative surgery for rectal carcinoma. An increased risk of intercurrent death may reduce the benefit especially in elderly patients.
Despite radiotherapy and improved surgical techniques, local recurrence rates after treatment of ... more Despite radiotherapy and improved surgical techniques, local recurrence rates after treatment of rectal cancer still vary between 3 and 30 per cent. Tumour involvement of the circumferential resection margin (CRM) predicts a high risk of local recurrence. Magnetic resonance imaging (MRI) allows accurate description of the tumour and its spread within the mesorectum. The aim of this study was to assess the prognostic impact of an involved CRM identified at preoperative MRI in patients with rectal cancer. Preoperative MRI was performed in 115 patients with rectal cancer between 1995 and 1999. The images were evaluated retrospectively. The shortest distance from the tumour to the CRM was measured, correlated with patient outcome and compared with histopathological findings. The risk of any recurrence in patients with or without a tumour-involved margin on MRI was nine of 29 and nine of 57 respectively (P = 0.036). Overall survival at 5 years was 43 and 77 per cent (P = 0.012) respectively. Twenty-four of 30 patients who had an involved CRM on histopathology were correctly identified by MRI. Patients with a potentially involved CRM identified by MRI had a significantly higher risk of recurrence and cancer-related death. Preoperative MRI may be of prognostic value in rectal cancer and may be used to select patients for neoadjuvant radiochemotherapy and/or more radical surgery.
To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rect... more To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. Some 303 patients were randomized to either short-course RT (5 x 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long-course RT (25 x 2 Gy) and surgery after 4-8 weeks (group 3). Demographic data were similar between groups and there were few protocol violations (5.0-6 per cent). Eight patients (2.6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46.6, 40.0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0.164). Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37). Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. NCT00904813 (http://www.clinicaltrials.gov).
Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatm... more Total mesorectal excision (TME) and use of adjuvant radiotherapy are major advances in the treatment of rectal cancer that have emerged in the past 20 years. The aim of this study was to evaluate the effects of an initiative to teach the TME technique on outcomes at 5 years after surgery. TME-based surgery was introduced in Stockholm in 1994. The study population comprised all 447 patients who underwent abdominal operations for rectal cancer in Stockholm County during 1995 and 1996. Outcomes were compared with those in the Stockholm I (790 patients) and Stockholm II (542 patients) radiotherapy trials. The permanent stoma rate was reduced from 60.3 and 55.3 per cent in the Stockholm I and II trials respectively to 26.5 per cent in the TME project (P < 0.001). Five-year local recurrence rates decreased from 21.9 and 19.1 per cent to 8.2 per cent respectively (P < 0.001). Five-year cancer-specific survival rates increased from 66.0 and 65.7 per cent in the Stockholm trials to 77.3 per cent in the TME project (hazard ratio 0.62 (95 per cent confidence interval 0.49 to 0.80); P < 0.001). A surgical teaching programme had a major impact on rectal cancer outcome.
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