Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The role of adjuvant chemotherapy for patients with rectal cancer after preoperative (chemo)radiotherapy and surgery is uncertain. We did a meta-analysis of individual patient data to compare adjuvant chemotherapy with observation for patients with rectal cancer. METHODS: We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library, CENTRAL, and conference abstracts to identify European randomised, controlled, phase 3 trials comparing observation with adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with non-metastatic rectal cancer. The primary endpoint of interest was overall survival. FINDINGS: We analysed data from four eligible trials, including data from 1196 patients with (y)pTNM stage II or III disease, who had an R0 resection, had a low anterior resection or an abdominoperineal resection, and had a tumour located within 15 cm of the anal verge. We found no significant differences in overall survival between patients who received adjuvant chemotherapy and those who underwent observation (hazard ratio [HR] 0.97, 95% CI 0.81-1.17; p=0.775); there were no significant differences in overall survival in subgroup analyses. Overall, adjuvant chemotherapy did not significantly improve disease-free survival (HR 0.91, 95% CI 0.77-1.07; p=0.230) or distant recurrences (0.94, 0.78-1.14; p=0.523) compared with observation. However, in subgroup analyses, patients with a tumour 10-15 cm from the anal verge had improved disease-free survival (0.59, 0.40-0.85; p=0.005, p(interaction)=0.107) and fewer distant recurrences (0.61, 0.40-0.94; p=0.025, p(interaction)=0.126) when treated with adjuvant chemotherapy compared with patients undergoing observation. INTERPRETATION: Overall, adjuvant fluorouracil-based chemotherapy did not improve overall survival, disease-free survival, or distant recurrences. However, adjuvant chemotherapy might benefit patients with a tumour 10-15 cm from the anal verge in terms of disease-free survival and distant recurrence. Further studies of preoperative and postoperative treatment for this subgroup of patients are warranted. FUNDING: None.

EURECCA colorectal: multidisciplinary management: European consensus conference colon & rectum.

BACKGROUND: Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. METHODS: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process. RESULTS: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. CONCLUSIONS: Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

EURECCA colorectal: multidisciplinary mission statement on better care for patients with colon and rectal cancer in Europe.

BACKGROUND: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. METHODS: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th-20th March 2013) and were invited to lecture on the subjects during the meeting (13th-15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. RESULTS: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. CONCLUSIONS: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe.

Impact of the interval between short-course radiotherapy and surgery on outcomes of rectal cancer patients.

AIMS: Pre-operative radiotherapy has proven to reduce local recurrences after curative surgery for rectal cancer. Radiotherapy is generally well tolerated, although postoperative morbidity and mortality was increased in some patients. Current study was undertaken to analyse whether the interval between preoperative radiotherapy and surgery influences post-operative mortality and recurrence for two cohorts. METHODS: All Dutch patients included in the total mesorectal excision (TME)-trial receiving radiotherapy for resectable rectal cancer were included in this study (n=642). The verification set consisted of all patients receiving short-course radiotherapy for resectable rectal cancer in two radiotherapy clinics in The Netherlands (n=600). Univariate and multivariable survival analyses for overall survival, disease-free survival, local recurrence-free survival and non-cancer related survival were calculated. RESULTS: Patients aged 75 years and older treated during the TME-trial showed a worse overall and non-cancer-related survival when surgically treated 4-7 days after the last fraction of radiotherapy. No differences in survival between the interval groups were found in the verification set. CONCLUSION: Present study found that elderly patients aged 75 years and older operated 4-7 days after the last fraction of radiotherapy had a higher chance of dying due to non-cancer-related causes during the TME-trial as compared to patients with an interval of 0-3 days. In the verification set similar differences could not be confirmed, which could be due to awareness of the clinicians who avoided delayed surgery after radiotherapy since the results have been presented during congresses. A longer than recommended interval between radiotherapy and surgery should be avoided. Besides, the verification set suggests that radiotherapy duration of 7 days is acceptable.

Time trends in chemotherapy (administration and costs) and relative survival in stage III colon cancer patients - a large population-based study from 1990 to 2008.

BACKGROUND: Use of adjuvant chemotherapy for stage III colon cancer has increased since several trials have shown the beneficial effect on survival. In this population-based study we show time trends in the administration and costs of chemotherapy and relative survival of patients with stage III colon cancer. METHODS: All patients surgically treated for adenocarcinoma of the colon stage III between 1990 and 2008 in The Netherlands were included. Relative survival (using period analyses) and Relative Excess Risks of death (RER) were calculated. The costs of chemotherapy were estimated. RESULTS: A total of 24 111 colon cancer patients with stage III were included in the cohort. The administration (from 9.5% in 1990 to 61.8% in 2008; p < 0.001) and costs of chemotherapy (from €38 467 in 1990 to €3 876 150 in 2008) increased during the study period. Multivariable relative survival improved for patients receiving adjuvant chemotherapy (RER 0.93; 95% CI 0.92-0.94; p < 0.001). In contrast, relative survival remained stable for patients, younger than 80 years, who did not receive chemotherapy (RER 1.00; 95% CI 1.00-1.01; p = 0.3). Patients aged 80 years and older without chemotherapy, relative survival increased during the study period (RER 0.98; 95% CI 0.97-0.99; p < 0.001). CONCLUSIONS: The administration, the costs of chemotherapy and the survival of patients with stage III colon cancer increased over time. Whereas the costs and administration of chemotherapy increased extensively, relative survival increased to a lesser extent. For patients treated with adjuvant chemotherapy relative survival increased equally in all age groups.

Aspirin use after diagnosis improves survival in older adults with colon cancer: a retrospective cohort study.

OBJECTIVES: To assess survival in relation to aspirin use after diagnosis in older adults with colon cancer. DESIGN: Subgroup analysis of a previously published cohort and retrospective study. SETTING: Individuals registered in the Eindhoven Cancer Registry (ECR) between 1998 and 2007, linked to prescriptions of low-dose aspirin (80 mg) registered in a community pharmacy database. PARTICIPANTS: Five hundred thirty-six individuals aged 70 and older diagnosed with colon cancer with or without aspirin use after diagnosis. MEASUREMENTS: Survival was analyzed with user status as a time-dependent covariate. Multivariate Poisson regression survival models were used to study the effect of aspirin on overall survival. RESULTS: One hundred seven participants (20.0%) started aspirin after being diagnosed with colon cancer; 429 (80.0%) were not prescribed aspirin. Three hundred thirty-nine participants (63.2%) had died by the end of follow-up. Aspirin use after diagnosis was associated with longer overall survival (rate ratio (RR) = 0.51, 95% confidence interval (CI) = 0.38-0.70, P < .001). Multivariate proportional hazards regression analysis revealed that aspirin use was associated with longer overall survival (adjusted RR = 0.59, 95% CI = 0.44-0.81, P = .001). CONCLUSION: Aspirin use after the diagnosis of colon cancer in older adults was associated with longer survival. Low-dose aspirin could be used as an effective adjuvant therapy in older adults with colon cancer.