High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study.

BACKGROUND: Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer. METHODS: Patients with primary, resectable, T2 or T3, N0-N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m(2)) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints. FINDINGS: Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23·9 months (IQR 15·3-31·0). Local recurrence in the observation group at 1 year was 15·5% (95% CI 3·3-26·3). The most common acute grade 3 adverse event during treatment was diarrhoea, which affected four (8%) of 51 patients. Sphincter function in the observation group was excellent, with 18 (72%) of 25 patients at 1 year and 11 (69%) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 (IQR 0-0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths. INTERPRETATION: High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer. FUNDING: CIRRO-The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research.

Effect of high perioperative oxygen fraction on surgical site infection and pulmonary complications after abdominal surgery: the PROXI randomized clinical trial.

CONTEXT: Use of 80% oxygen during surgery has been suggested to reduce the risk of surgical wound infections, but this effect has not been consistently identified. The effect of 80% oxygen on pulmonary complications has not been well defined. OBJECTIVE: To assess whether use of 80% oxygen reduces the frequency of surgical site infection without increasing the frequency of pulmonary complications in patients undergoing abdominal surgery. DESIGN, SETTING, AND PATIENTS: The PROXI trial, a patient- and observer-blinded randomized clinical trial conducted in 14 Danish hospitals between October 2006 and October 2008 among 1400 patients undergoing acute or elective laparotomy. INTERVENTIONS: Patients were randomly assigned to receive either 80% or 30% oxygen during and for 2 hours after surgery. MAIN OUTCOME MEASURES: Surgical site infection within 14 days, defined according to the Centers for Disease Control and Prevention. Secondary outcomes included atelectasis, pneumonia, respiratory failure, and mortality. RESULTS: Surgical site infection occurred in 131 of 685 patients (19.1%) assigned to receive 80% oxygen vs 141 of 701 (20.1%) assigned to receive 30% oxygen (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.72-1.22; P = .64). Atelectasis occurred in 54 of 685 patients (7.9%) assigned to receive 80% oxygen vs 50 of 701 (7.1%) assigned to receive 30% oxygen (OR, 1.11; 95% CI, 0.75-1.66; P = .60), pneumonia in 41 (6.0%) vs 44 (6.3%) (OR, 0.95; 95% CI, 0.61-1.48; P = .82), respiratory failure in 38 (5.5%) vs 31 (4.4%) (OR, 1.27; 95% CI, 0.78-2.07; P = .34), and mortality within 30 days in 30 (4.4%) vs 20 (2.9%) (OR, 1.56; 95% CI, 0.88-2.77; P = .13). CONCLUSION: Administration of 80% oxygen compared with 30% oxygen did not result in a difference in risk of surgical site infection after abdominal surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00364741.

Perioperative oxygen fraction - effect on surgical site infection and pulmonary complications after abdominal surgery: a randomized clinical trial. Rationale and design of the PROXI-Trial.

BACKGROUND: A high perioperative inspiratory oxygen fraction may reduce the risk of surgical site infections, as bacterial eradication by neutrophils depends on wound oxygen tension. Two trials have shown that a high perioperative inspiratory oxygen fraction (FiO(2) = 0.80) significantly reduced risk of surgical site infections after elective colorectal surgery, but a third trial was stopped early because the frequency of surgical site infections was more than doubled in the group receiving FiO(2) = 0.80. It has not been settled if a high inspiratory oxygen fraction increases the risk of pulmonary complications, such as atelectasis, pneumonia and respiratory failure. The aim of our trial is to assess the potential benefits and harms of a high perioperative oxygen fraction in patients undergoing abdominal surgery. METHODS AND DESIGN: The PROXI-Trial is a randomized, patient- and assessor blinded trial of perioperative supplemental oxygen in 1400 patients undergoing acute or elective laparotomy in 14 Danish hospitals. Patients are randomized to receive either 80% oxygen (FiO(2) = 0.80) or 30% oxygen (FiO(2) = 0.30) during surgery and for the first 2 postoperative hours. The primary outcome is surgical site infection within 14 days. The secondary outcomes are: atelectasis, pneumonia, respiratory failure, re-operation, mortality, duration of postoperative hospitalization, and admission to intensive care unit. The sample size allows detection of a 33% relative risk reduction in the primary outcome with 80% power. DISCUSSION: This trial assesses benefits and harms of a high inspiratory oxygen fraction, and the trial may be generalizable to a general surgical population undergoing laparotomy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00364741.