Effect of PET before liver resection on surgical management for colorectal adenocarcinoma metastases: a randomized clinical trial.

IMPORTANCE: Patients with colorectal cancer with liver metastases undergo hepatic resection with curative intent. Positron emission tomography combined with computed tomography (PET-CT) could help avoid noncurative surgery by identifying patients with occult metastases. OBJECTIVES: To determine the effect of preoperative PET-CT vs no PET-CT (control) on the surgical management of patients with resectable metastases and to investigate the effect of PET-CT on survival and the association between the standardized uptake value (ratio of tissue radioactivity to injected radioactivity adjusted by weight) and survival. DESIGN, SETTING, AND PARTICIPANTS: A randomized trial of patients older than 18 years with colorectal cancer treated by surgery, with resectable metastases based on CT scans of the chest, abdomen, and pelvis within the previous 30 days, and with a clear colonoscopy within the previous 18 months was conducted between 2005 and 2013, involving 21 surgeons at 9 hospitals in Ontario, Canada, with PET-CT scanners at 5 academic institutions. INTERVENTIONS: Patients were randomized using a 2 to 1 ratio to PET-CT or control. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in surgical management defined as canceled hepatic surgery, more extensive hepatic surgery, or additional organ surgery based on the PET-CT. Survival was a secondary outcome. RESULTS: Of the 263 patients who underwent PET-CT, 21 had a change in surgical management (8.0%; 95% CI, 5.0%-11.9%). Specifically, 7 patients (2.7%) did not undergo laparotomy, 4 (1.5%) had more extensive hepatic surgery, 9 (3.4%) had additional organ surgery (8 of whom had hepatic resection), and the abdominal cavity was opened in 1 patient but hepatic surgery was not performed and the cavity was closed. Liver resection was performed in 91% of patients in the PET-CT group and 92% of the control group. After a median follow-up of 36 months, the estimated mortality rate was 11.13 (95% CI, 8.95-13.68) events/1000 person-months for the PET-CT group and 12.71 (95% CI, 9.40-16.80) events/1000 person-months for the control group. Survival did not differ between the 2 groups (hazard ratio, 0.86 [95% CI, 0.60-1.21]; P = .38). The standardized uptake value was associated with survival (hazard ratio, 1.11 [90% CI, 1.07-1.15] per unit increase; P < .001). The C statistic for the model including the standardized uptake value was 0.62 (95% CI, 0.56-0.68) and without it was 0.50 (95% CI, 0.44-0.56). The difference in C statistics is 0.12 (95% CI, 0.04-0.21). The low C statistic suggests that the standard uptake value is not a strong predictor of overall survival. CONCLUSIONS AND RELEVANCE: Among patients with potentially resectable hepatic metastases of colorectal adenocarcinoma, the use of PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265356.

Prostate radiotherapy clinical trial quality assurance: how real should real time review be? (A TROG-OCOG Intergroup Project).

BACKGROUND AND PURPOSE: Review of plans early in treatment offers the potential to reduce the chance of sub-optimal treatment delivery. We compare the use of real time reviews (RTR) either before randomization (pre-rand 3D RTR) or following randomization (post-rand 2D RTR). MATERIALS AND METHODS: PROFIT is an international randomised trial for men with prostate cancer which had credentialing via multiple dummy runs. In Australia, but not Canada, all plans were submitted for pre-rand 3D RTR using 3D software, and resubmission was requested if significant protocol deviations (PD) were seen. All plans from Canada and Australia then underwent post-rand 2D RTR using a 2D assessment. RESULTS: For 147 Australian patients, pre-rand 3D RTR was fast (median 1 day, 95% range 0-4 days). 51 minor and 5 major PD were observed and 15 of the 147 cases (10%) required resubmission. Of the 5 major PD, 4 were remedied on resubmission and 1 was withdrawn from study. For the post-rand 2D RTR, reports from 147 Australian cases and 193 Canadian cases were reviewed. No major PD were reported from Australian cases, but 3 were seen in Canadian cases (0% versus 1.5%; p=0.26). There was also no difference in the rate of minor PD (14.3% versus 15.3%; p=NS). CONCLUSIONS: In a study using relatively simple treatment volumes after comprehensive credentialing, pre-rand 3D RTR offers only modest benefits compared with post-rand 2D RTR. In the future the intensity of RTR may need to vary according to protocol and site specific factors.

Expectant management versus immediate treatment for low-grade cervical intraepithelial neoplasia : a randomized trial in Canada and Brazil.

BACKGROUND: The optimal management strategy for women with low-grade biopsy-proven cervical intraepithelial neoplasia (CIN) is not clear. Our objective was to compare the effectiveness of regular colposcopic follow-up and treatment of progressive disease only versus immediate treatment. METHODS: Data were accrued between November 2000 and March 2006 for a noninferiority randomized clinical trial of 415 women with biopsy-proven grade 1 CIN from 8 Canadian and 2 Brazilian colposcopy clinics. Subjects were randomly assigned to either undergo immediate treatment with a loop electrical excision procedure (LEEP) or receive regular colposcopic follow-up for 18 months. The primary outcome was progression of disease to CIN 2 to 3 was based on histology obtained during 18 months of follow-up. Treatments were compared using differences of proportion with a 9% noninferiority margin. Analysis was conducted on the basis of intention-to-treat. RESULTS: An initial LEEP was performed on 179 women. Disease progression was found in 32. Easily controlled vaginal bleeding occurred in 16 (8.9%). During follow-up, disease progression was identified in 3 (1.7%) women in the immediate treatment arm and 9 (4.4%) in the colposcopic follow-up arm-a tolerable difference of 2.7% with 1-sided 95% confidence interval (CI) upper limit of 6.0%. Compliance with all 3 follow-up visits was 61% overall, but significantly worse in women ≤30 years of age (P < .05). CONCLUSIONS: The risk of progression to CIN grade 2 or 3 or cancer over 18 months was similar in the 2 treatment groups. In Canada and Brazil, follow-up for 18 months is a reasonable management strategy for women with persistent low-grade cytology who are found to have grade 1 CIN on referral for colposcopy and cervical biopsy.

A randomized trial of diagnostic strategies after normal proximal vein ultrasonography for suspected deep venous thrombosis: D-dimer testing compared with repeated ultrasonography.

BACKGROUND: With suspected deep venous thrombosis and normal results on proximal vein ultrasonography, a negative d-dimer result may exclude thrombosis and a positive D-dimer result may be an indication for venography. OBJECTIVE: To evaluate and compare the safety of 2 diagnostic strategies for deep venous thrombosis. DESIGN: Randomized, multicenter trial. SETTING: Four university hospitals. PATIENTS: 810 outpatients with suspected deep venous thrombosis and negative results on proximal vein ultrasonography. INTERVENTIONS: Erythrocyte agglutination D-dimer testing followed by no further testing if the result was negative and venography if the result was positive (experimental) or ultrasonography repeated after 1 week in all patients (control). MEASUREMENTS: Symptomatic deep venous thrombosis diagnosed initially and symptomatic venous thromboembolism during 6 months of follow-up. RESULTS: Nineteen of 408 patients (4.7%) in the D-dimer group and 3 of 402 patients (0.7%) in the repeated ultrasonography group initially received a diagnosis of deep venous thrombosis (P < 0.001). During follow-up of patients without a diagnosis of deep venous thrombosis on initial testing, 8 patients (2.1% [95% CI, 0.9% to 4.0%]) in the D-dimer group and 5 patients (1.3% [CI, 0.4% to 2.9%]) in the repeated ultrasonography group developed symptomatic venous thromboembolism (difference, 0.8 percentage point [CI, -1.1 to 2.9 percentage points]; P > 0.2). Venous thromboembolism occurred in 1.0% (CI, 0.2% to 2.8%) of those with a negative D-dimer result. LIMITATIONS: Seventy patients (8.6%) deviated from the diagnostic protocols, and 9 patients (1.1%) had inadequate follow-up. CONCLUSION: In outpatients with suspected deep venous thrombosis who initially had normal results on ultrasonography of the proximal veins, a strategy based on D-dimer testing followed by no further testing if the result was negative and venography if the result was positive had acceptable safety and did not differ from the safety of a strategy based on withholding anticoagulant therapy and routinely repeating ultrasonography after 1 week.