Data maturity and follow-up in time-to-event analyses

NHMR

VESPRO: Statistical Report

An individual patient data prospective meta-analysis (IPD_PMA) of selective internal radiation therapy (SIRT) versus sorafenib for advanced, locally advanced or recurrent hepatocellular carcinoma (HCC) of the SARAH and SIRveNIB trial

Is home warfarin self-management effective? Results of the Randomised Self-Management of Anticoagulation Research Trial

Aims The Warfarin Self-Management Anticoagulation Research Trial (Warfarin SMART) was designed to determine whether patients self-managing warfarin (PSM) using the CoaguChek device and a dosing algorithm developed for the trial could keep the INR (International Normalised Ratio) test in target range at least as often as patients managed by usual care by the family doctor or hospital clinic. Methods and Results 310 patients were randomly assigned to PSM or usual care. The PSM group was trained to perform home INR testing and warfarin dosing using a validated ColourChart algorithm. The primary endpoint was the proportion of times over 12 months that a monthly, blinded “outcome INR test”, measured in a central laboratory, was outside the patients’ target therapeutic range. The rate of out-of-range outcome INRs was lower in PSM, and non-inferior to the usual care group (PSM: 36% vs. usual care: 41%, P<0.0001 for non-inferiority; P=0.08 for superiority in closed-loop testing). The deviations from the patients’ midpoint of target INR range (P=0.02) and number of extreme INRs (P=0.03) were significantly less in the PSM group than the usual-care group. There was no significant difference between groups in rates of bleeding or thrombotic adverse events. Conclusion Patient self-management performed at least as well as usual care in maintaining the INR within the target range, without any safety concerns. This treatment modality for the long-term use of warfarin has the potential to change current local and international practice

Spaces of representation, places of identity : the case of post-communist Romania

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Sentinel-lymph-node-based management or routine axillary clearance? Three-year outcomes of the RACS Sentinel Node Biopsy versus Axillary Clearance (SNAC) 1 trial

Purpose We sought to determine whether the benefits of sentinel-node-based management (SNBM) over routine axillary clearance (RAC) at 1 year persisted to 3 years of follow-up. Methods 1088 women with clinically node negative breast cancer were randomly assigned to SNBM versus RAC. Upper limb volume, symptoms and function were assessed at 1, 6, 12, 24 and 36 months after surgery objectively with upper limb measurements by clinicians, and subjectively by patients’ using validated self-rating scales. Results Upper limb volume increased in both groups over the first 2 years and differed between the two groups all time points beyond 1 month (P<0.02), but then plateaued. Upper limb swelling was no worse in women who had axillary clearance as two-stage procedure than in women assigned RAC as a one-stage procedure. Upper limb volume had increased 15% or more in 6.0% at 6 months and 17.6% at 3 years in those assigned RAC versus 4.2% and 11.9% in those assigned SNBM. Reductions in upper limb movement were also greater with RAC than SNBM over 6 months, but improved and were similar in the two groups from 1 to 3 years. Subjective ratings of upper limb swelling, symptoms, dysfunction, and disability over 3 years were worse in the RAC group. Upper limb swelling at 3 years was rated severe by few women (1.1%), but moderate by 9.4% in the RAC group and 2.5% in the SNBM group (P<0.001). Conclusions The benefits of SNBM over RAC persist 3 years after surgery.Royal Australasian College of Surgeon

Pelvic floor functional outcomes after total abdominal versus total laparoscopic hysterectomy for endometrial cancer

Pelvic floor functioning is an important concern for women requiring a hysterectomy for endometrial cancer. The incidence of pelvic floor symptoms has not been reported in women who have undergone a hysterectomy for early-stage endometrial cancer.To evaluate pelvic floor function in women who have had surgical treatment for early stage endometrial cancer as part of the multinational Laparoscopic Approach to Cancer of the Endometrium (LACE) trial and to compare patients' outcomes who had total abdominal total versus total laparoscopic hysterectomy.Multinational, phase 3, randomized non-inferiority trial comparing disease-free survival of patients who had total abdominal hysterectomy versus total laparoscopic hysterectomy. This substudy analyses the results from a self-administered validated questionnaire on pelvic floor symptoms (Pelvic Floor Distress Inventory (PFDI)) administered pre-operatively, and at follow-up visits 6, 18, 30, 42, and 54 months post-operatively.Overall, 381 patients with endometrial cancer were included in the analysis (total abdominal hysterectomy n=195; total laparoscopic hysterectomy n=186). At 6-months post-surgery both groups experienced an improvement in Pelvic Floor Distress Inventory scores compared to presurgical pelvic floor wellbeing (total abdominal hysterectomy: mean change -11.17, 95% CI: -17.11 to -5.24; total laparoscopic hysterectomy mean change -10.25, 95% CI: -16.31 to -4.19). The magnitude of change from baseline in pelvic floor symptoms did not differ between both treatment groups up to 54 months post-surgery.These findings suggest that pelvic floor function in terms of urinary, bowel and prolapse symptoms are unlikely to deteriorate following abdominal or laparoscopic hysterectomy and are reassuring for women undergoing hysterectomy for early stage endometrial cancer

Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer: A randomized clinical trial

IMPORTANCE Current standard treatment for endometrial cancer involves removal of uterus, adnexa ± lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. OBJECTIVE To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. DESIGN, SETTING, AND PARTICIPANTS Multinational, randomized equivalence trial evaluating the laparoscopic approach to endometrial cancer (LACE). Between October 7, 2005 and June 30, 2010, 27 surgeons from 20 tertiary gynaecological cancer centres in Australia, New Zealand, and Hong Kong randomised 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended 3rd March 2016. INTERVENTIONS 353 patients were randomized to TAH, 407 to TLH. MAIN OUTCOMES AND MEASURES Analysis according to intention-to-treat assessed the primary outcome of disease-free survival (DFS, time interval between surgery and date of first recurrence including any new localized or distant endometrial cancer recurrence or any new cancers, at 4.5 years post-randomization). The pre-specified equivalence boundary was ∆=±7%. Among seven pre-specified secondary outcomes, disease recurrence and overall survival are reported. RESULTS Patients were followed for a median of 4.5 years. Of 760 patients who were randomized (mean age 63 years), 679 (89%) completed the trial. At 4.5 years follow-up, DFS was 81.3% in the TAH and 81.6% in the TLH group. Equivalence was established with a DFS rate difference of 0.3% (favoring TLH) [95% CI: -5.53% to 6.13], p for equivalence =0.007. There was no statistical difference in endometrial cancer recurrences between the two groups (TAH 28 of 353 (7.9%) and TLH 33 of 407 (8.1%), risk difference 0.2%, 95% CI: -3.7 to 4.0%, p=0.93) or in overall survival (TAH 24 of 353 (6.8%) and TLH 30 of 407 (7.4%), risk difference 0.6%, 95% CI: -3.0 to 4.2%, p=0.76). CONCLUSIONS AND RELEVANCE Among women with stage I endometrioid endometrial cancer, the use of TAH compared with TLH resulted in equivalent DFS at 4.5 years and no difference in overall survival was observed. These findings support the use of laparoscopic hysterectomy for stage 1 endometrial cancer

Il monastero benedettino di S. Giorgio in Braida a Verona: nuove prospettive di ricerca sulla rifabbrica romanica (sec. XII)

L’attuale aspetto rinascimentale della chiesa di San Giorgio in Braida è frutto di una serie di interventi promossi dai canonici veneziani di San Giorgio in Alga a partire dalla fine del XV secolo. Il monastero benedettino, tuttavia, fu fondato nella metà dell’XI secolo e completamente ricostruito fra il terzo e il quarto decennio del secolo successivo per volere del vescovo Bernardo. L’articolo ripercorre le vicende storiche dell’istituzione in età medievale e rende nota l’esistenza di alcune parti della compagine romanica tuttora inedite, che permettono d’inserire il cantiere di San Giorgio in Braida nel contesto delle coeve manifestazioni architettoniche veronesi

Gastrointestinal perforation in metastatic colorectal cancer patients with peritoneal metastases receiving bevacizumab

AIM To investigate the safety and efficacy of adding bevacizumab to first-line chemotherapy in metastatic colorectal cancer patients with peritoneal disease. METHODS We compared rates of gastrointestinal perforation in patients with metastatic colorectal cancer and peritoneal disease receiving first-line chemotherapy with and without bevacizumab in three distinct cohorts: (1) the AGITG MAX trial (Phase III randomised clinical trial comparing capecitabine vs capecitabine and bevacizumab vs capecitabine, bevacizumab and mitomycinC); (2) the prospective Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry (any first-line regimen ± bevacizumab); and (3) two cancer centres in New South Wales, Australia [Macarthur Cancer Therapy Centre and Liverpool Cancer Therapy Centre (NSWCC) from January 2005 to Decenber 2012, (any first-line regimen ± bevacizumab). For the AGITG MAX trial capecitabine was compared to the other two arms (capecitabine/bevacizumab and capecitabine/bevacizumab/mitomycinC). In the AGITG MAX trial and the TRACC registry rates of gastrointestinal perforation were also collected in patients who did not have peritoneal metastases. Secondary endpoints included progression-free survival, chemotherapy duration, and overall survival. Time-to-event outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS Eighty-four MAX, 179 TRACC and 69 NSWCC patients had peritoneal disease. There were no gastrointestinal perforations recorded in either the MAX subgroup or the NSWCC cohorts. Of the patients without peritoneal disease in the MAX trial, 4/300 (1.3%) in the bevacizumab arms had gastrointestinal perforations compared to 1/123 (0.8%) in the capecitabine alone arm. In the TRACC registry 3/126 (2.4%) patients who had received bevacizumab had a gastrointestinal perforation compared to 1/53 (1.9%) in the chemotherapy alone arm. In a further analysis of patients without peritoneal metastases in the TRACC registry, the rate of gastrointestinal perforations was 9/369 (2.4%) in the chemotherapy/bevacizumab group and 5/177 (2.8%) in the chemotherapy alone group. The addition of bevacizumab to chemotherapy was associated with improved progression-free survival in all three cohorts: MAX 6.9 m vs 4.9 m, HR = 0.64 (95%CI: 0.42-1.02); P = 0.063; TRACC 9.1 m vs 5.5 m, HR = 0.61 (95%CI: 0.37-0.86); P = 0.009; NSWCC 8.7 m vs 6.8 m, HR = 0.75 (95%CI: 0.43-1.32); P = 0.32. Chemotherapy duration was similar across the groups. CONCLUSION Patients with peritoneal disease do not appear to have an increased risk of gastrointestinal perforations when receiving first-line therapy with bevacizumab compared to systemic therapy alone