Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial.

OBJECTIVE: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years. SUMMARY BACKGROUND DATA: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer. METHODS: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS). RESULTS: Secondary endpoint analyses included 450 patients (95%) without metastases at baseline (mean age 64; 34% women) who received Lap (n = 225) or Open (n = 225). Median follow-up was 3.2 years (range: 0.1-5.4 yrs). LRR cumulative incidence at 2 years: Lap 5.4%; Open 3.1% [difference, 2.3%; 95% confidence interval (CI), -1.5% to 6.1%; hazard ratio (HR) 1.7; 95% CI, 0.74-3.9]. DFS at 2 years: Lap 80%; Open 82% (difference, 2.0%; 95% CI, -9.3% to 5.4%; HR for recurrence or death, 1.17; 95% CI, 0.81-1.68; P = 0.41). After adjustment for baseline factors HR = 1.07 (95% CI, 0.7-1.6). OS at 2 years: Lap 94%; Open 93% (difference 0.9%; 95% CI, -3.6% to 5.4%). CONCLUSIONS: Laparoscopic surgery for rectal cancer did not differ significantly from open surgery in effects on 2-year recurrence or DFS and OS. Confidence intervals included potentially clinically important differences favoring open resection, so that the combination of primary and secondary study endpoints may not support laparoscopic resection of rectal cancer as a routine standard of care and further follow-up is required.

Randomized phase 2 study of carboplatin and bevacizumab in recurrent glioblastoma.

BACKGROUND: The optimal use of bevacizumab in recurrent glioblastoma (GBM), including the choice of monotherapy or combination therapy, remains uncertain. The purpose of this study was to compare combination therapy with bevacizumab monotherapy. METHODS: This was a 2-part randomized phase 2 study. Eligibility criteria included recurrent GBM after radiotherapy and temozolomide, no other chemotherapy for GBM, and Eastern Cooperative Oncology Group performance status 0-2. The primary objective (Part 1) was to determine the effect of bevacizumab plus carboplatin versus bevacizumab monotherapy on progression-free survival (PFS) using modified Response Assessment in Neuro-Oncology criteria. Bevacizumab was given every 2 weeks, 10 mg/kg; and carboplatin every 4 weeks, (AUC 5). On progression, patients able to continue were randomized to continue or cease bevacizumab (Part 2). Secondary endpoints included objective radiological response rate (ORR), quality of life, toxicity, and overall survival (OS). RESULTS: One hundred twenty-two patients (median age, 55y) were enrolled to Part 1 from 18 Australian sites. Median follow-up was 32 months, and median on-treatment time was 3.3 months. Median PFS was 3.5 months for each arm (hazard ratio [HR]: 0.92, 95% CI: 0.64-1.33, P = .66). ORR was 14% (combination) versus 6% (monotherapy) (P = .18). Median OS was 6.9 (combination) versus 7.5 months (monotherapy) (HR: 1.18, 95% CI: 0.82-1.69, P = .38). The incidence of bevacizumab-related adverse events was similar to prior literature, with no new toxicity signals. Toxicities were higher in the combination arm. Part 2 data (n = 48) will be reported separately. CONCLUSIONS: Adding carboplatin resulted in more toxicity without additional clinical benefit. Clinical outcomes in patients with recurrent GBM treated with bevacizumab were inferior to those in previously reported studies. CLINICAL TRIALS REGISTRATION NR: ACTRN12610000915055.

Patterns of care in adult medulloblastoma: results of an international online survey.

The literature on medulloblastoma in adults is generally limited to case reports and retrospective series, and there is no accepted standard of care. The Cooperative Trials Group for Neuro-Oncology (COGNO) sought to determine the range and consistency of clinicians' approaches to management as a basis for future trials. We aimed to identify current treatment strategies for adult medulloblastoma through an online survey launched at the 2012 Society of Neuro-Oncology meeting and by email invitation. Clinicians who had treated at least one adult patient with medulloblastoma, primitive neuroectodermal tumor (PNET), or pineoblastoma in the preceding year were asked about their most recent patient and invited to discuss their approach to a typical clinical scenario. Between November 2012 and January 2013, 45 clinicians (11 medical oncologists, 8 radiation oncologists, 5 pediatric oncologists, and 21 others) from Australia (24), United States (3), Europe (4) and other countries (14) completed the survey. Responding clinicians had treated 54 cases in the past 12 months. The most common histological type was medulloblastoma (64%), then PNET (20%). Most patients were male (68%), and had high-risk disease (65%). Complete surgical resection in 56 and 32% had molecular testing. Radiotherapy was predominantly cranio-spinal (92%) and given mostly post-resection (80%). Combination chemotherapy was more common than single-agent chemotherapy. The choice of chemotherapy varied considerably. There is substantial variation in the treatment of adult medulloblastoma, most pronounced in the choice of chemotherapeutic agents, highlighting the need for further collaborative research to guide evidence-based treatment strategies.

Intravesical chemotherapy plus bacille Calmette-Guérin in non-muscle invasive bladder cancer: a systematic review with meta-analysis.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Non-muscle-invasive bladder cancer has a significant recurrence and progression rate despite transurethral resection. The current standard of care to lower the risk of recurrence and progression is adjuvant BCG followed by maintenance BCG. Despite this, a significant number of patients experience recurrence and progress to invasive cancer. Several randomized trials have studied combination therapy (BCG with chemotherapy) to try to reduce the recurrence and progression rate. We performed a systematic review with meta-analysis and found that adjuvant BCG followed by maintenance therapy is the appropriate standard of care when compared with combination therapy. We conclude that further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone. OBJECTIVE: To determine if the combination of intravesical chemotherapy and maintenance bacille Calmette-Guérin (BCG), used in sequence, is superior to maintenance BCG alone in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: We searched biomedical literature databases for randomized controlled trials that compared sequential, intravesical chemotherapy added to maintenance BCG with maintenance BCG alone. Studies that did not use maintenance BCG were excluded. The meta-analysis was performed using the fixed effects model. RESULTS: Four trials were identified, including 801 patients. Adding chemotherapy to maintenance BCG did not result in a significant reduction in recurrence (relative risk [RR] 0.92; 95% confidence interval [CI] 0.79-1.09; P = 0.32) or progression (RR 0.88; 95% CI 0.61-1.27; P = 0.5). The risk of recurrence (RR 0.75; 95% CI 0.61-0.92; P = 0.006) and progression (RR 0.45; 95% CI 0.25-0.81; P = 0.007) were reduced when the single trial that included isolated Tis was excluded. Toxicity was similar for both groups. CONCLUSIONS: Adjuvant therapy with induction BCG followed by maintenance BCG is the appropriate standard of care for patients with resected NMIBC at high risk of recurrence. Further trials are warranted to test the effects of adding chemotherapy to BCG in patients with Ta or T1 disease, but not in those with Tis alone.