Chronic Liver Disease and Liver Cancer: What the Hepatologists, Oncologists, and Surgeons Want to Know from Radiologists.

Effective communication between radiologists and physicians involved in the management of patients with chronic liver disease is paramount to ensuring appropriate and advantageous incorporation of liver imaging findings into patient care. This review discusses the clinical benefits of innovations in radiology reporting, what information the various stakeholders wish to know from the radiologist, and how radiology can help to ensure the effective communication of findings.

Apixaban to Prevent Venous Thromboembolism in Patients with Cancer.

BACKGROUND: Patients with active cancer have an increased risk of venous thromboembolism, which results in substantial morbidity, mortality, and health care expenditures. The Khorana score (range, 0 to 6, with higher scores indicating a higher risk of venous thromboembolism) has been validated to identify patients with cancer at elevated risk for this complication and may help select those who could benefit from thromboprophylaxis. METHODS: We conducted a randomized, placebo-controlled, double-blind clinical trial assessing the efficacy and safety of apixaban (2.5 mg twice daily) for thromboprophylaxis in ambulatory patients with cancer who were at intermediate-to-high risk for venous thromboembolism (Khorana score, ≥2) and were initiating chemotherapy. The primary efficacy outcome was objectively documented venous thromboembolism over a follow-up period of 180 days. The main safety outcome was a major bleeding episode. RESULTS: Of the 574 patients who underwent randomization, 563 were included in the modified intention-to-treat analysis. Venous thromboembolism occurred in 12 of 288 patients (4.2%) in the apixaban group and in 28 of 275 patients (10.2%) in the placebo group (hazard ratio, 0.41; 95% confidence interval [CI], 0.26 to 0.65; P<0.001). In the modified intention-to-treat analysis, major bleeding occurred in 10 patients (3.5%) in the apixaban group and in 5 patients (1.8%) in the placebo group (hazard ratio, 2.00; 95% CI, 1.01 to 3.95; P = 0.046). During the treatment period, major bleeding occurred in 6 patients (2.1%) in the apixaban group and in 3 patients (1.1%) in the placebo group (hazard ratio, 1.89; 95% CI, 0.39 to 9.24). CONCLUSIONS: Apixaban therapy resulted in a significantly lower rate of venous thromboembolism than did placebo among intermediate-to-high-risk ambulatory patients with cancer who were starting chemotherapy. The rate of major bleeding episodes was higher with apixaban than with placebo. (Funded by the Canadian Institutes of Health Research and Bristol-Myers Squibb-Pfizer Alliance; AVERT ClinicalTrials.gov number, NCT02048865.).

Leukoerythroblastosis with Cytopenia as an Initial Presentation of Lung Adenocarcinoma.

A 74-year-old male with a history of chronic lymphocytic leukemia (CLL) previously treated with fludarabine/cyclophosphamide/rituximab (FCR) 5 years ago, presented with progressive fatigue, mucocutaneous bleeding, and cytopenias (hemoglobin 51 g/L, platelets 8.0 × 109/L, lymphocytes 0.4 × 109/L). He had normal respiratory findings, and no lymphadenopathy or hepatosplenomegaly. Further workup revealed a small spiculated lung nodule and multiple sclerotic bony lesions. Due to bleeding/profound thrombocytopenia, lung biopsy was not feasible. Peripheral smear revealed leukoerythroblastosis with few nucleated red blood cells and left shift of granulocytes. Bone marrow (BM) aspirate yielded a dry tap with clusters of extrinsic atypical cells on touch preparations. BM core biopsy showed infiltration and near complete replacement by a population of highly atypical cells with surrounding fibrosis. Cells were positive for cytokeratins CK7 and CK8/18, Napsin A, and thyroid transcription factor-1, specific for a primary poorly differentiated lung adenocarcinoma. Leukoerythroblastosis in association with cytopenia often indicates a BM infiltration and warrants an early BM biopsy to rule out hematological and solid malignancies, particularly in CLL patients treated with FCR. In our case, a diagnosis of a lung adenocarcinoma was established by BM examination, the only clinically feasible diagnostic modality.

Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer.

BACKGROUND: This exploratory analysis evaluated second-line (2L) therapy for metastatic pancreatic cancer in a large phase 3 trial (MPACT). METHODS: Patients who received first-line (1L) nab-paclitaxel+gemcitabine (nab-P+Gem) or Gem were assessed for survival based on 2L treatment received. Multivariate analyses tested influence of treatment effect and prognostic factors on survival. RESULTS: The majority of 2L treatments (267 out of 347, 77%) contained a fluoropyrimidine (5-fluorouracil or capecitabine). Median total survival (1L randomisation to death) for patients who received 2L treatment after 1L nab-P+Gem vs Gem alone was 12.8 vs 9.9 months (P=0.015). Median total survival for patients with a fluoropyrimidine-containing 2L therapy after nab-P+Gem vs Gem was 13.5 vs 9.5 months (P=0.012). Median 2L survival (duration from start of 2L therapy to death) was 5.3 vs 4.5 months for nab-P+Gem vs Gem, respectively (P=0.886). Factors significantly associated with longer post-1L survival by multivariate analyses included 1L nab-P+Gem, receiving 2L treatment, longer 1L progression-free survival, and Karnofsky performance status⩾70 and neutrophil-to-lymphocyte ratio⩽5 at the end of 1L treatment. CONCLUSIONS: These findings support the use of 2L therapy for patients with metastatic pancreatic cancer. Fluoropyrimidine-containing treatment after 1L nab-P+Gem is an active regimen with significant clinical effect.

nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3 MPACT Trial.

INTRODUCTION: The phase III MPACT trial in patients with metastatic pancreatic cancer (MPC) demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) compared with Gem monotherapy, including the primary endpoint of overall survival (OS; median 8.7 vs. 6.6 months; hazard ratio [HR] 0.72; P < 0.001). A significant treatment difference favoring nab-P + Gem over Gem was observed for OS in patients treated in North America. The majority of patients were from the US (88%) with only 12% from Canada. Healthcare systems and treatment patterns are different between the 2 countries, and there is limited published information on outcomes of Canadian patients treated with first-line nab-P + Gem. This analysis evaluated efficacy and safety outcomes in Canadian patients in the MPACT trial. METHODS: Treatment-naive patients with MPC (N = 861) received either nab-P 125 mg/m(2) + Gem 1000 mg/m(2) on days 1, 8, and 15 every 4 weeks or Gem 1000 mg/m(2) weekly for the first 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle ≥2). RESULTS: The MPACT trial enrolled 63 patients in Canada. Baseline characteristics were well balanced and comparable with those of the intent-to-treat population. Both OS (median 11.9 vs. 7.1 months; HR 0.76; P = 0.373) and progression-free survival (median 7.2 vs. 5.2 months; HR 0.65; P = 0.224) were numerically longer and overall response rate (27% vs. 17%; P = 0.312) was numerically higher with nab-P + Gem vs. Gem. The most common grade ≥3 adverse events with nab-P + Gem vs. Gem were neutropenia (22% vs. 10%), fatigue (34% vs. 33%), and neuropathy (25% vs. 0%). CONCLUSION: This subanalysis confirmed that nab-P + Gem is an efficacious treatment option and has a manageable safety profile in patients with MPC treated in Canada. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00844649. FUNDING: Celgene Corporation, Summit, NJ, USA.

nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial.

BACKGROUND: Positive findings from the phase III MPACT trial led to the regulatory approval of nab-paclitaxel plus gemcitabine as a treatment option for patients with metastatic pancreatic cancer. This report is an update of overall survival (OS) based on longer follow-up. METHODS: Patients (n = 861) with metastatic pancreatic cancer and a Karnofsky performance status of 70 or greater were randomly assigned one to one to receive nab-paclitaxel + gemcitabine or gemcitabine alone. Efficacy data for this post hoc analysis were collected through May 9, 2013. Exploratory analyses of carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) were conducted. The primary efficacy endpoint was OS, which was analyzed for all randomly assigned patients by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS: The median OS was statistically significantly longer for nab-paclitaxel plus gemcitabine vs gemcitabine alone (8.7 vs 6.6 months, hazard ratio [HR] = 0.72, 95% confidence interval [CI] = 0.62 to 0.83, P < .001). Long-term (>three-year) survivors were identified in the nab-paclitaxel plus gemcitabine arm only (4%). In pooled treatment arm analyses, higher CA19-9 level and NLR at baseline were statistically significantly associated with worse OS. There appeared to be a treatment effect for OS favoring nab-paclitaxel plus gemcitabine over gemcitabine alone in poor-prognosis subgroups defined by these factors (HR = 0.612, P < .001 for CA19-9 level ≥ median and HR = 0.81, P = .079 for NLR > 5). CONCLUSIONS: These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer.

Retrospective review of efficacy of radiofrequency ablation for treatment of colorectal cancer liver metastases from a Canadian perspective.

PURPOSE: A retrospective single-center review of ultrasound-guided radiofrequency ablation (RFA) treatment of colorectal cancer liver metastases was performed. This study reviews the primary and secondary technical effectiveness, overall survival of patients, recurrence-free survival, tumour-free survival, rates of local recurrence, and postprocedural RFA complications. Technical effectiveness and rates of complication with respect to tumour location and size were evaluated. Our results were compared with similar studies from Europe and North America. METHODS: A total of 63 patients (109 tumours) treated with RFA between February 2004 and December 2009 were reviewed. Average and median follow-up time was 19.4 and 16.5 months, respectively (range, 1-54 months). Data from patient charts, pathology, and Picture Archiving and Communication System was integrated into an Excel database. Statistical Analysis Software was used for statistical analysis. RESULTS: Primary and secondary technical effectiveness of percutaneous and intraoperative RFA were 90.8% and 92.7%, respectively. Average (SE) tumour-free survival was 14.4 ± 1.4 months (range, 1-43 months), and average (SE) recurrence-free survival was 33.5 ± 2.3 months (range, 2-50 months). Local recurrence was seen in 31.2% of treated tumours (range, 2-50 months) (34/109). Overall survival was 89.4% at 1 year, 70.0% at 2 years, and 38.1% at 3 years, with an average (SE) overall survival of 37.0 ± 2.8 months. There were 14 postprocedural complications. There was no statistically significant difference in technical effectiveness for small tumours (1-2 cm) vs intermediate ones (3-5 cm). There was no difference in technical effectiveness for peripheral vs parenchymal tumours. CONCLUSIONS: This study demonstrated good-quality outcomes for RFA treatment of colorectal cancer liver metastases from a Canadian perspective and compared favorably with published studies.

Improving equitable access to imaging under universal-access medicine: the ontario wait time information program and its impact on hospital policy and process.

In Canada, equal access to health care is the goal, but this is associated with wait times. Wait times should be fair rather than uniform, taking into account the urgency of the problem as well as the time an individual has already waited. In November 2004, the Ontario government began addressing this issue. One of the first steps was to institute benchmarks reflecting "acceptable" wait times for CT and MRI. A public Web site was developed indicating wait times at each Local Health Integration Network. Since starting the Wait Time Information Program, there has been a sustained reduction in wait times for Ontarians requiring CT and MRI. The average wait time for a CT scan went from 81 days in September 2005 to 47 days in September 2009. For MRI, the resulting wait time was reduced from 120 to 105 days. Increased patient scans have been achieved by purchasing new CT and MRI scanners, expanding hours of operation, and improving patient throughput using strategies learned from the Lean initiative, based on Toyota's manufacturing philosophy for car production. Institution-specific changes in booking procedures have been implemented. Concurrently, government guidelines have been developed to ensure accountability for monies received. The Ontario Wait Time Information Program is an innovative first step in improving fair and equitable access to publicly funded imaging services. There have been reductions in wait times for both CT and MRI. As various new processes are implemented, further review will be necessary for each step to determine their individual efficacy.

CT colonography versus optical colonoscopy for screening asymptomatic patients for colorectal cancer a patient, intervention, comparison, outcome (PICO) analysis.

RATIONALE AND OBJECTIVES: The American College of Radiology has recently endorsed the use of computed tomographic colonography (CTC) for colon cancer screening. With advances in technology and postprocessing software, the quality of computed tomographic colonographic studies has improved, and new techniques are being developed to reduce radiation exposure and increase patient acceptance of the procedure. The aim of colorectal cancer screening is to reduce the incidence of malignancy by identifying and removing presymptomatic lesions. The aim of this study was to answer the clinical question: In an asymptomatic patient at average risk for colon cancer, is CTC equivalent to optical colonoscopy (OC) for detecting clinically significant polyps? MATERIALS AND METHODS: A systematic literature review was conducted to evaluate CTC compared to OC, using the patient, intervention, comparison intervention, outcome (PICO) search strategy. The PubMed search used Medical Subject Headings, including the terms "computed tomography colonography," "colonoscopy," "screening," and "polyp." Each of the retrieved articles was assigned a level of evidence using the Centre for Evidence-Based Medicine's hierarchy of validity for diagnostic studies. RESULTS: PICO search criteria and review of abstracts identified 16 relevant studies. Using the Centre for Evidence-Based Medicine's hierarchy of validity, there were three level 1c studies, two level 2a studies, three level 2b studies, four level 3b studies, two level 4 studies, and two level 5 studies. All relevant studies demonstrated that CTC had high or moderately high per patient and per polyp sensitivity and specificity compared to OC for clinically relevant polyps (>5 mm). CONCLUSIONS: The majority of evidence suggests that CTC is an acceptable alternative to OC, particularly in the group of patients who are either unwilling or unable to undergo OC. The results of the large, multicenter American College of Radiology Imaging Network study are pending. This trial presented preliminary results in 2007 suggesting that the sensitivity and specificity of CTC are high and comparable to those of OC.

PET vs sentinel lymph node biopsy for staging melanoma: a patient intervention, comparison, outcome analysis.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the gold standard to assess local lymph nodes in patients with melanoma. Positron emission tomography (PET) has been investigated as a noninvasive alternative to SLNB. METHODS: A systematic literature review was conducted to evaluate PET and PET/computed tomography (CT) compared with SLNB for staging local lymph nodes in patients with intermediate-risk melanoma using the patient, intervention, comparison, outcome (PICO) search strategy. The PubMed, Medline, CancerLit, and Cochrane Library databases were searched for relevant published materials. Guidelines of the American Society of Clinical Oncology (ASCO), and Cancer Care Ontario (CCO) were reviewed, as was the clinical resource, UpToDate. Studies were classified on the basis of levels of evidence delineated by the Oxford Centre for Evidence-Based Medicine. RESULTS: The PICO search criteria identified 20 studies. There was no level 1 evidence. There were 7 level 2b articles. One review article was consecutive and thus classified as level 3a evidence. Three review articles were retrieved and categorized as level 3b. Three single-center studies were classified as level 3b, and another 3 were classified as level 4. There were two published letters, considered expert opinion and thus classified as level 5 evidence. All identified papers favored SLNB over PET or PET/CT for identifying occult locoregional lymph node metastases. CONCLUSION: Despite a lack of high-level evidence, the studies concluded that SLNB is superior to PET for local lymph node staging in patients with intermediate-risk melanoma. National guidelines confirmed these conclusions. The likelihood of PET/CT identifying distant metastases in this patient population is equally low because of the small risk for having distant metastases at diagnosis. Further study is required, including larger multicenter prospective trials.

Review of phase II trial designs used in studies of molecular targeted agents: outcomes and predictors of success in phase III.

PURPOSE: Because the appropriate design and end points for phase II evaluation of targeted anticancer agents are unclear, we undertook a review of recent reports of phase II trials of targeted agents to determine the types of designs used, the planned end points, the outcomes, and the relationship between trial outcomes and regulatory approval. METHODS: We retrieved reports of single-agent phase II trials in six solid tumors for 19 targeted drugs. For each, we abstracted data regarding planned design and actual results. Response rates were examined for any relationship to eventual success of the agents, as determined by US Food and Drug Administration approval for at least one indication. RESULTS: Eighty-nine trials were identified. Objective response was the primary or coprimary end point in the majority of trials (61 of 89 trials). Fourteen reports were of randomized studies generally evaluating different doses of agents, not as controlled experiments. Enrichment for target expression was uncommon. Objective responses were seen in 38 trials; in 19 trials, response rates were more than 10%, and in eight, they were more than 20%. Agents with high response rates tended to have high nonprogression rates; renal cell carcinoma was the exception to this. Higher overall response rates were predictive of regulatory approval in the tumor types reviewed (P = .005). CONCLUSION: In practice, phase II design for targeted agents is similar to that for cytotoxics. Objective response seems to be a useful end point for screening new targeted agents because, in our review, its observation predicted for eventual success. Improvements in design are recommended, as is more frequent inclusion of biological questions as part of phase II trials.