Michael J. Wallace

Safety and Activity of PD1 Blockade by Pidilizumab in Combination with Rituximab in Patients with Relapsed Follicular Lymphoma: a Single Group, Open-label, Phase 2 Trial

BACKGROUND Endogenous or iatrogenic antitumour immune responses can improve the course of follicular lymphoma, but might be diminished by immune checkpoints in the tumour microenvironment. These checkpoints might include effects of programmed cell death 1 (PD1), a co-inhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. We did this phase 2 trial to investigate the activity of pidilizumab, a humanised anti-PD1 monoclonal antibody, with rituximab in patients with relapsed follicular lymphoma. METHODS We did this open-label, non-randomised trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). Adult (≥18 years) patients with rituximab-sensitive follicular lymphoma relapsing after one to four previous therapies were eligible. Pidilizumab was administered at 3 mg/kg intravenously every 4 weeks for four infusions, plus eight optional infusions every 4 weeks for patients with stable disease or better. Starting 17 days after the first infusion of pidilizumab, rituximab was given at 375 mg/m(2) intravenously weekly for 4 weeks. The primary endpoint was the proportion of patients who achieved an objective response (complete response plus partial response according to Revised Response Criteria for Malignant Lymphoma). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00904722. FINDINGS We enrolled 32 patients between Jan 13, 2010, and Jan 20, 2012. Median follow-up was 15.4 months (IQR 10.1-21.0). The combination of pidilizumab and rituximab was well tolerated, with no autoimmune or treatment-related adverse events of grade 3 or 4. The most common adverse events of grade 1 were anaemia (14 patients) and fatigue (13 patients), and the most common adverse event of grade 2 was respiratory infection (five patients). Of the 29 patients evaluable for activity, 19 (66%) achieved an objective response: complete responses were noted in 15 (52%) patients and partial responses in four (14%). INTERPRETATION The combination of pidilizumab plus rituximab is well tolerated and active in patients with relapsed follicular lymphoma. Our results suggest that immune checkpoint blockade is worthy of further study in follicular lymphoma. FUNDING National Institutes of Health, Leukemia and Lymphoma Society, Cure Tech, and University of Texas MD Anderson Cancer Center.

Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry.

Objective(s):This study aimed to determine the effect of preoperative liver volumetry on postoperative outcomes after extended right hepatectomy. Primary end point was to evaluate whether future liver remnant (FLR)/standardized liver volume ratio (sFLR) >20% is sufficient for a safe hepatic resection. Secondary end point was to assess whether preoperative portal vein embolization (PVE) is associated with improved outcome in patients with initial sFLR ≤20%. Background Data:An sFLR >20% of the total liver volume has been proposed as sufficient for safe hepatic resection, but this concept has not been validated in a large series. In addition, recent reports suggest preoperative PVE is indicated for sFLR <30%. Methods:The impact of sFLR and PVE on short-term outcomes (postoperative complications, liver insufficiency, and 90-day mortality) was analyzed in 301 consecutive patients after extended right hepatectomy. Liver volumetry accounted for partial resection of segment IV. Liver insufficiency was defined as peak postoperative serum bilirubin >7 mg/dL. Predictors of liver insufficiency were identified by multivariate logistic regression. Results:Postoperative liver insufficiency occurred in 45 patients (15%) and accounted for 61% of deaths. Among 290 patients who underwent liver volumetry, sFLR was <20% in 38 patients, 20.1% to 30% in 144, and ≥30% in 108. Rates of postoperative liver insufficiency and death from liver failure were similar between patients with sFLR 20.1% to 30% and sFLR ≥30% but higher in patients with sFLR ≤20% (P < 0.05). Postoperative outcomes were similar between patients with increase in sFLR from ≤20% to >20% after PVE and patients with initial sFLR >20%. Multivariate analysis revealed that body mass index >25 kg/m2, intraoperative blood transfusion, and sFLR ≤20% (odds ratio = 3.18; 95% CI, 1.34–7.54) independently predicted postoperative liver insufficiency. Conclusions:Systematic measurement of FLR volume is important to select patients for PVE and extended right hepatectomy. A sFLR >20% is sufficient for safe hepatic resection and sFLR 20.1% to 30% is not an indication for preoperative PVE.

C-arm Cone-beam CT: General Principles and Technical Considerations for Use in Interventional Radiology

Digital flat-panel detector cone-beam computed tomography (CBCT) has recently been adapted for use with C-arm systems. This configuration provides projection radiography, fluoroscopy, digital subtraction angiography, and volumetric computed tomography (CT) capabilities in a single patient setup, within the interventional suite. Such capabilities allow the interventionalist to perform intraprocedural volumetric imaging without the need for patient transportation. Proper use of this new technology requires an understanding of both its capabilities and limitations. This article provides an overview of C-arm CBCT with particular attention to trade-offs between C-arm CBCT systems and conventional multi-detector CT.

Three-Dimensional C-arm Cone-beam CT: Applications in the Interventional Suite

C-arm cone-beam computed tomography (CT) with a flat-panel detector represents the next generation of imaging technology available in the interventional radiology suite and is predicted to be the platform for many of the three-dimensional (3D) roadmapping and navigational tools that will emerge in parallel with its integration. The combination of current and unappreciated capabilities may be the foundation on which improvements in both safety and effectiveness of complex vascular and nonvascular interventional procedures become possible. These improvements include multiplanar soft tissue imaging, enhanced pretreatment target lesion roadmapping and guidance, and the ability for immediate multiplanar posttreatment assessment. These key features alone may translate to a reduction in the use of iodinated contrast media, a decrease in the radiation dose to the patient and operator, and an increase in the therapeutic index (increase in safety-vs-benefit ratio). In routine practice, imaging information obtained with C-arm cone-beam CT provides a subjective level of confidence factor to the operator that has not yet been thoroughly quantified.

Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: The M.D. Anderson experience

BACKGROUNDCarcinoid tumors have a predilection for metastasizing to the liver. The presence of liver metastases is associated with poor prognosis and also results in significant deterioration of patients quality of life. Several reports suggest that hepatic artery embolization or chemoembolization can be used for control of liver disease in these patients. We retrospectively reviewed our experience with the use of hepatic arterial embolization or chemoembolization in patients with liver-dominant metastatic carcinoid disease, evaluating the clinical and radiologic response rates, duration of response, and progression-free and overall survival rates of these patients. MATERIALS AND METHODSThe medical records of all patients with carcinoid tumors metastatic to the liver who underwent hepatic artery embolization or chemoembolization between January 1992 and December 2000 were reviewed. For the purposes of this study, we compared the follow-up computed tomography or magnetic resonance imaging with the baseline imaging to determine each patients objective tumor response. The interval between the dates of response and disease progression was considered the response duration. Progression-free survival duration was calculated from the date of initial treatment to the date disease progression was recorded or the date of death. Survival durations were calculated using the Kaplan-Meier method. RESULTSEighty-one patients (48 men and 33 women; age range, 38–79 years) were included in this study. The mean duration of disease from the initial discovery of liver metastases until embolization was 24.5 months. Fifty patients were treated with bland hepatic artery embolization, and 31 underwent chemoembolization. Of the 69 patients in whom radiologic response could be evaluated, partial response was observed in 46 patients (67%), minimal response (MR) in six (8.7%), stable disease in 11 (16%), and progressive disease in six (8.7%). The median duration of response in the 42 patients with partial response was 17 months (range, 4–51 months). Sixty-three percent of patients had a reduction in their tumor-related symptoms. The median progression-free survival duration was 19 months (95% confidence interval, 17–21 months); the probability of progression-free survival was 75%, 35%, and 11% at 1, 2, and 3 years, respectively. The median overall survival time was 31 months (95% confidence interval, 23–38 months); the survival probability was 93% at 1 year, 62% at 2 years, and 24% at 5 years. CONCLUSIONSHepatic arterial occlusive therapy using hepatic artery embolization or chemoembolization results in symptomatic and radiologic response in most patients with carcinoid metastases in the liver. The progression-free survival of 19 months achieved with embolization in our study is encouraging, given that most patients had extensive liver involvement and had shown disease progression while receiving systemic treatment.

Transhepatic Ipsilateral Right Portal Vein Embolization Extended to Segment IV: Improving Hypertrophy and Resection Outcomes with Spherical Particles and Coils

PURPOSE To analyze outcomes after right portal vein embolization extended to segment IV (right PVE + IV) before extended right hepatectomy, including liver hypertrophy, resection rates, and complications after embolization and resection, and to assess differences in outcomes with two different particulate embolic agents. MATERIALS AND METHODS Between 1998 and 2004, transhepatic ipsilateral right PVE + IV with particles and coils was performed in 44 patients with malignant hepatobiliary disease, including metastases (n = 24), biliary cancer (n = 14), and hepatocellular carcinoma (n = 6). Right PVE + IV was considered if the future liver remnant (FLR; segments II/III with or without I) was less than 25% of the total estimated liver volume (TELV). Tris-acryl microspheres (100-700 microm; n = 21) or polyvinyl alcohol (PVA) particles (355-1,000 microm; n = 23) were administered in a stepwise fashion. Smaller particles were used to occlude distal branches, followed by larger particles to occlude proximal branches until near-complete stasis. Coils were then placed in secondary portal branches. Computed tomographic volumetry was performed before and 3-4 weeks after right PVE + IV to assess FLR hypertrophy. Liver volumes and postembolization and postoperative outcomes were measured. RESULTS After right PVE + IV with PVA particles, FLR volume increased 45.5% +/- 40.9% and FLR/TELV ratio increased 6.9% +/- 5.6%. After right PVE + IV with tris-acryl microspheres, FLR volume increased 69.0% +/- 30.7% and FLR/TELV ratio increased 9.7% +/- 3.3%. Differences in FLR volume (P = .0011), FLR/TELV ratio (P = .027), and resection rates (P = .02) were statistically significant. Seventy-one percent of patients underwent extended right hepatectomy (86% after receiving tris-acryl microspheres, 57% after receiving PVA). Thirteen patients (29%) did not undergo resection (extrahepatic spread [n = 9], inadequate hypertrophy [n = 3], other reasons [n = 1]). No patient developed postembolization syndrome or progressive liver insufficiency after embolization or resection. One death after resection occurred as a result of sepsis and hemorrhage. Median hospital stays were 1 day after right PVE + IV and 7 days after resection. CONCLUSION Transhepatic ipsilateral right PVE + IV with use of particles and coils is a safe, effective method for inducing contralateral hypertrophy before extended right hepatectomy. Embolization with small spherical particles provides improved hypertrophy and resection rates compared with larger, nonspherical particles.

Yttrium 90 Resin Microspheres for the Treatment of Unresectable Colorectal Hepatic Metastases after Failure of Multiple Chemotherapy Regimens: Preliminary Results

PURPOSE Responses to liver-directed therapy with yttrium 90 microspheres (SIR-Spheres) and adjuvant intraarterial chemotherapy have occurred in patients with unresectable colorectal hepatic metastases who had received less than one chemotherapy regimen. Now, SIR-Spheres are being used to treat patients with advanced disease who have received multiple chemotherapy regimens. A retrospective analysis was performed to determine the technical feasibility of SIR-Sphere treatment in this population. MATERIALS AND METHODS The medical records of 12 patients with hepatic metastatic disease and intrahepatic progression after multiple chemotherapy regimens for unresectable colorectal hepatic metastases who were treated with one or two infusions of SIR-Spheres were retrospectively analyzed for demographics, tumor characteristics, treatment details, response, and survival. RESULTS Twelve patients underwent 17 outpatient infusions of SIR-Spheres. Percent hepatic tumor volume was less than 25% in four patients, 25%-50% in three, and more than 50% in five. Treatment in 11 patients with bilobar disease was accomplished via single infusions in six cases and sequential unilobar infusions in five patients. A single infusion was used to treat unilobar disease in the remaining patient. Median prescribed dose was 39.6 mCi (mean, 37.2 mCi; range, 17-67.5 mCi); the prescribed dose exceeded the delivered dose in six infusions (35%) as a result of embolic arterial occlusion. Radiologic response was stable in five of nine patients. Carcinoembryonic antigen levels decreased in four of seven patients. Four patients received chemotherapy concomitantly or after completion of treatment. Gastric ulceration in one patient was managed nonoperatively. Median survival times from diagnosis and treatment were 24.6 and 4.5 months, respectively. CONCLUSIONS Treatment with SIR-Spheres induces responses in patients with advanced unresectable colorectal hepatic metastases after multiple chemotherapy regimens. Inability to deliver the prescribed dose is related to the embolic effect of SIR-Spheres.

Quality improvement guidelines for central venous access.

Curtis A. Lewis, MD, Timothy E. Allen, MD, Dana R. Burke, MD, John F. Cardella, MD, Steven J. Citron, MD, Patricia E. Cole, MD, PhD, Alain T. Drooz, MD, Elizabeth A. Drucker, MD, JD, Ziv J. Haskal, MD, Louis G. Martin, MD, A. Van Moore, MD, Calvin D. Neithamer, MD, Steven B. Oglevie, MD, Kenneth S. Rholl, MD, Anne C. Roberts, MD, David Sacks, MD, Orestes Sanchez, MD, Anthony Venbrux, MD, Curtis W. Bakal, MD, MPH, for the Society of Interventional Radiology Standards of Practice Committee

Quality Improvement Guidelines for Percutaneous Needle Biopsy

THE membership of the Society of Interventional Radiology (SIR) Standards of Practice Committee represents experts in a broad spectrum of interventional procedures from both the private and academic sectors of medicine. Generally Standards of Practice Committee members dedicate the vast majority of their professional time to performing interventional procedures; as such they represent a valid broad expert constituency of the subject matter under consideration for standards production.

Quality improvement guidelines for percutaneous transcatheter embolization: Society of interventional radiology standards of practice committee

THE membership of the Society of Interventional Radiology (SIR) Standards of Practice Committee represents experts in a broad spectrum of interventional procedures from both the private and academic sectors of medicine. Generally Standards of Practice Committee members dedicate the vast majority of their professional time to performing interventional procedures; as such they represent a valid broad expert constituency of the subject matter under consideration for standards production. Technical documents specifying the exact consensus and literature review methodologies as well as the institutional affiliations and professional credentials of the authors of this document are available upon request from SIR,