Systemic thrombolysis for the treatment of acute pulmonary embolism (PE) carries an estimated 20% risk of major hemorrhage, including a 3%-5% risk of hemorrhagic stroke. The authors used ...evidence-based methods to evaluate the safety and effectiveness of modern catheter-directed therapy (CDT) as an alternative treatment for massive PE.
The systematic review was initiated by electronic literature searches (MEDLINE, EMBASE) for studies published from January 1990 through September 2008. Inclusion criteria were applied to select patients with acute massive PE treated with modern CDT. Modern techniques were defined as the use of low-profile devices (< or =10 F), mechanical fragmentation and/or aspiration of emboli including rheolytic thrombectomy, and intraclot thrombolytic injection if a local drug was infused. Relevant non-English language articles were translated into English. Paired reviewers assessed study quality and abstracted data. Meta-analysis was performed by using random effects models to calculate pooled estimates for complications and clinical success rates across studies. Clinical success was defined as stabilization of hemodynamics, resolution of hypoxia, and survival to hospital discharge.
Five hundred ninety-four patients from 35 studies (six prospective, 29 retrospective) met the criteria for inclusion. The pooled clinical success rate from CDT was 86.5% (95% confidence interval CI: 82.1%, 90.2%). Pooled risks of minor and major procedural complications were 7.9% (95% CI: 5.0%, 11.3%) and 2.4% (95% CI: 1.9%, 4.3%), respectively. Data on the use of systemic thrombolysis before CDT were available in 571 patients; 546 of those patients (95%) were treated with CDT as the first adjunct to heparin without previous intravenous thrombolysis.
Modern CDT is a relatively safe and effective treatment for acute massive PE. At experienced centers, CDT should be considered as a first-line treatment for patients with massive PE.
To evaluate the safety and technical success rate of percutaneous fiducial marker implantation in preparation for image-guided radiation therapy.
From January 2003 to January 2008, we retrospectively ...reviewed 139 percutaneous fiducial marker implantations in 132 patients. Of the 139 implantations, 44 were in the lung, 61 were in the pancreas, and 34 were in the liver. Procedure-related major and minor complications were documented. Technical success was defined as implantation enabling adequate treatment planning and computed tomographic simulation.
The major and minor complication rates were 5% and 17.3%, respectively. Pneumothorax after lung implantation was the most common complication. Pneumothoraces were seen in 20 of the 44 lung implantations (45%); a chest tube was required in only seven of the 44 lung transplantations (16%). Of the 139 implantations, 133 were successful; in six implantations (4.3%) the fiducial markers migrated and required additional procedures or alternate methods of implantation.
Percutaneous implantation of fiducial marker is a safe and effective procedure with risks that are similar to those of conventional percutaneous organ biopsy.
We are constantly faced with decisions between alternatives defined by multiple attributes, necessitating an evaluation and integration of different information sources. Time-varying signals in ...multiple brain areas are implicated in decision-making; but we lack a rigorous biophysical description of how basic circuit properties, such as excitatory-inhibitory (E/I) tone and cascading nonlinearities, shape attribute processing and choice behavior. Furthermore, how such properties govern choice performance under varying levels of environmental uncertainty is unknown. We investigated two-attribute, two-alternative decision-making in a dynamical, cascading nonlinear neural network with three layers: an input layer encoding choice alternative attribute values; an intermediate layer of modules processing separate attributes; and a final layer producing the decision. Depending on intermediate layer E/I tone, the network displays distinct regimes characterized by linear (I), convex (II) or concave (III) choice indifference curves. In regimes I and II, each option's attribute information is additively integrated. In regime III, time-varying nonlinear operations amplify the separation between offer distributions by selectively attending to the attribute with the larger differences in input values. At low environmental uncertainty, a linear combination most consistently selects higher valued alternatives. However, at high environmental uncertainty, regime III is more likely than a linear operation to select alternatives with higher value. Furthermore, there are conditions where readout from the intermediate layer could be experimentally indistinguishable from the final layer. Finally, these principles are used to examine multi-attribute decisions in systems with reduced inhibitory tone, leading to predictions of different choice patterns and overall performance between those with restrictions on inhibitory tone and neurotypicals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To optimize surveillance schedules for the detection of recurrent hepatocellular carcinoma (HCC) after liver-directed therapy.
New methods have emerged that allow quantitative analysis and ...optimization of surveillance schedules for diseases with substantial rates of recurrence such as HCC. These methods were applied to 1,766 consecutive chemoembolization, radioembolization, and radiofrequency ablation procedures performed on 910 patients between 2006 and 2011. Computed tomography or magnetic resonance imaging performed just before repeat therapy was set as the time of "recurrence," which included residual and locally recurrent tumor as well as new liver tumors. Time-to-recurrence distribution was estimated by Kaplan-Meier method. Average diagnostic delay (time between recurrence and detection) was calculated for each proposed surveillance schedule using the time-to-recurrence distribution. An optimized surveillance schedule could then be derived to minimize the average diagnostic delay.
Recurrence is 6.5 times more likely in the first year after treatment than in the second. Therefore, screening should be much more frequent in the first year. For eight time points in the first 2 years of follow-up, the optimal schedule is 2, 4, 6, 8, 11, 14, 18, and 24 months. This schedule reduces diagnostic delay compared with published schedules and is cost-effective.
The calculated optimal surveillance schedules include shorter-interval follow-up when there is a higher probability of recurrence and longer-interval follow-up when there is a lower probability. Cost can be optimized for a specified acceptable diagnostic delay or diagnostic delay can be optimized within a specified acceptable cost.
To calculate absorbed radiation doses in patients treated with resin microspheres prescribed by the body surface area (BSA) method and to analyze dose-response and toxicity relationships.
A ...retrospective review was performed of 45 patients with colorectal carcinoma metastases who received single-session whole-liver resin microsphere radioembolization. Prescribed treatment activity was calculated using the BSA method. Liver volumes and whole-liver absorbed doses (D(WL)) were calculated. D(WL) was correlated with toxicity and radiographic and biochemical response.
The standard BSA-based administered activity (range, 0.85-2.58 GBq) did not correlate with D(WL) (mean, 50.4 Gy; range, 29.8-74.7 Gy; r = -0.037; P = .809) because liver weight was highly variable (mean, 1.89 kg; range, 0.94-3.42 kg) and strongly correlated with D(WL) (r = -0.724; P < .001) but was not accounted for in the BSA method. Patients with larger livers were relatively underdosed, and patients with smaller livers were relatively overdosed. Patients who received D(WL) > 50 Gy experienced more toxicity and adverse events (> grade 2 liver toxicity, 46% vs 17%; P < .05) but also responded better to the treatment than patients who received D(WL)< 50 Gy (disease control, 88% vs 24%; P < .01).
Using the standard BSA formula, the administered activity did not correlate with D(WL). Based on this short-term follow-up after salvage therapy in patients with late stage metastatic colorectal carcinoma, dose-response and dose-toxicity relationships support using a protocol based on liver volume rather than BSA to prescribe the administered activity.
To evaluate the utility of C-arm computed tomography (CT) on treatment algorithms in patients undergoing transhepatic arterial chemoembolization for hepatocellular carcinoma (HCC).
From March 2008 to ...July 2008, 84 consecutive patients with HCC underwent 100 consecutive transhepatic arterial chemoembolizations with iodized oil. Unenhanced and iodinated contrast medium-enhanced C-arm CT with planar and three-dimensional imaging were performed in addition to conventional digital subtraction angiography (DSA) in all patients. The effect on diagnosis and treatment was determined by testing the hypotheses that C-arm CT, in comparison to DSA, provides (a) improved lesion detection, (b) expedient identification and mapping of arterial supply to a tumor, (c) improved characterization of a lesion to allow confident differentiation of HCC from pseudolesions such as arterioportal shunts, and (d) an improved evaluation of treatment completeness. The effect of C-arm CT was analyzed on the basis of information provided with C-arm CT that was not provided or readily apparent at DSA.
C-arm CT was technically successful in 93 of the 100 procedures (93%). C-arm CT provided information not apparent or discernible at DSA in 30 of the 84 patients (36%) and resulted in a change in diagnosis, treatment planning, or treatment delivery in 24 (28%). The additional information included, amongst others, visualization of additional or angiographically occult tumors in 13 of the 84 patients (15%) and identification of incomplete treatment in six (7.1%).
C-arm CT is a useful collaborative tool in patients undergoing transhepatic arterial chemoembolization and can affect patient care in more than one-fourth of patients.
To evaluate safety of resin microsphere radioembolization (RE) without prophylactic embolization of the gastroduodenal artery (GDA).
Between July 2013 and April 2015, all patients undergoing RE with ...resin microspheres for liver-dominant metastatic disease were treated without routine embolization of the GDA. Selective embolization of distal hepaticoenteric vessels was performed if identified by digital subtraction angiography, cone-beam computed tomography, or technetium-99m macroaggregated albumin scintigraphy. Resin microspheres were administered using 5% dextrose flush distal to the origin of the GDA in lobar or segmental fashion, with judicious use of an antireflux microcatheter in recognized high-risk situations. Gastrointestinal toxicity was evaluated by the performing physician for at least 3 months.
RE with resin microspheres was performed in 62 patients undergoing 69 treatments. During planning angiography, embolization of 0 or 1 vessel (median, 1; range, 0-4) was performed in 86% of patients, most commonly the right gastric and supraduodenal arteries. Prophylactic embolization of the GDA was performed in only 2 patients (3%). In 6 treatments (9%), adjunctive embolization was required immediately before RE, and an antireflux microcatheter was used in 14% of treatments. Clinical follow-up was available in 60 of 62 patients (median, 134 d; range, 15-582 d). No signs or symptoms of gastric or duodenal ulceration were observed.
RE using resin microspheres without embolization of the GDA can be performed safely.
To study the comparative short-term safety and efficacy of transcatheter arterial chemoembolization (TACE) with drug-eluting LC Beads loaded with doxorubicin (DEBDOX), doxorubicin-eluting ...QuadraSpheres (hqTACE), and conventional TACE using ethiodized oil for superselective C-arm computed tomography (CT)-guided treatment of hepatocellular carcinoma (HCC) after the onset of drug shortages.
From March 2010 to March 2011, 166 patients with HCC were treated with 232 superselective TACE procedures using C-arm cone-beam CT at one institution. Patients underwent treatment depending on the availability of materials after the onset of drug shortages. Conventional TACE with doxorubicin, cisplatin, and Ethiodol was performed for 159 procedures, DEBDOX TACE was performed for 47, and hqTACE was performed for 26. Toxicity and objective response were compared at 3 months after treatment. Data were stratified for the high-risk population (Child-Pugh class B, performance status 1, bilobar disease, and/or post-resection recurrence) and initial versus repeat treatment. Kruskal-Wallis H test, Mann-Whitney U test, and Fisher exact test were used to compare the groups, with Bonferroni correction where needed.
Whole liver response rates trended higher for conventional TACE (conventional TACE, 65.4%; DEBDOX, 63.8%; hqTACE, 53.8%) (P = .085). Only minor trends for differences in toxicity were observed between the three groups. Low-risk patients had higher whole liver (P = .001) and treated lesion (P = .007) response rates when treated with conventional TACE, but no significant differences were seen for DEBDOX and hqTACE. Treatment-naive patients also had higher whole liver (P = .012) and treated lesion (P = .056) response rates. No advantages for drug-eluting microspheres were found.
Within statistical power limitations, overall toxicity and efficacy were equivalent in patients treated with LC Beads, QuadraSpheres, or ethiodized oil emulsions, including in high-risk patients, when performed superselectively with cone-beam C-arm CT guidance.
Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, ...particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody-drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors.
This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days.
In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response.
ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.
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