Imaging-based Selection Research Articles

Does Ischemic Core Volume Modify the Treatment Effect of Endovascular Thrombectomy?

Imaging-based selection has become integral in guiding endovascular thrombectomy for large vessel occlusive stroke, driven by positive trial outcomes incorporating parenchymal and perfusion imaging criteria. While small-moderate core trials transformed acute reperfusion therapy, uncertainties persisted for large ischemic strokes. This was recently addressed in several treatment trials which demonstrated a benefit of endovascular thrombectomy in patients with large ischemic strokes, defined by parenchymal and/or perfusion imaging. Although individual trials suggest treatment benefits regardless of core size, patient-level meta-analyses are essential to clarify this relationship. Our aim was to summarize the imaging ramifications of the major endovascular thrombectomy trials of the past decade focusing on the interaction between the core and the treatment effect, to assist in the design of future meta-analyses. The core-treatment relationship that will be investigated in these meta-anlalyses will likely have major implications in our systems of care designs and in determining the utility of imaging-based selection.

Live cell pool and rare cell isolation using Enrich TROVO system

Although several technologies have been developed to isolate cells of interest from a heterogenous sample, clogging and impaired cell viability limit such isolation. We have developed the Enrich TROVO system as a novel, nonfluidic technology to sort live cells. The TROVO system combines imaging-based cell selection and photo-crosslinking of (gelatin methacrylate) gelMA-hydrogel to capture cells. After capture, cells are released by enzymatic digestion of the hydrogel and then retrieved for downstream analysis or further cell culturing. The system can capture cells with a recovery rate of 48% while maintaining 90% viability. Moreover, TROVO can enrich rare cells 506-fold with 93% efficiency using single step isolation from a 1:104 cell mixture, and can also capture one target cell from 1 million cells, reaching an enrichment ratio of 9128. In addition, 100% purity and 49% recovery rate can be achieved by a following negative isolation process. Compared to existing technologies, the TROVO system is clog-resistant, highly biocompatible, and can process a wide range of sample sizes.

A live-cell platform to isolate phenotypically defined subpopulations for spatial multi-omic profiling.

Numerous techniques have been employed to deconstruct the heterogeneity observed in normal and diseased cellular populations, including single cell RNA sequencing, in situ hybridization, and flow cytometry. While these approaches have revolutionized our understanding of heterogeneity, in isolation they cannot correlate phenotypic information within a physiologically relevant live-cell state with molecular profiles. This inability to integrate a live-cell phenotype-such as invasiveness, cell:cell interactions, and changes in spatial positioning-with multi-omic data creates a gap in understanding cellular heterogeneity. We sought to address this gap by employing lab technologies to design a detailed protocol, termed Spatiotemporal Genomic and Cellular Analysis (SaGA), for the precise imaging-based selection, isolation, and expansion of phenotypically distinct live cells. This protocol requires cells expressing a photoconvertible fluorescent protein and employs live cell confocal microscopy to photoconvert a user-defined single cell or set of cells displaying a phenotype of interest. The total population is then extracted from its microenvironment, and the optically highlighted cells are isolated using fluorescence activated cell sorting. SaGA-isolated cells can then be subjected to multi-omics analysis or cellular propagation for in vitro or in vivo studies. This protocol can be applied to a variety of conditions, creating protocol flexibility for user-specific research interests. The SaGA technique can be accomplished in one workday by non-specialists and results in a phenotypically defined cellular subpopulations for integration with multi-omics techniques. We envision this approach providing multi-dimensional datasets exploring the relationship between live cell phenotypes and multi-omic heterogeneity within normal and diseased cellular populations.

Outcome of Patients with PSMA PET/CT Screening Failure by VISION Criteria and Treated with 177Lu-PSMA: A Multicenter Retrospective Analysis.

Selection of patients for treatment with prostate-specific membrane antigen (PSMA)–targeted therapy is somewhat controversial. There are those who have suggested that no selection is necessary and those who have suggested that tight imaging-based selection criteria are required. What is optimal,

Imaging selection for reperfusion therapy in acute ischemic stroke beyond the conventional time window.

Originally, the efficacy of acute ischemic stroke treatment with thrombolysis or thrombectomy was only proven in narrow time windows of, respectively, 4.5 and 6h after onset. Introducing imaging-based selection beyond non-contrast enhanced computed tomography has expanded the treatment window, focusing on presumed tissue status rather than solely on time after stroke onset. Different mismatch concepts have been adopted in clinical practice to select patients in the extended and unknown time window based on findings from randomized controlled trials. Since various concepts exist that can identify patients likely to benefit from reperfusion strategies, clinicians may wonder which imaging modality may be preferred in the emergency setting. In this review, we will discuss the different mismatch concepts and their practical implementation for patient selection for thrombolysis or thrombectomy, beyond the conventional time window.

Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers.

In acute stroke management, time window has been rigidly used as a guide for decades and the reperfusion treatment is only available in the first few limited hours. Recently, imaging-based selection of patients has successfully expanded the treatment window out to 16 and even 24 h in the DEFUSE 3 and DAWN trials, respectively. Recent guidelines recommend the use of imaging techniques to guide therapeutic decision-making and expanded eligibility in acute ischemic stroke. A tissue window is proposed to replace the time window and serve as the surrogate marker for potentially salvageable tissue. This article reviews the evolution of time window, addresses the advantage of a tissue window in precision medicine for ischemic stroke, and discusses both the established and emerging techniques of neuroimaging and their roles in defining a tissue window. We also emphasize the metabolic imaging and molecular imaging of brain pathophysiology, and highlight its potential in patient selection and treatment response prediction in ischemic stroke.

Abstract 1: Thrombolytic Therapy for ‘Wake-Up Stroke’ - A Systematic Review and Meta-Analysis

Introduction: Twenty-five percent of strokes are detected upon awakening (‘wake-up strokes’; WUS) and are not amenable to thrombolytic therapy via existing time-based treatment approaches. We performed a systematic review and meta-analysis of the efficacy and safety of thrombolysis in patients with WUS using imaging-based selection algorithms. Methods: This systematic review was registered through PROSPERO (CRD42020151552). We searched PubMed, Web of Science, and Scopus between January 1, 2006 and April 30, 2020 for controlled trials and observational cohort studies (prospective or retrospective), in which adults with WUS were administered thrombolysis after MR- or CT-based imaging. Our primary outcome was recovery (mRS 0-2) at 90 days and our secondary outcome was symptomatic intracranial hemorrhage (sICH). We assessed risk of bias using the Cochrane Risk of Bias 2.0 and ROBINS-I tools. Results: We included 16 studies that enrolled a total of 14,017 patients. Sixty-one percent of patients receiving tPA achieved a functional recovery at 90 days (95% CI: 51% to 70%; 12 studies), with a relative risk (RR) of recovery of 1.21 compared with patients not receiving tPA (95% CI 1.01 to 1.46; 4 comparative studies). As shown in Figure 1, 3% of patients receiving tPA in the treated WUS stroke group experienced sICH, an RR of 4.0 (95% CI 2.85-5.61) compared with patients not receiving tPA. On meta-regression, advancing age was negatively associated with the RR of recovery (p<0.001) and there was a trend that increased NIHSS was associated with the RR of sICH (p=0.083). Conclusions: In patients with WUS, thrombolysis is associated with functional recovery and with a low risk of sICH. This risk is comparable to the sICH rate from tPA-treatment of stroke utilizing the standard protocol timeframe (2.4% in ECASS III). Thrombolysis should be considered in the treatment of WUS in patients with favorable neuroimaging.

The frontiers of acute stroke management

The field of stroke has rapidly advanced in recent years with more effective reperfusion therapies (thrombolysis and endovascular thrombectomy) applied to a broader range of patients, including using imaging-based selection to treat beyond standard time windows. Recent trials have provided signals that neuroprotection and specific treatments for intracerebral haemorrhage may be achievable. The range of targeted secondary prevention strategies has also expanded, particularly with direct oral anticoagulants, more potent lipid lowering agents and patent foramen ovale closure.

Multimodal CT or MRI for IV thrombolysis in ischemic stroke with unknown time of onset.

To investigate differences in procedure times, safety, and efficacy outcomes comparing 2 different protocols to enable thrombolysis in the extended or unknown time window after stroke onset with either multimodal CT or MRI. Patients with ischemic stroke in the extended or unknown time window who received IV thrombolysis between January 2011 and May 2019 were identified from an institutional registry. Imaging-based selection was done by multimodal CT or MRI according to institutional treatment algorithms. IV thrombolysis was performed in 100 patients (54.3%) based on multimodal CT imaging and in 84 patients (45.7%) based on MRI. Baseline clinical data, including stroke severity and time from last seen normal to hospital admission, were similar in patients with CT and MRI. Door-to-needle times were shorter in patients with CT-based selection (median [interquartile range] 45 [37-62] minutes vs 75 [59-90] minutes; mean difference [95% confidence interval (CI)] -28 minutes [-35 to -21]). No differences were detected regarding the incidence of symptomatic intracranial hemorrhage (2 [2.0%] vs 4 [4.8%]; adjusted odds ratio [aOR] [95% CI] 0.47 [0.08-2.83]) and favorable outcome at day 90 (25 [33.8%] vs 33 [42.9%]; aOR 0.95 [0.45-2.02]). IV thrombolysis in ischemic stroke in the unknown or extended time window appeared safe in CT- and MRI-selected patients, while the use of CT imaging led to faster door-to-needle times. This study provides Class IV evidence that for patients with ischemic stroke in the extended or unknown time window, imaging-based selection for IV thrombolysis by multimodal CT compared to MRI led to shorter door-to-needle times.

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes.

Recent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0-6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP). We retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90-day outcomes (mRS 0-2 vs. 3-6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0-2) 90-day outcome. A total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0-2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90-day outcome (P = .14). After adjustment; age (P< .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P<.001) were predictive of favorable outcome. Penumbral imaging-based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.

Ischemic Core Volume Combined with the Relative Perfusion Ratio for Stroke Outcome Prediction after Endovascular Thrombectomy.

Imaging-based selection of stroke patients for endovascular thrombectomy (EVT) remains an ongoing challenge. Our aim was to determine the value of a combined parameter of ischemic core volume (ICV) and the relative degree of cerebral blood flow in the penumbra for morphologic and clinical outcome prediction. In this Institutional Review Board (IRB)-approved prospective observational study, 221 consecutive patients with large vessel occlusion anterior circulation stroke within 6 hours of symptom onset and subsequent EVT were included between June 2015 and August 2017. Admission computed tomography perfusion was analyzed using automated threshold-based algorithms. Perfusion-weighted ICV (pw-ICV) was calculated by multiplying ICV with the relative cerebral blood flow reduction within the penumbra. Functional outcome was assessed by standardized assessment of the modified Rankin scale (mRS) after 3 months. In multivariate analyses, pw-ICV was significantly associated with final infarction volume (FIV) (β = .38, P < .001) after adjustment for penumbra volume, age, sex and time from symptom onset. In separate multivariate analysis with either pw-ICV or ICV, pw-ICV outperformed ICV for the prediction of FIV (Akaike's information criterion: 1,072 vs. 1,089; conditional variable importance: 1,494 vs. 955). There was also a highly significant association between FIV and clinical outcome as measured by an mRS score of 2 or less (odds ratio per 10 mL = .78, P < .001). Both pw-ICV and ICV were significantly associated with NIHSS improvement (both P<.05). In EVT-treated stroke patients, pw-ICV outperforms the more commonly used ICV in the prediction of morphological and functional outcome.

Current Standards for Organ Preservation in Locoregionally Advanced Non-nasopharyngeal Head and Neck Cancer and Evolving Strategies for Favorable-Risk and Platinum-Ineligible Populations.

Standard-of-care treatment for the majority of patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) is either upfront surgery followed by adjuvant treatment as indicated by intraoperative or pathologic findings or concurrent chemoradiation reserving surgical salvage for non-responsive disease. An attempt at upfront complete resection should be pursued if feasible in patients with oral cavity or paranasal sinus primary tumors. Given multimodality treatment paradigms, patients with locoregionally advanced SCCHN should be managed in a multidisciplinary setting. Modern radiation therapy, whether postoperative or definitive in intent, is based on target delineation guided by high-quality imaging, using an intensity-modulated radiation technique to spare organs at risk. In select groups of low-risk patients, most notably those with HPV-associated oropharyngeal SCC (OPSCC), several treatment deintensification approaches are currently under investigation. Major experimental strategies within this non-surgical organ preservation domain include reductions in the intensity of the chemotherapy or radiation therapy components of the chemoradiation program, use of induction chemotherapy, or imaging-based selection of patients eligible for deintensified radiation-based treatment. Of note, recent efforts to substitute cetuximab for cisplatin in low-risk HPV-associated OPSCC have demonstrated the inferiority of cetuximab to cisplatin in cisplatin-eligible patients, re-confirming cisplatin as the standard systemic therapy of choice in HNSCC. In patients who are not candidates for any type of cisplatin administration, carboplatin-based therapy or cetuximab remain options, and other non-cisplatin therapies are under investigation. Altered fractionation may be considered in patients who are not candidates for any type of systemic therapy. The role of immunotherapy in the management of locoregional SCCHN remains investigational.

Invited Commentary on "Imaging-based Selection for Endovascular Treatment in Stroke".

Invited Commentary on "Imaging-based Selection for Endovascular Treatment in Stroke".

Imaging-based Selection for Endovascular Treatment in Stroke.

Treatment of acute ischemic stroke (AIS) has evolved significantly in the past few years. Endovascular treatment (EVT) is now proved to be efficacious up to 24 hours from onset in properly selected patients. The recently updated 2018 American Heart Association-American Stroke Association guidelines reflect the important role of imaging in triage and patient selection for EVT of AIS. Pretreatment imaging in patients with acute stroke should (a) allow assessment for intracranial hemorrhage and demonstrate (b) the extent of early ischemic changes, (c) the presence of large arterial occlusion, and (d) in some cases potential salvageable tissue before the decision to proceed with EVT. The authors review how multimodality imaging can be used for EVT selection in the context of the recent guidelines. They highlight the importance of having streamlined imaging workflows that are integrated with clinical decision making to maximize treatment efficiency. Knowledge of the various imaging criteria including perfusion imaging used for EVT selection is highlighted. The authors discuss variable imaging paradigms used for selection of patients in the early and late windows (who present before vs after 6 hours from onset of symptoms), as reflected in the latest guidelines and in relation to their level of evidence. Finally, they focus on challenges in the subgroups of patients who were excluded from recent EVT trials and with limited evidence to prove the efficacy of EVT, such as patients with low NIHSS (National Institutes of Health Stroke Scale) score, distal occlusion, or large ischemic core. ©RSNA, 2019 See discussion on this article by Leslie-Mazwi.

Efficacy and Safety of Endovascular Thrombectomy for Ischemic Stroke in Nonagenarians

Introduction: Increased life expectancy results in a rapid increase of nonagenarian patients presenting with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). We conducted this study to assess the efficacy and safety of endovascular thrombectomy (ET) in this age group with use of imaging-based selection. Methods: We retrospectively analyzed clinical and imaging data from 2 different comprehensive stroke centers and compared the outcomes of ET versus intravenous thrombolysis (IVT) alone among eligible nonagenarians with LVO in anterior circulation and evidence of salvageable tissue on brain magnetic resonance imaging (MRI). Results: A total of 617 patients of AIS had been treated with IVT or ET, including 23 eligible nonagenarians. Among these, 9 patients were treated with IVT alone (IVT group) and 14 patients received ET group. Notably, the symptomatic intracranial hemorrhage rates were significantly lower after ET than after IVT (European-Australasian Acute Stroke Study II criteria, 0 vs. 33.3%; p = 0.047; National Institute of Neurological Disorders and Stroke criteria, 7.1 vs. 66.7%; p = 0.005). Moreover, although there were no statistically significant differences between the 2 groups on efficacy, ET tended to lead to greater early neurologic recovery at discharge (71.4 vs. 33.3%, p = 0.102) and improve functional outcome at 90 days (71.4 vs. 44.4%, p = 0.383), respectively. Conclusion: By using MRI-based selection, ET in nonagenarians with AIS caused by LVO within anterior circulation was safe and may lead to improve early neurologic recovery and functional independence at 90 days, as compared with IVT alone. Randomized trial in larger sample size testing efficacy of ET using diffusion-weighted imaging-fluid attenuated inversion recovery mismatch selection in this age group appears feasible.

Survival after primary liver resection in metastatic colorectal cancer: A comparative analysis of the LICC trial with historical controls (FFCD ACHBTH AURC 9002 trial and EORTC Intergroup trial 40983).

e15019 Background: Metastatic colorectal cancer (mCRC) patients (pts) with liver-limited disease (LLD) have a chance of long-term survival and cure after hepatic metastasectomy. The optimal treatment after primary liver resection remains controversial. Here we compare results from the LICC trial with historical controls, the FFCD ACHBTH AURC 9002 trial (FFCD; Portier et al., 2006) and the EORTC Intergroup trial 40983 (EORTC; Nordlinger et al., 2008, 2013). The three trials investigated pts with mCRC LLD who underwent primary hepatic resection. Methods: LICC, FFCD and EORTC were compared regarding pts characteristics, treatment, surveillance and efficacy outcomes. LICC pts received the adjuvant antigen-specific cancer vaccine tecemotide (L-BLP25) or placebo after primary LLD resection for up to 2 years. The FFCD trial compared postoperative 5-FU/leucovorin and the EORTC trial perioperative FOLFOX versus surgery alone. Results: Primary resected pts in LICC (n = 80; R0 n = 76), FFCD (R0 n = 171; postoperative chemotherapy n = 86) and EORTC (n = 364) showed different pt characteristics concerning median age (60, 63 and 63 years) and rate of synchronous metastases (46.8%, 27.9% and 34.0%). In LICC, &gt; 5 liver metastases were resected in 11.6% of pts, in FFCD and EORTC all eligible pts had &lt; 5 liver metastases resected. In contrast to EORTC, LICC and FFCD had a close surveillance until recurrence or a maximum of 2 years. Median OS (mOS) in LICC was not yet estimable in primary resected pts (tecemotide arm: 62.8 months; placebo arm: not yet estimable). In the FFCD and the EORTC trial, mOS was 62.1 and 61.3 months, respectively. Further details will be presented. Conclusions: Despite unfavorable disease characteristic in LICC compared with the earlier EORTC and FFCD studies, primary liver resection without adjuvant chemotherapy led to surprisingly good survival outcomes. Improvements in imaging-based pt selection and liver resection techniques might in part explain our finding. Surgery alone appears to be an option for selected pts with resectable LLD. Better systemic chemo(immune-)therapy may have also contributed to the OS benefit. Clinical trial information: LICC: NCT01462513; EORTC: NCT00006479; FFCD: not registered.

Results of Transcranial Resection of Olfactory Groove Meningiomas in Relation to Imaging-Based Case Selection Criteria for the Endoscopic Approach.

Endoscopic endonasal surgery (EES) is increasingly used for olfactory groove meningiomas (OGMs). The role of EES for large (≥4 cm) or complex OGMs is debated. Specific imaging features have been reported to affect the degree of gross total resection (GTR) and complications following EES for OGMs. The influence of these factors on transcranial resection (TCR) is unknown. To examine the impact of specific imaging features on outcome following TCR to provide a standard for large and endoscopically less favorable OGMs against which endoscopic outcomes can be compared. Retrospective study of patients undergoing TCR for OGMs 2002 to 2016. Fifty patients (mean age 62.1 yr, mean maximum tumor diameter 5.04 cm and average tumor volume of 48.8 cm3) were studied. Simpson grade 1 and 2 resections were achieved in 80% and 12%, respectively. A favorable functional outcome (modified Rankin Scale [mRS] 0-2) was attained in 86%. The degree of resection, mRS, mortality (4%), recurrence (6%), infection (8%), and cerebrospinal fluid leak requiring intervention (12%) were not associated with tumor calcification, absence of cortical cuff, T2 hyperintensity, tumor configuration, tumor extension beyond midpoint of superior orbital roof, or extension to posterior wall of frontal sinus. There was no difference in resection rates but a trend towards greater complications between 3 arbitrarily divided groups of large meningiomas of increasing complexity based on extensive extension or vascular adherence. Favorable outcomes can be achieved with TCR for large and complex OGMs Factors that may preclude endoscopic resection do not negatively affect outcome following TCR.

Commentary: Results of Transcranial Resection of Olfactory Groove Meningiomas in Relation to Imaging-Based Case Selection Criteria for the Endoscopic Approach.

Commentary: Results of Transcranial Resection of Olfactory Groove Meningiomas in Relation to Imaging-Based Case Selection Criteria for the Endoscopic Approach.

Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window

Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management-only groups. To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients. Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded-end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018. Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone. The primary outcome was the distribution of 90-day modified Rankin Scale scores. Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P = .05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P = .01; transfer OR, 2.6; 95% CI, 1.3-4.8; P = .009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ. In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged. ClinicalTrials.gov identifier: NCT02586415.

Abstract 113: Late Window Transfer Patients had Favorable Outcomes Following Thrombectomy in DEFUSE 3

Background: Although the treatment benefit of endovascular thrombectomy (EVT) was maintained in transfer patients in the early window trials, overall rates of functional independence were lower in both the EVT and control groups among transfer patients. We hypothesized that the imaging-based selection criteria employed in DEFUSE 3 would lead to comparable outcome rates and treatment efficacy in transfer vs. direct admission patients. Methods: DEFUSE 3 patients were stratified based on if they presented directly to the study site or were transferred from a primary center. The primary and secondary efficacy and safety outcomes of DEFUSE 3 were compared. Results: Of 182 patients randomized, 121 (66%) were transfers and 61 (34%) direct. The 2 groups had similar baseline characteristics, other than transfers had 30 min longer median times from last known well time to arrival at the study site. The primary efficacy outcome (mRS shift at day 90) did not differ in the direct vs. transfer groups, OR 2.9, 95% CI 1.2-7.2, P=0.014 for direct and OR=2.6, 95% CI 1.3-4.8, P=0.009 for transfer (Fig 1). The overall rate of functional independence (mRS 0-2 at day 90) in the EVT group did not differ (44% direct, 45% transfer) nor did the treatment effect: RR 2.0 (0.9-4.4) direct vs. 3.1 (1.6-6.1) for transfer. EVT reperfusion rates were identical (mTICI≥2b 76%) in both groups. The rates of death and SICH did not differ. Transfer patients had more favorable collateral profiles (based on the hypoperfusion intensity ratio) median (IQR) for transfer 0.35 (0.18-0.47) vs. 0.42 (0.25-0.56) for direct, p=0.050. Conclusions: In late window patients selected by penumbral mismatch criteria, both the favorable outcome rates and treatment effects did not decline in transfer patients. These results have healthcare implications indicating transferring potential candidates for late window thrombectomy to EVT centers is associated with substantial clinical benefits and should be strongly encouraged.