Clinical Outcome After Endovascular Treatment in Patients With Active Cancer and Ischemic Stroke: A MR CLEAN Registry Substudy

Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013316
Author(s):  
Merelijne Anthoesa Verschoof ◽  
Adrien E. Groot ◽  
Sebastiaan F.T.M. de Bruijn ◽  
Bob Roozenbeek ◽  
H. Bart van der Worp ◽  
...  

Objective:To explore clinical and safety outcomes of patients with acute ischemic stroke (AIS) and active cancer after endovascular treatment (EVT).Methods:Using data from the MR CLEAN Registry, we compared patients with active cancer (defined as cancer diagnosed within 12 months prior to stroke, metastatic disease, or current cancer treatment) to patients without cancer. Outcomes were 90-day modified Rankin Scale (mRS) score, mortality, successful reperfusion (eTICI scores≥2b), symptomatic intracranial hemorrhage (sICH), and recurrent stroke. Subgroup analyses were performed in patients with a pre-stroke mRS score of 0 or 1 and according to treatment setting (curative or palliative). Analyses were adjusted for prognostic variables.Results:Of 2583 patients who underwent EVT, 124 (4.8%) had active cancer. They more often had pre-stroke disability (mRS≥2: 34.1% vs. 16.6%). The treatment setting was palliative in 25.3% of the patients. There was a shift towards worse functional outcome at 90 days in patients with active cancer (adjusted common OR 2.2, 95% CI 1.5-3.2). At 90 days, patients with active cancer were less often independent (mRS 0-2: 22.6% vs. 42.0%, aOR 0.5, 95% CI 0.3-0.8), and more often dead (52.2% vs. 26.5%, aOR 3.2, 95% CI 2.1-4.9). Successful reperfusion (67.8% vs. 60.5%, aOR 1.4, 95% CI 1.0-2.1) and sICH rates (6.5% vs. 5.9%, aOR 1.1, 95 %CI 0.5-2.3) did not differ. Recurrent stroke within 90 days was more common in patients with active cancer (4.0% vs. 1.3%, aOR 3.1, 95% CI 1.2-8.1). The sensitivity analysis of patients with a pre-stroke mRS of 0 or 1 showed that patients with active cancer still had a worse outcome at 90 days (acOR 1.9, 95% CI 1.2-3.0). Patients with active cancer in a palliative treatment setting regained functional independence less often compared to patients in a curative setting (18.2% vs. 32.1%) and mortality was also higher (81.8% vs. 39.3%).Conclusions:Despite similar technical success, patients with active cancer had significantly worse outcomes after EVT for AIS. Moreover, they had an increased risk of recurrent stroke. Nevertheless, about a quarter of the patients regained functional independence and the risk of other complications, most notably sICH, was not increased.Classification of Evidence:This study provides Class I evidence that patients with active cancer undergoing EVT for AIS have worse functional outcomes at 90 days compared to those without active cancer.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanni Merlino ◽  
Carmelo Smeralda ◽  
Gian Luigi Gigli ◽  
Simone Lorenzut ◽  
Sara Pez ◽  
...  

AbstractTo date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42–20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kars C Compagne ◽  
Manon Kappelhof ◽  
Robert-Jan B Goldhoorn ◽  
Charles B Majoie ◽  
Yvo B Roos ◽  
...  

Introduction: Outcomes after endovascular treatment (EVT) for acute ischemic stroke are highly time dependent, but whether active reduction of time to treatment leads to better outcome has not been demonstrated. We compared data of the two subsequent MR CLEAN Registry cohorts, comprising all patients in the Netherlands who had EVT for acute ischemic stroke from 2014-2017, for a trend in time to treatment and its association with outcome. Methods: We compared workflow, successful reperfusion (eTICI 2B-3), NIHSS at 24h, functional outcome (mRS) at 90 days, occurrence of symptomatic intracranial hemorrhage (sICH) and mortality in patients with ischemic stroke and a proximal intracranial occlusion in the anterior circulation included in the second cohort of the Registry (June 2016-November 2017; n = 1779) to those in patients included in the first cohort (March 2014-June 2016; n = 1526) using logistic regression. Results: Baseline NIHSS was 16 in both cohorts. Times from onset-to-groin and onset-to-reperfusion were shorter in the second cohort than in the first (185 versus 210 minutes; p<0.01 and 238 versus 270 minutes; p<0.01, respectively) (Figure 1). Successful reperfusion was achieved more often in the second than in the first cohort (72% versus 58%; p<0.01). Rates of sICH and mortality did not differ (5.9% versus 5.7%; p=0.94 and 29% versus 29%; p=0.60). However, follow-up NIHSS was lower (median 10 versus 11; p<0.001) and more patients achieved functional independence at 90 days (42.6% versus 38.9%; p = 0.012) in the second cohort (Figure 1). In a logistic regression model, the difference in good outcome between the two cohorts (aOR 1.27; 95%CI 1.08-1.50) was reduced after additional adjustment for time to reperfusion (aOR 1.15; 95%CI 0.96-1.36) as well as successful reperfusion (aOR 1.16; 95%CI 0.95-1.41). Discussion: Our data show that outcomes after EVT in routine clinical practice are improving, likely attributable to improved workflow and experience.


2021 ◽  
pp. 1-11
Author(s):  
Agnetha A. E. Bruggeman ◽  
Manon Kappelhof ◽  
Nerea Arrarte Terreros ◽  
Manon L. Tolhuisen ◽  
Praneeta R. Konduri ◽  
...  

OBJECTIVE Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and mortality. Furthermore, they aimed to assess the effectiveness of intravenous alteplase treatment and endovascular treatment (EVT), as well as the best first-line EVT approach in patients with CCE. METHODS The Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry is a prospective, observational multicenter registry of patients treated with EVT for acute ischemic stroke in 16 intervention hospitals in the Netherlands. The association of CCE with functional outcome, reperfusion, and mortality was evaluated using logistic regression models. Univariable comparisons were made to determine the effectiveness of intravenous alteplase treatment and the best first-line EVT approach in CCE patients. RESULTS The study included 3077 patients from the MR CLEAN Registry. Fifty-five patients (1.8%) had CCE. CCE were not significantly associated with worse functional outcome (adjusted common OR 0.71, 95% CI 0.44–1.15), and 29% of CCE patients achieved functional independence. An extended Thrombolysis in Cerebral Infarction score ≥ 2B was significantly less often achieved in CCE patients compared to non-CCE patients (adjusted OR [aOR] 0.52, 95% CI 0.28–0.97). Symptomatic intracranial hemorrhage occurred in 8 CCE patients (15%) vs 171 of 3022 non-CCE patients (6%; p = 0.01). The median improvement on the National Institutes of Health Stroke Scale (NIHSS) was 2 in CCE patients versus 4 in non-CCE patients (p = 0.008). CCE were not significantly associated with mortality (aOR 1.16, 95% CI 0.64–2.12). Intravenous alteplase use in CCE patients was not associated with functional outcome or reperfusion. In CCE patients with successful reperfusion, stent retrievers were more often used as the primary treatment device (p = 0.04). CONCLUSIONS While patients with CCE had significantly lower reperfusion rates and less improvement on the NIHSS after EVT, CCE were not significantly associated with worse functional outcome or higher mortality rates. Therefore, EVT should still be considered in this specific group of patients.


Stroke ◽  
2021 ◽  
Author(s):  
Esmee Venema ◽  
Bob Roozenbeek ◽  
Maxim J.H.L. Mulder ◽  
Scott Brown ◽  
Charles B.L.M. Majoie ◽  
...  

Background and Purpose: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice. Methods: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0–2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C ) statistic. Results: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C -statistic for functional independence was 0.74 (95% CI, 0.72–0.77) in HERMES and, after model updating, 0.80 (0.78–0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%–14.4%). Patients with low (<1%) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at www.mrpredicts.com . Conclusions: Because of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center.


2021 ◽  
pp. neurintsurg-2021-017726
Author(s):  
Rob A van de Graaf ◽  
Noor Samuels ◽  
Vicky Chalos ◽  
Geert J Lycklama a Nijeholt ◽  
Heleen van Beusekom ◽  
...  

BackgroundApproximately one-third of patients with ischemic stroke treated with endovascular treatment do not recover to functional independence despite rapid and successful recanalization. We aimed to quantify the importance of predictors of poor functional outcome despite successful reperfusion.MethodsWe analyzed patients from the MR CLEAN Registry between March 2014 and November 2017 with successful reperfusion (extended Thrombolysis In Cerebral Infarction ≥2B). First, predictors were selected based on expert opinion and were clustered according to acquisition over time (ie, baseline patient factors, imaging factors, treatment factors, and postprocedural factors). Second, several models were constructed to predict 90-day functional outcome (modified Rankin Scale (mRS)). The relative importance of individual predictors in the most extensive model was expressed by the proportion of unique added χ2 to the model of that individual predictor.ResultsOf 3180 patients, 1913 (60%) had successful reperfusion. Of these 1913 patients, 1046 (55%) were functionally dependent at 90 days (mRS >2). The most important predictors for mRS were baseline patient factors (ie, pre-stroke mRS, added χ2 0.16; National Institutes of Health Stroke Scale score at baseline, added χ2 0.12; age, added χ2 0.10), and postprocedural factors (ie, symptomatic intracranial hemorrhage (sICH), added χ2 0.12; pneumonia, added χ2 0.09). The probability of functional independence for a typical stroke patient with sICH was 54% (95% CI 36% to 72%) lower compared with no sICH, and 21% (95% CI 4% to 38%) for pneumonia compared with no pneumonia.ConclusionBaseline patient factors and postprocedural adverse events are important predictors of poor functional outcome in successfully reperfused patients with ischemic stroke. This implies that prevention of postprocedural adverse events has the greatest potential to further improve outcomes in these patients.


2019 ◽  
Vol 11 (9) ◽  
pp. 866-873 ◽  
Author(s):  
Ivo GH Jansen ◽  
Maxim JHL Mulder ◽  
Robert-Jan B Goldhoorn ◽  
Anna MM Boers ◽  
Adriaan CGM van Es ◽  
...  

BackgroundCollateral status modified the effect of endovascular treatment (EVT) for stroke in several randomized trials. We assessed the association between collaterals and functional outcome in EVT treated patients and investigated if this association is time dependent.MethodsWe included consecutive patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN) Registry (March 2014–June 2016) with an anterior circulation large vessel occlusion undergoing EVT. Functional outcome was measured on the modified Rankin Scale (mRS) at 90 days. We investigated the association between collaterals and mRS in the MR CLEAN Registry with ordinal logistic regression and if this association was time dependent with an interaction term. Additionally, we determined modification of EVT effect by collaterals compared with MR CLEAN controls, and also investigated if this was time dependent with multiplicative interaction terms.Results1412 patients were analyzed. Functional independence (mRS score of 0–2) was achieved in 13% of patients with grade 0 collaterals, in 27% with grade 1, in 46% with grade 2, and in 53% with grade 3. Collaterals were significantly associated with mRS (adjusted common OR 1.5 (95% CI 1.4 to 1.7)) and significantly modified EVT benefit (P=0.04). None of the effects were time dependent. Better collaterals corresponded to lower mortality (P<0.001), but not to lower rates of symptomatic intracranial hemorrhage (P=0.14).ConclusionIn routine clinical practice, better collateral status is associated with better functional outcome and greater treatment benefit in EVT treated acute ischemic stroke patients, independent of time to treatment. Within the 6 hour time window, a substantial proportion of patients with absent and poor collaterals can still achieve functional independence.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kilian M. Treurniet ◽  
◽  
Natalie E. LeCouffe ◽  
Manon Kappelhof ◽  
Bart J. Emmer ◽  
...  

Abstract Background Endovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO. Methods MR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included. Discussion IVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT. Trial registration www.isrctn.com: ISRCTN80619088. Registered on 31 October 2017.


2018 ◽  
Vol 46 (1-2) ◽  
pp. 46-51 ◽  
Author(s):  
Jun Fujinami ◽  
Tomoyuki Ohara ◽  
Fukiko Kitani-Morii ◽  
Yasuhiro Tomii ◽  
Naoki Makita ◽  
...  

Background: This study assessed the incidence and predictors of short-term stroke recurrence in ischemic stroke patients with active cancer, and elucidated whether cancer-associated hypercoagulation is related to early recurrent stroke. Methods: We retrospectively enrolled acute ischemic stroke patients with active cancer admitted to our hospital between 2006 and 2017. Active cancer was defined as diagnosis or treatment for any cancer within 12 months before stroke onset, known recurrent cancer or metastatic disease. The primary clinical outcome was recurrent ischemic stroke within 30 days. Results: One hundred ten acute ischemic stroke patients with active cancer (73 men, age 71.3 ± 10.1 years) were enrolled. Of those, recurrent stroke occurred in 12 patients (11%). When patients with and without recurrent stroke were compared, it was found that those with recurrent stroke had a higher incidence of pancreatic cancer (33 vs. 10%), systemic metastasis (75 vs. 39%), multiple vascular territory infarctions (MVTI; 83 vs. 40%), and higher ­D-dimer levels (16.9 vs. 2.9 µg/mL). Multivariable logistic regression analysis showed that each factor mentioned above was not significantly associated with stroke recurrence independently, but high D-dimer (hDD) levels (≥10.4 µg/mL) and MVTI together were significantly associated with stroke recurrence (OR 6.20, 95% CI 1.42–30.7, p = 0.015). Conclusions: Ischemic stroke patients with active cancer faced a high risk of early recurrent stroke. The concurrence of hDD levels (≥10.4 µg/mL) and MVTI was an independent predictor of early recurrent stroke in active cancer patients. Our findings suggest that cancer-associated hypercoagulation increases the early recurrent stroke risk.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Trung Nguyen ◽  
Huong Nguyen ◽  
Thanh Nguyen ◽  
Triet Ngo ◽  
Binh Pham ◽  
...  

Introduction: DAWN and DEFUSE 3 trials utilized advanced imaging to prove the benefit of endovascular treatment (EVT) in patients within 6-24 hours. There is increasing evidence to suggest the limitations of advanced imaging in real-world practice. Non-contrast-enhanced computed tomography (NCCT) has proved with good sensitivity and specificity in the definition of infarct core. It is still unknown if a simpler and faster protocol may adequately select patients within 6-24 hours for EVT. Hypothesis: To compare outcomes of patients submitted to EVT presenting within 6 hours or 6-24 hours, selected using simple imaging protocol. Methods: An observational study was performed, which included consecutive patients with anterior circulation ischemic stroke eligible for EVT within 6 hours or 6-24 hours. Patients within early window received routine treatment, while patients presenting within late window were treated if they had a mismatch between the clinical deficit, the infarct volume, and collateral blood blow: (NIHSS score was ≥10 and ASPECTS was ≥7) or (ASPECTS was =6, and the collateral score was ≥2). ASPECTS of NCCT/DWI-MRI and collateral status on CTA/DSA were assessed by a blinded neuroradiologist. The collateral grading system was scored on a scale of 0-3 as in the ESCAPE trial. Results: Of the 184 patients were included, 77 (41,8%) received thrombectomy in late window, 107 (58,2%) received acute treatment in early window. Baseline characteristics were similar between groups, except for longer onset to groin puncture time (median, 300 vs 705 min; P<0,0001), higher admission NIHSS (median, 13 vs 16; P<0,0001), lower in ASPECTS (median, 9 vs 8; P<0,0001), and large artery atherosclerosis etiology (61,7 vs 72,7%, P=0,002) in the late window group. No significant differences in successful reperfusion rate and rates of parenchymal hematoma type 2 (81,3 vs 83,1%, P=0,75; 4/107 vs 4/77, P=0,63, respectively). Functional independence (mRS 0-2) and mortality at 90 days did not differ significantly (65,4 vs 57,1%, P=0,25; 10,3 vs 6,5%, P=0,43; respectively). Conclusions: This real-world observational study suggests that EVT may be safe and effective in patients presenting within 6-24 hours selected using clinical-core mismatch and collateral blood blow.


2019 ◽  
Vol 30 (11) ◽  
pp. 1759-1764.e6 ◽  
Author(s):  
Robert-Jan B. Goldhoorn ◽  
Nele Duijsters ◽  
Charles B.L.M. Majoie ◽  
Yvo B.W.E.M. Roos ◽  
Diederik W.J. Dippel ◽  
...  

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