CAM and Pediatric Oncology: Where Are All the Best Cases?

Background. Use of complementary and alternative medicine (CAM) by children with cancer is high; however, pediatric best cases are rare.Objectives. To investigate whether best cases exist in pediatric oncology using a three-phase approach and to compare our methods with other such programs.Methods. In phase I, Children’s Oncology Group (COG) oncologists were approached via email and asked to recall patients who were (i) under 18 when diagnosed with cancer, (ii) diagnosed between 1990 and 2006, (iii) had unexpectedly positive clinical outcome, and (iv) reported using CAM during or after cancer treatment. Phase II involved partnering with CAM research networks; patients who were self-identified as best cases were asked to submit reports completed in conjunction with their oncologists. Phase III extended this partnership to 200 CAM associations and training organizations.Results. In phase I, ten cases from three COG sites were submitted, and most involved use of traditional Chinese medicine to improve quality of life. Phases II and III did not yield further cases.Conclusion. Identification of best cases has been suggested as an important step in guiding CAM research. The CARE Best Case Series Program had limited success in identifying pediatric cases despite the three approaches we used.</jats:p

Abstract T P35: Baseline Diffusion Weighted Imaging Lesion Volume Predicts Disappearance of Infarct on Fluid Attenuated Inverse Recovery Sequences Within 30 Days of TIA/Minor Stroke

Introduction: Evidence of infarction on MRI is predictive of early stroke recurrence after TIA/minor stroke. It has recently been reported that diffusion-weighted imaging (DWI) changes are not associated with evidence of infarction on Fluid Attenuated Inverse Recovery (FLAIR) sequences 90 days later in 30% of patients. We completed a serial MRI study to determine the time course of infarct resolution. We tested the hypothesis that acute DWI lesion volume predicts infarct disappearance by 30 days. Methods: Acute TIA/minor stroke patients (NIHSS≤3) were prospectively imaged at baseline, 7 and 30 days after symptom onset. Lesion volumes were measured planimetrically by a blinded rater at each time point on DWI and FLAIR sequences. Mean and relative (to contralateral tissue) Apparent Diffusion Coefficient ((r)ADC) values were also calculated. Results: Acute DWI lesions were found in 94/172 patients. Median time between symptom onset and baseline MRI was 20.9(19.3) h. DWI volume decreased from baseline (1.51 ml (4.36)) at 7 days (1.13 ml (2.96), P =0.001) and at 30 days (0.40 ml (0.97), P &lt;0.0001). DWI lesions at 7 days pseudo-normalized (infarct visible on FLAIR) in 3.4% and resolved without evidence of infarction in 8% of patients. Seventy-seven (82%) patients had persistent lesions on FLAIR at 30 days (FLAIR+). Baseline NIHSS scores were similar between FLAIR+ (1.40±1.21) and FLAIR– patients (1.18±1.19, P =0.64). Baseline rADC was similar in FLAIR+ (0.84(0.17)) and FLAIR– patients (0.89(0.21), P =0.155). Baseline DWI volumes were larger in FLAIR+ (2.08 ml (6.9)) than FLAIR– patients (0.69 ml (0.95), P =0.007). ROC analysis indicated that a baseline DWI volume &lt;2.04 ml predicted absence of FLAIR lesion at 30 days with a specificity of 100% and sensitivity of 50.6%. Good functional outcome (modified Rankin Score ≤2) at 90 days was similar in FLAIR+ (54/62, 87%) and FLAIR– patients (12/12, 100%, P =0.339). Conclusion: Acute DWI lesions are transient and not always associated with visible infarction on FLAIR, even as early as 7 days after symptom onset. Delaying MRI results in a failure to demonstrate evidence of infarction in the majority of patients, particularly those with DWI lesion volumes below 2 ml. </jats:p

Abstract TP439: Temporary Cognitive Impairment in Transient Ischemic Attack and Minor Stroke Patients is Predicted by Chronic White Matter Hyperintensity Volume

Background: Cognitive changes have been described in subacute TIA/minor stroke (TIA/MIS), but the temporal profile is unknown. We tested the hypothesis that TIA/MIS patients experience transient cognitive impairment, and that this can be predicted by Diffusion-Weighted Imaging (DWI) lesion volume. Methods: Acute TIA/MIS stroke (NIH stroke scale score ≤3) patients with no history of cognitive impairment were prospectively recruited within 72 h of onset. Patients underwent Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE) and MRI, including DWI and Fluid-Attenuated Inverse Recovery (FLAIR) sequences, at baseline, days 7 and 30. DWI lesion and FLAIR chronic white matter hyperintensity (WMH) volumes were measured planimetrically. Results: Fifty patients (mean age 68 ±15.1 years) were imaged at a median (IQR) of 26.5 (28.5) h after onset. Cognitive impairment (scores ≤26) was detected more frequently with MoCA (31/50, 62%) than MMSE (13/50, 26%, p=0.009). Acute ischemic lesions (DWI) were present in 33 (66%) patients. Mean DWI volume at baseline was 4.5 ± 11.1ml. Patients with DWI lesions (22/33, 67%) had similar impairment rates as those without (9/17, 53%; p=0.34). Linear regression indicated no relationship between acute DWI lesion volume (log transformed) and baseline MoCA scores (β=0.028, 95% CI [-2.09, 2.44]). Impaired patients had larger WMH volumes (13.6 ± 21.9 ml) than unaffected patients (2.6 ± 3.2 ml, p=0.01). Log transformed WMH volumes were inversely predictive of baseline MoCA scores (β=-0.54, 95% CI [-7.84, -2.28]). Median MoCA scores improved over time (27(5) at day 7 and 28(5) at day 30). Patients with baseline impairment and an increase of ≥2 points on MoCA by day 30 were defined as reverters (N=20). DWI lesion frequency was similar in reverters and those with persisting impairment (75% vs 64%, p= 0.50), as was DWI (6.9 ±14.3 ml vs 1.2 ±1.9 ml; p= 0.113) and WMH lesion volume (17.0 ± 26.2 ml vs 8.1 ± 8.1 ml; p= 0.18). Conclusions: Most TIA/MIS patients have evidence of temporary acute cognitive impairment when assessed with MoCA. Deficits are correlated with chronic WMH, suggesting an unmasking of subclinical cognitive impairment. Temporary cognitive deficits should be considered in the management of TIA/MIS patients

Abstract TP439: Temporary Cognitive Impairment in Transient Ischemic Attack and Minor Stroke Patients is Predicted by Chronic White Matter Hyperintensity Volume

Background: Cognitive changes have been described in subacute TIA/minor stroke (TIA/MIS), but the temporal profile is unknown. We tested the hypothesis that TIA/MIS patients experience transient cognitive impairment, and that this can be predicted by Diffusion-Weighted Imaging (DWI) lesion volume. Methods: Acute TIA/MIS stroke (NIH stroke scale score ≤3) patients with no history of cognitive impairment were prospectively recruited within 72 h of onset. Patients underwent Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE) and MRI, including DWI and Fluid-Attenuated Inverse Recovery (FLAIR) sequences, at baseline, days 7 and 30. DWI lesion and FLAIR chronic white matter hyperintensity (WMH) volumes were measured planimetrically. Results: Fifty patients (mean age 68 ±15.1 years) were imaged at a median (IQR) of 26.5 (28.5) h after onset. Cognitive impairment (scores ≤26) was detected more frequently with MoCA (31/50, 62%) than MMSE (13/50, 26%, p=0.009). Acute ischemic lesions (DWI) were present in 33 (66%) patients. Mean DWI volume at baseline was 4.5 ± 11.1ml. Patients with DWI lesions (22/33, 67%) had similar impairment rates as those without (9/17, 53%; p=0.34). Linear regression indicated no relationship between acute DWI lesion volume (log transformed) and baseline MoCA scores (β=0.028, 95% CI [-2.09, 2.44]). Impaired patients had larger WMH volumes (13.6 ± 21.9 ml) than unaffected patients (2.6 ± 3.2 ml, p=0.01). Log transformed WMH volumes were inversely predictive of baseline MoCA scores (β=-0.54, 95% CI [-7.84, -2.28]). Median MoCA scores improved over time (27(5) at day 7 and 28(5) at day 30). Patients with baseline impairment and an increase of ≥2 points on MoCA by day 30 were defined as reverters (N=20). DWI lesion frequency was similar in reverters and those with persisting impairment (75% vs 64%, p= 0.50), as was DWI (6.9 ±14.3 ml vs 1.2 ±1.9 ml; p= 0.113) and WMH lesion volume (17.0 ± 26.2 ml vs 8.1 ± 8.1 ml; p= 0.18). Conclusions: Most TIA/MIS patients have evidence of temporary acute cognitive impairment when assessed with MoCA. Deficits are correlated with chronic WMH, suggesting an unmasking of subclinical cognitive impairment. Temporary cognitive deficits should be considered in the management of TIA/MIS patients. </jats:p

Dabigatran Therapy in Acute Ischemic Stroke Patients Without Atrial Fibrillation

Background and Purpose— Acute ischemic stroke patients are at risk of early recurrence. We tested the feasibility and safety of initiating dabigatran in patients, within 24 hours of minor stroke in patients without atrial fibrillation. Methods— Minor stroke patients (National Institutes of Health Stroke Scale score ≤3) without atrial fibrillation and evidence of acute infarction on magnetic resonance imaging were treated with dabigatran. Treatment began within 24 hours of onset and was continued for 30 days. The primary end point was symptomatic hemorrhagic transformation. Results— A total of 53 patients with median (interquartile range) age of 68 (57–77) years and National Institutes of Health Stroke Scale score of 1 (0–2) were enrolled. Baseline diffusion-weighted imaging volume was 0.8 (0.3–2.4) mL. No patients experienced symptomatic hemorrhagic transformation. Three patients had evidence of asymptomatic petechial hemorrhagic transformation on day 7, which remained stable at day 30, while continuing dabigatran. Conclusions— Dabigatran treatment within 24 hours of minor stroke is feasible. A larger randomized trial is required to confirm the safety and efficacy of this treatment approach. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT 01769703. </jats:sec

Dynamic Evolution of Diffusion-Weighted Imaging Lesions in Patients With Minor Ischemic Stroke

Background and Purpose— Diffusion-weighted imaging (DWI) lesion volume on magnetic resonance imaging is increasingly being used as a surrogate outcome measure in clinical trials. We aimed to characterize the evolution of DWI lesion volumes within 30 days of symptom onset after minor stroke. Methods— Minor stroke patients with DWI lesions on magnetic resonance imaging within 48 hours of symptom onset were prospectively followed with magnetic resonance imaging brain scan at 7 and 30 days. Change in the lesion volume was defined as the difference between day 30 Fluid-Attenuated Inversion Recovery and baseline DWI lesion volumes. Results— Three patterns of infarct evolution were observed: reduction (72 [63%]), no change (26 [23%]), and growth (16 [14%]). Patients with infarct reduction at 30 days had larger baseline DWI lesion volumes (2.5 [0.9–8.5] mL) than those with stable infarcts (0.5 [0.3–0.9] mL; P =0.01). Complete DWI reversal at day 30, was seen in only 6 (5.3%) patients. Conclusions— The most common pattern of infarct evolution in patients with minor stroke is a reduction in volume, but complete resolution is uncommon. </jats:sec

Abstract WMP83: Rivaroxaban Therapy Is Not Associated with Hemorrhagic Transformation After Acute Cardioembolic Stroke: A Prospective MRI Study

Introduction: Early anticoagulation after cardioembolic stroke remains controversial, due to the potential for symptomatic hemorrhagic transformation (HT). The safety profile of rivaroxaban within 14 days of cardioembolic stroke onset has not been assessed prospectively. Methods: We conducted a prospective, open label study of patients with atrial fibrillation treated with rivaroxaban ≤14 days of mild/moderate ischemic stroke/TIA (NIHSS score≤8) onset. Informed consent was obtained after the decision to treat with rivaroxaban was made by the treating physician. All patients underwent MRI, including susceptibility-weighted sequences, within 24 hours of rivaroxaban initiation and at day 7, with clinical assessment at 90 days. HT was classified using ECASS criteria (hemorrhagic infarct (HI) 1/2, or parenchymal hemorrhage (PH) 1/2). The primary endpoint was symptomatic HT (defined as PH2 associated with an NIHSS increase ≥4 within the study period). Secondary outcomes included any PH at day 7 and recurrent stroke within 90 days of enrolment. Results: Sixty patients were enrolled (mean±SD age 71±19 years, 82% stroke/18% TIA). Median (IQR) time from onset to first rivaroxaban dose was 3(5) days. At treatment initiation, median NIHSS was 2(4) and median DWI volume was 7.9(13.7) ml (range 0-175 ml). Baseline DWI volume was correlated with time to first dose (r=0.58, p&lt;0.001). On baseline MRI, HT was present in 25 patients (42%) (HI1=19, HI2=6). Fifty patients had follow-up MRI at a median 7(4) days after rivaroxaban initiation (4 patients withdrew consent and 6 were lost to follow-up). No patients developed symptomatic HT or PH at any point. New asymptomatic HI1 developed in 3 patients. There was asymptomatic progression from HI1 to HI2 in 5 patients. In the remaining 18 patients with baseline HI and follow-up MRI, there was no change at day 7. Two recurrent ischemic strokes occurred (day 5 and day 28). Two additional patients had new asymptomatic DWI lesions at day 7. Two patients died within 90 days (one recurrent stroke and one pneumonia). Conclusion: These data support the safety of rivaroxaban initiation within 14 days of mild/moderate cardioembolic stroke/TIA. MRI evidence of petechial HT, which is common, does not appear to increase the risk of symptomatic HT. </jats:p

Early Dabigatran Treatment After Transient Ischemic Attack and Minor Ischemic Stroke Does Not Result in Hemorrhagic Transformation

ABSTRACT:Objectives:The optimal timing of anticoagulation after ischemic stroke in atrial fibrillation (AF) patients is unknown. Our aim was to demonstrate the feasibility and safety of initiating dabigatran therapy within 14 days of transient ischemic attack (TIA) or minor stroke in AF patients.Patients and Methods:A prospective, multi-center registry (NCT02415855) in patients with AF treated with dabigatran within 14 days of acute ischemic stroke/TIA (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) onset. Baseline and follow-up computed tomography (CT) scans were assessed for hemorrhagic transformation (HT) and graded by using European Cooperative Acute Stroke Study criteria.Results:One hundred and one patients, with a mean age of 72.4 ± 11.5 years, were enrolled. Median infarct volume was 0 ml. Median time from index event onset to dabigatran initiation was 2 days, and median baseline NIHSS was 1. Pre-treatment HT was present in seven patients. No patients developed symptomatic HT. On the day 7 CT scan, HT was present in six patients (one progressing from baseline hemorrhagic infarction type 1). Infarct volume was a predictor of incident HT (odds ratio = 1.063 [1.020–1.107], p &lt; 0.003). All six (100%) patients with new/progressive HT were functionally independent (modified Rankin Scale (mRS) = 0–2) at 30 days, which was similar to those without HT (90%, p = 0.422). Recurrent ischemic events occurred within 30 days in four patients, two of which were associated with severe disability and death (mRS 5 and 6, respectively).Conclusion:Early dabigatran treatment did not precipitate symptomatic HT after minor stroke. Asymptomatic HT was associated with larger baseline infarct volumes. Early recurrent ischemic events may be clinically more important.</jats:sec