On apples, oranges, and ARUBA

Meling, Torstein R.; Proust, F.; Gruber, Andreas; Niemelä, Mika; Regli, Luca; Ph, Roche; Vajkoczy, Peter

doi:10.1007/s00701-014-2140-7

Cited by 47 publications

(23 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meling and the support of a constructive strategy regarding unruptured brain AVM. The results of the ARUBA trial have been widely commented on and the weaknesses of the study have been pointed out, i.e., the lack of differentiation between Spetzler-Martin grades and treatment modalities, and the fact that the effect of microsurgical removal was not assessed by the study design [4,8,9]. The report of the Scottish Audit of Intracranial Vascular Malformations drew less attention, but provided essentially the same result that intervention led to a worse outcome compared to the natural history [1].…”

mentioning

confidence: 99%

Treatment of unruptured brain AVM in the aftermath of ARUBA and the Scottish Audit of Intracranial Vascular Malformations

Steiger

Schaller

2015

Acta Neurochir

View full text Add to dashboard Cite

We appreciate the thoughtful comments of T.R. Meling and the support of a constructive strategy regarding unruptured brain AVM. The results of the ARUBA trial have been widely commented on and the weaknesses of the study have been pointed out, i.e., the lack of differentiation between Spetzler-Martin grades and treatment modalities, and the fact that the effect of microsurgical removal was not assessed by the study design [4,8,9]. The report of the Scottish Audit of Intracranial Vascular Malformations drew less attention, but provided essentially the same result that intervention led to a worse outcome compared to the natural history [1]. The results of ARUBA and the Scottish Audit of Intracranial Vascular Malformations showed an almost identical pattern of strokes following intervention, with initially a higher rate of events than in untreated patients and secondary regression to the rate of the natural history. Therefore, we have to accept that the way we have been treating unruptured AVM was not right and needs correction.As pointed out by Meling, the treatment-associated morbidity rates as given in the ARUBA trial, and also the Scottish Audit, are very different from the rates given in microsurgical series. The high morbidity rates of ARUBA and the Scottish Audit are the footprint of destabilized and incompletely eliminated AVM, i.e., the pattern of endovascular embolization [19]. Without any doubt, radiosurgery contributed to the continuing stroke rate in the interventional cohorts but was unlikely a major factor for the increased rate following intervention.Despite the obvious pattern of the delayed hemorrhages in the ARUBA and the Scottish Audit cohorts, questions remain. All non-randomized series provided rates of stroke after microsurgery, radiosurgery, and embolization far below the 9-10 % per year rate of ARUBA and the Scottish Audit. Probability of hemorrhage after successful microsurgery appears, however, to be approximately one-tenth the rate after endovascular embolization, according to the meta-analysis of van Beijnum [19]. Although the numbers of hemorrhages given in nonrandomized series remain far below the incidence rates in ARUBA and the Scottish cohort, it appears likely that endovascular therapy was the primary factor for the exorbitant event rate following intervention. Analyzing all published series, van Beijnum and coworkers found reported annual hemorrhage rates of 0.18 % after microsurgery 1.7 % after stereotactic radiosurgery and 1.7 % after embolization. The obvious destabilizing effect resulting from treatment as seen in the ARUBA and Scottish Audit cohorts is hardly explainable by radiosurgery.Endovascular intranidal embolization emerged in the 1980s as a minimally invasive alternative to surgical elimination. It was soon realized, however, that complete elimination could not be routinely achieved. The introduction of Onyx, offering more controllable intranidal dispersion, did not change the picture fundamentally, achieving complete elimination in maximally 50 % [5,13,16]. Emboliza...

show abstract

mentioning

confidence: 99%

Treatment of unruptured brain AVM in the aftermath of ARUBA and the Scottish Audit of Intracranial Vascular Malformations

Steiger

Schaller

2015

Acta Neurochir

View full text Add to dashboard Cite

show abstract

“…[2][3][4]10,11,20,[22][23][24]31,36,43 A related concern was the aggregation of the various treatment modalities that perhaps preferably should have been tested separately. 2,5,10,11,13,18,20,[23][24][25]33,43,46,53 The approach adopted by ARUBA's designers was that the variety of patients and treatment choices were a fact of life, to be accepted as such. 29 Heterogeneity can provide in ductive strength to pragmatic trial results.…”

Section: Concerns Regarding the Heterogeneity Of Patients And The Gromentioning

confidence: 99%

“…3,20,[22][23][24][25]33,46,49 The protocol mentioned that this (12) Amin choice of primary end point would "avert judgment about severity," while a secondary end point (modified Rankin Scale [mRS] score > 1) concentrated on significant events associated with impairment. The reasoning behind these choices is that most patients with unruptured AVMs are neurologically intact.…”

Section: Concerns Regarding the Choice Of Outcome Measuresmentioning

confidence: 99%

“…Many authors noted the gap between the number of screened patients and those enrolled, 1,20,24,44 and either sus pected that selection had taken place, [2][3][4] or hypothesized that many patients must have been treated outside the trial. 3,4,22,49 Others remarked that few (American) major surgical centers participated, [2][3][4]22 or that few patients were treated with resection alone.…”

Section: Slow Recruitmentmentioning

confidence: 99%

See 1 more Smart Citation

Responses to ARUBA: a systematic review and critical analysis for the design of future arteriovenous malformation trials

Magro

Gentric

Darsaut

et al. 2017

JNS

View full text Add to dashboard Cite

Brain arteriovenous malformations (AVMs) are a heterogeneous group of rare lesions that can pre sent with headaches, seizures, neurological deficits, and intracranial hemorrhages. Risks of hemorrhage have been estimated in the range of 2%-4% per year. 8,15,32,47 Risk factors for future ruptures have been identified, but their use to inform decision making is errorprone, given the methodological problems with AVM observational studies and the modest relative risks. The comments were categorized as items related to the design, the conduct, and the analysis and interpretation of the trial. results Thirty-one articles or letters were identified. The pragmatic design, with heterogeneity of patients and lack of standardization of the treatment arm, were frequently stated concerns. The choice of outcome measures was repeatedly criticized. During the trial, low enrollment rates, selection bias, and premature interruption of enrollment were frequent comments. The short follow-up period, the lack of subgroup analyses, the lack of details on the results of the various treatments, and a contentious interpretation of results were noted at the analysis stage. A fundamental problem was the primary hypothesis testing conservative management. The authors believe that other trials are needed. Future trials could be pragmatic, test interventions stratified at the time of randomization, and look for long-term, hard clinical outcomes in a large number of patients. coNclusioNs In the authors' view, the ARUBA trial is a turning point in the history of brain AVM management; future trials should aim at integrating trial methodology and clinical care in the presence of uncertainty.

show abstract

“…However, no treatment modality is without inherent risks, and in 2014, the ARUBA study concluded that the risk of any form of neurosurgical treatment was inferior to the natural history of unruptured bAVMs [13]. However, the ARUBA study has been heavily criticized because of its perceived lack of external validity, the wide heterogeneity of treatment modalities, and the scarcity of patients treated with microsurgery [12,16]. More recently, a European consensus conference, on behalf of the European Association of Neurosurgical Societies (EANS), the European Society of Interventional Therapy (ESMINT), and the European Society for Radiosurgery (EGKS), stated that BThe results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities^ [3].…”

Section: Treatmentmentioning

confidence: 99%