Correspondence
3
4
5
Spetzler-Martin grade I or II, only five (4%) patients were treated with surgery alone. Most underwent embolisation or stereotactic radiosurgery, not the usual approach for low Spetzler-Martin grade arteriovenous malformations at many institutions. In a mean followup of less than 3 years, a staggering 33 haemorrhagic events occurred. For comparison, in a published series of 220 surgically treated SpetzlerMartin grade I or II arteriovenous malformations, there was an overall morbidity of only 0·9% with no postoperative haemorrhage over more than 1143 patient-years of follow-up.2 Additionally, our own experience with unruptured arteriovenous malformations in children (table), a cohort excluded in ARUBA, shows surgical outcomes are comparable to short-term natural history, suggesting a conferred long-term benefit. Although ARUBA might suggest poor early outcomes after stereotactic radiosurgery, embolisation, or both, of unruptured arteriovenous malformations, the analyses shown by the authors do not allow any conclusions to be drawn about surgical management.
Pierot L, Cognard C, Herbreteau D, et al. Endovascular treatment of brain arteriovenous malformations using a liquid embolic agent: results of a prospective, multicentre study (BRAVO). Eur Radiol 2013; 23: 2838–45. Starke RM, Yen CP, Ding D, Sheehan JP. A practical grading scale for predicting outcome after radiosurgery for arteriovenous malformations: analysis of 1012 treated patients. J Neurosurg 2013; 119: 981–87. Knopman J, Stieg PE. Management of unruptured brain arteriovenous malformations. Lancet 2014; 383: 581–83.
We read with interest the Article by J P Mohr and colleagues. 1 We submit that the authors’ conclusions regarding surgical therapy need to be reassessed. First, mean follow-up in the non-interventional group was 33·7 months (109 patients), corresponding to 306·1 patientyears. Eight haemorrhages (2·6% annual rate) and four ischaemic strokes (1·3%) occurred. Therefore, the overall annual stroke rate was 3·9% for untreated patients—an ominous natural history for untreated arteriovenous malformations, particularly in view of the young ages of the patients studied (mean 45 years). Second, although most of the 114 arteriovenous malformations in the interventional group were
Patients with unruptured AVMs (n)
We declare that we have no competing interests.
ARUBA Nat Hx
ARUBA Tx
109
114
Boston Children’s Hospital Tx 37
Spetzler-Martin grade I–II
55%
68%
68%
III
31%
25%
26%
IV
14%
7%
6%
..
4%
73%
Surgical treatment (%) Surgery with embolisation (%)
..
11%
27%
SRS/embolisation/SRS+embolisation (%)
..
68%
..
100%
18%
..
5·5%
21·9%
5·4%*
10·1%
30·7%
10·8%
2·8
2·7
3·2
No treatment (%) Haemorrhagic stroke (%) Death or stroke (%) Mean follow-up (years)
Nat Hx=natural history cohort. Tx=treatment cohort. AVM=arteriovenous malformation. SRS=stereotactic radiosurgery. *Two cases: one after preoperative embolisation and another from a recurrence. Table: Results of surgical treatment of unruptured arteriovenous malformations at Boston Children’s Hospital compared with in ARUBA1
www.thelancet.com Vol 383 May 10, 2014
*Bradley A Gross, R M Scott, Edward R Smith [email protected] Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA (BAG); and Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA (RMS, ERS) 1
2
Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unrupured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 2014; 383: 614–621. Morgan MK, Rochford AM, Tsahtsarlis A, Little N, Faulder KC. Surgical risks associated with the management of grade I and II brain arteriovenous malformations. Neurosurgery 2004; 54: 832–39.
Authors’ reply ARUBA1 is the first-ever randomised controlled trial comparing clinical outcome in patients with unruptured brain arteriovenous malformations managed either with or without preventive interventional therapy. The as-treated analysis showed a more than 5-fold increased risk of primary outcome events (ie, death or symptomatic stroke) for patients undergoing invasive therapy (hazard ratio 5·26, 95% CI 2·63–11·11), as well as a significantly increased risk of, at times, devastating neurological deficits after intervention (relative risk 2·77, 95% CI 1·20–6·25). Several letters to The Lancet have expressed concerns in regard to the actual representativeness of the ARUBA results. We are grateful to Rustam Al–Shahi Salman for alerting the readers to similar outcomes in the most recent Scotland epidemiological data: these prospective population-based data show patient characteristics, distribution of treatment methods, and clinical outcome results similar to those recorded in ARUBA1—another strong argument supporting the plausibility and generalisability of the trial results.2 In view of the unexpectedly high rate of primary outcome events in the interventional arm, the National Institutes of Health (NIH)-appointed Data and Safety Monitoring Board 1635
3
4
5
Spetzler-Martin grade I or II, only five (4%) patients were treated with surgery alone. Most underwent embolisation or stereotactic radiosurgery, not the usual approach for low Spetzler-Martin grade arteriovenous malformations at many institutions. In a mean followup of less than 3 years, a staggering 33 haemorrhagic events occurred. For comparison, in a published series of 220 surgically treated SpetzlerMartin grade I or II arteriovenous malformations, there was an overall morbidity of only 0·9% with no postoperative haemorrhage over more than 1143 patient-years of follow-up.2 Additionally, our own experience with unruptured arteriovenous malformations in children (table), a cohort excluded in ARUBA, shows surgical outcomes are comparable to short-term natural history, suggesting a conferred long-term benefit. Although ARUBA might suggest poor early outcomes after stereotactic radiosurgery, embolisation, or both, of unruptured arteriovenous malformations, the analyses shown by the authors do not allow any conclusions to be drawn about surgical management.
Pierot L, Cognard C, Herbreteau D, et al. Endovascular treatment of brain arteriovenous malformations using a liquid embolic agent: results of a prospective, multicentre study (BRAVO). Eur Radiol 2013; 23: 2838–45. Starke RM, Yen CP, Ding D, Sheehan JP. A practical grading scale for predicting outcome after radiosurgery for arteriovenous malformations: analysis of 1012 treated patients. J Neurosurg 2013; 119: 981–87. Knopman J, Stieg PE. Management of unruptured brain arteriovenous malformations. Lancet 2014; 383: 581–83.
We read with interest the Article by J P Mohr and colleagues. 1 We submit that the authors’ conclusions regarding surgical therapy need to be reassessed. First, mean follow-up in the non-interventional group was 33·7 months (109 patients), corresponding to 306·1 patientyears. Eight haemorrhages (2·6% annual rate) and four ischaemic strokes (1·3%) occurred. Therefore, the overall annual stroke rate was 3·9% for untreated patients—an ominous natural history for untreated arteriovenous malformations, particularly in view of the young ages of the patients studied (mean 45 years). Second, although most of the 114 arteriovenous malformations in the interventional group were
Patients with unruptured AVMs (n)
We declare that we have no competing interests.
ARUBA Nat Hx
ARUBA Tx
109
114
Boston Children’s Hospital Tx 37
Spetzler-Martin grade I–II
55%
68%
68%
III
31%
25%
26%
IV
14%
7%
6%
..
4%
73%
Surgical treatment (%) Surgery with embolisation (%)
..
11%
27%
SRS/embolisation/SRS+embolisation (%)
..
68%
..
100%
18%
..
5·5%
21·9%
5·4%*
10·1%
30·7%
10·8%
2·8
2·7
3·2
No treatment (%) Haemorrhagic stroke (%) Death or stroke (%) Mean follow-up (years)
Nat Hx=natural history cohort. Tx=treatment cohort. AVM=arteriovenous malformation. SRS=stereotactic radiosurgery. *Two cases: one after preoperative embolisation and another from a recurrence. Table: Results of surgical treatment of unruptured arteriovenous malformations at Boston Children’s Hospital compared with in ARUBA1
www.thelancet.com Vol 383 May 10, 2014
*Bradley A Gross, R M Scott, Edward R Smith [email protected] Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA (BAG); and Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA (RMS, ERS) 1
2
Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unrupured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet 2014; 383: 614–621. Morgan MK, Rochford AM, Tsahtsarlis A, Little N, Faulder KC. Surgical risks associated with the management of grade I and II brain arteriovenous malformations. Neurosurgery 2004; 54: 832–39.
Authors’ reply ARUBA1 is the first-ever randomised controlled trial comparing clinical outcome in patients with unruptured brain arteriovenous malformations managed either with or without preventive interventional therapy. The as-treated analysis showed a more than 5-fold increased risk of primary outcome events (ie, death or symptomatic stroke) for patients undergoing invasive therapy (hazard ratio 5·26, 95% CI 2·63–11·11), as well as a significantly increased risk of, at times, devastating neurological deficits after intervention (relative risk 2·77, 95% CI 1·20–6·25). Several letters to The Lancet have expressed concerns in regard to the actual representativeness of the ARUBA results. We are grateful to Rustam Al–Shahi Salman for alerting the readers to similar outcomes in the most recent Scotland epidemiological data: these prospective population-based data show patient characteristics, distribution of treatment methods, and clinical outcome results similar to those recorded in ARUBA1—another strong argument supporting the plausibility and generalisability of the trial results.2 In view of the unexpectedly high rate of primary outcome events in the interventional arm, the National Institutes of Health (NIH)-appointed Data and Safety Monitoring Board 1635
