Surgical treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial
Authors: Darsaut Tim E. , Magro Elsa , Bojanowski Michel W. , Chaalala Chiraz , Nico Lorena , Bacchus Emma , Klink Ruby , Iancu Daniela , Weill Alain , Roy Daniel , Sabatier Jean-Francois , Cognard Christophe , Januel Anne-Christine , Pelissou-Guyotat Isabelle , Eker Omer , Roche Pierre-Hugues , Graillon Thomas , Brunel Hervé , Proust Francois , Beaujeux Rémy , Aldea Sorin , Piotin Michel , Cornu Philippe , Shotar Eimad , Gaberel Thomas , Barbier Charlotte , Corre Marine Le , Costalat Vincent , Jecko Vincent , Barreau Xavier , Morandi Xavier , Gauvrit Jean-Yves , Derrey Stéphane , Papagiannaki Chrysanthi , Nguyen Thanh N. , Abdalkader Mohamad , Tawk Rabih G. , Huynh Thien , Viard Geraldine , Gevry Guylaine , Gentric Jean-Christophe , Raymond Jean , _ _ , _ _ , Raymond Jean , Roy Daniel , Weill Alain , Iancu Daniela , Bojanowski Michel W. , Chaalala Chiraz , Darsaut Tim E. , Rempel Jeremy L. , O’Kelly Cian J. , Chow Michael M. C. , Findlay J. Max , Fahed Robert , Lesiuk Howard , Drake Brian , Santos Marlene dos , Gentric Jean-Christophe , Magro Elsa , Seizeur Romuald , Nonent Michel , Timsit Serge , Pradier Olivier , Ognard Julien , El-Aouni Mourad Cheddad , Desal Hubert , Boursier Romain , Thillays François , Roualdes Vincent , Piotin Michel , Aldea Sorin , Blanc Raphael , Cognard Christophe , Januel Anne-Christine , Sabatier Jean-François , Calviere Lionel , Gauvrit Jean Yves , Lecouillard Isabelle , Morandi Xavier , Nouhaud Elodie , Raoult Hélène , Eugene François , Bras Anthony Le , Ferre Jean-Christophe , Paya Christophe , Ronziere Thomas , Trystram Denis , Naggara Olivier , Rodriguez-Regent Christine , Kerleroux Basile , Gaberel Thomas , Barbier Charlotte , Emery Evelyne , Touze Emmanuel , Papagiannaki Chrysanthi , Derrey Stephane , Pellisou-Guyotat Isabelle , Eker Omer , Guyotat Jacques , Berhouma Monsef , Riva Roberto , Dumot Chloé , Biondi Alessandra , Thines Laurent , Charbonnier Guillaume , Bougaci Nassim , Bracard Serge , Anxionnat René , Bernier-Chastagner Valérie , Civit Thierry , Gory Benjamin , Barreau Xavier , Jecko Vincent , Penchet Guillaume , Gimbert Edouard , Marnat Gaulthier , Huchet Aymeri , Herbreteau Denis , Boulouis Grégoire , Velut Stéphane , Bibi Richard , Ifergan Héloïse , Janot Kévin , Roche Pierre-Hugues , Graillon Thomas , Brunel Hervé , Peyriere Hadrien , Kaya Jean-Marc , Touta Adamou , Troude Lucas , Boissonneau Sébastien , Shotar Eimad , Boch Anne-Laure , Cornu Philippe , Clarençon Frédéric , Sourour Nader , Nouet Aurélien , Lenck Stéphanie , Premat Kévin , Costalat Vincent , Corre Marine Le , Bonafe Alain , Dargazanli Cyril , Gascou Gregory , Lefevre Pierre-Henri , Riquelme Carlos , Proust Francois , Beaujeux Rémy , Cebula Hélène , Ollivier Irène , Pop Raoul , Spatola Giorgio , Spelle Laurent , Chalumeau Vanessa , Gallas Sophie , Ikka Léon , Mihalea Cristian , Ozanne Augustin , Caroff Jildaz , Chabert Emmanuel , Mounayer Charbel , Rouchaud Aymeric , Caire Francois , Ricolfi Frédéric , Cao Catherine , Mourier Klaus-Luc , Thouant Pierre , Farah Walid , Nguyen Thanh N. , Abdalkader Mohamad , Tawk Rabih G. , Huynh Thien , Carlson Andrew P. , Silva Luciana Alves Oliveira , Froio Nayara de Lima , Silva Gisele Sampaio , Mont’Alverne Francisco J. A. , Martins Jose Luri , Mendes George Nunes , Miranda Rodrigo Rivera 
Published: September 2022

OBJECTIVE
The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry.

METHODS
TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2.

RESULTS
From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I–II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%–93%) and 105/110 low-grade (95%, 95% CI 90%–98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%–18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%–28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%–9%), 5 (83%) of whom had complications due to preoperative embolization.

CONCLUSIONS
The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs.
Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov)