RARE-17. SURVIVAL BENEFIT FOR INDIVIDUALS WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME AND BRAIN TUMORS WHO UNDERGO SURVEILLANCE PROTOCOL. A REPORT FROM THE INTERNATIONAL REPLICATION REPAIR CONSORTIUM
Authors: Ayse Bahar Ercan, Carol Durno, Vanessa J Bianchi, Melissa Edwards, Melyssa Aronson, Eric Bouffet, Abeer Al-Battashi, Musa Alharbi, Donald Basel, Raymond Bedgood, Anne Bendel, Deborah T Blumenthal, Miriam Bornhorst, Annika Bronsema, Elizabeth Cairney, Sara Carroll, Aghiad Chamdin, Stefano Chiaravalli, Shlomi Constantini, Anirban Das, Rina Dvir, Roula Farah, William Foulkes, Zehavit Frenkel, Sharon Gardner, Mithra Ghalibafian, Cathy Gilpin, Catherine Goudie, Syed Ahmer Hamid, Jordan Hansford, Craig Harlos, Nobuko Hijiya, Saunders Hsu, Junne Kamihara, Jeffrey Knipstein, Carl Koschmann, Valerie Larouche, Alvaro Lassaletta, Scott Lindhorst, Simon Ling, Michael Link, Rebecca Loret De Mola, Rebecca Luiten, Michal Lurye, Jamie Maciaszek, Vanan Magimairajan, Ossama Maher, Maura Massimino, Naureen Mushtaq, Monica Newmark, Garth Nicholas, Kim Nichols, Theodore Nicolaides, Enrico Opocher, Michael Osborn, Benjamin Oshrine, Rachel Pearlman, Daniel Pettee, Jan Rapp, Mohsin Rashid, Alyssa Reddy, Lara Reichman, Marc Remke, Gabriel Robbins, Magnus Sabel, David Samuel, Isabelle Scheers, Santanu Sen, Duncan Stearns, David Sumerauer, Carol Swallow, Leslie Taylor, Helen Toledano, Patrick Tomboc, An Van Damme, Ira Winer, Michal Yalon, Lee Yi Yen, Michal Zapotocky, Vahid Fallah Azad, Shayna Zelcer, David Ziegler, Stefanie Zimmerman, Uri Tabori
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Constitutional mismatch repair deficiency syndrome (CMMRD) is a severe cancer predisposition syndrome resulting in early onset central nervous system (CNS) and other cancers. International guidelines for surveillance exist but no study has systematically evaluated the efficacy of this protocol. METHODS We surveyed all confirmed CMMRD patients in the International Replication Repair Deficiency Consortium. A surveillance protocol consisting of frequent biochemical, endoscopic and imaging (CNS and total body MRI) studies were employed. Survival analyses and efficacy of each method were assessed. RESULTS Surveillance data were collected from 105 CMMRD individuals from 41 countries. Of the 193 malignant tumors, CNS malignancies were the most common (44%). The surveillance protocol uncovered 49 asymptomatic tumors including 16 glioblastomas and medulloblastomas. Five-year overall survival was 89% for tumors discovered by surveillance, and 61% for symptomatic tumors (p&amp;lt;0.004). Similarly, 5-year survival was 82+/-11% and 24+/-6% for surveillance and non-surveillance of brain tumors (p=0.005). Yearly total body and q6 month brain MRI detected asymptomatic cancers in all but 3 symptomatic CNS gliomas. These were tumors uncovered when time between scans was &amp;gt;6 months as per protocol. Finally, of the low grade tumors identified asymptomatically, 5 were low grade gliomas. All of the low grade gliomas, which were not resected transformed to high grade tumors at a median of 1.6 ± 0.9 years. CONCLUSION These data support a survival benefit in CMMRD patients undergoing a surveillance protocol. Adherence to protocol and resection of lower grade lesions may improve survival for patients with CNS tumors.