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

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&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 &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.