Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance. Issue 25 (1st September 2021)

• Record Type: Journal Article
• Authors: Durno, Carol; Ercan, Ayse Bahar; Bianchi, Vanessa; Edwards, Melissa; Aronson, Melyssa; Galati, Melissa; Atenafu, Eshetu G.; Abebe-Campino, Gadi; Al-Battashi, Abeer; Alharbi, Musa; Azad, Vahid Fallah; Baris, Hagit N.; Basel, Donald; Bedgood, Raymond; Bendel, Anne; Ben-Shachar, Shay; Blumenthal, Deborah T.; Blundell, Maude; Bornhorst, Miriam; Bronsema, Annika; Cairney, Elizabeth; Rhode, Sara; Caspi, Shani; Chamdin, Aghiad; Chiaravalli, Stefano; Constantini, Shlomi; Crooks, Bruce; Das, Anirban; Dvir, Rina; Farah, Roula; Foulkes, William D.; Frenkel, Zehavit; Gallinger, Bailey; Gardner, Sharon; Gass, David; Ghalibafian, Mithra; Gilpin, Catherine; Goldberg, Yael; Goudie, Catherine; Hamid, Syed Ahmer; Hampel, Heather; Hansford, Jordan R.; Harlos, Craig; Hijiya, Nobuko; Hsu, Saunders; Kamihara, Junne; Kebudi, Rejin; Knipstein, Jeffrey; Koschmann, Carl; Kratz, Christian; Larouche, Valerie; Lassaletta, Alvaro; Lindhorst, Scott; Ling, Simon C.; Link, Michael P.; Loret De Mola, Rebecca; Luiten, Rebecca; Lurye, Michal; Maciaszek, Jamie L.; MagimairajanIssai, Vanan; Maher, Ossama M.; Massimino, Maura; McGee, Rose B.; Mushtaq, Naureen; Mason, Gary; Newmark, Monica; Nicholas, Garth; Nichols, Kim E.; Nicolaides, Theodore; Opocher, Enrico; Osborn, Michael; Oshrine, Benjamin; Pearlman, Rachel; Pettee, Daniel; Rapp, Jan; Rashid, Mohsin; Reddy, Alyssa; Reichman, Lara; Remke, Marc; Robbins, Gabriel; Roy, Sumita; Sabel, Magnus; Samuel, David; Scheers, Isabelle; Schneider, Kami Wolfe; Sen, Santanu; Stearns, Duncan; Sumerauer, David; Swallow, Carol; Taylor, Leslie; Thomas, Gregory; Toledano, Helen; Tomboc, Patrick; Van Damme, An; Winer, Ira; Yalon, Michal; Yen, Lee Yi; Zapotocky, Michal; Zelcer, Shayna; Ziegler, David S.; Zimmermann, Stefanie; Hawkins, Cynthia; Malkin, David; Bouffet, Eric; Villani, Anita; Tabori, Uri;
• Is Part Of: Journal of clinical oncology. Volume 39:Issue 25(2021)
• Page Start: 2779
• Page End: 2790
• Publication Date: 2021-09-01
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.20.02636
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed a surveillance protocol for early tumor detection in these individuals. PATIENTS AND METHODS: Data were collected from patients with confirmed CMMRD who were registered in the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of the surveillance protocol, and malignant transformation of low-grade lesions were examined for the entire cohort. Survival outcomes were analyzed for patients followed prospectively from the time of surveillance implementation. RESULTS: A total of 193 malignant tumors in 110 patients were identified. Median age of first cancer diagnosis was 9.2 years (range: 1.7-39.5 years). For patients undergoing surveillance, all GI and other solid tumors, and 75% of brain cancers were detected asymptomatically. By contrast, only 16% of hematologic malignancies were detected asymptomatically ( P < .001). Eighty-nine patients were followed prospectively and used for survival analysis. Five-year overall survival (OS) was 90% (95% CI, 78.6 to 100) and 50% (95% CI, 39.2 to 63.7) when cancer was detected asymptomatically and symptomatically, respectively ( P = .001). Patient outcome measured by adherence to the surveillance protocol revealed 4-year OS of 79% (95% CI, 54.8 to 90.9) for patients undergoing full surveillance, 55% (95% CI, 28.5 to 74.5) for partial surveillance, and 15% (95% CI, 5.2 to 28.8) for those not under surveillance ( P < .0001). Of the 64 low-grade tumors detected, the cumulative likelihood of transformation from low-to high-grade was 81% for GI cancers within 8 years and 100% for gliomas in 6 years. CONCLUSION: Surveillance and early cancer detection are associated with improved OS for individuals with CMMRD.