| Title: |
Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance |
| Authors: |
Durno, C; Ercan, AB; Bianchi, V; Edwards, M; Aronson, M; Galati, M; Atenafu, EG; Abebe-Campino, G; Al-Battashi, A; Alharbi, M; Azad, VF; Baris, HN; Basel, D; Bedgood, R; Bendel, A; Ben-Shachar, S; Blumenthal, DT; Blundell, M; Bornhorst, M; Bronsema, A; Cairney, E; Rhode, S; Caspi, S; Chamdin, A; Chiaravalli, S; Constantini, S; Crooks, B; Das, A; Dvir, R; Farah, R; Foulkes, WD; Frenkel, Z; Gallinger, B; Gardner, S; Gass, D; Ghalibafian, M; Gilpin, C; Goldberg, Y; Goudie, C; Hamid, SA; Hampel, H; Hansford, JR; Harlos, C; Hijiya, N; Hsu, S; Kamihara, J; Kebudi, R; Knipstein, J; Koschmann, C; Kratz, C; Larouche, V; Lassaletta, A; Lindhorst, S; Ling, SC; Link, MP; De Mola, RL; Luiten, R; Lurye, M; Maciaszek, JL; MagimairajanIssai, V; Maher, OM; Massimino, M; McGee, RB; Mushtaq, N; Mason, G; Newmark, M; Nicholas, G; Nichols, KE; Nicolaides, T; Opocher, E; Osborn, M; Oshrine, B; Pearlman, R; Pettee, D; Rapp, J; Rashid, M; Reddy, A; Reichman, L; Remke, M; Robbins, G; Roy, S; Sabel, M; Samuel, D; Scheers, I; Schneider, KW; Sen, S; Stearns, D; Sumerauer, D; Swallow, C; Taylor, L; Thomas, G; Toledano, H; Tomboc, P; Van Damme, A; Winer, I; Yalon, M; Yen, LY; Zapotocky, M; Zelcer, S; Ziegler, DS |
| Publisher Information: |
LIPPINCOTT WILLIAMS & WILKINS |
| Publication Year: |
2021 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0732-183X |
| Relation: |
https://hdl.handle.net/11343/281718 |
| Availability: |
https://hdl.handle.net/11343/281718 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.F423841B |
| Database: |
BASE |