Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

TY - JOUR

T1 - Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance

AU - Durno, Carol

AU - Ercan, Ayse Bahar

AU - Bianchi, Vanessa

AU - Edwards, Melissa

AU - Aronson, Melyssa

AU - Galati, Melissa

AU - Atenafu, Eshetu G

AU - Abebe-Campino, Gadi

AU - Al-Battashi, Abeer

AU - Alharbi, Musa

AU - Azad, Vahid Fallah

AU - Baris, Hagit N

AU - Basel, Donald

AU - Bedgood, Raymond

AU - Bendel, Anne

AU - Ben-Shachar, Shay

AU - Blumenthal, Deborah T

AU - Blundell, Maude

AU - Bornhorst, Miriam

AU - Bronsema, Annika

AU - Cairney, Elizabeth

AU - Rhode, Sara

AU - Caspi, Shani

AU - Chamdin, Aghiad

AU - Chiaravalli, Stefano

AU - Constantini, Shlomi

AU - Crooks, Bruce

AU - Das, Anirban

AU - Dvir, Rina

AU - Farah, Roula

AU - Foulkes, William D

AU - Frenkel, Zehavit

AU - Gallinger, Bailey

AU - Gardner, Sharon

AU - Gass, David

AU - Ghalibafian, Mithra

AU - Gilpin, Catherine

AU - Goldberg, Yael

AU - Goudie, Catherine

AU - Hamid, Syed Ahmer

AU - Hampel, Heather

AU - Hansford, Jordan R

AU - Harlos, Craig

AU - Hijiya, Nobuko

AU - Hsu, Saunders

AU - Kamihara, Junne

AU - Kebudi, Rejin

AU - Knipstein, Jeffrey

AU - Koschmann, Carl

AU - Kratz, Christian

AU - Larouche, Valerie

AU - Lassaletta, Alvaro

AU - Lindhorst, Scott

AU - Ling, Simon C

AU - Link, Michael P

AU - Loret De Mola, Rebecca

AU - Luiten, Rebecca

AU - Lurye, Michal

AU - Maciaszek, Jamie L

AU - MagimairajanIssai, Vanan

AU - Maher, Ossama M

AU - Massimino, Maura

AU - McGee, Rose B

AU - Mushtaq, Naureen

AU - Mason, Gary

AU - Newmark, Monica

AU - Nicholas, Garth

AU - Nichols, Kim E

AU - Nicolaides, Theodore

AU - Opocher, Enrico

AU - Osborn, Michael

AU - Oshrine, Benjamin

AU - Pearlman, Rachel

AU - Pettee, Daniel

AU - Rapp, Jan

AU - Rashid, Mohsin

AU - Reddy, Alyssa

AU - Reichman, Lara

AU - Remke, Marc

AU - Robbins, Gabriel

AU - Roy, Sumita

AU - Sabel, Magnus

AU - Samuel, David

AU - Scheers, Isabelle

AU - Schneider, Kami Wolfe

AU - Sen, Santanu

AU - Stearns, Duncan

AU - Sumerauer, David

AU - Swallow, Carol

AU - Taylor, Leslie

AU - Thomas, Gregory

AU - Toledano, Helen

AU - Tomboc, Patrick

AU - Van Damme, An

AU - Winer, Ira

AU - Yalon, Michal

AU - Yen, Lee Yi

AU - Zapotocky, Michal

AU - Zelcer, Shayna

AU - Ziegler, David S

AU - Zimmermann, Stefanie

AU - Hawkins, Cynthia

AU - Malkin, David

AU - Bouffet, Eric

AU - Villani, Anita

AU - Tabori, Uri

PY - 2021/9/1

Y1 - 2021/9/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Brain Neoplasms/diagnosis

KW - Child

KW - Child, Preschool

KW - Colorectal Neoplasms/diagnosis

KW - DNA Mismatch Repair

KW - DNA Repair Enzymes/deficiency

KW - Early Detection of Cancer/methods

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Male

KW - Neoplastic Syndromes, Hereditary/diagnosis

KW - Population Surveillance

KW - Prognosis

KW - Prospective Studies

KW - Survival Rate

KW - United States/epidemiology

KW - Young Adult

U2 - 10.1200/JCO.20.02636

DO - 10.1200/JCO.20.02636

M3 - SCORING: Journal article

C2 - 33945292

VL - 39

SP - 2779

EP - 2790

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 25

ER -