Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance
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Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance. / 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.
In: J CLIN ONCOL, Vol. 39, No. 25, 01.09.2021, p. 2779-2790.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -