Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance
(2021) Journal of clinical oncology — Vol. 39, n° 25, p. 2779-2790 (2021)
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- Authors
Ercan, Ayse Bahar 
Tabori, Uri
- Abstract
- (en) 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.
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Citations
Durno, C., Ercan, A. B., Bianchi, V., Edwards, M., Aronson, M., Galati, M., Atenafu, E. G., Abebe-Campino, G., Al-Battashi, A., Alharbi, M., Azad, V. F., Baris, H. N., Basel, D., Bedgood, R., Bendel, A., Ben-Shachar, S., Blumenthal, D. T., Blundell, M., Bornhorst, M., et al. (2021). Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance. Journal of clinical oncology, 39(25), 2779-2790. https://doi.org/10.1200/jco.20.02636 (Original work published 2021)