Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

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.

Comparison of treatment outcomes of childhood Hodgkin lymphoma in two US centers and a center in Recife, Brazil.

BACKGROUND: Pediatric Hodgkin lymphoma (HL) has a cure rate of more than 80% in high-income countries (HIC). However, more than 80% of the world's children live in low-income countries (LIC), where the cure rate is often much lower. PROCEDURE: We compared the outcome of HL of 371 patients treated at two pediatric oncology centers in the US to that of 62 patients treated at one center in Recife, Brazil (IMIP) to determine whether the same treatment strategy should be used in both high-income and LIC. The logrank test was used to compare event-free and overall survival. RESULTS: The percentages of patients with unfavorable disease at each center were similar (P = 0.72). Patients with favorable disease at IMIP had estimated 5-year survival rates comparable to those of the US centers (100% and 99%, respectively). Among patients with unfavorable disease, those treated at IMIP had a 5-year event-free survival (EFS) rate of 60%, compared to 78% at the US centers; (P = 0.08). The 5-year survival estimate after relapse was 25% at IMIP versus 61% at the US centers (P = 0.08). The 5-year overall survival for patients with unfavorable disease was 72% at IMIP versus 90% at the US centers (P = 0.01). CONCLUSIONS: Intensive frontline therapy should be considered for patients with unfavorable HL in LIC where the relapse rate is high and the salvage rate is low, provided that supportive care is adequate.