Health-related quality of life in children and adolescents with pleuropulmonary blastoma: A report from the International PPB/DICER1 Registry.

PURPOSE: Pleuropulmonary blastoma (PPB) is the most common lung cancer of infancy and early childhood and is associated with germline DICER1 variants. Type I and Ir PPB are cystic lesions treated surgically, with a subset of children with type I receiving chemotherapy. Type II and III are more aggressive lesions, treated with surgery, intensive chemotherapy and potentially radiation. We sought to assess health-related quality of life (HRQoL) in children with PPB and known germline DICER1 variants. METHODS: Children with a diagnosis of PPB or germline DICER1 pathogenic variant without history of PPB or other DICER1-related neoplasm (DICER1+ only) were enrolled in the International PPB/DICER1 Registry. Parent reports for participants aged 2-17 years for the PedsQL v.4 and PedsQL Multidimensional Fatigue Scale v.3 were collected. Fatigue, physical, and psychosocial function scores were compared. RESULTS: Analysis included 84 participants (PPB type Ir = 20, type I = 15, type II/III = 27, DICER1+ only = 22). Total fatigue scores of participants with type I and II/III PPB were lower compared to DICER1+ only, with effect size larger in type II/III (-0.82 vs. -0.40). Total psychosocial and physical functioning scores were lower in participants with type I and type II/III PPB compared to DICER1+ only, with larger effects noted in type II/III. Female sex was suggestive of worse HRQoL for both type I/Ir and type II/III cohorts. CONCLUSIONS: These data demonstrate the importance of regular HRQoL assessment in patients with a history of PPB as well as the importance and feasibility of studying HRQoL in children with rare tumors.

DICER1-Related Tumor Predisposition: Identification of At-risk Individuals and Recommended Surveillance Strategies.

BACKGROUND: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the Registry's goals is to continue to refine these guidelines as additional data becomes available. EXPERIMENTAL DESIGN: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the National Cancer Institute Natural History of DICER1 Syndrome study. RESULTS: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli-Leydig cell tumor (SLCT) at a median age of 14 years (range: 11 months-66 years); 13% were diagnosed under age 8 years, the current age of onset of pelvic surveillance. Additionally, 4% of SLCTs were diagnosed before the age of 4 years. CONCLUSION: Ongoing data collection highlights the role of lung surveillance in the detection of early PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before age 8 years, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.