Children ’ s Hospitals and Clinics of Minnesota

Background: Pleuropulmonary blastoma (PPB) is a rare malignant neoplasm of the lung presenting in early childhood. Three pathologic “Types” are recognized. The Types are manifestations of one disease along a time spectrum from birth to age ~72 months (7% of cases occur after age 72 months). Type I PPB is an air-filled purely cystic neoplasm (median diagnosis age 10 months) for which treatment is surgery with or without adjuvant chemotherapy. Type II PPB (cystic/solid) and Type III PPB (solid) are aggressive sarcomas (median diagnosis ages 33 and 44 months, respectively) for which treatments are surgery and multi-agent chemotherapy with or without radiation therapy. PPB has strong genetic implications with a unique set of associated neoplasia and dysplasia in the patient or family occurring mostly in childhood and adolescence. Lung cysts and cystic nephroma are the most common associated conditions. The International PPB Registry (IPPBR) has recently reported germline loss-of-function mutations in the gene DICER1 in PPB patients and family members. There has never been a large prospective study of PPB therapy. It is estimated that 30-50 cases of Type I PPB and 40-60 cases of Types II and III PPB are diagnosed annually worldwide. Consultations among international pediatric sarcoma experts concluded that because of (1) the rarity of PPB, (2) regulatory complexity and (3) regulatory differences between countries, a prospective treatment study could not be organized. Therefore, to collect a large group of Types I, II and III PPB patients for event-free and overall survival analysis, this project is organized as a “Treatment and Biology Registry” for the collection of treatment data on patients for whom therapy decisions are made by each institution. PPB therapy choices are the decision of each institution. This Treatment and Biology Registry presents surgery and chemotherapy guidelines. Through this Registry, it is anticipated that analysis of a group of similarly treated children with PPB will advance the knowledge of effective ways to treat PPB. Treatment and Biology Registry Design and Goals:  Type I PPB: Type I PPB is an early manifestation of this malignant disease, cured in some cases by surgery. Therapy decisions are the responsibility of the treating institution. Surgical guidelines are presented. It is unknown whether adjuvant chemotherapy improves cure rates for Type I PPB patients. If the treating physicians select adjuvant chemotherapy treatment, the Treatment and Biology Registry guideline is a 41-week “VAC” regimen.  Types II and III PPB: Types II and III PPB are aggressive sarcomas. Surgery and chemotherapy are necessary in all cases. Specific therapy decisions are the responsibility of the treating institution. Surgical guidelines are presented. The Treatment and Biology Registry chemotherapy guideline is a single-arm multi-agent chemotherapy neo-adjuvant/adjuvant regimen (“IVADo”) for 36 weeks. Second and