International PPB/DICER1 Registry

Официальное название

International Pleuropulmonary Blastoma/DICER1 Registry (for PPB, DICER1 and Associated Conditions)

Обзор

Pleuropulmonary blastoma (PPB) is a rare malignant neoplasm of the lung presenting in early childhood. Type I PPB is a purely cystic lesion, Type II is a partially cystic, partially solid tumor, Type III is a completely solid tumor. Treatment of children with PPB is at the discretion of the treating institution. This study builds off of the 2009 study and will also seek to enroll individuals with DICER1-associated conditions, some of whom may present only with the DICER1 gene mutation, which will help the Registry understand how these tumors and conditions develop, their clinical course and the most effective treatments.

Подробное описание

PPB is a rare cancer of the lung presenting in early childhood, mostly commonly from birth to age \~72 months. PPB occurs within the lung or between the lung and the chest wall. There are three primary forms of PPB called Types I, II, and III PPB. PPB is related to an underlying change/mutation in a gene called DICER1 which impacts gene expression and cell growth. DICER1 mutations may also lead to the development of other tumors in children and adults.

The International PPB/DICER1 Registry offers information based on previous data from Registry participants and the medical literature and collaborative efforts with international rare tumor groups.

Retrospective and real-time central pathology review is encouraged. Therapy decisions remain at the discretion of the treating institution.

Children with Type I PPB require surgery and sometimes chemotherapy. 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. Chemotherapy options include a 22-week regimen: 4 courses of vincristine, actinomycin D and cyclophosphamide (VAC) followed by 3 courses of vincristine and actinomycin D (VA).

Children with Types II and III PPB, require surgery, chemotherapy and sometimes radiation therapy. Many children with Types II or III PPB receive a single-arm multi-agent chemotherapy neo-adjuvant/adjuvant regimen of IVADo (ifosfamide, vincristine, actinomycin, doxorubicin) for 36 weeks. Second and possible 3rd look surgery may be considered for local control. Radiation therapy may be considered.

Первичные конечные точки

• Event-free survival [Срок оценки: 7 years]

Вторичные конечные точки (6)

• Overall response to chemotherapy [Срок оценки: 7 years]
• Overall survival [Срок оценки: 7 years]
• Quality of life outcomes in individuals diagnosed with PPB. [Срок оценки: 7 years]
• Cardiac outcomes in individuals diagnosed with PPB. [Срок оценки: 7 years]
• Pulmonary function testing results in individuals diagnosed with PPB [Срок оценки: 7 years]
• Incidence of neoplasms in individuals with DICER1-related conditions or germline DICER1 variants. mutation. [Срок оценки: 7 years]

Критерии участия

Критерии включения

• Known or suspected PPB or related thoracic tumor
• Known or suspected sex-cord stromal tumor including Sertoli-Leydig cell tumor and gynandroblastoma (males or females)
• Other known or suspected DICER1-related condition including ovarian sarcoma, cystic nephroma, renal sarcoma, pineoblastoma, pituitary blastoma, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma and others
• Individuals with known or suspected DICER1 pathogenic variation regardless of whether they have an established DICER1-associated condition
• Informed consent by patient/ or parent/guardian (also, where appropriate: assent and HIPAA consent)

Критерии исключения

Absence of appropriate consent for Registry participation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• Children's Minnesota — Minneapolis

Публикации

• Vasta LM, McMaster ML, Harney LA, Ling A, Kim J, Harris AK, Carr AG, Damrauer SM, Rader DJ, Kember RL, Kanetsky PA, Nathanson KL, Pyle LC, Greene MH, Schultz KA, Stewart DR; Regeneron Genetics Center (RGC) Research Team. Lack of pathogenic germline DICER1 variants in males with testicular germ-cell tumors. Cancer Genet. 2020 Oct;248-249:49-56. doi: 10.1016/j.cancergen.2020.10.002. Epub 2020 Oct 24 PMID 33158809
• Bisogno G, Sarnacki S, Stachowicz-Stencel T, Minard Colin V, Ferrari A, Godzinski J, Gauthier Villars M, Bien E, Hameury F, Helfre S, Schneider DT, Reguerre Y, Lopez Almaraz R, Janic D, Cesen M, Kolenova A, Rascon J, Martinova K, Cosnarovici R, Pourtsidis A, Ben Ami T, Roganovic J, Koscielniak E, Schultz KAP, Brecht IB, Orbach D. Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PAR PMID 33826235
• Schneider DT, Orbach D, Ben-Ami T, Bien E, Bisogno G, Brecht IB, Cecchetto G, Ferrari A, Godzinski J, Janic D, Lopez Almaraz R, Pourtsidis A, Roganovic J, Schultz KAP, Stachowicz-Stencel T, Fresneau B. Consensus recommendations from the EXPeRT/PARTNER groups for the diagnosis and therapy of sex cord stromal tumors in children and adolescents. Pediatr Blood Cancer. 2021 Jun;68 Suppl 4:e29017. doi: PMID 33760357
• Ferguson MJ, Ivanovich J, Stansell P, Vik TA, Helvie AE, Schmitt MR, Schultz KA, Dehner LP, Renbarger JL, Marshall MS. Previously unreported somatic variants in two patients with pleuropulmonary blastoma with metastatic brain recurrence. Pediatr Blood Cancer. 2021 May;68(5):e28825. doi: 10.1002/pbc.28825. Epub 2020 Nov 30. No abstract available. PMID 33258270
• Schneider KW, Cost NG, Schultz KAP, Svihovec S, Suttman A. Germline predisposition to genitourinary rhabdomyosarcoma. Transl Androl Urol. 2020 Oct;9(5):2430-2440. doi: 10.21037/tau-20-76. PMID 33209717
• Schultz KAP, Rednam SP, Kamihara J, Doros L, Achatz MI, Wasserman JD, Diller LR, Brugieres L, Druker H, Schneider KA, McGee RB, Foulkes WD. PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood. Clin Cancer Res. 2017 Jun 15;23(12):e76-e82. doi: 10.1158/1078-0432.CCR-17-0629. PMID 28620008
• Schultz KAP, Nelson AT, Kamihara J, Bauer AJ, Hatton J, Merideth MA, Stratton P, Harris AK, Field A, Dehner LP, Stewart DR, Hill DA, Messinger YH. DICER1-Related Tumor Predisposition. 2014 Apr 24 [updated 2026 Mar 25]. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http: PMID 24761742
• Gonzalez IA, Stewart DR, Schultz KAP, Field AP, Hill DA, Dehner LP. DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma. Mod Pathol. 2022 Jan;35(1):4-22. doi: 10.1038/s41379-021-00905-8. Epub 2021 Oct 1. PMID 34599283

Идентификаторы

NCT: NCT03382158 · FDAAA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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