International Pleuropulmonary Blastoma (PPB) Treatment and Biology Registry

This Registry will collect family medical history and establishes a collection of specimens
from PPB patients and their parents for future research. Primary goals of the biology
research are (1) to identify new scientific ways to learn about PPB and the best way to treat
it in the future and (2) to establish a collection of PPB biologic specimens for future
research.

Background: PPB is a rare cancer of the lung presenting in early childhood, mostly from birth
to age ~72 months. PPB occurs within the lung or between the lung and the chest wall. There
are three forms of PPB called Types I, II, and III PPB. Children with Type I PPB require
surgery and sometimes chemotherapy. Children with Types II and III PPB, require surgery,
chemotherapy and sometimes radiation therapy. Because there has never been a consensus as to
the best treatment for PPB, the Registry will provide treatment guidelines. It is the goal of
the Treatment and Biology Registry that by offering specific regimens the Registry will be
able to prospectively review and analyze the regimen for the first time.

Design:

- Diagnostic central pathology review will be required for patients who will be
prospectively evaluated.

- This Treatment Registry will offer surgery and chemotherapy regimen guidelines, and
optional radiation therapy guidelines for prospectively enrolled patients.

- The Treatment and Biology Registry will create a PPB biologic specimens reference bank
for tumor.

Methods:

- For Type I PPB, surgery is necessary. Some doctors use chemotherapy after surgery. If
chemotherapy is used the Registry will suggest that it be combination chemotherapy with
vincristine, dactinomycin, cyclophosphamide (VAC ).

- For Types II and III PPB patients surgery is necessary, followed by chemotherapy. The
Registry will suggest that subjects receive combination chemotherapy with Ifosphamide,
Vincristine, Actinomycin-D and Doxorubicin (IVADo). Second look and possible 3rd look
surgery may be required. Radiation therapy is recommended only for residual disease
after maximum surgery.

Analysis: Statistical data analysis will include only centrally confirmed cases. Additionally
only patients with PPB Type II or Type III who were enrolled and treated with IVADo as per
the regimen will be compared to historical controls. No statistical analysis is planned for
patients with Type I PPB. Future treatment will be compared to the IVADo regimen in order to
measure improvements.

Inclusion Criteria:

1. Age : Patients from birth to < 21 years of age at the time of diagnosis will be
included in the Treatment and Biology Registry.

Patients of any age will be included in the Associated Diseases arm of this study.

2. Pathology Diagnosis: Patients with newly-diagnosed PPB Types I, II or III. Diagnosis
is made by the local pathologist. Real-time central pathology review is encouraged but
is not required. All cases must be submitted for central pathology review. Only
centrally-reviewed cases confirmed as PPB will be analyzed prospectively.

Cases in which the initial diagnosis is "suggestive" or "supportive" of PPB, but not
diagnostic, and in which later resection specimens, including resections following
chemotherapy, confirm a PPB diagnosis will be included. Patients diagnosed by fine
needle aspiration biopsy will be included only if a later resection specimen,
including resections following chemotherapy, is diagnostic of PPB.

Diagnostic pathology for cases of diseases associated with PPB will also require
registry central pathology review.

3. Prior Therapy: PPB Type I: All patients are eligible and will be followed in the
study.

PPB Types II or III: Newly-diagnosed Types II and III PPB patients will be included in
the Treatment and Biology Registry.

DICER1-related condition and DICER1 gene mutation: all patients are eligible and will
be followed in the study.

4. Prior corticosteroid therapy is allowed.

5. Patients who have received other chemotherapy regimens or radiation therapy will not
be statistical analysis.

6. Types II and III PPB patients with PRIOR Type I PPB diagnosis: Types II and III PPB
cases which are recurrences of an earlier Type I PPB are included.

7. Informed consent by patient or parent/guardian. (also, where appropriate: assent and
HIPPA consent)

Exclusion Criteria:

1. Inability of patient, or parent/guardian to obtain informed consent.

2. Patients who have their PPB diagnosed ruled out by Registry central pathology review.