International Ovarian & Testicular Stromal Tumor Registry

Обзор

Rare tumors are understudied, yet have the potential to shed light on vast areas of cancer research. Ovarian sex cord-stromal tumors, rare tumors of childhood and young adulthood, have recently been found to be associated with a lung cancer of early childhood called pleuropulmonary blastoma (PPB). The cause of these ovarian tumors is unknown. DICER1 mutations are seen in the majority of children with PPB. Research shows DICER1 mutations are also seen in some patients with ovarian tumors. Like PPB, ovarian stromal tumors are highly curable when found in early stage; however, later forms of the disease are aggressive and often fatal. The International Ovarian Stromal Tumor Registry collects clinical and biologic data to understand why these tumors occur and how to treat them. Current work involves the study of the role of DICER1 and miRNA expression in ovarian stromal tumors. Understanding the clinical history, predisposing factors and DICER1 and miRNA expression in these ovarian tumors of childhood will lead to targeted screening and risk stratification for evidence-based treatment and biologically rational therapies. These efforts will improve the lives of children by increasing survival and reducing late effects. The specific goals of the International Ovarian and Testicular Stromal Tumor Registry are: 1. to understand risk factors by studying age, pathologic subtype, histopathologic features, tumor invasiveness, degree of differentiation, presence of metastasis 2. to collect information on personal and family history in order to refine the clinical characteristics of patients and families with and without germline DICER1 mutations and other genetic predisposing factors 3. to determine whether there is a pattern of gene expression or DNA alterations that correlate with predisposition to ovarian tumors, biologic behavior and clinical outcome 4. to determine optimal screening regimens 5. to use clinical data obtained through the Registry to refine treatment algorithms 6. to establish a collection of annotated biology specimens (tumor tissue and germline DNA) for future research

Подробное описание

The Registry collects and analyzes case-by-case data on ovarian and testicular stromal tumors. Cases are identified:

1. by referrals from clinicians or pathologists 2. by families initiating contact with the Registry 3. by Registry requests to authors of published cases to share further details

The data collected include:

1. clinical and laboratory findings 2. family history 3. imaging studies 4. surgery records 5. pathology records including review and study of pathology materials 6. treatment (surgery, chemotherapy, radiation) 7. recurrences or metastases 8. long-term follow-up

The demographic and clinical data are abstracted into a database secured by password protection. Each record in the database has a unique Registry number.

Enrollment in the OTST Registry is based on local diagnosis, but central pathology review is offered as a part of Registry procedures.

For each patient enrolled, the Registry will request 1) whole blood for DNA extraction and lymphoblastoid cell line generation 2) slides or snap frozen tumor tissue (if available), 3) paraffin blocks and/or scrolls and 4) fresh tissue. In some cases, saliva samples, buccal swabs or urine samples will be obtained for DNA extraction.

Pathology materials are centrally reviewed when available. Any discrepancies in the diagnostic interpretation are discussed with the submitting pathologist or clinician. When the central review pathologist cannot confirm diagnosis of a stromal tumor, the referring physician is notified. The local pathologist retains responsibility for the final pathological diagnosis. It is the responsibility of the referring physician to notify the patient regarding any discrepancy found.

Biologic specimens will be banked and stored for future research.

Первичные конечные точки

• DICER1 mutations in ovarian and testicular stromal tumors [Срок оценки: 3 years]

Вторичные конечные точки (2)

• Clinical factors associated with outcome in ovarian and testicular stromal tumors [Срок оценки: 10 years]
• Pathologic and Genetic Correlations [Срок оценки: 5 years]

Критерии участия

Критерии включения

• Previous or current diagnosis of an ovarian sex cord stromal including but not limited to: Sertoli-Leydig cell tumor, gynandroblastoma (now enrolling these patients on PPB/DICER1 Registry), juvenile granulosa cell tumor, Sertoli cell tumor, sex cord-stromal tumor with annular tubules or undifferentiated stromal tumor
• Previous or current diagnosis of a testicular stromal tumor including but not limited to: juvenile granulosa cell tumor, Sertoli cell tumor, Leydig cell tumor or undifferentiated stromal tumor

Критерии исключения

• Unable to provide informed consent/assent
• Adult Granulosa cell tumor (unless otherwise specified by Medical Director)

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

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

США · 1 центр

• Children's Minnesota — Minneapolis

Публикации

• Schultz KA, Schneider DT, Pashankar F, Ross J, Frazier L. Management of ovarian and testicular sex cord-stromal tumors in children and adolescents. J Pediatr Hematol Oncol. 2012 May;34 Suppl 2:S55-63. doi: 10.1097/MPH.0b013e31824e3867. PMID 22525408
• Schultz KA, Sencer SF, Messinger Y, Neglia JP, Steiner ME. Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer. 2005 Feb;44(2):167-73. doi: 10.1002/pbc.20233. PMID 15490488
• Schultz KA, Ness KK, Nagarajan R, Steiner ME. Adnexal masses in infancy and childhood. Clin Obstet Gynecol. 2006 Sep;49(3):464-79. doi: 10.1097/00003081-200609000-00007. PMID 16885654
• Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O'Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M. DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig c PMID 21205968
• 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
• Pappo AS, Furman WL, Schultz KA, Ferrari A, Helman L, Krailo MD. Rare Tumors in Children: Progress Through Collaboration. J Clin Oncol. 2015 Sep 20;33(27):3047-54. doi: 10.1200/JCO.2014.59.3632. Epub 2015 Aug 24. PMID 26304909
• Pashankar F, Bisogno G, Ribeiro R, Messinger Y, Schultz KA, Rodriguez-Galindo C. The role of registries and tumor banking in rare pediatric tumors. Curr Pediatr Rep 2015:1-9. Avail online 15 Mar 2015. DOI 10.1007/s40124-015-0077-9.
• Schultz KAP and Miller R. (2014) Adnexal Masses in Infancy and Childhood. Coomarasamy A, Davuka W, Shafi M, Chan C (eds): Gynecology and Obstetric Surgery: Challenges and Management Options. Wiley-Blackwell. [BOOK.] [In press; avail may 2015].

Идентификаторы

NCT: NCT01970696 · International OTST Registry

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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