International Ovarian & Testicular Stromal Tumor Registry

NCT01970696 | Recruiting

• 1 other identifier: International OTST Registry
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.to understand risk factors by studying age, pathologic subtype, histopathologic features, tumor invasiveness, degree of differentiation, presence of metastasis
2. 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. 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. 4.to determine optimal screening regimens
5. 5.to use clinical data obtained through the Registry to refine treatment algorithms
6. 6.to establish a collection of annotated biology specimens (tumor tissue and germline DNA) for future research

Conditions

Ovarian Sex-cord Stromal Tumor; Testicular Stromal Tumors; Ovarian Small Cell Carcinoma

Keywords

ovarian; testicular; stromal; sertoli; leydig; juvenile granulosa cell tumor; gynandroblastoma

Outcome Measures

Primary Outcomes (1)

• DICER1 mutations in ovarian and testicular stromal tumors

  We will analyze germline DNA from patients with gonadal stromal tumors to determine the presence of DICER1 mutations. The tumor tissue will also be sequenced. mRNA and miRNA expression will be analyzed on tumor tissue. Results of the above will be correlated with clinical outcome.

  3 years

Secondary Outcomes (2)

• Clinical factors associated with outcome in ovarian and testicular stromal tumors

  10 years

• Pathologic and Genetic Correlations

  5 years

Study Arms (3)

Ovarian Stromal Tumors

Testicular Stromal Tumors

Ovarian Small Cell Carcinoma

Eligibility Criteria

• Age: 0 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Prospectively or retrospectively diagnosed patients with ovarian or testicular stromal tumors or ovarian small cell carcinoma

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Children's Hospitals and Clinics of Minnesota: lead
• Children's National Research Institute: collaborator
• Dana-Farber Cancer Institute: collaborator
• Washington University School of Medicine: collaborator
• University of Texas Southwestern Medical Center: collaborator
• M.D. Anderson Cancer Center: collaborator
• Children's Hospital Colorado: collaborator
• Rutgers University: collaborator
• Massachusetts General Hospital: collaborator
• Klinikum Dortmund Wirbelsäulenchirurgie: collaborator
• ResourcePath, LLC: collaborator
• Allina Health System: collaborator
• Phoenix Children's Hospital: collaborator
• University of Cambridge: collaborator

Study Sites (1)

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

Related Publications (27)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 cell tumors. JAMA. 2011 Jan 5;305(1):68-77. doi: 10.1001/jama.2010.1910.

  PMID: 21205968 BACKGROUND

• Schultz KAP, Stewart DR, Kamihara J, Bauer AJ, Merideth MA, Stratton P, Huryn LA, Harris AK, Doros L, Field A, Carr AG, Dehner LP, Messinger Y, Hill DA. DICER1 Tumor Predisposition. 2014 Apr 24 [updated 2020 Apr 30]. 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://www.ncbi.nlm.nih.gov/books/NBK196157/

  PMID: 24761742 BACKGROUND

• 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 BACKGROUND

• 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.

  BACKGROUND

• 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].

  BACKGROUND

• Schultz KAP, Frazier L, Schneider DT. (2014) Ovarian and Testicular Sex Cord Stromal Tumors. Frazier, AL, Amatruda JF (eds): Textbook Pediatric Germ Cell Tumors, Pediatric Oncology 1. Berlin Heidelberg. Springer-Verlag. [BOOK.].

  BACKGROUND

• 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: 10.1002/pbc.29017. Epub 2021 Mar 24.

  PMID: 33760357 BACKGROUND

• Doros L, Yang J, Dehner L, Rossi CT, Skiver K, Jarzembowski JA, Messinger Y, Schultz KA, Williams G, Andre N, Hill DA. DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome. Pediatr Blood Cancer. 2012 Sep;59(3):558-60. doi: 10.1002/pbc.24020. Epub 2011 Dec 16.

  PMID: 22180160 RESULT

• Schultz KA, Pacheco MC, Yang J, Williams GM, Messinger Y, Hill DA, Dehner LP, Priest JR. Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: a report from the International Pleuropulmonary Blastoma Registry. Gynecol Oncol. 2011 Aug;122(2):246-50. doi: 10.1016/j.ygyno.2011.03.024. Epub 2011 Apr 17.

  PMID: 21501861 RESULT

• Schultz KA, Harris A, Williams GM, Baldinger S, Doros L, Valusek P, Frazier AL, Dehner LP, Messinger Y, Hill DA. Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma. Pediatr Blood Cancer. 2014 Sep;61(9):1695-7. doi: 10.1002/pbc.25092. Epub 2014 May 13.

  PMID: 24821309 RESULT

• Schultz KA, Harris A, Messinger Y, Sencer S, Baldinger S, Dehner LP, Hill DA. Ovarian tumors related to intronic mutations in DICER1: a report from the international ovarian and testicular stromal tumor registry. Fam Cancer. 2016 Jan;15(1):105-10. doi: 10.1007/s10689-015-9831-y.

  PMID: 26289771 RESULT

• Rutter MM, Jha P, Schultz KA, Sheil A, Harris AK, Bauer AJ, Field AL, Geller J, Hill DA. DICER1 Mutations and Differentiated Thyroid Carcinoma: Evidence of a Direct Association. J Clin Endocrinol Metab. 2016 Jan;101(1):1-5. doi: 10.1210/jc.2015-2169. Epub 2015 Nov 10.

  PMID: 26555935 RESULT

• Rove KO, Maroni PD, Cost CR, Fairclough DL, Giannarini G, Harris AK, Schultz KA, Cost NG. Pathologic Risk Factors in Pediatric and Adolescent Patients With Clinical Stage I Testicular Stromal Tumors. J Pediatr Hematol Oncol. 2015 Nov;37(8):e441-6. doi: 10.1097/MPH.0000000000000445.

  PMID: 26479987 RESULT

• Golmard L, Vasta LM, Duflos V, Corsini C, Dubois d'Enghien C, McMaster ML, Harney LA, Carr AG, Ling A, Dijoud F, Gauthier A, Miettinen M, Cost NG, Gauthier-Villars M, Orbach D, Irtan S, Haouy S, Schultz KA, Stoppa-Lyonnet D, Coupier I, Stewart DR, Sirvent N. Testicular Sertoli cell tumour and potentially testicular Leydig cell tumour are features of DICER1 syndrome. J Med Genet. 2022 Apr;59(4):346-350. doi: 10.1136/jmedgenet-2020-107434. Epub 2021 Mar 29.

  PMID: 33782093 RESULT

• Kebudi R, Dural O, Bay SB, Gorgun O, Onder S, Bilgic B, Yilmaz I, Iribas A, Arndt CA, Harris AK, Field A, Schultz KAP, Hill DA. Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes. J Pediatr Adolesc Gynecol. 2021 Aug;34(4):449-453. doi: 10.1016/j.jpag.2021.01.011. Epub 2021 Jan 20.

  PMID: 33484847 RESULT

• 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 RESULT

• 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 RESULT

• Dural O, Kebudi R, Yavuz E, Yilmaz I, Buyukkapu Bay S, Schultz KAP, Hill DA. DICER1-Related Embryonal Rhabdomyosarcoma of the Uterine Corpus in a Prepubertal Girl. J Pediatr Adolesc Gynecol. 2020 Apr;33(2):173-176. doi: 10.1016/j.jpag.2019.12.002. Epub 2019 Dec 12.

  PMID: 31838154 RESULT

• Schultz KAP, Harris AK, Finch M, Dehner LP, Brown JB, Gershenson DM, Young RH, Field A, Yu W, Turner J, Cost NG, Schneider DT, Stewart DR, Frazier AL, Messinger Y, Hill DA. DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: Clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry. Gynecol Oncol. 2017 Dec;147(3):521-527. doi: 10.1016/j.ygyno.2017.09.034. Epub 2017 Oct 14.

  PMID: 29037807 RESULT

• Merideth MA, Harney LA, Vyas N, Bachi A, Carr AG, Hill DA, Dehner LP, Schultz KAP, Stewart DR, Stratton P. Gynecologic and reproductive health in patients with pathogenic germline variants in DICER1. Gynecol Oncol. 2020 Mar;156(3):647-653. doi: 10.1016/j.ygyno.2019.12.037. Epub 2020 Jan 15.

  PMID: 31952842 RESULT

• Schultz KA, Harris AK, Schneider DT, Young RH, Brown J, Gershenson DM, Dehner LP, Hill DA, Messinger YH, Frazier AL. Ovarian Sex Cord-Stromal Tumors. J Oncol Pract. 2016 Oct;12(10):940-946. doi: 10.1200/JOP.2016.016261.

  PMID: 27858560 RESULT

• Rove KO, Maroni PD, Cost CR, Fairclough DL, Giannarini G, Harris AK, Schultz KA, Cost NG. Pathologic Risk Factors for Metastatic Disease in Postpubertal Patients With Clinical Stage I Testicular Stromal Tumors. Urology. 2016 Nov;97:138-144. doi: 10.1016/j.urology.2016.06.066. Epub 2016 Aug 15.

  PMID: 27538802 RESULT

• Terry W, Carlisle EM, Mallinger P, Nelson AT, Gordon D, Messinger YH, Field A, Dehner LP, Hill DA, Schultz KAP. Thoracic Sertoli-Leydig cell tumor: An alternative type of pleuropulmonary blastoma associated with DICER1 variation. Pediatr Blood Cancer. 2021 Nov;68(11):e29284. doi: 10.1002/pbc.29284. Epub 2021 Aug 16.

  PMID: 34398502 RESULT

• Nelson AT, Harris AK, Watson D, Kamihara J, Chen KS, Stall JN, Devins KM, Young RH, Olson DR, Mallinger PHR, Mitchell SG, Hoffman LM, Halliday G, Suleymanova AM, Glade Bender JL, Messinger YH, Herzog CE, Field AL, Frazier AL, Stewart DR, Dehner LP, Hill DA, Billmire DF, Schneider DT, Schultz KAP. Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries. Gynecol Oncol. 2024 Jul;186:117-125. doi: 10.1016/j.ygyno.2024.04.005. Epub 2024 Apr 23.

  PMID: 38657450 RESULT

Related Links

• International OTST Registry official website
• International PPB/DICER1 Registry

Biospecimen

Retention: SAMPLES WITH DNA

1\) whole blood for DNA extraction and lymphoblastoid cell line generation, 2) stained and unstained slides 3) paraffine blocks and/or scrolls 4) snap frozen tumor tissue (if available), and 5) fresh tissue (if available).

MeSH Terms

Conditions

Sex Cord-Gonadal Stromal Tumors

Condition Hierarchy (Ancestors)

Neoplasms, Gonadal Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Kris Ann P Schultz, MD

  Children's Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Harris, MPH

CONTACT

612-813-5861; anne.harris@childrensmn.org

Paige Mallinger, MS

CONTACT

612-813-7121; paige.mallinger@childrensmn.org

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 10 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Kris Ann P. Schultz, MD, MS

Study Record Dates

• First Submitted: October 23, 2013
• First Posted: October 28, 2013
• Study Start: December 8, 2011
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: August 22, 2024

Record last verified: 2024-08

Locations

US (1)