Osteosarcoma
Conditions
Brief summary
This research trial studies saliva, semen, and blood samples to determine effects of chemotherapy on fertility in osteosarcoma survivors. Study biospecimen samples from osteosarcoma survivors in the laboratory may help doctors learn whether chemotherapy causes fertility problems and to learn more about the long term effects.
Detailed description
PRIMARY OBJECTIVES: I. Determine whether infertility and/or biomarkers of spermatogenesis and steroidogenesis differ in male osteosarcoma survivors treated with cisplatin with or without ifosfamide compared to male controls without a history of cancer. II. Evaluate whether cisplatin with or without ifosfamide for the treatment of osteosarcoma alters sperm deoxyribonucleic acid (DNA) methylation. EXPLORATORY OBJECTIVES: I. Evaluate the role of genetic susceptibility in the development of impairments in spermatogenesis or steroidogenesis with contemporary regimens for the treatment of osteosarcoma. OUTLINE: Participants complete a health questionnaire over 30-45 minutes. Patients also provide saliva and semen samples and undergo collection of blood.
Interventions
PROCEDUREBiospecimen Collection
Undergo collection of blood and provide saliva and semen samples
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Children's Oncology Group
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Received upfront therapies for osteosarcoma, which included cisplatin, (with or without other agents) * Patient must have completed cancer treatment \>= 2 years prior to study enrollment * Osteosarcoma survivors without a systemically treated relapse or subsequent malignancy * Note: History of relapse or second malignancy is permitted if treated with local therapy only (e.g. surgery, radiation) * Able to speak, read and write in English, French or Spanish * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sperm deoxyribonucleic acid methylation | Up to 4 years | Genome-wide differentially methylated regions will be identified using methylated deoxyribonucleic acid immunoprecipitation followed by next generation sequencing analysis methylated deoxyribonucleic acid immunoprecipitation sequencing using pooled deoxyribonucleic acid. Sperm deoxyribonucleic acid differentially methylated regions will be confirmed in the pooled samples by bisulfite treatment of genomic deoxyribonucleic acid to convert cytosine to thymine followed by next generation sequencing for a bisulfite-sequencing analysis. Thus, methylated deoxyribonucleic acid immunoprecipitation- sequencing is used to identify the differentially methylated regions and bisulfite sequencing used to confirm the differentially methylated regions at the CpG level resolution. Pyrosequencing will be used involving next generation sequencing after polymerase chain reaction of individual sperm deoxyribonucleic acid samples to assess individual differentially methylated regions. |
| Infertility | Up to 4 years | The American Society of Reproductive Medicine's definition of infertility as … the failure to achieve a successful pregnancy after 12 months or more of regular unprotected intercourse will be used to categorize patients as to a history of infertility. Based on interview questions regarding each subject's personal and partner's history of medical investigations and treatment for infertility, an attempt will be made to further distinguish each subject's history of infertility as being due to the male (study subject), the female or indeterminate. Will determine whether infertility differ in male osteosarcoma survivors treated with cisplatin with or without ifosfamide compared to male controls without a history of cancer. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
| Follicle stimulating hormone levels | Up to 4 years | Will be measured by immunofluorometric assay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
| Luteinizing hormone levels | Up to 4 years | Will be measured by immunofluorometric assay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
| Testosterone levels | Up to 4 years | Will be measured by radioimmunoassay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
| Serum inhibin B | Up to 4 years | Will be measured by enzyme-linked immunosorbent assay. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
| Sperm concentration | Up to 4 years | Sperm concentration (per mL) will be assessed by Computer Assisted Sperm Analysis. Three separate counts will be performed and the results averaged. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
| Sperm morphology | Up to 4 years | Sperm morphology will be assessed. Will be analyzed using unconditional logistic regression models to estimate odds ratios and 95% confidence intervals for the associations of chemotherapy group with abnormal values as defined in clinical practice. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Role of genetic susceptibility in the development of impairments in spermatogenesis or steroidogenesis with contemporary regimens for the treatment of osteosarcoma | Up to 4 years | Analysis will be descriptive in nature and will be used to generate hypotheses for future studies. |
Countries
Canada, Puerto Rico, United States
Outcome results
None listed