The purpose of this study is to examine if we can predict sensitivity of osteosarcoma to different chemotherapy agents using tissue cultures in the laboratory. We know that different chemotherapy agents can be used in the treatment, but not every sarcoma responds to them equally. It is important to understand if testing of the tissue obtained during a routine biopsy or surgery may be useful in selecting appropriate treatments. In addition, additional testing of the tumor, including genetic testing, will help us to understand osteosarcoma better.
Investigators successfully established a miniaturized system that allows the setup of hundreds of wells and perform assays with minimal manipulation. The adapted geometry used to plate tumor cells in Matrigel, to generate mini-rings around the rim of the wells. This is attained by plating single-cell suspensions obtained from a cell line or a surgical specimen pre-mixed with cold Matrigel in a ring shape around the rim in 96-well plates. Rings can be established using a single-well or multichannel pipette. Cancer cell lines grown in mini-ring format give rise to organized tumor organoids that recapitulate features of the original histology. Treatment protocols and readouts for the mini-ring approach have been optimized. Seeding cells takes place on day 0, 2-3 days are allowed to establish organoids and it is followed by two consecutive daily drug treatments. The assay is flexible and can be easily adapted to single treatments followed by longer incubations, multiple consecutive recurring treatments, multi-drug combinations, or other screening strategies. Assays were implemented to quantify drug response by measuring cell viability after staining of live organoids with specific dyes followed by imaging. The pipeline has been extended to sarcomas: the team characterized organoids established from over 120 sarcoma biopsies, resections, and metastasectomies. Sarcoma organoids showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. Organoid screening can provide information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma.
Study Type
OBSERVATIONAL
Enrollment
40
Image-guided or surgical biopsy of the lesion that is suspected to be osteosarcoma in a patient with localized disease (Group 1)
Image-guided or surgical biopsy or excision of the lesion that is suspected to be recurrent or metastatic osteosarcoma (Group 2).
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGorganoids from initial biopsy
To assess the feasibility of establishing organoids from initial biopsy and from postsurgical sample in patients with osteosarcoma, both in patients with localized disease and metastatic disease
Time frame: two years
drug sensitivity of organoids
To compare drug sensitivity of organoids established from the original biopsy to drug sensitivity of organoids established from the surgical excision of the primary tumor after neoadjuvant chemotherapy
Time frame: two years
degree of necrosis in the tumor
To correlate the degree of necrosis in the tumor obtained by the surgical excision of the primary tumor after neoadjuvant chemotherapy with the chemotherapeutic drug sensitivity in the organoids.
Time frame: two years
clinical benefit
To correlate the magnitude of clinical benefit in patients with metastatic osteosarcoma treated with systemic chemotherapy with the chemotherapeutic drug sensitivity in the organoids established from biopsy or surgical excision of metastatic disease.
Time frame: two years
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