title: Diagnostic assessment of osteosarcoma chemoresistance based on Virtual Clinical Trials.
abstract: Osteosarcoma is the most common primary bone tumor in pediatric and young adult patients. Successful treatment of osteosarcomas requires a combination of surgical resection and systemic chemotherapy, both neoadjuvant (prior to surgery) and adjuvant (after surgery). The degree of necrosis following neoadjuvant chemotherapy correlates with the subsequent probability of disease-free survival. Tumors with less than 10% of viable cells after treatment represent patients with a more favorable prognosis. However, being able to predict early, such as at the time of the pre-treatment tumor biopsy, how the patient will respond to the standard chemotherapy would provide an opportunity for more personalized patient care. Patients with unfavorable predictions could be studied in a protocol, rather than a standard setting, towards improving therapeutic success. The onset of necrotic cells in osteosarcomas treated with chemotherapeutic agents is a measure of tumor sensitivity to the drugs. We hypothesize that the remaining viable cells, i.e., cells that have not responded to the treatment, are chemoresistant, and that the pathological characteristics of these chemoresistant tumor cells within the osteosarcoma pre-treatment biopsy can predict tumor response to the standard-of-care chemotherapeutic treatment. This hypothesis can be tested by comparing patient histopathology samples before, as well as after treatment to identify both morphological and immunochemical cellular features that are characteristic of chemoresistant cells, i.e., cells that survived treatment. Consequently, using computational simulations of dynamic changes in tumor pathology under the simulated standard of care chemotherapeutic treatment, one can couple the pre- and post-treatment morphological and spatial patterns of chemoresistant cells, and correlate them with patient clinical diagnoses. This procedure, that we named 'Virtual Clinical Trials', can serve as a potential predictive biomarker providing a novel value-added decision support tool for oncologists.
authors.affiliation: Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Center of Excellence in Cancer Imaging and Technology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Oncologic Sciences Department, School of Medicine, University of South Florida, Tampa, FL, United States. Electronic address: Kasia.Rejniak@moffitt.org.
authors.forename: K A
authors.initials: KA
authors.lastname: Rejniak
authors.affiliation: Analytic Microscopy Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Department of Biological Sciences, University of Illinois in Chicago, Chicago, IL, United States.
authors.forename: M C
authors.initials: MC
authors.lastname: Lloyd
authors.affiliation: Sarcoma Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Adolescent and Young Adult Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Oncologic Sciences Department, School of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: D R
authors.initials: DR
authors.lastname: Reed
authors.affiliation: Sarcoma Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Department of Anatomic Pathology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Analytic Microscopy Core, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States; Oncologic Sciences Department, School of Medicine, University of South Florida, Tampa, FL, United States.
authors.forename: M M
authors.initials: MM
authors.lastname: Bui
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D012516:Osteosarcoma / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents