(P 70) ICONIC (IMPROVING OUTCOMES THROUGH COLLABORATION IN OSTEOSARCOMA): A PROSPECTIVE OBSERVATIONAL COHORT STUDY FOR NEWLY DIAGNOSED OSTEOSARCOMA PATIENTS IN THE UNITED KINGDOM (UK)

Objective: Osteosarcoma (OS) is a rare cancer which has seen few changes to its standard of care treatment over the last 25 years. There is an unmet need for novel therapeutic approaches if outcomes are to improve. Understanding variations in current management of the disease and identifying new prognostic and predictive markers are vital steps towards achieving this goal.

Methods: ICONIC (NCT04132895) is a multicentre prospective observational cohort study initiated to establish a platform for recruitment of newly diagnosed OS patients across the UK with matched longitudinal collection of clinical and biological samples along with patient-reported outcomes. Key objectives are to describe patient characteristics and variations in treatment across the country and correlate biological and clinical data with patient outcomes to develop prognostic biomarkers and inform development of future clinical trials, as well as better understand patient experience. The study opened to recruitment in October 2019. Here we present preliminary data for patients recruited up to February 2023.

Results: There have been 219 patients recruited to date from 24 UK sites, median age 19 (range 3-83), 57% male (Table 1). Femur (50%, 108/215), tibia/fibula (24%, 51/215) and humerus (9% 19/215) the most common anatomical sites, though less usual sites are also represented including craniofacial disease (7%, 14/215), pelvis/sacrum (5% 10/215) and rib/chest wall disease (3%, 6/215). Treatment data from 151 patients demonstrated 129 (85%) patients received a methotrexate-containing neo-adjuvant regimen. A total of 166 patients have undergone surgery, of which 36 (22%) were amputations. Multi-agent adjuvant chemotherapy treatment has been initiated in 133 patients, 99 (74%) of which included methotrexate and 50/78 (64%) of patients eligible to receive adjuvant mifamurtide following NICE recommendations have received at least 1 dose (median 27, range 1-49). A total of 41 patients have relapsed/recurrent disease during follow up (10 local, 22 metastatic, 9 both) and there have been 34 deaths to date. With a median follow-up of 12.1 months, 1-year PFS and OS rates are 74.2% (95% CI 66.1%-80.6%) and 86.9% (95% CI 80.1%-91.5%) respectively (Figure 1).

Baseline blood for germline analysis is available from 186 pts (85%), and ctDNA in 81 patients (83%). Blood samples were also received for a pilot study to identify CTC in 78 patients. We have agreement to access archival FFPE from diagnostic, and resection tissue samples as well as relapsed samples if a biopsy is performed and frozen specimens have been collected from 128 patients). PROs have been collected from 200 patients. Funding from the Bone Cancer Research Trust has been secured to extend recruitment and follow up for an additional 2 years; to perform comprehensive spatial transcriptomic and genetic analysis of longitudinal tissue samples and to develop tumour models to identify novel targets, as well as establishing an imaging repository to facilitate imaging biomarker studies and validating PROs within this cohort.

Conclusion: ICONIC is the first prospective observational cohort study to recruit UK patients of all ages with newly diagnosed OS. Initial analyses have demonstrated the feasibility of comprehensive data and sample collection and identified differences in systemic management of patients across the country worthy of further investigation ICONIC provides a unique resource that will allow for better understanding of the biology of OS and aid development of new biomarkers and novel therapeutic approaches. Analyses are aligned with objectives within the newly formed European consortium, Fight Osteosarcoma Through European Research (FOSTER) where possible and provide opportunities for wider collaboration.