ICONIC (Improving Outcomes Through Collaboration in Osteosarcoma): Insights from a national prospective cohort trial for newly diagnosed osteosarcoma patients.

11524 Background: There has been little change in osteosarcoma (OS) treatment over the last two decades. Understanding management patterns, better understanding of biology and identifying new biomarkers are key to improving outcomes. Methods: ICONIC is a UK-wide prospective observational trial of newly diagnosed OS pts with longitudinal clinical, imaging, tissue and pt experience data collection to address key objectives. These include describing variation in management and outcomes for specific pt groups, establishing an imaging repository to develop imaging biomarkers, analysis of plasma cfDNA, and use of tumor tissue to develop pt-derived models and decode tumor-immune cross talk. Pts were recruited from Oct 2019 to Jan 2025. Progression-free (PFS) and overall survival were analysed using Kaplan-Meier survival statistics and Cox regression. Results: A total of 337 pts were recruited from 27 sites. Median age was 19 (range 3-83); 17% had metastases. In total, 229/253 (91%) pts receiving neoadjuvant treatment had methotrexate, doxorubicin, cisplatin (MAP); 259 underwent surgery, of which 52 (20%) had amputations; 101/161 (63%) of eligible pts received mifamurtide. With median follow-up of 2.5 years, 2-year PFS and overall survival were 57% (95% CI 51-63) and 78% (95% CI 72-83) (Table 1). Age, raised ALP, pelvis or trunk primary sites, metastases and inoperability were associated with worse PFS. Pts with a good pathological response to treatment and ≥2mm resection margin had the lowest risk of local recurrence (p=0.02). A pilot radiomics analysis of 32 pts undergoing resection after MAP, demonstrated baseline tumour volume (p=0.044) pre-treatment T2 Gray Level Non-Uniformity (GLNU) (p=0.002), and post-treatment GLNU difference (p=0.008) to be associated with overall survival. Longitudinal blood samples for cfDNA analysis were collected from 226 pts. Patient-derived primary cultures were successfully developed from 12 pts. Spatially-resolved genomic and transcriptomic analysis of tumor tissue to study genomic evolution and immune evasion is ongoing. Conclusions: ICONIC trial has identified variation in management and outcomes of OS, which will guide future practice and provided a successful platform for imaging and biomarker analysis, which is ongoing. Clinical trial information: NCT04132895 . Pt characteristics and outcomes according to age and primary site. All patientsN=337 <16 yearsN=115 16-24 yearsN=101 25-39 yearsN=60 >40 yearsN=61 Lower limb 228 (68%) 90 (78%) 74 (73%) 34 (57%) 30 (49%) Upper limb 40 (12%) 18 (16%) 9 (9%) 6 (10%) 7 (11%) Craniofacial 23 (7%) 3 (3%) 6 (6%) 7 (12%) 7 (11%) Pelvis/sacrum 22 (7%) 1 (1%) 8 (8%) 4 (7%) 9 (15%) Trunk 12 (4%) 1 (1%) 4 (4%) 5 (8%) 2 (3%) Unknown 12 (4%) 2 (2%) 0 (0%) 4 (7%) 6 (10%) Survival outcome analysis 2-year PFS (95% CI) 57% (51-63) 65% (55-74) 55% (44-66) 60% (45-73) 44% (30-57) 2-year OS (95% CI) 78% (72-83) 77% (66-84) 87% (77-93) 78% (62-88) 64% (49-75)