Background: Outcomes of adolescents and young adults (AYA) with bone sarcomas inclusive of osteosarcoma (OGS) and Ewing’s sarcoma (ES) are impacted by various factors including inadvertent prior treatment and poor compliance. We aimed to identify prognostic factors and derive prognostic models for these patients. Methods: All AYA OGS and ES cases treated at our institute with the “OGS-12” and Ewing’s family of tumors-2001 (“EFT-2001”) protocols from 2011 to 2021, and 2013 to 2018 respectively, were prospectively analyzed. Results:. Among 606/748 (81.0%) AYA with non-metastatic osteosarcoma, significant factors included in the prognostic model were failure to complete protocol (hazard ratio (HR) 2.65, 95% confidence interval (CI) 1.65-4.26), prior treatment (HR 2.93, CI 1.4-6.1), necrosis <90% (HR 1.63, CI 1.24-2.1), joint involvement (HR 2.0, CI 1.49-2.69) and SAP> median (204 U/l) (HR 1.63, CI 1.24-2.14). Of 104/263 (39.5%) AYA ES, significant factors were failure to complete protocol (HR 2.84, CI 1.03-7.8), prior treatment (HR 6.37, CI 1.8-22.0), necrosis <100% (HR 8.73, CI 2.16-35.3), and tumor size >8cm (HR 2.64, CI 1.04-6.7). For 142/366 (38.8%) AYA with metastatic OGS, significant factors were failure to complete protocol (HR 5.29), metastases not amenable to local treatment (HR 1.96), necrosis <90% (HR 1.96), and >10 metastases (HR 2.44). For 38/82 (43.6%) AYA with metastatic extremity ES, significant factors were failure to complete protocol (HR 3.88) and metastases not amenable to local treatment (HR 10.6). Conclusion: We developed simple, effective prognostic models for AYA with bone sarcomas with wide applicability in LMIC.

1 Background Persisting residual mass at treatment completion are known in rhabdomyosarcoma(RMS) who have been treated with definitive radiotherapy to the primary site, but their prognostic significance is uncertain. Tumour response as assessed by anatomic imaging is not prognostic and there are only limited studies based on FDG-PET response. We report the prognostic significance of persistent FDG avidity in residual masses, assessed 3-months post completion of radiotherapy, in paediatric RMS who have undergone definitive RT as primary local therapy. 2 Materials and Methods Children≤15 years with Group 3 or 4 RMS treated on a uniform chemotherapy protocol, who received definitive radiotherapy for local control from June 2013-December 2018, and had FDG-PET CT at 3-months post radiotherapy were retrospectively analysed for outcomes. 3 Results Sixty-three children formed the study cohort, (55 Group3 and 8 Group4) FDG-PET CT scan done 3-months post-radiotherapy showed FDG-avid residual mass in 11 patients(17.5%), morphologic only (FDG negative) residual mass in 24 patients(38.1%) and no residual in 28 patients(44.4%). At a median follow-up of 41months (range,10-83months), 3-year Event Free Survival of patients with FDG-avid residual are 45.5% (95%CI:23.8%-86.8%) and for those with morphologic only or no residual are 71.4% (95%CI:59.6%-85.5%). Presence of FDG-avid residual on PET-CT scan 3-months post definitive RT [HR-2.92(95%CI:1.13-7.57),p=0.028] and regional lymph node involvement [HR-3.14(95%CI:1.26-7.78),p=0.014] affected outcomes, which retained significance on multivariate analysis too. 4 Conclusions Persistent metabolic activity in residual disease at the end of therapy in RMS may portend poorer prognosis, and help identify patients who would benefit from alternative treatment strategy.