1 Background Parameningeal Rhabdomyosarcomas (PM-RMS) in children are challenging to treat. While ten-year Event Free Survival (EFS) of 62% have been reported from High-Middle Income Countries (HMICs) for localized disease, data is limited from Low-Middle Income Countries (LMICs). We studied the clinical profile, outcomes, and prognostic factors in PM-RMS. 2 Materials and Methods Children≤15 years with PM-RMS treated on a uniform chemotherapy protocol from January 2013-December 2021 were retrospectively analysed. Local therapy at 10-12weeks of induction was radiotherapy (RT)+/-surgery where possible with early RT for intracranial extension (ICE). 3 Results Seventy-six patients with a median age of 6.7years (range,3.2-15years), male to female ratio of 1.8:1 formed the study cohort. Eleven patients (14.5%) had metastasis (lungs-8, bone-2, bone marrow-1) and ICE seen in 46.1%(n=35). Twenty-five patients (49.0%) had alveolar histology with PAX3/7 positive in 17/59 (28.8%). Median tumor size(t size) at baseline was 5.2cm(range,1.2-12.8cm). Seventy-one patients received RT, 5 also underwent surgery. At a median follow-up of 65months (range,53-76months) 4year EFS, OS of the whole cohort were 47.3%(95%CI:34.8%-58.8%), 51.7%(95%CI:38.0%-64.0%) respectively. Four-year EFS, OS of localized and metastatic cohort were 54.7%(95%CI:41.3%-68.1%), 56.0%(95%CI:42.0%-70.0%) and 9.1%(95%CI:0%-26.5%), 18.2%(95%CI:0%-47.8%) respectively. Metastases (HR-3.38,95%CI:1.57-7.26,p=0.002), t size (HR-1.17,95%CI:1.02-1.34,p=0.026) were prognostic for survival on multivariate analysis. 4 Conclusions Survival of children with localized PM-RMS in our study is relatively fair compared to the reported literature probably due to application of RT in all despite higher proportion of larger tumors, unfavorable sites of primary and intracranial extension. Identification of high-risk subsets and optimizing current treatment strategies, both systemic and local therapy may partly improve outcomes.

1 Background Histopathological response to neoadjuvant-chemotherapy(NACT) measured as tumor necrosis(TN) has been reported to be prognostic of outcomes post HDMTX- based chemotherapy. We studied outcomes based on different cut-offs of TN and delineated clinical-laboratory parameters predictive of TN on a non-HDMTX chemotherapy backbone. 2 Materials and Methods Children ≤15years, with osteosarcoma treated on OGS-2012 protocol and surgery post-NACT from January 2013-December 2020 were retrospectively analysed. TN was reported as percentage necrosis. Kaplan-Meier, log-rank, Pearson’s Chi-square tests were used. 3 Results Analysis was done in 258 patients. Median age-12years(range,3-15years), M:F-1.7:1. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38months(range,34-45months), 3year Event Free Survival(EFS) and Overall Survival(OS) of the whole cohort were 56.1%(SE,3.3%) and 87.8%(SE,2.4%). For entire cohort, TN-70%(29.3%vs60.7%), 90% (38.7%vs69.0%), 100%(50.8%vs84.1%), were prognostic for EFS(p=0.0001), while TN-90%(80.3%vs92.9%,p=0.006) and 100%(85.5%vs97.7%,p=0.023) were prognostic for OS. For localized disease, TN-70%(35.4%vs 66.4%), 90%(41.6%vs77.0%), 100%(54.8%vs96.2%) were prognostic for EFS(p=0.0001), and OS(p=0.0001). For metastatic disease, TN-70% was prognostic for EFS(16.6%vs50.1%,p=0.0047). Receptor-Operator Curve derived cut-off of 85.5%TN for EFS, 83.5%TN for OS prognosticated whole and localized cohorts the best. For metastatic cohort, 84.5%TN best prognosticated EFS. Among clinical-laboratory parameters, male gender(OR:1.9,p=0.01), amputation (OR:2.1,p=0.014) had a higher risk of <90%TN. 4 Conclusions Tumor necrosis at 90% cut-off in localized disease is prognostic of survival on a non-HDMTX based backbone, though best outcomes are seen with 100%TN, but 70%TN and other cut-offs require further exploration. A lower cut-off of 70%(or other) in metastatic disease could be used for prognostication. Amputation, male gender predicts poor histological necrosis.

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.