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.

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.

Background: The purpose of this single-centre study was to analyse the outcomes of extracranial germ cell tumors (GCTs) in children treated on a multi-modality regimen at a single-centre. Methods: Retrospective study of children (<18 years) with a histopathologically confirmed diagnosis of extracranial GCT over a period of 10 years (January’09-December’18) treated on a uniform institution-based protocol. All completely excised teratomas and stage I gonadal tumors received no further therapy (low risk); Stage IV Ovarian, Stage III-IV extragonadal GCTs received 6 cycles of chemotherapy (high risk) and the remaining received 4 cycles of chemotherapy (intermediate risk). Results: A total of 336 kids were treated of which the analysable cohort comprised of 297with a boy-girl ratio of 1.72:1 and median age of 4 years. Gonadal GCTs(n-180) were commoner than extragonadal GCTs(n-117) with ovary as primary site in 128 children(43%) and sacrococcygeal site being the commonest extragonadal location(n-41;14%). LR, IR and HR disease were noted in 60(20.2%) patients, 125(42%)patients and 112(37.8%)patients respectively. Forty-one patients relapsed and 43 children expired (disease related-33; toxic deaths-9; unknown-1). The 5-year EFS/OS was 79.3%/84.4% respectively with gonadal site, low-risk and non-metastatic disease associated with statistically better EFS (median follow-up:52.1±37.3 months). Conclusion(s): Both cisplatin and carboplatin based regimens had comparable outcomes. The low and intermediate GCTs had an excellent outcome, thus warranting a gradual shift in the approach to these tumors by reducing therapy and decreasing late effects of therapy. In high risk GCTs however, intensifying therapies to improve outcomes must be balanced against the risk of cumulative toxicity.