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.

Background Outcome and toxicity data in adolescent-adult Ewing’s Sarcoma (AA-ES) patients is sparse and merits exploration. Methods Histopathologically confirmed, non-metastatic AA- ES patients, who received standard institutional combination chemotherapy regimen (EFT-2001) comprising of ifosfamide plus etoposide and vincristine, doxorubicin, plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS) and overall survival (OS). Results There were 235 patients (primary safety cohort, PSC) with median age of 23 (15-61) years; 159(67.7%) were males, 155 (65.9%) had skeletal primary and 114(48.5%) had extremity tumors. 196(83.4%) were treatment naïve (primary efficacy cohort, PEC) and of these 119 (60.7%) had surgery. In PEC, at a median follow up of 36.4 (IQR 20 – 55) months, estimated 5 year EFS and OS were 60.9% (95% CI 53.1% - 69.9%) and 84.5% (95% CI 77.7% - 91.9%) respectively. Of these, 158 (80.6%) complying with intended treatment, at a median follow up of 39 (IQR 26- 57) months had an estimated 5 year EFS of 63.1% (95% CI 54.8%-72.6%). In multivariable analysis good prognostic factors included, longer symptom(s) duration (HR=0.93, 95% CI 0.86-0.994), ≥ 99% necrosis (HR=0.30, 95% CI 0.11-0.77) and treatment completion (HR=0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile-neutropenia (119, 50.6%), anemia (130,55.3%), peripheral neuropathy (37,15.7%), with 3(1.3%) chemo-toxic deaths . Conclusions The outcomes of AA non-metastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen could be considered a standard-of-care in AA-ES.

Introduction: Vascular endothelial growth factor (VEGF)is an angiogenic marker and implicated in carcinogenesis and prognostication of cancers. However its prognostic potential in a rare cancer-Ewing’s sarcoma merits exploration. Methods: Histopathologically confirmed consecutive ES cases registered at our institute from 2014 to 2018 were analysed. Immunohistochemical staining for VEGF was performed on tumour tissues and they were further classified based on VEGF intensity. Results: There were 105 patients including 53 non-metastatic and 52 metastatic. VEGF immunostaining in non-metastatic and metastatic cohort was negative in 20 (37.7%) and 21 (40.4%), mildly positive in 13 (24.5%) and 9 (17.3%) cases, moderately positive in 14 (26.4%) and 16 (30.8%), and was intensely positive in 6 (11.3%) and 7 (13.5%) patients, respectively. VEGF immunoexpression up to 25% was seen in 14 (13.3%) and 10 (9.5%) patients within the non-metastatic and metastatic cohort, respectively. The median EFS and OS for the entire cohort were 26.4 (95% CI 17.6-NA) and 32.5 (21.3-NA) months, respectively. Metaststatic ES patients having either VEGF immunostaining in >25% tumor cells or moderate /strong immunostaining were found to inferior EFS and OS [p= 0.017, HR-0.153; p=0.013, HR-0.109 respectively].Additionally, treatment-naïve, compliant and non-metastatic patients had superior EFS (p=0.000, 0.000, 0.020, 0.022 respectively) and OS (p=0.000, 0.000, 0.006, 0.041 respectively). Conclusion: VEGF expression and intensity were found as independent negative prognostic marker in Ewing sarcoma .This may translate to therapeutic relevance but needs validation in the subsequent, larger prospective studies.

Background Outcomes of Ewing sarcoma (ES) in low and middle income countries lags behind the rest of the world owing to multiple tumoral, logistical and socio-economic factors. The data of outcomes and toxicity in these countries is sparse, especially in the adolescent and adult (AA) population and merits exploration Procedure This was a retrospective analysis of prospectively collected data of non-metastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (EFT-2001) along with surgery or definitive radiotherapy. Various cohorts were analyzed for treatment-related toxicities, event- free survival (EFS) and overall survival (OS). Results There were 235 patients (primary safety cohort, PSC) with median age of 23 years. One hundred and ninety six were treatment naïve (primary efficacy cohort, PEC) and of these 119 had surgery. In PEC, at a median follow up of 36.4 months, estimated 5 year EFS and OS were 60.9% (95% CI 53.1% - 69.9%) and 84.5% (95% CI 77.7% - 91.9%), respectively. Of these, 158 complying with intended treatment, had an estimated 5 year EFS of 63.1% (95% CI 54.8%-72.6%). In multivariate analysis, good prognostic factors included longer symptom duration, ≥ 99% necrosis and treatment completion. Among PSC, grade 3-4 toxicities were febrile-neutropenia (50.6%), anemia (55.3%), peripheral neuropathy (15.7%), with 3 (1.3%) chemo-toxic deaths. Conclusions The outcomes of AA non-metastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity and can be considered as standard-of-care, especially in LMICs.

Background: Pediatric B-Lymphoblastic lymphoma(pB-LBL) is a rare entity, and appropriate treatment for pB-LBL is not well defined. While intensive Acute Lymphoblastic leukemia(ALL) type regimens achieve long term event free survival of 90% across western co-operative group trials, published data from Asian studies on long term outcomes in pB-LBL are scarce. We evaluated the outcomes and prognostic factors of pediatric B-LBL patients treated at our center. Methods: We retrospectively analyzed the data of pediatric B-LBL patients treated between January 2010 and December 2017 on a uniform protocol(modified BFM 90). Patients were evaluated for early response post-induction and monitored for toxicity and long term outcomes. Kaplan-Meier method was used to estimate the event free survival(EFS) and overall survival(OS). Cox regression models were performed to identify prognostic factors. Results: Of 21 patients who received treatment on the modified BFM 90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality(TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months(range 6–114), 5-year Event free survival(EFS) and overall survival(OS) were 80%(95% CI:71–89%) and 91% (95% CI:85–97%), respectively. While delayed presentation (≥3 months) had inferior EFS(p-0.030), patients with elevated baseline Lactate Dehydrogenase(LDH) had a worse OS(p-0.037). Age, gender, site of origin, stage, and post-induction response had no bearing on outcome. Conclusions: Outcomes of pB-LBL patients treated on modified BFM 90 protocol are excellent. Higher disease burden manifested by elevated baseline LDH and delayed presentation(≥3 months) portend poorer survival.

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.