Outcomes Based on Histological Tumor Necrosis and Predictive Clinical and Laboratory Parameters for Necrosis in Children With Osteosarcoma Treated on a Non-High Dose Methotrexate-Based Chemotherapy Backbone.
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BACKGROUND: Histopathological response to neoadjuvant chemotherapy (NACT) measured as tumor necrosis (TN) has been reported to be prognostic post-high-dose methotrexate (HDMTX)-based chemotherapy. We studied this on a non-HDMTX chemotherapy backbone. MATERIALS AND METHODS: Children ≤15 years, with osteosarcoma treated on OGS-2012 protocol and surgery post NACT from January 2013 to December 2020 were retrospectively analyzed. TN was expressed as percentage. Outcomes based on different TN cutoffs (used in a dichotomized manner dividing the cohort into two groups of less than/greater than the particular cutoff) and clinical-laboratory parameters predictive of TN were studied. RESULTS: Analysis was done in 258 patients. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38 months (range: 34-45 months), 3-year 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% vs. 60.7%), 90% (38.7% vs. 69.0%), 100% (50.8% vs. 84.1%), were prognostic for EFS (p = 0.0001), while TN-90% (80.3% vs. 92.9%, p = 0.006) and 100% (85.5% vs. 97.7%, p = 0.023) were prognostic for OS. For localized disease, TN-70% (35.4% vs. 66.4%), 90% (41.6% vs. 77.0%), 100% (54.8% vs. 96.2%) were prognostic for EFS (p = 0.0001) and OS (p = 0.0001). For metastatic disease, TN-70% was prognostic for EFS (16.6% vs. 50.1%, p = 0.0047). Receiver-operator curve derived cutoff 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) and amputation (OR: 2.1, p = 0.014) had a higher risk of less than 90% TN. CONCLUSIONS: Tumor necrosis at 90% cutoff in localized disease is prognostic of survival even on a non-HDMTX-based backbone, but exploring other cutoffs for survival predictive and prognostic value could guide future treatment modification strategies and resource allocation in LMICs. Amputation, male gender predicts poor histological necrosis.