1 INTRODUCTION
Osteosarcoma is the most common malignant bone tumor of childhood and adolescence with outcomes of 60-70% in localized disease with multidisciplinary treatment approach.1–3 Chemotherapy for osteosarcoma across co-operative groups mainly consists of high-dose methotrexate (HDMTX), cisplatin, doxorubicin, ifosfamide, carboplatin in combinations dividing these into two main categories of MAP (HDMTX, doxorubicin, cisplatin) and non-MAP protocols. MAP protocol is widely practiced worldwide, though the logistics associated with inpatient admission, unavailability of pharmacokinetic monitoring warranted during HDMTX infusion and associated mucositis and myelosuppression precludes its wider application in resource-limited settings where non-MAP protocols are used.4,5 This led to the development of indigenous non-MAP chemotherapy protocol, OGS 2012 delivered at our institute.4
Histological necrosis in post-neoadjuvant chemotherapy surgical specimens measured as tumor necrosis (TN) compared to residual viable tumor has been shown to be prognostic of outcomes.2,3,6–8 A cut-off of 90%TN was arbitrarily used to categorize responders, though strategies to improve outcomes in poor responders by modifying chemotherapy has largely been unsuccessful.9,10 But cut-offs of tumor necrosis prognostic of outcomes on an HDMTX-based chemotherapy protocol have been variable at 50%, 70%, 90% across studies.11,12 The loss of predictive value of 90%TN for survival even with modification of treatment strategies may be due to this arbitrary selection of the cut-off and warrants exploration of alternative cut-offs. This study assesses the prognostic significance of TN at various cut-offs on a non-HDMTX based chemotherapy and analyses the predictive clinical and laboratory parameters for TN.