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.