2.1 Methods
Treatment-naïve children ≤15years with biopsy-proven, osteosarcoma uniformly treated on OGS-2012 chemotherapy protocol and surgery post-NACT from January 2013-December 2020 were retrospectively analysed. OGS-2012 is an indigenous non-MAP protocol with lesser cumulative doses of alkylating agents and anthracyclines compared to MAP and St Jude OS99 (Supplemental Figure S1, Supplemental TABLE S1).2,3,4MRI scan was the imaging modality of the primary with staging done by Non-Contrast Computed Tomography (NCCT) of thorax and bone scan. In metastatic disease, only oligometastatic lung metastases or other sites which were surgically resectable were treated. Children were started on NACT if there was no indication for upfront surgery otherwise. Reassessment was done at 10-12 weeks with MRI scan of the primary and if initially metastatic to lungs, with NCCT of the thorax. Type of surgery was decided by the surgical team based on imaging and clinical profile. Limb Salvage Surgery (LSS) was done wherever feasible. There was a higher threshold for amputation, being reserved for cases with fungating or bleeding primary, with excruciating pain and where LSS was not possible. Those who had progressive disease prior to attaining local control were excluded from this cohort. Response to preoperative chemotherapy was assessed histologically on the surgical specimen and tumor necrosis noted in percentage.13 All metastatic sites which persisted on response assessment were also addressed surgically in this curative cohort. All children received uniform adjuvant chemotherapy with ifosfamide and cisplatin irrespective of the histological response. Those who had high frequency sensorineural hearing loss (SNHL) as detected by pure tone audiometry performed as per protocol were prescribed carboplatin or etoposide or HDMTX depending on the degree of SNHL. The primary objective of this study was to assess Event Free Survival (EFS) and Overall Survival (OS) based on TN at various cut-offs on a non-HDMTX based chemotherapy protocol, OGS-2012 in whole cohort, localized and metastatic osteosarcoma who were treated with a curative intent. The secondary objective was to delineate clinical and laboratory parameters predictive of TN on the same chemotherapy backbone. Children who had extracorporeal radiotherapy or cryoablation as limb salvage procedure where whole specimen was not available for assessment of TN were excluded from the analysis.