(P 09) OUTCOMES, PROGNOSTIC FACTORS AND TREATMENT COMPLIANCE IN OSTEOSARCOMA CASES TREATED WITH AN INDIGENOUS, LOW-COST PROTOCOL, OGS-12, IN A TERTIARY CARE CANCER CENTRE IN INDIA

Objective: Osteosarcoma (OGS) is a model to show chemotherapy effectiveness wherein survival statistics jumped from < 20% to >60% in the best of the centres. However, outcomes vary in Low-Middle Income Countries (LMIC) due to various unique challenges.
High dose methotrexate regimen is labor–intensive and demands costly inpatient treatment, so, non-HDMTX based regimens are prevalent in LMIC. Our novel, non-HDMTX based “OGS-12” protocol has previously shown to have internationally comparable outcomes.
Prevalent issues in LMIC consist of inadvertent prior treatment at peripheral centres with resultant compromised outcomes. High dropout rates immediately after diagnosis and later non-adherence to protocols (poor compliance) may compromise outcomes.
The current study aimed to expand our understanding of the care pattern in LMIC including compliance, treatment abandonment, outcomes and prognosticators.
Additionally, since the majority of patients with OGS are primarily adolescents and young adults (AYAs), we have also explored additional concerns such as fertility, side effects and social implications among survivors.

Methods: All OGS cases treated at our centre from July 2018 to January 2021 were analyzed. The protocol is a non-HDMTX based, dose-dense OGS-12 regimen, consisting of eight sequential doublets of doxorubicin, ifosfamide and cisplatin chemotherapy (CT) in four courses each, given in neoadjuvant (NACT) and adjuvant(ACT) settings.
Baseline characteristics including tumor size, histological subtype, pre-treatment hemoglobin, alkaline phosphatase and lactate dehydrogenase were collected prospectively.
Primary outcome was event-free survival (EFS), which was calculated from registration to any event (recurrence/progression/death) and correlated with baseline characteristics and total treatment duration and histological response. Good responders were defined ≥90% histological necrosis post NACT. Treatment naïve versus prior treated patients were compared. Unique challenges to AYA population including fertility issues were assessed as indicators of holistic care and patients were asked during follow-up for their satisfaction towards these parameters.

Results: There were 856 histologically diagnosed OGS cases and 632 were treated with the OGS-12 protocol including 484 (76.6%) non-metastatic cases. There were predominantly males (64%) and with high tumor burden (table 1). At a median follow-up of 37 (4 – 69) months, 5-year EFS was 57%, and estimated 5-year OS was 78%. Median EFS was not reached; mean EFS was 39 months (95% CI 36.2-42.3), and OS was 77 months (95%CI 74-80) (Figure 1 and 2). There were 61% good responders. The median total treatment duration was 38 (29-49) weeks, and a lower treatment duration along with good histological response and lower baseline SAP was associated with better EFS (table 2). Prior treated patients had inferior median EFS (27 months, CI 23.5-29.7) compared to treatment naïve cases.
Treatment was not continued after diagnosis (either abandoned or continued elsewhere) in 71 (14.6%) patients. Among the patients where we could capture details during follow-up, majority (90%) of patients were counseled about potential impact on fertility in some form, however only 25% males and 5% females actually reached out to fertility specialists and/or underwent fertility preservation measures.
Common patient perception about fertility counseling was the need for additional time to understand these issues appropriately; most were anxious to start chemotherapy early. Visiting other institutes to see fertility specialists is challenging and facility in the same institute may be preferable. In female patients, extra time and cost involved was prohibitive.

Conclusion: The OGS 12 protocol continues to demonstrate outcomes comparable to international standardsand merits wider recognition. Good responders and maintenance of dose stand out as independent predictor for outcomes. Prior inadvertent treatment and not completing entire protocol were associated with had poorer outcomes. This underscores the importance of awareness and compliance. The results are widely applicable in LMIC settings and highlights the importance of focused AYA clinics and holistic care including appropriate fertility counseling, referral and assistance to improve fertility related outcomes.

tables.docx

efs.docx

OS.docx