Introduction:
Bone sarcomas inclusive of osteosarcoma (OGS) and Ewing’s sarcoma (ES) are rare, aggressive yet chemosensitive tumors with variable survival rates in Low and Middle-Income Countries (LMIC). There are various factors including delayed presentation with advanced disease and higher rates of metastatic disease, inadvertent prior treatment by primary care physicians, high dropout rates and poor adherence due to socioeconomic constraints with resultant compromised outcomes. Non-High-Dose-Methotrexate (Non-HDMTX) based regimens for osteosarcoma have gained popularity in these regions due to ease of administration on daycare basis, low cost and convenience. Therefore, finding valuable prognostic factors specifically targeting LMIC is crucial for predicting high-risk patients and early intervention to improve survival rates.
Among patients with osteosarcoma, possible prognostic factors, tumor size, metastatic disease at the time of diagnosis, histological grade, histologic response to neoadjuvant chemotherapy (NACT), and adequate surgical margins have consistently shown a strong correlation with survival. [1-2] Non-uniformity of chemotherapy protocols for osteosarcoma preclude generalisability of results. We have previously published our experience with our institutional standard low cost, non-HDMTX based “OGS-12” protocol where serum alkaline phosphatase level for EFS and performance status for OS were found to be independent prognosticators, concordant with other reports, including those from India [3-6]. Histological response to NACT was an independent predictor of both EFS and OS which is also well-established.
For Ewing’s sarcoma, multiple prognostic factors have been reported, such as age, gender, localization, volume and size of the primary tumor, presence of metastasis, treatment regimens, a baseline level of hemoglobin or lactate dehydrogenase, and pathologic response to neoadjuvant chemotherapy [7-9]. In our published data on patients with Ewing’s sarcoma at our institute treated with the “EFT-2001” protocol, statistically significant prognostic factors included longer symptom duration, >= 99% necrosis, and protocol completion. [10]
There are unique challenges with rare cancers like bone sarcomas globally and a prognostic model with wide applicability including for the patients in LMIC wherein including social challenges also play a role is an unmet need. Special challenges in LMIC include lack of awareness among patients and primary health care providers with resultant delayed presentation, upstaging and high tumor burden.
We have aimed to identify prognostic factors including those specific to LMIC. Additionally, we have derived and validated a prognostic score for osteosarcoma that integrates biologic and social factors and is tailored for patients from an LMIC setting using a non-HDMTX-based protocol.