Primary bone sarcomas are rare tumors, comprising approximately 0.2% of all cancers. Because of distant metastasis, cure after surgical treatment alone is uncommon. The development of effective adjuvant or induction chemotherapy regimens has dramatically improved the prognosis and cure rate of 50%–70% and limb salvage in > 90% of cases. For nonmetastatic osteosarcoma(NMO), optimal treatment consists of multiagent neoadjuvant/adjuvant chemotherapy and limb-sparing surgical procedures. The degree of tumor necrosis (TN) after neoadjuvant chemotherapy is one of the most important pronostic indicators. Intraarterial cisplatin and intravenous adriamycin (IC-IA) could achieve a good tumor response.
Based on achievement of a maximized angiographic response, 106 patients with NMO of the extremities received IC-IA monthly for 3-6 courses between January 1995 and December 2008 followed by limb salvage surgery then adjuvant intravenous (IV) chemotherapy with adriamycin and cisplatin. After resection, if patients had a good response (the extent of TN was ≥ 90%), the same regimen was administered IV every 3 weeks for a total of 6 courses of chemotherapy. Poor responders (tumor necrosis < 90%) were treated with a regimen of high-dose methotrexate with leucovorin rescue (HD-MTX) or ifosfamide, cisplatin, and etoposide (ICE).
Patients received an average of 5 cycles of neoadjuvant IC-IV chemotherapy. 96 patients underwent limb-preservation surgery and 72 had > 90% TN. With an average follow-up of 8years, 60 patients were continuously disease free, 32 died of disease and 14 had no evidence of disease within 5 years after relapse. The 5-year overall survival rate was 70%. No patient developed clinically detectable cardiac toxicity or ototoxicity after adriamycin and cisplatin administration. Febrile neutropenia occurred in few.
This study shows the effectiveness of treating primary NMO of extremities with IC-IA infusion. Advanced bone and soft tissue sarcomas are challenging diseases to treat with an unmet need for effective systemic therapy. Checkpoint inhibitors and Adoptive T cell therapy based immunotherapy could be a new ray of hope in treating bone sarcomas.
Clinical trial identification
Trial Protocol Number IND18745J
Legal entity responsible for the study
Gandhi Medical College and Hamidia Hospital, Bhopal, India
All authors have declared no conflicts of interest.