Primary Osteogenic Sarcoma of the Femur: A Model for the Use of Preoperative Chemotherapy in High Risk Malignant Tumors

Abstract

The value of adjuvant chemotherapy in primary osteogenic sarcoma (OSA) is still considered controversial by some. One reason may be that various reported series include patients with widely varying prognostic variables. To address this, the effect of chemotherapy on the continuous disease-free (CNED) survival was analyzed in 100 patients aged 21 yr or less with OSA of the femur. This classically poor prognostic group of patients represented 51% of all primary OSA seen at the Memorial Sloan-Kettering Cancer Center during the study interval. This study includes all patients aged 21 yr or less with fully malignant (Grade III-IV/IV) OSA of the femur and no metastases treated from November 1973 through November 1981. The first (T-4) protocol (31 patients) consisted of high dose methotrexate (HDMTX) with leucovorin rescue, cyclophosphamide (Cyc), and adriamycin. In the second (T-7) protocol (23 patients) the dose of HDMTX was increased to 12 g/m2 for prepubescent patients, and bleomycin, Cyc, and dactinomycin replaced Cyc. The current (T-10) protocol (46 patients) uses the same CT as T-7, but patients not having a complete response of the primary tumor to preoperative CT receive additional cisplatinum (120 mg/m2) with adriamycin (30 mg/m2/day for two consecutive days). In 31 patients treated with T-4 the CNED survival was 32% with a minimum follow up of over 7 yr. On T-7, 15/23 patients with femur primaries had a CNED survival of 65% with all of the surviving patients followed for more than 5 yr. The addition of cisplatinum in T-10 has resulted in CNED survival rate of 77% in 34/44 patients (excluding two patients that died CNED during and after treatment); the median follow-up patients who are alive CNED is 33 months, with a minimum of 2 yr follow up on the last patient entered.

Osteosarcomas of flat bones in adolescents and adults

“…[1][2][3][4][5] In addition to prolonged adjuvant chemotherapy, most treatment programs for osteosarcoma now also incorporate preoperative (neoadjuvant) chemotherapy. Rosen et al 1,[32][33][34] were the first to advocate preoperative chemotherapy and proposed a rationale for this therapeutic approach. Also, preoperative chemotherapy provides early treatment for patients with systemic, occult micrometastases and a detailed histologic evaluation of their response to chemotherapy in the resected specimen by grading the degree of tumor necrosis.…”

“…Moreover, preoperative chemotherapy causes shrinkage of the tumor by necrosis, which makes conservative surgical resections feasible and allows time to plan definitive local therapy for primary tumors. 1,[32][33][34][35] This conservative surgery may include en bloc resection of the tumor. 32,35,36 By convention, patients with osteosarcoma of the flat bones are excluded from clinical trials of new adjuvant therapies; hence, little is known about the impact of such therapy on this subgroup of tumors.…”

Prognostic Significance of Tumor Response at the End of Therapy in Group III Rhabdomyosarcoma: A Report From the Children's Oncology Group

“…[1][2][3][4][5][6] European rhabdomyosarcoma (RMS) clinical trials use radiographic response to initial therapy to tailor subsequent therapy in an attempt to minimize toxicity yet maximize survival. 7,8 This treatment philosophy assumes that initial response to therapy is associated with ultimate outcome and can identify chemotherapy-sensitive tumors more likely to be cured with systemic therapy.…”

Misdiagnosis and Mistreatment for Osteosarcoma: Analysis of Cause and Its Strategy

“…Neoadjuvant chemptherapy increased survival in patients without metastasis, however, the patient who benefit from neoadjvant chemotherapy are those had good histopathological response to chemotherapy [1][2][3][4][5] . Therefore, it's important to develop an effective method to evaluate tumor response to chemotherapy, so that we can choose right patient to surgery and avoid overtreatment.…”

“…They can show the tumor size, location and the relationship to normal tissue more clearly. Furthermore they provide the most important evidence to osteosarcoma clinical stage, surgical approach 2,3 . Author thought those osteosarcoma suspected in clinic should be checked routine lateral X-ray compared with the healthy side.…”