Two studies now, which have incorporated not only Adriamycin, methotrexate and cisplatin, but also looking at the use of higher doses of ifosfamide, one by Dr. Meiser where ifosfamide was incorporated with Adriamycin and high dose methotrexate, gave a very high limb-sparing surgery rate, very high tumor necrosis rate and very good relapse free and overall survival. Another institution, the Rizzoli Institute in Italy looking at two different studies. This was not prospectively randomized but retrospective, but in one where ifosfamide was given postoperatively and another where ifosfamide was given preoperatively. You can see that in the study where it was given preoperatively there is a much higher limb-salvage rate, much higher amount of tumor necrosis, local recurrence is the same and disease free survival is better.

So now for osteogenic sarcoma, I think what I’ve tried to show you is that in the 70’s and before the 70’s for historical controls, those patients who just received surgery or radiation, about 20% of patients survived. With the benefit of adjuvant and neoadjuvant chemotherapy with agents like platinum, Adriamycin and high dose methotrexate, that’s increased to about 60%. With ifosfamide now added to the regimens there is about another 10-20% benefit, but still approximately 30%, 20-30% of our patients, those with chondroblastic osteogenic sarcomas, those with metastasis on presentation still do very poorly. So we need new approaches.

So in overview now of osteosarcoma; a core or incisional biopsy, surgery – limb-sparing if possible – metastasectomy beneficial in select patients. In terms of chemotherapy, adjuvant is the standard. That’s been shown in two prospective studies of significant benefit, so that is the standard and has definite survival benefit. Whether tailoring is beneficial, the studies do not pan that out. It’s probably more important to give more aggressive chemotherapy as induction. Neoadjuvant, although there has been no study to show any definite improvement, it appears to be at least equivalent with probably more patients having limb-sparing surgery. This is favored, as I said, by most orthopedic oncologists and should include at least platinum and Adriamycin. Some regimens also include high dose methotrexate, but that has to be given properly. And probably now also to include higher doses of ifosfamide.