Probably our most important prognostic factors, specifically if you are going to be giving neoadjuvant induction chemotherapy, is histologic tumor necrosis. That’s probably the gold standard. In those patients who have at least 90% necrosis or a Houvus score of IV – which I will show you what that is – have an extremely good prognosis. Surgical margin quality is important. You want to have negative margins. Those patients who have positive margins have a high incidence of local recurrence and then have a worse prognosis. So again, this is where pathology becomes important and you want, if we are going to give neoadjuvant induction chemotherapy at our institution we have a pathologist, Barry Schmukler, who samples multiple areas in a grid fashion of the bone, and looks in all these areas for the amount of necrosis and then gives us a number of the amount of tumor cells that are destroyed. This is based on work by Dr. Houvus who was a pathologist at Memorial Sloan-Kettering who developed the Houvus classification of I-IV, IV being no histological evidence of any tumor. This is now at many institutions been changed to greater than 90% being a good response.

In terms of work-up now. What kind of a work-up do you do for osteogenic sarcomas? Well, on plane x-ray you can see a sunburst sign. You need, as I talked to you before for soft tissue, you have to have a properly placed core on incisional biopsy. We usually obtain alkaline phosphatases and LDH’s as markers because they can be elevated, but they are not always elevated. We want to obtain an MR or a CT scan of the bone area plus a chest CT scan because this metastasizes to lung, plus a bone scan because it can metastasize to other bones. We use angiograms and thallium scans to assess the response to induction chemotherapy. If limb salvage is contemplated, if possible you want to have the surgeon who is going to perform the definitive operation do the incision placement, because if it’s not placed properly that may unfortunately mean that the patient will require an amputation. This is the sunburst sign that I was talking about. There can be elevation of the periosteum, which we call Codman’s triangle. This is this paraostial osteogenic sarcoma, which is low grade, which has the better prognosis.

In terms of staging, our staging again is a bi-gradal system, as for soft tissue sarcomas. Whether the tumor is in the cortex or beyond the cortex, size although important is not part of the grading system. And then metastasis. So it’s actually I, II, IV with nothing in the stage III group. So this is very similar to the previous Enneking staging system I showed you.