Well, what about neoadjuvant chemotherapy? Neoadjuvant chemotherapy has the benefit of eradicating possible micro-metastases and decreasing the emergence of drug resistant cells. You are perfusing a tumor that is intact with an intact blood supply, you are reducing possible tumor size and neovascularity for possibly facilitating a resection with better surgical margins and more limb salvage, and it also may have the benefit of giving you an in vivo evaluation of chemotherapy. Chemotherapy neoadjuvantly has been given multiple ways; IV, continuous IV infusion, intra-arterial with or without radiation, tourniquet IM infusion, and isolated limb perfusion. Most of these studies have been small. They have been single institution with a short duration of follow-up. Three of the major studies have been at UCLA using very high doses of ifosfamide, 14 gm per meter squared, with radiation followed by platinum and Adriamycin, and then operating. At Mass. General using the MAID regimen with radiation therapy interdigitated, in between the chemotherapy. Our institution using Adriamycin/ifosfamide as well as intra-arterial platinum with Adriamycin. What these studies suggest is that there is improved local control, there appears to be an increase in the histologic necrosis when you sample the tumor. The limb salvage rate appears to be very good when compared to studies at these institutions previously. So they are retrospective rather than prospective. And survival appears to be somewhat better.
So based on this now, several of the groups are looking at neoadjuvant chemotherapy, and one of them being done by the intergroup is looking at this MAID plus RT. But there are other groups considering using the Adriamycin/ifosfamide regimen.
So as an overview for neoadjuvant, I would consider this for patients who are at high risk for local recurrence and mets, those with large high grade inadequately resected tumors. I would tend to use a more aggressive regimen, which appears to reduce local recurrence and has a higher complete pathologic response rate. This may convert more patients from an amputation to a limb-sparing surgical option. There is less normal tissue removed, preserving extremity function. Single institution studies show that this is feasible and safe. I can’t tell you at this point which is the best regimen. We are going to need more multi-center prospectively randomized studies and probably more and better chemotherapy.
Now what about the patient who recurs after receiving adjuvant chemotherapy or who recurs just after having surgery and radiation therapy? There are some patients who will just have recurrences in the lung, with a small number of lesions. If the primary tumor has been eradicated, there is no extrapulmonary metastasis, the patient is a good surgical risk, the patient is deemed to be fully resectable by a thoracic surgeon who does a lot of these, they may be eligible for a metastasectomy and we usually do a median sternotomy unless the patient has a left posterior lower lobe which can’t be visualized well. It’s usually a clam-shell median sternotomy. In multiple studies – and these are in your handout – the five year survival for the patient receiving a metastasectomy – which we normally don’t think about for a patient who has a solid tumor with metastasis – for soft tissue sarcoma there’s a five year survival of 25-30%. For osteogenic sarcoma there is 35-40%. So this is something to consider for your patient. Whether you should give chemotherapy before the metastasectomy or whether chemotherapy after the metastasectomy in terms of further increasing survival, whether this will be of benefit is unknown. There is a study being done by the EORTC which is also involved with our intergroup here, which is looking at that, in terms of at least adjuvant chemotherapy.