SLIDES & TRANSCRIPTS
Tuesday, June 18

Breakout Group C Summary and Recomendations with Group Discussion: Improving Therapy and Reducing Morbidity of Primary Therapy for Localized Disease

Robert S. Bell, MD

So, we thought this was a very timely opportunity to move forward with local management, starting off for this group with the consensus around what we know about local management, what the group could agree upon. First of all, for extremity and trunk tumors, local control is probably not the major issue to be investigating at present.

Probably most of the group thought that our local control was at least satisfactory. ertainly, there are issues related to the biology of local failures, that failures in local management offer an opportunity for biological investigation; but we shouldn't really base any clinical trials related to extremity or truncal management on an issue of local control, since rates currently show eight percent failure -- less than 10 percent failure in most groups, and this is not something that is likely to be improved upon. On the other hand, in retroperitoneal sarcoma, local control is probably the major issue, and we are going to talk about developments and trials in extremity and in retroperitoneal sarcoma based on these assumptions.

In the extremity, probably the most important issue for clinical trials is the issue of decreasing morbidity while maintaining current local control rates. We thought this was something that was very appropriate for clinical study at this point. We also thought it was important to recognize the fact that the local control methodologies that we use dramatically impact the availability of tissue for tumor banking initiatives, and that we should address this, and that relates back to what Sharon was discussing earlier.

TOP

So, the three issues that we are going to bring to you for discussion this morning relate to the issue of the biopsy and how that relates to acquisition of tissue for molecular correlation studies; secondly, extremity sarcoma multi-modality management and the issue of morbidity; and then, finally, a proposal for a randomized control trial of retroperitoneal sarcoma management with radiation and surgery that Peter will discuss.

TOP

So, to look at the issue of how biopsy impacts on the acquisition of tissue for molecular studies. We have to look at the issue of what do we need tissue for in the performance of a biopsy. Of course, the key issue for the patient is the diagnosis. That would include the parameters that we have heard discussed today -- the subtype, the grade, the molecular alterations evident in the tumor. If those molecular alteration are currently part of the disease management and diagnostic process.

I think a group like this also has to be interested in banking material and processing material in a way that is going to advance science for this group, since we recognize that target recognition and identification is a critical part of what this group should be offering for the future care of sarcoma patients.

There are a variety of things that we should be considering in multidisciplinary centers: certainly, availability of viable tissue for cytogenetics, tissue culture and xenograft models, for development of pre-clinical testing with xenografts, to tissue culture, determination of cell line characteristics. These are important things that we have to consider in planning biopsy protocols. We certainly should all be banking frozen material for later cDNA microarray analysis, SNIPS for normal tissue, for blood, for the separation of blood into somatic cell studies as well as for proteomic serum analysis. This is stuff that we have to be doing. We shouldn't let the biopsy technique get in the way of developing resources that are going to provide information that changes therapy in the future.

TOP

So, if we look at biopsy tissue acquisition and how it impacts on tissue and tumor banking, the first priority has to be diagnosis. If the tumor is going to be resected without neoadjuvant therapy, then diagnosis with core needle biopsy is certainly sufficient in most cases, and tissue for corollary studies can be obtained at the time of resection. In fact, having this enormous tumor in front of you, with the ability to harvest various parts of that tumor in a defined fashion, probably represents a real opportunity for molecular correlative studies.

So, if the patient is going to have a tumor resected without neoadjuvant treatment, needle biopsy for diagnosis is probably sufficient. Core needle biopsy will suffice in most cases. However, with the increasing numbers of patients who are being treated with neoadjuvant therapy prior to surgery, we feel it is important to consider open biopsy as the only method that may provide sufficient tissue for the kinds of studies that we want to do in the future.

My sense is, multiple needle biopsies, first of all, may be more injurious to the patient, and maybe more morbid to the patient, and certainly there is nothing that suggests that multiple core biopsies are going to be sufficient for doing, for example, cDNA microarray studies with the necessary validation of the material that is required prior to subjecting material to cDNA studies.

TOP

I think open biopsy has to be recognized as potentially necessary.

We thought that the best practice necessary recommendation -- All multidisciplinary sarcoma groups should collect well-annotated tumor material for later correlative studies. The well annotated aspect would include a clinical informatics database that corresponds to the tumor-banking database, at a minimum. In patients receiving neoadjuvant therapy, open biopsy may be necessary to obtain sufficient tumor for later banking purposes.

We thought that it should be recognized, in cases that were not receiving neoadjuvant therapy, that we should be looking at the resection sample as a research opportunity for studying tumor heterogeneity and potentially some of the molecular mechanisms of tumorigenesis that we have heard about from Marc Ladanyi, related to mechanisms of instability and heterogeneity of expression within tumors.

Of course, the issue that we have heard several times during this meeting -- there should be international collaboration in terms of sharing, both the tumor bank resources but also the cDNA microarray databases that are generated by various groups. We should have some way of sharing this information and assuring that we are developing similar information.

So, perhaps I could stop there. Murray, is that a reasonable thing to do in terms of that best practice recommendation?

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