Radiation therapy is more effective on well-oxygenated cells that have not been devascularized by surgery.
Peritoneal tumor cell implantation due to the manipulation of surgery may be prevented by preoperative chemoradiation.
The high frequency of positive-margin resections recently reported supports the concern that the retroperitoneal margin of excision, even when negative, may be only a few millimeters; surgery alone may therefore be an inadequate strategy for local tumor control.
Patients with disseminated disease evident on restaging studies after chemoradiation will not be subjected to laparotomy.
Because radiation therapy and chemotherapy will be given first, delayed postoperative recovery will have no effect on the delivery of multimodality therapy, a frequent problem in adjuvant therapy studies.

In patients who receive chemoradiation before surgery, a repeat staging CT scan after chemoradiation reveals liver metastases in 25%. If these patients had undergone pancreaticoduodenectomy at the time of diagnosis, it is probable that the liver metastases would have been subclinical; these patients would therefore have undergone a major surgical procedure only to have liver metastases found soon after surgery. In the MDACC trial, patients who were found to have disease progression at the time of restaging had a median survival of only 6.7 months. The avoidance of a lengthy recovery period and the potential morbidity of pancreaticoduodenectomy in patients with such a short expected survival duration represent distinct advantages of preoperative over postoperative chemoradiation. When delivering multimodality therapy for any disease, it is beneficial, when possible, to deliver the most toxic therapy last, thereby avoiding morbidity in patients who experience rapid disease progression not amenable to currently available therapies. Cheap soma online
The survival advantage for the combination of chemoradiation and surgery compared with surgery alone likely results from improved local-regional tumor control. Because of the poor rates of response to 5-FU-based systemic therapy in patients with measurable metastatic disease, it is unlikely that current chemoradiation regimens significantly impact the development of distant metastatic disease. Recent data from Staley and colleagues at MDACC support this belief. Thirty-nine patients received preoperative 5-FU-based chemoradiation, pancreaticoduodenectomy, and electron-beam intraoperative radiation therapy (EB-IORT) for adenocarcinoma of the pancreatic head. Thirty-eight of them were evaluable for patterns of treatment failure; there was one perioperative death. Overall, there were 38 recurrences in 29 patients: 8 (21%) were local-regional (pancreatic bed or peritoneal cavity or both), and 30 (79%) were distant (lung, liver, or bone). The liver was the most frequent site of tumor recurrence, and liver metastases were a component of treatment failure in 53% of patients (69% of all patients who had recurrences). Fourteen patients (37% of all patients; 48% of patients who had recurrences) had liver metastases as their only site of recurrence. Isolated local or peritoneal recurrences were documented in only four patients (11%). This improvement in local-regional control was seen despite the fact that 14 of 38 evaluable patients had undergone laparotomy with tumor manipulation and biopsy before referral for chemoradiation and reoperation. If these 14 patients were excluded, only two patients (8%) would have experienced local or peritoneal recurrence as any component of treatment failure. However, because of the large percentage of patients who developed distant metastatic disease, predominantly in the liver, improved local-regional tumor control translated into only a small improvement in median survival compared with that in other recently published studies. Therefore, in the absence of effective systemic therapy, the goal of chemoradiation (preoperative or postoperative) and pancreatectomy should be to maximize local-regional tumor control while minimizing treatment-related toxicity and cost. Canadian viagra

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.
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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.

What about classical adjuvant chemotherapy for earlier stage disease, stage I or stage II? This is a very typical design. You would look at surgery and radiation, in some cases surgery alone, versus surgery, radiation and chemo. Well, to make it brief, to date there is no proven role for adjuvant chemotherapy. I’m showing you this trial as the most recent example of a negative trial. This was a large U.S. intergroup trial, designed just as this: surgery, radiation, surgery, radiation with platinum, etoposide. Two cycles concurrent and two cycles adjuvant afterwards. Preliminary analysis shown at ASCO this year, long term follow-up already. Median 41 months and median survival identical, 38 months on both arms. The only thing that is encouraging about this is that the median survival was really high on both arms. Surprisingly so, maybe, and the five year survival rate particularly encouraging at 39% and 33%. But this does not support a role for adjuvant chemotherapy, not yet.
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This is a positive trial, a European trial, that actually suggests that induction chemotherapy may be of benefit in stage Ib to IIIa where patients had either surgery or MIP, mitomycin ifosfamide, platinum, and then surgery. And radiation was given to some patients according to individual preference. In this trial, if you look at the two and three year survival, there is a suggestion of benefit. But it’s confounded by a number of things. The number of patients getting radiation on the surgical arm is much higher and paradoxically we now think that adjuvant radiation for at least some of these patients actually decreases their chances of survival or cure rather than increasing it. That’s again fairly recent literature looking at the role of radiation. So I’m showing you this to say that not all data are negative, but it’s certainly not yet conclusively supporting induction chemotherapy.

Now finally then, looking at current affairs here, here in early stage disease – much like in the advanced stages – we are looking at the newer regimens and what is called the bi-modality lung oncology trial, or BLOT. Bi-modality because it is chemo and surgery, looks at induction chemotherapy with carboplatin and paclitaxel in stage Ib through IIIa disease. This has been piloted in 94 patients with an objective response rate of the chemotherapy of 54%, which is not bad, and based on this the phase III trial has been activated where patients received either surgery or induction, not adjuvant, carbo and paclitaxel for three cycles.

In CLGB we’ve now looked at giving induction and concomitant but multi-agent therapies. And several other groups are looking at this and then adding the new drugs into this menu. We have some preliminary data that suggests that this can be done. We’ve looked at gemcitabine in this setting, paclitaxel and vinorelbine. All three are feasible but how good they are and what kind of long term survival rates we get, we are not sure of yet. So this was a randomized phase II trial, about 60 patients per arm, and we do now that all three arms are feasible and that these new drugs may have a role in stage III disease, much as they do in stage IV disease.
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So in the last few minutes then, let’s move down to the earlier stage disease settings. If chemotherapy has a role in stage IV for palliation and in stage IIIb to increase survival, then moving to the earlier stages you have fewer patients to evaluate, you bring in surgery as a third modality, randomized trials are very few and the conclusions are much less clear. So I just want to leave you with a few impressions. This is stage IIIa disease where again you have large primary lymph nodal disease but usually the surgeon has an option of at least attempting a curative intent resection. There have been two very small trials that are frequently cited that have looked at induction chemotherapy for stage IIIa disease and in this case surgery versus chemotherapy, followed by surgery. If you look at the three year survival there was a large difference favoring induction chemotherapy. A very similar trial from Spain, published in the New England Journal 1994, again about 30 patients – these are much harder to do these trials than stage IV or IIIb – surgery followed by radiation, versus chemotherapy followed by surgery and radiation. You look at the median survival, eight versus 26 months, and again a suggestion also of long term benefit. But both are very small trials and I could show you similar small trials that did not show that benefit. So for IIIa disease, induction chemotherapy, we’re really not sure yet.