There have been a number of preoperative radiation trials looking at preoperative radiation by itself

prior to surgical resection and those haven't shown any benefit. In fact, even in Pancoast's tumors, the
classic treatment that was developed back in the '50s and '60s was to treat these patients with
preoperative radiation therapy then resection. That is still done in most places now. But the more that
we view their data in terms of the radiation therapy and in looking at intraoperative administration,
preoperative or postoperative, patients did the same no matter what they did so that the combination
of chemotherapy and radiation is important but the order is not necessarily important. So there are
some areas like in St. Louis where they don't get preoperative therapy, just resect the tumor and give
them postoperative therapy and it seems to work out the same. So preoperative radiation has never
really been shown to be definitively better than the surgery alone with postoperative adjuvant if
needed. So what I want to do is look at some of the data from stage 3A disease and what I mean by 3A,
there are a lot of different types of 3As. They used to be T3N0 which is now 2B but I am going to talk
about them anyway because all of the trials have included those patients. You can see survival for those
patients with T3N0 is 40-50%. Usually closer to 50% so that is why they have been changed recently to
2B because their survival really doesn't fit into 3A. Then N2 disease is not even a single disease. An N2
can be a micrometastatic deposit in one lymph node or it can be bulky disease in multiple station lymph
nodes and their survival is dramatically different as well. N2 positive patients. If you look at just a single
station, that is one lymph node area on that map that has been involved with tumor and the rest of
them were all biopsied and negative, which gives you about a 35% survival with surgery alone. If you
look at a LUNG CANCER Page 6 6 single station lymph node excluding the subcarinal area which tends to
be a somewhat bilateral station and more difficult and poor prognostically input implications is actually
a better survival if you can eliminate those patients and look at a single station that is not subcarinal. Up
to 45%. Then if you look at patients with more than one area involved, they go down to 9%. If you again
exclude the subcarinal area, it goes up to 22% so you can see that depending on which group you look at
you can have anywhere from less than 10% survival up to 45% survival. In terms of preoperative or
induction therapy, there are a number of advantages that have been proposed. One of them is that you
treat the patient then when primary tumor size is as small as it can be, malignant metastases are also
presumably small and they would be several months later. You potentially might decrease surgical
seating which may or may not happen. The disadvantages that have been worried about have been the
increased morbidity and mortality from the surgical procedure, which actually has not turned out to be
the case, and delayed primary tumor control. That, as you can see from the other data, is not the biggest
worry. The metastatic disease is what kills the patient so that has turned out not to be the case. There
are other factors in all of this. When the Lung Cancer Study Group evaluated their adjuvant trials, one of
the primary things and possible reasons for failure was that the patients didn't tolerate the therapy very
well. After undergoing a major operation and trying to recover from that and then getting
chemotherapy. Also patients psychologically weren't ready to take more chemotherapy because their
tumor was already out and they would give up easily and say, "I don't want anymore chemotherapy
because my tumor is gone. It may not be there anymore and I don't want anymore." So, preoperative
therapies tend to get a higher dose intensity of chemotherapy than postoperative treatment so that
may be one of the key reasons why the preoperative seemed to be work better