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Pancreas
Fifth, trial design needs to be thoroughly anchored in valid statistical of patient subsets for whom radiotherapy may be particularly useful or
methodology, and statistical input needs to be sophisticated and detailed not helpful at all; improving efficacy or safety through field, fraction size,
with respect to the complexity of pancreatic cancer management and the and total dose modification; and combination with rationally selected,
potential confounders of therapeutic outcomes. newly developed targeted agents.
Finally, we need to ask: At what level should our discourse be aimed? In summary, the current controversy regarding the use of radiotherapy as
part of the adjuvant management of pancreatic cancer seems to stem
We have perhaps a few systemic agents of convincing but very modest from several distinct sources: the limitations of older studies; the
activity (gemcitabine, xeloda, erlotinib, 5-FU), and we have locoregional numerous confounders of patient outcome that relate to clinical biology
irradiation with, again, modest but definite antitumor effect. We seek and/or statistical design and not to therapy; the limitations of current
the best for our patients and we wish to avoid futile interventions, therapies; and the need for further study. For those who feel that
toxicity for no therapeutic gain, and toxicity that is disproportionate to radiotherapy should remain an integral part of this management, there is
the clinical gain achieved. Just as no-one would offer in 2008 surgery a large amount of phase III data from other GI and non-GI disease
performed using the standards, techniques, and supportive care of the presentations characterized by both locoregional and systemic risk of
1970s, so too we should not be arguing about the benefit (or lack failure, where randomized trials have consistently shown the benefit
thereof) of 1970s-style irradiation. In other words, whether radiotherapy of the addition of radiotherapy to chemotherapy. For those who
planned without the benefit of dedicated axial imaging and modern challenge the role of radiotherapy in this context, there is the reality that
treatment planning systems and given in split-course, low-dose fashion is at present there is no modern, adequately powered and stratified study
effective is simply no longer relevant. Similarly, we already know and do that demonstrates that radiotherapy added to chemotherapy provides
not need to repeat painful lessons already learned regarding the toxicity additional benefit. The EORTC has attempted to resolve this issue, at
of fields too large or doses too high to be safe and acceptable when least in part, through trial 40013, now closed, which randomized
applied to the organs of the upper abdomen. However, there are many patients after resection to gemcitabine or gemcitabine followed by
relevant questions that remain to be explored regarding the use of irradiation. This trial closed early in 2007, and results are awaited
radiotherapy: optimal sequencing with other modalities; definition with interest. ■
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22 US GASTROENTEROLOGY
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