Panel Discussion: Randomized Trials vs. Prospective Registry

Reviewer: Christine Hill, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 26, 2008

Presenter: Andre Konski, M.D. and Andrew Lee, M.D.
Presenter's Affiliation: Fox Chase Cancer Center and M. D. Anderson Cancer Center
Type of Session: Reporting

Drs. Konski and Lee engaged in a panel discussion of the most efficient and appropriate ways in which to gather clinical data regarding patients undergoing proton-and particle-based radiotherapy. Dr. Konski initiated the discussion by pointing out historical situations in which radiotherapy has been misused, or has caused results that were not anticipated. Specifically, he pointed out situations in which use of radiation for benign disease, such as tinea capis and thymic enlargement, has caused much more severe issues such as second malignancies. Awareness of these situations certainly drives home the point that the radiation oncology community at large must stay aware of the potential risks and benefits of all new technologies, knowing that outcomes from their use may not be as we expect. Dr. Konski explained his concern that the field of radiation oncology could put itself at risk of scrutiny if new techniques and technologies are not properly tested. Dr. Konski went on to point out the barriers that may limit thorough testing of the roles of proton radiotherapy in the form of randomized clinical trials, including the cost of placing centers for testing, the cost of initiating randomized controlled trials, and the reluctance of both patients and physicians to participate in the randomization process. A much simpler way to attempt to evaluate proton technologies as opposed to others, such as intensity modulated radiotherapy (IMRT) with photons, would be to consider comparative studies between prospective registries. Such registries could be kept prospectively when patients initiate treatment, and could then be compared to one another. The Radiation Therapy Oncology Group (RTOG) is currently initiating such a comparison between registries of multiple institutions. Dr. Lee went on to support Dr. Konski’s points, and enforced them with several of his own. He explained that he believes that randomized controlled trials evaluating proton radiotherapy versus photon irradiation should be carried out, but that their feasibility, at least in certain circumstances, is doubtful. He cited a review recently published in Lancet Oncology of proton beam trials that have been performed, and noted that only one study of 41 was actually a randomized controlled trial. Additionally, he pointed out that results from most of the reviewed studies with regards to benefits in local control and/ or overall survival were inconclusive. Certainly, other endpoints may be just as valuable as these, including toxicities, which we expect to be reduced by use of proton therapy. Dr. Lee explained his own experience at M.D. Anderson Cancer Center, during which he attempted to enroll patients on a randomized controlled trial comparing IMRT with photons and proton radiotherapy. He reported that very few patients were willing to undergo randomization. In light of these difficulties, he also described the potential role of prospective registries, explaining that comparison of prospective registries is likely more valid than comparison of retrospective registries with regard to bias and objectivity. He noted that with more proton centers opening, possibilities for randomized controlled trials might come to more fruition, but that currently prospective registries are essential for centers with access to protons. Comparison of such registries will hopefully provide valuable information with regards to toxicities, tumor control, quality of life, and cost, and results from these comparisons could easily serve a springboard function for randomized controlled trials in the future.

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